FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thong, T Raitt, MH AF Thong, Tran Raitt, Merritt H. TI Predicting imminent episodes of ventricular tachyarrhythmia using heart rate SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE prediction; ventricular tachyarrhythmia; R-R intervals; ICD; prevention; VT; VF ID RATE-VARIABILITY; SPONTANEOUS INITIATION; RATE DYNAMICS; TACHYCARDIA; ONSET; ARRHYTHMIAS; FIBRILLATION; MECHANISMS; DISEASE; DEATH AB Background: A reliable Predictor of an imminent episode of ventricular tachyarrhythmia that could be incorporated in an implantable defibrillator capable of preventive therapy would have important clinical utility, Method: A test set of 208 R-R records saved by defibrillators spanning a mean of 1.6 hours before sustained tachyarrhythmia were used to derive criteria that would improve the specificity of the previously identified monotonic heart rate acceleration predictor. Additional criteria were used, namely two such patterns need to occur within a period of 1.8 hour and the heart rate during these accelerations exceeds 86 bpm (700 ms). The specificity was tested using R-R records matched in duration from 26 control patients with defibrillators during normal periods. Results: The basic acceleration pattern was found during sinus rhythm in the 1.8-hour period prior to 83% of episodes of ventricular tachyarrhythmia. It was also found in 43% of the matched set of nonarrhythmic records, corresponding to a specificity of 57%. With the two extra requirement of multiplicity within 1.8 hour and peak heart rate, the sensitivity of the proposed predictor is reduced to 53%, but the specificity is increased to 91%, which corresponds to an average false positive rate of 0.8 event/day across the patient population. Conclusion: A ventricular tachyarrhythmia predictor based on a pattern of heart rate acceleration has been proposed that can yield sensitivity from 53% to 69%, with specificity up to 91%. Instances of this predictor increase significantly prior to an episode of tachyarrhythmia. C1 Oregon Hlth & Sci Univ, Dept Biomed Engn, OGI Sch Sci & Engn, Beaverton, OR 97006 USA. Portland VA Med Ctr, Portland, OR USA. RP Thong, T (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, OGI Sch Sci & Engn, 20000 NW Walker Rd,MS OGI 602, Beaverton, OR 97006 USA. EM trant@bme.ogi.edu NR 18 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2007 VL 30 IS 7 BP 874 EP 884 DI 10.1111/j.1540-8159.2007.00775.x PG 11 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 187OE UT WOS:000247856800008 PM 17584269 ER PT J AU Edwards, RR Klick, B Buenaver, L Max, MB Haythornthwaite, JA Keller, RB Atlas, SJ AF Edwards, Robert R. Klick, Brendan Buenaver, Luis Max, Mitchell B. Haythornthwaite, Jennifer A. Keller, Robert B. Atlas, Steven J. TI Symptoms of distress as prospective predictors of pain-related sciatica treatment outcomes SO PAIN LA English DT Article DE sciatica; pain; disability; discectomy; mood; distress; psychosocial ID MAINE LUMBAR SPINE; LOW-BACK-PAIN; HEALTH SURVEY SF-36; QUALITY-OF-LIFE; NONSURGICAL MANAGEMENT; PERSISTENT PAIN; BIOPSYCHOSOCIAL PERSPECTIVE; GENERAL-POPULATION; LONGITUDINAL DATA; DISC HERNIATION AB Prior studies evaluating predictors of pain-related outcomes following treatment for sciatica have been limited by methodological problems, including retrospective study design, use of unvalidated outcome measures, and short-term follow-up periods. Despite these limitations, some reports have suggested that symptoms of psychological distress may predict individual differences in pain treatment-related outcomes (e.g., higher levels of depressive and anxious symptomatology are associated with greater pain and disability after treatment). In this study, we sought to determine whether acute symptoms of depression and anxiety were prospectively associated with treatment outcomes over a 3-year follow-up period in surgically treated and non-surgically treated patients with sciatica. Patients were recruited from the practices of community-based physicians throughout the state of Maine, and underwent in-person baseline assessments, with mailed follow-up questionnaires at 3, 6, 12, 24, and 36 months. Study outcomes included patient-reported symptoms of pain and disability. For each outcome variable, we examined whether baseline mood (i.e., mood assessed prior to the initiation of treatment), as well as mood at the immediately preceding assessment point, prospectively predicted outcomes over 3 years in multivariate repeated-measures analyses. Tn most analyses, symptoms of depression and anxiety, both at baseline and at the preceding time point, were significant independent predictors of worse pain and function after controlling for relevant covariates. Collectively, elevated distress appears to be a significant risk factor for reduced treatment benefit (i.e., less improvement in pain and disability) over short and medium-term follow-up periods in patients with sciatica. Future research should determine whether the prospective identification and treatment of patients with high levels of distress (a "yellow flag") is associated with improved treatment outcomes. (C) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. NIH, Natl Inst Dent & Cranofacial Res, DHHS, Div Intramural Res, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Massachusetts Gen Hosp, Harvard Med Sch, Med Serv, Gen Med Div,Clin Epidemiol Unit, Boston, MA 02114 USA. RP Edwards, RR (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 1-108, Baltimore, MD 21287 USA. EM redwar10@jhmi.edu FU AHRQ HHS [HS-06344, HS-08194, HS-09804]; NIAMS NIH HHS [K23-AR051315, P60-AR048094-01A1]; NINDS NIH HHS [K24-NS02225, R21-NS048593] NR 47 TC 35 Z9 35 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2007 VL 130 IS 1-2 BP 47 EP 55 DI 10.1016/j.pain.2006.10.026 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 186BO UT WOS:000247754300009 PM 17156925 ER PT J AU Bradesi, S Lao, L McLean, PG Winchester, WJ Lee, K Hicks, GA Mayer, EA AF Bradesi, Sylvie Lao, Lijun McLean, Peter G. Winchester, Wendy J. Lee, Kevin Hicks, Gareth A. Mayer, Emeran A. TI Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia SO PAIN LA English DT Article DE 5-HT3 receptors; visceral nociception; hyperalgesia; stress ID IRRITABLE-BOWEL-SYNDROME; COLORECTAL DISTENSION; ANESTHETIZED RAT; SPINAL-CORD; ALOSETRON; RESPONSES; BRAIN; HYPERSENSITIVITY; TROPISETRON; NOCICEPTION AB Despite its beneficial effect in IBS patients, the mechanism of action of the 5-HT3 receptor (5-HT3R) antagonist alosetron is still incompletely understood. We aimed to characterize the effect and site(s) of action in a model of stress-induced sensitization of visceral nociception in rats. Adult male Wistar rats were equipped for recording of visceromotor response (VMR) to phasic colorectal distension (CRD; 10-60 mm Hg). VMR to CRD was recorded 24 h after an acute session of water avoidance (WA) stress (post-WA). Baseline and post-WA responses were measured in rats exposed to WA or sham-WA, treated with alosetron at 0.3 mg/kg subcutaneously (s.c.) 25 nmol intrathecally (i.t.) or vehicle before post-WA CRD. Some rats were treated with capsaicin/vehicle on the cervical vagus nerve and received alosetron (0.3 mg/kg, s.c.) 15 min before post-WA CRD. WA stress led to visceral hyperalgesia 24 h later. Alosetron (0.3 mg/kg, s.c.) failed to inhibit WA-induced exacerbation of VMR to CRD. Stress-induced visceral hyperalgesia was abolished when alosetron was injected intrathecally (P < 0.05) in intact rats or subcutaneously (0.3 mg/kg) in capsaicin-pretreated animals (P < 0.05). Capsaicin-pretreatment did not affect the exacerbating effect of stress on visceral sensitivity. Alosetron had no inhibitory effect on normal visceral pain responses when administered subcutaneously or intrathecally. We demonstrated that 5-HT(3)Rs on central terminals of spinal afferents are engaged in the facilitatory effect of stress on visceral sensory information processing. In addition, we showed that stress-induced sensitization of visceral nociception is independent of 5-HT3R activation on vagal afferents. (C) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Nova Pharmaceut Corp, E Hanover, NJ 07936 USA. RP Mayer, EA (reprint author), Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM emayer@ucla.edu FU NCCIH NIH HHS [R24 AT00281]; NIDDK NIH HHS [P50 DK64539] NR 34 TC 30 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2007 VL 130 IS 1-2 BP 56 EP 65 DI 10.1016/j.pain.2006.10.028 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 186BO UT WOS:000247754300010 PM 17161536 ER PT J AU Parmelee, PA Harralson, TL Smith, LA Schumacher, HR AF Parmelee, Patricia A. Harralson, Tina L. Smith, Lori A. Schumacher, H. Ralph TI Necessary and discretionary activities in knee osteoarthritis: Do they mediate the pain-depression relationship? SO PAIN MEDICINE LA English DT Article DE pain; depression; osteoarthritis; functional status; leisure ID ACTIVITY RESTRICTION; CANCER-PATIENTS; MENTAL-HEALTH; OLDER ADULTS; ARTHRITIS; DISABILITY; AGE; SYMPTOMS; SCALES; IMPACT AB Objective. This study examined direct vs indirect associations of pain and physical function with depression in 369 older adults with osteoarthritis (OA) of the knee. A key focus was the distinction of functional disability in necessary tasks (basic and instrumental activities of daily living) from discretionary, leisure activities. Design. A naturalistic longitudinal study examined effects of demographic variables, indicators of arthritis status, general health, pain, and several measures of functional disability upon depressive symptoms at baseline and 1 year later. Setting and Patients. Participants with diagnosed knee OA were recruited from rheumatological and general geriatric outpatient clinics, as well as public service announcements. Outcome Measure. Depressive symptoms, measured with the Center for Epidemiologic Studies Depression scale. Results. At baseline, the relationships of depression with functional disability and activity limitation were wholly mediated by pain. In contrast, activity participation was independently linked with depression, even controlling health and demographic variables. A 1-year follow-up revealed that depressive symptoms increased with increasing health problems, and with reduction in activity participation over time. Having and retaining favorite pastimes were also associated with reduced depressive symptomatology at baseline and follow-up, respectively. Conclusions. These data highlight the disease-specific nature of paths among depression, pain, and disability, and the importance of considering discretionary as well as necessary activities in evaluating effects of pain upon quality of life. C1 Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, Atlanta, GA 30329 USA. Albert Einstein Med Ctr, Ctr Urban Hlth Policy & Res, Philadelphia, PA 19141 USA. Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Parmelee, PA (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM pparmel@emory.edu FU PHS HHS [1 R01-51800] NR 46 TC 24 Z9 26 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUL-AUG PY 2007 VL 8 IS 5 BP 449 EP 461 DI 10.1111/j.1526-4637.2007.00310.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 197SA UT WOS:000248575600011 PM 17661863 ER PT J AU Cote, CJ Wax, DF Jennings, MA Gorski, CL Kurczak-Klippsteln, K AF Cote, Charles J. Wax, David F. Jennings, Melissa A. Gorski, Carla L. Kurczak-Klippsteln, Kimberly TI Endtidal carbon dioxide monitoring in children with congenital heart disease during sedation for cardiac catheterization by nonanesthesiologists SO PEDIATRIC ANESTHESIA LA English DT Article; Proceedings Paper CT Meeting of the World-Federation-of-Societies-of-Anesthesiologists CY APR, 2004 CL Paris, FRANCE SP World Federat Soc Anesthesiol DE monitoring; safety; blood gases; capnography; expired carbon dioxide ID END-TIDAL CO2; PEDIATRIC-PATIENTS; THERAPEUTIC PROCEDURES; ADVERSE SEDATION; PULSE OXIMETRY; SINGLE-BLIND; CAPNOGRAPHY; MANAGEMENT; GUIDELINES; EMERGENCY AB Background: This prospective observational study compared endtidal carbon dioxide (PECO2) with blood gas carbon dioxide (PaCO2) values in children sedated by nonanesthesiologists for cardiac catheterization. Methods: A nasal cannula designed to obtain gas sampling simultaneously from over the mouth and nares was taped into place after assuring a good waveform. Patients' cardiac lesions, site of blood gas sampling and P(E)CO(2)were recorded. Results: Two hundred and one blood/PECO2 pairs were measured in 59 patients from 4 days to 18 years of age. Linear regression, Pearson correlation, and Bland-Altman analysis revealed a reasonable relationship (r = 0.493, P < 0.01, bivariate Pearson correlation) for all blood/expired CO2 pairs even when the blood sample was obtained from an area of the circulation with shunting. There was no significant difference in the accuracy of the blood/PECO2 pairs between infants who weighed <= 15 kg compared with children who weighed > 15 kg. Thirteen children were diagnosed with partial or complete airway obstruction. Conclusions: Endtidal CO2 measurement provides a reasonable reflection of blood CO2 values if the expired gas-sampling catheter is taped in place after assuring a good waveform. The veracity of the data was the same throughout the patient size range. Expired CO2 monitoring is useful for assessing the adequacy of respirations and the patency of the airway in children 3-89 kg. C1 Harvard Univ, Dept Anesthesia & Crit Care Med, Div Pediat Anesthesia, Sch Med,Massachusetts Gen Hosp, Boston, MA USA. Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Div Pediat Cardiol, Chicago, IL 60611 USA. Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Dept Pediat Anesthesiol, Chicago, IL 60611 USA. Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Cardiac Catheterizat Lab, Chicago, IL 60611 USA. RP Cote, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Intens Care Med, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org NR 29 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JUL PY 2007 VL 17 IS 7 BP 661 EP 666 DI 10.1111/j.1460-9592.2007.02193.x PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 185AM UT WOS:000247683700008 PM 17564648 ER PT J AU Zacharoulis, S Levy, A Chi, SN Gardner, S Rosenblum, M Miller, DC Dunkel, I Diez, B Sposto, R Ji, LY Asgharzadeh, S Hukin, J Belasco, J Dubowy, R Kellie, S Termuhlen, A Finlay, J AF Zacharoulis, Stergios Levy, Adam Chi, Susan N. Gardner, Sharon Rosenblum, Marc Miller, Douglas C. Dunkel, Ira Diez, Blanca Sposto, Richard Ji, Lingyun Asgharzadeh, Shahab Hukin, Juliette Belasco, Jean Dubowy, Ronald Kellie, Stewart Termuhlen, Amanda Finlay, Jonathan TI Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue SO PEDIATRIC BLOOD & CANCER LA English DT Article DE CNS tumors; transplantation; ependymoma; chemotherapy ID MALIGNANT BRAIN-TUMORS; HIGH-DOSE CHEMOTHERAPY; BONE-MARROW RESCUE; PROGNOSTIC-FACTORS; INTRACRANIAL EPENDYMOMA; ADJUVANT CHEMOTHERAPY; POSTOPERATIVE CHEMOTHERAPY; RADIATION-THERAPY; CANCER GROUP; PEDIATRIC-ONCOLOGY AB Background:. The purpose of this study is to investigate the efficacy of an intensive chemotherapy induction regimen followed by myeloablative chemotherapy and autologous hematopoietic stem cell rescue (AHSCR) in children with newly diagnosed ependymoma. Patients and Methods:. Twenty-nine children less than 10 years of age at diagnosis of ependymoma were enrolled on the "Head Start" studies. Twenty-four patients with localized disease received an induction regimen including five cycles of chemotherapy (cisplatin, vincristine, etoposide cyclophosphamide, and high dose methotrexate for patients with metastatic disease). Following induction, individuals without evidence of disease proceeded to marrow-ablative chemotherapy (thiotepa, carboplatin, and etoposide) with AHSCR. Results:. The estimated 5-year event free survival (EFS) and overall survival (OS) from diagnosis were 12% ( 6%) and 38% (+/- 10%), respectively. The toxic mortality amongst this group of 29 patients was 10.3%. Younger age (less than 18 months at diagnosis) was the only statistically significant prognostic factor. The estimated 5-year OS rate for the five patients with metastatic disease at presentation was 80% (+/- 18%). Overall, radiation-free survival at 5 years from diagnosis was 8% (+/- 5%). Conclusions:. The use of an intensive induction chemotherapy regimen including myeloablative chemotherapy followed by AHSCR in newly diagnosed young children with ependymoma is not superior to other previously reported chemotherapeutic strategies. C1 Childrens Hosp, Dept Pediat Hematol Oncol, Neural Tumors Program, Los Angeles, CA 90027 USA. Montefiore Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NYU, Med Ctr, New York, NY 10012 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. BC Childrens Hosp, Vancouver, BC, Canada. Childrens Hosp, Philadelphia, PA 19104 USA. Suny Univ Hosp, Syracuse, NY USA. Childrens Hosp, Westmead, NSW, Australia. Ohio State Univ, Columbus Childrens Hosp, Columbus, OH 43210 USA. RP Zacharoulis, S (reprint author), Childrens Hosp, Dept Pediat Hematol Oncol, Neural Tumors Program, 4650 Sunset Blvd Mail Stop 54, Los Angeles, CA 90027 USA. EM szacharoulis@chla.usc.edu OI Dunkel, Ira/0000-0001-8091-6067; gardner, sharon/0000-0002-8857-5487 NR 33 TC 49 Z9 50 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2007 VL 49 IS 1 BP 34 EP 40 DI 10.1002/pbc.20935 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 172EO UT WOS:000246787100008 PM 16874765 ER PT J AU Sedik, HA Barr, RG Clark, S Camargo, CA AF Sedik, Hanan A. Barr, R. Graham Clark, Sunday Camargo, Carlos A., Jr. TI Prospective study of sudden-onset asthma exacerbations in children SO PEDIATRIC EMERGENCY CARE LA English DT Article DE sudden-onset; asthma ID CLINICAL-FEATURES; DISTINCT ENTITY; THERAPY AB Objectives: Sudden-onset asthma exacerbations among adults have more rapid treatment responses than do slower-onset exacerbations. We hypothesized that a similar pattern would be evident in children presenting to the emergency department (ED) with an asthma exacerbation. Methods: Prospective cohort study at 44 North American EDs. Parents of children, aged 2 to 17 years, underwent a structured interview in the ED and follow-up interview by telephone 2 weeks later. Results: Of 1184 enrolled children, 11% had sudden-onset asthma (ED presentation <= 3 hours after symptom onset). Sudden-onset patients were older than slower-onset patients (8.9 vs. 7.7 years, respectively; P = 0.004) and more likely to be white (26% vs. 17%, P = 0.01). They were less likely to report a history of steroid use or asthma hospitalization and reported fewer ED asthma visits during the past year (all P < 0.05). Although initial pulmonary index scores were similar (4.0 vs. 4.3, P = 0.24), patients with sudden-onset asthma were less likely to receive steroid treatment (73% vs. 84%, P = 0.002), had shorter ED length of stay (128 minutes vs. 150 minutes, P = 0.01), and in unadjusted analyses, were less likely to be admitted (16% vs. 24%, P = 0.04). Conclusions: Patients with sudden-onset exacerbations had similar acute asthma severity as those with slower-onset exacerbations but had shorter ED length of stay and were less likely to be admitted to the hospital, suggesting a more rapid response to treatment. C1 Childrens Hosp Los Angeles, Div Emergency Med, Los Angeles, CA 90027 USA. Columbia Univ, Div Gen Med, New York, NY 10027 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Sedik, HA (reprint author), Childrens Hosp Los Angeles, Div Emergency Med, 1650 Sunset Blvd,Mailstop 113, Los Angeles, CA 90027 USA. EM hsedik@chla.usc.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD JUL PY 2007 VL 23 IS 7 BP 439 EP 444 DI 10.1097/01.pec.0000280507.83042.03 PG 6 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 191XI UT WOS:000248164900002 PM 17666923 ER PT J AU Vargas, PA Brenner, B Clark, S Boudreaux, ED Camargo, CA AF Vargas, Perla A. Brenner, Barry Clark, Sunday Boudreaux, Edwin D. Camargo, Carlos A., Jr. TI To environmental tobacco smoke among children presenting to the emergency department with acute asthma: A multicenter study SO PEDIATRIC PULMONOLOGY LA English DT Article DE smoking; second-hand smoke; acute asthma; children; emergency medical services ID NUTRITION EXAMINATION SURVEY; HEALTH-CARE UTILIZATION; INNER-CITY CHILDREN; QUALITY-OF-LIFE; PASSIVE SMOKING; RISK-FACTORS; RESPIRATORY ILLNESS; HOSPITAL ADMISSIONS; PARENTAL SMOKING; NATIONAL-HEALTH AB Environmental tobacco smoke (ETS) exposure has been associated with increased use of the emergency department (ED) for acute asthma care. The purpose of this study was to determine the prevalence of ETS exposure among children presenting to the ED for acute asthma care and whether ETS exposure affects acute asthma severity or response to therapy We conducted a multi-center study of children 2-11 years with physician-diagnosed acute asthma presenting to 44 EDs in 18 states. Chi-square test, Student's t-test, Wilcoxon rank sum test, and logistic regression were used for the analyses. The study population included 954 children. Thirty-six percent (95% Cl, 33-39%) of caregivers reported that their child was exposed to ETS. Among exposed children, 35% were exposed 1-6 days/week, and 65% were exposed daily. Compared to unexposed children, ETS-exposed children were older at asthma diagnosis, older at ED presentation, and were less likely to be Hispanic. Indicators of chronic asthma severity were higher among unexposed children (i.e., total number of medications, use of controller medications, use of beta(2) agonists, number of urgent clinic visits, and lifetime hospitalizations). There was a weak association between ETS and acute asthma severity Response to therapy (including ED disposition) did not differ between groups. On multivariate analysis, ETS-exposed children were more likely to be older, female, non-Hispanic, have lower household income, not use controller medications, and have a pet at home (all P < 0.05). Our study showed that the prevalence of ETS exposure among children presenting to the ED with acute asthma differs across demographic factors. There were no significant differences in acute asthma symptoms or response to ED therapy between ETS-exposed and unexposed children. Lower use of controller medications and less frequent urgent clinic visits among ETS-exposed children suggest inadequate asthma care or milder disease. The weak association between ETS exposure and acute asthma severity might reflect confounding by psychological factors and/or chronic asthma severity The frequency of ETS exposure suggests that the ED may be an appropriate venue to engage caregivers of children with asthma in asthma education and smoking cessation efforts. C1 Univ Arkansas Med Sci, Little Rock, AR 72204 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. UMDNJ, Cooper Univ Hosp, Robert Wood Johnson Med Sch, Camden, NSW, Australia. RP Vargas, PA (reprint author), Arkansas Childrens Hosp, CARE, 800 Marshall St,Slot 512-26, Little Rock, AR 72202 USA. EM vargasperlaa@uanis.edu OI Vargas, Perla/0000-0003-2852-3922 FU NIDA NIH HHS [DA16698-01] NR 69 TC 13 Z9 14 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JUL PY 2007 VL 42 IS 7 BP 646 EP 655 DI 10.1002/ppul.20637 PG 10 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 184NI UT WOS:000247648300012 PM 17534978 ER PT J AU Wigal, SB Wilens, TE Wolraich, M Lerner, M AF Wigal, Sharon B. Wilens, Timothy E. Wolraich, Mark Lerner, Marc TI Hematologic and blood biochemistry monitoring during methylphenidate treatment in children with attention-deficit/hyperactivity disorder: 2-year, open-label study results SO PEDIATRICS LA English DT Article DE ADHD; hematologic monitoring; blood biochemistry; methylphenidate; stimulant; Concerta ID DAILY OROS METHYLPHENIDATE; TERM OPEN-LABEL; ONCE-A-DAY; ADHD TREATMENT; ADOLESCENTS AB OBJECTIVES. Patients receiving methylphenidate for the management of attention-deficit/hyperactivity disorder are recommended to receive periodic hematologic monitoring. The objective of this study was to evaluate the long-term effects of methylphenidate treatment on blood biochemistry and hematologic values. METHODS. This study involved a detailed analysis of changes in hematologic and blood biochemistry values over the course of a 2-year study of once-daily OROS methylphenidate in otherwise healthy children aged 6 to 13 years with attention-deficit/hyperactivity disorder. Routine hematologic and blood biochemistry assessments were performed at baseline, at 6 and 12 months during study treatment, and at the end of the study. RESULTS. Of the 407 subjects enrolled in the study, 289 completed year 1, and 229 completed 21 of 24 months. No subject was excluded from entry into the study or discontinued from the study because of abnormalities of any of the blood chemistries evaluated. There were no clinically significant changes from baseline in mean values for hematologic or blood biochemistry parameters. For most values, the mean change in value over the course of the study was < 5%. CONCLUSIONS. These longer-term data suggest that chronic therapy with OROS methylphenidate has no clinically significant impact on laboratory values, challenging the necessity of routine hematologic monitoring in otherwise healthy children with attention-deficit/hyperactivity disorder who are treated with methylphenidate. C1 Univ Calif Irvine, Dept Pediat, Irvine, CA 92612 USA. Massachusetts Gen Hosp, Psychopharmacol Res Unit, Boston, MA 02114 USA. Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. RP Wigal, SB (reprint author), Univ Calif Irvine, Dept Pediat, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM sbwigal@uci.edu NR 33 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2007 VL 120 IS 1 BP E120 EP E128 DI 10.1542/peds.2006-1402 PG 9 WC Pediatrics SC Pediatrics GA 185OC UT WOS:000247719300068 PM 17548486 ER PT J AU Gallun, FJ Mason, CR Kidd, G AF Gallun, Frederick J. Mason, Christine R. Kidd, Gerald, Jr. TI Task-dependent costs in processing two simultaneous auditory stimuli SO PERCEPTION & PSYCHOPHYSICS LA English DT Article; Proceedings Paper CT 149th Meeting of the Acoustical-Society-of-America CY MAY 16-20, 2005 CL Vancouver, CANADA SP Acoust Soc Amer ID ACROSS-EAR INTERFERENCE; PARTY LISTENING TASK; INFORMATIONAL MASKING; SELECTIVE ATTENTION; SPEECH IDENTIFICATION; SPATIAL SEPARATION; ENERGETIC MASKING; DICHOTIC MEMORY; PERCEPTION; RECOGNITION AB A listener presented with two speech signals must at times sacrifice the processing of one signal in order to understand the other. This study was designed to distinguish costs related to interference from a second signal (selective attention) from costs related to performing two tasks simultaneously (divided attention). Listeners presented with two processed speech-in-noise stimuli, one to each ear, either (1) identified keywords in both or (2) identified keywords in one and detected the presence of speech in the other. Listeners either knew which ear to report in advance (single task) or were cued afterward (partial-report dual task). When the dual task required two identification judgments, performance suffered relative to the single-task condition (as measured by percent correct judgments). Two different tasks (identification for one stimulus and detection for the other) resulted in much smaller reductions in performance when the cue came afterward. We concluded that the degree to which listeners can simultaneously process dichotic speech stimuli seems to depend not only on the amount of interference between the two stimuli, but also on whether there is competition for limited processing resources. We suggest several specific hypotheses as to the structural mechanisms that could constitute these limited resources. C1 Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. Boston Univ, Boston, MA 02215 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM frederick.gallun@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU NIDCD NIH HHS [F32 DC006526-03, DC00100, DC04545, DC04663, F32 DC006526, R01 DC004545] NR 68 TC 20 Z9 20 U1 1 U2 5 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0031-5117 J9 PERCEPT PSYCHOPHYS JI Percept. Psychophys. PD JUL PY 2007 VL 69 IS 5 BP 757 EP 771 DI 10.3758/BF03193777 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA 212MQ UT WOS:000249601000010 PM 17929698 ER PT J AU Mylonakis, E Casadevall, A Ausubel, FM AF Mylonakis, Eleftherios Casadevall, Arturo Ausubel, Frederick M. TI Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi SO PLOS PATHOGENS LA English DT Review ID INNATE IMMUNE-RESPONSE; GENOME-WIDE ANALYSIS; CRYPTOCOCCUS-NEOFORMANS; CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA; IN-VIVO; DROSOPHILA-MELANOGASTER; GALLERIA-MELLONELLA; PEPTIDOGLYCAN RECOGNITION; ASPERGILLUS-FUMIGATUS AB Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [AI63084, K08 AI063084] NR 66 TC 99 Z9 102 U1 1 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2007 VL 3 IS 7 BP 859 EP 865 AR e101 DI 10.1371/journal.ppat.0030101 PG 7 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196VY UT WOS:000248511600001 PM 17676994 ER PT J AU Brumme, ZL Brumme, CJ Heckerman, D Korber, BT Daniels, M Carlson, J Kadie, C Bhattacharya, T Chui, C Szinger, J Mo, T Hogg, RS Montaner, JSG Frahm, N Brander, C Walker, BD Harrigan, PR AF Brumme, Zabrina L. Brumme, Chanson J. Heckerman, David Korber, Bette T. Daniels, Marcus Carlson, Jonathan Kadie, Carl Bhattacharya, Tanmoy Chui, Celia Szinger, James Mo, Theresa Hogg, Robert S. Montaner, Julio S. G. Frahm, Nicole Brander, Christian Walker, Bruce D. Harrigan, P. Richard TI Evidence of differential HLA class I-Mediated viral evolution in functional and Accessory/Regulatory genes of HIV-1 SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTE ESCAPE; CELL RESPONSES; DISEASE PROGRESSION; PRIMARY INFECTION; TYPE-1 INFECTION; IMMUNE PRESSURE; PEPTIDE MOTIFS; SELECTION; VARIANTS AB Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT), Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naive individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps,'' which identify known and putative cytotoxic T lymphocyte (CTL) epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+) T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other genes investigated indicates differential HLA class I-driven evolution in different viral genes. The relationship between HLA class I-associated polymorphisms and lower CD4(+) cell count suggests that immune escape correlates with disease status, supporting an essential role of maintenance of effective CTL responses in immune control of HIV-1. The design of preventative and therapeutic CTL-based vaccine approaches could incorporate information on predictable escape pathways. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Microsoft Res, Redmond, WA USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. RP Brumme, ZL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM zbrumme@partners.org RI Hogg, Robert/B-2783-2012; Bhattacharya, Tanmoy/J-8956-2013; OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Brander, Christian/0000-0002-0548-5778; Hogg, Robert/0000-0003-3463-5488; Korber, Bette/0000-0002-2026-5757; Brumme, Chanson/0000-0003-2722-5288 FU PHS HHS [N01-AL-15422] NR 43 TC 114 Z9 116 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2007 VL 3 IS 7 BP 913 EP 927 AR e94 DI 10.1371/journal.ppat.0030094 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196VY UT WOS:000248511600007 PM 17616974 ER PT J AU Sevick, MA Napolitano, MA Papandonatos, GD Gordon, AJ Reiser, LM Marcus, BH AF Sevick, Mary Ann Napolitano, Melissa A. Papandonatos, George D. Gordon, Adam J. Reiser, Lorraine M. Marcus, Bess H. TI Cost-effectiveness of alternative approaches for motivating activity in sedentary adults: Results of Project STRIDE SO PREVENTIVE MEDICINE LA English DT Article DE economics; exercise; health promotion; physical fitness; primary prevention; randomized controlled trials ID PHYSICAL-ACTIVITY PROMOTION; PRIMARY-CARE; ACTIVITY INTERVENTION; RECOMMENDATION; RATIONALE; TELEPHONE; URBAN; MEN AB Objective. To evaluate the cost-effectiveness of non-face-to-face interventions for increasing physical activity in sedentary adults. The took place in Providence, Rhode Island between the years 2000 and 2004. Methods. Two hundred and thirty-nine participants were randomized to Phone, Print or a contact control. Phone and Print groups were regular surveys regarding their level of physical activity, motivational readiness and self-efficacy. Surveys were scanned by a computer system to generate feedback reports. Phone group participants received feedback by telephone. Print group participants received feedback by The contact control group received mailings unrelated to physical activity. Intervention costs were assessed prospectively, from a payer Physical activity was measured using the 7-day Physical Activity Recall. Ambulatory health service use was assessed via monthly surveys. Results. The Print intervention was more economically efficient than the Phone intervention in engaging participants in a more active Conclusion. The Print intervention provides an efficient approach to increasing physical activity. Research is needed to determine the effectiveness of the intervention in a more diverse population, within the context of the health service delivery system and over a longer period time. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Miriam Hosp, Providence, RI 02906 USA. Brown Med Sch, Providence, RI USA. Carlow Univ, Pittsburgh, PA USA. RP Sevick, MA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Suite 600,230 McKee Pl, Pittsburgh, PA 15213 USA. EM sevick@pitt.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X FU NHLBI NIH HHS [HL64342, R01 HL064342, R01 HL064342-01A1] NR 29 TC 35 Z9 36 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2007 VL 45 IS 1 BP 54 EP 61 DI 10.1016/j.ypmed.2007.04.008 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 196GH UT WOS:000248469200012 PM 17573103 ER PT J AU Klyushnenkova, EN Kouiavskaia, DV Kodak, JA Vandenbark, AA Alexander, RB AF Klyushnenkova, Elena N. Kouiavskaia, Diana V. Kodak, James A. Vandenbark, Arthur A. Alexander, Richard B. TI Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase SO PROSTATE LA English DT Article DE CD4 T lymphocytes; DR2 transgenic mice; HLA-DR15; prostate cancer; prostatitis ID I CLINICAL-TRIAL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; ANTIGEN-PRESENTING CELLS; CANCER-PATIENTS; GRANULOMATOUS PROSTATITIS; DENDRITIC CELLS; TRANSGENIC MICE; SELF-ANTIGEN; PEPTIDE AB BACKGROUND. The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. METHODS. We immunized transgenic (tg) mice engineered to express HLA-DRB1 *1501 with human PAP. A library of overlapping 20-mer pepticles spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. RESULTS. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1 *1501 -positive patients with GP and normal donors. CONCLUSIONS. These peptides can be used for the design of a new generation of peptidebased vaccines against prostate cancer. The study can also be helpful in understanding the role of autoirnmunity in the development of some forms of chronic prostatitis. C1 Univ Maryland, Sch Med, Div Urol, Baltimore, MD 21201 USA. VA Maryland Hlth Care Syst, Baltimore, MD USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neuroimmunol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Mol & Microbiol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Immunol, Portland, OR 97201 USA. RP Klyushnenkova, EN (reprint author), Univ Maryland, Sch Med, Dept Surg, 10 S Pine St MSTF,Room 4-00A, Baltimore, MD 21201 USA. EM eklyushnenkova@smail.umaryland.edu NR 49 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUL 1 PY 2007 VL 67 IS 10 BP 1019 EP 1028 DI 10.1002/pros.20575 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 180KU UT WOS:000247362800002 PM 17455230 ER PT J AU Laudi, S Steudel, W Jonscher, K Schoning, W Schniedewind, B Kaisers, U Christians, U Trump, S AF Laudi, Sven Steudel, Wolfgang Jonscher, Karen Schoening, Wenzel Schniedewind, Bjoern Kaisers, Udo Christians, Uwe Trump, Saskia TI Comparison of lung proteome profiles in two rodent models of pulmonary arterial hypertension SO PROTEOMICS LA English DT Article DE hypoxia; monocrotaline; protein expression analysis; pulmonary arterial hypertension ID SMOOTH-MUSCLE-CELLS; CHLORIDE-ION CHANNEL; ENDOTHELIAL-CELLS; MONOCROTALINE PYRROLE; GROWTH-FACTOR; TRYPTOPHAN 5-MONOOXYGENASE; BILIVERDIN REDUCTASE; HEME OXYGENASE-1; HYPOXIA; RAT AB We studied the lung proteome changes in two widely used models of pulmonary arterial hypertension (PAH): monocrotaline (MCT) injection and chronic hypoxia (CH); untreated rats were used as controls (n = 6/group). After 28 days, invasive right ventricular systolic pressure (RVSP) was measured. Lungs were immunostained for alpha-smooth muscle actin (alpha SMA). 2-DE (n = 4/group) followed by nano-LC-MS/MS was applied for protein identification. Western blotting was used additionally if possible. RVSP was significantly increased in MCT- and CH-rats (MCT 62.5 +/- 4.4 mmHg, CH 62.2 +/- 4.1 mmHg, control 25.0 +/- 1.7 mmHg, p<0.001). This was associated with an increase of alpha SMA positive vessels. In both groups, there was a significantly increased expression of proteins associated with the contractile apparatus (diphosphoHsp27 (p<0.001), Septin2 (p<0.001), F-actin capping protein (p<0.01), and tropomyosin beta (p<0.02)). In CH, proteins of the nitric oxide (Hsc70; p = 0.002), carbon monoxide (biliverdin reductase; p = 0.005), and vascular endothelial growth factor (VEGF) pathway (annexin 3; p<0.001) were significantly increased. In MCT, proteins involved in serotonin synthesis (14-3-3; p = 0.02), the enhanced unfolded protein response (ERp57; p = 0.02), and intracellular chloride channels (CLIC 1; p = 0.002) were significantly elevated. Therefore, MCT- and CH-induced vasoconstriction and remodeling seemed to be mediated via different signaling pathways. These differences should be considered in future studies using either PAH model. C1 Univ Leipzig, Fac Med, Dept Anesthesiol & Intens Care Med, D-04103 Leipzig, Germany. Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol, Clin Res & Dev, Denver, CO 80202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Laudi, S (reprint author), Univ Leipzig, Fac Med, Dept Anesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany. EM sven.laudi@medizin.uni-leipzig.de FU NIDDK NIH HHS [P30DK048520] NR 61 TC 25 Z9 26 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JUL PY 2007 VL 7 IS 14 BP 2469 EP 2478 DI 10.1002/pmic.200600848 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194SB UT WOS:000248363000016 PM 17623304 ER PT J AU Ehman, RL Hendee, WR Welch, MJ Dunnick, NR Bresolin, LB Arenson, RL Baum, S Hricak, H Thrall, JH AF Ehman, Richard L. Hendee, William R. Welch, Michael J. Dunnick, N. Reed Bresolin, Linda B. Arenson, Ronald L. Baum, Stanley Hricak, Hedvig Thrall, James H. TI Blueprint for imaging in biomedical research SO RADIOLOGY LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; INTRAOPERATIVE 3D ULTRASOUND; GREEN FLUORESCENT PROTEIN; MAGNETIC-RESONANCE; PHOTOACOUSTIC TOMOGRAPHY; CLINICAL-APPLICATIONS; RADIONUCLIDE THERAPY; SIGNAL-TRANSDUCTION; INVERSION ALGORITHM; ALZHEIMERS-DISEASE C1 Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55902 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI USA. Radiol Soc N Amer, Oak Brook, IL USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ehman, RL (reprint author), Mayo Clin & Mayo Fdn, Dept Radiol, 200 1st St SW, Rochester, MN 55902 USA. EM ehman.richard@mayo.edu OI Hricak, Hedvig/0000-0003-2240-9694 NR 177 TC 16 Z9 18 U1 1 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 JUL PY 2007 VL 244 IS 1 BP 12 EP 27 DI 10.1148/radiol.2441070058 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 181KV UT WOS:000247436500002 PM 17507725 ER PT J AU Saam, T Hatsukami, TS Takaya, N Chu, BC Underhill, H Kerwin, WS Cai, JM Ferguson, MS Yuan, C AF Saam, Tobias Hatsukami, Thomas S. Takaya, Norihide Chu, Baocheng Underhill, Hunter Kerwin, William S. Cai, Jianming Ferguson, Marina S. Yuan, Chun TI The vulnerable, or high-risk, atherosclerotic plaque: Noninvasive MR imaging for characterization and assessment SO RADIOLOGY LA English DT Review ID MAGNETIC-RESONANCE ANGIOGRAPHY; CORONARY-ARTERY-DISEASE; CONTRAST-ENHANCED MR; HIGH-RESOLUTION MRI; ACUTE MYOCARDIAL-INFARCTION; INTERNAL CAROTID-ARTERY; IN-VIVO ACCURACY; FIBROUS CAP; ENDOTHELIAL DYSFUNCTION; INTRAPLAQUE HEMORRHAGE AB "Vulnerable" plaques are atherosclerotic plaques that have a high likelihood to cause thrombotic complications, such as myocardial infarction or stroke. Plaques that tend to progress rapidly are also considered to be vulnerable. Besides luminal stenosis, plaque composition and morphology are key determinants of the likelihood that a plaque will cause cardiovascular events. Noninvasive magnetic resonance ( MR) imaging has great potential to enable characterization of atherosclerotic plaque composition and morphology and thus to help assess plaque vulnerability. A classification for clinical, as well as pathologic, evaluation of vulnerable plaques was recently put forward in which five major and five minor criteria to define vulnerable plaques were proposed. The purpose of this review is to summarize the status of MR imaging with regard to depiction of the criteria that define vulnerable plaques by using existing MR techniques. The use of MR imaging in animal models and in human disease in various vascular beds, particularly the carotid arteries, is presented. (c) RSNA, 2007. C1 Univ Washington, Dept Radiol, Seattle, WA USA. Univ Washington, Dept Surg, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. RP Saam, T (reprint author), Univ Munich, Dept Clin Radiol, Marchioninistr 15,Grosshadern Campus, D-81377 Munich, Germany. EM Tobias_Saam@med.uni-muenchen.de NR 106 TC 182 Z9 199 U1 0 U2 19 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 JUL PY 2007 VL 244 IS 1 BP 64 EP 77 DI 10.1148/radiol.2441051769 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 181KV UT WOS:000247436500007 PM 17581895 ER PT J AU Alencar, H Funovics, MA Figueiredo, J Sawaya, H Weissleder, R Mahmood, U AF Alencar, Herlen Funovics, Martin A. Figueiredo, Jose Sawaya, Heloisa Weissleder, Ralph Mahmood, Umar TI Colonic adenocarcinomas: Near-infrared microcatheter imaging of smart probes for early detection - Study in mice SO RADIOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 28-DEC 03, 2004 CL Chicago, IL SP Radiol Soc N Amer ID MAGNIFICATION-CHROMOSCOPIC COLONOSCOPY; SERVICES TASK-FORCE; COLORECTAL-CANCER; CATHEPSIN-B; GENE-EXPRESSION; ENZYME-ACTIVITY; MOUSE MODEL; MISS RATES; FEASIBILITY; DISEASE AB Purpose: To prospectively evaluate the ability of micro-fiberoptic catheters, which simultaneously record white light and near-infrared (NIR) images, to reveal colonic neoplasms after the intravenous administration of activatable " smart" probes that increase in NIR fluorescence subsequent to protease activation. Materials and Methods: The institutional animal care committee approved all animal experiments. CT26 tumor cells were orthotopically implanted into the descending colon of C57BL6/ J mice (n = 10). Thirteen days later, mice intravenously received either 2 nmol of a protease-sensing probe that had cathepsin B as a major activator (n = 5) or saline (control animals [ n = 5]). One day later, animals were noninvasively examined to the point of the splenic flexure by using microcatheter imaging. Excised colons were subsequently evaluated with epifluorescence imaging, histologic examination, and cathepsin B immunohistochemistry. Student t test was used for statistical analysis, with P < .05 considered to indicate a significant difference. Results: Results with fiberoptic imaging demonstrated that all tumors were visible with the protease- activatable probe, even when they were not readily apparent at white light imaging. A target-to-background ratio (TBR) of 8.86 for tumor to adjacent normal mucosa was achieved in the NIR channel after probe administration ( P = .001), whereas white light images resulted in a TBR of 1.14 ( P > .5) based on luminosity. The tumoral NIR fluorescence intensity was more than 30-fold greater in probe- injected animals than in control animals, indicating that essentially all of the signal recorded in lesions was from activatable probe administration. Results of immunohistochemistry confirmed cathepsin B overexpression in the tumor compared with adjacent mucosa. Conclusion: The use of NIR imaging microcatheters combined with protease-activatable smart probes results in a beacon effect that highlights tumors with high TBRs; this technique thus may be a potentially useful adjunct to white light colonoscopy in the future. (c) RSNA, 2007. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5408, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [R24 CA92782]; NIBIB NIH HHS [R01 EB001872] NR 28 TC 71 Z9 75 U1 0 U2 6 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 JUL PY 2007 VL 244 IS 1 BP 232 EP 238 DI 10.1148/radiol.2441052114 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 181KV UT WOS:000247436500026 PM 17507718 ER PT J AU Fritz, LB Ouellette, HA O'Hanley, TA Kassarjian, A Palmer, WE AF Fritz, L. Benjamin Ouellette, Hugue A. O'Hanley, Tara A. Kassarjian, Ara Palmer, William E. TI Cystic changes at supraspinatus and infraspinatus tendon insertion sites: Association with age and rotator cuff disorders in 238 patients SO RADIOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 28-DEC 03, 2004 CL Chicago, IL SP Radiol Soc N Amer ID GREATER TUBEROSITY; SHOULDER; TEARS; RADIOGRAPHY; DIAGNOSIS; DISEASE; JOINT; US AB Purpose: To retrospectively determine the frequency of posterior and anterior cystic abnormalities at rotator cuff insertion site on the greater tuberosity and to determine their relationship to patient age and rotator cuff disorders. Materials and Methods: Institutional review board approval was given; informed consent was waived. The study was HIPAA compliant. In 238 patients with rotator cuff diagnoses at surgery, preoperative magnetic resonance ( MR) imaging studies were reviewed to localize osseous cystic changes as anterior ( supraspinatus insertion site) or posterior (infraspinatus insertion site) on the greater tuberosity. If rotator cuff tear was present, tendon retraction and location of partial tear ( articular or bursal surface) were recorded. Two radiologists reached conclusions by consensus. Locations of cysts were correlated to surgical cuff diagnoses: no tear, tendinopathy, partial- thickness tear, and complete tear. Prospective interpretations from original MR reports were compared with surgical results. Statistical analyses included one- way analysis of variance, X-2, Fisher exact, and Student t tests, as well as logistic regression and receiver operating characteristic curve comparison. Results: There were 238 consecutive patients ( 150 men, 88 women; mean age, 43 years). Cysts were located at or near footprint of cuff tendon and demonstrated fluid or soft- tissue signal intensities. Posterior cysts occurred in 56.7% of shoulders and showed no statistical correlation to age or cuff diagnosis. Anterior cysts occurred in 22.7% of shoulders and were strongly associated with cuff disorders ( P < .001). Controlling for cuff disorders, there was no relationship between anterior cysts and age ( P > .50). Anterior cysts were more common in partial- thickness articular ( 48%) than in bursal ( 13%) tears ( P < .001). Conclusion: Posterior cysts were more common than anterior cysts and showed nearly random distribution among patients, regardless of age and cuff diagnosis. Anterior cysts were closely associated with cuff disorders. (c) RSNA, 2007. C1 Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, 55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM palmer.william@mgh.harvard.edu NR 24 TC 22 Z9 25 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2007 VL 244 IS 1 BP 239 EP 248 DI 10.1148/radiol.2441050029 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 181KV UT WOS:000247436500027 PM 17581904 ER PT J AU Hess, DR AF Hess, Dean R. TI The 22nd annual new horizons symposium: Clinical respiratory pharmacology - Foreword SO RESPIRATORY CARE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Cardiol Dept, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Cardiol Dept, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUL PY 2007 VL 52 IS 7 BP 819 EP 819 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 187HU UT WOS:000247839100001 ER PT J AU Bartzokis, G Lu, PH Nuechterlein, KH Gitlin, M Doi, C Edwards, N Lieu, C Altshuler, LL Mintz, J AF Bartzokis, George Lu, Po H. Nuechterlein, Keith H. Gitlin, Michael Doi, Clarissa Edwards, Nancy Lieu, Christopher Altshuler, Lori L. Mintz, Jim TI Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat DE schizophrenia; antipsychotic; medication; typical; atypical; frontal lobe; myelin; white matter; gray matter; oligodendrocyte; trajectory; development; lipid; intracortical; age; treatment; prevention; human; primate ID MAJOR DEPRESSIVE DISORDER; INCREASES CELL-PROLIFERATION; RAT FRONTAL-CORTEX; WHITE-MATTER; PREFRONTAL CORTEX; BIPOLAR DISORDER; GRAY-MATTER; ADULT-RAT; HIPPOCAMPAL-FORMATION; MORPHOMETRIC ANALYSIS AB Context: Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination even in adulthood. Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia. Objective: To test the a priori hypothesis that antipsychotic medications may differentially impact frontal lobe myelination in patients with schizophrenia. Design, setting, and participants: Participants ranged in age from 18-35 years, were all male, and were recruited by a single group of investigators using the same criteria. Two cohorts of subjects with schizophrenia early in their disease who were treated either with oral risperidone (Ris) or fluphenazine decanoate (Fd) were imaged in conjunction with cohorts of healthy controls. Each cohort was imaged using a different MRI instrument using identical imaging sequences. Main outcome measure: MRI measures of frontal lobe white matter volume. Results: We estimated differences due to differences in the MRI instruments used in the two studies in the two healthy control groups matched to the patient samples, adjusting for age and other covariates. We then statistically removed those differences (which we assumed were due to instrument effects) from the data in the schizophrenia samples by subtraction. Relative to the differences seen in controls, the two groups of schizophrenic patients differed in their pattern of frontal lobe structure with the Ris-treated group having significantly larger white matter volume than the Fd group. Conclusions: The results suggest that the choice of antipsychotic treatment may differentially impact brain myelination in adults with schizophrenia. Prospective studies are needed to confirm this finding. MRI can be used to dissect subtle differences in brain tissue characteristics and thus could help clarify the effect of pharmacologic treatments on neurodevelopmental and pathologic processes in vivo. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuroimaging,Div Brain Mapping, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NCRR NIH HHS [U54 RR021813]; NIA NIH HHS [P50 AG 16570, P50 AG016570]; NIMH NIH HHS [R01 MH037705-09S1, MH066029-01A2, MH37705, MH51928, MH6357-01A1, P50 MH066286, R01 MH037705, R01 MH066029] NR 88 TC 50 Z9 51 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2007 VL 93 IS 1-3 BP 13 EP 22 DI 10.1016/j.schres.2007.02.011 PG 10 WC Psychiatry SC Psychiatry GA 184SU UT WOS:000247663200002 PM 17407804 ER PT J AU Risch, SC Horner, MD McGurk, SR Palecko, S Markowitz, JS Nahas, Z DeVane, CL AF Risch, S. Craig Horner, Michael D. McGurk, Susan R. Palecko, Simmy Markowitz, John S. Nahas, Ziad DeVane, C. Lindsay TI Double-blind donepezil-placebo crossover augmentation study of atypical antipsychotics in chronic, stable schizophrenia: A pilot study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; cholinesterase inhibitors; pharmacological augmentation ID ADJUNCTIVE DONEPEZIL; COGNITIVE IMPAIRMENT; NICOTINIC RECEPTORS; ALZHEIMERS-DISEASE; DEMENTIA; DEFICITS; GALANTAMINE; TRIAL; SCALE; RIVASTIGMINE AB Thirteen outpatients with chronic but stable schizophrenia received donepezil and placebo augmentation of their maintenance antipsychotic medication regimen. Each subject received in a randomized, counterbalanced order 1) donepezil 5 mg for 6 weeks then donepezil 10 mg for six weeks and 2) placebo donepezil for 12 weeks. Serial ratings of the Positive and Negative Symptom Scale (PANSS) [Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13(2): 261-276] were performed by a trained rater blind to the donepezil order and condition: at baseline, 12 weeks and 24 weeks. On donepezil as compared to baseline or placebo, there was a significant improvement in PANSS negative scores (p = .018, n = 13). These results are discussed with respect to other studies using cholinesterase inhibitors as an augmentation strategy in schizophrenia. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Risch, SC (reprint author), Univ Calif San Francisco, Langley Porter Psychiat Inst, Room 375,Box F-0984,401 Parnassus Ave, San Francisco, CA 94143 USA. EM craigr@lppi.ucsf.edu NR 36 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2007 VL 93 IS 1-3 BP 131 EP 135 DI 10.1016/j.schres.2007.01.001 PG 5 WC Psychiatry SC Psychiatry GA 184SU UT WOS:000247663200014 PM 17391930 ER PT J AU Gard, DE Kring, AM Gard, MG Horan, WP Green, MF AF Gard, David E. Kring, Ann M. Gard, Marja Germans Horan, William P. Green, Michael F. TI Anhedonia in schizophrenia: Distinctions between anticipatory and consummatory pleasure SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-for-Research-in-Psychopathology CY OCT, 2003 CL Toronto, CANADA SP Soc Res Psychopathol DE schizophrenia; pleasure; anhedonia; anticipation; consummatory; TEPS ID STRIATAL REWARD PREDICTION; DYSFUNCTION; EXPERIENCE; COMPONENTS; DOPAMINE; EMOTION; SCALE AB Research on anhedonia in schizophrenia has revealed mixed results, with patients reporting greater anhedonia than healthy controls on self-report measures and semi-structured interviews, but also reporting comparable experiences of positive emotions in response to pleasurable stimuli. Basic science points to the importance of distinguishing between anticipatory and consummatory (or in-the-moment) pleasure experiences, and this distinction may help to reconcile the mixed findings on anhedonia in schizophrenia. In two studies, we tested the hypothesis that anhedonia in schizophrenia reflects a deficit in anticipatory pleasure but not consummatory pleasure. In Study 1, we used experience sampling methodology to assess reported experiences of consummatory, and anticipated pleasure among schizophrenia patients and controls. In Study 2, schizophrenia patients and controls completed a self-report trait measure of anticipatory and consummatory pleasure and interviews that assessed negative symptoms, including anhedonia, and community functioning. In both studies, we found evidence for an anticipatory but not a consummatory pleasure deficit in schizophrenia. In addition, anticipatory pleasure was related to clinical ratings of anhedonia and functional outcome. Clinical and research implications of these findings are discussed. (c) 2007 Elsevier B.V. All rights reserved. C1 San Francisco State Univ, Dept Psychol, San Francisco, CA 94132 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Gard, DE (reprint author), San Francisco State Univ, Dept Psychol, 1600 Holloway Ave, San Francisco, CA 94132 USA. EM dgard@sfsu.edu; akring@berkeley.edu OI Gard, David/0000-0002-0446-4000 FU NIMH NIH HHS [MH43292, MH65707, R01 MH043292, R01 MH043292-16, R01 MH065707, R01 MH065707-05] NR 38 TC 320 Z9 325 U1 4 U2 49 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2007 VL 93 IS 1-3 BP 253 EP 260 DI 10.1016/j.schres.2007.03.008 PG 8 WC Psychiatry SC Psychiatry GA 184SU UT WOS:000247663200029 PM 17490858 ER PT J AU Hazlett, EA Romero, MJ Haznedar, MM New, AS Goldstein, KE Newmark, RE Siever, LJ Buchsbaum, MS AF Hazlett, Erin A. Romero, Michelle J. Haznedar, M. Mehmet New, Antonia S. Goldstein, Kim E. Newmark, Randall E. Siever, Larry J. Buchsbaum, Monte S. TI Deficient attentional modulation of startle eyeblink is associated with symptom severity in the schizophrenia spectrum SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; schizotypal personality disorder; startle; attention; prepulse inhibition; prepulse facilitation ID SCHIZOTYPAL PERSONALITY-DISORDER; PREPULSE INHIBITION; ACOUSTIC STARTLE; REFLEX; PERSPECTIVES; HABITUATION AB Patients with schizophrenia-spectrum disorders show deficient prepulse inhibition (PPI) of the startle eyeblink reflex which is thought to reflect an early stage of information processing called automatic sensorimotor gating. They also exhibit deficient attentional modulation of PPI and prepulse facilitation (PPF) of startle which is thought to reflect deficient early and later controlled attentional processing. This is the first study to assess attentional modulation of PPI and PPF in a 3-group schizophrenia-spectrum sample of age- and sex-matched unmedicated schizotypal personality disorder (SPD) and schizophrenia patients, and healthy controls. Participants performed a tone-length judgment task involving attended, ignored, and novel tone prepulses while the acoustic startle eyeblink reflex was measured. Healthy controls showed greater PPI and PPF during the attended prepulses compared with the ignored prepulses. In contrast, both the SPD and schizophrenia patient groups failed to show this pattern, indicating deficient early and later controlled attentional processing. These findings suggest abnormal attentional modulation of PPI and PPF may be a trait-like feature found in patients with schizophrenia-spectrum disorders. Among the schizophrenia-spectrum sample, more deficient PPI during the attended prepulses was associated with greater symptom severity as measured by the total 18-item Brief Psychiatric Rating Scale score. (c) 2007 Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. EM erin.hazlett@mssm.edu NR 28 TC 28 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2007 VL 93 IS 1-3 BP 288 EP 295 DI 10.1016/j.schres.2007.03.012 PG 8 WC Psychiatry SC Psychiatry GA 184SU UT WOS:000247663200033 PM 17478083 ER PT J AU Fishman, JA AF Fishman, Jay A. TI Infection in renal transplant recipients SO SEMINARS IN NEPHROLOGY LA English DT Review DE renal transplantation; opportunistic infection; virus; fungus; immunosuppression; donor-derived infection; prophylaxis ID SOLID-ORGAN TRANSPLANTATION; POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; CLINICAL-PRACTICE GUIDELINES; CYTOMEGALOVIRUS-INFECTION; PNEUMOCYSTIS-CARINII; CADAVER DONOR; BK VIRUS; T-CELLS; DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH Transplant Ctr,Infect Dis Div, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH Transplant Ctr,Infect Dis Div, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 50 TC 30 Z9 33 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JUL PY 2007 VL 27 IS 4 BP 445 EP 461 DI 10.1016/j.semnephrol.2007.03.006 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA 192MP UT WOS:000248206400007 PM 17616276 ER PT J AU Ng, AK AF Ng, Andrea K. TI Diffuse large B-cell lymphoma SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; 3-WEEKLY CHOP CHEMOTHERAPY; DETUDE-DES-LYMPHOMES; ELDERLY-PATIENTS; AGGRESSIVE LYMPHOMA; PLUS RADIOTHERAPY; R-CHOP; MALIGNANT-LYMPHOMAS C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Ng, AK (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 46 TC 21 Z9 23 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2007 VL 17 IS 3 BP 169 EP 175 DI 10.1016/j.semradonc.2007.02.002 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 187GF UT WOS:000247834900003 PM 17591563 ER PT J AU Tsai, HK Mauch, PM AF Tsai, Henry K. Mauch, Peter M. TI Nodular lymphocyte-predominant Hodgkin lymphoma SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID INVOLVED FIELD RADIOTHERAPY; DOSE LOCAL RADIOTHERAPY; CLINICAL PRESENTATION; PHASE-2 TRIAL; DISEASE; RADIATION; PARAGRANULOMA; RITUXIMAB; PATHOLOGY; SUBTYPES C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mauch, PM (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 33 TC 18 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2007 VL 17 IS 3 BP 184 EP 189 DI 10.1016/j.semradonc.2007.02.004 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 187GF UT WOS:000247834900005 PM 17591565 ER PT J AU Beland, M Mueller, PR Gervais, DA AF Beland, Michael Mueller, Peter R. Gervais, Debra A. TI Thermal ablation in interventional oncology SO SEMINARS IN ROENTGENOLOGY LA English DT Review ID INTENSITY FOCUSED ULTRASOUND; PERCUTANEOUS RADIOFREQUENCY ABLATION; SMALL RENAL TUMORS; METASTASES INVOLVING BONE; RADIO-FREQUENCY ABLATION; LIVER-TUMORS; MICROWAVE ABLATION; TISSUE ABLATION; COLORECTAL-CANCER; OSTEOID OSTEOMA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, White 270,34 Fruit St, Boston, MA 02114 USA. EM dgervais@partners.org NR 103 TC 9 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2007 VL 42 IS 3 BP 175 EP 190 DI 10.1053/j.ro.2007.04.005 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189ZN UT WOS:000248027600005 PM 17599551 ER PT J AU Torriani, M AF Torriani, Martin TI Measuring muscle lipids with 1H-MR spectroscopy SO SKELETAL RADIOLOGY LA English DT Editorial Material ID SKELETAL-MUSCLE; MR SPECTROSCOPY; QUANTIFICATION; HUMANS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu NR 9 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUL PY 2007 VL 36 IS 7 BP 607 EP 608 DI 10.1007/s00256-006-0252-8 PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 171YA UT WOS:000246770100001 PM 17219228 ER PT J AU Peteet, J AF Peteet, John TI Suicide and spirituality: A clinical perspective SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID DEPRESSION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peteet, J (reprint author), Dana Farber Canc Inst, 44 Binney St,Gossman 411, Boston, MA 02115 USA. EM John_Peteet@dfci.harvard.edu NR 15 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUL PY 2007 VL 100 IS 7 BP 752 EP 754 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 189JY UT WOS:000247986400030 PM 17639769 ER PT J AU Santen, RJ Demers, L Ohorodnik, S Settlage, J Langecker, P Blanchett, D Goss, PE Wang, S AF Santen, Richard J. Demers, Lawrence Ohorodnik, Susan Settlage, J. Langecker, Peter Blanchett, D. Goss, Paul E. Wang, Shuping TI Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy SO STEROIDS LA English DT Article DE estradiol; aromatase inhibitor; breast cancer; GC/tandem mass spectrometry ID BREAST-CANCER PATIENTS; RECOMBINANT CELL BIOASSAY; PLASMA ESTROGEN-LEVELS; POSTMENOPAUSAL WOMEN; PERIPHERAL AROMATIZATION; ULTRASENSITIVE BIOASSAY; LETROZOLE CGS-20267; PHASE-I; ANASTROZOLE; AMINOGLUTETHIMIDE AB Currently available radioimmunoassay methods for estradiol in serum lack sufficient sensitivity and precision to monitor estradiol levels in patients placed on third generation aromatase inhibitors. We recently validated a gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol and determined estrogen levels in normal post-menopausal women and in women with breast cancer before and during administration of aromatase inhibitors. Validation of the GC/MS/MS assay in human plasma and human serum included determination of assay sensitivity (< 0.63 pg/ml), precision (all CVs less than 17.8%), recovery (98-103%), and linearity of recovery (R = 0.998). Levels of estradiol were lower when assayed by GC/MS/MS compared to RIA under all conditions (7.26 +/- 4.82 pg/ml versus 11.9 + 12.0 pg/ml in normal post-menopausal women; 5.88 +/- 3.43 pg/ml versus 13.8 +/- 7.5 pg/ml in breast cancer patients prior to treatment; and < 0.63 pg/ml versus 5.8 +/- 4.1 pg/ml during aromatase inhibitor therapy). Fifty-five women treated either with atamestane/toremiphene or letrozole/placebo were monitored for estradiol levels at 4, 8 and 12 weeks of therapy. The mean levels of estradiol during aromatase inhibitor therapy was 5.8 +/- 4.1 pg/ml as measured by RIA and < 0.63 pg/ml by GC/MS/MS. The degree of suppression with the aromatase inhibitors as detected by RIA was 58% versus > 89% by GC/MS. These results suggest that most RIA methods detect cross-reacting estrogen metabolites and yield higher measured levels than GC/MS/MS. Several pharmacological and clinical considerations suggest that GC/MS/MS should become the preferred method for monitoring aromatase inhibitor therapy. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Virginia, Charlottesville, VA 22908 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Taylor Technol, Sparks, MD 21152 USA. Intarcia Therapeut Inc, Emeryville, CA USA. Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Santen, RJ (reprint author), Univ Virginia, POB 801416, Charlottesville, VA 22908 USA. EM rjs5Y@virginia.edu NR 39 TC 82 Z9 86 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X EI 1878-5867 J9 STEROIDS JI Steroids PD JUL PY 2007 VL 72 IS 8 BP 666 EP 671 DI 10.1016/j.steroids.2007.05.003 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 193SY UT WOS:000248296100007 PM 17588628 ER PT J AU Lev, MH AF Lev, Michael H. TI CT/NIHSS mismatch for detection of salvageable brain in acute stroke triage beyond the 3-hour time window - Overrated or undervalued? SO STROKE LA English DT Editorial Material DE brain imaging; brain infarction; brain ischemia; CT; diffusion-weighted imaging; mismatch; neuroradiology ID ACUTE ISCHEMIC-STROKE; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; CT PERFUSION; DIFFUSION; MRI; PENUMBRA; INFARCT; IDENTIFICATION; DESMOTEPLASE C1 Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Gray Bldg 241H,Fruit St, Boston, MA 02114 USA. EM mlev@partners.org NR 20 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2007 VL 38 IS 7 BP 2028 EP 2029 DI 10.1161/STROKEAHA.107.488379 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 182OG UT WOS:000247513300002 PM 17540959 ER PT J AU Schmid, A Duncan, PW Studenski, S Lai, SM Richards, L Perera, S Wu, SS AF Schmid, Arlene Duncan, Pamela W. Studenski, Stephanie Lai, Sue Min Richards, Lorie Perera, Subashan Wu, Samuel S. TI Improvements in speed-based gait classifications are meaningful SO STROKE LA English DT Article DE functional recovery; gait velocity; quality of life; rehabilitation ID STROKE IMPACT SCALE; COMMUNITY AMBULATION; REHABILITATION; RELIABILITY; EXERCISE; VELOCITY; TRIALS AB Background and Purpose - Gait velocity is a powerful indicator of function and prognosis after stroke. Gait velocity can be stratified into clinically meaningful functional ambulation classes, such as household ambulation (< 0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (> 0.8 m/ s). The purpose of the current study was to determine whether changes in velocity-based community ambulation classification were related to clinically meaningful changes in stroke-related function and quality of life. Methods - In subacute stroke survivors with mild to moderate deficits who participated in a randomized clinical trial of stroke rehabilitation and had a baseline gait velocity of 0.8 m/ s or less, we assessed the effect of success versus failure to achieve a transition to the next class on function and quality of life according to domains of the Stroke Impact Scale (SIS). Results - Of 64 eligible participants, 19 were initially household ambulators, and 12 of them (68%) transitioned to limited community ambulation, whereas of 45 initially limited community ambulators, 17 (38%) became full community ambulators. Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not. Among household ambulators, those who transitioned to limited or full community ambulation had significantly better SIS scores in mobility (P=0.0299) and participation (P=0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (P=0.0085). Conclusions - A gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators. Household ambulators possibly had more severe stroke deficits, reducing the risk of "ceiling" effects in SIS-measured activities of daily living and instrumental activities of daily living. Outcome assessment based on transitions within a mobility classification scheme that is rooted in gait velocity yields potentially meaningful indicators of clinical benefit. Outcomes should be selected that are clinically meaningful for all levels of severity. C1 Indiana Univ, Dept Occupat Therapy, Sch Hlth & Rehabil Sci, Indianapolis, IN 46202 USA. Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. Duke Univ, Dept Community & Family Med, Div Phys Therapy, Duke Ctr Clin Hlth Policy Res, Durham, NC USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Theo & Alfred London Ctr Aging, Kansas City, KS USA. Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Vet Affairs, Gainesville, FL 32611 USA. Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Occupat Therapy, Gainesville, FL 32611 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Florida, Coll Med, Div Biostat, Rehabil Outcomes Res Ctr, Gainesville, FL 32611 USA. RP Schmid, A (reprint author), Indiana Univ, Dept Occupat Therapy, Sch Hlth & Rehabil Sci, 1140 W Michigan St,CF 311, Indianapolis, IN 46202 USA. EM araschmi@iupui.edu FU NIA NIH HHS [5P60AG14635] NR 23 TC 203 Z9 212 U1 4 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2007 VL 38 IS 7 BP 2096 EP 2100 DI 10.1161/STROKEAHA.106.475921 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 182OG UT WOS:000247513300033 PM 17510461 ER PT J AU Rattner, DW Hawes, R AF Rattner, David W. Hawes, Robert TI What is NOSCAR? SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Chief Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Chief Div Gen & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. NR 2 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JUL PY 2007 VL 21 IS 7 BP 1045 EP 1046 DI 10.1007/s00464-007-9469-4 PG 2 WC Surgery SC Surgery GA 190TV UT WOS:000248084400001 PM 17576510 ER PT J AU Nguyen, TN Hoh, BL Amin-Hanjani, S Pryor, JC Ogilvy, CS AF Nguyen, Thanh N. Hoh, Brian L. Amin-Hanjani, Sepideh Pryor, Johnny C. Ogilvy, Christopher S. TI Comparison of ruptured vs unruptured aneurysms in recanalization after coil embolization SO SURGICAL NEUROLOGY LA English DT Article DE recanalization; coil compaction; endovascular therapy; intracranial aneurysm; ruptured aneurysm ID GUGLIELMI DETACHABLE COILS; INTRACRANIAL ANEURYSMS; ENDOVASCULAR TREATMENT; CEREBRAL ANEURYSMS; FOLLOW-UP; EXPERIENCE; OUTCOMES AB Background: Aneurysm recanalization is a significant problem in coil-treated intracranial aneurysms. We hypothesize ruptured aneurysms are more likely to demonstrate this phenomenon than unruptured aneurysms. Methods: This was a retrospective study over 4 years. Initial and follow-up angiography results were reviewed and aneurysm obliteration was classified: 1, complete; 11, residual neck; 111, residual aneurysm; and IV, partial treatment. Recanalization was classified as significant, mild, and none. Results: Two hundred twelve aneurysms were coiled in 199 patients, of which 180 patients survived to 6 months after treatment. Follow-up angiography (> 6 months) was available for 116 (64.4%) aneurysms (44 ruptured, 72 unruptured). Mean angiographic follow-up was 20 months. Recanalization was significant in 16 (13.8%) aneurysms, mild in 23 (19.8%), and absent in 87 (75%). Sixteen aneurysms underwent recoiling. Factors significant for recanalization by univariate analysis were ruptured vs unruptured (53.5% vs 22.5%; P =.001), larger aneurysm size (t test, P <.0001; median, 8-mm cut point, P <.01), aneurysm location (basilar tip and ICA terminus, P <.05), posterior circulation (P <.05), and younger age (t test, P <.05), whereas aneurysm neck size (4 mm) demonstrated a trend (P =.09). Incomplete initial aneurysm obliteration (II-IV, 20.6% vs 1, 4.3%; P <.05) was associated with significant recanalization. In multivariate analysis, younger age (age < 52 years; OR, 2.4; 95% Cl, 0.194-2.08), ruptured aneurysm (OR, 3.2; 95% Cl, 1.25-8.13), and larger aneurysm size (OR, 1.14; 95% Cl, 1.04-1.24 linearly; OR, 3.5; 95% Cl, 1.38-8.72) significantly predicted aneurysm recanalization. Performance of recoiling was significant with larger aneurysm size (OR, 2.0; 95% CI, 0.02-3.25) and younger age (age <52, OR, 2.4; 95% Cl, 0.34-3.3 1) by multivariate analysis, whereas ruptured aneurysm demonstrated a trend. Conclusions: In multivariate analyses, ruptured aneurysms, larger aneurysms, and younger patient age were significantly associated with recanalization. Larger aneurysms and younger age were significantly associated with recoiling. Published by Elsevier Inc. C1 Univ Florida, Coll Med, Dept Neurosurg & Radiol, Gainesville, FL 32611 USA. Univ Montreal, Ctr Hosp, Dept Radiol, Montreal, PQ H2L 4M1, Canada. Univ Illinois, Dept Neurosurg, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hoh, BL (reprint author), Univ Florida, Coll Med, Dept Neurosurg & Radiol, Gainesville, FL 32611 USA. EM brian.hoh@neurosurgery.ufl.edu NR 14 TC 44 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JUL PY 2007 VL 68 IS 1 BP 19 EP 23 DI 10.1016/j.surneu.2006.10.021 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 187DD UT WOS:000247826600005 PM 17586214 ER PT J AU Creaney, J Yeoman, D Naumoff, LK Hof, M Segal, A Musk, AW De Klerk, N Horick, N Skates, SJ Robinson, BWS AF Creaney, Jenette Yeoman, Deborah Naumoff, Leanne K. Hof, Michelle Segal, Amanda Musk, Arthur William De Klerk, Nicholas Horick, Nora Skates, Steven J. Robinson, Bruce W. S. TI Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma SO THORAX LA English DT Article ID PLEURAL EFFUSIONS; TUMOR-MARKERS; DIFFERENTIAL-DIAGNOSIS; FLUID; CEA; CYFRA-21-1; REGRESSION; ANTIGEN; CA-19-9; PROTEIN AB Background: The diagnosis of malignant mesothelioma is frequently difficult, the most common differential diagnosis being reactive pleural conditions and metastatic adenocarcinoma. Soluble mesothelin levels in serum have recently been shown to be highly specific and moderately sensitive for mesothelioma. As most patients with mesothelioma present with exudative effusions of either the pleura or the peritoneum, a study was undertaken to determine if levels of mesothelin were raised in these fluids and if the increased levels could help to distinguish mesothelioma from other causes of exudative effusion. Methods: Pleural fluid was collected from 192 patients who presented to respiratory clinics (52 with malignant mesothelioma, 56 with non-mesotheliomatous malignancies and 84 with effusions of nonneoplastic origin). Peritoneal fluid was collected from 42 patients (7 with mesothelioma, 14 with nonmesotheliomatous malignancies and 21 with benign effusions). Mesothelin levels were determined in effusion and serum samples by ELISA. Results: Significantly higher levels of mesothelin were found in effusions of patients with mesothelioma; with a specificity of 98%, the assay had a sensitivity of 67% comparing patients with mesothelioma and those with effusions of non-neoplastic origin. In 7 out of 10 cases mesothelin levels were raised in the effusion collected 3 weeks to 10 months before the diagnosis of mesothelioma was made; in 4 out of 8 of these, mesothelin levels were increased in the effusion but not in the serum. Conclusions: Measurement of mesothelin concentrations in the pleural and/or peritoneal effusion of patients may aid in the differential diagnosis of mesothelioma in patients presenting with effusions. C1 Univ Western Australia, Sir Charles Gairdner Hosp, Natl Res Ctr Asbestos Related Dis, Western Australian Inst Med Res, Nedlands, WA 6009, Australia. Sir Charles Gairdner Hosp, Australian Mesothelioma Tissue Bank, Perth, WA, Australia. Queen Elizabeth II Med Ctr, Path W Lab Med WA, Perth, WA, Australia. Sir Charles Gairdner Hosp, Dept Resp Med, Perth, WA, Australia. Massachusetts Gen Hosp, Harvard Med Sch, Australiabiostat Ctr, Telethon Inst Child Hlth Res, Boston, MA 02114 USA. RP Creaney, J (reprint author), Univ Western Australia, Sir Charles Gairdiner Hosp, Dept Med & Pharmacol, Verdun Ave, Nedlands, WA 6009, Australia. EM creaneyj@cyllene.uwa.edu.au RI Robinson, Bruce/N-1900-2014; de Klerk, Nicholas/D-8388-2016 OI de Klerk, Nicholas/0000-0001-9223-0767 NR 29 TC 71 Z9 74 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD JUL PY 2007 VL 62 IS 7 BP 569 EP 576 DI 10.1136/thx.2006.068114 PG 8 WC Respiratory System SC Respiratory System GA 184DH UT WOS:000247620800004 PM 17356060 ER PT J AU Glover, L Brown, RH AF Glover, Louise Brown, Robert H., Jr. TI Dysferlin in membrane trafficking and patch repair SO TRAFFIC LA English DT Review DE C2 domain; Ca2+-regulated exocytosis; membrane fusion; membrane repair; muscular dystrophy ID GIRDLE MUSCULAR-DYSTROPHY; CELL-SUBSTRATE INTERACTION; FIBROBLAST-GROWTH-FACTOR; MUSCLE SATELLITE CELLS; PLASMA-MEMBRANE; SKELETAL-MUSCLE; CA2+-REGULATED EXOCYTOSIS; NEUROTRANSMITTER RELEASE; GLYCOPROTEIN COMPLEX; GENE-EXPRESSION AB The muscular dystrophies are a heterogeneous group of inherited disorders, defined by progressive muscle weakness and atrophy. Following the discovery of dystrophin, remarkable progress has been made in defining the molecular properties of proteins involved in the various dystrophies. This has underlined the importance of the dystrophin-associated protein complex as a cell membrane scaffold, providing structural stability to muscle cells (McNeil PL, Khakee R. Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am J Pathol 1992;140:1097-1109). While the dystrophies linked to loss of function of dystrophin and its associated proteins are caused by diminished membrane integrity, it is now believed that a new class of dystrophies arises because of a diminished capacity for rapid muscle membrane repair after injury. Dysferlin is the first identified member of a putative muscle-specific repair complex that permits rapid resealing of membranes disrupted by mechanical stress. Membrane resealing is a function conserved by most cells and is mediated by a mechanism closely resembling regulated, Ca2+-dependent exocytosis. A primary role for dysferlin in this pathway, as a Ca2+-regulated fusogen, has been suggested, and a number of candidate partner proteins have been identified. This review outlines the current understanding of the role of dysferlin in membrane repair and the evolving picture of dysferlin-related signaling pathways in muscle cell physiology and pathology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Brown, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. EM rhbrown@partners.org FU NIAMS NIH HHS [5R21 AR053257-02]; NINDS NIH HHS [5P01 NS040828-05] NR 79 TC 80 Z9 87 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD JUL PY 2007 VL 8 IS 7 BP 785 EP 794 DI 10.1111/j.1600-0854.2007.00573.x PG 10 WC Cell Biology SC Cell Biology GA 181MM UT WOS:000247440800001 PM 17547707 ER PT J AU Perner, S Schmidt, FH Hofer, MD Kuefer, R Rubin, M AF Perner, S. Schmidt, F. H. Hofer, M. D. Kuefer, R. Rubin, M. TI TMPRSS2-ETS gene fusion in prostate cancer SO UROLOGE LA German DT Article DE TMPRSS2; ERG; ETS; gene fusion; prostate cancer ID OVEREXPRESSION; URINE AB Background. Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. Using a novel bioinformatics approach, our group recently described a novel gene fusion in PCa. This fusion involves the androgen-regulated gene TMPRSS2 and so far three members of the ETS family of transcription factors already described as rearranged in the Ewing's family of tumors. By analogy, fusion status in prostate cancer may determine clinical outcome and secondary genetic alterations as witnessed in Ewing's tumors. Material. These novel gene fusions occur in the majority of prostate cancers identified by PSA screening and are the driving mechanism for overexpression of the three members of the ETS transcription factor family, either ERG (21q22.3), ETV1 (7p21.2), or ETV4 (17q21). Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusion is the most common genetic aberration so far described in human malignancies. Results. So far, this is the only gene rearrangement in any of the most prevalent cancers. As confirmed by other groups, we demonstrated that, within the group of ETS transcription factors, ERG is the most common fusion partner of the ETS genes with TMPRSS2. This gene fusion is considered to be an early event in PCa development. Emerging data suggest that gene fusion PCa demonstrates a distinct clinical course and thus support its use as a diagnostic test and prognostic biomarker. Also similar to the Philadelphia chromosome in chronic myelogenous leukemia (CML), the gene fusion in prostate cancer has potential as an important candidate for the development of targeted therapy. C1 Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Ulm Klinikum, Abt Pathol, D-7900 Ulm, Germany. Univ Ulm Klinikum, Urol Univ Klin, D-7900 Ulm, Germany. Ctr Comprehens Canc, Ulm, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Cambridge, MA USA. RP Rubin, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC 442A, Boston, MA 02115 USA. EM marubin@partners.org NR 24 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1433-0563 J9 UROLOGE JI Urologe PD JUL PY 2007 VL 46 IS 7 BP 754 EP 760 DI 10.1007/s00120-007-1347-0 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 192SQ UT WOS:000248223700005 PM 17458530 ER PT J AU Porter, MP Lin, DW AF Porter, Michael P. Lin, Daniel W. TI Trends in renal cancer surgery and patient provider characteristics associated with partial nephrectomy in the United States SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE neoplasms; kidney; nephrectomy; trends ID CELL CARCINOMA; COMPLICATIONS; EPIDEMIOLOGY; EXPERIENCE AB Objective: Many renal tumors are amenable to either partial or total nephrectomy, but little is known about the relative frequency that these procedures are performed in the United States. We describe recent temporal trends in surgery for renal neoplasm and identified factors associated with partial nephrectomy. Methods: Data from the 1998 through 2002 National Inpatient Sample was analyzed to identify adult patients discharged after renal cancer surgery. The frequency of partial and total nephrectomy in the United States was estimated, and multivariate regression was used to examine patient and provider factors associated with partial nephrectomy. Results: The number of nephrectomies performed for tumor in the United States increased yearly, with an estimated 23,375 total nephrectomies and 4272 partial nephrectomies performed in 2002. The ratio of partial nephrectomies to total nephrectomies also increased (P < 0.001), with partial nephrectomy representing 15.5% of all nephrectomies in 2002. In the multivariate analysis, patient and provider factors significantly associated with undergoing partial nephrectomy included female sex (odds ratio [OR] = 0.86, 95% confidence interval [CI] 0.79-0.94), age (OR = 0.38, 95% CI 0.30-0.49 comparing age older than 79 to younger than 40 years), teaching hospital status (OR = 1.54, 95% CI 1.34-1.76), annual hospital nephrectomy volume (OR = 1.96, 95% CI 1.62-2.39 comparing highest to lowest quartiles), annual surgeon nephrectomy volume (OR = 2.60, 95% CI 2.12-3.20 comparing highest to lowest quartiles), and private insurance/health maintenance organization coverage (OR = 1.25, 95% CI 1.11-1.40 compared to Medicare). Conclusions: The total number of nephrectomies and the proportion of partial nephrectomies performed in the United States increased yearly from 1998 to 2002. Male sex, hospital teaching status, higher hospital and surgeon volume, and insurance status are associated with receiving partial nephrectomy. Published by Elsevier Inc. C1 Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Porter, MP (reprint author), Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM mporter@u.washington.edu NR 17 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 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2007 VL 25 IS 4 BP 298 EP 302 DI 10.1016/j.urolonc.2006.07.016 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 193TY UT WOS:000248299100004 PM 17628295 ER PT J AU Cozzi, E Sykes, M AF Cozzi, Emanuele Sykes, Megan TI Satellite Symposium held in conjunction with the World Transplant Congress, Boston, 2006 - Xenotransplantation - current standards for clinical trials SO XENOTRANSPLANTATION LA English DT Editorial Material ID PORCINE ENDOGENOUS RETROVIRUS; TO-PRIMATE XENOTRANSPLANTATION; PATHOGEN-FREE SWINE; LIVING PIG-TISSUE; HUMAN-CELLS; LYMPHOPROLIFERATIVE DISEASE; BABOON XENOTRANSPLANTATION; MINIATURE SWINE; CYTOMEGALOVIRUS; INFECTION C1 Univ Padua, Dept Med & Surg Sci, Clin Chirurg 3, I-35128 Padua, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Cozzi, E (reprint author), Univ Padua, Dept Med & Surg Sci, Clin Chirurg 3, Via Giustiniani 2, I-35128 Padua, Italy. EM emanuele.cozzi@unipd.it NR 76 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2007 VL 14 IS 4 BP 347 EP 359 DI 10.1111/j.1399-3089.2007.00407.x PG 13 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 201QI UT WOS:000248847300010 ER PT J AU Woo, CJ Kingston, RE AF Woo, Caroline J. Kingston, Robert E. TI HOTAIR lifts noncoding RNAs to new levels SO CELL LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; DEVELOPMENTAL REGULATORS; POLYCOMB; TRANSCRIPTION; TRITHORAX AB It is not clear to what extent noncoding RNAs regulate the homeobox (HOX) genes that encode key regulators of development in the embryo. In this issue, Rinn et al. (2007) characterize noncoding RNAs that regulate HOX genes and discover one, HOTAIR, that unexpectedly regulates a HOX gene cluster on a different chromosome than the HOX cluster that encodes it. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu NR 9 TC 52 Z9 56 U1 4 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 29 PY 2007 VL 129 IS 7 BP 1257 EP 1259 DI 10.1016/j.cell.2007.06.014 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188HQ UT WOS:000247911400012 PM 17604716 ER PT J AU Benn, CL Slow, EJ Farrell, LA Graham, R Deng, Y Hayden, MR Cha, JHJ AF Benn, C. L. Slow, E. J. Farrell, L. A. Graham, R. Deng, Y. Hayden, M. R. Cha, J.-H. J. TI Glutamate receptor abnormalities in the YAC128 transgenic mouse model of Huntington's disease SO NEUROSCIENCE LA English DT Article DE in situ hybridization; receptor binding; subcellular fractionation; preproenkephalin; NMDA receptor; AMPA receptor ID GENE-EXPRESSION CHANGES; MUTANT HUNTINGTIN; MESSENGER-RNA; NEUROTRANSMITTER RECEPTORS; MEDIATED EXCITOTOXICITY; QUINOLINIC ACID; NMDA RECEPTORS; SPINY NEURONS; MICE; POLYGLUTAMINE AB A yeast artificial chromosome (YAC) mouse model of Huntington's disease (YAC128) develops motor abnormalities, age-dependent striatal atrophy and neuronal loss. Alteration of neurotransmitter receptors, particularly glutamate and dopamine receptors, is a pathological hallmark of Huntington's disease. We therefore analyzed neurotransmitter receptors in symptomatic YAC128 Huntington's disease mice. We found significant increases in N-methyl-D-aspartate, AMPA and metabotropic glutamate receptor binding, which were not due to increases in receptor subunit mRNA expression levels. Subcellular fractionation analysis revealed increased levels of glutamate receptor subunits in synaptic membrane fractions from YAC128 mice. We found no changes in dopamine, GABA or adenosine receptor binding, nor did we see alterations in dopamine D1, D2 or adenosine A2a receptor mRNA levels. The receptor abnormalities in YAC128 transgenic mice thus appear limited to glutamate receptors. We also found a significant decrease in preproenkephalin mRNA in the striatum of YAC128 mice, which contrasts with the lack of change in levels of mRNA encoding neurotransmitter receptors. Taken together, the abnormal and selective increases in glutamate receptor subunit expression and binding are not due to increases in receptor subunit expression and may exert detrimental effects. The decrease in preproenkephalin mRNA suggests a selective transcriptional deficit, as opposed to neuronal loss, and could additionally contribute to the abnormal motor symptoms in YAC128 mice. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Univ British Columbia, Ctr Mol Med & Therapeut, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu RI Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU NIA NIH HHS [R37 AG013617-08, AG13617, R01 AG013617, R37 AG013617]; NINDS NIH HHS [NS38106, NS45242, P01 NS045242, P01 NS045242-010004, R01 NS038106, R01 NS038106-08] NR 43 TC 28 Z9 29 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN 29 PY 2007 VL 147 IS 2 BP 354 EP 372 DI 10.1016/j.neuroscience.2007.03.010 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 187NA UT WOS:000247853400011 PM 17544587 ER PT J AU Engelman, A AF Engelman, Alan TI AIDS/HIV - A reversal of fortune in HIV-1 integration SO SCIENCE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUBSTRATE; RECOMBINASE; EVOLUTION; STRATEGY; CELLS; LOXP; SITE; CRE C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu NR 13 TC 6 Z9 6 U1 0 U2 1 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 JUN 29 PY 2007 VL 316 IS 5833 BP 1855 EP 1857 DI 10.1126/science.1145015 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 183WI UT WOS:000247602700025 PM 17600205 ER PT J AU Frank, DA AF Frank, David A. TI STAT3 as a central mediator of neoplastic cellular transformation SO CANCER LETTERS LA English DT Review DE signal transduction; molecular oncology; protein phosphorylation; transcription factors; gene expression ID POTENT ANTITUMOR-ACTIVITY; EPIDERMAL-GROWTH-FACTOR; SIGNALING INDUCES APOPTOSIS; CYCLIN D1 OVEREXPRESSION; PROSTATE-CANCER CELLS; CONSTITUTIVE ACTIVATION; BREAST-CANCER; SERINE PHOSPHORYLATION; MULTIPLE-MYELOMA; LUNG-CANCER AB Much of the focus in understanding the molecular pathogenesis of tumors has centered on kinases that are activated in cancer. However, cancers driven by a diversity of activated kinases may have very similar pathological and clinical properties. This likely relates to the fact that the biological characteristics of a tumor are driven by the pattern of gene expression in that tumor, and that a wide spectrum of activating events at the cell surface and in the cytoplasm converge on a relatively small number of transcription factors that regulate the expression of key target genes. One transcription factor that has been found to be activated inappropriately in a wide range of human cancers is STAT3. STAT3 target genes are involved in fundamental events of tumor development including proliferation, survival, self-renewal, invasion, and angiogenesis. Furthermore, there is strong evidence that STAT3 is critical for these processes, in that inhibition of STAT3 by a variety of means can exert an anti-cancer effect. Since normal cells are relatively tolerant of interruption in STAT3 signaling, these findings suggest that STAT3 may also be an excellent target for the molecular therapy of cancer. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, Boston, MA 02115 USA. RP Frank, DA (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 72 TC 167 Z9 177 U1 2 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 28 PY 2007 VL 251 IS 2 BP 199 EP 210 DI 10.1016/j.canlet.2006.10.017 PG 12 WC Oncology SC Oncology GA 183CJ UT WOS:000247550000003 PM 17129668 ER PT J AU Cunningham, MJ Lin, DT Curry, WT Ebb, DH Yock, TI Curtin, HD Faquin, WC AF Cunningham, Michael J. Lin, Derrick T. Curry, William T., Jr. Ebb, David H. Yock, Torunn I. Curtin, Hugh D. Faquin, William C. TI A boy with a calcified mass in the nose - Olfactory neuroblastoma, grade 1 of 4, with extensive calcification and invasion of bone. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SINONASAL TRACT; ESTHESIONEUROBLASTOMA; TUMORS; RESECTION; NASAL; RADIOTHERAPY; IRRADIATION; METASTASES; EXPERIENCE; SURGERY C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 28 PY 2007 VL 356 IS 26 BP 2721 EP 2730 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500013 PM 17596608 ER PT J AU Greene, MF AF Greene, Michael F. TI Teratogenicity of SSRIs - Serious concern or much ado about little? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SEROTONIN REUPTAKE INHIBITORS; CONGENITAL-MALFORMATIONS; MATERNAL USE; PAROXETINE; RISK C1 Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. NR 8 TC 35 Z9 36 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 28 PY 2007 VL 356 IS 26 BP 2732 EP 2733 DI 10.1056/NEJMe078079 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500014 PM 17596609 ER PT J AU Mello, MM Joffe, S AF Mello, Michelle M. Joffe, Steven TI Compact versus contract - Industry sponsors' obligations to their research subjects SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CLINICAL-TRIAL AGREEMENTS; LITIGATION; ETHICS C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Mello, MM (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA96872] NR 23 TC 9 Z9 9 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 28 PY 2007 VL 356 IS 26 BP 2737 EP 2743 DI 10.1056/NEJMhle067499 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500016 PM 17596610 ER PT J AU Onnela, JP Saramaki, J Hyvonen, J Szabo, G de Menezes, MA Kaski, K Barabasi, AL Kertesz, J AF Onnela, Jukka-Pekka Saramaki, Jari Hyvonen, Jorkki Szabo, Gabor Argollo de Menezes, M. Kaski, Kimmo Barabasi, Albert-Laszlo Kertesz, Janos TI Analysis of a large-scale weighted network of one-to-one human communication SO NEW JOURNAL OF PHYSICS LA English DT Article ID COMPLEX NETWORKS; INTERNET; ATTACK; WEB AB We construct a connected network of 3.9 million nodes from mobile phone call records, which can be regarded as a proxy for the underlying human communication network at the societal level. We assign two weights on each edge to reflect the strength of social interaction, which are the aggregate call duration and the cumulative number of calls placed between the individuals over a period of 18 weeks. We present a detailed analysis of this weighted network by examining its degree, strength, and weight distributions, as well as its topological assortativity and weighted assortativity, clustering and weighted clustering, together with correlations between these quantities. We give an account of motif intensity and coherence distributions and compare them to a randomized reference system. We also use the concept of link overlap to measure the number of common neighbours any two adjacent nodes have, which serves as a useful local measure for identifying the interconnectedness of communities. We report a positive correlation between the overlap and weight of a link, thus providing strong quantitative evidence for the weak ties hypothesis, a central concept in social network analysis. The percolation properties of the network are found to depend on the type and order of removed links, and they can help understand how the local structure of the network manifests itself at the global level. We hope that our results will contribute to modelling weighted large-scale social networks, and believe that the systematic approach followed here can be adopted to study other weighted networks. C1 Aalto Univ, Lab Computat Engn, FIN-02150 Espoo, Finland. Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England. Univ Notre Dame, Dept Physdics, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Complex Networks Res, Notre Dame, IN 46556 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Budapest Univ Technol & Econ, Dept Theoret Phys, Budapest, Hungary. RP Onnela, JP (reprint author), Aalto Univ, Lab Computat Engn, FIN-02150 Espoo, Finland. EM kertesz@phy.bme.hu RI Kertesz, Janos/B-3411-2012; Kaski, Kimmo/G-8067-2012; Saramaki, Jari/E-5226-2011 NR 52 TC 140 Z9 146 U1 4 U2 45 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1367-2630 J9 NEW J PHYS JI New J. Phys. PD JUN 28 PY 2007 VL 9 AR 179 DI 10.1088/1367-2630/9/6/179 PG 27 WC Physics, Multidisciplinary SC Physics GA 188XO UT WOS:000247952800008 ER PT J AU Kim, M Qiao, ZS Yu, J Montefiori, D Reinherz, EL AF Kim, Mikyung Qiao, Zhisong Yu, Jessica Montefiori, David Reinherz, Ellis L. TI Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state SO VACCINE LA English DT Article DE HIV; gp41; MPER; immunogen; immunodominance; neutralizing antibody; 2F5; 4E10; virus-like particle; vaccine ID NEUTRALIZING ANTIBODY-RESPONSE; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; B-LYMPHOCYTE STIMULATOR; ENVELOPE GLYCOPROTEIN; HIV-1 GP41; MEMBRANE-FUSION; IN-VITRO; TRANSMEMBRANE GLYCOPROTEIN; IMMUNODOMINANT EPITOPE AB The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type I (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against immunogens bearing these epitopes. Given that structural and biochemical studies suggest that the lipid membrane of the virion is involved in their proper configuration, HIV-1 gp41 derivatives in a pre-fusion state were expressed on the surface of immature virus like particles (VLP) derived from Sf9 cells. Guinea pigs were immunized with three doses of VLPs or Sf9 cells presenting gp41 derivatives with or without E. coli heat-labile enterotoxin (LT) as an adjuvant. While immune sera contained high titer anti-VLP antibodies, the specific anti-gp41 antibody responses were low with no neutralizing antibodies detected. An explanation for this absence may be the low level of gp41 expression relative to the many other proteins derived from host cells which are incorporated onto the VLP surface. In addition, the anti-gp41 immune response was preferentially directed to the C-helical domain, away from the MPER. Future vaccine design needs to contend with the complexity of epitope display as well as immunodominance. (C) 2006 Elsevier Ltd. All fights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Lab Immunobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Duke Univ, Ctr Med, Dept Surg, Durham, NC 27710 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lab Immunobiol, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI 43649, P01 AI043649-05, P01 AI043649] NR 87 TC 46 Z9 46 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 28 PY 2007 VL 25 IS 27 BP 5102 EP 5114 DI 10.1016/j.vaccine.2006.09.071 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 188MM UT WOS:000247924000016 PM 17055621 ER PT J AU Freeman, JL Adeniyi, A Banerjee, R Dallaire, S Maguire, SF Chi, JX Ng, BL Zepeda, C Scott, CE Humphray, S Rogers, J Zhou, Y Zon, LI Carter, NP Yang, FT Lee, C AF Freeman, Jennifer L. Adeniyi, Adeola Banerjee, Ruby Dallaire, Stephanie Maguire, Sean F. Chi, Jianxiang Ng, Bee Ling Zepeda, Cinthya Scott, Carol E. Humphray, Sean Rogers, Jane Zhou, Yi Zon, Leonard I. Carter, Nigel P. Yang, Fengtang Lee, Charles TI Definition of the zebrafish genome using flow cytometry and cytogenetic mapping SO BMC GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; IN-SITU HYBRIDIZATION; RADIATION HYBRID MAP; RIBOSOMAL-RNA GENES; DANIO-RERIO; EXPRESSED SEQUENCES; CHROMOSOMES; RESOLUTION; LOCALIZATION; KARYOTYPE AB Background: The zebrafish ( Danio rerio) is an important vertebrate model organism system for biomedical research. The syntenic conservation between the zebrafish and human genome allows one to investigate the function of human genes using the zebrafish model. To facilitate analysis of the zebrafish genome, genetic maps have been constructed and sequence annotation of a reference zebrafish genome is ongoing. However, the duplicative nature of teleost genomes, including the zebrafish, complicates accurate assembly and annotation of a representative genome sequence. Cytogenetic approaches provide "anchors" that can be integrated with accumulating genomic data. Results: Here, we cytogenetically define the zebrafish genome by first estimating the size of each linkage group (LG) chromosome using flow cytometry, followed by the cytogenetic mapping of 575 bacterial artificial chromosome (BAC) clones onto metaphase chromosomes. Of the 575 BAC clones, 544 clones localized to apparently unique chromosomal locations. 93.8% of these clones were assigned to a specific LG chromosome location using fluorescence in situ hybridization (FISH) and compared to the LG chromosome assignment reported in the zebrafish genome databases. Thirty-one BAC clones localized to multiple chromosomal locations in several different hybridization patterns. From these data, a refined second generation probe panel for each LG chromosome was also constructed. Conclusion: The chromosomal mapping of the 575 large-insert DNA clones allows for these clones to be integrated into existing zebrafish mapping data. An accurately annotated zebrafish reference genome serves as a valuable resource for investigating the molecular basis of human diseases using zebrafish mutant models. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca 62191, Morelos, Mexico. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lee, C (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jfreeman7@partners.org; aadeniyi@partners.org; rb4@sanger.ac.uk; sdallaire@rics.bwh.harvard.edu; sjh@sanger.ac.uk; jc8@sanger.ac.uk; bln@sanger.ac.uk; czepeda@lcg.unam.mx; ces@sanger.ac.uk; sjh@sanger.ac.uk; jrh@sanger.ac.uk; yzhou@enders.tch.harvard.edu; zon@enders.tch.harvard.edu; npc@sanger.ac.uk; fy1@sanger.ac.uk; clee@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA111560, R01-CA111560]; Wellcome Trust NR 41 TC 23 Z9 24 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 27 PY 2007 VL 8 AR 195 DI 10.1186/1471-2164-8-195 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 191HZ UT WOS:000248123600003 PM 17597531 ER PT J AU Perrin, JM Bloom, SR Gortmaker, SL AF Perrin, James M. Bloom, Sheila R. Gortmaker, Steven L. TI The increase of childhood chronic conditions in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID YOUNG ADULTHOOD; CHILDREN; OBESITY; PREVALENCE; OVERWEIGHT; ASTHMA; ADOLESCENTS; DISABILITY; DISORDERS; TRENDS C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jperrin@partners.org FU PHS HHS [U 53 MC 04473, U48/CCU115807] NR 25 TC 195 Z9 198 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2007 VL 297 IS 24 BP 2755 EP 2759 DI 10.1001/jama.297.24.2755 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 182UE UT WOS:000247528700026 PM 17595277 ER PT J AU Zuccato, C Belyaev, N Conforti, P Ooi, L Tartari, M Papadimou, E MacDonald, M Fossale, E Zeitlin, S Buckley, N Cattaneo, E AF Zuccato, Chiara Belyaev, Nikolai Conforti, Paola Ooi, Lezanne Tartari, Marzia Papadimou, Evangelia MacDonald, Marcy Fossale, Elisa Zeitlin, Scott Buckley, Noel Cattaneo, Elena TI Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; genome; Huntington's disease; neuronal death; REST/NRSF; transcription ID WILD-TYPE HUNTINGTIN; RECEPTOR-MEDIATED EXCITOTOXICITY; MOUSE MODEL; STRIATAL CELLS; EXPRESSION; PROTEIN; BRAIN; REST; INACTIVATION; DYSFUNCTION AB Huntingtin is a protein that is mutated in Huntington's disease (HD), a dominant inherited neurodegenerative disorder. We previously proposed that, in addition to the gained toxic activity of the mutant protein, selective molecular dysfunctions in HD may represent the consequences of the loss of wild- type protein activity. We first reported that wild-type huntingtin positively affects the transcription of the brain-derived neurotrophic factor (BDNF) gene, a cortically derived survival factor for the striatal neurons that are mainly affected in the disease. Mutation in huntingtin decreases BDNF gene transcription. One mechanism involves the activation of repressor element 1/neuron-restrictive silencer element (RE1/NRSE) located within the BDNF promoter. We now show that increased binding of the RE1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) repressor occurs at multiple genomic RE1/NRSE loci in HD cells, in animal models, and in postmortem brains, resulting in a decrease of RE1/NRSE-mediated gene transcription. The same molecular phenotype is produced in cells and brain tissue depleted of endogenous huntingtin, thereby directly validating the loss- of-function hypothesis of HD. Through a ChIP (chromatin immunoprecipitation)-on-chip approach, we examined occupancy of multiple REST/NRSF target genes in the postmortem HD brain, providing the first example of the application of this technology to neurodegenerative diseases. Finally, we show that attenuation of REST/NRSF binding restores BDNF levels, suggesting that relief of REST/NRSF mediated repression can restore aberrant neuronal gene transcription in HD. C1 Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. Univ Milan, Ctr Stem Cell Res, I-20133 Milan, Italy. Univ Leeds, Inst Membrane & Syst Biol, Leeds LS2 9JT, W Yorkshire, England. Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. Kings Coll London, Inst Psychiat, James Black Ctr, Ctr Cellular Basis Behav, London SE5 9NU, England. RP Cattaneo, E (reprint author), Univ Milan, Dept Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. EM noel.buckley@iop.kcl.ac.uk; elena.cattaneo@unimi.it RI Buckley, Noel/B-9675-2012; OI Buckley, Noel/0000-0003-1152-0653; ZUCCATO, CHIARA/0000-0003-1771-3392; Ooi, Lezanne/0000-0001-9241-8268; CATTANEO, ELENA/0000-0002-0755-4917 FU NINDS NIH HHS [NS16367, NS32765]; Telethon [GGP06250]; Wellcome Trust NR 41 TC 141 Z9 144 U1 0 U2 7 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 JUN 27 PY 2007 VL 27 IS 26 BP 6972 EP 6983 DI 10.1523/JNEUROSCI.4278-06.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 184CV UT WOS:000247619600013 PM 17596446 ER PT J AU Onorati, M Cremisi, F Liu, Y He, RQ Barsacchi, G Vignali, R AF Onorati, Marco Cremisi, Federico Liu, Yang He, Rong-Qiao Barsacchi, Giuseppina Vignali, Robert TI A specific box switches the cell fate determining activity of XOTX2 and XOTX5b in the Xenopus retina SO NEURAL DEVELOPMENT LA English DT Article ID LEBER CONGENITAL AMAUROSIS; HOMEOBOX GENE VSX1; CONE-ROD DYSTROPHY; HUMAN OTX GENES; TRANSCRIPTION-FACTOR; GANGLION-CELL; ANTERIOR NEUROECTODERM; HOMEODOMAIN PROTEIN; ORTHODENTICLE GENE; BRAIN-DEVELOPMENT AB Background: Otx genes, orthologues of the Drosophila orthodenticle gene (otd), play crucial roles in vertebrate brain development. In the Xenopus eye, Xotx2 and Xotx5b promote bipolar and photoreceptor cell fates, respectively. The molecular basis of their differential action is not completely understood, though the carboxyl termini of the two proteins seem to be crucial. To define the molecular domains that make the action of these proteins so different, and to determine whether their retinal abilities are shared by Drosophila OTD, we performed an in vivo molecular dissection of their activity by transfecting retinal progenitors with several wild-type, deletion and chimeric constructs of Xotx2, Xotx5b and otd. Results: We identified a small 8-10 amino acid divergent region, directly downstream of the homeodomain, that is crucial for the respective activities of XOTX2 and XOTX5b. In lipofection experiments, the exchange of this 'specificity box' completely switches the retinal activity of XOTX5b into that of XOTX2 and vice versa. Moreover, the insertion of this box into Drosophila OTD, which has no effect on retinal cell fate, endows it with the specific activity of either XOTX protein. Significantly, in cell transfection experiments, the diverse ability of XOTX2 and XOTX5b to synergize with NRL, a cofactor essential for vertebrate rod development, to transactivate the rhodopsin promoter is also switched depending on the box. We also show by GST-pull down that XOTX2 and XOTX5b differentially interact with NRL, though this property is not strictly dependent on the box. Conclusion: Our data provide molecular evidence on how closely related homeodomain gene products can differentiate their functions to regulate distinct cell fates. A small 'specificity box' is both necessary and sufficient to confer on XOTX2 and XOTX5b their distinct activities in the developing frog retina and to convert the neutral orthologous OTD protein of Drosophila into a positive and specific XOTX-like retinal regulator. Relatively little is known of what gives developmental specificity to homeodomain regulators. We propose that this box is a major domain of XOTX proteins that provides them with the appropriate developmental specificity in retinal histogenesis. C1 [Onorati, Marco; Cremisi, Federico; Barsacchi, Giuseppina; Vignali, Robert] Univ Pisa, Unita Biol Cellulare & Sviluppo, Dipartimento Biol, I-56010 Pisa, Italy. [Onorati, Marco; Cremisi, Federico] Scuola Normale Super Pisa, I-56100 Pisa, Italy. [Liu, Yang; He, Rong-Qiao] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China. [Liu, Yang] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barsacchi, Giuseppina; Vignali, Robert] Univ Pisa, Study Environm Damage Endocrine & Nervous Syst, Ctr High Technol, AMBISEN Ctr, I-56010 Pisa, Italy. RP Vignali, R (reprint author), Univ Pisa, Unita Biol Cellulare & Sviluppo, Dipartimento Biol, Via G Carducci 13, I-56010 Pisa, Italy. EM m.onorati@sns.it; fcremisi@biologia.unipi.it; yang_liu@dfci.harvard.edu; herq@sun5.ibp.ac.cn; gbarsacchi@biologia.unipi.it; rvignali@biologia.unipi.it FU Telethon [GGP04268] NR 59 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8104 J9 NEURAL DEV JI Neural Dev. PD JUN 27 PY 2007 VL 2 AR 12 DI 10.1186/1749-8104-2-12 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 345FG UT WOS:000258980900001 PM 17597530 ER PT J AU Wu, YN Johnson, SW AF Wu, Yan-Na Johnson, Steven W. TI Rotenone potentiates NMDA currents in substantia nigra dopamine neurons SO NEUROSCIENCE LETTERS LA English DT Article DE brain slice; excitotoxicity; glutamate; rotenone; strophanthidin; substantia nigra pars compacta ID ELECTROGENIC SODIUM-PUMP; PARKINSONS-DISEASE; MITOCHONDRIAL RESPIRATION; METABOLISM IMPAIRMENT; TYROSINE KINASE; NA+/K+ ATPASE; CELL-DEATH; RECEPTOR; PHOSPHORYLATION; INHIBITION AB Rotenone is a pesticide that produces a rodent model of Parkinson's disease. Although much evidence suggests that oxidative stress mediates the toxicity of rotenone on dopamine neurons, rotenone can also potentiate glutamate excitotoxicity. We used whole-cell patch pipettes to investigate actions of rotenone on currents evoked by N-methyl-D-aspartate (NMDA) in dopamine neurons in slices of rat midbrain. After superfusing the slice for 20-30 min, rotenone (100 nM) caused a 162% increase in the average amplitude of inward current evoked by 30 mu M NMDA. This effect of rotenone was mimicked by the sodium pump inhibitor strophanthidin (10 mu M) and was abolished when pipettes contained an ATP regeneration solution. Although strophanthidin also significantly increased the amplitude of inward currents evoked by (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 10 mu M), rotenone failed to potentiate AMPA currents. Because rotenone potentiated NMDA- but not AMPA-dependent currents, this suggests that rotenone acts selectively to augment NMDA receptor function. Furthermore, the failure of rotenone to mimic strophanthidin suggests that rotenone does not inhibit sodium pump activity. Our results suggest that an excitotoxic mechanism might contribute to rotenone neurotoxicity. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, RD 61,3710SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu NR 34 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 27 PY 2007 VL 421 IS 2 BP 96 EP 100 DI 10.1016/j.neulet.2007.05.030 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 192IX UT WOS:000248195900002 PM 17560718 ER PT J AU Badr, CE Hewett, JW Breakefield, XO Tannous, BA AF Badr, Christian E. Hewett, Jeffrey W. Breakefield, Xandra O. Tannous, Bakhos A. TI A Highly Sensitive Assay for Monitoring the Secretory Pathway and ER Stress SO PLOS ONE LA English DT Article AB Background. The secretory pathway is a critical index of the capacity of cells to incorporate proteins into cellular membranes and secrete proteins into the extracellular space. Importantly it is disrupted in response to stress to the endoplasmic reticulum that can be induced by a variety of factors, including expression of mutant proteins and physiologic stress. Activation of the ER stress response is critical in the etiology of a number of diseases, such as diabetes and neurodegeneration, as well as cancer. We have developed a highly sensitive assay to monitor processing of proteins through the secretory pathway and endoplasmic reticulum ( ER) stress in real-time based on the naturally secreted Gaussia luciferase ( Gluc). Methodology/Principle Findings. An expression cassette for Gluc was delivered to cells, and its secretion was monitored by measuring luciferase activity in the conditioned medium. Gluc secretion was decreased down to 90% when these cells were treated with drugs that interfere with the secretory pathway at different steps. Fusing Gluc to a fluorescent protein allowed quantitation and visualization of the secretory pathway in real-time. Expression of this reporter protein did not itself elicit an ER stress response in cells; however, Gluc proved very sensitive at sensing this type of stress, which is associated with a temporary decrease in processing of proteins through the secretory pathway. The Gluc secretion assay was over 20,000-fold more sensitive as compared to the secreted alkaline phosphatase (SEAP), a well established assay for monitoring of protein processing and ER stress in mammalian cells. Conclusions/Significance. The Gluc assay provides a fast, quantitative and sensitive technique to monitor the secretory pathway and ER stress and its compatibility with high throughput screening will allow discovery of drugs for treatment of conditions in which the ER stress is generally induced. C1 [Badr, Christian E.; Hewett, Jeffrey W.; Breakefield, Xandra O.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Breakefield, Xandra O.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Badr, Christian E.; Breakefield, Xandra O.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. EM btannous@hms.harvard.edu FU NARSAD; Bachmann-Strauss Foundation; NINDS [5P01 NS037409, P30NS4577-05]; NIH [P50 CA86355-04, NS45776]; Brain Tumor Society FX This work was supported by grants from NARSAD, Bachmann-Strauss Foundation, NINDS (5P01 NS037409 and P30NS4577-05), NIH (P50 CA86355-04 and NS45776) and Brain Tumor Society. NR 30 TC 77 Z9 80 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 27 PY 2007 VL 2 IS 6 AR e571 DI 10.1371/journal.pone.0000571 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GF UT WOS:000207451800015 PM 17593970 ER PT J AU Graham, SM Baeten, JM Richardson, BA Bankson, DD Lavreys, L Ndinya-Achola, JO Mandaliya, K Overbaugh, J McClelland, RS AF Graham, Susan M. Baeten, Jared M. Richardson, Barbra A. Bankson, Daniel D. Lavreys, Ludo Ndinya-Achola, Jeckoniah O. Mandaliya, Kishorchandra Overbaugh, Julie McClelland, R. Scott TI Higher pre-infection vitamin E levels are associated with higher mortality in HIV-1-infected Kenyan women: a prospective study SO BMC INFECTIOUS DISEASES LA English DT Article ID HIV-1 INFECTION; DISEASE PROGRESSION; VIRAL LOAD; HIGH-RISK; PLASMA; SERUM; DEFICIENCY; SUBTYPE; RETINOL AB Background: Low vitamin E levels are often found in HIV-1 infection, and studies have suggested that higher levels may decrease the risk of disease progression. However, vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV-1 replication. We hypothesized that vitamin E levels at HIV- 1 acquisition may influence disease progression. Methods: Vitamin E status was measured in stored samples from the last pre-infection visit for 67 Kenyan women with reliably estimated dates of HIV- 1 acquisition. Regression analyses were used to estimate associations between pre-infection vitamin E and plasma viral load, time to CD4 count < 200 cells/mu L, and mortality. Results: After controlling for potential confounding factors, each 1 mg/L increase in pre-infection vitamin E was associated with 0.08 log(10) copies/mL (95% Cl -0.01 to +0.17) higher set point viral load and 1.58-fold higher risk of mortality (95% Cl 1.15-2.16). The association between higher pre-infection vitamin E and mortality persisted after adjustment for set point viral load (HR 1.55, 95% Cl 1.13-2.13). Conclusion: Higher pre-infection vitamin E levels were associated with increased mortality. Further research is needed to elucidate the role vitamin E plays in HIV- 1 pathogenesis. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Seattle, WA 98108 USA. Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya. Coast Prov Gen Hosp, Mombasa, Kenya. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. RP Graham, SM (reprint author), Univ Washington, Dept Med, Box 356420, Seattle, WA 98195 USA. EM grahamsm@u.washington.edu; jbaeten@u.washington.edu; barbrar@u.washington.edu; daniel.bankson@va.gov; llavreys@wanadoo.fr; Ndinya-Achola@kaviuon.org; kishor@ikenya.com; joverbau@fhcrc.org; mcclell@africaonline.co.ke OI Graham, Susan/0000-0001-7847-8686 FU FIC NIH HHS [D43 TW000007]; NIAID NIH HHS [R01 AI043844, AI-43844, AI-38518, R37 AI038518] NR 21 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUN 26 PY 2007 VL 7 AR 63 DI 10.1186/1471-2334-7-63 PG 5 WC Infectious Diseases SC Infectious Diseases GA 190YQ UT WOS:000248097200001 PM 17594484 ER PT J AU Wolpin, BM Michaud, DS Giovannucci, EL Schernhammer, ES Stampfer, MJ Manson, JE Cochrane, BB Rohan, TE Ma, J Pollak, MN Fuchs, CS AF Wolpin, B. M. Michaud, D. S. Giovannucci, E. L. Schernhammer, E. S. Stampfer, M. J. Manson, J. E. Cochrane, B. B. Rohan, T. E. Ma, J. Pollak, M. N. Fuchs, C. S. TI Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts SO BRITISH JOURNAL OF CANCER LA English DT Article DE pancreatic cancer; insulin-like growth factor; insulin; like growth factor binding protein; insulin ID IGF-BINDING PROTEIN-3; FACTOR-I RECEPTOR; COLORECTAL-CANCER; FACTOR (IGF)-I; CIGARETTE-SMOKING; MALE SMOKERS; C-PEPTIDE; GLUCOSE; WOMEN; MEN AB Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity. The association of plasma IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been investigated in two small studies, with conflicting results. We conducted a nested case-control study within four large, prospective cohorts to investigate whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression, with adjustment for other known pancreatic cancer risk factors. No association was observed between plasma levels of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer. Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP-3 were 0.94 (95% confidence interval (CI), 0.60 - 1.48), 0.96 (95% CI, 0.61 - 1.52), and 1.21 (95% CI, 0.75 - 1.92), respectively. The relative risk for the molar ratio of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54 - 1.31). Additionally, no association was noted in stratified analyses or when requiring longer follow-up. In four prospective cohorts, we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I, IGF-II, or IGFBP-3. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Inst Translat Res Vienna, Appl Canc Res, Vienna, Austria. Univ Washington, Sch Nursing, Div Publ Hlth Sci, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org RI Pollak, Michael/G-9094-2011; Michaud, Dominique/I-5231-2014 OI Pollak, Michael/0000-0003-3047-0604; FU NCI NIH HHS [P01 CA055075, CA55075, CA86102, CA87969, CA95589, P01 CA087969, R01 CA086102, R01 CA095589, R01 CA124908, T32 CA009172]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 43 TC 35 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 26 PY 2007 VL 97 IS 1 BP 98 EP 104 DI 10.1038/sj.bjc.6603826 PG 7 WC Oncology SC Oncology GA 183UH UT WOS:000247597200014 PM 17533398 ER PT J AU Cruz-Gonzalez, I Martin-Herrero, F Gonzalez-Santos, JM Gutierrez-Diez, JA Sanchez-Ledesma, M Maree, AO AF Cruz-Gonzalez, Ignacio Martin-Herrero, Francisco Gonzalez-Santos, Jose M. Gutierrez-Diez, Jose A. Sanchez-Ledesma, Maria Maree, Andrew O. TI Anaphylaxis and recurrent hydatid disease SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Hosp Salamanca, Div Cardiol, Salamanca, Spain. Univ Hosp Salamanca, Div Radiol, Salamanca, Spain. RP Cruz-Gonzalez, I (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM i-cruz@secardiologia.ed NR 4 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 26 PY 2007 VL 115 IS 25 BP E643 EP E645 DI 10.1161/CIRCULATIONAHA.106.684126 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 182SR UT WOS:000247524800014 PM 17592084 ER PT J AU Giugliano, RP Wiviott, SD Stone, PH Simon, DI Schweiger, MJ Bouchard, A Leesar, MA Goulder, MA Deitcher, SR McCabe, CH Braunwald, E AF Giugliano, Robert P. Wiviott, Stephen D. Stone, Peter H. Simon, Daniel I. Schweiger, Marc J. Bouchard, Alain Leesar, Massoud A. Goulder, Michael A. Deitcher, Steven R. McCabe, Carolyn H. Braunwald, Eugene CA ANTHEM-TIMI-32 Investigators TI Recombinant nematode anticoagulant protein c2 in patients with non-ST-Segment elevation acute coronary syndrome - The ANTHEM-TIMI-32 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE FACTOR/FACTOR VIIA; HIGH-RISK PATIENTS; UNFRACTIONATED HEPARIN; THROMBIN GENERATION; RECURRENT ISCHEMIA; RANDOMIZED-TRIAL; EPTIFIBATIDE; INTERVENTION; ENOXAPARIN; INHIBITOR AB Objectives We sought to evaluate the safety and efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). Background Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor Vila complex that has the potential to reduce ischemic complications mediated by thrombin generation. Methods A total of 203 patients were randomized 4:1 to double-blinded intravenous rNAPc2 or placebo every 48 h for a total of 1 to 3 doses in 8 ascending panels (1.5 to 10 mu g/kg). All patients received aspirin, unfractionated heparin (UFH), or enoxaparin and early catheterization; clopidogrel and glycoprotein IIb/IIIa blockers were encouraged. Two subsequent open-label panels evaluated 10 mu g/kg rNAPc2 with half-dose UFH (n = 26) and no UFH (n = 26). The primary end point was the rate of major plus minor bleeding. Pharmacokinetics, pharmacodynamics, continuous electrocardiography, and clinical events were assessed. Results Recombinant NAPc2 did not significantly increase major plus minor bleeding (3.7% vs. 2.5%; p = NS) despite increasing the international normalized ratio in a dose-related fashion (trend p <= 0.0001). Higher-dose rNAPc2 (>= 7.5 mu g/kg) suppressed prothrombin fragment F1.2 generation compared with placebo and reduced ischemia by > 50% compared to placebo and lower-dose rNAPc2. Thrombotic bailout requiring open-label anticoagulant occurred in 5 of 26 patients treated without UFH, but none in the half-dose UFH group (19% vs. 0%; p = 0.051). Conclusions In patients with nSTE-ACS managed with standard antithrombotics and an early invasive approach, additional proximal inhibition of the coagulation cascade with rNAPc2 was well tolerated. rNAPc2 doses >= 7.5 mu g/kg suppressed F1.2 and reduced ischemia, though some heparin may be necessary to avoid procedure-related thrombus formation. (Anticoagulation With rNAPc2 to Eliminate MACE/TIMI 32; http://www.clinicaltrial.gov/ct/show/NCT00116012?order=1; NCT00116012) (J Am Coll Cardiol 2007;49:2398-407) (c) 2007 by the American College of Cardiology Foundation. . C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. Baystate Med Ctr, Springfield, MA USA. Baptist Med Ctr, Birmingham, AL USA. Univ Louisville, Louisville, KY 40292 USA. Nottingham Clin Res, Nottingham, England. Nuvelo Inc, San Carlos, CA USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 27 TC 35 Z9 38 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 JUN 26 PY 2007 VL 49 IS 25 BP 2398 EP 2407 DI 10.1016/j.jacc.2007.02.065 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 182GG UT WOS:000247492500003 PM 17599602 ER PT J AU Ha, L Ichikawa, T Anver, M Dickins, R Lowe, S Sharpless, NE Krimpenfort, P DePinho, RA Bennett, DC Sviderskaya, EV Merlino, G AF Ha, Linan Ichikawa, Takeshi Anver, Miriam Dickins, Ross Lowe, Scott Sharpless, Norman E. Krimpenfort, Paul DePinho, Ronald A. Bennett, Dorothy C. Sviderskaya, Elena V. Merlino, Glenn TI ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetically engineered mice; MET; nevi; p16INK4A; rhabdomyosarcoma ID CELLULAR SENESCENCE; TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; MICE; P53; P16(INK4A); PATHWAYS; P14(ARF); RB; IMMORTALIZATION AB inactivation of the p53 pathway represents the most common molecular defect of human cancer. But in the setting of melanoma, a highly aggressive and invariably fatal malignancy in its advanced disseminated form, mutation/deletion of p53 is relatively rare, whereas its positive regulator ARF is often lost. Here, we show that genetic deficiency in Arf but not p53 facilitates rapid development of melanoma in a genetically engineered mouse model. This difference is accounted for, at least in part, by the unanticipated observation that, unlike fibroblasts, senescence control in melanocytes is strongly regulated by Arf and not p53. Moreover, oncogenic NRAS collaborates with deficiency in Arf, but not p53, to fully transform melanocytes. Our data demonstrate that ARF and p53, although linked in a common pathway, suppress tumorigenesis through distinct, lineage-dependent mechanisms and suggest that ARF helps restrict melanoma progression by executing the oncogene-induced senescence program in benign nevi. Thus, therapeutics designed to restore wild-type p53 function may be insufficient to counter melanoma and other malignancies in which ARF holds p53-independent tumor suppressor activity. C1 NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. Natl Canc Inst, Pathol Histotechnol Lab, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Belfer Fdn Inst Innovat Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ London, Div Basic Med Sci, London SW17 0RE, England. RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM esviders@sgul.ac.uk; gmerlino@helix.nih.gov RI Sviderskaya, Elena/D-2419-2009; Bennett, Dorothy/C-2418-2008; Dickins, Ross/K-2852-2012 OI Bennett, Dorothy/0000-0002-3639-7527; Dickins, Ross/0000-0003-4112-5304 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, P30 CA008748]; Wellcome Trust [064583, 078327] NR 36 TC 101 Z9 102 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 JUN 26 PY 2007 VL 104 IS 26 BP 10968 EP 10973 DI 10.1073/pnas.0611638104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 184LC UT WOS:000247641900041 PM 17576930 ER PT J AU Hasnain-Wynia, R Baker, DW Nerenz, D Feinglass, J Beal, AC Landrum, MB Behal, R Weissman, JS AF Hasnain-Wynia, Romana Baker, David W. Nerenz, David Feinglass, Joe Beal, Anne C. Landrum, Mary Beth Behal, Raj Weissman, Joel S. TI Disparities in health care are driven by where minority patients seek care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RACIAL DISPARITIES; UNITED-STATES; RACE; PHYSICIANS; OUTCOMES; QUALITY AB Background: Racial/ethnic disparities in health care are well documented, but less is known about whether disparities occur within or between hospitals for specific inpatient processes of care. We assessed racial/ethnic disparities using the Hospital Quality Alliance Inpatient Quality of Care Indicators. Methods: We performed an observational study using patient-level data for acute myocardial infarction (5 care measures), congestive heart failure (2 measures), community-acquired pneumonia (2 measures), and patient counseling (4 measures). Data were obtained from 123 hospitals reporting to the University HealthSystem Consortium from the third quarter of 2002 to the first quarter of 2005. A total of 320 970 patients 18 years or older were eligible for at least 1 of the 13 measures. Results: There were consistent unadjusted differences between minority and nonminority patients in the quality of care across 8 of 13 quality measures (from 4.63 and 4.55 percentage points for angiotensin-converting enzyme inhibitors for acute myocardial infarction and congestive heart failure [P <.01] to 14.58 percentage points for smoking cessation counseling for pneumonia [P=.02]). Disparities were most pronounced for counseling measures. In multivariate models adjusted for individual patient characteristics and hospital effect, the magnitude of the disparities decreased substantially, yet remained significant for 3 of the 4 counseling measures; acute myocardial infarction ( unadjusted, 9.00 [P <. 001]; adjusted, 3.82 [P < 01]), congestive heart failure (unadjusted, 8.45 [P=.02]; adjusted, 3.54 [P=.02]), and community-acquired pneumonia (unadjusted, 14.58 [P=. 02]; adjusted, 4.96 [P=. 01]). Conclusions: Disparities in clinical process of care measures are largely the result of differences in where minority and nonminority patients seek care. However, disparities in services requiring counseling exist within hospitals after controlling for site of care. Policies to reduce disparities should consider the underlying reasons for the disparities. C1 American Hosp Assoc, Hlth Res & Educ Trust, Chicago, IL 60606 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gen Internal Med, Chicago, IL USA. Henry Ford Hlth Syst, Ctr Hlth Serv Res, Detroit, MI USA. Commonwealth Fund, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hlth Policy, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. Univ Healthsyst Consortium, Oak Brook, IL USA. RP Hasnain-Wynia, R (reprint author), American Hosp Assoc, Hlth Res & Educ Trust, 1 N Franklin St,30th Floor, Chicago, IL 60606 USA. NR 19 TC 150 Z9 150 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 25 PY 2007 VL 167 IS 12 BP 1233 EP 1239 DI 10.1001/archinte.167.12.1233 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 181ZM UT WOS:000247474900003 PM 17592095 ER PT J AU Diem, SJ Blackwell, TL Stone, KL Yaffe, K Haney, EM Bliziotes, MM Ensrud, KE AF Diem, Susan J. Blackwell, Terri L. Stone, Katie L. Yaffe, Kristine Haney, Elizabeth M. Bliziotes, Michael M. Ensrud, Kristine E. TI Use of antidepressants and rates of hip bone loss in older women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MINERAL DENSITY; SEROTONIN; DEPRESSION; TRANSPORTER; FRACTURES; RISK; AGE; EXPRESSION; SYSTEM AB Background: Serotonin transporters have recently been described in bone, raising the possibility that medications that block serotonin reuptake could affect bone metabolism. Methods: We assessed current use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) and obtained serial bone mineral density (BMD) measurements in a cohort of 2722 older women (mean age, 78.5 years) participating in the Study of Osteoporotic Fractures, a prospective cohort study of community-dwelling women. Hip BMD was measured at the sixth examination and an average of 4.9 years later at the eighth examination. We categorized women as nonusers (used no SSRIs or TCAs at either examination; n= 2406), SSRI users (used SSRIs but no TCAs at either examination; n= 198), or TCA users (used TCAs but no SSRIs at either examination; n= 118). Depressive symptoms were identified using a cutoff score of at least 6 on the Geriatric Depression Scale. Results: After adjustment for potential confounders, including the Geriatric Depression Scale score, mean total hip BMD decreased 0.47% per year in nonusers compared with 0.82% in SSRI users (P <. 001) and 0.47% in TCA users (P=. 99). Higher rates of bone loss were also observed at the 2 hip subregions for SSRI users. Results were not substantially altered when women who scored at least 6 on the Geriatric Depression Scale were excluded from the analysis. Conclusion: Use of SSRIs but not TCAs is associated with an increased rate of bone loss at the hip in this cohort of older women. C1 Univ Minnesota, Epidemiol Clin Res Ctr, Minneapolis, MN 55415 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55415 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55415 USA. Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol & Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. RP Diem, SJ (reprint author), Univ Minnesota, Epidemiol Clin Res Ctr, 1100 Washington Ave S,Suite 201, Minneapolis, MN 55415 USA. EM sdiem@umn.edu RI Diem, Susan/B-6479-2013 FU NIA NIH HHS [AG05394, AG05407, AG08415]; NIAMS NIH HHS [AR35583, AR35582, AR35584, K23 AR051926] NR 31 TC 167 Z9 176 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 25 PY 2007 VL 167 IS 12 BP 1240 EP 1245 DI 10.1001/archinte.167.12.1240 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 181ZM UT WOS:000247474900004 PM 17592096 ER PT J AU Imperiale, TF Dominitz, JA Provenzale, DT Boes, LP Rose, CM Bowers, JC Musick, BS Azzouz, F Perkins, SM AF Imperiale, Thomas F. Dominitz, Jason A. Provenzale, Dawn T. Boes, Lynn P. Rose, Cynthia M. Bowers, Jill C. Musick, Beverly S. Azzouz, Faouzi Perkins, Susan M. TI Predicting poor outcome from acute upper gastrointestinal hemorrhage SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CLINICAL GUIDELINE; HOSPITAL LENGTH; ULCER; SCORE; STAY AB Background: Uncertainty about the outcome of acute upper gastrointestinal bleeding often results in a longer-than-necessary hospital stay. Methods: We derived and internally validated clinical prediction rules (CPRs) to predict outcome from upper gastrointestinal bleeding. This multisite, prospective cohort study involved consecutive patients admitted for acute upper gastrointestinal bleeding. Multivariate logistic regression was used to derive CPRs on two thirds of the cohort (derivation set) that predicted bleeding-specific outcomes (rebleeding, need for urgent surgery, or hospital death [poor outcome 1]) and bleeding-specific outcomes plus new or worsening comorbidity (poor outcome 2). Both CPRs were then tested on the remaining third of the cohort (validation set). Results: A total of 391 individuals (99% men; mean age, 63.4 years) were enrolled, of which 4.6% rebled and 3.1% died. Independent predictors of poor outcome 1 were APACHE (Acute Physiology and Chronic Health Evaluation) II score of 11 or greater, esophageal varices, and stigmata of recent hemorrhage. Predictors of poor outcome 2 were these 3 factors plus unstable comorbidity on admission. Of patients with no risk factors, only 1 (1.1%) of 92 experienced poor outcome 1 and only 6 (6.2%) of 97 experienced poor outcome 2. Risks in the validation set were comparable. The CPRs identified 37.8% and 32.2% of patients in the derivation and validation sets, respectively, who were eligible for a shorter hospital stay. Conclusions: Patients admitted with acute upper gastrointestinal bleeding were unlikely to have a poor outcome if these risk factors were absent. These CPRs might make hospital management more efficient by identifying low-risk patients for-whom-early hospital discharge is possible. C1 Regenstrief Inst Inc, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46204 USA. Indiana Univ, Sch Med, Ctr Excellence Implementing Evidence Based Practi, Indianapolis, IN 46204 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Vet Affairs Med Ctr, Dept Med, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. RP Imperiale, TF (reprint author), Regenstrief Inst Inc, 1050 Wishard Blvd RG-6, Indianapolis, IN 46202 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 18 TC 29 Z9 31 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 25 PY 2007 VL 167 IS 12 BP 1291 EP 1296 DI 10.1001/archinte.167.12.1291 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 181ZM UT WOS:000247474900011 PM 17592103 ER PT J AU Xia, Y Yu, PB Sidis, Y Beppu, H Bloch, KD Schneyer, AL Lin, HY AF Xia, Yin Yu, Paul B. Sidis, Yisrael Beppu, Hideyuki Bloch, Kenneth D. Schneyer, Alan L. Lin, Herbert Y. TI Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA; IDENTIFICATION; MEMBRANE; INHIBIN; DRAGON; CORECEPTOR; ANTAGONIST; MECHANISMS; EXPRESSION; PATHWAYS AB Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily of multifunctional ligands that transduce their signals through type I and II serine/ threonine kinase receptors and intracellular Smad proteins. Recently, we identified the glycosylphosphatidylinositol-anchored repulsive guidance molecules RGMa, DRAGON (RGMb), and hemojuvelin (RGMc) as coreceptors for BMP signaling (Babbit, J. L., Huang, F. W., Wrighting, D. W., Xia, Y., Sidis, Y., Samad, T. A., Campagna, J. A., Chung, R., Schneyer, A., Woolf, C. J., Andrews, N. C., and Lin, H. Y. (2006) Nat. Genet. 38, 531-539; Babbit, J. L., Zhang, Y., Samad, T. A., Xia, Y., Tang, J., Schneyer, A., Woolf, C. J., and Lin, H. Y. (2005) J. Biol. Chem. 280, 29820-29827; Samad, T. A., Rebbapragada, A., Bell, E., Zhang, Y., Sidis, Y., Jeong, S. J., Campagna, J. A., Perusini, S., Fabrizio, D. A., Schneyer, A. L., Lin, H. Y., Brivanlou, A. H., Attisano, L., and Woolf, C. J. (2005) J. Biol. Chem. 280, 14122-14129). However, the mechanism by which RGM family members enhance BMP signaling remains unknown. Here, we report that RGMa bound to radiolabeled BMP2 and BMP4 with K-d values of 2.4 +/- 0.2 and 1.4 +/- 0.1 nM, respectively. In KGN human ovarian granulosa cells and mouse pulmonary artery smooth muscle cells, BMP2 and BMP4 signaling required BMP receptor type II (BMPRII), but not activin receptor type IIA (ActRIIA) or ActRIIB, based on changes in BMP signaling by small interfering RNA inhibition of receptor expression. In contrast, cells transfected with RGMa utilized both BMPRII and ActRIIA for BMP2 or BMP4 signaling. Furthermore, in BmpRII-null pulmonary artery smooth muscle cells, BMP2 and BMP4 signaling was reduced by inhibition of endogenous RGMa expression, and RGMa-mediated BMP signaling required ActRIIA expression. These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Nephrol,Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Lin, HY (reprint author), Richard B Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM hlin@partners.org OI Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [K08 HL079943, HL74352, K08 HL079943-01A1]; NIDDK NIH HHS [DK071837, DK069533, DK076158, DK076143] NR 33 TC 68 Z9 73 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 JUN 22 PY 2007 VL 282 IS 25 BP 18129 EP 18140 DI 10.1074/jbc.M701679200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 179PK UT WOS:000247302000019 PM 17472960 ER PT J AU Long, XM Lin, YS Ortiz-Vega, S Busch, S Avruch, J AF Long, Xiaomeng Lin, Yenshou Ortiz-Vega, Sara Busch, Susann Avruch, Joseph TI The rheb switch 2 segment is critical for signaling to target of rapamycin complex 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70 S6 KINASE; AMINO-ACID SUFFICIENCY; GTP-BINDING PROTEINS; CELL-GROWTH; MAMMALIAN TARGET; RAS; ACTIVATION; DROSOPHILA; MTOR; TSC2 AB The small GTPase Rheb is a positive upstream regulator of the target of rapamycin ( TOR) complex 1 in mammalian cells and can bind directly to TOR complex 1. To identify the regions of the Rheb surface most critical for signaling to TOR complex 1, we created a set of 26 mutants wherein clusters of 1 - 5 putative solvent-exposed residues were changed to alanine, ultimately changing 65 residues distributed over the entire Rheb surface. The signaling function of these mutants was assessed by their ability, in comparison to wild type Rheb, to restore the phosphorylation of S6K1(Thr(389)) when expressed transiently in amino acid-deprived 293T cells. The major finding is that two mutants situated in the Rheb switch 2 segment, Y67A/I69A and I76A/ D77A, exhibit a near total loss of function, whereas extensive replacement of the switch 1 segment and other surface residues with alanines causes relatively little disturbance of Rheb rescue of S6K1 from amino acid withdrawal. This is surprising in view of the minimal impact of guanyl nucleotide on Rheb switch 2 configuration. The loss of function Rheb switch 2 mutants are well expressed and exhibit partial agonist function in amino acid-replete cells. They are unimpaired in their ability to bind GTP or mammalian ( m) TOR in vivo or in vitro, and the mTOR polypeptides retrieved with these inactive Rheb mutants exhibit kinase activity in vitro comparable with mTOR bound to wild type Rheb. We conclude that Rheb signaling to mTOR in vivo requires a Rheb switch 2-dependent interaction with an element other than the three known polypeptide components of TOR complex 1. C1 Massachusetts Gen Hosp, Harvard Med Sch, Diabet & Unit Serv, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA73818, R01 CA073818]; NIDDK NIH HHS [P30 DK040561, DK17776, P30 DK040561-12, R37 DK017776] NR 29 TC 21 Z9 22 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 JUN 22 PY 2007 VL 282 IS 25 BP 18542 EP 18551 DI 10.1074/jbc.M610736200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 179PK UT WOS:000247302000059 PM 17470430 ER PT J AU Lu, J Meng, WY Poy, F Maiti, S Goode, BL Eck, MJ AF Lu, Jun Meng, Wuyi Poy, Florence Maiti, Sankar Goode, Bruce L. Eck, Michael J. TI Structure of the FH2 domain of Daam1: Implications for formin regulation of actin assembly SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein structure; formin; FH2 domain; actin assembly; dishevelled ID HOMOLOGY-2 DOMAIN; INDUCED NUCLEATION; CAPPING PROTEIN; BINDING PROTEIN; FILAMENT; RHO; POLYMERIZATION; MECHANISM; PROFILIN; MODEL AB Daam1 (dishevelled-associated activator of morphogenesis-1) is a diaphanous-related formin first studied as a novel dishevelled binding protein and shown to be crucial for the planar cell polarity (PCP) pathway in Xenopus. Daam1, like other formins, directs nucleation and elongation of new actin filaments using its conserved formin-homology-2 (FH2) domain. Here we report the crystal structure of a large C-terminal fragment of human Daam1 containing the FH2 domain. The structure, determined at 2.25 angstrom resolution using the single-wavelength anomalous diffraction (SAD) phasing method, reveals a "tethered dimer" architecture that is similar to that previously described for the FH2 domain of the yeast formin Bni1, which shares similar to 21% sequence identity with Daarrn1. Despite the overall similarity with the dimeric FH2 domain of Bni1 and with a truncated monomeric structure of mDia1, the Daam1 FH2 structure reveals a number of differences in secondary structure elements and in the "lasso/post" dimerization interface that may be functionally important. Most strikingly, the two halves of the crystallographic dimer pack together in a manner that occludes their actin binding surfaces. This "locked" conformation is stabilized by two novel, interacting beta-strands formed by the ends of the linkers that connect the two sides of the dimer. The Daam1 FH2 domain has weak actin assembly activity as compared with other mammalian formins, but mutations that disrupt the beta-strand lock increase activity about tenfold to a level comparable to other formins, suggesting that this occluded conformation may represent an auto-inhibited conformation of the Daam1 FH2 domain. (C) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NCRR NIH HHS [P41 RR015301, P41 RR015301-05S17362, P41 RR015301-040042, P41 RR015301-050042]; NIGMS NIH HHS [R56 GM071834, R01 GM071834-03, R01 GM071834-02, GM071834, R01 GM071834-01, R01 GM083137, R01 GM071834] NR 43 TC 45 Z9 49 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 22 PY 2007 VL 369 IS 5 BP 1258 EP 1269 DI 10.1016/j.jmb.2007.04.002 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176OZ UT WOS:000247096100010 PM 17482208 ER PT J AU Li, HM Zhang, L Rao, A Harrison, SC Hogan, PG AF Li, Huiming Zhang, Lan Rao, Anjana Harrison, Stephen C. Hogan, Patrick G. TI Structure of calcineurin in complex with PVIVIT peptide: Portrait of a low-affinity signalling interaction SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE calcineurin; NFAT; VIVIT peptide; crystal structure; docking site ID DOCKING SITE; PROTEIN PHOSPHATASE-1; CYCLOSPORINE-A; SUBSTRATE RECOGNITION; SELECTIVE-INHIBITION; T-CELLS; NFAT; CALCIUM; DOMAINS; ASSOCIATION AB The protein phosphatase calcineurin recognizes a wide assortment of substrates and controls diverse developmental and physiological pathways in eukaryotic cells. Dephosphorylation of the transcription factor NFAT and certain other calcineurin substrates depends on docking of calcineurin at a PxIxIT consensus site. We describe here the structural basis for recognition of the PxIxIT sequence by calcineurin. We demonstrate that the high-affinity peptide ligand PVIVIT adds as a beta-strand to the edge of a beta-sheet of calcineurin; that short peptide segments containing the PxIxIT consensus sequence suffice for calcineurin-substrate docking; and that sequence variations within the PxIxIT core modulate the Kd of the interaction within the physiological range 1 mu M to 1 mM. Calcineurin can adapt to a wide variety of substrates, because recognition requires only a PxIxIT sequence and because variation within the core PxIxIT sequence can fine-tune the affinity to match the physiological signalling requirements of individual substrates. (C) 2007 Elsevier Ltd. All rights reserved. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Hogan, PG (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM hogan@cbr.med.harvard.edu FU NIAID NIH HHS [AI40127] NR 47 TC 67 Z9 72 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 22 PY 2007 VL 369 IS 5 BP 1296 EP 1306 DI 10.1016/j.jmb.2007.04.032 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176OZ UT WOS:000247096100013 PM 17498738 ER PT J AU Cohen, T Colijn, C Finklea, B Murray, M AF Cohen, Ted Colijn, Caroline Finklea, Bryson Murray, Megan TI Exogenous re-infection and the dynamics of tuberculosis epidemics: local effects in a network model of transmission SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE tuberculosis; re-infection; exogenous; mathematical model; network; epidemic ID CONTROL STRATEGIES; DISEASE; IMPACT; INFECTION AB Infection with Mycobacterium tuberculosis leads to tuberculosis (TB) disease by one of the three possible routes: primary progression after a recent infection; re-activation of a latent infection, or exogenous re-infection of a previously infected individual. Recent studies show that optimal TB control strategies may vary depending on the predominant route to disease in a specific population. It is therefore important for public health policy makers to understand the relative frequency of each type of TB within specific epidemiological scenarios. Although molecular epidemiologic tools have been used to estimate the relative contribution of recent transmission and re-activation to the burden of TB disease, it is not possible to use these techniques to distinguish between primary disease and re-infection on a population level. Current estimates of the contribution of re-infection therefore rely on mathematical models which identify the parameters most consistent with epidemiological data; these studies find that exogenous re-infection is important only when TB incidence is high. A basic assumption of these models is that people in a population are all equally likely to come into contact with an infectious case. However, theoretical studies demonstrate that the social and spatial structure can strongly influence the dynamics of infectious disease transmission. Here, we use a network model of TB transmission to evaluate the impact of non-homogeneous mixing on the relative contribution of re-infection over realistic epidemic trajectories. In contrast to the findings of previous models, our results suggest that re-infection may be important in communities where the average disease incidence is moderate or low as the force of infection can be unevenly distributed in the population. These results have important implications for the development of TB control strategies. C1 Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequal, 1 Brigham Circle,1620 Tremont St, Boston, MA 02120 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011 FU NIAID NIH HHS [K08 AI055985, K08 AI055985-05] NR 44 TC 56 Z9 57 U1 0 U2 5 PU ROYAL SOCIETY PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD JUN 22 PY 2007 VL 4 IS 14 BP 523 EP 531 DI 10.1098/rsif.2006.0193 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 179SZ UT WOS:000247311700008 PM 17251134 ER PT J AU Maser, RS Choudhury, B Campbell, PJ Feng, B Wong, KK Protopopov, A O'Neil, J Gutierrez, A Ivanova, E Perna, I Lin, E Mani, V Jiang, S McNamara, K Zaghlul, S Edkins, S Stevens, C Brennan, C Martin, ES Wiedemeyer, R Kabbarah, O Nogueira, C Histen, G Aster, J Mansour, M Duke, V Foroni, L Fielding, AK Goldstone, AH Rowe, JM Wang, YQA Look, AT Stratton, MR Chin, L Futreal, PA DePinho, RA AF Maser, Richard S. Choudhury, Bhudipa Campbell, Peter J. Feng, Bin Wong, Kwok-Kin Protopopov, Alexei O'Neil, Jennifer Gutierrez, Alejandro Ivanova, Elena Perna, Ilana Lin, Eric Mani, Vidya Jiang, Shan McNamara, Kate Zaghlul, Sara Edkins, Sarah Stevens, Claire Brennan, Cameron Martin, Eric S. Wiedemeyer, Ruprecht Kabbarah, Omar Nogueira, Cristina Histen, Gavin Aster, Jon Mansour, Marc Duke, Veronique Foroni, Letizia Fielding, Adele K. Goldstone, Anthony H. Rowe, Jacob M. Wang, Yaoqi A. Look, A. Thomas Stratton, Michael R. Chin, Lynda Futreal, P. Andrew DePinho, Ronald A. TI Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers SO NATURE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA COPY NUMBER; LI-FRAUMENI-SYNDROME; HUMAN LUNG-CANCER; TELOMERE DYSFUNCTION; PANCREATIC ADENOCARCINOMA; GENE AMPLIFICATION; SUPPRESSOR PATHWAY; MUTATIONS; MICE AB Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. Royal Free & Univ Coll Med Sch, London NW3 2PF, England. UCL Hosp, London NW1 2BU, England. Technion Israel Inst Technol, IL-31096 Haifa, Israel. Rambam Med Ctr, IL-31096 Haifa, Israel. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu RI Fielding, adele/B-2848-2009; Choudhury, Bhudipa/D-3863-2011; Maser, Richard/B-2970-2012; Fielding, Adele/J-6949-2013; Nogueira, Cristina/N-4574-2015; OI Choudhury, Bhudipa/0000-0002-1392-6414; Fielding, Adele/0000-0002-4746-7789; Nogueira, Cristina/0000-0002-0853-5304; Brennan, Cameron/0000-0003-4064-8891; Gutierrez, Alejandro/0000-0002-0249-9007; wong, kwok kin/0000-0001-6323-235X FU Medical Research Council [G0500389]; Wellcome Trust [, 077012, 088340] NR 50 TC 241 Z9 247 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 21 PY 2007 VL 447 IS 7147 BP 966 EP U3 DI 10.1038/nature05886 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180NU UT WOS:000247373100039 PM 17515920 ER PT J AU North, TE Goessling, W Walkley, CR Lengerke, C Kopani, KR Lord, AM Weber, GJ Bowman, TV Jang, IH Grosser, T FitzGerald, GA Daley, GQ Orkin, SH Zon, LI AF North, Trista E. Goessling, Wolfram Walkley, Carl R. Lengerke, Claudia Kopani, Kamden R. Lord, Allegra M. Weber, Gerhard J. Bowman, Teresa V. Jang, Il-Ho Grosser, Tilo FitzGerald, Garret A. Daley, George Q. Orkin, Stuart H. Zon, Leonard I. TI Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis SO NATURE LA English DT Article ID ZEBRAFISH; EXPRESSION; MICE; CYCLOOXYGENASE-2; TRANSPLANTATION; EMBRYO; BLOOD; STAT5; RUNX1 AB Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. Definitive HSCs derived during embryogenesis in the aorta gonad - mesonephros region subsequently colonize fetal and adult haematopoietic organs(1,2). To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta - gonad - mesonephros region. Here, we show that chemicals that enhance prostaglandin ( PG) E2 synthesis increased HSC numbers, and those that block prostaglandin synthesis decreased stem cell numbers. The cyclooxygenases responsible for PGE2 synthesis were required for HSC formation. A stable derivative of PGE2 improved kidney marrow recovery following irradiation injury in the adult zebrafish. In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. Furthermore, ex vivo exposure to stabilized PGE2 enhanced spleen colony forming units at day 12 post transplant and increased the frequency of long-term repopulating HSCs present in murine bone marrow after limiting dilution competitive transplantation. The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu RI Grosser, Tilo/A-1057-2007; FitzGerald, Garret/A-4222-2010; OI Grosser, Tilo/0000-0001-8569-8396; Goessling, Wolfram/0000-0001-9972-1569; Walkley, Carl/0000-0002-4784-9031; Lengerke, Claudia/0000-0001-5442-2805 FU NHLBI NIH HHS [R01 HL048801, R01 HL048801-16] NR 30 TC 548 Z9 564 U1 7 U2 60 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 21 PY 2007 VL 447 IS 7147 BP 1007 EP U7 DI 10.1038/nature05883 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180NU UT WOS:000247373100048 PM 17581586 ER PT J AU Vergo, MT Davis, BT Harris, NL Pasternack, MS AF Vergo, Maxwell T. Davis, Benjamin T. Harris, Nancy Lee Pasternack, Mark S. TI Case 19-2007: A 19-year-old college student with fever and joint pain - Meningococcal arthritis. Infectious mononucleosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DISSEMINATED GONOCOCCAL-INFECTION; BARR-VIRUS-INFECTION; NEISSERIA-GONORRHOEAE; PROTEIN-I; SUSCEPTIBILITY; DISEASE C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. RP Vergo, MT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 21 TC 4 Z9 4 U1 2 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 21 PY 2007 VL 356 IS 25 BP 2631 EP 2637 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 180GN UT WOS:000247351200011 ER PT J AU Hirsch, MS AF Hirsch, Martin S. TI Entecavir surprise SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEPATITIS-B-VIRUS; ANTIRETROVIRAL THERAPY; HIV; RISK C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Partners AIDS Res Ctr, Cambridge, MA USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 11 TC 13 Z9 14 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 21 PY 2007 VL 356 IS 25 BP 2641 EP 2643 DI 10.1056/NEJMe078045 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 180GN UT WOS:000247351200013 PM 17582076 ER PT J AU Parent, L Fielding, AL Dance, DR Seco, J Evans, PM AF Parent, L. Fielding, A. L. Dance, D. R. Seco, J. Evans, P. M. TI Amorphous silicon EPID calibration for dosimetric applications: comparison of a method based on Monte Carlo prediction of response with existing techniques SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PORTAL IMAGING DEVICE; DOSE-RESPONSE; OPTIMAL BACKSCATTER; IMRT VERIFICATION; IMAGES; BEAM AB For EPID dosimetry, the calibration should ensure that all pixels have a similar response to a given irradiation. A calibration method (MC), using an analytical fit of a Monte Carlo simulated flood field EPID image to correct for the flood field image pixel intensity shape, was proposed. It was compared with the standard flood field calibration (FF), with the use of a water slab placed in the beam to flatten the flood field (WS) and with a multiple field calibration where the EPID was irradiated with a fixed 10 x 10 field for 16 different positions (MF). The EPID was used in its normal configuration (clinical setup) and with an additional 3 mm copper slab (modified setup). Beam asymmetry measured with a diode array was taken into account in MC and WS methods. For both setups, the MC method provided pixel sensitivity values within 3% of those obtained with the MF and WS methods (mean difference < 1%, standard deviation < 2%). The difference of pixel sensitivity between MC and FF methods was up to 12.2% (clinical setup) and 11.8% (modified setup). MC calibration provided images of open fields (5 x 5 to 20 x 20 cm(2)) and IMRT fields to within 3% of that obtained with WS and MF calibrations while differences with images calibrated with the FF method for fields larger than 10 x 10 cm2 were up to 8%. MC, WS and MF methods all provided a major improvement on the FF method. Advantages and drawbacks of each method were reviewed. C1 Inst Canc Res, Joint Dept Phys, Sutton, Surrey, England. Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. Queensland Univ Technol, Sch Phys & Chem Sci, Brisbane, Qld, Australia. Inst Canc Res, Joint Dept Phys, London SW3 6JB, England. Royal Marsden NHS Fdn Trust, London, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Francis Burr Proton Therapy Ctr, Boston, MA USA. RP Parent, L (reprint author), Inst Canc Res, Joint Dept Phys, Sutton, Surrey, England. EM laure.parent@gmail.com RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012; OI Fielding, Andrew/0000-0001-9955-4609 NR 30 TC 23 Z9 25 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2007 VL 52 IS 12 BP 3351 EP 3368 DI 10.1088/0031-9155/52/12/003 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 175XR UT WOS:000247047800003 PM 17664548 ER PT J AU Parodi, K Ferrari, A Sommerer, F Paganetti, H AF Parodi, K. Ferrari, A. Sommerer, F. Paganetti, H. TI Clinical CT-based calculations of dose and positron emitter distributions in proton therapy using the FLUKA Monte Carlo code SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID IN-BEAM PET; QUALITY-ASSURANCE; TISSUE PARAMETERS; FEASIBILITY; SIMULATIONS; NUMBERS; NUCLEI; CARBON AB Clinical investigations on post- irradiation PET/ CT ( positron emission tomography/ computed tomography) imaging for in vivo verification of treatment delivery and, in particular, beam range in proton therapy are underway at Massachusetts General Hospital ( MGH). Within this project, we have developed a Monte Carlo framework for CT- based calculation of dose and irradiation- induced positron emitter distributions. Initial proton beam information is provided by a separate Geant4 Monte Carlo simulation modelling the treatment head. Particle transport in the patient is performed in the CT voxel geometry using the FLUKA Monte Carlo code. The implementation uses a discrete number of different tissue types with composition and mean density deduced from the CT scan. Scaling factors are introduced to account for the continuous Hounsfield unit dependence of the mass density and of the relative stopping power ratio to water used by the treatment planning system (XiO (Computerized Medical Systems Inc.)). Resulting Monte Carlo dose distributions are generally found in good correspondence with calculations of the treatment planning program, except a few cases (e. g. in the presence of air/ tissue interfaces). Whereas dose is computed using standard FLUKA utilities, positron emitter distributions are calculated by internally combining proton fluence with experimental and evaluated cross- sections yielding C-11, O-15, O-14, N-13, K-38 and P-30. Simulated positron emitter distributions yield PET images in good agreement with measurements. In this paper, we describe in detail the specific implementation of the FLUKA calculation framework, which may be easily adapted to handle arbitrary phase spaces of proton beams delivered by other facilities or include more reaction channels based on additional cross- section data. Further, we demonstrate the effects of different acquisition time regimes (e. g., PET imaging during or after irradiation) on the intensity and spatial distribution of the irradiation-induced beta(+)- activity signal for the cases of head and neck and para-spinal tumour sites. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. CERN, CH-1211 Geneva, Switzerland. RP Parodi, K (reprint author), Heidelberg Ion Therapy Ctr, Neuenheimer Feld 450, D-69120 Heidelberg, Germany. EM Katia.Parodi@med.uni-heidelberg.de FU NCI NIH HHS [5 P01 CA21239-25, P01 CA021239, P01 CA021239-28] NR 33 TC 73 Z9 74 U1 1 U2 10 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2007 VL 52 IS 12 BP 3369 EP 3387 DI 10.1088/0031-9155/52/12/004 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 175XR UT WOS:000247047800004 PM 17664549 ER PT J AU Boverman, G Fang, Q Carp, SA Miller, EL Brooks, DH Selb, J Moore, RH Kopans, DB Boas, DA AF Boverman, Gregory Fang, Qianqian Carp, Stefan A. Miller, Eric L. Brooks, Dana H. Selb, Juliette Moore, Richard H. Kopans, Daniel B. Boas, David A. TI Spatio-temporal imaging of the hemoglobin in the compressed breast with diffuse optical tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PHOTON MIGRATION MEASUREMENTS; L-CURVE; POSED PROBLEMS; TISSUE; REGULARIZATION; MAMMOGRAPHY; SPECTROSCOPY; OXYGENATION; CALIBRATION; FRAMEWORK AB We develop algorithms for imaging the time-varying optical absorption within the breast given diffuse optical tomographic data collected over a time span that is long compared to the dynamics of the medium. Multispectral measurements allow for the determination of the time-varying total hemoglobin concentration and of oxygen saturation. To facilitate the image reconstruction, we decompose the hemodynamics in time into a linear combination of spatiotemporal basis functions, the coefficients of which are estimated using all of the data simultaneously, making use of a Newton-based nonlinear optimization algorithm. The solution of the extremely large least-squares problem which arises in computing the Newton update is obtained iteratively using the LSQR algorithm. A Laplacian spatial regularization operator is applied, and, in addition, we make use of temporal regularization which tends to encourage similarity between the images of the spatio-temporal coefficients. Results are shown for an extensive simulation, in which we are able to image and quantify localized changes in both total hemoglobin concentration and oxygen saturation. Finally, a breast compression study has been performed for a normal breast cancer screening subject, using an instrument which allows for highly accurate co-registration of multispectral diffuse optical measurements with an x-ray tomosynthesis image of the breast. We are able to quantify the global return of blood to the breast following compression, and, in addition, localized changes are observed which correspond to the glandular region of the breast. C1 Rensselaer Polytech Inst, Dept Biomed Engn, Jonsson Engn Ctr, Troy, NY 12180 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02153 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Massachusetts Gen Hosp, Breast Imaging Ctr, Boston, MA 02114 USA. RP Boverman, G (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, Jonsson Engn Ctr, Troy, NY 12180 USA. EM boverg@rpi.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 NR 42 TC 45 Z9 45 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 21 PY 2007 VL 52 IS 12 BP 3619 EP 3641 DI 10.1088/0031-9155/52/12/018 PG 23 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 175XR UT WOS:000247047800018 PM 17664563 ER PT J AU Rohatiner, AZS Nadler, L Davies, AJ Apostolidis, J Neuberg, D Matthews, J Gribben, JG Mauch, PM Lister, TA Freedman, AS AF Rohatiner, Ama Z. S. Nadler, Lee Davies, Andrew J. Apostolidis, John Neuberg, Donna Matthews, Janet Gribben, John G. Mauch, Peter M. Lister, T. Andrew Freedman, Arnold S. TI Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: Long-term follow-up SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; STEM-CELL TRANSPLANTATION; DOXORUBICIN-BASED CHEMOTHERAPY; ACUTE MYELOGENOUS LEUKEMIA; SINGLE-AGENT CHEMOTHERAPY; PROGRESSION-FREE SURVIVAL; MYELODYSPLASTIC SYNDROME; RANDOMIZED-TRIAL; MALIGNANT-LYMPHOMA AB Purpose The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. Patients and Methods One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. Results Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY + TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. Conclusion These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up. C1 St Bartholomews Hosp, Canc Res UK Med Oncol Unit, London EC1A 7BE, England. Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. RP Rohatiner, AZS (reprint author), St Bartholomews Hosp, Canc Res UK Med Oncol Unit, 45 Little Britain, London EC1A 7BE, England. EM ama.rohatiner@cancer.org.uk NR 40 TC 130 Z9 135 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2007 VL 25 IS 18 BP 2554 EP 2559 DI 10.1200/JCO.2006.09.8327 PG 6 WC Oncology SC Oncology GA 187PZ UT WOS:000247861800011 PM 17515573 ER PT J AU Smith, ZM Delgutte, B AF Smith, Zachary M. Delgutte, Bertrand TI Sensitivity to interaural time differences in the inferior colliculus with bilateral cochlear implants SO JOURNAL OF NEUROSCIENCE LA English DT Article DE binaural hearing; electric stimulation; neural prosthesis; cochlear implant; inferior colliculus; ITD ID LOW-FREQUENCY NEURONS; MEDIAL SUPERIOR OLIVE; INTRACOCHLEAR ELECTRICAL-STIMULATION; AUDITORY-NERVE FIBERS; TEMPORAL RESPONSE PATTERNS; NEONATALLY DEAFENED CAT; SOUND PRESSURE LEVEL; BINAURAL INTERACTION; INTENSITY DIFFERENCES; SPEECH-PERCEPTION AB Bilateral cochlear implantation attempts to increase performance over a monaural prosthesis by harnessing the binaural processing of the auditory system. Although many bilaterally implanted human subjects discriminate interaural time differences ( ITDs), a major cue for sound localization and signal detection in noise, their performance is typically poorer than that of normal- hearing listeners. We developed an animal model of bilateral cochlear implantation to study neural ITD sensitivity for trains of electric current pulses delivered via bilaterally implanted intracochlear electrodes. We found that a majority of single units in the inferior colliculus of acutely deafened, anesthetized cats are sensitive to ITD and that electric ITD tuning is as sharp as found for acoustic stimulation with broadband noise in normal- hearing animals. However, the sharpness and shape of ITD tuning often depended strongly on stimulus intensity; some neurons had dynamic ranges of ITD sensitivity as low as 1 dB. We also found that neural ITD sensitivity was best at pulse rates below 100 Hz and decreased with increasing pulse rate. This rate limitation parallels behavioral ITD discrimination in bilaterally implanted individuals. The sharp neural ITD sensitivity found with electric stimulation at the appropriate intensity is encouraging for the prospect of restoring the functional benefits of binaural hearing in bilaterally implanted human subjects and suggests that neural plasticity resulting from previous deafness and deprivation of binaural experience may play a role in the poor ITD discrimination with current bilateral implants. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, MIT, Speech Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Res Lab Elect, Cambridge, MA 02139 USA. RP Smith, ZM (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 505 Taylor Bldg,720 Rutlands Ave, Baltimore, MD 21205 USA. EM zsmith@alum.mit.edu RI Smith, Zachary/B-2879-2009; OI Smith, Zachary/0000-0002-0819-4562; , /0000-0003-1349-9608 FU NIDCD NIH HHS [T32 DC000038, R01 DC005775-03, T32 DC000038-12, R01 DC005775-05, T32 DC00038, T32 DC000038-11, P30 DC005209-019001, R01 DC005775-04, T32 DC000038-14, P30 DC005209, R01 DC005775, R01 DC005775-01, T32 DC000038-13, R01 DC005775-02] NR 78 TC 25 Z9 25 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 20 PY 2007 VL 27 IS 25 BP 6740 EP 6750 DI 10.1523/JNEUROSCI.0052-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 180XK UT WOS:000247401100016 PM 17581961 ER PT J AU Melov, S Adlard, PA Morten, K Johnson, F Golden, TR Hinerfeld, D Schilling, B Mavros, C Masters, CL Volitakis, I Li, QX Laughton, K Hubbard, A Cherny, RA Gibson, B Bush, AI AF Melov, Simon Adlard, Paul A. Morten, Karl Johnson, Felicity Golden, Tamara R. Hinerfeld, Doug Schilling, Birgit Mavros, Christine Masters, Colin L. Volitakis, Irene Li, Qiao-Xin Laughton, Katrina Hubbard, Alan Cherny, Robert A. Gibson, Brad Bush, Ashley I. TI Mitochondrial Oxidative Stress Causes Hyperphosphorylation of Tau SO PLOS ONE LA English DT Article AB Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral A beta load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD. C1 [Melov, Simon; Morten, Karl; Johnson, Felicity; Golden, Tamara R.; Hinerfeld, Doug; Schilling, Birgit; Gibson, Brad] Buck Inst Age Res, Novato, CA USA. [Adlard, Paul A.; Mavros, Christine; Masters, Colin L.; Volitakis, Irene; Li, Qiao-Xin; Laughton, Katrina; Cherny, Robert A.; Bush, Ashley I.] Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Adlard, Paul A.; Mavros, Christine; Masters, Colin L.; Volitakis, Irene; Li, Qiao-Xin; Laughton, Katrina; Cherny, Robert A.; Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Hubbard, Alan] Univ Calif Berkeley, Sch Publ Hlth, EHS Biostat, Berkeley, CA 94720 USA. [Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Melov, S (reprint author), Buck Inst Age Res, Novato, CA USA. EM smelov@buckinsti-tute.org; bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU National Institutes of Health [AG18679, PO1 AG25901, AG12686]; American Health Assistance Foundation; Institute for the Study of Aging; Ellison Medical Foundation; Australian Research Council; National Health and Medical Research Council FX This work was supported by National Institutes of Health grants AG18679 and PO1 AG25901 (S. M), AG12686 (A. I. B.), and a grant from the American Health Assistance Foundation (A. I. B.). It was also supported by an award from the Institute for the Study of Aging and an Ellison Medical Foundation award (S. M); the Australian Research Council Federation Fellowship (A. I. B.); the National Health and Medical Research Council Howard Florey Centenary Research Fellowship (P. A). We would like to thank Nicole Nagulko and Lawreen Asuncion for excellent animal work, and Sue Doctrow for helpful comments. NR 55 TC 142 Z9 144 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 20 PY 2007 VL 2 IS 6 AR e536 DI 10.1371/journal.pone.0000536 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GE UT WOS:000207451700004 PM 17579710 ER PT J AU Bihl, F Mosam, A Henry, LN Chisholm, JV Dollard, S Gumbi, P Cassol, E Page, T Mueller, N Kiepiela, P Martin, JN Coovadia, HA Scadden, DT Brander, C AF Bihl, Florian Mosam, Anisa Henry, Leah N. Chisholm, John V., III Dollard, Sheila Gumbi, Pamela Cassol, Edana Page, Taryn Mueller, Nicolas Kiepiela, Photini Martin, Jeff N. Coovadia, Hoosen A. Scadden, David T. Brander, Christian TI Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma SO AIDS LA English DT Article DE chemotherapy; cytotoxic T lymphocytes; Kaposi's sarcoma; Kaposi's sarcoma-associated herpesvirus; viral immune control; viral load ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SUB-SAHARAN AFRICA; HUMAN-HERPESVIRUS-8 DNA; PERIPHERAL-BLOOD; TYPE-1 INFECTION; HLA-B; AIDS; RESPONSES; VIREMIA AB Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in South Africa and the clinical manifestation of AIDS-associated Kaposi's sarcoma (KS) represents a significant clinical problem. Whereas the positive effects of HAART on the regression of KS have been well established, less is known about the role of herpesvirus-specific cellular immunity in disease improvement. Design: Thirty-three treatment-naive HIV clade C-infected individuals with KS were randomly assigned into two treatment arms (HAART plus systemic chemotherapy versus HAART alone). KSHV-specific cellular immune responses, viral loads and clinical outcome were evaluated. Methods: KSHV, Epstein-Barr virus and HIV-specific cellular immunity was measured using an IFN-gamma enzyme-linked immunospot assay in samples obtained at baseline and up to 11 months after treatment initiation. Cell-associated KSHV viremia was determined by real-time polymerase chain reaction. Results: Robust increases in CD4 cell counts and suppressed HIV viral loads were seen in parallel with significant increases in the KSHV-specific cellular immune responses over time. Although slowly increasing after 5 months, KSHV-specific T-cell responses were significantly elevated only after I I months, with both lytic and latent antigens being more frequently targeted. A trend towards better clinical outcome with HAART plus chemotherapy treatment was observed compared with HAART alone, and was accompanied by a significant reduction in cellular KSHV viral load in the HAART plus chemotherapy-treated subjects but not those treated with HAART alone after 11 months of treatment. Conclusion: The data show a temporal association between the clinical improvement of KS and the re-appearance of KSHV-specific cellular immunity, and demonstrate an effective suppression of KSHV viral replication using combination therapy.(C)V 2007 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Ctr Regenerat Med & Technol, Boston, MA USA. Univ KwaZulu Natal, Dept Dermatol, Durban, South Africa. Univ KwaZulu Natal, HIV Pathogenesis Program, Doris Duke Med Res Inst, Durban, South Africa. Univ KwaZulu Natal, Dept Virol, Durban, South Africa. Univ KwaZulu Natal, Fac Hlth Sci, Nelson R Mandela Sch Med, Ctr HIV AIDS Res, Durban, South Africa. Ctr Dis Control & Prevent, Atlanta, GA USA. Ist Sci San Raffaele, AIDS Immunopathogenesis Unit DIBIT, I-20132 Milan, Italy. Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. Univ Pretoria, HIV1 Immune Pathogenesis & Therapeut Res Program, ZA-0002 Pretoria, South Africa. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. RP Brander, C (reprint author), Partners AIDS Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org RI Infektiologie, USZ/A-6921-2011; Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 NR 38 TC 52 Z9 53 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 19 PY 2007 VL 21 IS 10 BP 1245 EP 1252 DI 10.1097/QAD.0b013e328182df03 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 183EZ UT WOS:000247556800003 PM 17545700 ER PT J AU Mphatswe, W Blanckenberg, N Tudor-Williams, G Prendergast, A Thobakgale, C Mkhwanazia, N McCarthy, N Walker, BD Kiepiela, P Goulder, P AF Mphatswe, Wendy Blanckenberg, Natasha Tudor-Williams, Gareth Prendergast, Andrew Thobakgale, Christina Mkhwanazia, Nompumelelo McCarthy, Noel Walker, Bruce D. Kiepiela, Photini Goulder, Philip TI High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis SO AIDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TO-CHILD TRANSMISSION; DISEASE PROGRESSION; HIV-1-INFECTED CHILDREN; PROSPECTIVE COHORT; VIRAL REPLICATION; SOUTH-AFRICA; MORTALITY; RNA; INTRAPARTUM AB Objectives: To determine the natural history of HIV infection following periparturn single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. Methods: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% <= 20%. Results: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P=0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P<0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P<0.001). Median viral load at birth in IU-infected infants (1 55 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to <= 20% in 70% and <= 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. Conclusions: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Oxford, Dept Pediat, Oxford OX1 3SY, England. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. Univ London Imperial Coll Sci Technol & Med, Dept Paediat, Div Med, London SW7 2AZ, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Goulder, P (reprint author), Univ Oxford, Dept Pediat, Peter Medawar Bldg Pathogen Res,South Pk Rd, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk RI McCarthy, Noel/K-3314-2012 FU Medical Research Council [G0500384]; Wellcome Trust NR 31 TC 54 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 19 PY 2007 VL 21 IS 10 BP 1253 EP 1261 DI 10.1097/QAD.0b013e3281a3bec2 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 183EZ UT WOS:000247556800004 PM 17545701 ER PT J AU Levy, D Hwang, SJ Kayalar, A Benjamin, EJ Vasan, RS Parise, H Larson, MG Wang, TJ Selhub, J Jacques, PF Vita, JA Keyes, MJ Mitchell, GF AF Levy, Daniel Hwang, Shih-Jen Kayalar, Atilla Benjamin, Emelia J. Vasan, Ramachandran S. Parise, Helen Larson, Martin G. Wang, Thomas J. Selhub, Jacob Jacques, Paul F. Vita, Joseph A. Keyes, Michelle J. Mitchell, Gary F. TI Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness the Framingham heart study SO CIRCULATION LA English DT Article DE arteries; elasticity; epidemiology; hemodynamics; homocysteine; natriuretic peptides ID BLOOD-PRESSURE TRACKING; AORTIC INPUT IMPEDANCE; PULSE-WAVE VELOCITY; CARDIOVASCULAR MORTALITY; MYOCARDIAL-INFARCTION; HORDALAND-HOMOCYSTEINE; ESSENTIAL-HYPERTENSION; INDEPENDENT PREDICTOR; LOADING SEQUENCE; RISK AB Background - Increased arterial stiffness and higher plasma natriuretic peptide and homocysteine levels are associated with elevated risk for cardiovascular disease. Little is known about the relations of natriuretic peptides and homocysteine to arterial wall stiffness in the community. Methods and Results - We assessed the relations of plasma N- terminal atrial natriuretic peptide, B- type natriuretic peptide, adrenomedullin, and homocysteine concentrations to arterial stiffness in participants in the Framingham Heart Study. Central pulse pressure, forward pressure wave, reflected pressure wave, carotid- femoral pulse wave velocity, and carotid- radial pulse wave velocity were assessed by tonometry in 1962 participants ( mean age, 61 years; 56% women) in the Framingham Heart Study. Central systolic and diastolic blood pressures were 123/75 mm Hg in men and 119/66 mm Hg in women. After adjustment for age and clinical covariates, N- terminal atrial natriuretic peptide and B- type natriuretic peptide were associated with carotid- femoral pulse wave velocity ( men: partial correlation, 0.069, P = 0.043 and r = 0.115, P = 0.001, respectively; women: r = -0.063, P = 0.037 and r = -0.062, P = 0.040), and carotid- radial pulse wave velocity ( men: r = -0.090, P = 0.009 and r = -0.083, P <= 0.015; women: r = -0.140, P <= 0.001 and r = -0.104, P = 0.001, respectively). In men, N- terminal atrial natriuretic peptide and B- type natriuretic peptide also were associated with forward and reflected wave and carotid pulse pressure. In men, adrenomedullin was associated with mean arterial pressure ( r = 0.089, P = 0.009), and homocysteine was associated with carotid- femoral pulse wave velocity ( r = 0.072, P = 0.036), forward pressure ( r = 0.079, P = 0.02), and central pulse pressure ( r = 0.072, P = 0.035). Interaction tests indicated sex differences in the relations of several biomarkers to measures of arterial stiffness. Conclusions - Plasma natriuretic peptide, adrenomedullin, and homocysteine levels are associated with alterations in conduit vessel properties that differ in men and women. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. MetroW Med Ctr, Dept Med, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Freidman Sch Nutr Sci Policy, Boston, MA 02111 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Stat, Boston, MA 02215 USA. Boston Univ, Cardiol Sect, Boston, MA 02215 USA. Cardiovasc Engn Inc, Waltham, MA USA. RP Levy, D (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01-HL60040, 1R01-HL70100, N01-HC25195] NR 51 TC 35 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 19 PY 2007 VL 115 IS 24 BP 3079 EP 3085 DI 10.1161/CIRCULATIONAHA.106.652842 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180GH UT WOS:000247350200009 PM 17533184 ER PT J AU Moe, GW Howlett, J Januzzi, JL Zowall, H AF Moe, Gordon W. Howlett, Jonathan Januzzi, James L. Zowall, Hanna CA IMPROVE-CHF Study Investigators TI N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure SO CIRCULATION LA English DT Article DE costs and cost analysis; healthcare economics and organizations; heart failure; natriuretic peptides ID COST-EFFECTIVENESS; EMERGENCY DIAGNOSIS; ACUTE DYSPNEA; CANADA; RECOMMENDATIONS; HOSPITALIZATION; PROGNOSIS; MORTALITY; ILLNESS; BURDEN AB Background - The diagnostic utility of N- terminal pro-B-type natriuretic peptide ( NT- proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare resource use, and randomized evidence for utility of NT- proBNP was lacking. Methods and Results - We tested the hypothesis that NT- proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT- proBNP results or without knowledge of NT- proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT- proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure ( P < 0.00001). Knowledge of NT- proBNP results reduced the duration of ED visit by 21% ( 6.3 to 5.6 hours; P = 0.031), the number of patients rehospitalized over 60 days by 35% ( 51 to 33; P = 0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services ( US $ 6129 to US $ 5180 per patient; P = 0.023) over 60 days from enrollment. Adding NT- proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver- operating characteristic curve increased from 0.83 to 0.90 ( P < 0.00001). Conclusions - In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT- proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes. C1 Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. McGill Univ, Montreal, PQ H3A 2T5, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Dalhousie Univ, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS B3H 1R2, Canada. RP Moe, GW (reprint author), Univ Toronto, St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM moeg@smh.toronto.on.ca NR 27 TC 143 Z9 153 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 19 PY 2007 VL 115 IS 24 BP 3103 EP 3110 DI 10.1161/CIRCULATIONAHA.106.666255 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180GH UT WOS:000247350200012 PM 17548729 ER PT J AU Rubin, SA AF Rubin, Stanley A. TI Exercise training in heart failure - Contradictory or conventional? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID METAANALYSIS; CAPACITY; TRIAL; HF AB The paintings of the Belgian surrealist Rene Magritte (1898 to 1967) juxtapose 2 incongruous, illogical, or even contradictory objects: a steam locomotive projecting from a domestic fireplace (Time Transfixed, 1939); a bright daytime sky over a nighttime scene of a dimly lighted street (The Empire of Light, 1954); or a picture of a pipe with a caption on the canvas that reads, in French, "This is not a pipe" (The Treachery of Images, 1929). On the basis of conventional wisdom, the current palette of therapy for heart failure also would seem incongruous, illogical, or contradictory if it included exercise therapy. However, change is at hand. C1 Univ Calif Los Angeles, Med Program, VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Rubin, SA (reprint author), Univ Calif Los Angeles, Med Program, VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, 11301 Wilshire Blvd,Cardiol 111E, Los Angeles, CA 90073 USA. EM sarubin@ucla.edu NR 23 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 19 PY 2007 VL 49 IS 24 BP 2337 EP 2340 DI 10.1016/j.jacc.2007.04.013 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 181NK UT WOS:000247443200006 PM 17572249 ER PT J AU Yang, DK Choi, BY Lee, YH Kim, YG Cho, MC Hong, SE Kim, DH Hajjar, RJ Park, WJ AF Yang, Dong Kwon Choi, Bo Youn Lee, Young-Hoon Kim, Young-Gyu Cho, Myeong-Chan Hong, Seong-Eui Kim, Do Han Hajjar, Roger J. Park, Woo Jin TI Gene profiling during regression of pressure overload-induced cardiac hypertrophy SO PHYSIOLOGICAL GENOMICS LA English DT Article DE remodeling; eya2 ID LEFT-VENTRICULAR HYPERTROPHY; AORTIC-VALVE REPLACEMENT; ASSIST DEVICE SUPPORT; EYES ABSENT; DILATED CARDIOMYOPATHY; SIGNALING PATHWAYS; HEART-FAILURE; EYA; EXPRESSION; PHOSPHATASE AB Regression of cardiac hypertrophy and improvement of the functional capacity of failing hearts have reportedly been achieved by mechanical unloading in cardiac work. In this study, cardiac hypertrophy was first induced in rats by transverse aortic constriction and then mechanically unloaded by relieving the constriction after significant cardiac hypertrophy had developed. Hypertrophy was significantly regressed at the cellular and molecular levels at day 1, 3, and 7 after constriction relief. Gene profiling analysis revealed that 52 genes out of 9,911 genes probed on a gene array were specifically upregulated during the early regression period. Among these regression-induced genes, Eyes absent 2 (eya2) was of particular interest because it is a transcriptional cofactor involved in mammalian organogenesis as well as Drosophila eye development. Adenovirus-mediated overexpression of eya2 in rat neonatal cardiomyocytes completely abrogated phenylephrine-induced development of cardiomyocyte hypertrophy as determined by cell size, sarcomere rearrangement and fetal gene re-expression. Our data strongly suggest that transcriptional programs distinct from those mediating cardiac hypertrophy may be operating during the regression of hypertrophy, and eya2 may be a key regulator of one of these programs. C1 Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Chungbuk Natl Univ, Dept Oral Anat, Chonju 360763, South Korea. Chungbuk Natl Univ, Dept Internal Med, Chonju 360763, South Korea. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Park, WJ (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, 1 Oryong Dong, Kwangju 500712, South Korea. EM wjpark@gist.ac.kr FU NHLBI NIH HHS [HL-080498-01] NR 30 TC 14 Z9 15 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 19 PY 2007 VL 30 IS 1 BP 1 EP 7 DI 10.1152/physiolgenomics.00246.2006 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 180OA UT WOS:000247373700001 PM 17327491 ER PT J AU Jakobs, TC Ben, YX Masland, RH AF Jakobs, Tatjana C. Ben, Yixin Masland, Richard H. TI Expression of mRNA for glutamate receptor subunits distinguishes the major classes of retinal neurons, but is less specific for individual cell types SO MOLECULAR VISION LA English DT Article ID CONE BIPOLAR CELLS; GANGLION-CELLS; RAT RETINA; MAMMALIAN RETINA; MOUSE RETINA; AMACRINE CELLS; KAINATE RECEPTORS; PRIMATE RETINA; DEVELOPMENTAL REGULATION; SYNAPTIC-TRANSMISSION AB Purpose: To investigate the expression of ionotropic glutamate receptor subunits by retinal neurons, to assess the extent to which different functional types of retinal neurons are characterized by the expression of the receptor subtypes. Methods: Rod photoreceptor cells and bipolar cells were identified in retina dissociates. Amacrine cells were identified in dissociates from transgenic mice or by staining with an antibody against the extracellular carbohydrate epitope CD15. Ganglion cells were identified by retrograde axonal transport of FITC-dextran or by green fluorescent protein (GFP) fluorescence in a transgenic strain. We examined the receptors simultaneously using non-quantitative single-cell reverse transcriptase polymerase chain reaction for GluR1-R4 (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors), GluR5-R7, and KA1 and 2 (kainate receptors), delta 1 and delta 2 subunits, and the N-methyl-D-aspartate (NMDA) receptor subunits NR1, 2a-d, and 3a. Results: The expression of glutamate receptors on bipolar cells and rod photoreceptors was limited: Neither expressed functional NMDA receptors, and rods were also negative for AMPA receptors. The sample of ganglion cells included examples of many ganglion cell types; these were distinguished morphologically using quantitative parameters defined in a previous cluster analysis. All types of ionotropic glutamate receptors were found to be expressed on ganglion cells. The iGluR subunits GluR4, KA2, delta 1, and NR1 were expressed on almost all ganglion cells examined. Conclusions: Despite the heterogeneity of ganglion cell types, differences among them in this PCR-based method were minor. Thus, retinal interneurons are characterized by expression of distinctive glutamate receptor types, but functional differences among ganglion cells seem to be reflected instead in the amounts as well as spatial distributions of a widely expressed group of receptors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jakobs, TC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 50 Blossom St, Res Bldg 429, Boston, MA 02114 USA. EM Jakobs@helix.mgh.harvard.edu FU NEI NIH HHS [R01 EY017169, R01 EY017169-01A1] NR 52 TC 35 Z9 35 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 18 PY 2007 VL 13 IS 98-100 BP 933 EP 948 PG 16 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 193YQ UT WOS:000248311500002 PM 17653033 ER PT J AU Hilderbrand, SA Weissleder, R AF Hilderbrand, Scott A. Weissleder, Ralph TI One-pot synthesis of new symmetric and asymmetric xanthene dyes SO TETRAHEDRON LETTERS LA English DT Article ID FLUORESCENT; CELLS AB Symmetric and asymmetric xanthene dyes have been prepared by a convenient one-step procedure from aldehyde and diol or m-aminophenol precursors using concentrated phosphoric acid as a solvent. This protocol provides access to water-soluble dyes with large Stoke's shifts and far-red fluorescence emission. These compounds are envisioned as components of fluorescencebased sensors for a variety of imaging applications. (c) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Harvard Med Sch, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Hilderbrand, SA (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM Scott_Hilderbrand@hms.harvard.edu FU NCI NIH HHS [P50 CA086355-07, P50 CA086355]; NHLBI NIH HHS [U01 HL080731, U01 HL080731-01] NR 12 TC 43 Z9 44 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 18 PY 2007 VL 48 IS 25 BP 4383 EP 4385 DI 10.1016/j.tetlet.2007.04.088 PG 3 WC Chemistry, Organic SC Chemistry GA 179GQ UT WOS:000247278100016 PM 19834587 ER PT J AU Chandra, D Kar, B Idelchik, G Simpson, L Loyalka, P Gregoric, ID Delgado, RM Frazier, OH AF Chandra, Divay Kar, Biswajit Idelchik, Gary Simpson, Leo Loyalka, Pranav Gregoric, Igor D. Delgado, Reynolds M., III Frazier, O. H. TI Usefulness of percutaneous left ventricular assist device as a bridge to recovery from myocarditis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOGENIC-SHOCK; SUPPORT AB The TandemHeart percutaneous left ventricular assist device is a left atrial-to-femoral artery bypass system that can be implanted percutaneously within 30 minutes and provides active circulatory support. The TandemHeart has been used mainly for temporary hemodynamic assistance during high-risk coronary interventions and postcardiotomy heart failure. This report describes initial experience with this device as a successful bridge to cardiac recovery in 3 patients with acute myocarditis. All patients presented with severe cardiogenic shock (mean cardiac index 1.1 L/min/m(2)), and end-organ perfusion could not be maintained despite intra-aortic balloon counterpulsation and the maximal use of vasopressive agents. The patients were successfully bridged to myocardial recovery with the TandemHeart (mean duration of support 5 days, range 2 to 8). The only complication was a short episode of ventricular fibrillation during device placement in 1 patient, which did not result in any morbidity or mortality. All patients were discharged home (mean duration of stay 15 days). In conclusion, the TandemHeart proved to be a safe and effective bridge to myocardial recovery in these patients with acute myocarditis. (c) 2007 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Div Cardiol, Houston, TX USA. Texas Heart Inst, Dept Cardiol, Houston, TX 77025 USA. Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX 77025 USA. RP Kar, B (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. EM kar@bcm.edu NR 6 TC 15 Z9 16 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2007 VL 99 IS 12 BP 1755 EP 1756 DI 10.1016/j.amjcard.2007.01.067 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 187RX UT WOS:000247867100026 PM 17560889 ER PT J AU Aryana, A Sobota, KD Esterbrooks, DJ Gelbman, AI AF Aryana, Arash Sobota, Kristi D. Esterbrooks, Dennis J. Gelbman, Andrew I. TI Superior vena cava syndrome induced by endocardial defibrillator and pacemaker leads SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ENDOVASCULAR TREATMENT; IMPLANTATION; THROMBOSIS; DISEASE; STENTS AB Two cases of superior vena cava syndrome induced by endocardial defibrillator and pacemaker leads are described. The 2 patients had histories of multiple endocardial leads and device upgrades and venous thrombosis. The first patient was treated with laser lead extraction followed by percutaneous venoplasty and stenting. The second patient was treated conservatively with long-term anticoagulation. The 2 patients had symptomatic reduction. In conclusion, superior vena cava syndrome induced by transvenous leads is an uncommon but serious complication. Anticoagulation can be effective in select patients, but in severe cases, thrombolytic therapy or surgical or percutaneous intervention may be required. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Creighton Univ, Med Ctr, Dept Med, Div Cardiol, Omaha, NE USA. Creighton Univ, Med Ctr, Dept Radiol, Omaha, NE USA. RP Aryana, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM aaryana@partners.org NR 13 TC 12 Z9 13 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2007 VL 99 IS 12 BP 1765 EP 1767 DI 10.1016/j.amjcard.2007.01.065 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 187RX UT WOS:000247867100029 PM 17560892 ER PT J AU Kahn, KL MacLean, CH Wong, AL Rubenstein, LZ Liu, H Fitzpatrick, DM Harker, JO Chen, WP Traina, SB Mittman, BS Hahn, BH Paulus, HE AF Kahn, K. L. MacLean, C. H. Wong, A. L. Rubenstein, L. Z. Liu, H. Fitzpatrick, D. M. Harker, J. O. Chen, W. P. Traina, S. B. Mittman, B. S. Hahn, B. H. Paulus, H. E. TI Assessment of American college of rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE rheumatoid arthritis; quality of care ID MEDICARE MANAGED CARE; UNITED-STATES; PERFORMANCE; GUIDELINES; TRENDS AB Objective. To evaluate the American College of Rheumatology (ACR) starter set of quality measures for rheumatoid arthritis (RA) in an actual patient cohort that preceded publication of the quality measures. Methods. We retrospectively applied the 2006 ACR quality criteria to a prospectively studied cohort of 568 patients with RA treated by 1,932 unique physicians including 255 different rheumatologists between the years 1999 and 2003. Data on performance were obtained from self-report surveys and medical record review within 12 months. Results. At least 1 joint examination was performed in 98% of patients. Patient and physician global assessments were reported for 79% and 74% of patients, respectively. A total of 85% of patients received disease-modifying antirheumatic drugs (DMARDs). DMARD adjustments were made for 50% of patients in whom increasing disease activity was noted at least once and for 64% of patients in whom increasing disease activity was noted during 2 (of 4) 3-month periods within the year. Compared with self-report surveys, medical records substantially underreported performance on quality measures. Conclusion. The ACR-endorsed quality measures for RA can be assessed using available data sources. When both self-report and medical record data are used, adherence rates, designed to serve as minimum standards of care, were moderate or high for most measures. Prior to using indicators to compare quality across groups, specific strategies for operationalizing measures and for using accurate data sources to assess adherence to the measures should be defined. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles Cty Olive View, Med Ctr, Sylmar, CA USA. RP Kahn, KL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza,Box 951736, Los Angeles, CA 90095 USA. EM kkahn@mednet.ucla.edu FU NIAMS NIH HHS [5-P60-AR-36834] NR 21 TC 21 Z9 21 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2007 VL 57 IS 5 BP 707 EP 715 DI 10.1002/art.22781 PG 9 WC Rheumatology SC Rheumatology GA 177BZ UT WOS:000247129900003 PM 17530663 ER PT J AU Singh, JA Hodges, JS Toscano, JP Asch, SM AF Singh, Jasvinder A. Hodges, James S. Toscano, John P. Asch, Steven M. TI Quality of care for gout in the US needs improvement SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE gout; veterans; quality of care; quality indicators; physician adherence ID VETERANS-AFFAIRS; UNITED-STATES; HEALTH-CARE; ALLOPURINOL; MANAGEMENT; HYPERURICEMIA; EPIDEMIOLOGY; PREVALENCE; INDICATORS; ARTHRITIS AB Objective. To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care. Methods. Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics. Results. Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of >= 1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers. Conclusion. Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts. C1 VA Med Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Singh, JA (reprint author), VA Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Jasvinder.Singh@med.va.gov OI singh, jasvinder/0000-0003-3485-0006 FU NCRR NIH HHS [KL2 RR024151] NR 27 TC 84 Z9 87 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2007 VL 57 IS 5 BP 822 EP 829 DI 10.1002/art.22767 PG 8 WC Rheumatology SC Rheumatology GA 177BZ UT WOS:000247129900018 PM 17530682 ER PT J AU Park, Y Downing, SR Kim, D Hahn, WC Lil, C Kantoff, PW Weil, LJ AF Park, Yuhyun Downing, Sean R. Kim, Dohyun Hahn, William C. Lil, Cheng Kantoff, Philip W. Weil, L. J. TI Simultaneous and exact interval estimates for the contrast of two groups based on an extremely high dimensional variable: application to mass spec data SO BIOINFORMATICS LA English DT Article ID OVARIAN-CANCER; BIOMARKER DISCOVERY; PROTEOMIC PATTERNS; SERUM; SPECTROMETRY; CLASSIFICATION; MICROARRAYS AB Motivation: Analysis of high-throughput proteomic/genomic data, in particular, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) data and microarray data, has led to a multitude of techniques aimed at identifying potential biomarkers. Most of the statistical techniques for comparing two groups are based on qualitative measures such as lo-value. A quantitative way such as interval estimation for the contrasts of two groups is more appealing. Results: We have devised a simultaneous confidence bands method capable of detecting potential biomarkers, while controlling for overall confidence coverage level, in high-dimensional datasets that discriminate two treatment groups using a permutation scheme. For example, for the SELDI-TOF MS data, we deal with the entire spectrum simultaneously and construct (1 - alpha) confidence bands for the mean differences between groups. Furthermore, peaks were identified based on the maximal differences between the groups as determined by the confidence bands. The analysis method herein described gives both qualitative (P-value) and quantitative data (magnitude of difference). The Clinical Proteomics Programs Databank's ovarian cancer dataset and data from in-house samples containing known spiked-in proteins were analyzed. We were able to identify potential biomarkers similar to those described in previous analysis of the ovarian cancer data, however, while these markers are highly significant between cancer and normal groups, our analysis indicated the absolute difference between the two groups was minimal. In addition, we found additional markers than those previously described with greater differences in average intensities. The proposed confidence bands method successfully detected the spiked-in peaks, as well as, secondary peaks generated by adducts and double-charged species. We also illustrate our method utilizing paired gene expression data from a prostate cancer microarray experiment by constructing confidence bands for the fold changes between cancer and normal samples. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Med Sch, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. Seoul Natl Univ, Dept Stat, Seoul, South Korea. RP Park, Y (reprint author), Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. EM parkyuhyun@gmail.com NR 21 TC 9 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2007 VL 23 IS 12 BP 1451 EP 1458 DI 10.1093/bioinformatics/btm130 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 193KA UT WOS:000248271700003 PM 17459967 ER PT J AU Valera, EM Faraone, SV Murray, KE Seidman, LJ AF Valera, Eve M. Faraone, Stephen V. Murray, Kate E. Seidman, Larry J. TI Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT, 2005 CL Toronto, CANADA SP Amer Acad Child & Adolescent Psychiat DE ADHD; cerebellum; corpus callosum; meta-analysis; MRI; structural imaging ID DEFICIT-HYPERACTIVITY DISORDER; CORPUS-CALLOSUM; CAUDATE-NUCLEUS; PSYCHIATRIC COMORBIDITY; HYPERKINETIC DISORDER; MORPHOMETRIC ANALYSIS; RESPONSE-INHIBITION; WORKING-MEMORY; FUNCTIONAL MRI; CHILDREN AB Background: Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. Methods: We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Results: Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference = .408, p < .001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. Conclusions: This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies. C1 Massachusetts Gen Hosp, MGH Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. SUNY Upstate Med Ctr, Med Genet Res Ctr, Syracuse, NY USA. SUNY Upstate Med Ctr, Dept Psychiat, Syracuse, NY USA. Arizona State Univ, Dept Psychol, Tempe, AZ USA. Massachusetts Mental Hlth Ctr, Publ Psyciat Div, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Valera, EM (reprint author), Massachusetts Gen Hosp, MGH Psychiat, Room 2651,149 Thirteenth St, Charlestown, MA 02129 USA. EM eve_valera@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 K23 MH071535-01A1, MH 62152, R21MH/NS66191] NR 68 TC 362 Z9 375 U1 7 U2 38 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 JUN 15 PY 2007 VL 61 IS 12 BP 1361 EP 1369 DI 10.1016/j.biopsych.2006.06.011 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 177AX UT WOS:000247127100006 PM 16950217 ER PT J AU Spencer, TJ Adler, LA McGough, JJ Muniz, R Jiang, H Pestreich, L AF Spencer, Thomas J. Adler, Lenard A. McGough, James J. Muniz, Rafael Jiang, Hai Pestreich, Linda CA Adult Res Grp TI Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; adults; capsules; d-MPH-ER; efficacy; safety ID DEFICIT HYPERACTIVITY DISORDER; QUALITY-OF-LIFE; DOUBLE-BLIND; THREO-METHYLPHENIDATE; PSYCHIATRIC STATUS; CHILDREN; ADHD; PHARMACOKINETICS; TOLERABILITY; PLACEBO AB Background: This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD). Methods: Randomized adults with ADHD (n = 221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement >= 30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-1) scale. Results: Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p = .006); d-MPH-ER, 30 mg, improved by 13.4 (p = .012); and d-MPH-ER, 40 mg, improved by 16.9 (p < .001). Overall distribution of CGH ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children. Conclusions: Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Clin, Pediatr Psychopharmacol Unit, Boston, MA 02114 USA. NYU, Sch Med, New York, NY USA. New York VA Harbor Healthcare Syst, New York, NY USA. UCLA Neuropsychiat Inst, Los Angeles, CA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Clin, Pediatr Psychopharmacol Unit, 15 Parkman St,Warren 705, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu OI Adler, Len/0000-0002-9812-8234 NR 31 TC 83 Z9 83 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2007 VL 61 IS 12 BP 1380 EP 1387 DI 10.1016/j.biopsych.2006.07.032 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 177AX UT WOS:000247127100008 PM 17137560 ER PT J AU Geller, D Petty, C Vivas, F Johnson, J Pauls, D Biederman, J AF Geller, Daniel Petty, Carter Vivas, Fe Johnson, Jessica Pauls, David Biederman, Joseph TI Further evidence for co-segregation between pediatric obsessive compulsive disorder and attention deficit hyperactivity disorder: A familial risk analysis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention deficit hyperactivity disorder; child and adolescent; familial risk; genetic; obsessive-compulsive disorder ID LA-TOURETTES SYNDROME; DEFICIT/HYPERACTIVITY DISORDER; ANXIETY DISORDERS; LEARNING-DISABILITIES; GENETIC-RELATIONSHIP; CHILDREN; ADOLESCENTS; EPIDEMIOLOGY; PARENTS; COMORBIDITY AB Background: To examine the relationship between obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) in children and adolescents using familial risk analysis. Methods: We assessed for ADHD and OCD in the 1057 first-degree relatives of three groups of index children: those with OCD and ADHD, those with OCD but no ADHD and matched controls with neither disorder. Results: The age-corrected risk for OCD was similarly elevated in families of OCD youth with (14.8%) and without ADHD (17.5%) (p = .78), and both groups had significantly higher rates of OCD compared with controls (.5%) (p < .001). In contrast, the risk for ADHD was significantly elevated only among relatives of youth who had ADHD (15.3%) compared with controls (4.6%) (p < .001). Relatives affected with ADHD also had a significantly elevated risk for OCD compared to relatives unaffected by ADHD (20% vs. 4.9%, hazard ratio 4.8) (p < .001) and the two disorders occurred together with higher than expected frequency in affected relatives of OCD+ADHD probands (p < .001) suggesting co-segregation between these two disorders. There was no evidence of nonrandom mating between OCD- and ADHD-affected spouses. Conclusions: These results extend previous findings regarding the familiality of both OCD and ADHD and provide further evidence of a familial relationship between ADHD and pediatric OCD which best fit the hypothesis of a unique familial subtype. C1 Massachusetts Gen Hosp, Pediatr Psychopharmacol Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Geller, D (reprint author), Massachusetts Gen Hosp, Pediatr Psychopharmacol Program, Fruit St, Boston, MA 02114 USA. EM dageller@partners.org NR 65 TC 17 Z9 17 U1 9 U2 10 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 JUN 15 PY 2007 VL 61 IS 12 BP 1388 EP 1394 DI 10.1016/j.biopsych.2006.09.026 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 177AX UT WOS:000247127100009 PM 17241617 ER PT J AU DeAngelo, DJ Yu, D Johnson, JL Coutre, SE Stone, RM Stopeck, AT Gockerman, JP Mitchell, BS Appelbaum, FR Larson, RA AF DeAngelo, Daniel J. Yu, Daohai Johnson, Jeffrey L. Coutre, Steven E. Stone, Richard M. Stopeck, Alison T. Gockerman, Jon P. Mitchell, Beverly S. Appelbaum, Frederick R. Larson, Richard A. TI Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801 SO BLOOD LA English DT Article ID BONE-MARROW RELAPSE; HEMATOLOGIC MALIGNANCIES; ARABINOSYL-GUANINE; COMPOUND GW506U78; CELL MALIGNANCIES; R-87 PROTOCOL; CYTO-TOXICITY; PHASE-I; 9-BETA-D-ARABINOFURANOSYLGUANINE; CHILDREN AB Nelarabine (5061.1178) is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine(ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m(2)/day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc Leukemia Grp B Stat Ctr, Durham, NC USA. Stanford Univ, Sch Med, Stanford, CA USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Chicago, Chicago, IL 60637 USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [U10 CA032291, U10 CA047559, CA31946, U10 CA047577, CA41287, U10 CA033601, N01 CA013612, U10 CA031946, CA20319, U10 CA013612, U10 CA020319, CA32291, CA47577, U10 CA041287, CA47559, CA33601] NR 21 TC 90 Z9 94 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5136 EP 5142 DI 10.1182/blood-2006-11-056754 PG 7 WC Hematology SC Hematology GA 180JW UT WOS:000247360200020 PM 17344466 ER PT J AU Harousseau, JL Lancet, JE Reiffers, J Lowenberg, B Thomas, X Huguet, F Fenaux, P Zhang, S Rackoff, W De Porre, P Stone, R AF Harousseau, Jean-Luc Lancet, Jeffrey E. Reiffers, Josy Lowenberg, Bob Thomas, Xavier Huguet, Francoise Fenaux, Pierre Zhang, Steven Rackoff, Wayne De Porre, Peter Stone, Richard CA FIGHT AMLSG TI A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia SO BLOOD LA English DT Article; Proceedings Paper CT 9th Annual Congress of the European-Hematology-Association CY JUN 10-13, 2004 CL Geneva, SWITZERLAND SP European Hematol Assoc ID ACUTE MYELOGENOUS LEUKEMIA; HEMATOLOGIC MALIGNANCIES; IN-VITRO; R115777; FLT3; T(12/15)(P13,Q25); COMBINATION; CANCER; RISK; TRKC AB This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n = 252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or older. Eleven (4%) of 252 patients achieved complete remission (CR) or complete remission with incomplete platelet recovery (CRp; 9 CR and 2 CRp). Nineteen patients (8%), including those who achieved CR/ CRp, achieved a reduction in bone marrow blasts to less than 5% blasts. Bone marrow blasts were reduced more than 50% in an additional 8 patients (total = 27; 11%). Median survival was 369 days for patients who achieved CR/CRp. Myelosuppression was the most common adverse event. The most common nonhematologic toxicities were fever, nausea, and hypokalemia. Single-agent treatment with tipifarnib induced durable CR/CRp, which was associated with prolonged survival, in some patients with refractory or relapsed AML. The response rate observed in this heavily pretreated group of patients suggests the requirement to enhance the response rate either by combining tipifarnib with other active agents or determining factors that are predictive of response. C1 Hop Hotel Dieu, Serv Hematol, Nantes, France. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33620 USA. Hop Haut Leveque, Serv Malad Sang, Pessac, France. Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. Hop Edouard Herriot, Serv Malad Sang, Lyon, France. CHU Purpan, Serv Hematol, Toulouse, France. Hop Avicenne, Paris, France. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. RP Harousseau, JL (reprint author), Hop Hotel Dieu, Serv Hematol, Nantes, France. NR 27 TC 50 Z9 56 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5151 EP 5156 DI 10.1182/blood-2006-09-046144 PG 6 WC Hematology SC Hematology GA 180JW UT WOS:000247360200022 PM 17351110 ER PT J AU Guo, ZY Dose, M Kovalovsky, D Chang, R O'Neil, J Look, AT von Boehmer, H Khazaie, K Gounari, F AF Guo, Zhuyan Dose, Marei Kovalovsky, Damian Chang, Rui O'Neil, Jennifer Look, A. Thomas von Boehmer, Harald Khazaie, Khashayarsha Gounari, Fotini TI beta-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation SO BLOOD LA English DT Article ID WNT SIGNALING PATHWAY; T-CELL DEVELOPMENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADENOMATOUS POLYPOSIS-COLI; HEMATOPOIETIC STEM-CELL; C-MYC; TRANSGENIC MICE; NEGATIVE REGULATOR; GENE-EXPRESSION; ALPHA GENE AB Activation of beta-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T cells promotes thymocyte development without the requirement for pre-TCR signaling. We show here that activated beta-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. beta-Catenin-induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional up-regulation of c-Myc, whose activity is required for transformation because its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DIP thymocytes with stabilized beta-catenin and remains low in the lymphomas, indicating that Notch activation is not required or selected for in beta-catenininduced lymphomas. Thus, beta-catenin activation may provide a mechanism forthe induction of T-cell-acute lymphoblastic leukemia (T-ALL) that does not depend on Notch activation. C1 Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. Dana Farber Canc Inst, Harvard Med Sch, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Mol Imaging Res, Charlestown, MA USA. RP Gounari, F (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. EM fgounari@tufts-nemc.org FU NCI NIH HHS [R01 CA104547-01A1, R01 CA104547]; NIAID NIH HHS [R01 AI059676, R01 AI059676-01]; NIDDK NIH HHS [P30 DK034928, P30 DK34928] NR 56 TC 71 Z9 71 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5463 EP 5472 DI 10.1182/blood-2006-11-059071 PG 10 WC Hematology SC Hematology GA 180JW UT WOS:000247360200063 PM 17317856 ER PT J AU Chen, WY Rosner, B Colditz, GA AF Chen, Wendy Y. Rosner, Bernard Colditz, Graham A. TI Moving forward with breast cancer prevention SO CANCER LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; CARDIOVASCULAR EVENTS; RALOXIFENE EVALUATION; ECONOMIC-EVALUATION; COST-EFFECTIVENESS; MULTIPLE OUTCOMES; RISK PREDICTION C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chen, WY (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM wendy.chen@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [P01 CA 087969] NR 22 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2007 VL 109 IS 12 BP 2387 EP 2391 DI 10.1002/cncr.22711 PG 5 WC Oncology SC Oncology GA 176VR UT WOS:000247113500001 PM 17464950 ER PT J AU Pekow, JR Han, AK Zheng, H Chung, RT AF Pekow, Joel R. Han, Atul K. Zheng, Hui Chung, Raymond T. TI Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis c-related cirrhosis SO CANCER LA English DT Article DE hepatitis C virus; hepatocellular carcinoma; hepatc steatosis; cirrhosis ID NONALCOHOLIC FATTY LIVER; VIRUS CORE PROTEIN; INSULIN-RESISTANCE; TRANSGENIC MICE; RISK-FACTORS; CRYPTOGENIC CIRRHOSIS; NATURAL-HISTORY; UNITED-STATES; IKK-BETA; STEATOHEPATITIS AB BACKGROUND. Chronic hepatitis C can result in fatty changes in the liver. Previous studies have suggested that hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus (HCV) infection. The authors sought to determine whether hepatic steatosis is associated with hepatocellular carcinoma (HCC) in a cohort of patients with hepatitis C-related cirrhosis. METHODS. The authors retrospectively identified 94 consecutive patients with hepatitis C cirrhosis who underwent liver transplantation from 1992 to 2005 and had pathology available for review. Of these, 32 had evidence of HCC, and 62 had no HCC on explant histology. All explant specimens were graded again for steatosis bV a single, blinded pathologist. Steatosis, age, sex, body mass index, HCV RNA, HCV genotype, Model for End-Stage Liver Disease (MELD) score, chronic alcohol use, and diabetes were examined in univariate and multivariate analyses for association with HCC. RESULTS. In total, 69% of patients in the HCC group and 50% of patients in the control group had evidence of steatosis (1+) on histology. Odds ratios for the development of HCC for each grade of steatosis compared with grade 0 were as follows: grade 1 (1.61 [0.6-4.3]), grade 2 (3.68 (1.1-12.8]), and grade 3 or 4 (8.02 [0.6-108.31) (P =.03 for the trend). In univariate analysis, there was a significant association between increasing steatosis grade (P =.03), older age (56 years vs 49 years; P <.02), higher aspartate aminotransferase (122.5 U/L vs 91.5 U/L; P =.005), higher alanine amino transferase (95.8 U/L vs 57.2 U/L; P =.002), higher alpha- feto protein (113.5 ng/mL vs 17.8 ng/mL; P <.001), lower median HCV RNA (239,000 IU/mL vs 496,500 IU/mL; P =.02), higher biologic MELD score (21.8 vs 20.3; P =.03), and risk of HCC. In multivariate analysis, age (P =.02), AFP (P.007), and steatosis (P =.045) were significantly associated with HCC. CONCLUSIONS. in patients with HCV-related cirrhosis, the presence of hepatic steatosis is independently associated with the development of hepatocellular carcinoma. These findings suggest that steatosis poses an additional risk for HCC and that increased vigilance should be practiced in surveillance of persons with both HCV and steatosis. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 41 TC 110 Z9 113 U1 1 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 JUN 15 PY 2007 VL 109 IS 12 BP 2490 EP 2496 DI 10.1002/cncr.22701 PG 7 WC Oncology SC Oncology GA 176VR UT WOS:000247113500014 PM 17487861 ER PT J AU Yang, G Curley, D Bosenberg, MW Tsao, H AF Yang, Guang Curley, David Bosenberg, Marcus W. Tsao, Hensin TI Loss of Xeroderma pigmentosum C (Xpc) enhances melanoma photocarcinogenesis in Ink4a-Arf-deficient mice SO CANCER RESEARCH LA English DT Article ID INDUCED CARCINOGENESIS; ULTRAVIOLET-RADIATION; SKIN TUMORS; TRANSGENIC MICE; HAIRLESS MICE; KNOCKOUT MICE; DNA-REPAIR; RAS; SUSCEPTIBILITY; MUTATIONS AB Despite an extensive body of evidence linking UV radiation and melanoma turnorigenesis, a clear mechanistic understanding of this process is still lacking. Because heritable mutations in both INK4a and the nucleotide excision repair (NER) pathway predispose individuals to melanoma development, we set out to test the hypothesis that abrogation of NER, by deletion of the xeroderma pigmentosum C (Xpc) gene, will heighten melanoma photocarcinogenesis in an Ink4a-Arf-deficient background. Experimentally, we generated a strain of mice doubly deficient in Xpc and Ink4a-Arf and subjected wild-type, Xpc(-/-)Ink4a-Arf(+/+), Xpc(-/-) Ink4a-Arf(-/-), and Xpc(+/+) Ink4a-Arf(-/-) mice to a single neonatal (day P3) dose of UVB without additional chemical promotion. Indeed, there was a significant increase in the development of dermal spindle/ epithelioid cell melanomas in Xpc(-/-)Ink4a-ArJ(-/-) mice when compared with Xpc(+/+),Ink4a-Arf(-/-) mice (P = 0.005); wild-type and Xpc(-/-)Ink4a-Arf(+/+) mice failed to develop tumors. These neoplasms bore a striking histologic resemblance to melanomas that arise in the Tyr-vHRAS/Ink4a-Arf(-/-) context and often expressed melanocyte differentiation marker Tyrp1, thus supporting their melanocytic origination. All strains, except wild-type mice, developed pigmented and non-pigmented epidermal-derived keratinocytic cysts, whereas Xpc(+/+) Ink4a-Arf(-/-) mice exhibited the greatest propensity for squamous cell carcinoma development. We then screened for NRas, HRas, Kras, and BRaf mutations in tumor tissue and detected a higher frequency of rare Kras(Q61) alterations in tumors from Xpc(-/-)Ink4a-Arf(-/-) mice compared with Xpc(+/+) Ink4a-Arf(-/-) mice (50% versus 7%, P = 0.033). Taken together, results from this novel UV-inducible melanoma model suggest that NER loss, in conjunction with Ink4a-Arf inactivation, can drive melanoma photocarcinogenesis possibly through signature Kras mutagenesis. C1 Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Ctr Canc, Boston, MA 02114 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU NCI NIH HHS [K08 CA095532, R01 CA112054, R01CA112054-02, K08CA095532] NR 27 TC 24 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2007 VL 67 IS 12 BP 5649 EP 5657 DI 10.1158/0008-5472.CAN-06-3806 PG 9 WC Oncology SC Oncology GA 180JV UT WOS:000247360100013 PM 17575131 ER PT J AU Boehm, JS Zhao, JJ Yao, J Kim, SY Firestein, R Dunn, IF Sjostrom, SK Garraway, LA Weremowicz, S Richardson, AL Greulich, H Stewart, CJ Mulvey, LA Shen, RR Ambrogio, L Hirozane-Kishikawa, T Hill, DE Vidal, M Meyerson, M Grenier, JK Hinkle, G Root, DE Roberts, TM Lander, ES Polyak, K Hahn, WC AF Boehm, Jesse S. Zhao, Jean J. Yao, Jun Kim, So Young Firestein, Ron Dunn, Ian F. Sjostrom, Sarah K. Garraway, Levi A. Weremowicz, Stanislawa Richardson, Andrea L. Greulich, Heidi Stewart, Carly J. Mulvey, Laura A. Shen, Rhine R. Ambrogio, Lauren Hirozane-Kishikawa, Tomoko Hill, David E. Vidal, Marc Meyerson, Matthew Grenier, Jennifer K. Hinkle, Greg Root, David E. Roberts, Thomas M. Lander, Eric S. Polyak, Kornelia Hahn, William C. TI Integrative genomic approaches identify IKBKE as a breast cancer oncogene SO CELL LA English DT Article ID NF-KAPPA-B; IKK-EPSILON; INDUCED SENESCENCE; GENETIC SCREEN; LUNG-CANCER; RNAI SCREEN; KINASE; MUTATIONS; CELLS; PHOSPHORYLATION AB The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKK epsilon), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKK epsilon expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKK epsilon activates the nuclear factor-kappaB (NF-kappa B) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-kappa B activation in breast cancer, implicate the NF-kappa B pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu; william_hahn@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Hill, David/B-6617-2011; OI Boehm, Jesse/0000-0002-6795-6336 FU NCI NIH HHS [R01 CA094074-04, CA015607, CA30002, CA89021, K01 CA94223, P50 CA089393, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, P50 CA112962, R01 CA094074, R01 CA094074-01A1, R01 CA094074-02, R01 CA094074-03, R01 CA094074-05] NR 55 TC 309 Z9 317 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1065 EP 1079 DI 10.1016/j.cell.2007.03.052 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400012 PM 17574021 ER PT J AU Walkley, CR Shea, JM Sims, NA Purton, LE Orkin, SH AF Walkley, Carl R. Shea, Jeremy M. Sims, Natalie A. Purton, Louise E. Orkin, Stuart H. TI Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment SO CELL LA English DT Article ID LONG-TERM REPOPULATION; SELF-RENEWAL; MULTIPLE-MYELOMA; MYELOPROLIFERATIVE DISORDER; NONAUTONOMOUS FUNCTION; TUMOR-SUPPRESSOR; PROGENITOR CELLS; VIVO EXPANSION; DEFICIENT MICE; DIFFERENTIATION AB Hematopoiesis is maintained by stem cells (HSCs) that undergo fate decisions by integrating intrinsic and extrinsic signals, with the latter derived from the bone marrow (BM) microenvironment. Cell-cycle regulation can modulate stem cell fate, but it is unknown whether this represents an intrinsic or extrinsic effector of fate decisions. We have investigated the role of the retinoblastoma protein (RB), a central regulator of the cell cycle, in hematopoiesis. Widespread inactivation of RB in the murine hematopoietic system resulted in profound myeloproliferation. HSCs were lost from the BM due to mobilization to extramedullary sites and differentiation. This phenotype was not intrinsic to HSCs, but, rather, was the consequence of an RB-dependent interaction between myeloid-derived cells and the microenvironment. These findings demonstrate that myeloproliferation may result from perturbed interactions between hematopoietic cells and the niche. Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div HematolOncol,Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Childrens Hosp Boston,Stem Cell Program, Boston, MA 02115 USA. Univ Melbourne, St Vincents Hosp, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. Harvard Univ, Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div HematolOncol,Dept Pediat Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Sims, Natalie/0000-0003-1421-8468; Walkley, Carl/0000-0002-4784-9031 FU Howard Hughes Medical Institute; NHLBI NIH HHS [R01 HL032259-27, R01 HL032259] NR 78 TC 221 Z9 231 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1081 EP 1095 DI 10.1016/j.cell.2007.03.055 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400013 PM 17574022 ER PT J AU Walkley, CR Olsen, GH Dworkin, S Fabb, SA Swann, J McArthur, GA Westmoreland, SV Chambon, P Scadden, DT Purton, LE AF Walkley, Carl R. Olsen, Gemma Haines Dworkin, Sebastian Fabb, Stewart A. Swann, Jeremy McArthur, Grant A. Westmoreland, Susan V. Chambon, Pierre Scadden, David T. Purton, Louise E. TI A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency SO CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TUMOR-NECROSIS-FACTOR; BONE-MARROW; SELF-RENEWAL; IN-VIVO; DIFFERENTIATION; ALPHA; MICE; PROGENITORS; EXPRESSION AB Myeloproliferative syndromes (IMPS) are a heterogeneous subclass of nonlymphoid hematopoietic neoplasms which are considered to be intrinsic to hematopoietic cells. The causes of MPS are largely unknown. Here, we demonstrate that mice deficient for retinoic acid receptor gamma (RAR gamma), develop MPS induced solely by the RAR gamma-deficient microenvironment. RAR gamma(-/-) mice had significantly increased granulocyte/macrophage progenitors and granulocytes in bone marrow (BM), peripheral blood, and spleen. The MPS phenotype continued for the lifespan of the mice and was more pronounced in older mice. Unexpectedly, transplant studies revealed this disease was not intrinsic to the hematopoietic cells. BM from wild-type mice transplanted into mice with an RAR gamma(-/-) microenvironment rapidly developed the MPS, which was partially caused by significantly elevated TNF alpha in RAR gamma(-/-) mice. These data show that loss of RAR gamma results in a nonhematopoietic cell-intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic disorders. C1 Peter MacCallum Canc Ctr, Trescowthick Res Labs, Melbourne, Vic 3002, Australia. Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Peter MacCallum Canc Ctr, Dept Haematol & Oncol, Melbourne, Vic 3002, Australia. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. ULP, INSERM, CNRS, Coll France,Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, CU Strasbourg, France. Harvard Univ, Stem Cell Inst, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Purton, LE (reprint author), Peter MacCallum Canc Ctr, Trescowthick Res Labs, Melbourne, Vic 3002, Australia. EM lpurton@partners.org OI Walkley, Carl/0000-0002-4784-9031 FU NHLBI NIH HHS [R01 HL044851, R01 HL044851-14]; NIDDK NIH HHS [DK84551, DK71773, R21 DK071773, R21 DK071773-01A1, R21 DK071773-02] NR 44 TC 241 Z9 251 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1097 EP 1110 DI 10.1016/j.cell.2007.05.014 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400014 PM 17574023 ER PT J AU Lietha, D Cai, XM Ceccarelli, DFJ Li, YQ Schaller, MD Eck, MJ AF Lietha, Daniel Cai, Xinming Ceccarelli, Derek F. J. Li, Yiqun Schaller, Michael D. Eck, Michael J. TI Structural basis for the autoinhibition of focal adhesion kinase SO CELL LA English DT Article ID PROTEIN-TYROSINE KINASE; SRC FAMILY KINASES; FERM DOMAIN; CRYSTAL-STRUCTURE; CELL-MIGRATION; GROWTH-FACTOR; PHOSPHORYLATION; FAK; BINDING; AUTOPHOSPHORYLATION AB Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu RI Lietha, Daniel/L-8041-2014 OI Lietha, Daniel/0000-0002-6133-6486 FU NCI NIH HHS [5T32CA09361, CA080942, R01 CA080942, R01 CA080942-07, T32 CA009361]; NCRR NIH HHS [P41 RR001646, P41 RR001646-220082, P41 RR001646-230082]; NHLBI NIH HHS [HL048675, HL45100, P01 HL045100, P01 HL048675, P01 HL048675-135389] NR 57 TC 213 Z9 221 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1177 EP 1187 DI 10.1016/j.cell.2007.05.041 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400020 PM 17574028 ER PT J AU Rajendran, RR Kao, GD AF Rajendran, Ramji R. Kao, Gary D. TI "No turning Bax" in the combined battle against prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ANDROGEN DEPRIVATION THERAPY; BCL-2; RADIOTHERAPY; EXPRESSION; APOPTOSIS; ADJUVANT; CHEMOSENSITIVITY; CHEMOTHERAPY; PARAMETERS; CARCINOMA C1 Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kao, GD (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, John Morgan 180 H, Philadelphia, PA 19104 USA. EM Kao@xrt.upenn.edu FU NCI NIH HHS [R01 CA107956] NR 32 TC 3 Z9 5 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3435 EP 3438 DI 10.1158/1078-0432.CCR-07-0810 PG 4 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200001 PM 17575204 ER PT J AU Stubbs, MC Armstrong, SA AF Stubbs, Matthew C. Armstrong, Scott A. TI Therapeutic implications of leukemia stem cell development SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITORS; BCR-ABL; MICE; TRANSFORMATION; DISORDER; MLL-AF9; LINEAGE; CD44 AB Acute myelogenous leukemias, and perhaps many other cancers, are maintained by a population of cancer stem cells that can regenerate themselves as well as give rise to more differentiated and less proliferative cells that constitute the bulk of the disease. Recent discoveries have shed light on both the nature of leukemia stem cells (LSC) and their cells of origin. Here, we review which hematopoietic cells could give rise to LSC, and the phenotype of fully developed LSC. The perturbed developmental pathways and cellular context of LSC development have implications for the development of new therapeutic approaches. C1 Childrens Hosp Boston, Karp Family Res Labs, Dept Pediat Oncol,Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Armstrong, SA (reprint author), Childrens Hosp Boston, Karp Family Res Labs, Dept Pediat Oncol,Div Hematol Oncol, Dana Farber Canc Inst, 1 Blackfan Circle, Boston, MA 02215 USA. EM Scott.Armstrong@childrens.harvard.edu NR 23 TC 12 Z9 14 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3439 EP 3442 DI 10.1158/1078-0432.CCR-06-3090 PG 4 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200002 PM 17575205 ER PT J AU Khor, LY Moughan, J Al-Saleem, T Hammond, EH Venkatesan, V Rosenthal, SA Ritter, MA Sandler, HM Hanks, GE Shipley, WU Pollack, A AF Khor, Li Yan Moughan, Jennifer Al-Saleem, Tahseen Hammond, Elizabeth H. Venkatesan, Varagur Rosenthal, Seth A. Ritter, Mark A. Sandler, Howard M. Hanks, Gerald E. Shipley, William U. Pollack, Alan TI Bcl-2 and Bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on Radiation Therapy Oncology Group protocol 92-02 SO CLINICAL CANCER RESEARCH LA English DT Article ID NEOADJUVANT HORMONAL-THERAPY; IMMUNOHISTOCHEMICAL ANALYSIS; IN-VIVO; RADICAL PROSTATECTOMY; PROGNOSTIC VALUE; TUMOR-MODEL; CARCINOMA; APOPTOSIS; KI-67; P53 AB Purpose: Bcl-2 is antiapoptotic, and its overexpression has been associated with resistance to androgen deprivation and poor outcome in some patients treated with radiotherapy. Bax is proapoptotic, regulating Bcl-2 through heterodimer formation. In a prior study, Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term androgen deprivation + radiotherapy (STAD+RT) on another Radiation Therapy Oncology Group trial (86-10). A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92-02 with STAD+RT or long-term AD+RT (LTAD+RT). Experimental Design: Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax. Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure. Results: Bcl-2 was positive in 45.6% cases, and Bax expression altered in 53.9% cases. Abnormal Bcl-2 was not related to any of the failure end points tested. Altered Bax expression was significantly associated with any failure (P = 0.023) and marginally with biochemical failure (P = 0.085). The combination of negative Bcl-2/normal Bax expression seemed more robust, being significantly related to reduced biochemical failure (P = 0.036) and any failure (P = 0.046). The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT, as opposed to LTAD+RT Conclusions: Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. Amer Coll Radiol, Radiat Therapy Oncol Grp, Philadelphia, PA USA. LDS Hosp, Dept Pathol, Salt Lake City, UT USA. Univ Western Ontario, Dept Radiat Oncol, London, ON, Canada. Radiol Associates Sacramento Med Grp Inc, Sacramento, CA USA. Univ Wisconsin, Dept Radiat Oncol, Madison, WI USA. Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Pollack, A (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Alan.Pollack@FCCC.EDU FU NCI NIH HHS [CA-006927, CA-101984-01, CA-109556, P30 CA006927, R01 CA101984, R01 CA101984-05, R01 CA109556] NR 37 TC 44 Z9 47 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3585 EP 3590 DI 10.1158/1078-0432.CCR-06-2972 PG 6 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200020 PM 17575222 ER PT J AU Ewend, MG Brem, S Gilbert, M Goodkin, R Penar, PL Varia, M Cush, S Carey, LA AF Ewend, Matthew G. Brem, Steven Gilbert, Mark Goodkin, Robert Penar, Paul L. Varia, Mahesh Cush, Sharon Carey, Lisa A. TI Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM METASTASES; INTERSTITIAL CHEMOTHERAPY; BREAST-CANCER; BIODEGRADABLE POLYMERS; RECURRENT GLIOMAS; RANDOMIZED-TRIAL; RADIOTHERAPY; PACLITAXEL; DELIVERY; RADIOSURGERY AB Purpose: To define the safety and efficacy of carmustine polymer wafers when added to a regimen of surgery and external beam radiotherapy for treatment of a single brain metastasis. Experimental Design: Adult patients underwent craniotomy for a single brain metastasis, and carmustine polymer wafers were placed in the tumor resection cavity. Patients then received whole-brain radiotherapy and were followed for patterns of recurrence in the central nervous system, toxicity, and survival. Results: We enrolled 25 patients with solitary brain metastases from lung (13 patients), melanoma (4 patients), breast (3 patients), and renal carcinoma (3 patients). Two patients had severe adverse events thought to be related to wafer placement, one with seizures alone, and one with seizures and subsequent respiratory compromise. Both responded to medical therapy. There were no wound infections. The local recurrence rate was surprisingly low (0%). Four patients (16%) relapsed elsewhere in the brain, and two patients (8%) relapsed in the spinal cord. Median survival was 33 weeks; 33% of patients survived 1 year, and 25% survived 2 years. Conclusions: The addition of local chemotherapy delivered via carmustine polymer wafers to a regimen of surgical resection and external beam radiotherapy was well tolerated by patients undergoing surgery for a single brain metastasis. There were no local recurrences, suggesting that this treatment further reduced the risk of local relapse. C1 Univ N Carolina, Div Neurosurg, Chapel Hill, NC 27599 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Vermont, Burlington, VT USA. RP Ewend, MG (reprint author), Univ N Carolina, Div Neurosurg, 3013 Burnett Womack Bldg, Chapel Hill, NC 27599 USA. EM ewend@med.unc.edu NR 28 TC 38 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3637 EP 3641 DI 10.1158/1078-0432.CCR-06-2095 PG 5 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200028 PM 17575228 ER PT J AU Holmes, MD Morin, S Chen, WY Kroenke, CH Spiegelman, D Colditz, GA AF Holmes, Michelle D. Morin, Susan Chen, Wendy Y. Kroenke, Candyce H. Spiegelman, Donna Colditz, Graham A. TI Smoking and survival after breast cancer diagnosis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast neoplasms; survival; smoking; cohort studies; women ID MARGINAL STRUCTURAL MODELS; NATIONAL DEATH INDEX; CIGARETTE-SMOKING; LUNG-CANCER; WOMEN; RISK; METASTASES; CHEMOTHERAPY; EXPRESSION; CARCINOMA AB We examined whether a history of smoking is associated with an increased risk of death from any cause or from breast cancer, among women diagnosed with breast cancer. This was a prospective observational study among 5,056 women from the Nurses' Health Study with Stages I-III invasive breast cancer diagnosed between 1978 and 2002 and for whom we had information on smoking, and who were followed until January 2002 or death, whichever came first. Subjects were classified as current, former or never smokers based upon smoking status at the biennial questionnaire immediately preceding the breast cancer diagnosis. In multivariate-adjusted analyses, compared with never smokers, women who were current smokers had a 43% increased adjusted relative risk (RR) [95% confidence interval (95% CI): 1.24-1.65] of death from any cause. A strong linear gradient was observed with the number of cigarettes per day smoked, p-trend <0.0001; the RR (95% Cl) for 1-14, 15-24 and 25 or more cigarettes per day was 1.27 (1.01-1.61), 1.30 (1.08-1.57) and 1.79 (1.47-2.19). In contrast, there was no association with current smoking and breast cancer death; the RR (95% CI) was 1.00 (0.83-1.19). Current and past smokers were more likely than never smokers to die from primary lung cancer, chronic obstructive pulmonary disease and other lung diseases. We conclude that a history of smoking increased mortality following diagnosis with breast cancer, but did not increase mortality from breast cancer. (c) 2007 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. No Calif Vet Adm Hlth Syst, Dept Internal Med, Sacramento, CA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Holmes, MD (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM michelle.holmes@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969] NR 35 TC 42 Z9 42 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2672 EP 2677 DI 10.1002/ijc.22575 PG 6 WC Oncology SC Oncology GA 159NO UT WOS:000245873000019 PM 17278091 ER PT J AU Oei, AL Verheijen, RH Seiden, MV Benigno, BB Lopes, A Soper, JT Epenetos, AA Massuger, LF AF Oei, Angele L. Verheijen, Rene H. Seiden, Michael V. Benigno, Benedict B. Lopes, Alberto Soper, John T. Epenetos, Agamemnon A. Massuger, Leon F. TI Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HMFG1; intraperitoneal; ovarian cancer; yttrium ID NEGATIVE 2ND-LOOK LAPAROTOMY; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; CISPLATIN; CHEMOTHERAPY; PACLITAXEL; CARCINOMA AB This study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium-90-labeled murine monoclonal antibody HMFG1 (Y-90-muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic-IV were randomized between standard treatment plus a single IP Y-90-labeled muHMFG1 versus standard treatment alone after negative second-look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow-up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse-free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences. (c) 2007 Wiley-Liss, Inc. C1 Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Obstet & Gynecol, NL-6500 HB Nijmegen, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Obstet & Gynecol, Amsterdam, Netherlands. Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. Southeastern Gynecol Oncol, Dept Gynecol Oncol, Atlanta, GA USA. Queen Elizabeth Hosp, No Gynecol Oncol Ctr, Dept Gynecol Oncol, Gateshead, England. Duke Univ, Med Ctr, Dept Radiotherapy Oncol, Durham, NC USA. St Bartholomews Hosp, Dept Obstet & Gynecol, London, England. RP Massuger, LF (reprint author), Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Obstet & Gynecol, 791,POB 9101, NL-6500 HB Nijmegen, Netherlands. EM L.Massuger@obgyn.umcn.nl RI Massuger, Leon/H-8072-2014; OI de Barros Lopes, Alberto/0000-0002-8796-3891 NR 16 TC 41 Z9 43 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2710 EP 2714 DI 10.1002/ijc.22663 PG 5 WC Oncology SC Oncology GA 159NO UT WOS:000245873000024 PM 17354223 ER PT J AU Lejard, V Brideau, G Blais, F Salingcarnboriboon, R Wagner, G Roehrl, MHA Noda, M Duprez, D Houillier, P Rossert, J AF Lejard, Veronique Brideau, Gaelle Blais, Frederic Salingcarnboriboon, Ruchanee Wagner, Gerhard Roehrl, Michael H. A. Noda, Masaki Duprez, Delphine Houillier, Pascal Rossert, Jerome TI Scleraxis and NFATc regulate the expression of the pro-alpha 1(I) collagen gene in tendon fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; TRANSGENIC MICE; TRANSCRIPTION FACTOR; CONNECTIVE-TISSUE; CARDIAC VALVES; REPORTER GENES; BONE-FORMATION; NF-ATC; CELLS; PROMOTER AB The combinatorial action of separate cis-acting elements controls the cell-specific expression of type I collagen genes. In particular, we have shown that two short elements located between -3.2 and -2.3 kb and named TSE1 and TSE2 are needed for expression of the mouse COL1a1 gene in tendon fibroblasts. In this study, we analyzed the trans-acting factors binding to TSE1 and TSE2. Gel shift experiments showed that scleraxis ( SCX), which is a basic helix-loop-helix transcription factor that is expressed selectively in tendon fibroblasts, binds TSE2, preferentially as a SCX/E47 heterodimer. In transfection experiments, overexpression of SCX and E47 strongly enhanced the activity of reporter constructs harboring either four copies of TSE2 cloned upstream of the COL1a1 minimal promoter or a 3.2-kb segment of the COL1a1 proximal promoter. Analysis of TSE1 showed that it contains a consensus binding site for NFATc transcription factors. This led us to show that the NFATc4 gene is expressed in tendons of developing mouse limbs and in TT-D6 cells, a cell line that has characteristics of tendon fibroblasts. In gel shift assays, TSE1 bound NFATc proteins present in nuclear extracts from TT-D6 cells. In transfection experiments, overexpression of NFATc transactivated a reporter construct harboring four copies of TSE1 cloned upstream of the COL1a1 minimal promoter. By contrast, inhibition of the nuclear translocation of NFATc proteins in TT-D6 cells strongly inhibited the expression of the COL1a1 gene. Taken together, these results suggest that SCX and NFATc4 cooperate to activate the COL1a1 gene specifically in tendon fibroblasts. C1 Inst Biomed Cordeliers, INSERM U652, F-75006 Paris, France. Univ Paris 06, F-75005 Paris, France. Univ Paris 05, F-75006 Paris, France. CNRS, UMR 7622, F-75005 Paris, France. Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Pharmacol, Tokyo 1010062, Japan. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rossert, J (reprint author), Inst Biomed Cordeliers, INSERM U652, 15 Rue Ecole Med, F-75006 Paris, France. EM jerome.rossert@egp.aphp.fr NR 41 TC 108 Z9 113 U1 3 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 JUN 15 PY 2007 VL 282 IS 24 BP 17665 EP 17675 DI 10.1074/jbc.M610113200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176KS UT WOS:000247084500039 PM 17430895 ER PT J AU Alter, G Suscovich, TJ Teigen, N Meier, A Streeck, H Brander, C Altfeld, M AF Alter, Galit Suscovich, Todd J. Teigen, Nickolas Meier, Angela Streeck, Hendrik Brander, Christian Altfeld, Marcus TI Single-stranded RNA derived from HIV-1 serves as a potent activator of NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELL; TOLL-LIKE RECEPTORS; VIRUS-INFECTED PATIENTS; DENDRITIC CELLS; VIRAL-INFECTION; T-CELLS; CYTOLYTIC FUNCTION; INNATE RESISTANCE; PERIPHERAL-BLOOD; KAPPA-B AB Persistent immune activation is a hallmark of chronic viremic HIV-1 infection. Activation of cells of the innate immune system, such as NK cells, occurs rapidly upon infection, and is sustained throughout the course of the disease. However, the precise underlying mechanism accounting for the persistent HIV-1-induced activation of NK cells is poorly understood. In this study, we assessed the role of uridine-rich ssRNA derived from the HIV-1 long terminal repeat (ssRNA40) on activation of NK cells via TLR7/8. Although dramatic activation of NK cells was observed following stimulation of PBMC with ssRNA40, negligible activation was observed following stimulation of purified NK cells despite their expression of TLR8 mRNA and protein. The functional activation of NK cells by this HIV1-encoded TLR7/8 ligand could not be reconstituted with exogenous IL-12, IFN-alpha, or TNF-alpha, but was critically dependent on the direct contact of NK cells with plasmacytoid dendritic cells or CD14(+) monocytes, indicating an important level of NK cell cross-talk and regulation by accessory cells during TLR-mediated activation. Coincubation of monocyte/plasmacytoid dendritic cells, NK cells, and ssRNA40 potentiated NK cell EFN-gamma secretion in response to MHC-devoid target cells. Studies using NK cells derived from individuals with chronic HIV-1 infection demonstrated a reduction of NK cell responsiveness following stimulation with TLR ligands in viremic HIV-1 infection. These data demonstrate that HIV-1-derived TLR ligands can contribute to the immune activation of NK cells and may play an important role in HIV-1-associated immunopathogenesis and NK cell dysfunction observed during acute and chronic viremic HIV-1 infection. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr,Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr,Infect Dis Unit, Boston, MA 02129 USA. EM maltfeld@partners.org FU NIAID NIH HHS [R01 AI 067031] NR 59 TC 63 Z9 65 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 JUN 15 PY 2007 VL 178 IS 12 BP 7658 EP 7666 PG 9 WC Immunology SC Immunology GA 177YX UT WOS:000247189500023 PM 17548602 ER PT J AU Bae, J Mitsiades, C Tai, YT Bertheau, R Shammas, M Batchu, RB Li, C Catley, L Prabhala, R Anderson, KC Munshi, NC AF Bae, Jooeun Mitsiades, Constantine Tai, Yu-Tzu Bertheau, Robert Shammas, Masood Batchu, Ramesh Babu Li, Cheng Catley, Lawrence Prabhala, Rao Anderson, Kenneth C. Munshi, Nikhil C. TI Phenotypic and functional effects of heat shock protein 90 inhibition on dendritic cell SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; HSP90 MOLECULAR CHAPERONE; TYROSINE KINASE; MAJOR HISTOCOMPATIBILITY; CANCER-CELLS; ATP BINDING; HSP90-SPECIFIC INHIBITOR; PROSTATE-CANCER; T-LYMPHOCYTES; IN-VIVO AB The 90-kDa heat shock protein (Hsp90) plays an important role in conformational regulation of cellular proteins and thereby cellular signaling and function. As Hsp90 is considered a key component of immune function and its inhibition has become an important target for cancer therapy, we here evaluated the role of Hsp90 in human dendritic cell (DQ phenotype and function. Hsp90 inhibition significantly decreased cell surface expression of costimulatory (CD40, CD80, CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in immature DC and mature DC and was associated with down-regulation of both RNA and intracellular protein expression. Importantly, Hsp90 inhibition significantly inhibited DC function. It decreased Ag uptake, processing, and presentation by immature DC, leading to reduced T cell proliferation in response to tetanus toxoid as a recall Ag. It also decreased the ability of mature DC to present Ag to T cells and secrete IL-12 as well as induce IFN-gamma secretion by allogeneic T cells. These data therefore demonstrate that Hsp90-mediated protein folding is required for DC function and, conversely, Hsp90 inhibition disrupts the DC function of significant relevance in the setting of clinical trials evaluating novel Hsp90 inhibitor therapy in cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 NR 65 TC 28 Z9 30 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2007 VL 178 IS 12 BP 7730 EP 7737 PG 8 WC Immunology SC Immunology GA 177YX UT WOS:000247189500031 PM 17548610 ER PT J AU Schaubert, KL Price, DA Frahm, N Li, JZ Ng, HL Joseph, A Paul, E Majumder, B Ayyavoo, V Gostick, E Adams, S Marincola, FM Sewell, AK Altfeld, M Brenchley, JM Douek, DC Yang, OO Brander, C Goldstein, H Kan-Mitchell, J AF Schaubert, Keri L. Price, David A. Frahm, Nicole Li, Jinzhu Ng, Hwee L. Joseph, Aviva Paul, Elyse Majumder, Biswanath Ayyavoo, Velpandi Gostick, Emma Adams, Sharon Marincola, Francesco M. Sewell, Andrew K. Altfeld, Marcus Brenchley, Jason M. Douek, Daniel C. Yang, Otto O. Brander, Christian Goldstein, Harris Kan-Mitchell, June TI Availability of a diversely avid CD8(+) T cell repertoire specific for the subdominant HLA-A2-restricted HIV-1 Gag p24(19-27) epitope SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTE RESPONSES; ESCAPE VARIANTS; IN-VIVO; HETEROLOGOUS IMMUNITY; PRIMARY INFECTION; VACCINE DESIGN; TCR REPERTOIRE; CTL RESPONSE AB HLA-A2-restricted CTL responses to immunodominant HIV-1 epitopes do not appear to be very effective in the control of viral replication in vivo. In this study, we studied human CD8(+) T cell responses to the subdominant HEA-A2-restricted epitope TV9 (Gag p24(19-27), TLNAWVKVV) to explore the possibility of increasing its immune recognition. We confirmed in a cohort of 313 patients, infected by clade B or clade C viruses, that TV9 is rarely recognized. Of interest, the functional sensitivity of the TV9 response can be relatively high. The potential T cell repertoires for TV9 and the characteristics of constituent clonotypes were assessed by ex vivo priming of circulating CD8(+) T cells from healthy seronegative donors. TV9-specific CTLs capable of suppressing viral replication in vitro were readily generated, suggesting that the cognate T cell repertoire is not limiting. However, these cultures contained multiple discrete populations with a range of binding avidities for the TV9 tetramer and correspondingly distinct functional dependencies on the CD8 coreceptor. The lack of dominant clonotypes was not affected by the stage of maturation of the priming dendritic cells. Cultures primed by dendritic cells transduced to present endogenous TV9 were also incapable of clonal maturation. Thus, a diffuse TCR repertoire appeared to be an intrinsic characteristic of TV9-specific responses. These data indicate that subdominance is not a function of poor immunogenicity, cognate TCR repertoire availability, or the potential avidity properties thereof, but rather suggest that useful responses to this epitope are suppressed by competing CD8(+) T cell populations during HIV-1 infection. C1 Univ Texas, Dept Biol Sci, El Paso, TX 79968 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Nuffield Dept Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02192 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. NIH, Sect Immunogenet, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Cardiff Wales, Dept Med Biochem & Immunol, Cardiff, Wales. RP Kan-Mitchell, J (reprint author), Univ Texas, Dept Biol Sci, Biol Sci Bldg,500 W Univ Ave, El Paso, TX 79968 USA. EM jkanmitchell@utep.edu RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Ayyavoo, Velpandi/0000-0002-9043-0885 FU Intramural NIH HHS [Z01 AI001029-01, Z99 AI999999, ZIA AI001029-02]; Medical Research Council [G0501963]; NCRR NIH HHS [5G12 RR 008124, G12 RR008124]; NIAID NIH HHS [R01 AI 064069, R01 AI064069] NR 93 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2007 VL 178 IS 12 BP 7756 EP 7766 PG 11 WC Immunology SC Immunology GA 177YX UT WOS:000247189500034 PM 17548613 ER PT J AU Assarsson, E Sidney, J Oseroff, C Pasquetto, V Bui, HH Frahm, N Brander, C Peters, B Grey, H Sette, A AF Assarsson, Erika Sidney, John Oseroff, Carla Pasquetto, Valerie Bui, Huynh-Hoa Frahm, Nicole Brander, Christian Peters, Bjoern Grey, Howard Sette, Alessandro TI A quantitative analysis of the variables affecting the repertoire of T cell specificities recognized after vaccinia virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MHC CLASS-I; LYMPHOCYTIC CHORIOMENINGITIS; TRANSGENIC MICE; SUBDOMINANT EPITOPES; ANTIGENIC PEPTIDES; SMALLPOX VACCINES; KINETIC STABILITY; CTL RESPONSES; BALB/C MICE AB Many components contribute to immunodominance in the response to a complex virus, but their relative importance is unclear. This was addressed using vaccinia virus and HLA-A*0201 as the model system. A comprehensive analysis of 18 viral proteins recognized by CD8(+) T cell responses demonstrated that approximately one-fortieth of all possible 9- to 10-mer peptides were high-affinity HLA-A*0201 binders. Peptide immunization and T cell recognition data generated from 90 peptides indicated that about one-half of the binders were capable of eliciting T cell responses, and that one-seventh of immunogenic peptides are generated by natural processing. Based on these results, we estimate that vaccinia virus encodes similar to 150 dominant and subdominant epitopes restricted in by HLA-A*0201. However, of all these potential epitopes, only 15 are immunodominant and actually recognized in vivo during vaccinia virus infection of HLA-A*0201 transgenic mice. Neither peptide-binding affinity, nor complex stability, nor TCR avidity, nor amount of processed epitope appeared to strictly correlate with immunodominance status. Additional experiments suggested that vaccinia infection impairs the development of responses directed against subdominant epitopes, This suggested that additional factors, including immunoregulatory mechanisms, restrict the repertoire of T cell specificities after vaccinia infection by a factor of at least 10. C1 La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02116 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. RP Sette, A (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, 9420 Athena Circle, La Jolla, CA 92037 USA. EM alex@liai.org FU NIAID NIH HHS [R01 AI 067077, R01 AI 56268] NR 64 TC 97 Z9 97 U1 2 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2007 VL 178 IS 12 BP 7890 EP 7901 PG 12 WC Immunology SC Immunology GA 177YX UT WOS:000247189500048 PM 17548627 ER PT J AU Grinspoon, S AF Grinspoon, Steven TI Use of thiazolidinediones in HIV-infected patients: What have we learned? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID CONTROLLED-TRIAL; DOUBLE-BLIND; ROSIGLITAZONE; LIPODYSTROPHY; METFORMIN C1 Massachusetts Gen Hosp, MGH Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, MGH Program Nutr Metab, L0N 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 10 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2007 VL 195 IS 12 BP 1731 EP 1733 DI 10.1086/518008 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BK UT WOS:000246986900001 PM 17492586 ER PT J AU Blackard, JT Hiasa, Y Smeaton, L Jamieson, DJ Rodriguez, I Mayer, KH Chung, RT AF Blackard, Jason T. Hiasa, Yoichi Smeaton, Laura Jamieson, Denise J. Rodriguez, Irma Mayer, Kenneth H. Chung, Raymond T. TI Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; HYPERVARIABLE REGION 1; HIV-INFECTED PATIENTS; NEGATIVE-STRAND RNA; PERIPHERAL-BLOOD; EXTRAHEPATIC REPLICATION; INTERFERON THERAPY; HEMATOPOIETIC-CELLS AB Extrahepatic replication has important implications for the transmission and treatment of hepatitis C virus (HCV). We analyzed longitudinal HCV diversity in peripheral-blood mononuclear cells (PBMCs) and serum during HCV monoinfection and HCV/HIV coinfection to determine whether distinct amino acid signatures characterized HCV replicating within PBMCs. Analysis of E1-HVR1 sequences demonstrated higher serum genetic distances among HCV/human immunodeficiency virus (HIV)-coinfected persons. Moreover, consensus PBMC sequences were rarely identical to those in the corresponding serum, suggesting divergence in these 2 compartments. Three of 5 HCV/HIV-coinfected participants showed evidence of HCV compartmentalization in PBMCs. Additionally, signature sequence analysis identified PBMC-specific amino acids in all HCV/HIV coinfected persons. To our knowledge, this is the first study to identify specific amino acids that may distinguish HCV variants replicating in PBMCs. It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection. C1 Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Miriam Hosp, Dept Med, Providence, RI 02906 USA. Brown Univ, Dept Med, Providence, RI 02912 USA. Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Matsuyama, Ehime 790, Japan. RP Blackard, JT (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, ML 0595, Cincinnati, OH 45267 USA. EM jason.blackard@uc.edu FU NIAID NIH HHS [P30-AI42851, P30 AI042851, P30 AI42853, P30 AI042853]; NIDA NIH HHS [R21 DA022148, R21 DA022148-02, R21 DA022148-01]; PHS HHS [U64/CCU106795] NR 40 TC 37 Z9 37 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2007 VL 195 IS 12 BP 1765 EP 1773 DI 10.1086/518251 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BK UT WOS:000246986900007 PM 17492592 ER PT J AU Franciosi, S De Gasperi, R Dickstein, DL English, DF Rocher, AB Janssen, WGM Christoffel, D Sosa, MAG Hof, PR Buxbaum, JD Elder, GA AF Franciosi, Sonia De Gasperi, Rita Dickstein, Dara L. English, Daniel F. Rocher, Anne B. Janssen, William G. M. Christoffel, Daniel Sosa, Miguel A. Gama Hof, Patrick R. Buxbaum, Joseph D. Elder, Gregory A. TI Pepsin pretreatment allows collagen IV immunostaining of blood vessels in adult mouse brain SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE adult; antigen retrieval; blood vessels; brain; collagen IV; immunohistochemistry; mouse; pepsin ID ALZHEIMERS-DISEASE; IMMUNOHISTOCHEMICAL DETECTION; LAMININ IMMUNOHISTOCHEMISTRY; NERVOUS-TISSUE; SECTIONS; MICE; MICROVASCULATURE; IMMUNOREACTIVITY; NEUROGENESIS; EXPRESSION AB While the brain vasculature can be imaged with many methods, immunohistochemistry has distinct advantages due to its simplicity and applicability to archival tissue. However, immumohistochemical staining of the murine brain vasculature in aldehyde fixed tissue has proven elusive and inconsistent using current protocols. Here we investigated whether antigen retrieval methods could improve vascular staining in the adult mouse brain. We found that pepsin digestion prior to immunostaining unmasked widespread collagen IV staining of the cerebrovasculature in the adult mouse brain. Pepsin treatment also unmasked widespread vascular staining with laminin, but only marginally improved isolectin B4 staining and did not enhance vascular staining with fibronectin, perlecan or CD 146. Collagen IV immunoperoxidase staining was easily combined with cresyl violet counterstaining making it suitable for stereological analyses of both vascular and neuronal parameters in the same tissue section. This method should be widely applicable for labeling the brain vasculature of the mouse in aldehyde fixed tissue from both normal and pathological states. (c) 2007 Elsevier B.V. All rights reserved. C1 James J Peters Dept Vet Adm Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY 10029 USA. RP Elder, GA (reprint author), James J Peters Dept Vet Adm Med Ctr, Res & Dev Serv, 3F22,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu RI Dickstein, Dara/F-3036-2013; OI Buxbaum, Joseph/0000-0001-8898-8313; Christoffel, Dan/0000-0002-6303-5134 FU NIA NIH HHS [P01 AG002219-26, AG002219, AG005138, AG010491, AG020139, P01 AG002219, P01 AG010491, P01 AG010491-11, P50 AG005138, P50 AG005138-23, R01 AG020139, R01 AG020139-04] NR 30 TC 30 Z9 30 U1 1 U2 4 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 JUN 15 PY 2007 VL 163 IS 1 BP 76 EP 82 DI 10.1016/j.jneumeth.2007.02.020 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 174HX UT WOS:000246934100011 PM 17403541 ER PT J AU Eckert, DJ DougMcEvoy, R George, KE Thomson, KJ Catcheside, PG AF Eckert, Danny J. DougMcEvoy, R. George, Kate E. Thomson, Kieron J. Catcheside, Peter G. TI Genioglossus reflex inhibition to upper-airway negative-pressure stimuli during wakefulness and sleep in healthy males SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HUMAN INSPIRATORY MUSCLES; EYE-MOVEMENT SLEEP; RESPIRATORY ACTIVITY; PHARYNGEAL PRESSURE; ACTIVATION; APNEA; OCCLUSION; HUMANS; RESPONSES; PATHOGENESIS AB During wakefulness, obstructive sleep apnoea patients appear to compensate for an anatomically narrow upper airway by increasing upper airway dilator muscle activity, e.g. genioglossus, at least partly via a negative-pressure reflex that may be diminished in sleep. Previous studies have assessed the negative-pressure reflex using multi-unit, rectified, moving-time-average EMG recordings during brief pulses of negative upper-airway pressure. However, moving-time averaging probably obscures the true time-related reflex morphology, potentially masking transient excitatory and inhibitory components. This study aimed to re-examine the genioglossus negative-pressure reflex in detail, without moving-time averaging. Bipolar fine-wire electrodes were inserted per orally into the genioglossus muscle in 17 healthy subjects. Two upper airway pressure catheters were inserted per nasally. Genioglossus EMG reflex responses were generated via negative-pressure stimuli (similar to -10 cmH(2)O at the choanae, 250 ms duration) delivered during wakefulness and sleep. Ensemble-averaged, rectified, genioglossus EMG recordings demonstrated reflex activation (onset latency 26 +/- 1 ms; peak amplitude 231 +/- 29% of baseline) followed by a previously unreported suppression (peak latency 71 +/- 4 ms; 67 +/- 8% of baseline). Single-motor-unit activity, clearly identifiable in similar to 10% of trials in six subjects, showed a concomitant increase in the interspike interval from baseline (26 +/- 9 ms, P = 0.01). Genioglossus negative-pressure reflex morphology and amplitude of the initial peak were maintained in non-rapid eye movement (NREM) sleep but suppression amplitude was more pronounced during NREM and declined further during REM sleep compared to wakefulness. These data indicate there are both excitatory and inhibitory components to the genioglossus negative-pressure reflex which are differentially affected by state. C1 Repatriat Gen Hosp, Adelaide Inst Sleep Hlth, Daw Pk, SA 5041, Australia. Univ Adelaide, Discipline Physiol, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. Flinders Univ S Australia, Dept Med, Bedford Pk, SA 5043, Australia. RP Eckert, DJ (reprint author), Brigham & Womens Hosp, Div Sleep Med, Sleep Disorders Program, BIDMC, 75 Francis St, Boston, MA 02115 USA. EM deckert@rics.bwh.harvard.edu RI Eckert, Danny/A-6145-2012 OI Eckert, Danny/0000-0003-3503-2363 NR 42 TC 37 Z9 38 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN 15 PY 2007 VL 581 IS 3 BP 1193 EP 1205 DI 10.1113/j.physiol.2007.132332 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 177TF UT WOS:000247174700028 PM 17395627 ER PT J AU Buchholz, TA Haffty, BG Harris, JR AF Buchholz, Thomas A. Haffty, Bruce G. Harris, Jay R. TI Should all patients undergoing breast conserving therapy for DCIS receive radiation therapy? Yes. Radiation therapy, an important component of breast conserving treatment for patients with ductal carcinoma in situ of the breast SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material ID CANCER; RADIOTHERAPY; AUSTRALIA; WOMEN C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ 08901 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Buchholz, TA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Unite 1202,1515 Holcombe Blvd, Houston, TX 77030 USA. EM tbuchhol@mdanderson.org NR 11 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 15 PY 2007 VL 95 IS 8 BP 610 EP 613 DI 10.1002/jso.20711 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA 174JP UT WOS:000246938500002 PM 17221862 ER PT J AU Meyer, JS Huang, JB Chowdhury, MH AF Meyer, John Stirling Huang, Juebin Chowdhury, Munir H. TI MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson-Lewy body dementias SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress on Vascular Dementia CY OCT 20-23, 2005 CL Oporto, PORTUGAL DE mild cognitive impairment (MCI); dementia of Alzheimer's type (DAT); vascular dementia (VaD); Parkinson-Lewy body dementia (PLBD); combined mini-mental-cognitive capacity screening examination (CMC); magnetic resonance imaging (MRI) ID WHITE-MATTER LESIONS; CLINICAL-DIAGNOSIS; CEREBRAL ATROPHY; TEMPORAL-LOBE; INTERNATIONAL WORKSHOP; HIPPOCAMPAL ATROPHY; RATING-SCALE; DISEASE; BODIES; AD AB Objectives: MRI assessments were correlated with serial Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC). Vascular-MCI (VMCI), Neurodegenerative MCI (NMCI) and Parkinson-Lewy body MCI (PLB-MCI) were compared during conversions to dementia. Mild cognitive impairments (MCI) are identifiable prodromes for all dementia subtypes. MRI abnormalities are characterized among MCI subjects prodromal for dementia of Alzheimer's disease (DAT), vascular dementia (VaD) and Parkinson-Lewy body dementia (PLBD). Methods: Aging volunteers (n = 166) were recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia. Cognitively normal (CN, n = 52), MCIs of neurodegenerative (N-MCI, n-30), vascular (V-MCI, n=35) and Parkinson-Lewy Body (PLB-MCI, n = 8) subtypes, plus converted DAT (n = 19), VaD (n = 17) and PLBD (n = 5) were all diagnosed according to established protocol recommendations. Cerebral MRI abnormalities were likewise intercorrelated utilizing quantitative volumetric measurements. Results: V-MCI and converted VAD showed extensive leukoaraiosis with more lacunar infarcts than subjects with N-MCI or PLB-MCI. NMCI, prodromal for DAT, showed medial temporal atrophy, greater enlargement of temporal horns, and fewer vascular lesions. PLB-MCI, prodromal for PLBD, displayed third ventricular enlargement greater than N-MCI and V-MCI, with similar but less severe atrophy of medial temporal lobe than N-MCI and fewer vascular lesions than V-MCI. Cognitive Impairments due to PLB with vascular features (V-PLB-CI) showed more lacunar and microvascular lesions involving both white matter and basal ganglia with greater frontal horn enlargement. Conclusions: This study confirms different MCI subtypes prior to conversion to different dementias listed, recognizable by specific MRI abnormalities. (c) 2007 Elsevier B.V, All rights reserved. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77098 USA. Michael E DeBakey Vet Adm Med Ctr, Cerebrovasc Res Labs, Houston, TX 77098 USA. RP Meyer, JS (reprint author), Baylor Coll Med, Dept Neurol, 2321 SW Freeway, Houston, TX 77098 USA. EM johnstirlingmeyer@yahoo.com NR 65 TC 34 Z9 37 U1 1 U2 7 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 JUN 15 PY 2007 VL 257 IS 1-2 BP 97 EP 104 DI 10.1016/j.jns.2007.01.016 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 184MV UT WOS:000247646700017 PM 17316690 ER PT J AU Ansell, PJ Zhou, YL Schjeide, BM Kerner, A Zhao, J Zhang, X Klibanski, A AF Ansell, Peter J. Zhou, Yunli Schjeide, Brit-Maren Kerner, Alissa Zhao, Jing Zhang, Xun Klibanski, Anne TI Regulation of growth hormone expression by Delta-like protein 1 (Dlk1) SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Dlk1; growth hormone; promoter ID INHIBITS ADIPOCYTE DIFFERENTIATION; FETAL ANTIGEN-1 FA1; GENE-EXPRESSION; NEUROENDOCRINE TUMORS; TRANSCRIPTION FACTORS; PITUITARY; PROTEIN; CELLS; PREF-1; REPRESSION AB Delta-like protein 1 (Dlk1) is a transmembrane protein characterized by epidermal growth factor (EGF)-like repeats. Dlk1, which is also known as preadipocyte factor 1 (pref-1) because of its ability to inhibit preadipocyte differentiation, regulates the differentiation of several other cell types through unknown mechanisms. To elucidate DIM functions, identification of Dlk1-regulated target genes is critical. The observation that Dlk1 is expressed in many endocrine tissues suggests that Dlk1 may have endocrine-related functions. Because Dlk1 is expressed in GH producing cells, we hypothesize that one function of Dlk1 is to regulate GH expression. We found that GH mRNA, protein, and secretion were significantly decreased in GH3 pituitary cell clones that stably express Dlk1. In contrast, Dlk1 expression was unable to alter prolactin expression. Co-transfection of GH3 cells with a GH promoter-regulated reporter gene showed that Dlk1 repressed GH promoter activity. Deletion and mutation analysis of the GH promoter indicated that Pit-1 binding sites in the GH promoter are required for Dlk1-mediated repression. Furthermore, Dlk1 expression represses Pit-1-mediated transcription when both proteins are co-expressed in MCF-7 cells. Deletion analysis of Dlk1 revealed that the ability of Dlk1 to regulate GH promoter activity is independent of both its EGF-like repeats and its ability to modulate MAP kinase activity. The observation that Dlk1 regulates GH expression identifies the first endocrine function of Dlk1, establishes GH as a Dlk1-regulated target gene, and provides a model system to facilitate studies of Dlk1-mediated signaling. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01 DK040947, P30 DK040561, R01-DK-40947, R01 DK040947-14, P30 DK040561-12]; NIGMS NIH HHS [R01 GM110090] NR 45 TC 20 Z9 22 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 15 PY 2007 VL 271 IS 1-2 BP 55 EP 63 DI 10.1016/j.mce.2007.04.002 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 184ZV UT WOS:000247682000006 PM 17485162 ER PT J AU Kim, Y Hilderbrand, SA Weissleder, R Tung, CH AF Kim, Youngmi Hilderbrand, Scott A. Weissleder, Ralph Tung, Ching-Hsuan TI Sugar sensing based on induced pH changes SO CHEMICAL COMMUNICATIONS LA English DT Article ID INDICATOR-DISPLACEMENT ASSAYS; BORONIC ACIDS; GLUCOSE; BINDING; WATER; FLUORESCENCE; CHEMOSENSORS; RECOGNITION; RECEPTORS; DIOLS AB A sensory assembly consisting of a pH sensitive NIR dye and an arylboronic acid shows ratiometric absorption changes with increased fluorescence intensity upon addition of sugar in aqueous media; this demonstrates a new signal transduction mechanism for the detection of sugar based on pH changes induced in the microenvironment of the sensory assembly. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA099385, R33 CA114149] NR 22 TC 22 Z9 23 U1 0 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PD JUN 14 PY 2007 IS 22 BP 2299 EP 2301 DI 10.1039/b700741h PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 180GE UT WOS:000247349800040 PM 17534523 ER PT J AU Higashi, T Wenger, NS Adams, JL Fung, C Roland, M McGlynn, EA Reeves, D Asch, SM Kerr, EA Shekelle, PG AF Higashi, Takahiro Wenger, Neil S. Adams, John L. Fung, Constance Roland, Martin McGlynn, Elizabeth A. Reeves, David Asch, Steven M. Kerr, Eve A. Shekelle, Paul G. TI Relationship between number of medical conditions and quality of care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VULNERABLE OLDER-PEOPLE; UNITED-STATES; HEALTH-CARE; PRACTICE GUIDELINES; PERFORMANCE DATA; DIABETES CARE; DISEASES; ELDERS; PAY; GENERALIST AB BACKGROUND: There is emerging concern that the methods used to measure the quality of care unfairly penalize providers caring for patients with multiple chronic conditions. We therefore sought to study the relationship between the quality of care and the number of medical conditions a patient has. METHODS: We assessed measurements of the quality of medical care received in three cohorts of community-dwelling adult patients in the Community Quality Index study, the Assessing Care of Vulnerable Elders study, and the Veterans Health Administration project (7680 patients in total). We analyzed the relationship between the quality of care that patients received, defined as the percentage of quality indicators satisfied among those for which patients were eligible, and the number of chronic medical conditions each patient had. We further explored the roles of characteristics of patients, use of health care (number of office visits and hospitalizations), and care provided by specialists as explanations for the observed relationship. RESULTS: The quality of care increased as the number of medical conditions increased. Each additional condition was associated with an increase in the quality score of 2.2% (95% confidence interval [CI], 1.7 to 2.7) in the Community Quality Index cohort, of 1.7% (95% CI, 1.1 to 2.4) in the Assessing Care of Vulnerable Elders cohort, and of 1.7% (95% CI, 0.7 to 2.8) in the Veterans Health Administration cohort. The relationship between the quality of care and the number of conditions was little affected by adjustment for the difficulty of delivering the care recommended in a quality indicator and for the fact that, because of multiple conditions requiring the same care, a patient could be eligible to receive the same care process more than once. Adjustment for characteristics of patients, use of health care, and care provided by specialists diminished the relationship, but it remained positive. CONCLUSIONS: The quality of care, measured according to whether patients were offered recommended services, increases as a patient's number of chronic conditions increases. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Kyoto Univ, Kyoto, Japan. Univ Manchester, Natl Primary Care Res & Dev Ctr, Manchester, Lancs, England. Vet Affairs Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Shekelle, PG (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM shekelle@rand.org RI Kerr, Eve/I-3330-2013; reeves, david/H-6203-2014 OI reeves, david/0000-0001-6377-6859 NR 34 TC 151 Z9 151 U1 1 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2007 VL 356 IS 24 BP 2496 EP 2504 DI 10.1056/NEJMsa066253 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 178DR UT WOS:000247201900009 PM 17568030 ER PT J AU Kaufman, DS Young, RH McDougal, WS Zietman, AL Tabatabaei, S Harris, NL AF Kaufman, Donald S. Young, Robert H. McDougal, W. Scott Zietman, Anthony L. Tabatabaei, Shahin Harris, Nancy Lee TI A 54-year-old man with early-stage prostate cancer - Adenocarcinoma of the prostate, Gleason score 7 of 10 (predominantly grade 3), organ confined. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PERMANENT SEED IMPLANTATION; RADIATION; RADIOTHERAPY; SURVIVAL; THERAPY; TRIAL C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Urol, Boston, MA USA. Harvard Med Sch, Dept Radiat Oncol, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2007 VL 356 IS 24 BP 2515 EP 2520 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 178DR UT WOS:000247201900013 PM 17568033 ER PT J AU Blumenthal, D Glaser, JP AF Blumenthal, David Glaser, John P. TI Information technology comes to medicine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ELECTRONIC HEALTH RECORDS; ORDER ENTRY SYSTEMS; PRIMARY-CARE; INCREASED MORTALITY; IMPLEMENTATION; EXPERIENCES; COSTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners Hlth Care Syst, Boston, MA USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Tao, Youyou/D-2367-2014 NR 33 TC 153 Z9 157 U1 7 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2007 VL 356 IS 24 BP 2527 EP 2534 DI 10.1056/NEJMhpr066212 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 178DR UT WOS:000247201900016 PM 17568035 ER PT J AU Wu, WC Schifftner, TL Henderson, WG Eaton, CB Poses, RM Uttley, G Sharma, SC Vezeridis, M Khuri, SF Friedmann, PD AF Wu, Wen-Chih Schifftner, Tracy L. Henderson, William G. Eaton, Charles B. Poses, Roy M. Uttley, Georgette Sharma, Satish C. Vezeridis, Michael Khuri, Shukri F. Friedmann, Peter D. TI Preoperative Hematocrit levels and postoperative outcomes in older patients undergoing noncardiac surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-ARTERY DISEASE; AFFAIRS SURGICAL RISK; CARDIOVASCULAR-DISEASE; BLOOD-VISCOSITY; ANEMIA; TRANSFUSION; MORBIDITY; MORTALITY; QUALITY; CARE AB Context Elderly patients are at high risk of both abnormal hematocrit values and cardiovascular complications of noncardiac surgery. Despite nearly universal screening of patients for abnormal preoperative hematocrit levels, limited evidence demonstrates the adverse effects of preoperative anemia or polycythemia. Objective To evaluate the prevalence of preoperative anemia and polycythemia and their effects on 30-day postoperative outcomes in elderly veterans undergoing major noncardiac surgery. Design Retrospective cohort study using the VA National Surgical Quality Improvement Program database. Based on preoperative hematocrit levels, we stratified patients into standard categories of anemia ( hematocrit < 39.0%), normal hematocrit (39.0%- 53.9%), and polycythemia ( hematocrit >= 54%). We then estimated increases in 30-day postoperative cardiac event and mortality risks in relation to each hematocrit point deviation from the normal category. Setting and Patients A total of 310 311 veterans aged 65 years or older who underwent major noncardiac surgery between 1997 and 2004 in 132 Veterans' Affairs medical centers across the United States. Main Outcome Measures The primary outcome measure was 30-day postoperative mortality; a secondary outcome measure was composite 30-day postoperative mortality or cardiac events ( cardiac arrest or Q-wave myocardial infarction). Results Thirty-day mortality and cardiac event rates increased monotonically, with either positive or negative deviations from normal hematocrit levels. We found a 1.6% (95% confidence interval, 1.1%-2.2%) increase in 30-day postoperative mortality associated with every percentage-point increase or decrease in the hematocrit value from the normal range. Additional analyses suggest that the adjusted risk of 30-day postoperative mortality and cardiac morbidity begins to rise when hematocrit levels decrease to less than 39% or exceed 51%. Conclusions Even mild degrees of preoperative anemia or polycythemia were associated with an increased risk of 30-day postoperative mortality and cardiac events in older, mostly male veterans undergoing major noncardiac surgery. Future studies should determine whether these findings are reproducible in other populations and if preoperative management of anemia or polycythemia decreases the risk of postoperative mortality. C1 Providence Vet Affairs Med Ctr, Target Res Enhancement Program, Providence, RI USA. Mem Hosp Rhode Isl, Ctr Primary Care & Prevent, Dept Community Med, Providence, RI USA. Mem Hosp Rhode Isl, Ctr Primary Care & Prevent, Dept Med, Providence, RI USA. Providencey Vet Affairs Med Ctr, Dept Family Med, Providence, RI USA. Providencey Vet Affairs Med Ctr, Surg Serv, Providence, RI USA. Providencey Vet Affairs Med Ctr, Med Serv, Providence, RI USA. Brown Med Sch, Dept Surg, Providence, RI USA. Univ Colorado, Hlth Outcomes Program, Denver VA Med Ctr,Denver Data Anal Ctr, Natl Surg Qual Improvement Program, Denver, CO 80202 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, Surg Serv, Boston, MA USA. RP Wu, WC (reprint author), 830 Chalkstone Ave, Providence, RI 02908 USA. EM Wen-Chih.Wu@va.gov NR 46 TC 222 Z9 240 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 13 PY 2007 VL 297 IS 22 BP 2481 EP 2488 DI 10.1001/jama.297.22.2481 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 177TX UT WOS:000247176500022 PM 17565082 ER PT J AU Ingelsson, E Larson, MG Vasan, RS O'Donnell, CJ Yin, X Hirschhorn, JN Newton-Cheh, C Drake, JA Musone, SL Heard-Costa, NL Benjamin, EJ Levy, D Atwood, LD Wang, TJ Kathiresan, S AF Ingelsson, Erik Larson, Martin G. Vasan, Ramachandran S. O'Donnell, Christopher J. Yin, Xiaoyan Hirschhorn, Joel N. Newton-Cheh, Christopher Drake, Jared A. Musone, Stacey L. Heard-Costa, Nancy L. Benjamin, Emelia J. Levy, Daniel Atwood, Larry D. Wang, Thomas J. Kathiresan, Sekar TI Heritability, linkage, and genetic associations of exercise treadmill test responses SO CIRCULATION LA English DT Article DE blood pressure; exercise; genetics; heart rate ID BLOOD-PRESSURE RESPONSE; ACUTE MYOCARDIAL-INFARCTION; HEART-RATE RECOVERY; HERITAGE FAMILY; INSULIN-RESISTANCE; RISK; POLYMORPHISMS; HYPERTENSION; DISEASE; WOMEN AB Background - The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. Methods and Results - We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43 - 44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing. Conclusions - Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise. C1 Framingham Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, 25 New Chardon St,Suite 301, Boston, MA 02114 USA. EM skathiresan@partners.org OI Heard-Costa, Nancy/0000-0001-9730-0306; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL04334, K23-HL074077-01, K23-HL083102-01, U01-HL-66582] NR 41 TC 15 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2007 VL 115 IS 23 BP 2917 EP 2924 DI 10.1161/CIRCULATIONAHA.106.683821 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 177KZ UT WOS:000247153300004 PM 17548724 ER PT J AU Fung, E Tang, SMT Canner, JP Morishige, K Arboleda-Velasquez, JF Cardoso, AA Carlesso, N Aster, JC Aikawa, M AF Fung, Erik Tang, Sai-Man Timothy Canner, James P. Morishige, Kunio Arboleda-Velasquez, Joseph F. Cardoso, Angelo A. Carlesso, Nadia Aster, Jon C. Aikawa, Masanori TI Delta-like 4 induces notch signaling in macrophages implications for inflammation SO CIRCULATION LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE atherosclerosis; DLL4 protein, human; inflammation; macrophages; receptors; Notch ID INHIBITS TUMOR-GROWTH; NF-KAPPA-B; ATHEROSCLEROTIC PLAQUES; COLLAGEN ACCUMULATION; INNATE IMMUNITY; IN-VIVO; CELLS; RECEPTOR; TRANSCRIPTION; ANGIOGENESIS AB Background - Activated macrophages contribute to the pathogenesis of inflammatory diseases such as atherosclerosis. Although Notch signaling participates in various aspects of immunity, its role in macrophage activation remains undetermined. Methods and Results - To explore the role of Notch signaling in inflammation, we examined the expression and activity of Notch pathway components in human primary macrophages in vitro and in atherosclerotic plaques. Macrophages in culture express various Notch pathway components including all 4 receptors (Notch1 to Notch4). Notch3 selectively increased during macrophage differentiation; however, silencing by RNA interference demonstrated that all receptors are functional. The ligand Delta-like 4 (Dll4) increased in macrophages exposed to proinflammatory stimuli such as lipopolysaccharide, interleukin-1 beta, or minimally-modified low-density lipoprotein in a Toll-like receptor 4 - and nuclear factor-kappa B-dependent fashion. Soluble Dll4 bound to human macrophages. Coincubation of macrophages with cells that expressed Dll4 triggered Notch proteolysis and activation; increased the transcription of proinflammatory genes such as inducible nitric oxide synthase, pentraxin 3 and Id1; resulted in activation of mitogen-activated protein kinase, Akt, and nuclear factor-kappa B pathways; and increased the expression of Dll4 in macrophages. Notch3 knockdown during macrophage differentiation decreased the transcription of genes that promote inflammation, such as inducible nitric oxide synthase, pentraxin 3, Id1, and scavenger receptor-A. These in vitro findings correlate with results of quantitative immunohistochemistry, which demonstrated the presence of Dll4 and other Notch components within macrophages in atherosclerotic plaques. Conclusion - Dll4-triggered Notch signaling may mediate inflammatory responses in macrophages and promote inflammation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02115 USA. RP Aikawa, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM maikawa@rics.bwh.harvard.edu FU NCI NIH HHS [CA82308]; NHLBI NIH HHS [HL 66086] NR 50 TC 97 Z9 107 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2007 VL 115 IS 23 BP 2948 EP 2956 DI 10.1161/CIRCULATIONAHA.107.675462 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 177KZ UT WOS:000247153300008 PM 17533181 ER PT J AU Bao, J Zhang, DW Zhang, JZH Huang, PL Huang, PL Lee-Huang, S AF Bao, J. Zhang, D. W. Zhang, J. Z. H. Huang, P. Lee Huang, P. Lin Lee-Huang, S. TI Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41 SO FEBS LETTERS LA English DT Article DE HIV-1 entry inhibition; olive leaf extract (OLE); oleuropein; hydroxytyrosol; binding modes; Gp41; binding free energy; PBSA ID INTEGRASE INHIBITORS OLEUROPEIN; MOLECULAR-MECHANICS; CONTINUUM SOLVENT; FREE-ENERGIES; ENTRY; MODELS; CORE; HYDROXYTYROSOL; RECEPTORS; INFECTION AB Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41 Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors. (c) 2007 Published bv Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NYU, Dept Chem, New York, NY 10003 USA. NYU, Sch Med, Dept Biochem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Amer Biosci Inc, New York, NY 10021 USA. RP Zhang, JZH (reprint author), NYU, Dept Chem, New York, NY 10003 USA. EM john.zhang@nyu.edu RI Zhang, Dawei/C-5981-2008; Bao, Ju/E-6242-2012; Zhang, John/A-3372-2013; OI Lee-Huang, Sylvia/0000-0003-3302-241X FU NCCIH NIH HHS [R01 AT001383, R01 AT001383-01A2, R01 AT001383-02, R01 AT001383-03, R01 AT01383] NR 27 TC 29 Z9 30 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 12 PY 2007 VL 581 IS 14 BP 2737 EP 2742 DI 10.1016/j.febslet.2007.05.029 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 179XQ UT WOS:000247324300028 PM 17537437 ER PT J AU Ariyarajah, V Fernandes, J Kranis, M Apiyasawat, S Mercado, K Spodick, DH AF Ariyarajah, Vignendra Fernandes, Jaxon Kranis, Mark Apiyasawat, Sirin Mercado, Kristin Spodick, David H. TI Prospective evaluation of atrial tachyarrhythmias in patients with interatrial block SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE interatrial block; electrocardiogram; P-wave; atrial fibrillation; risk ID P-WAVE DURATION; PANDEMIC PREVALENCE; FIBRILLATION AB Introduction: Interatrial block (P-wave >= 110 ms) is clinically associated with left atrial enlargement and electromechanical dysfunction as well as atrial tachyarrhythmias. We prospectively evaluated the incidence of such arrhythmias, especially atria] fibrillation among patients with interatrial block over the course of 1 year. Methods: 118 patients (aged 48 to 104 years; female 56.6%) who had been hospitalized between December 15, 2004 and January 14, 2005 were identified and divided into 3 groups based on their respective baseline electrocardiogram (interarrial block=41 patients, sinus noninteratrial block=51 patients and atrial tachyarrhythmia=24 patients). Patients were subsequently followed for 12 months for pertinent cardiovascular events (heart failure, peripheral embolism, transient ischemic attacks and stroke), atrial tachyaffhythmias (atrial fibrillation and atrial flutter) and death as endpoints. Results: 19 patients (17.9%) had atrial fibrillation during the 12-month follow-up (sinus non-interatrial block group=4 [9.1%], interatrial block group= 12 [29.3%] and atrial tachyarrhythmia group=3 [14.3%]). Coronary artery disease, hypertension, pre-existing atrial fibrillation history, dilated cardiornyopathy, atrioventricular valvular disease and interatrial block (age- and sex-adjusted hazard ratio=4.2; 95% confidence interval 1.2-14.4; p=0.02) were significantly associated with future events of atrial fibrillation. However, logistic regression analysis indicated that interatrial block was not an independent predictor of future atrial fibrillation whereas only history of pre-existing atrial tachyarrhythmias was (hazard ratio = 23.6; 95% confidence interval 4.5-121.7; 19 = 0.0002). Conclusion: Interatrial block may be associated with atrial fibrillation but in a 12-month period, does not appear to be an independent predictor of future atrial fibrillation. Continued prospective investigation of such a relationship is certainly warranted given its already known consequences. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA USA. St Vincent Hosp, Dept Med, Worcester, MA USA. St Vincent Hosp, Dept Med, Worcester, MA USA. St Vincent Hosp, Div Cardiol, Worcester, MA USA. Univ Massachusetts, Sch Med, Div Cardiovasc Med, Dept Med, Worcester, MA USA. RP Ariyarajah, V (reprint author), VA Boston Healthcare Syst, MAVERIC, 150 S Huntingdon Ave, Boston, MA 02130 USA. EM vignendra@hotmail.com NR 16 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUN 12 PY 2007 VL 118 IS 3 BP 332 EP 337 DI 10.1016/j.ijcard.2006.07.021 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 175NT UT WOS:000247021000008 PM 17027099 ER PT J AU Fox, KAA Antman, EM Montalescot, G Agewall, S SomaRaju, B Verheugt, FWA Lopez-Sendon, J Hod, H Murphy, SA Braunwald, E AF Fox, Keith A. A. Antman, Elliott M. Montalescot, Gilles Agewall, Stefan SomaRaju, Bhupathi Verheugt, Freek W. A. Lopez-Sendon, Jose Hod, Hanoch Murphy, Sabina A. Braunwald, Eugene TI The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; ACUTE-CORONARY-SYNDROME; GLOMERULAR-FILTRATION-RATE; MOLECULAR-WEIGHT HEPARIN; SERUM CREATININE; UNFRACTIONATED HEPARIN; CARDIOVASCULAR OUTCOMES; SUBSEQUENT MORTALITY; GLOBAL-REGISTRY AB Objectives The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial provided the opportunity to evaluate the impact of renal dysfunction on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and compare enoxaparin (ENOX) and unfractionated heparin (UFH). Background It is unclear how renal dysfunction influences the balance between benefit and risk of antithrombotic therapy. Methods In the ExTRACT-TIMI 25 trial, 20,479 patients were randomized to UFH or ENOX A reduced ENOX dose was administered to patients age >= 75 years and those with an estimated creatinine clearance (CrCI) <30 ml/min. Results A powerful relationship was observed between the severity of renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke, intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There was a progressive increase in the treatment benefit with ENOX on death or nonfatal myocardial infarction (p < 0.01) with better renal function. Net clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was significantly superior with ENOX (p < 0.001) for patients with a CrCI >60 ml/min (79.1% of the study population). Major bleeding and intracranial hemorrhage did not differ for patients with preserved renal function (CrCl >90 ml/ min), but in those with renal dysfunction there was a progressively greater increase in the risk of major and minor bleeding with ENOX. Conclusions Enoxaparin was superior to UFH for the majority of subjects. With more severe renal dysfunction, the net clinical benefit between ENOX and UFH did not differ, despite the rise in adverse events in both treatment groups. Future studies should take renal dysfunction into account when assessing antithrombotic regimens. C1 Univ Edinburgh, Edinburgh, Midlothian, Scotland. Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. Karolinska Univ Hosp, Karolinska Inst, Coronary Care Unit, Stockholm, Sweden. CARE Hosp, Hyderabad, Andhra Pradesh, India. Univ Hosp Nijmegen, Nijmegen, Netherlands. Hosp Univ La Paz Madrid, Madrid, Spain. Chaim Sheba Med Ctr, Heart Inst, Tel Hashomer, Israel. RP Antman, EM (reprint author), Univ Edinburgh, Edinburgh, Midlothian, Scotland. EM eantman@rics.bwh.harvard.edu RI Verheugt, F.W.A./H-8105-2014 NR 26 TC 55 Z9 60 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 JUN 12 PY 2007 VL 49 IS 23 BP 2249 EP 2255 DI 10.1016/j.jacc.2006.02.049 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 177YZ UT WOS:000247189700004 PM 17560289 ER PT J AU Sabatine, MS Morrow, DA Dalby, A Pfisterer, M Duris, T Lopez-Sendon, J Murphy, SA Gao, RL Antman, EM Braunwald, E AF Sabatine, Marc S. Morrow, David A. Dalby, Anthony Pfisterer, Mathias Duris, Tibor Lopez-Sendon, Jose Murphy, Sabina A. Gao, Runlin Antman, Elliott M. Braunwald, Eugene CA ExTRACT-TIMI 25 Investigators TI Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-Segment elevation myocardial infarction also treated with clopidogrel SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; II TRIAL; ASPIRIN; THROMBOLYSIS; THERAPY; FIBRINOLYSIS; TIMI AB Objectives The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. Background The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. Methods We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. Results Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [ORadj] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, ORadj 0.85, p = 0.003) with no evidence of heterogeneity (P-interaction = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (P-interaction = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (P-interaction 0.61). Conclusions In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Milpark Hosp, S African Cardiol Clin Trials Grp, Johannesburg, South Africa. Kantonsspital, Basel, Switzerland. FnsP, Zamky, Slovakia. Hosp Univ La Paz, Madrid, Spain. Fu Wai Hosp, Beijing, Peoples R China. RP Antman, EM (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu NR 13 TC 21 Z9 21 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 JUN 12 PY 2007 VL 49 IS 23 BP 2256 EP 2263 DI 10.1016/j.jacc.2007.01.092 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 177YZ UT WOS:000247189700005 PM 17560290 ER PT J AU Pearlman, AS Ryan, T Picard, MH Douglas, PS AF Pearlman, Alan S. Ryan, Thomas Picard, Michael H. Douglas, Pamela S. TI Evolving trends in the use of echocardiography - A study of medicare beneficiaries SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CRITERIA WORKING GROUP; APPROPRIATENESS CRITERIA; COMPUTED-TOMOGRAPHY; REGIONAL-VARIATIONS; NUCLEAR-CARDIOLOGY; AMERICAN-SOCIETY; POPULATION; QUALITY; CARE AB Objectives We studied the use of echocardiography among Medicare beneficiaries between 1999 and 2004 to determine the rate of growth in these services and evaluate the drivers of growth. Background Concerned about increasing health care costs, federal and private payers have highlighted growth in diagnostic imaging studies and begun to develop approaches to curb this growth. Methods Medicare Part B Physician/Supplier Procedure Summary Master File and enrollment data from 1999 to 2004 were reviewed. Total Medicare carrier-paid spending for echocardiography services was determined from procedure volumes and allowed charges. The 5% standard analytic file of physician claims was used to evaluate geographic variations in use and to document the specialties of physicians who request and those who interpret echocardiograms. Results Between 1999 and 2004, echocardiography services grew at a rate similar to that for all medical services subject to Medicare's sustainable growth rate (SGR) calculation. Increasing provision of echocardiograms in physicians' offices contributed to increased spending under the SGR. Accounting for this shift, actual annualized per capita growth in echocardiography was 7.7%. Variations in the prevalence of heart disease contributed to geographic variations in use. Although cardiologists were the most common providers of echocardiographic services, primary care physicians ordered the majority of these diagnostic procedures. Conclusions Growth in the use of echocardiography is in keeping with the general growth in medical services. Nonetheless, physicians who order echocardiograms and those who provide them must work together to ensure that in the future these diagnostic services are used appropriately and not excessively. C1 Univ Washington, Ctr Med, Dept Med, Div Cardiol,Sch Med, Seattle, WA 98195 USA. Duke Univ, Ctr Med, Div Cardiovasc Med, Durham, NC USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. RP Pearlman, AS (reprint author), Univ Washington, Ctr Med, Dept Med, Div Cardiol,Sch Med, Box 356422,1959 NE Pacific St, Seattle, WA 98195 USA. EM apearlmn@u.washington.edu OI Picard, Michael/0000-0002-9264-3243 NR 18 TC 77 Z9 78 U1 0 U2 2 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 JUN 12 PY 2007 VL 49 IS 23 BP 2283 EP 2291 DI 10.1016/j.jacc.2007.02.048 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 177YZ UT WOS:000247189700009 PM 17560294 ER PT J AU Keene, CD Sonnen, A Swanson, PD Kopyov, O Leverenz, JB Bird, TD Montine, TJ AF Keene, C. D. Sonnen, A. Swanson, P. D. Kopyov, O. Leverenz, J. B. Bird, T. D. Montine, T. J. TI Neural transplantation in Huntington disease - Long-term grafts in two patients SO NEUROLOGY LA English DT Article ID FETAL STRIATAL TRANSPLANTATION; EFFERENT PROJECTIONS; HOST; MODEL; NEUROTRANSPLANTATION; INTERNEURONS; INNERVATION; ALLOGRAFTS; AFFERENTS; NEURONS AB Objective: Clinical trials of fetal neural tissue transplantation for Huntington disease (HD) have been conducted with variable clinical results. However, no long-term analysis of graft survival and integration has been published. Here, we report the pathologic findings in two patients with HD who died 74 and 79 months after transplantation. Methods: Methods used were pathologic examination, histochemistry, and immunohistochemistry. Results: Neostriatum from both patients showed typical neuropathologic changes of advanced HD. Surviving grafts were identified in both patients (6/6 sites and 7/8 sites, respectively) as well-demarcated nests within host neostriatum with associated needle tracts. Grafted neurons adopted either dominant calbindin/parvalbumin or calretinin immunoreactivity (IR). Few neurofilament, MAP-2, DARPP-32, tyrosine hydroxylase, or calbindin IR processes traversed the host parenchyma - graft interface despite minimal junctional gliosis. Immunohistochemistry for CD68 showed microgliosis that was more pronounced in host striatum than graft. Scattered CD45 and CD3IR cells were present within grafts and host parenchyma. No ubiquitin IR neuronal intranuclear inclusions were identified in graft neurons, although these were prevalent in host cells. Conclusions: These two autopsies confirm previous findings of neuronal differentiation and survival of transplanted fetal tissue from the ganglionic eminence and also demonstrate viability of neurons from fetal transplants in human neostriatum for more than 6 years. Despite prolonged survival, these grafts had poor integration with host striatum that is likely responsible for lack of clear clinical improvement in these patients. C1 Univ Washington, Med Ctr, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Dept Neurol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Mental Illness&Parkinsons Dis Res Educ & Clin Ctr, Dept Neurol, Seattle, WA USA. St Johns Reg Med Ctr, Inst Neurosci, Oxnard, CA USA. RP Montine, TJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, Box 359791, Seattle, WA 98104 USA. EM tmontine@u.washington.edu RI Sonnen, 37382016/H-3738-2016; Keene, Christopher/N-1806-2015 OI Sonnen, 37382016/0000-0001-9267-8705; FU NIA NIH HHS [P50-AG005136-22] NR 26 TC 49 Z9 54 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 12 PY 2007 VL 68 IS 24 BP 2093 EP 2098 DI 10.1212/01.wnl.0000264504.14301.f5 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 177JK UT WOS:000247149200007 PM 17562830 ER PT J AU Martins, D Wolf, M Pan, D Zadshir, A Tareen, N Thadhani, R Felsenfeld, A Levine, B Mehrotra, R Norris, K AF Martins, David Wolf, Myles Pan, Deyu Zadshir, Ashraf Tareen, Naureen Thadhani, Ravi Felsenfeld, Arnold Levine, Barton Mehrotra, Rajnish Norris, Keith TI Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States - Data from the Third National Health and Nutrition Examination Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 20th Anniversary Symposium of the Research-Centers-for-Minority-Institutions CY DEC 10, 2004 CL Balitmore, MD SP Res Ctr Minor Inst ID VITAMIN-D INSUFFICIENCY; PLASMA-RENIN ACTIVITY; HYPOVITAMINOSIS-D; BLOOD-PRESSURE; 1,25-DIHYDROXYVITAMIN D-3; ESSENTIAL-HYPERTENSION; NOD MICE; BODY-FAT; METABOLISM; PREVENTION AB Background: Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. Methods: We examined the association between serum levels of 25-hydroxyvitamin D ( 25[ OH] D) and select cardiovascular disease risk factors in US adults. A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey, a national probability survey conducted by the National Center for Health Statistics between January 1, 1988, and December 31, 1994, with oversampling of persons 60 years and older, non-Hispanic black individuals, and Mexican American individuals. Results: There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey. The mean 25( OH) D level in the overall sample was 30 ng/mL ( 75 nmol/L). The 25( OH) D levels were lower in women, elderly persons ( >= 60 years), racial/ethnic minorities, and participants with obesity, hypertension, and diabetes mellitus. The adjusted prevalence of hypertension ( odds ratio [ OR], 1.30), diabetes mellitus ( OR, 1.98), obesity ( OR, 2.29), and high serum triglyceride levels ( OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25( OH) D levels ( P < .001 for all). Conclusions: Serum 25( OH) D levels are associated with important cardiovascular disease risk factors in US adults. Prospective studies to assess a direct benefit of cholecalciferol ( vitamin D) supplementation on cardiovascular disease risk factors are warranted. C1 Charles R Drew Univ Med & Sci, Dept Med, Lynwood, CA 90262 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. VA Greater LA Healthcare Syst, Dept Med, Los Angeles, CA USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. RP Norris, K (reprint author), Charles R Drew Univ Med & Sci, Dept Med, 11705 Deputy Yamamoto Pl,Suite B, Lynwood, CA 90262 USA. EM knorris@ucla.edu FU NCRR NIH HHS [RR03026, RR019234, RR11145, RR14616, RR18298]; NIA NIH HHS [AG-02-004]; NIDDK NIH HHS [DK71674]; NIMHD NIH HHS [MD00148] NR 48 TC 447 Z9 484 U1 0 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 11 PY 2007 VL 167 IS 11 BP 1159 EP 1165 DI 10.1001/archinte.167.11.1159 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 177HE UT WOS:000247143400008 PM 17563024 ER PT J AU Yuan, Q Bromley, SK Means, TK Jones, KJ Hayashi, F Bhan, AK Luster, AD AF Yuan, Qian Bromley, Shannon K. Means, Terry K. Jones, Krister J. Hayashi, Fumitaka Bhan, Atul K. Luster, Andrew D. TI CCR4-dependent regulatory T cell function in inflammatory bowel disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DENDRITIC CELLS; CUTTING EDGE; CHEMOKINE RECEPTORS; IN-VIVO; CD4(+)CD25(+); COLITIS; CCR4; SUBPOPULATION; RECRUITMENT; ACTIVATION AB Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the intestine. CD4(+) T lymphocytes play an important role in both initiating and regulating intestinal inflammatory immune responses. CD4(+) CD25(+)CD45RB(low) regulatory T (T reg) cells are capable of preventing the development of colitis in a mouse model of IBD. The precise mechanism of T reg cell - mediated prevention of colitis in this model is unclear, and the role of chemokine receptors in the trafficking and function of T reg cells in this model has not been determined. We examined the role of the chemokine receptor CCR4 in in vivo trafficking and suppressive function of T reg cells in a mouse adoptive transfer model of IBD. CCR4-deficient T reg cells failed to accumulate in the mesenteric lymph nodes (MLNs) at early time points (2 - 5 d) after adoptive transfer, resulting in a failure to suppress the generation of pathogenic T cells and the development of colitis. Moreover, although CCR4-deficent T cells had equivalent in vitro suppressive activity and accumulated in MLNs at later time points (42 - 56 d), they were unable to suppress colitis. Our study demonstrates that CCR4 plays an important role in T reg cell trafficking in LNs and that this is critical for T reg cell suppressive function in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol A, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol A, Boston, MA 02114 USA. EM luster.andrew@mgh.harvard.edu FU NIAID NIH HHS [R01 AI040618, R01-AI40618]; NIDDK NIH HHS [K08 DK068085, K08-DK68085, R01 DK047677, R01-DK47677] NR 27 TC 81 Z9 81 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 11 PY 2007 VL 204 IS 6 BP 1327 EP 1334 DI 10.1084/jem.20062076 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 177MX UT WOS:000247158300013 PM 17548518 ER PT J AU Meyer, H Garofaiakis, A Zacharakis, G Psycharakis, S Mamalaki, C Kioussis, D Economou, EN Ntziachristos, V Ripoll, J AF Meyer, Heiko Garofaiakis, Anikitos Zacharakis, Giannis Psycharakis, Stylianos Mamalaki, Clio Kioussis, Dimitris Economou, Eleftherios N. Ntziachristos, Vasilis Ripoll, Jorge TI Noncontact optical imaging in mice with full angular coverage and automatic surface extraction SO APPLIED OPTICS LA English DT Article ID FLUORESCENCE MOLECULAR TOMOGRAPHY; SINGULAR-VALUE ANALYSIS; PROJECTION TOMOGRAPHY; TURBID MEDIA; PROTEIN; RECONSTRUCTION; APPROXIMATION; OPTIMIZATION; EXPRESSION; SCANNER AB During the past decade, optical imaging combined with tomographic approaches has proved its potential in offering quantitative three-dimensional spatial maps of chromophore or fluorophore concentration in vivo. Due to its direct application in biology and biomedicine, diffuse optical tomography (DOT) and its fluorescence counterpart, fluorescence molecular tomography (FMT), have benefited from an increase in devoted research and new experimental and theoretical developments, giving rise to a new imaging modality. The most recent advances in FMT and DOT are based on the capability of collecting large data sets by using CCDs as detectors, and on the ability to include multiple projections through recently developed noncontact approaches. For these to be implemented, we have developed an imaging setup that enables three-dimensional imaging of arbitrary shapes in fluorescence or absorption mode that is appropriate for small animal imaging. This is achieved by implementing a noncontact approach both for sources and detectors and coregistering surface geometry measurements using the same CCD camera. A thresholded shadowgrammetry approach is applied to the geometry measurements to retrieve the surface mesh. We present the evaluation of the system and method in recovering three-dimensional surfaces from phantom data and live mice. The approach is used to map the measured in vivo fluorescence data onto the tissue surface by making use of the free-space propagation equations, as well as to reconstruct fluorescence concentrations inside highly scattering tissuelike phantom samples. Finally, the potential use of this setup for in vivo small animal imaging and its impact on biomedical research is discussed. (C) 2007 Optical Society of America. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Crete, Greece. Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece. Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Meyer, H (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion 71110, Crete, Greece. EM heimeyer@iesl.forth.gr RI Economou, Eleftherios /E-6374-2010; Zacharakis, Giannis/A-2544-2014; Ripoll, Jorge/J-8134-2012 OI Zacharakis, Giannis/0000-0002-6438-0773; Ripoll, Jorge/0000-0001-8856-7738 FU Medical Research Council [MC_U117512796]; NCI NIH HHS [R33-CA91807]; NIBIB NIH HHS [R01 EB000750-1] NR 38 TC 52 Z9 54 U1 0 U2 8 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 JUN 10 PY 2007 VL 46 IS 17 BP 3617 EP 3627 DI 10.1364/AO.46.003617 PG 11 WC Optics SC Optics GA 174QY UT WOS:000246958800029 PM 17514324 ER PT J AU Temel, JS Jackson, VA Billings, JA Dahlin, C Block, SD Buss, MK Ostler, P Fidias, P Muzikansky, A Greer, JA Pirl, WF Lynch, TJ AF Temel, Jennifer S. Jackson, Vicki A. Billings, J. Andrew Dahlin, Constance Block, Susan D. Buss, Mary K. Ostler, Patricia Fidias, Panos Muzikansky, Alona Greer, Joseph A. Pirl, William F. Lynch, Thomas J. TI Phase II study: Integrated palliative care in newly diagnosed advanced non-small-cell lung cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; THERAPY; END; CHEMOTHERAPY; DEPRESSION; GEFITINIB; SYMPTOMS AB Purpose To assess the feasibility of early palliative care in the ambulatory setting in patients with newly diagnosed advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients were eligible if they had a performance status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC. Participants received integrated care from oncology and palliative care throughout the course of their disease. Participants were scheduled to meet with the palliative care team (PCT) and complete quality-of-life (QOL) and mood questionnaires monthly for 6 months. The study was deemed feasible if 64% of patients completed at least 50% of their scheduled visits and QOL assessments. Results Fifty-one patients were enrolled onto the trial. One died within 72 hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study participants complied with at least 50% of the palliative care visits. Eight-six percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility requirements by both meeting with the PCT and completing QOL assessments at least 50% of the time. QOL and mood analyses confirmed the high symptom burden in patients with newly diagnosed advanced NSCLC. At least 50% of participants experienced some degree of shortness of breath, cough, difficulty breathing, appetite loss, weight loss, or unclear thinking at their baseline assessment. More than one third of patients had a probable mood disorder at baseline. Conclusion Integrated palliative and oncology care is feasible in ambulatory patients with advanced NSCLC. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM jtemel@partners.org NR 37 TC 63 Z9 63 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2007 VL 25 IS 17 BP 2377 EP 2382 DI 10.1200/JCO.2006.09.2627 PG 6 WC Oncology SC Oncology GA 178SY UT WOS:000247241600009 PM 17557950 ER PT J AU Steyerberg, EW Neville, B Weeks, JC Earle, CC AF Steyerberg, Ewout W. Neville, Bridget Weeks, Jane C. Earle, Craig C. TI Referral patterns, treatment choices, and outcomes in locoregional esophageal cancer: A population-based analysis of elderly patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SEER-MEDICARE DATA; RANDOMIZED CONTROLLED-TRIALS; RACIAL-DIFFERENCES; CO-MORBIDITY; SOCIOECONOMIC-STATUS; COMORBIDITY INDEX; COLORECTAL-CANCER; RADIATION-THERAPY; PROSTATE-CANCER; LUNG-CANCER AB Purpose To determine the impact of demographics and comorbidity on access to specialists' services, treatment, and outcome for patients with locoregional esophageal cancer. Patients and Methods We performed a retrospective cohort study of 3,538 patients older than age 65 years who were diagnosed with locoregional esophageal cancer between 1991 and 1999 in one of 11 regions monitored by the Surveillance, Epidemiology, and End Results tumor program. We examined linked Medicare claims for assessment by a surgeon, radiation oncologist, or medical oncologist and subsequent treatment with surgery, radiation, or chemotherapy. Logistic regression analyses were performed for seeing a specialist and for undergoing treatment according to age, sex, race, socioeconomic status, geographic region, and presence of comorbidities. Cox proportional hazards analyses were performed to estimate hazard ratios (HRs) for survival with and without adjustment for treatment received. Results Seeing a cancer specialist depended especially on age and region of diagnosis. These same factors were also related to subsequent treatment decisions, but associations were reversed in some regions, such that treatment depended less on region. Older patients had poorer survival (HR = 2.0 for 85+ v 65 to 69 years), which was partly explained by treatment received (HR decreased to 1.5 when adjusted for treatment). Conclusion Older patients have less intensive treatment of esophageal cancer, which is explained by both a lower rate of seeing a cancer specialist and by less intensive treatment once seen. Referring physicians and treating specialists must ensure that elderly patients are not deprived of the opportunity to consider all of their treatment options. C1 Erasmus MC, Dept Publ Hlth, Ctr Med Decis Making, NL-3000 CA Rotterdam, Netherlands. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Steyerberg, EW (reprint author), Erasmus MC, Dept Publ Hlth, Ctr Med Decis Making, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM E.Steyerberg@ErasmusMC.nl OI Steyerberg, Ewout/0000-0002-7787-0122 NR 47 TC 44 Z9 50 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2007 VL 25 IS 17 BP 2389 EP 2396 DI 10.1200/JCO.2006.09.7931 PG 8 WC Oncology SC Oncology GA 178SY UT WOS:000247241600011 PM 17557952 ER PT J AU D'Amico, AV Denham, JW Crook, J Chen, MH Goldhaber, SZ Lamb, DS Joseph, D Tai, KH Malone, S Ludgate, C Steigler, A Kantoff, PW AF D'Amico, Anthony V. Denham, James W. Crook, Juanita Chen, Ming-Hui Goldhaber, Samuel Z. Lamb, David S. Joseph, David Tai, Keen-Hun Malone, Shawn Ludgate, Charles Steigler, Allison Kantoff, Philip W. TI Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; DEPRIVATION THERAPY; ARTERIAL STIFFNESS; RADIATION-THERAPY; COMPETING RISK; RADIOTHERAPY; NEOADJUVANT; CARDIOLOGY; CARCINOMA AB Purpose We evaluated whether the timing of fatal myocardial infarction (MI) was influenced by the administration of androgen suppression therapy (AST). Patients and Methods The study cohort comprised 1,372 men who were enrolled onto three randomized trials between February 1995 and June 2001. In the three trials, the men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6, 3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to determine the clinical factors associated with the time to fatal MI, and estimates of time to fatal MI were calculated using a cumulative incidence method. When comparing the cumulative incidence estimates using Gray's k-sample P values, increased weight was ascribed to the earlier data because recovery of testosterone is expected for most men within 2 years after short-course AST. Results Men age 65 years or older who received 6 months of AST experienced shorter times to fatal MIs compared with men in this age group who did not receive AST (P = .017) and men younger than 65 years (P = .016). No significant difference (P = .97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of AST compared with 3 months of AST. Conclusion The use of AST is associated with earlier onset of fatal MIs in men age 65 years or older who are treated for 6 months compared with men who are not treated with AST. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Radiat Oncol, Storrs, CT USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Newcastle Mater Hosp, Trans Tasman Radiat Oncol Grp, Newcastle, NSW, Australia. Peter MacCallum Canc Inst, Dept Radiat Oncol, Melbourne, Vic 3000, Australia. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Ottawa Reg Canc Ctr, Dept Radiat Oncol, Ottawa, ON K1Y 4K7, Canada. Vancouver Isl Canc Ctr, Dept Radiat Oncol, Vancouver, BC, Canada. Wellington Hosp, Dept Radiat Oncol, Wellington, New Zealand. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu RI DENHAM, JAMES/G-7505-2013 OI DENHAM, JAMES/0000-0002-4177-9503 NR 31 TC 302 Z9 306 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2007 VL 25 IS 17 BP 2420 EP 2425 DI 10.1200/JCO.2006.09.3369 PG 6 WC Oncology SC Oncology GA 178SY UT WOS:000247241600015 PM 17557956 ER PT J AU Kyle, RA Yee, GC Somerfield, MR Flynn, PJ Halabi, S Jagannath, S Orlowski, RZ Roodman, DG Twilde, P Anderson, K AF Kyle, Robert A. Yee, Gary C. Somerfield, Mark R. Flynn, Patrick J. Halabi, Susan Jagannath, Sundar Orlowski, Robert Z. Roodman, David G. Twilde, Patricia Anderson, Kenneth TI American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ZOLEDRONIC ACID; RISK-FACTORS; SKELETAL COMPLICATIONS; PAMIDRONATE DISODIUM; BREAST-CANCER; DOUBLE-BLIND; BONE METASTASES; RENAL TOXICITY; OSTEONECROSIS; JAW AB Purpose To update the recommendations for the use of bisphosphonates in the prevention and treatment of bone disease in multiple myeloma. The Update Committee expanded the guideline to include a discussion of osteonecrosis of the jaw (ONJ). Methods For the 2007 update, an Update Committee composed of members from the full panel completed a review and analysis of data published since 2002. Searches of Medline and the Cochrane Collaboration Library databases were performed. Recommendations For multiple myeloma patients who have, on plain radiograph(s) or imaging studies, lytic destruction of bone or spine compression fracture from osteopenia, intravenous pamidronate 90 mg delivered over at least 2 hours or zoledronic acid 4 mg delivered over at least 15 minutes every 3 to 4 weeks is recommended. Clodronate is an alternative bisphosphonate approved worldwide, except in the United States, for oral or intravenous administration. New dosing guidelines for patients with pre-existing renal impairment were added to the zoledronic acid package insert. Although no similar dosing guidelines are available for pamidronate, the Update Committee recommends that clinicians consider reducing the initial pamidronate dose in patients with pre-existing renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The Update Committee suggests that bisphosphonate treatment continue for a period of 2 years. At 2 years, physicians should seriously consider discontinuing bisphosphonates in patients with responsive or stable disease, but further use is at the discretion of the treating physician. The Update Committee also discusses measures regarding ONJ. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Minnesota Oncol Hematol PA, Minneapolis, MN USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Nebraska Med Ctr, Omaha, NE USA. RP Kyle, RA (reprint author), Amer Soc Clin Oncol, 1900 Duke St,Ste 200, Alexandria, VA 22314 USA. EM guidelines@asco.org NR 44 TC 234 Z9 244 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2007 VL 25 IS 17 BP 2464 EP 2472 DI 10.1200/JCO.2007.12.1269 PG 9 WC Oncology SC Oncology GA 178SY UT WOS:000247241600021 PM 17515569 ER PT J AU Goessling, W North, TE Zon, LI AF Goessling, Wolfram North, Trista E. Zon, Leonard I. TI New waves of discovery: Modeling cancer in zebrafish SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADENOMATOUS POLYPOSIS-COLI; ACUTE LYMPHOBLASTIC-LEUKEMIA; DIFFERENT DEVELOPMENTAL-STAGES; GENOMIC INSTABILITY MUTANTS; GENE-EXPRESSION SIGNATURES; DIAMOND-BLACKFAN ANEMIA; DANIO-RERIO; INTESTINAL DEVELOPMENT; TRANSGENIC ZEBRAFISH; ONCOGENIC PATHWAYS C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med,Harvard Stem Cell Inst, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, Karp Family Res Bldg,7th Flr,1 Blackfan Cir, Boston, MA 02115 USA. EM zon@zon-tchlab.org OI Goessling, Wolfram/0000-0001-9972-1569 NR 67 TC 69 Z9 76 U1 0 U2 22 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2007 VL 25 IS 17 BP 2473 EP 2479 DI 10.1200/JCO.2006.08.9821 PG 7 WC Oncology SC Oncology GA 178SY UT WOS:000247241600022 PM 17557959 ER PT J AU Outeiro, TF Grammatopoulos, TN Altmann, S Amore, A Standaert, DG Hyman, BT Kazantsev, AG AF Outeiro, Tiago Fleming Grammatopoulos, Tom N. Altmann, Steven Amore, Allison Standaert, David G. Hyman, Bradley T. Kazantsev, Aleksey G. TI Pharmacological inhibition of PARP-1 reduces alpha-synucleinand MPP+-induced cytotoxicity in Parkinson's disease in vitro models SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Parkinson's disease; PARP-1; inhibitors; neuroprotection; alpha-synuclein; MPP+; neurodegeneration ID LEWY BODY DISEASE; POLY(ADP-RIBOSE) POLYMERASE-1; CELL-DEATH; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MOUSE MODEL; AGGREGATION; MPTP; NEURODEGENERATION; ACTIVATION AB Treatments based on pharmacological inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) have been suggested for a broad variety of human disorders, including Parkinson's disease (PD). The neuroprotective effects underlying the efficacy of PARP-1 inhibitors in PD models suggest a role for PARP-I in neurodegeneration. In this study, we assessed the efficacy of PARP-I inhibition in two distinct PD models. First, we tested a panel of small molecule PARP-1 inhibitors in alpha-synuclein (aSyn) cytotoxicity assay, where we observed compound-dependent ameliorating effects. Next, we tested the same panel in primary ventral mesencephalic neuronal cultures, treated with MPP+. Dopaminergic neurons, the primary cells affected in PD, were selected and subjected to analysis. A significant ameliorating effect was achieved only with a highly potent PARP-1 inhibitor. Our data implicates aberrant PARP-1 function in different pathways of neurodegeneration. Further, our results suggest a rationale for the development of highly potent, bio-available, brain-penetrable PARP-1 inhibitors to provide therapeutic benefits for Parkinson's patients. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, Dept Neurol, Bldg 114-3300,16th St, Charlestown, MA 02129 USA. EM touteiro@gmail.com; akazantsev@partners.org RI Outeiro, Tiago/C-1067-2008; OI Outeiro, Tiago/0000-0003-1679-1727; Grammatopoulos, Tom/0000-0001-7175-051X FU NINDS NIH HHS [5P50-NS38372A-06, 2P50NS038372-06A1] NR 41 TC 27 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 8 PY 2007 VL 357 IS 3 BP 596 EP 602 DI 10.1016/j.bbrc.2007.03.163 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 166MJ UT WOS:000246382700005 PM 17449015 ER PT J AU Kraveka, JM Li, L Szulc, ZM Bielawski, J Ogretmen, B Hannun, YA Obeid, LM Bielawska, A AF Kraveka, Jacqueline M. Li, Li Szulc, Zdzislaw M. Bielawski, Jacek Ogretmen, Besim Hannun, Yusuf A. Obeid, Lina M. Bielawska, Alicja TI Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC STRESS-RESPONSE; PROTEIN PHOSPHATASE; TELOMERASE ACTIVITY; CANCER CELLS; CERAMIDE; APOPTOSIS; ACID; ACTIVATION; N-(4-HYDROXYPHENYL)RETINAMIDE; DIFFERENTIATION AB The role of dihydroceramide desaturase as a key enzyme in the de novo pathway of ceramide generation was investigated in human neuroblastoma cells (SMS-KCNR). A novel assay using water-soluble analogs of dihydroceramide, dihydroceramidoids (D-erythro-dhCCPS analogs), was used to measure desaturase activity in situ. Conversion of D-erythro-2-N-[12 '-(1 ''-pyridinium)-dodecanoyl]- 4,5-dihydrosphingosine bromide (C-12-dhCCPS) to its 4,5-desaturated counterpart, D-erythro-2-N-[12 '-(1 ''-pyridinium) dodecanoyl]sphingosine bromide (C-12-CCPS), was determined by liquid chromatography/mass spectrometry analysis. The validity of the assay was confirmed using C-8-cyclopropenylceramide, a competitive inhibitor of dihydroceramide desaturase. A human homolog (DEGS-1) of the Drosophila melanogaster des-1 gene was recently identified and reported to have desaturase activity. Transfection of SMS-KCNR cells with small interfering RNA to DEGS-1 significantly blocked the conversion of C-12-dhCCPS to C-12-CCPS. The associated accumulation of endogenous dihydroceramides confirmed DEGS-1 as the main active dihydroceramide desaturase in these cells. The partial loss of DEGS-1 inhibited cell growth, with cell cycle arrest at G(0)/G(1). This was accompanied by a significant decrease in the amount of phosphorylated retinoblastoma protein. This hypophosphorylation was inhibited by tautomycin and not by okadaic acid, suggesting the involvement of protein phosphatase 1. Additionally, we found that treatment of SMS-KCNR cells with fenretinide inhibited desaturase activity in a dose-dependent manner. An increase in dihydroceramides (but not ceramides) paralleled this process as measured by liquid chromatography/mass spectrometry. There were no effects on the mRNA or protein levels of DEGS-1, suggesting that fenretinide acts at the post-translational level as an inhibitor of this enzyme. Tautomycin was also able to block the hypophosphorylation of the retinoblastoma protein observed upon fenretinide treatment. These findings suggest a novel biological function for dihydroceramides. C1 Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Kraveka, JM (reprint author), Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, 135 Rutledge Ave,POB 250558, Charleston, SC 29425 USA. EM kravekjm@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [K01 CA100767, L40 CA110721, P01 CA097132]; NCRR NIH HHS [C06 RR018823, P20 RR017677]; NIA NIH HHS [R01 AG016583]; NIDCR NIH HHS [R01 DE016572] NR 43 TC 85 Z9 88 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 16718 EP 16728 DI 10.1074/jbc.M700647200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500003 PM 17283068 ER PT J AU Seto, AG Kingston, RE Lau, NC AF Seto, Anita G. Kingston, Robert E. Lau, Nelson C. TI The coming of age for Piwi proteins SO MOLECULAR CELL LA English DT Review ID SMALL INTERFERING RNA; CELL MAINTENANCE; STEM-CELLS; DROSOPHILA; GERMLINE; SPERMATOGENESIS; MACHINERY; ENCODES; FAMILY; PIRNAS AB Piwi proteins, a subfamily of Argonaute (Ago) proteins, have recently been shown to bind endogenous small RNAs. However, differences between Ago proteins (which bind microRNAs and small interfering RNAs) and Piwi proteins and Piwi-interacting RNAs (piRNAs) suggest novel functions for Piwi proteins. Here, we highlight the recent progress in understanding Piwi function and the implications for germline and stem cell development. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu NR 34 TC 122 Z9 144 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 8 PY 2007 VL 26 IS 5 BP 603 EP 609 DI 10.1016/j.molcel.2007.05.021 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180PM UT WOS:000247378000001 PM 17560367 ER PT J AU McKenna, JT Tartar, JL Ward, CP Thakkar, MM Cordeira, JW McCarley, RW Strecker, RE AF McKenna, J. T. Tartar, J. L. Ward, C. P. Thakkar, M. M. Cordeira, J. W. McCarley, R. W. Strecker, R. E. TI Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness SO NEUROSCIENCE LA English DT Article DE adenosine; sleep; rat; microdialysis; apnea; delta ID BASAL FOREBRAIN; ADENOSINERGIC MODULATION; PREOPTIC AREA; NREM SLEEP; REM-SLEEP; DEPRIVATION; RATS; MICRODIALYSIS; EEG; WAKEFULNESS AB Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, Sl), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24 h of Sl resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during Sl), whereas the total amount of NREM sleep time per 24 h approached basal levels. Both 6 and 24 h of SI made rats more sleepy, as indicated by a reduced latency to fall asleep upon SI termination. Electrographic measures in the recovery sleep period following either 6 or 24 h of SI also indicated an elevation of homeostatic sleep drive; specifically, the average NREM episode duration increased (e.g. for 24 h SI, from 2 min, 5 s baseline to 3 min, 19 s following SI), as did the NREM delta power during recovery sleep. Basal forebrain (BF) levels of extracellular adenosine (AD) were also measured with microdialysis sample collection and high performance liquid chromatography detection, as previous work suggests that increasing concentrations of BF AD are related to sleepiness. BF AD levels were significantly elevated during SI, peaking at 220% of baseline during 30 h of SI exposure. These combined findings imply an elevation of the homeostatic sleep drive following either 6 or 24 h of SI, and BF AD levels appear to correlate more with sleepiness than with the cumulative amount of prior wakefulness, since total NREM sleep time declined only slightly. SI may be partially responsible for the symptom of daytime sleepiness observed in a number of clinical disorders, and this may be mediated by mechanisms involving BF AD. Published by Elsevier Ltd on behalf of IBRO. C1 Harvard Med Sch, VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA 02301 USA. Harvard Med Sch, VA Boston Healthcare Syst, Neurosci Lab, In Vitro Electrophysiol Grp, Brockton, MA 02301 USA. RP McKenna, JT (reprint author), Harvard Med Sch, VA Boston Healthcare Syst, Neurosci Lab, Res 151-C,940 Belmont St,Bldg 46, Brockton, MA 02301 USA. EM james_mckenna@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Ward, Christopher/0000-0001-9932-3894; Tartar, Jaime/0000-0002-3452-0579 FU NHLBI NIH HHS [P50 HL060292, P50 HL060292-10, T32 HL007901, T32 HL007901-10, T32 HL07901]; NIMH NIH HHS [K01 MH001798, F32 MH070156, F32 MH070156-01A1, K01 MH001798-05, K01 MH01798, R37 MH039683, R37 MH039683-23] NR 46 TC 50 Z9 51 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN 8 PY 2007 VL 146 IS 4 BP 1462 EP 1473 DI 10.1016/j.neuroscience.2007.03.009 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 176RB UT WOS:000247101500004 PM 17442498 ER PT J AU Chanock, SJ Manolio, T Boehnke, M Boerwinkle, E Hunter, DJ Thomas, G Hirschhorn, JN Abecasis, G Altshuler, D Bailey-Wilson, JE Brooks, LD Cardon, LR Daly, M Donnelly, P Fraumeni, JF Freimer, NB Gerhard, DS Gunter, C Guttmacher, AE Guyer, MS Harris, EL Hoh, J Hoover, R Kong, CA Merikangas, KR Morton, CC Palmer, LJ Phimister, EG Rice, JP Roberts, J Rotimi, C Tucker, MA Vogan, KJ Wacholder, S Wijsman, EM Winn, DM Collins, FS AF Chanock, Stephen J. Manolio, Teri Boehnke, Michael Boerwinkle, Eric Hunter, David J. Thomas, Gilles Hirschhorn, Joel N. Abecasis, Goncalo Altshuler, David Bailey-Wilson, Joan E. Brooks, Lisa D. Cardon, Lon R. Daly, Mark Donnelly, Peter Fraumeni, Joseph F., Jr. Freimer, Nelson B. Gerhard, Daniela S. Gunter, Chris Guttmacher, Alan E. Guyer, Mark S. Harris, Emily L. Hoh, Josephine Hoover, Robert Kong, C. Augustine Merikangas, Kathleen R. Morton, Cynthia C. Palmer, Lyle J. Phimister, Elizabeth G. Rice, John P. Roberts, Jerry Rotimi, Charles Tucker, Margaret A. Vogan, Kyle J. Wacholder, Sholom Wijsman, Ellen M. Winn, Deborah M. Collins, Francis S. CA NCI-NHGRI Working Grp Rep TI Replicating genotype-phenotype associations SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON GENETIC-VARIANTS; FACTOR-H POLYMORPHISM; PARKINSON-DISEASE; MACULAR DEGENERATION; PROSTATE-CANCER; CROHNS-DISEASE; DYSBINDIN GENE; RISK LOCUS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA. Harvard Univ, Sch Med, Childrens Hosp, Broad Inst MIT & Harvard,Cambridge Ctr 7, Boston, MA 02114 USA. Massachusetts Gen Hosp, Broad Inst MIT & Harvard, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Univ Oxford, Oxford OX1 3TG, England. Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA. Nature, New York, NY 10013 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. DeCode Genet, IS-101 Reykjavik, Iceland. NIMH, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Western Australian Inst Med Res, Nedlands, WA 6009, Australia. Univ Western Australia, Queen Elizabeth II Med Ctr, Nedlands, WA 6009, Australia. New England Journal Med, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Howard Univ, Genet Epidemiol Unit, Natl Human Genome Ctr, Washington, DC 20060 USA. Nature Genet, Cambridge, MA 02141 USA. Univ Washington, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NCI, Epidemiol & Genet Res Program, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov; manoliot@nhgri.nih.gov RI Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Palmer, Lyle/K-3196-2014; Tucker, Margaret/B-4297-2015; OI Altshuler, David/0000-0002-7250-4107; Palmer, Lyle/0000-0002-1628-3055; Bailey-Wilson, Joan/0000-0002-9153-2920; Wijsman, Ellen/0000-0002-2725-6669; Abecasis, Goncalo/0000-0003-1509-1825 NR 81 TC 907 Z9 930 U1 2 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 7 PY 2007 VL 447 IS 7145 BP 655 EP 660 DI 10.1038/447655a PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175RI UT WOS:000247030700034 ER PT J AU Tesco, G Koh, YH Kang, EL Cameron, AN Das, S Sena-Esteves, M Hiltunen, M Yang, SH Zhong, ZY Shen, Y Simpkins, JW Tanzi, RE AF Tesco, Giuseppina Koh, Young Ho Kang, Eugene L. Cameron, Andrew N. Das, Shinjita Sena-Esteves, Miguel Hiltunen, Mikko Yang, Shao-Hua Zhong, Zhenyu Shen, Yong Simpkins, James W. Tanzi, Rudolph E. TI Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity SO NEURON LA English DT Article ID AMYLOID PRECURSOR PROTEIN; TRANSIENT CEREBRAL-ISCHEMIA; ALZHEIMERS-DISEASE; A-BETA; OXIDATIVE STRESS; FOCAL ISCHEMIA; CYTOSOLIC DOMAIN; CLEAVING ENZYME; SORTING SIGNAL; MESSENGER-RNA AB beta-site APP-cleaving enzyme (BACE) is required for production of the Alzheimer's disease (AD)-associated AD protein. BACE levels are elevated in AD brain, and increasing evidence reveals BACE as a stress-related protease that is upregulated following cerebral ischemia. However, the molecular mechanism responsible is unknown. We show that increases in BACE and beta-secretase activity are due to posttranslational stabilization following caspase activation. We also found that during cerebral ischemia, levels of GGA3, an adaptor protein involved in BACE trafficking, are reduced, while BACE levels are increased. RNAi silencing of GGA3 also elevated levels of BACE and AD. Finally, in AD brain samples, GGA3 protein levels were significantly decreased and inversely correlated with increased levels of BACE. In summary, we have elucidated a GGA3-dependent mechanism regulating BACE levels and beta-secretase activity. This mechanism may explain increased cerebral levels of BACE and AD following cerebral ischemia and existing in AD. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. Sun Hlth Res Inst, Sun City, AZ 85351 USA. RP Tesco, G (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM tescog@helix.mgh.harvard.edu; tanzi@helix.mgh.harvard.edu RI Yang, Shaohua/D-1738-2013 FU NIA NIH HHS [R01 AG025888, 1R01AG025952, R01 AG025952, R01 AG025952-01A2, R01 AG033016]; NIMH NIH HHS [1K12MH069281, 1R37MH60009, K12 MH069281, K12 MH069281-04, R37 MH060009, R37 MH060009-08] NR 69 TC 233 Z9 238 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 7 PY 2007 VL 54 IS 5 BP 721 EP 737 DI 10.1016/j.neuron.2007.05.012 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 179ZQ UT WOS:000247329900007 PM 17553422 ER PT J AU Eremeeva, ME Gerns, HL Lydy, SL Goo, JS Ryan, ET Mathew, SS Ferraro, MJ Holden, JM Nicholson, WL Dasch, GA Koehler, JE AF Eremeeva, Marina E. Gerns, Helen L. Lydy, Shari L. Goo, Jeanna S. Ryan, Edward T. Mathew, Smitha S. Ferraro, Mary Jane Holden, Judith M. Nicholson, William L. Dasch, Gregory A. Koehler, Jane E. TI Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CAT-SCRATCH DISEASE; BACILLARY ANGIOMATOSIS; 2-DIMENSIONAL ELECTROPHORESIS; IDENTIFICATION; HENSELAE; GENE; EPIDEMIOLOGY; PROTEINS; INFECTIONS; PATHOGEN AB Bartonella species cause serious human infections globally, including bacillary angiomatosis, Oroya fever, trench fever, and endocarditis. We describe a patient who had fever and splenomegaly after traveling to Peru and also had bacteremia from an organism that resembled Bartonella bacilliformis, the causative agent of Oroya fever, which is endemic to Peru. However, genetic analyses revealed that this fastidious bacterium represented a previously uncultured and unnamed bartonella species, closely related to B. clarridgeiae and more distantly related to B. bacilliformis. We characterized this isolate, including its ability to cause fever and sustained bacteremia in a rhesus macaque. The route of infection and burden of human disease associated with this newly described pathogen are currently unknown. C1 Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koehler, JE (reprint author), Univ Calif San Francisco, Div Infect Dis, Box 0654, San Francisco, CA 94143 USA. FU NIAID NIH HHS [R01 AI043703, R01 AI052813, R01 AI43703, R01 AI52813] NR 27 TC 98 Z9 104 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2007 VL 356 IS 23 BP 2381 EP 2387 DI 10.1056/NEJMoa065987 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 175QY UT WOS:000247029300007 PM 17554119 ER PT J AU Punglia, RS Morrow, M Winer, EP Harris, JR AF Punglia, Rinaa S. Morrow, Monica Winer, Eric P. Harris, Jay R. TI Current concepts: Local therapy and survival in breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CONSERVING THERAPY; RANDOMIZED-TRIAL; ADJUVANT CHEMOTHERAPY; TUMOR RECURRENCE; POSTOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; SYSTEMIC THERAPY; YOUNG-PATIENTS; PATIENTS PREFERENCES; PREMENOPAUSAL WOMEN C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Smith 274, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu NR 51 TC 149 Z9 153 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2007 VL 356 IS 23 BP 2399 EP 2405 DI 10.1056/NEJMra065241 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 175QY UT WOS:000247029300009 PM 17554121 ER PT J AU Gourcerol, G St-Pierre, DH Tache, Y AF Gourcerol, G. St-Pierre, D. H. Tache, Y. TI Lack of obestatin effects on food intake: Should obestatin be renamed ghrelin-associated peptide (GAP)? SO REGULATORY PEPTIDES LA English DT Review DE ghrelin; obestatin; food intake; gastric emptying; GPR39 ID GROWTH-HORMONE SECRETAGOGUE; COUPLED RECEPTOR GPR39; GASTROINTESTINAL HORMONES; SYNERGISTIC INTERACTION; PERIPHERAL GHRELIN; ENERGY-BALANCE; RATS; SECRETION; LEPTIN; RODENTS AB Obestatin is a newly identified ghrelin-associated peptide (GAP) that is derived from post-translational processing of the prepro-ghrelin gene. Obestatin has been reported initially to be the endogenous ligand for the orphan receptor G protein-coupled receptor 39 (GPR39), and to reduce refeeding- and ghrelin-stimulated food intake and gastric transit in fasted mice, and body weight gain upon chronic peripheral injection. However, recent reports indicate that obestatin is unlikely to be the endogenous ligand for GPR39 based on the lack of specific binding on GRP39 receptor expressing cells and the absence of signal transduction pathway activation. In addition, a number of studies provided convergent evidence that ghrelin injected intracerebroventricularly or peripherally did not influence food intake, body weight gain, gastric transit, gastrointestinal motility, and gastric vagal afferent activity, as well as pituitary hormone secretions, in rats or mice. Similarly, obestatin did not alter ghrelin-induced stimulation of food intake or gastric transit. Therefore, the present state-of-knowledge on obestatin and GPR39 is leaving many unanswered questions that deserve further consideration. Those relate not only to redefining the biological action of obestatin that should be renamed GAP, but also the identification of the native ligand for GPR39. (C) 2007 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Digest Dis, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, David Geffen Sch Med, Digest Dis Res Ctr, Los Angeles, CA USA. CURE, Los Angeles, CA USA. Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIDDK NIH HHS [DK-41301, R01 DK-33061] NR 41 TC 82 Z9 85 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUN 7 PY 2007 VL 141 IS 1-3 BP 1 EP 7 DI 10.1016/j.regpep.2006.12.023 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 165SZ UT WOS:000246327300001 PM 17321609 ER PT J AU Kaurah, P MacMillan, A Boyd, N Senz, J De Luca, A Chun, N Suriano, G Zaor, S Van Manen, L Gilpin, C Nikkel, S Connolly-Wilson, M Weissman, S Rubinstein, WS Sebold, C Greenstein, R Stroop, J Yim, D Panzini, B McKinnon, W Greenblatt, M Wirtzfeld, D Fontaine, D Coit, D Yoon, S Chung, D Lauwers, G Pizzuti, A Vaccaro, C Redal, MA Oliveira, C Tischkowitz, M Olschwang, S Gallinger, S Lynch, H Green, J Ford, J Pharoah, P Fernandez, B Huntsman, D AF Kaurah, Pardeep MacMillan, Andree Boyd, Niki Senz, Janine De Luca, Alessandro Chun, Nicki Suriano, Gianpaolo Zaor, Sonya Van Manen, Lori Gilpin, Cathy Nikkel, Sarah Connolly-Wilson, Mary Weissman, Scott Rubinstein, Wendy S. Sebold, Courtney Greenstein, Robert Stroop, Jennifer Yim, Dwight Panzini, Benoit McKinnon, Wendy Greenblatt, Marc Wirtzfeld, Debrah Fontaine, Daniel Coit, Daniel Yoon, Sam Chung, Daniel Lauwers, Gregory Pizzuti, Antonio Vaccaro, Carlos Redal, Maria Ana Oliveira, Carla Tischkowitz, Marc Olschwang, Sylviane Gallinger, Steven Lynch, Henry Green, Jane Ford, James Pharoah, Paul Fernandez, Bridget Huntsman, David TI Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID E-CADHERIN GENE; PROPHYLACTIC TOTAL GASTRECTOMY; GERMLINE MISSENSE MUTATIONS; BREAST-CANCER; COLORECTAL-CANCER; MESSENGER-RNA; CARCINOMA; PREDISPOSITION; NEWFOUNDLAND; MANAGEMENT AB Context Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin ( CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer. Objective To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry. Design, Setting, and Patients Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years. Main Outcome Measures Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations. Results Thirteen mutations ( 6 novel) were identified in 15 of the 38 families ( 40% detection rate). The 1137G > A splicing mutation and the 1901C > T ( A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G > A ( R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% ( 95% confidence interval [ CI], 12%91%) for males and 63% ( 95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% ( 95% CI, 29%-94%). Conclusions Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported. C1 British Columbia Canc Agcy, Hereditary Canc Program, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada. Hlth Sci Ctr, Prov Med Genet Program, St John, NF, Canada. Stanford Univ, Sch Med, Canc Genet Program, Div Oncol, Stanford, CA 94305 USA. Univ Porto, Inst Mol Pathol & Immunol, Fac Med, P-4100 Oporto, Portugal. Sir Mortimer B Davis Jewish Hosp, Canc Prevent Ctr, Montreal, PQ H3T 1E2, Canada. Kingston Gen Hosp, Familial Oncol Program, Canc Ctr SE Ontario, Kingston, ON K7L 2V7, Canada. Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. Evanston NW Healthcare, Ctr Med Genet, Evanston, IL USA. Wilford Hall USAF Med Ctr, Pediat Subspecialty Clin, San Antonio, TX 78236 USA. Univ Connecticut, Ctr Hlth, Hereditary Canc Program, Div Med Genet, Farmington, CT USA. Kaiser Permanente, Dept Pediat, Honolulu, HI USA. CHUM Hotel Dieu, Clin Canc Hereditaires, Montreal, PQ, Canada. CHUM Hop Notre Dame, Serv Gastroenterol, Montreal, PQ, Canada. Univ Vermont, Coll Med, Familial Canc Program, Burlington, VT USA. Mem Univ Newfoundland, Div Surg, St John, NF, Canada. Mem Univ Newfoundland, Div Clin Genet, St John, NF, Canada. Mem Univ Newfoundland, Dept Anat Pathol, St John, NF, Canada. Mem Univ Newfoundland, Discipline Genet, Fac Med, St John, NF, Canada. Mem Sloan Kettering Canc Ctr, Gastric & Mixed Tumor Serv, Dept Surg, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. IRCCS, CCS Hosp, San Giovanni Rotondo, Italy. CSS Mendel Inst, Rome, Italy. Hosp Italiano Buenos Aires, Serv Gen Surg, Buenos Aires, DF, Argentina. Hosp Italiano Buenos Aires, Inst Ciencias Basicas & Med Expt, Buenos Aires, DF, Argentina. McGill Univ, Program Canc Genet, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Inst J Paoli I Calmettes, INSERM, U599, F-13009 Marseille, France. Univ Toronto, Hepatobiliary & Pancreat Surg Grp, Div Gen Surg, Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. Univ Cambridge, Dept Oncol, Cambridge, England. RP Huntsman, D (reprint author), British Columbia Canc Agcy, Hereditary Canc Program, Ctr Translat & Appl Genom, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM dhuntsma@bccancer.bc.ca RI Gallinger, Steven/E-4575-2013; Olschwang, Sylviane/G-2716-2013; Oliveira, Carla/F-8188-2011; OI Oliveira, Carla/0000-0001-8340-2264; Vaccaro, Carlos/0000-0002-1299-5864 FU NCI NIH HHS [5UO1 CA86389] NR 56 TC 178 Z9 182 U1 5 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 6 PY 2007 VL 297 IS 21 BP 2360 EP 2372 DI 10.1001/jama.297.21.2360 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 175IL UT WOS:000247007200018 PM 17545690 ER PT J AU Glickman, SW Ou, FS DeLong, ER Roe, MT Lytle, BL Mulgund, J Rumsfeld, JS Gibler, WB Ohman, EM Schulman, KA Peterson, ED AF Glickman, Seth W. Ou, Fang-Shu DeLong, Elizabeth R. Roe, Matthew T. Lytle, Barbara L. Mulgund, Jyotsna Rumsfeld, John S. Gibler, W. Brian Ohman, E. Magnus Schulman, Kevin A. Peterson, Eric D. TI Pay for performance, quality of care, and outcomes in acute myocardial infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROMES; HEALTH-CARE; FINANCIAL INCENTIVES; IMPORTANT DIFFERENCE; FOR-PERFORMANCE; UNSTABLE ANGINA; IMPROVEMENT; MANAGEMENT; ASSOCIATION; STRATEGIES AB of Context Pay for performance has been promoted as a tool for improving quality of care. In 2003, the Centers for Medicare & Medicaid Services ( CMS) launched the largest pay-for-performance pilot project to date in the United States, including indicators for acute myocardial infarction. Objective To determine if pay for performance was associated with either improved processes of care and outcomes or unintended consequences for acute myocardial infarction at hospitals participating in the CMS pilot project. Design, Setting, and Participants An observational, patient-level analysis of 105 383 patients with acute non-ST-segment elevation myocardial infarction enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association ( ACC/AHA) Guidelines ( CRUSADE) national quality-improvement initiative. Patients were treated between July 1, 2003, and June 30, 2006, at 54 hospitals in the CMS program and 446 control hospitals. Main Outcome Measures The differences in the use of ACC/AHA class I guideline recommended therapies and in-hospital mortality between pay for performance and control hospitals. Results Among treatments subject to financial incentives, there was a slightly higher rate of improvement for 2 of 6 targeted therapies at pay-for-performance vs control hospitals ( odds ratio [ OR] comparing adherence scores from 2003 through 2006 at half-year intervals for aspirin at discharge, 1.31; 95% confidence interval [ CI], 1.181.46 vs OR, 1.17; 95% CI, 1.12-1.21; P=. 04) and for smoking cessation counseling ( OR, 1.50; 95% CI, 1.29-1.73 vs OR, 1.28; 95% CI, 1.22-1.35; P=. 05). There was no significant difference in a composite measure of the 6 CMS rewarded therapies between the 2 hospital groups ( change in odds per half-year period of receiving CMS therapies: OR, 1.23; 95% CI, 1.15-1.30 vs OR, 1.17; 95% CI, 1.14-1.20; P=. 16). For composite measures of acute myocardial infarction treatments not subject to incentives, rates of improvement were not significantly different ( OR, 1.09; 95% CI, 1.051.14 vs OR, 1.08; 95% CI, 1.06- 1.09; P=. 49). Overall, there was no evidence that improvements in in-hospital mortality were incrementally greater at pay-for-performance sites ( change in odds of in-hospital death per half-year period, 0.91; 95% CI, 0.84-0.99 vs 0.97; 95% CI, 0.94-0.99; P=. 21). Conclusions Among hospitals participating in a voluntary quality-improvement initiative, the pay-for-performance program was not associated with a significant incremental improvement in quality of care or outcomes for acute myocardial infarction. Conversely, we did not find evidence that pay for performance had an adverse association with improvement in processes of care that were not subject to financial incentives. Additional studies of pay for performance are needed to determine its optimal role in quality-improvement initiatives. C1 Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC 27715 USA. Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC 27715 USA. Duke Univ, Med Ctr, Dept Surg, Div Emergency Med, Durham, NC USA. Duke Univ, Med Ctr, Hlth Sector Management Program, Fuqua Sch Business, Durham, NC USA. Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA. RP Peterson, ED (reprint author), Duke Clin Res Inst, Outcomes Res & Assessment Grp, POB 17969, Durham, NC 27715 USA. EM peter016@mc.duke.edu FU NIA NIH HHS [R01 AG025312 01A1] NR 30 TC 181 Z9 181 U1 1 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 6 PY 2007 VL 297 IS 21 BP 2373 EP 2380 DI 10.1001/jama.297.21.2373 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 175IL UT WOS:000247007200019 PM 17551130 ER PT J AU Clark, DA Gabel, CV Gabel, H Samuel, ADT AF Clark, Damon A. Gabel, Christopher V. Gabel, Harrison Samuel, Aravinthan D. T. TI Temporal activity patterns in thermosensory neurons of freely moving Caenorhabditis elegans encode spatial thermal gradients SO JOURNAL OF NEUROSCIENCE LA English DT Article DE behavior; C. elegans; fluorescence microscopy; imaging; sensory neurons; temperature ID FLUORESCENT PROTEINS; C.-ELEGANS; THERMOTAXIS; BEHAVIOR; INDICATORS; ANIMALS; CA2+ AB Our understanding of the operation of neurons and neuronal circuits has come primarily from probing their activity in dissected, anesthetized, or restrained animals. However, the behaviorally relevant operation of neurons and neuronal circuits occurs within intact animals as they freely perform behavioral tasks. The small size and transparency of the nematode Caenorhabditis elegans make it an ideal system for noninvasive, optical measurements of neuronal activity. Here, we use a high signal-to-noise version of cameleon, a fluorescent calcium-binding protein, to quantify the activity of the AFD thermosensory neuron of individual worms freely navigating spatial thermal gradients. We find that AFD activity is directly coupled to the worm's exploratory movements in spatial thermal gradients. We show that the worm is able, in principle, to evaluate and guide its own thermotactic behaviors with respect to ambient spatial thermal gradients by monitoring the activity of this single thermosensory neuron. C1 Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Samuel, ADT (reprint author), 17 Oxford St, Cambridge, MA 02138 USA. EM samuel@physics.harvard.edu OI Clark, Damon/0000-0001-8487-700X NR 22 TC 45 Z9 46 U1 1 U2 5 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 JUN 6 PY 2007 VL 27 IS 23 BP 6083 EP 6090 DI 10.1523/JNEUROSCI.1032-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 175YG UT WOS:000247049300003 PM 17553981 ER PT J AU Klunk, WE Price, JC Mathis, CA Tsopelas, ND Lopresti, BJ Ziolko, SK Bi, W Hoge, JA Cohen, AD Ikonomovic, MD Saxton, JA Snitz, BE Pollen, DA Moonis, M Lippa, CF Swearer, JM Johnson, KA Rentz, DM Fischman, AJ Aizenstein, HJ DeKosky, ST AF Klunk, William E. Price, Julie C. Mathis, Chester A. Tsopelas, Nicholas D. Lopresti, Brian J. Ziolko, Scott K. Bi, Wenzhu Hoge, Jessica A. Cohen, Ann D. Ikonomovic, Milos D. Saxton, Judith A. Snitz, Beth E. Pollen, Daniel A. Moonis, Majaz Lippa, Carol F. Swearer, Joan M. Johnson, Keith A. Rentz, Dorene M. Fischman, Alan J. Aizenstein, Howard J. DeKosky, Steven T. TI Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; positron emission tomography; amyloid-beta; diagnosis; Pittsburgh Compound-B; striatum ID FAMILIAL ALZHEIMERS-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; MISSENSE MUTATIONS; BETA IMMUNIZATION; TEMPORAL CORTEX; BRAIN; PET; PLAQUES AB The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-beta protein is an initiating event in Alzheimer's disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (n = 5) and symptomatic (n = 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (n = 2) were studied with PiB -PET imaging and compared with sporadic AD subjects (n = 12) and controls from the general population (n = 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35 -49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms. C1 Western Psychiat Inst & Clin, Thomas Detre Hall, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19219 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Klunk, WE (reprint author), Western Psychiat Inst & Clin, Thomas Detre Hall, Room 1422,3811 OHara St, Pittsburgh, PA 15213 USA. EM klunkwe@upmc.edu RI Mathis, Chester/A-8607-2009; Lopresti, Brian/O-2465-2016; OI Lopresti, Brian/0000-0002-0595-0203; Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [K02 AG001039, P01 AG025204, P01 AG025204-04, P01 AG025204-04S1, P01 AG025204-05, P01 AG025204-06, P01 AG025204-07, P01 AG025204-08, P50 AG005133, P50 AG005133-25, P50 AG005133-26, P50 AG005133-27, P50 AG005133-28, P50 AG005133-29, R01 AG018402, R01 AG020226, R37 AG025516, R37 AG025516-01, R37 AG025516-02, R37 AG025516-03, R37 AG025516-04, R37 AG025516-05, R37 AG025516-05S1, R37 AG025516-06, R37 AG025516-07, R37 AG025516-08, RF1 AG025516]; NIMH NIH HHS [K01 MH001976, R01 MH070729] NR 87 TC 208 Z9 211 U1 0 U2 17 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 JUN 6 PY 2007 VL 27 IS 23 BP 6174 EP 6184 DI 10.1523/JNEUROSCI.0730-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 175YG UT WOS:000247049300011 PM 17553989 ER PT J AU Bihl, F Castelli, D Marincola, F Dodd, RY Brander, C AF Bihl, Florian Castelli, Damiano Marincola, Francesco Dodd, Roger Y. Brander, Christian TI Transfusion-transmitted infections SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID WEST-NILE-VIRUS; HEPATITIS-B-VIRUS; NUCLEIC-ACID TECHNOLOGY; PARVOVIRUS B19 TRANSMISSION; CREUTZFELDT-JAKOB-DISEASE; INACTINE PEN110 CHEMISTRY; PLASTIC CULTURE BOTTLES; SURFACE-ANTIGEN GENE; BLOOD-TRANSFUSION; PATHOGEN INACTIVATION AB Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens. C1 Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. Swiss Red Cross Blood Transfus Serv So Switzerlan, Lugano, Switzerland. NIH Clin Ctr, HLA Typing Lab, Bethesda, MD USA. Amer Red Cross, Holland Lab, Rockville, MD USA. RP Bihl, F (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM f.bihl@mac.com; damiano.castelli@eoc.ch; FMarincola@cc.nih.gov; Dodd@usa.redcross.org OI Brander, Christian/0000-0002-0548-5778 NR 145 TC 46 Z9 50 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 6 PY 2007 VL 5 AR 25 DI 10.1186/1479-5876-5-25 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 185CE UT WOS:000247688100001 PM 17553144 ER PT J AU Voisine, C Varma, H Walker, N Bates, EA Stockwell, BR Hart, AC AF Voisine, Cindy Varma, Hemant Walker, Nicola Bates, Emily A. Stockwell, Brent R. Hart, Anne C. TI Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans SO PLOS ONE LA English DT Article AB Background. The prolonged time course of Huntington's disease (HD) neurodegeneration increases both the time and cost of testing potential therapeutic compounds in mammalian models. An alternative is to initially assess the efficacy of compounds in invertebrate models, reducing time of testing from months to days. Methodology/Principal Findings. We screened candidate therapeutic compounds that were identified previously in cell culture/animal studies in a C. elegans HD model and found that two FDA approved drugs, lithium chloride and mithramycin, independently and in combination suppressed HD neurotoxicity. Aging is a critical contributor to late onset neurodegenerative diseases. Using a genetic strategy and a novel assay, we demonstrate that lithium chloride and mithramycin remain neuroprotective independent of activity of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging. Conclusions/Significance. These results suggest that pathways involved in polyglutamine-induced degeneration are distinct from specific aging pathways. The assays presented here will be useful for rapid and inexpensive testing of other potential HD drugs and elucidating pathways of drug action. Additionally, the neuroprotection conferred by lithium chloride and mithramycin suggests that these drugs may be useful for polyglutamine disease therapy. C1 [Voisine, Cindy; Walker, Nicola; Bates, Emily A.; Hart, Anne C.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Varma, Hemant; Stockwell, Brent R.] Columbia Univ, Fairchild Ctr, Dept Biol Sci, New York, NY 10027 USA. [Stockwell, Brent R.] Columbia Univ, Fairchild Ctr, Dept Chem, New York, NY 10027 USA. [Voisine, Cindy; Walker, Nicola; Bates, Emily A.; Hart, Anne C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hart, AC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. EM hart@helix.mgh.harvard.edu FU Hereditary Disease Foundation; Cure Huntington Disease Initiative; High Q Foundation; Ellison Medical Foundation; NIH [NS-040048, T32 AG20506]; Burroughs Wellcome Fund FX We gratefully acknowledge the support of the Hereditary Disease Foundation (C. V. and B. R. S.), Cure Huntington Disease Initiative (B. R. S.), the High Q Foundation (H. V. and B. R. S.), the Ellison Medical Foundation (A. C. H.) and the NIH (NS-040048 for A. C. H. and T32 AG20506 for C. V.). Brent R. Stockwell is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. NR 46 TC 65 Z9 67 U1 5 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 6 PY 2007 VL 2 IS 6 AR e504 DI 10.1371/journal.pone.0000504 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GC UT WOS:000207451500013 PM 17551584 ER PT J AU Chacon, P Rosario-Campos, MC Pauls, DL Hounie, AG Curi, M Akkerman, F Shimabokuro, FH de Mathis, MA Lopes, AC Hasler, G Miguel, EC AF Chacon, Priscila Rosario-Campos, Maria Conceicao Pauls, David L. Hounie, Ana Gabriela Curi, Mariana Akkerman, Fernando Shimabokuro, Fabiana Harumi Mathis, Maria Alice de Lopes, Antonio Carlos Hasler, Gregor Miguel, Euripedes Constantino TI Obsessive-compulsive symptoms in sibling pairs concordant for obsessive-compulsive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article; Proceedings Paper CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet DE obsessive; factors; age at onset; gender ID LA-TOURETTE-SYNDROME; SEGREGATION ANALYSIS; DIMENSIONS; PHENOTYPES; SUBTYPES; GENDER; ONSET; FAMILY; SCALE; OCD AB Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. Phenotypic studies of affected sib-pairs (SPs) may help to characterize familial components of the phenotype. To determine whether SPs affected with OCD are similar in age at onset of obsessive-compulsive symptoms (OCS), symptom dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from 13 to 59 years old were evaluated by expert psychiatrists or psychologists. Families with two or more siblings affected with OCD were recruited from several OCD clinics in Brazil. The Yale Brown Obsessive-Compulsive Scale Checklist was used to assess OCS and the severity of OCD. The OCD diagnoses were made according to the DSM-IV. The chi-square test was used to assess concordance of TD presence within SPs based on the TD frequency reported in the literature (30%). There were significantly more siblings with early-onset OCS than with late-onset OCS (P=0.002). Age at onset of OCS correlated positively and significantly between the two members of each SP (P = 0.005). Fourteen patients (35%) were diagnosed with TDs. There was no concordance of the TD presence within the SPs. When both were male, there was a significant sibling correlation in the contamination obsessions/cleaning compulsions dimension (ICC 0.74; P=0.002). Similarly, when both siblings were female, they were comparable in the hoarding obsessions/compulsions dimension (ICC=0.76; P=0.01). Familial factors seem to contribute to specific OCD phenotypic components such as age at onset of OCS and specific dimensions. The obvious influence of gender is as yet unexplained. (c) 2007 Wiley-Liss, Inc. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05403010 Sao Paulo, Brazil. Univ Fed Bahia, Salvador, BA, Brazil. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. RP Chacon, P (reprint author), Univ Sao Paulo, Sch Med, Dept Psychiat, Rua Dr Ovidio Pires de Campos,S-N, BR-05403010 Sao Paulo, Brazil. EM priscila@protoc.com.br RI Miguel, Euripedes/B-2871-2008; Curi, Mariana/E-8468-2011; Hasler, Gregor/E-4845-2012; Lopes, Antonio/A-7844-2010; do Rosario, Maria Conceicao/E-5213-2012; de mathis, maria alice/D-7269-2012; Chacon, Priscila/G-9401-2012 OI Hasler, Gregor/0000-0002-8311-0138; Lopes, Antonio/0000-0002-3075-6795; do Rosario, Maria Conceicao/0000-0002-9687-0072; NR 46 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN 5 PY 2007 VL 144B IS 4 BP 551 EP 555 DI 10.1002/ajmg.b.30457 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 174ZX UT WOS:000246982700023 PM 17440931 ER PT J AU Mega, JL Morrow, DA Ostor, E Dorobantu, M Qin, J Antman, EM Braunwald, E AF Mega, Jessica L. Morrow, David A. Ostor, Erika Dorobantu, Maria Qin, Jie Antman, Elliott M. Braunwald, Eugene TI Outcomes and optimal antithrombotic therapy in women undergoing fibrinolysis for ST-elevation myocardial infarction SO CIRCULATION LA English DT Article DE anticoagulants; fibrinolysis; myocardial infarction; sex ID ACUTE CORONARY SYNDROMES; UNFRACTIONATED HEPARIN; THROMBOLYTIC THERAPY; INTRACRANIAL HEMORRHAGE; GENDER-DIFFERENCES; RANDOMIZED TRIALS; EARLY MORTALITY; HEART-DISEASE; SEX; MEN AB Background-The manifestations, complications, and outcomes of cardiovascular disease differ between women and men. The safety and efficacy of pharmacological reperfusion therapy in women with ST-elevation myocardial infarction are of particular interest. Methods and Results-We investigated outcomes in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction ( ExTRACT- TIMI) 25 study, which randomized ST-elevation myocardial infarction patients with planned fibrinolysis to enoxaparin or unfractionated heparin. Compared with men (n = 15 696), women ( n = 4783) were older and more likely to have hypertension and diabetes ( P < 0.001). The unadjusted 30-day mortality rate for women was > 2-fold higher than for men (13.2% versus 5.4%; odds ratio, 2.66; 95% CI, 2.40 to 2.96). After adjustment for age, fibrinolytic therapy, revascularization, region, and elements of the TIMI Risk Score, women had a 1.25- fold- higher 30- day risk of death ( 95% CI, 1.08 to 1.46) but similar risk of intracerebral hemorrhage ( adjusted odds ratio, 0.81; 95% CI, 0.52 to 1.26). The 30- day rate of death or nonfatal MI in women was reduced by enoxaparin compared with unfractionated heparin in women (15.4% versus 18.3%; P = 0.007). Major bleeding was more frequent in women receiving enoxaparin compared with those receiving unfractionated heparin ( 2.3% versus 1.4%; P = 0.022) but similar among women and men receiving enoxaparin ( 2.3% versus 2.0%; P = 0.39). The rates of death, nonfatal myocardial infarction, or nonfatal major bleeding ( net clinical benefit) were lower with enoxaparin (absolute risk reduction, 2.6% in women [ P = 0.02] and 1.6% in men [ P = 0.001]). Conclusions-In ExTRACT- TIMI 25, women presented with a profile of higher baseline risk and increased short- term mortality. In this large, contemporary clinical trial, women had similar relative and greater absolute risk reductions than men when treated with enoxaparin compared with unfractionated heparin as adjunctive therapy with fibrinolysis. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. St Johns Hosp, Dept Cardiol, Budapest, Hungary. Emergency Hosp Bucharest, Bucharest, Romania. RP Mega, JL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM jmega@partners.org NR 31 TC 32 Z9 32 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 5 PY 2007 VL 115 IS 22 BP 2822 EP 2828 DI 10.1161/CIRCULATIONAHA.106.679548 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 174WD UT WOS:000246972600007 PM 17515461 ER PT J AU Heidenreich, PA Gholami, P Sahay, A Massie, B Goldstein, MK AF Heidenreich, Paul A. Gholami, Parisa Sahay, Anju Massie, Barry Goldstein, Mary K. TI Clinical reminders attached to echocardiography reports of patients with reduced left ventricular ejection fraction increase use of beta-blockers - A randomized trial SO CIRCULATION LA English DT Article DE adrenergic beta-antagonists; echocardiography; health services research; heart failure; reminder systems ID CHRONIC HEART-FAILURE; QUALITY-OF-CARE; COST-EFFECTIVENESS; RECOMMENDATIONS; ENDOCARDITIS; ASSOCIATION; CARVEDILOL; METOPROLOL; DIAGNOSIS; UPDATE AB Background-Although beta-blockers are known to prolong survival for patients with reduced left ventricular ejection fraction, they are often underused. We hypothesized that a reminder attached to the echocardiography report would increase the use of beta-blockers for patients with reduced left ventricular ejection fraction. Methods and Results-We randomized 1546 consecutive patients with a left ventricular ejection fraction < 45% found on echocardiography at 1 of 3 laboratories to a reminder for use of beta-blockers or no reminder. Patients were excluded from analysis if they died within 30 days of randomization (n = 89), did not receive medications through the Veterans Affairs system after 30 days ( n = 180), or underwent echocardiography at > 1 laboratory ( n = 6). The primary outcome was a prescription for an oral beta-blocker between 1 and 9 months after randomization. The mean age of the 1271 included patients was 69 years; 60% had a history of heart failure, and 51% were receiving treatment with beta- blockers at the time of echocardiography. More patients randomized to the reminder had a subsequent beta- blocker prescription (74%, 458 of 621) compared with those randomized to no reminder (66%, 428 of 650; P = 0.002). The effect of the reminder was not significantly different for subgroups based on patient location ( inpatient versus outpatient) or prior use of beta-blockers. Conclusions-A reminder attached to the echocardiography report increased the use of beta-blockers in patients with depressed left ventricular systolic function. C1 Palo Alto VA Hlth Care Syst, Palo Alto, CA 94304 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Heidenreich, PA (reprint author), Palo Alto VA Hlth Care Syst, 111C Cardiol,3801 Miranda Ave, Palo Alto, CA 94304 USA. EM heiden@stanford.edu OI Heidenreich, Paul/0000-0001-7730-8490 NR 20 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 5 PY 2007 VL 115 IS 22 BP 2829 EP 2834 DI 10.1161/CIRCULATIONAHA.106.684753 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 174WD UT WOS:000246972600008 PM 17515459 ER PT J AU Udelson, JE McGrew, FA Flores, E Ibrahim, H Katz, S Koshkarian, G O'Brien, T Kronenberg, MW Zimmer, C Orlandi, C Konstam, MA AF Udelson, James E. McGrew, Frank A. Flores, Enrique Ibrahim, Hassan Katz, Stewart Koshkarian, Gregory O'Brien, Terrence Kronenberg, Marvin W. Zimmer, Christopher Orlandi, Cesare Konstam, Marvin A. TI Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VASOPRESSIN RECEPTOR ANTAGONIST; CONVERTING-ENZYME-INHIBITOR; NEONATAL-RAT CARDIOMYOCYTE; CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; PROTEIN-SYNTHESIS; ENALAPRIL; HYPONATREMIA; OMAPATRILAT; PROGRESSION AB Objectives This study sought to examine the effects of vasopressin V-2 receptor antagonism with tolvaptan on the changes in left ventricular (LV) volumes over time. Background Vasopressin levels may be increased in patients with heart failure (HF) and may be a factor driving the progression of HF. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the effect of long-term administration of the vasopressin V-2-receptor antagonist tolvaptan (30 mg,/day) on reducing left ventricular end-diastolic volume (LVEDV) compared with placebo in patients with HF and reduced systolic function, using quantitative radionuclide ventriculography at baseline, repeated after 1 year of therapy, and repeated again approximately 1 week after withdrawal of study drug. Results A total of 120 patients were randomized to tolvaptan and 120 were randomized to placebo. In the placebo group, there was no change in LVEDV over the course of follow-up (change of 0.0 +/- 10.0 ml/m(2)). After 1 year of tolvaptan, there was a small reduction in LV volume (decrease of 1.8 +/- 10.7 ml/m(2)); the between-group difference was not significant (p = 0.21). During the course of the trial, there were 6 deaths (5%) and 21 HF hospitalizations (18%) in the tolvaptan group, compared with 11 deaths (9%) and 34 HF hospitalizations (28%) in the placebo group. In a time-to-event analysis, there was a significant favorable effect of tolvaptan on the composite of mortality or heart failure hospitalization (p < 0.03 by log-rank test). Conclusions In a well-treated population of stable HF patients, there was no significant effect of tolvaptan therapy on LV volumes observed during 1 year of therapy. Nonprespecified natural history data favored therapy with tolvaptan, with a reduction in the combined end point of mortality and heart failure hospitalization observed. (Multicenter, Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of Tolvaptan on Left Ventricuiar Dilatation in Congestive Heart Failure Patients; http://clinicaltrials.gov/ct/ show/NCT00043758?order = 1; NCT00043758). C1 Tufts Univ, New England Med Ctr, Sch Med, Div Cardiol, Boston, MA 02111 USA. Stern Cardiovasc Ctr, Memphis, TN USA. Georgia Heart Specialists, Covington, GA USA. N Ohio Res Ltd, Sandusky, OH USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Desert Cardiol Tucson, Tucson, AZ USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. RP Udelson, JE (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Div Cardiol, 750 Washington St,Box 70, Boston, MA 02111 USA. EM JUdelson@tufts-nemc.org NR 33 TC 76 Z9 83 U1 1 U2 6 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 JUN 5 PY 2007 VL 49 IS 22 BP 2151 EP 2159 DI 10.1016/j.jacc.2007.01.091 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 174EW UT WOS:000246925400002 PM 17543634 ER PT J AU Kelly, DF Lake, RJ Walz, T Artavanis-Tsakonas, S AF Kelly, Deborah F. Lake, Robert J. Walz, Thomas Artavanis-Tsakonas, Spyros TI Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biochemistry; electron microscopy ID IN-VIVO; CRYSTAL-STRUCTURE; ANKYRIN DOMAIN; TRANSCRIPTION; DISEASES; RECEPTOR; PATHWAY; COMPLEX AB The Notch receptor is the central element in an evolutionarily conserved signal transduction pathway that controls cell fates in metazoans. Receptor-ligand interactions trigger a cascade of proteolytic events that release the entire Notch intracellular domain (NICD) from the membrane, permitting its translocation into the nucleus and participation in a transcriptionally active complex. Using electron microscopy, we examined the structure of NICD and its interaction with the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In conjunction with biochemical analyses, we found that Drosophila NICD is monomeric and exists in two primary conformational states, only one of which can bind Su(H). Furthermore, we show that changes in divalent cation concentrations lead to NICD self-association, which seems to be mediated by the polyglutamine-containing, opa-repeat region of NICD. Our study suggests that conformational modulation of NICD may define a mechanism of Notch pathway control. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA. Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM tsakonas@helix.mgh.harvard.edu FU NCI NIH HHS [CA098402, R01 CA098402]; NIGMS NIH HHS [GM62580, GM62931, P01 GM062580, R01 GM062931]; NINDS NIH HHS [NS26084, R01 NS026084, R37 NS026084] NR 22 TC 8 Z9 8 U1 1 U2 1 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 JUN 5 PY 2007 VL 104 IS 23 BP 9591 EP 9596 DI 10.1073/pnas.0702887104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176VX UT WOS:000247114100011 PM 17535912 ER PT J AU Namekawa, SH VandeBerg, JL McCarrey, JR Lee, JT AF Namekawa, Satoshi H. VandeBerg, John L. McCarrey, John R. Lee, Jeannie T. TI Sex chromosome silencing in the marsupial male germ line SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE meiosis; X-inactivation ID INACTIVE X-CHROMOSOME; Y-CHROMOSOMES; MOUSE; MAMMALS; DNA; GENES; SPERMATOGENESIS; CHROMATIN; MICE; REGION AB In marsupials, dosage compensation involves silencing of the father's X-chromosome. Because no XIST orthologue has been found, how imprinted X-inactivation occurs is unknown. In eutherians, the X is subject to meiotic sex chromosome inactivation (MSCI) in the paternal germ line and persists thereafter as postmeiotic sex chromatin (PMSC). One hypothesis proposes that the paternal X is inherited by the eutherian zygote as a preinactive X and raises the possibility of a similar process in the marsupial germ line. Here we demonstrate that MSCI and PMSC occur in the opossum. Surprisingly, silencing occurs before X-Y association. After MSCI, the X and Y fuse through a dense plate without obvious synapsis. Significantly, sex chromosome silencing continues after meiosis, with the opossum PMSC sharing features of eutherian PMSC. These results reveal a common gametogenic program in two diverse clades of mammals and support the idea that male germ-line silencing may have provided an ancestral form of mammalian dosage compensation. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Univ Texas, Dept Biol, San Antonio, TX 78249 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NICHD NIH HHS [HD-46637, R01 HD046637]; NIGMS NIH HHS [GM-58839, R01 GM058839, R37 GM058839] NR 62 TC 60 Z9 61 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 5 PY 2007 VL 104 IS 23 BP 9730 EP 9735 DI 10.1073/pnas.0700323104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176VX UT WOS:000247114100035 PM 17535928 ER PT J AU Cannon, CP AF Cannon, Christopher P. TI Introduction: Rationale for tight control of hyperglycemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID INTENSIVE TREATMENT; DIABETES-MELLITUS; COMPLICATIONS; EPIDEMIOLOGY; PROGRESSION; OUTCOMES; DISEASE; RISK C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 14 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 4 PY 2007 VL 99 IS 11A SU S BP 1H EP 4H DI 10.1016/j.amjcard.2007.04.003 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 178IS UT WOS:000247215000001 PM 17665746 ER PT J AU Lee, JH Park, SY Shin, HK Kim, CD Lee, WS Hong, KW AF Lee, Jeong Hyun Park, So Youn Shin, Hwa Kyung Kim, Chi Dae Lee, Won Suk Hong, Ki Whan TI Poly(ADP-ribose) polymerase inhibition by cilostazol is implicated in the neuroprotective effect against focal cerebral ischemic infarct in rat SO BRAIN RESEARCH LA English DT Article DE neuroprotection; middle cerebral artery occlusion; cilostazol; poly(ADP-ribose) polymerase; anti-inflammation ID APOPTOSIS-INDUCING FACTOR; NECROSIS-FACTOR-ALPHA; CELL-DEATH; ENDOTHELIAL-CELLS; ARTERY OCCLUSION; BRAIN INJURY; ACTIVATION; DEPLETION; TRANSLOCATION; INFLAMMATION AB This study shows that cilostazol displayed a potent inhibition of PARP with IC50 of 883 41 nM in the enzyme assay, and also significantly reversed H2O2-evoked elevated PARP activity and reduced NAD(+) levels in the PC12 cells with improvement of cell viability. In in vivo study, inhibition of PARP activity by cilostazol prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct was significantly reduced in the rats that received cilostazol (30 mg/kg, twice orally) with improvement of neurological function. Moreover, cilostazol treatment significantly decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)- and poly(ADP-ribose)-positive cells associated with apoptosisinducing factor (AIF) translocation to the nucleus in the penumbral region. Further, cilostazol significantly reduced myeloperoxidase activity, a marker of neutrophil infiltration. In line with these findings, the OX-42- (a marker of microglia) and TNF-alpha-positive cells (a marker of proapoptotic protein) were markedly increased in the vehicle samples, both of which were significantly attenuated by treatment with cilostazol. Taken together, these results suggest that neuroprotective potentials of cilostazol against focal cerebral ischemic injury are, at least in part, ascribed to its anti-inflammatory effects and PARP inhibitory activity. (c) 2007 Elsevier B.V. All rights reserved. C1 Pusan Natl Univ, Coll Med, Dept Pharmacol, Pusan 602739, South Korea. Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Stroke & Neurovascular Regulat Lab, Charlestown, MA 02129 USA. Pusan Natl Univ, Med Res Ctr Ischem Tissue Regenerat, Pusan 602739, South Korea. RP Hong, KW (reprint author), Pusan Natl Univ, Coll Med, Dept Pharmacol, Pusan 602739, South Korea. EM kwhong@pusan.ac.kr RI Lee, Jeong Hyun/G-1676-2013 OI Lee, Jeong Hyun/0000-0003-0504-0119 NR 26 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 4 PY 2007 VL 1152 BP 182 EP 190 DI 10.1016/j.brainres.2007.03.035 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 181FY UT WOS:000247423700019 PM 17433265 ER PT J AU El-Amouri, SS Zhu, H Yu, J Gage, FH Verma, IM Kindy, MS AF El-Amouri, Salim S. Zhu, Hong Yu, Jin Gage, Fred H. Verma, Inder M. Kindy, Mark S. TI Neprilysin protects neurons against A beta peptide toxicity SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; neprilysin; amyloid beta peptide; lentiviral vectors; gene therapy; hippocampus ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; LENTIVIRUS VECTOR; MOUSE MODEL; PATHOLOGY; ENDOPEPTIDASE; DEGRADATION; METABOLISM; ENZYME AB In recent years, studies have suggested that accumulation of amyloid beta (A beta) peptide in the brain plays a key role in the development of Alzheimer's disease (AD). The steady-state level of A beta peptide in the brain is determined by the rate of production from amyloid precursor protein (APP) via beta- and gamma-secretases and degradation by the activity of several enzymes. Neprilysin (NEP) appears to be the most potent A beta peptide-degrading enzyme in the brain. Decreasing the activity of NEP (due to genetic mutations, age or diseases that alter the expression or activity of NEP) may lead to accumulation of the neurotoxic A beta peptide in the brain; in turn this leads to neuronal loss. We investigated the efficacy of lentivirus-mediated over-expression of NEP to protect neuronal cells from A beta peptide in vitro. Incubation of hippocampal neuronal cells (HT22) over-expressing NEP with the monomeric from of A beta peptide decreases the toxicity of A beta peptide on the neuronal cells, as measured through cell viability. We conclude that over-expression of NEP by a gene therapy approach in areas vulnerable to A beta peptide aggregation in AD brain may protect the neurons from the toxicity effects of A beta peptide and this promises a great potential target for altering the development of AD. (c) 2007 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Mol & Cellular Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Basic Bldg,Room 403,173 Ashley Ave, Charleston, SC 29425 USA. EM kindyms@musc.edu FU NIA NIH HHS [AG019323, R01 AG019323, R01 AG019323-04] NR 31 TC 36 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 4 PY 2007 VL 1152 BP 191 EP 200 DI 10.1016/j.brainres.2007.03.072 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 181FY UT WOS:000247423700020 PM 17459354 ER PT J AU Kraft, E Chen, AW Flaherty, AW Blood, AJ Kwony, KK Jenkins, BG AF Kraft, Eduard Chen, Anthony W. Flaherty, Alice W. Blood, Anne J. Kwony, Kenneth K. Jenkins, Bruce G. TI The role of the basal ganglia in bimanual coordination SO BRAIN RESEARCH LA English DT Article DE basal ganglia; bimanual coordination; motor cortex; fMRI; putamen ID SUPPLEMENTARY MOTOR AREA; SEQUENTIAL FINGER MOVEMENTS; PARKINSONS-DISEASE; NEURONAL-ACTIVITY; NEURAL SYSTEMS; MEDIAL WALL; 2 HANDS; CEREBELLAR; CORTEX; TASK AB The functional anatomical role of the basal ganglia in bimanual coordination is unknown. Utilizing functional MRI (fMRI) at 3 T, we analyzed brain activity during three different typing tasks. The first task consisted of typing with parallel finger movements (moving left to right with four fingers on both hands). The second task was mirror movements (moving little finger to index finger on both hands), and the third task compared a resting condition with right-handed unimanual typing (moving little finger to index finger). Task dependent BOLD activity in the supplementary motor area (SMA) and dorsolateral premotor areas was observed. In addition, activation patterns were present in the cerebellar vermis during bimanual coordination tasks, with greater activation in the parallel than in the mirror condition. Finally, we also identified activity in the putamen during the tasks described above. Interestingly, putaminal activity was greatest during the period of motor task initiation, and activity during this period was greatest in the parallel condition. our results suggest a critical role of the basal ganglia in the neural control of bimanual coordination. (C) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kraft, E (reprint author), Univ Munich, Univ Hosp, Dept Phys Med & Rehabil, Marchioninistr 15, D-81377 Munich, Germany. EM eduard.kraft@med.uni-muenchen.de NR 66 TC 23 Z9 23 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 2 PY 2007 VL 1151 BP 62 EP 73 DI 10.1016/j.brainres.2007.01.142 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 172TW UT WOS:000246828300007 PM 17448452 ER PT J AU Pines, JM Hollander, JE Lee, H Everett, WW Uscher-Pines, L Metlay, JP AF Pines, Jesse M. Hollander, Judd E. Lee, Hoi Everett, Worth W. Uscher-Pines, Lori Metlay, Joshua P. TI Emergency department operational changes in response to pay-for-performance and antibiotic timing in pneumonia SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE pneumonia; quality of care; pay for performance; emergency department; patient safety ID COMMUNITY-ACQUIRED PNEUMONIA; CARE; MEDICARE; OUTCOMES; QUALITY AB Background: The percentage of adult patients admitted with pneumonia who receive antibiotics within four hours of hospital arrival is publicly reported as a quality and pay-for-performance measure by the Department of Health and Human Services and is called PN-5b. Objectives: To determine attitudes among physician leaders at emergency medicine training programs toward using PN-5b as a quality measure for pay for performance, and to determine what operational changes academic emergency departments (EDs) have made to ensure early antibiotic administration for patients with pneumonia. Methods: The authors administered an online questionnaire to 129 chairpersons and medical directors of 135 academic ED training programs in the United States on attitudes toward performance measurement in pneumonia and changes that academic EDs have made in response to PN-5b; one response was sought from each institution. Respondents were identified through the Society for Academic Emergency Medicine Web site and e-mailed five times to maximize survey participation. Results: Ninety chairpersons and medical directors (70%) completed the survey; 47% were medical directors, 51% were chairpersons, and 2% were medical directors and chairpersons. Forty-five (50%) did not agree that PN-5b was an accurate quality measure, and 61 (69%) did not agree that pay for performance targeting this measure would lead to improved pneumonia care. The most common strategy to address PN-5b was to provide information to providers on the importance of early treatment with antibiotics (n = 63; 70%). For patients with suspected pneumonia, 46 (51 %) automate chest radiograph (CXR) ordering at triage, 37 (41 %) prioritize patients with suspected pneumonia, and 33 (37%) administer antibiotics before obtaining CXR results. Overall ED changes include improved turnaround time for CXR (n = 33; 37%), prioritized CXRs over other radiographs (n = 13; 14%), and improved inpatient bed availability (n = 12; 13%). Of 13 strategies identified to improve PN-5b, the median number that programs have implemented is five finterquartile range, 5-7). All sites reported engaging in at least three operational changes to address PN-5b. Conclusions: All EDs in this study have addressed early antibiotic administration with multiple operational changes despite mixed sentiment that these changes will improve care. Future research is needed to measure the impact of pay-for-performance initiatives. C1 Hosp Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. Johns Hopkins Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Pines, JM (reprint author), Hosp Univ Penn, Dept Emergency Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM pinesjes@uphs.upenn.edu OI Hollander, Judd/0000-0002-1318-2785 NR 15 TC 24 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2007 VL 14 IS 6 BP 545 EP 548 DI 10.1197/j.aem.2007.01.022 PG 4 WC Emergency Medicine SC Emergency Medicine GA 172UZ UT WOS:000246831300009 PM 17470905 ER PT J AU Murman, DH McDonald, AJ Pelletier, AJ Camargo, CA AF Murman, David H. McDonald, Alden J. Pelletier, Andrea J. Camargo, Carlos A., Jr. TI US emergency department visits for supraventricular tachycardia, 1993-2003 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE supraventricular tachycardia; epidemiology; disease management AB Background: Supraventricular tachycardia (SVT) is often described as a recurrent condition that leads to emergency department (ED) visits. However, the epidemiology of ED visits for SVT is unknown. Objectives: To define the frequency of SVT in U.S. EDs and to analyze patient characteristics, ED management, and disposition for such visits. Methods: The authors analyzed data from the National Hospital Ambulatory Medical Care Survey, 19932003. SVT cases were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 426.7 or 427.0 in any of the three diagnostic fields. Results: Of the 1.1 billion ED visits over the 11-year study period, an estimated 555,000 (0.05%; 95% confidence interval [CI] = 0.04% to 0.06%) were related to SVT. The annual frequency and population rate appear stable between 1993 and 2003 (p for trend = 0.35). Compared with non-SVT visits, those with SVT were more likely to be older than 65 years of age (26% vs. 15%, p < 0.01) and female (70% vs. 53%, p < 0.01). Electrocardiograms were documented for most visits (91 %; 95% CI = 85% to 96%). Approximately half of the patients (51 %; 95% CI = 40% to 61 %) received an atrioventricular nodal blocking medication, most frequently adenosine (26%; 95% CI = 17% to 36%). SVT visits ended in hospital admission for 24% (95% CI = 15% to 34%). At the other extreme, 44% (95% CI = 32% to 56%) were discharged without planned follow-up. Conclusions: Supraventricular tachycardia accounts for approximately 50,000 ED visits each year. Higher visit rates in older adults and female patients are consistent with prior studies of SVT in the general population. This study provides an epiderniologic foundation that will enable future research to assess and improve clinical management strategies of SVT in the ED. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM ccamargo@partners.org NR 9 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2007 VL 14 IS 6 BP 578 EP 581 DI 10.1197/j.aem.2007.01.013 PG 4 WC Emergency Medicine SC Emergency Medicine GA 172UZ UT WOS:000246831300017 PM 17449792 ER PT J AU Zivkovic, SA Ascherman, D Lacomis, D AF Zivkovic, S. A. Ascherman, D. Lacomis, D. TI Vasculitic neuropathy - electrodiagnostic findings and association with malignancies SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Editorial Material DE electromyography; malignancy; neuropathy; paraneoplastic; vasculitis ID PERIPHERAL NERVOUS-SYSTEM; MUSCLE MICROVASCULITIS; CLINICAL SPECTRUM; CANCER AB Background - Vasculitic neuropathies occur in the context of systemic disorders or in isolation. Histopathologic evaluation remains the gold standard for diagnosis, but certain electrodiagnostic findings may heighten suspicion of vasculitic neuropathy and improve the yield of nerve and muscle biopsy. Aim of the study - Description of electrodiagnostic patterns associated with vasculitic neuropathies, and a report of a possible association with malignancies. Methods Retrospective review of medical records of patients with histopathologically proven vasculitic and non-vasculitic axonal neuropathies evaluated at the University of Pittsburgh Medical Center from November 1995 to November 2003. Results - The most distinctive electrodiagnostic patterns associated with vasculitic neuropathy were mononeuritis multiplex (27.5% vs 4% in controls; P = 0.003) and axonal sensorimotor polyneuropathy with side-to-side amplitude asymmetry (50% vs 32%, P > 0.05). Additionally, six patients (15% vs 2%; P = 0.034) developed various malignancies within 2 years of onset of vasculitic neuropathy. Conclusions - While generalized polyneuropathy was the most common presentation of nerve vasculitis, our study affirms side-to-side amplitude asymmetry and mononeuritis multiplex as the most distinctive electrodiagnostic features. The frequent occurrence of malignancies suggests a possible association with the vasculitic neuropathy and warrants additional investigation. C1 Univ Pittsburgh, Med Ctr, Dept Neurol, Sch Med,Div Rheumatol & Clin Immunol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Pathol, Sch Med,Div Neuropathol, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Sch Med,Div Rheumatol & Clin Immunol, 3471 5th Ave 811, Pittsburgh, PA 15213 USA. EM zivkovics@upmc.edu NR 16 TC 21 Z9 24 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD JUN PY 2007 VL 115 IS 6 BP 432 EP 436 DI 10.1111/j.1600-0404.2006.00781.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 174RK UT WOS:000246960300012 PM 17511855 ER PT J AU Eisenman, D Bogart, LM Bird, CE Collins, RL Golinelli, D Fremont, A Beckman, R Cunningham, W AF Eisenman, David Bogart, Laura M. Bird, Chloe E. Collins, Rebecca L. Golinelli, Daniela Fremont, Allen Beckman, Robin Cunningham, William TI Differential diffusion of HIV technologies by gender: The case of highly active antiretroviral therapy SO AIDS PATIENT CARE AND STDS LA English DT Article ID PROTEASE INHIBITORS; UNITED-STATES; DRUG-USERS; ACCESS; WOMEN; CARE; DISEASE; COHORT; HAART; AIDS AB We sought to examine whether diffusion of new HIV technologies differed by gender in the United States, the source of any such disparities, and whether disparities narrow over time as technologies become more established. In particular, we assess how rates of use of highly active antiretroviral therapy ( HAART) varied between males and females during the late 1990s, when HAART was rapidly diffusing. We examined data from a prospective cohort study of a national probability sample of 1421 HIV- infected adults in medical care who were enrolled in the HIV Cost and Services Utilization Study ( HCSUS) from January 1996 to December 1998. We found that HAART use substantially increased between 1996 and early 1998 for all groups. Women were less likely to receive HAART at all time points, although the diffusion of HAART between 1996 and 1998 reduced gender disparities. Gender disparities in 1998 were only partially explained by women's lower income and educational levels. We conclude that HAART therapy diffused more slowly to HIV- positive females than other groups. Policies that reduce the impact of income and education inequalities on health care may help to narrow gender disparities for new HIV technologies, but other factors may also disadvantage women. C1 RAND Corp, Hlth Sci Program, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Hlth Serv Res, Los Angeles, CA 90024 USA. W Los Angeles VAMC, Div Med, Los Angeles, CA USA. RP Eisenman, D (reprint author), RAND Corp, Hlth Sci Program, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM David_Eisenman@rand.org RI Bird, Chloe/C-7107-2008; Fremont, Allen/A-7752-2009; Golinelli, Daniela/H-2287-2015 OI Golinelli, Daniela/0000-0002-6433-1752 FU AHRQ HHS [U-01HS08578]; NIA NIH HHS [AG-02-004]; NICHD NIH HHS [R01HD41878, R01HD35040]; NIMHD NIH HHS [1P20MD000148-01] NR 28 TC 8 Z9 8 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUN PY 2007 VL 21 IS 6 BP 390 EP 399 DI 10.1089/apc.2006.0061 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 182VG UT WOS:000247531500004 PM 17594248 ER PT J AU Leite-Morris, KA Ciraulo, DA AF Leite-Morris, K. A. Ciraulo, D. A. TI The novel anticonvulsant zonisamide reduces ethanol seeking and consumption in rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 26A EP 26A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600070 ER PT J AU Simpson, TL Meredith, CW Gross, CA Raskind, MA Saxon, AJ Rasmussen, DD AF Simpson, T. L. Meredith, C. W. Gross, C. A. Raskind, M. A. Saxon, A. J. Rasmussen, D. D. TI Pilottrial of prazosin for treatment of alcohol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 60A EP 60A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600207 ER PT J AU Feinberg-Zadek, PL Davies, PA AF Feinberg-Zadek, P. L. Davies, P. A. TI Comparison of the alcohol modulation of 5-HT3A receptors and the novel ligand-gated ion channel, ZAC SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 85A EP 85A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600306 ER PT J AU Dou, XD Wilkemeyer, MF Charness, ME AF Dou, X. D. Wilkemeyer, M. F. Charness, M. E. TI Ethanol inhibition of L1-mediated cell adhesion is regulated by L1 phosphorylation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 98A EP 98A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600361 ER PT J AU Hawkins, EJ Kivlahan, DR Williams, EC Wright, SM Craig, T Bradley, KA AF Hawkins, E. J. Kivlahan, D. R. Williams, E. C. Wright, S. M. Craig, T. Bradley, K. A. TI Comparison of medical record and survey-based alcohol misuse screening results in VA outpatients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 244A EP 244A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601326 ER PT J AU Donohue, TM Curry-McCoy, TV Todero, SL White, RL Kharbanda, KK Nanji, AA Osna, NA AF Donohue, Terrence M., Jr. Curry-McCoy, Tiana V. Todero, Sandra L. White, Ronda L. Kharbanda, Kusum K. Nanji, Amin A. Osna, Natalia A. TI L-buthionine (S, R) sulfoximine depletes hepatic glutathione but protects against ethanol-induced liver injury SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; glutathione; oxidative stress; alcohol dehydrogenase; cytochrome P450 2E1 ID CYTOCHROME-P450 2E1; OXIDIZED PROTEINS; RAT-LIVER; IN-VIVO; CELLS; INTOXICATION; DEGRADATION; INHIBITION; METABOLISM; PROTEASOME AB Background: L-Buthionine (S,R) sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and has been used as an effective means of depleting glutathione from cells and tissues. Here we investigated whether treatment with BSO enhanced ethanol-induced liver injury in mice. Methods: Female C57Bl/6 mice were pair fed with control and ethanol-containing liquid diets in which ethanol was 29.2% of total calories. During the final 7 days of pair feeding, groups of control-fed and ethanol-fed mice were given 0, 5 or 7.6 mM BSO in the liquid diets. Results: Compared with controls, ethanol given alone decreased total liver glutathione. This effect was exacerbated in mice given ethanol with 7.6 mM BSO, causing a 72% decline in hepatic glutathione. While ethanol alone caused no decrease in mitochondrial glutathione, inclusion of 7.6 mM BSO caused a 2-fold decline compared with untreated controls. L-Buthionine (S,R) sulfoximine did not affect ethanol consumption, but serum ethanol levels in BSO-treated mice were nearly 6-fold lower than in mice given ethanol alone. The latter decline in serum ethanol was associated with a significant elevation in the specific activities of cytochrome P450 2E1 and alcohol dehydrogenase in livers of BSO-treated animals. Ethanol consumption caused a 3.5-fold elevation in serum alanine aminotransferase levels but the enzyme fell to control levels when BSO was included in the diet. L-Buthionine (S,R) sulfoximine administration also attenuated ethanol-induced steatosis, prevented the leakage of lysosomal cathepsins into the cytosol, and prevented the ethanol-elicited decline in proteasome activity. Conclusions: L-Buthionine (S,R) sulfoximine, administered with ethanol, significantly depleted hepatic glutathione, compared with controls. However, despite the decrease in hepatic antioxidant levels, liver injury by ethanol was alleviated, due, in part, to a BSO-elicited acceleration of ethanol metabolism. C1 Univ Nebraska, Liver Study Unit, Omaha VA Med Ctr, Med Ctr,US Dept Vet Affairs, Omaha, NE 68105 USA. Univ Nebraska, Dept Internal Med, Med Ctr, Omaha, NE 68105 USA. Univ Nebraska, Dept Biochem & Mol Biol, Med Ctr, Omaha, NE 68105 USA. Univ Nebraska, Dept Pathol & Microbiol, Med Ctr, Omaha, NE 68105 USA. Univ Nebraska, Dept Environm Toxicol, Med Ctr, Omaha, NE 68105 USA. Dalhousie Univ, Dept Pathol & Lab Med, Sch Med, Halifax, NS, Canada. RP Donohue, TM (reprint author), Univ Nebraska, Liver Study Unit, Omaha VA Med Ctr, Med Ctr,US Dept Vet Affairs, 4101 Woolworth Ave, Omaha, NE 68105 USA. EM tdonohue@unmc.edu FU NIAAA NIH HHS [AA09384] NR 25 TC 17 Z9 17 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 BP 1053 EP 1060 DI 10.1111/j.1530-0277.2007.00393.x PG 8 WC Substance Abuse SC Substance Abuse GA 169EW UT WOS:000246576500017 PM 17428293 ER PT J AU Bosworth, HB Olsen, MK McCant, F Harrelson, M Gentry, P Rose, C Goldstein, MK Hoffman, BB Powers, B Oddone, EZ AF Bosworth, Hayden B. Olsen, Maren K. McCant, Felicia Harrelson, Mikeal Gentry, Pamela Rose, Cynthia Goldstein, Mary K. Hoffman, Brian B. Powers, Benjamin Oddone, Eugene Z. TI Hypertension Intervention Nurse Telemedicine Study (HINTS): Testing a multifactorial tailored behavioral/educational and a medication management intervention for blood pressure control SO AMERICAN HEART JOURNAL LA English DT Article ID SELF-MEASUREMENT; PATIENTS RESPONSES; RISK-FACTORS; ADHERENCE; PREVENTION; THRESHOLDS; GUIDELINES; PHYSICIANS; BENEFITS; VALIDITY AB Background Only 31% of Americans with hypertension have their blood pressure (BP) under effective control. We describe a study that tests 3 different interventions in a randomized controlled trial using home BP telemedicine monitoring. Methods A sample of hypertensive patients with poor BP control at baseline (N = 600) are randomized to 1 of 4 arms: (1) control group-a group of hypertensive patients who receive usual care; (2) nurse-administered tailored behavioral intervention; (3) nurse-administered medication management according to a hypertension decision support system; (4) combination of the 2 interventions. The interventions are triggered based on home BP values transmitted via telemonitoring devices over standard telephone lines. The tailored behavioral intervention involves promoting adherence with medication and health behaviors. Patients randomized to the medication management or the combined arm have their hypertension regimen changed by the study team using a validated hypertension decision support system based on evidence-based hypertension treatment guidelines and individualized to patients' comorbid illnesses. The primary outcome is BP control: <= 140/90 mm Hg (nondiabetic) and <= 130/80 mm Hg (diabetics) measured at 6-month intervals over 18 months (4 total measurements). Conclusions Given the increasing prevalence of hypertension and our inability to achieve adequate BP control using traditional models of care, testing novel interventions in patients' homes may improve access, quality, and outcomes. C1 Durham Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Div Gen Internal Med, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA. VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. VA Boston Hlth Care Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bosworth, HB (reprint author), Durham Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Bldg 16,Room 70,152,508 Fulton St, Durham, NC 27705 USA. EM hayden.bosworth@duke.edu NR 34 TC 60 Z9 60 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2007 VL 153 IS 6 BP 918 EP 924 DI 10.1016/j.ahj.2007.03.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 182YT UT WOS:000247540600005 PM 17540191 ER PT J AU Bossone, E Evangelista, A Isselbacher, E Trimarchi, S Hutchison, S Gilon, D Llovet, A O'Gara, P Cooper, JV Fang, JM Januzzi, JL Mehta, RH Distante, A Nienaber, CA Eagle, K Armstrong, WF AF Bossone, Eduardo Evangelista, Arturo Isselbacher, Eric Trimarchi, Santi Hutchison, Stuart Gilon, Dan Llovet, Alfredo O'Gara, Patrick Cooper, Jeanna V. Fang, Jianming Januzzi, James L. Mehta, Rajendra H. Distante, Alessandro Nienaber, Christoph A. Eagle, Kim Armstrong, William F. CA IRAD Investigators TI Prognostic role of transesophageal echocardiography in acute type A aortic dissection SO AMERICAN HEART JOURNAL LA English DT Article ID CLINICAL CHARACTERISTICS; INTERNATIONAL REGISTRY; TASK-FORCE; DIAGNOSIS; RECOMMENDATIONS; MANAGEMENT; IRAD AB Background Acute type A aortic dissection (AAD) remains a highly lethal entity for which emergent surgical correction is standard care. Prior studies have identified specific clinical findings as being predictive of outcome. The prognostic significance of specific findings on imaging studies is less well described. We sought to identify the prognostic value of transesophageal echocardiography (TEE) in medically and surgically treated patients with AAD. Methods We studied 522 AAD patients enrolled over 6 years in the International Registry of Acute Aortic Dissection who underwent TEE. Multivariate analysis identified independent associations of inhospital mortality, first using clinical variables (model 1), after which TEE data were added to build a final model (model 2). Results Inhospital mortality was 28.7%. Transesophageal echocardiographic evidences of pericardial effusion (P= .04), tamponade (P < .01), periaortic hematoma (P = .02), and patent false lumen (P = .08) were more frequent in nonsurvivors. Dilated ascending aorta (P = .03), dissection localized to the ascending aorta (P = .02), and thrombosed false lumen (P = .08) were less common in nonsurvivors. Model 1 identified age >= 70 years, any pulse deficit, renal failure, and hypotension/shock as independent predictors of death. Model 2 identified dissection flop confined to ascending aorta (odds ratio 0.2, 95% CI 0.1-0.6) and complete thrombosis of false lumen (odds ratio 0.15, 95% CI 0.03-0.86) as protective. In the medically treated group, mortality was 31% for subjects with a partially or completely thrombosed false lumen versus 66% in the presence of a patent false lumen. Conclusions Transesophageal echocardiography provides prognostic information in AAD beyond that provided by clinical risk variables. C1 CNR, Lecce, Italy. Ciudad Sanitaria & Univ Vall Hebron, Gen Hosp, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Policlin Sa Donato, San Donato Milanese, Italy. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Hosp Univ 12 Octubre, Madrid, Spain. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Duke Clin Res Inst, Durham, NC USA. RP Bossone, E (reprint author), Via Principe Amedeo,36, I-83023 Lauro, Italy. EM ebossone@hotmail.com RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 21 TC 19 Z9 22 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2007 VL 153 IS 6 BP 1013 EP 1020 DI 10.1016/j.ahj.2007.03.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 182YT UT WOS:000247540600018 PM 17540204 ER PT J AU Tickoo, S Roe, MT Peterson, ED Milford-Beland, S Ohman, EM Gibler, WB Pollack, CV Cannon, CP AF Tickoo, Sumit Roe, Matthew T. Peterson, Eric D. Milford-Beland, Sarah Ohman, E. Magnus Gibler, W. Brian Pollack, Charles V., Jr. Cannon, Christopher P. CA CRUSADE Investigators TI Patterns of aspirin dosing in non-ST-elevation acute coronary syndromes in the CRUSADE quality improvement initiative SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SEGMENT ELEVATION; UNSTABLE ANGINA; METAANALYSIS; CLOPIDOGREL; TRIALS AB Recent studies have suggested that low-dose aspirin has preserved benefit with less bleeding compared with standard-dose aspirin when given with or without clopidogrel in patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACSs). We evaluated 22,618 patients with NSTE ACSs and high-risk features (ischemic ST-segment changes and/or positive cardiac markers) from 369 hospitals included in the CRUSADE initiative from May 4, 2003 to September 30, 2004. We analyzed acute (< 24 hours of admission) and discharge aspirin doses in relation to concomitant clopidogrel use and other clinical predictors. Dosing of aspirin in the first 24 hours was as follows: 17.3% of patients (n = 3,911) received 81 mg, 13.5% (n = 3,062) received 162 mg, 67.4% (n = 15,247) received 325 m g, and 1.8% (n = 398) received > 325 mg. Use of lower dose aspirin increased at discharge: 40.2% (n = 7,524) received 81 mg, 3.1% (n = 579) received 162 mg, and 55.7% (n = 10,423) received 325 mg. In patients who received concomitant clopidogrel at discharge (n = 12,635), 37.6% received aspirin 81 mg and 58.5% received 325 mg. Compared with patients who did not receive concomitant discharge clopidogrel (n = 4,772),44.0% received aspirin 81 mg and 51.2% received 325 mg. Use of aspirin 81 mg was significantly lower in patients undergoing percutaneous coronary intervention (31.5% vs 46.2%, p < 0.0001). In conclusion, most patients with high-risk NSTE ACSs in the United States continue to be treated with aspirin 325 mg at discharge with and without concomitant clopidogrel, despite recent studies that have shown a better safety profile with low-dose aspirin. (c) 2007 Elsevier Inc. All rights reserved. C1 Bridgeport Hosp, Bridgeport, CT 06610 USA. Duke Clin Res Inst, Div Cardiol, Durham, NC USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Penn, Penn Hosp, Sch Med, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Schering Plough Corp, Kenilworth, NJ 07033 USA. Bristol Myers Squibb Co, New York, NY USA. RP Cannon, CP (reprint author), Bridgeport Hosp, Bridgeport, CT 06610 USA. EM cpcannon@partners.org NR 8 TC 8 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2007 VL 99 IS 11 BP 1496 EP 1499 DI 10.1016/j.amjcard.2007.01.021 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YV UT WOS:000247121700003 PM 17531568 ER PT J AU Thakore, AH Guo, CY Larson, MG Corey, D Wang, TJ Vasan, RS D'Agostino, RB Lipinska, I Keaney, JF Benjamin, EJ O'Donnell, CJ AF Thakore, Avni H. Guo, Chao-Yu Larson, Martin G. Corey, Diane Wang, Thomas J. Vasan, Ramachandran S. D'Agostino, Ralph B., Sr. Lipinska, Izabella Keaney, John F., Jr. Benjamin, Emelia J. O'Donnell, Christopher J. TI Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham heart study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; PUBLIC-HEALTH PRACTICE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK; ARTERY; ATHEROSCLEROSIS; STROKE; INTERLEUKIN-6; OBESITY AB Inflammatory markers, particularly C-reactive protein. (CRP), predict incident cardiovascular disease and are associated with the presence of subclinical atherosclerosis. The relations between multiple inflammatory markers and direct measures of atherosclerosis are less well established. Participants in the Offspring Cohort of the Framingham Heart Study (n = 2,885, 53% women, mean age 59 years) received routine assessments of common carotid artery intima-media thickness (CCA-IMT), internal carotid artery intima-media thickness (ICA-IMT), and the presence or absence of >= 25% carotid stenosis by ultrasonography. Circulating inflammatory markers assessed from an examination 4 years later included CRP, interleukin-6 (IL-6), intercellular adhesion molecule-1, monocyte chemoattractant protein-1, P-selectin, and CD40 ligand. Assessed as a group, inflammatory markers were significantly associated with ICA-IMT (p = 0.01), marginally with carotid stenosis (p = 0.08), but not with CCA-IMT. Individually, with an increase from the 25th to 75th percentile in IL-6, there were significant increases in ICA-IMT and carotid stenosis (for ICA-IMT, estimated fold increase 1.04, 95% confidence interval 1.03 to 1.06, p = 0.0004; for carotid stenosis, odds ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.007) after adjustment for age, gender, and established risk factors for atherosclerosis. There was a similar significant multivariate-adjusted association of CRP with ICA-IMT but not with carotid stenosis. Smoking appeared to modify the associations of ICA-IMT with CRP (p = 0.009) and with IL-6 (p = 0.006); the association was more pronounced in current (vs former or never) smokers. In conclusion, there were modest associations of inflammatory markers, particularly IL-6, with carotid atherosclerosis. This association appears more pronounced in current smokers than in former smokers and nonsmokers. (c) 2007 Elsevier Inc. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM emelia@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL70139, 1 R01 HL076784, HL04334, HL074077, HL60886, HL64753, N01-HC-25195]; NIDDK NIH HHS [DK55656] NR 25 TC 79 Z9 82 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2007 VL 99 IS 11 BP 1598 EP 1602 DI 10.1016/j.amjcard.2007.01.036 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YV UT WOS:000247121700023 PM 17531588 ER PT J AU Moore, A Lau, E Yang, C Mackool, B Kuter, DJ AF Moore, Allan Lau, Evan Yang, Clarissa Mackool, Bonnie Kuter, David J. TI Dalteparin-induced skin necrosis in a patient with metastatic lung adenocarcinoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE low molecular weight heparin; skin necrosis; heparin-induced thrombocytopenia; adenocarcinoma ID MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; THROMBOCYTOPENIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moore, A (reprint author), 32 River St,Unit 2, Boston, MA 02108 USA. EM afmoore@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2007 VL 30 IS 3 BP 329 EP 331 DI 10.1097/01.coc.0000182406.27232.40 PG 3 WC Oncology SC Oncology GA 177LJ UT WOS:000247154300022 PM 17551316 ER PT J AU Hasserjian, RP Harris, NL AF Hasserjian, Robert P. Harris, Nancy Lee TI NK-cell lymphomas and leukemias - A spectrum of tumors with variable manifestations and immunophenotype SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT Workshop of the Society-for-Hematopathology/European-Association-for-Haematopathology CY JUN, 2005 CL Houston, TX SP Soc Hematopathol, European Assoc Haematopathol, Univ Texas MD Anderson Canc Ctr DE natural killer cell; T cell; lymphoma; leukemia ID EPSTEIN-BARR-VIRUS; GRANULAR LYMPHOCYTE LEUKEMIA; KILLER; TRANSFORMATION; EXPRESSION AB Natural killer (NK) cells are lymphocytes that have some phenotypic and functional similarities to cytotoxic T cells but do not express the T-cell receptor complex. NK-cell malignancies may be localized or disseminated at initial examination, and most behave aggressively. The variable presentation of NK-cell lymphomas and leukemias suggests that they represent a spectrum Of disease, with Epstein-Barr virus (EBV) implicated in the pathogenesis of most cases. Using cases presented in Session 10 of the 2005 Society for Hematopathology/European Association for Haematopathology Workshop on T-cell and NK-cell malignancies, we discuss outstanding issues in the classification and diagnosis of NK-cell malignancies. These difficulties are related to unusual sites of manifestation, atypical immunophenotypic features, and EBV+ T-cell tumors that resemble classical extranodal NK/T-cell lymphoma, nasal-type (EN-NK/T-NT). Although some of these cases can be grouped into EN-NK/T-NT, classification of tumors that have atypical or discordant features will remain controversial, particularly when EBV is absent. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 58 Z9 65 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 JUN PY 2007 VL 127 IS 6 BP 860 EP 868 DI 10.1309/2F39NX1AL3L54WU8 PG 9 WC Pathology SC Pathology GA 170FL UT WOS:000246648000003 PM 17509983 ER PT J AU Lin, J Rexrode, KM Hu, F Albert, CM Chae, CU Rimm, EB Stampfer, MJ Manson, JE AF Lin, Jennifer Rexrode, Kathy M. Hu, Frank Albert, Christine M. Chae, Claudia U. Rimm, Eric B. Stampfer, Meir J. Manson, JoAnn E. TI Dietary intakes of flavonols and flavones and coronary heart disease in US women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary disease; diet; flavones; flavonols; myocardial infarction; women ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; FOOD FREQUENCY QUESTIONNAIRE; IMPROVE ENDOTHELIAL FUNCTION; MALE HEALTH-PROFESSIONALS; CARDIOVASCULAR-DISEASE; ANTIOXIDANT ACTIVITY; GRAPE JUICE; PLATELET-AGGREGATION; ARTERY-DISEASE; RED WINE AB Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990,1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHID. However, a weak risk reduction for CHID death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Lin, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM jhlin@rics.bwh.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA40356]; NHLBI NIH HHS [HL34594] NR 43 TC 65 Z9 67 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 BP 1305 EP 1313 DI 10.1093/aje/kwm016 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175HU UT WOS:000247005500012 PM 17379619 ER PT J AU Breen, N Rao, SR Meissner, H AF Breen, N. Rao, S. R. Meissner, H. TI Immigration, health care access and recent cancer screening use among Mexican-Americans in California. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500132 ER PT J AU Farwell, WR Scranton, RE Lawler, EV Lew, RA Gaziano, JM AF Farwell, W. R. Scranton, R. E. Lawler, E. V. Lew, R. A. Gaziano, J. M. TI Can statins prevent colorectal cancer? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 VA Boston Healthcare Syst, MAVERIC, Boston, MA 02445 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S136 EP S136 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500542 ER PT J AU Ficociello, LH Aschengrau, A Weinberg, JM Warram, JH Krolewski, AS AF Ficociello, L. H. Aschengrau, A. Weinberg, J. M. Warram, J. H. Krolewski, A. S. TI Elevated glomerular filtration rate (GFR) estimated by cystatin C and the risk of microalbuminuria (MA) in type I diabetes (T1DM). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S12 EP S12 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500048 ER PT J AU Gradus, JL Abramovitz, SM Shipherd, JC AF Gradus, J. L. Abramovitz, S. M. Shipherd, J. C. TI Prevalence of depression and suicidal behavior among marine recruits. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Womens Hlth Sci Div, Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02116 USA. Boston Univ, Sch Med, Boston, MA 02116 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S71 EP S71 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500285 ER PT J AU Halpern, LR AF Halpern, L. R. TI A predictive model to identify women with injuries related to intimate partner violence. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S141 EP S141 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500563 ER PT J AU Holmes, WC Cohen, A Foa, EB AF Holmes, W. C. Cohen, A. Foa, E. B. TI Men's own childhood physical abuse (CPA) histories as potential predictors of their adult abuse-perpetration. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RI Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S149 EP S149 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500596 ER PT J AU Inagami, S Cohen, DA Asch, SM AF Inagami, S. Cohen, D. A. Asch, S. M. TI Neighborhood fast food concentration, location of grocery stores and body mass index. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Greater Los Angeles VA Hlth Syst, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S129 EP S129 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500514 ER PT J AU Poel, A Haselkorn, J Leipertz, S AF Poel, A. Haselkorn, J. Leipertz, S. TI Pulmonary complications in veterans with multiple sclerosis, 2003-2004. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Univ Washington, VA Puget Sound, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S35 EP S35 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500139 ER PT J AU Rao, SR Graubard, BI Breen, N Gastwirth, JL AF Rao, S. R. Graubard, B. I. Breen, N. Gastwirth, J. L. TI Using the Peters-Belson approach to understand the factors underlying disparities in cancer screening rates: Results from the 1998 National Health Interview Survey SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500268 ER PT J AU Wittenberg, E AF Wittenberg, E. TI Measuring quality of life in intimate partner violence. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Harvard Univ, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S141 EP S141 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500562 ER PT J AU Kastrinos, F Stoffel, EM Balmana, J Syngal, S AF Kastrinos, Fay Stoffel, Elena M. Balmana, Judith Syngal, Sapna TI Attitudes toward prenatal genetic testing in patients with familial adenomatous polyposis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PREIMPLANTATION DIAGNOSIS; DISEASE; CANCER; ISSUES AB OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with > 95% risk of colorectal cancer without prophylactic colectomy. Classic FAP is commonly associated with adenomatous polyposis coli (APC) gene mutations. If a mutation is identified, prenatal testing can reveal whether an embryo or fetus is affected. We conducted a pilot study to assess FAP patients' attitudes toward prenatal testing. METHODS: Twenty individuals with FAP completed a 40-item survey on personal and family history related to FAP, demographics, and attitudes toward prenatal tests including amniocentesis, chorionic villous sampling (CVS), and preimplantation genetic diagnosis (PGD). RESULTS: Thirteen women and seven men participated. Ninety-five percent (19/20) would consider undergoing prenatal testing for FAP: 90% would consider PGD, 75% would consider amniocentesis or CVS. Having an affected child and experiencing a first-degree relative's (FDR) death secondary to FAP were associated with greater willingness to consider prenatal testing. Personal history of cancer or FAP-associated tumors did not influence the decision to consider prenatal testing. One hundred percent said it was ethical to provide prenatal testing for FAP and four of five subjects who self-reported strong religious backgrounds would consider prenatal testing for FAP. Early reassurance of having an unaffected child was the most important advantage of PGD and avoiding pregnancy termination was important for 64% and 71% of women and men, respectively. CONCLUSIONS: Patients with FAP are willing to consider prenatal testing to prevent transmission of disease to their children. Physicians caring for FAP patients should discuss available prenatal diagnostic options with patients of childbearing age. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Autonoma Barcelona, Hosp Gen Valle Hebron, E-08193 Barcelona, Spain. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA. NR 29 TC 30 Z9 30 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2007 VL 102 IS 6 BP 1284 EP 1290 DI 10.1111/j.1572-0241.2007.01168.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 170YM UT WOS:000246702100023 PM 17355417 ER PT J AU Dunaief, JL Hahn, P Dentchev, T Iacovelli, J King, C He, X Donovan, A Andrews, N Harris, ZL AF Dunaief, J. L. Hahn, P. Dentchev, T. Iacovelli, J. King, C. He, X. Donovan, A. Andrews, N. Harris, Z. L. TI Ceruloplasmin, hephaestin, and ferroportin in retinal iron homeostasis: Implications for the retinal disease macular degeneration SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. RI Iacovelli, Jared/G-3668-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 512 EP 512 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600052 ER PT J AU Marro, S Barisani, D Chiabrando, D Fagoonee, S Muckenthaler, M Stolte, J Meneveri, R Haile, D Silengo, L Altruda, F Tolosano, T AF Marro, S. Barisani, D. Chiabrando, D. Fagoonee, S. Muckenthaler, M. Stolte, J. Meneveri, R. Haile, D. Silengo, L. Altruda, F. Tolosano, T. TI Lack of haptoglobin affects iron transport across duodenum by modulating ferroportin expression SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, Turin, Italy. Univ Milano Bicocca, Dept Expt & Environm Med & Med Biotechnol, Monza, Italy. Univ Heidelberg, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany. Genom Core Facil, EMBL, Heidelberg, Germany. Univ Texas, Audie L Murphy Mem Vet Hosp, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 550 EP 550 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600170 ER PT J AU Zeber, JE Grazier, KL Valenstein, M Blow, FC Lantz, PM AF Zeber, John E. Grazier, Kyle L. Valenstein, Marcia Blow, Frederic C. Lantz, Paula M. TI Effect of a medication copayment increase in veterans with schizophrenia SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; PRESCRIPTION DRUG COSTS; ANTIPSYCHOTIC MEDICATION; CHRONICALLY ILL; ADHERENCE; CARE; IMPACT; BENEFITS; BENEFICIARIES; PHYSICIANS AB Objective: To assess the effect of the 2002 Veterans Millennium Health Care Act, which raised pharmacy copayments from $2 to $7 for lower-priority patients, on medication refill decisions and health services utilization among vulnerable veterans with schizophrenia. Study Design: Quasi-experimental. Methods:This study used secondary data contained in the National Psychosis Registry from June 1, 2000, through September 30, 2003, for all veterans diagnosed with schizophrenia and receiving healthcare through the Department of Veterans Affairs (VA). Longitudinal, mixed models were used to observe changes in prescriptions, health services utilization, and pharmacy costs in veterans subject to copayments (N = 40 654) and a control group of exempt individuals (N = 39 983). Analyses controlled for demographics, substance abuse, non-VA utilization, and medical comorbidities. The Health Belief Model supported analytical criteria for factors directly related to medication adherence issues. Results:Total prescriptions and overall pharmacy costs leveled among veterans with copayments after the medication cost increase. However, psychiatric drug refills dropped substantially, nearly 25%. Although outpatient visits were unaffected, psychiatric admissions and total inpatient days increased slightly, particularly 10 to 20 months after the policy change. Factoring in additional copayment revenue, the VA realized a $14.7-million annual net revenue gain from this subpopulation alone. Conclusion: These results suggest the new policy successfully reduced utilization and costs, with perhaps minimal clinical consequences to date. However, higher inpatient utilization resulting from cost-related nonadherence is troubling within an already high-risk and poorly adherent population, especially considering the reduction in psychiatric drug refills. C1 S Texas Vet Hlth Care Syst, VERDICT Ctr 11C6, Vet Affairs Hlth Serv Res & Dev, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Policy & Management, Ann Arbor, MI 48109 USA. Vet Affairs Hlth Serv Res & Dev, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Zeber, JE (reprint author), S Texas Vet Hlth Care Syst, VERDICT Ctr 11C6, Vet Affairs Hlth Serv Res & Dev, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM zeber@uthscsa.edu NR 49 TC 44 Z9 44 U1 1 U2 4 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 JUN PY 2007 VL 13 IS 6 BP 335 EP 346 PN 2 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 180VY UT WOS:000247395700003 PM 17567234 ER PT J AU Nemeth, AJ Henson, JW Mullins, ME Gonzalez, RG Schaefer, PW AF Nemeth, A. J. Henson, J. W. Mullins, M. E. Gonzalez, R. G. Schaefer, P. W. TI Improved detection of skull metastasis with diffusion-weighted MR imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Neuroradiology CY APR 29-MAY 05, 2006 CL San Diego, CA SP Amer Soc Neuroradiol ID VERTEBRAL COMPRESSION FRACTURES; BONE-MARROW; BENIGN; DIFFERENTIATION; SPINE; BODY; SCAN AB BACKGROUND AND PURPOSE: Metastasis to the skull is clinically important, but routine MR imaging offers moderate sensitivity for skull-metastasis detection in our experience. We sought to determine if diffusion-weighted MR imaging (DWI) could improve the detection of skull metastasis in patients with primary carcinomas that metastasized to bone compared with conventional MR imaging. MATERIALS AND METHODS: Seventy-five patients from the tumor registry of our institution with extracranial primary malignancy who had brain MR imaging with DWI and radionuclide bone scanning (RNBS, gold standard) within a 6-week interval were evaluated. Thirty-eight patients demonstrated increased radiopharmaceutical uptake on RNBS, consistent with skull metastasis of any size, and the remaining 37 were control subjects. Two readers correlated the DWI and conventional MR imaging with RNBS. RESULTS: The overall sensitivity of DWI for detection of skull metastases was 68.4%-71.1 % (K 0.68) versus 42.1%-55.3% (K = 0.65) for conventional MR imaging. Breast cancer (n = 20) was detected with greatest sensitivity of 86.7%-93.3% (K = 0.80) for DWI versus 60%-80% (K = 0.5) for conventional MR imaging. Lung cancer (n = 32) was detected with 63.6%-72.7% sensitivity (K = 0.56), and prostate cancer (n = 8) with 14.3% sensitivity (K = 0.5) for DWI versus 27.3%-36.4% (K = 0.81) and 14.3-42.9% (K = 0), respectively, for conventional MR imaging. CONCLUSIONS: DWI is a useful sequence for identifying focal skull metastases for breast and lung malignancies and, compared with conventional MR imaging, provides improved detection of these lesions. DWI is insensitive for detecting skull metastases from prostate carcinoma. C1 Harvard Univ, Neuroradiol Div, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Pappas Ctr Neurooncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. Emory Univ Hosp, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ Hosp, Dept Neurol Surg, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Schaefer, PW (reprint author), Harvard Univ, Neuroradiol Div, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Gray 2 Rm B-285, Boston, MA 02114 USA. EM pschaefer@partners.org OI Nemeth, Alexander/0000-0003-0579-3866 NR 23 TC 24 Z9 28 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2007 VL 28 IS 6 BP 1088 EP 1092 DI 10.3174/ajnr.A0501 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 180VZ UT WOS:000247395800022 PM 17569964 ER PT J AU Seley, JJ Weinger, K Mason, DJ AF Seley, Jane Jeffrie Weinger, Katie Mason, Diana J. TI Diabetes self-care: A challenge to nursing SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. Ctr Innovat Diabet Educ, Boston, MA USA. Joslin Diabet Ctr, Off Res Fellow Affairs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weinger, K (reprint author), New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. EM katie.weinger@joslin.harvard.edu RI Seley, Jane/D-1708-2013 FU NIDDK NIH HHS [DK60115] 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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUN PY 2007 VL 107 IS 6 SU S BP 4 EP 5 PG 2 WC Nursing SC Nursing GA 178IP UT WOS:000247214700001 PM 17563422 ER PT J AU Seley, JJ Weinger, K AF Seley, Jane Jeffrie Weinger, Katie TI Executive summary - The state of the science on nursing best practices for diabetes self-management. SO AMERICAN JOURNAL OF NURSING LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; GLYCEMIC CONTROL; EDUCATIONAL INTERVENTIONS; GLUCOSE CONTROL; DEPRESSION; ADULTS; CARE; COMPLICATIONS; METAANALYSIS; POPULATION C1 New York Presbyterian Weill Cornell Med Ctr, New York, NY 10021 USA. Ctr Innovat Diabet Educ, Boston, MA USA. Joslin Diabet Ctr, Off Res Fellow Affairs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Seley, JJ (reprint author), New York Presbyterian Weill Cornell Med Ctr, New York, NY 10021 USA. EM diabetesnp@gmail.com RI Seley, Jane/D-1708-2013 NR 22 TC 1 Z9 1 U1 0 U2 3 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 JUN PY 2007 VL 107 IS 6 SU S BP 6 EP 11 PG 6 WC Nursing SC Nursing GA 178IP UT WOS:000247214700002 PM 17563424 ER PT J AU Weinger, K AF Weinger, Katie TI Psychosocial issues and self-care - Mental health concerns and family dyrtamics. SO AMERICAN JOURNAL OF NURSING LA English DT Article ID NATIONAL DIABETES ATTITUDES; GLYCEMIC CONTROL; DISEASE MANAGEMENT; AMERICAN PATIENTS; METABOLIC-CONTROL; MEDICATION ADHERENCE; DEPRESSIVE SYMPTOMS; INTENSIVE TREATMENT; PREVENTION-PROGRAM; MEXICAN-AMERICANS C1 Ctr Innovat Diabet Educ, Boston, MA USA. Joslin Diabet Ctr, Off Res Fellow Affairs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weinger, K (reprint author), Ctr Innovat Diabet Educ, Boston, MA USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [DK60115] NR 57 TC 7 Z9 8 U1 1 U2 3 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 JUN PY 2007 VL 107 IS 6 SU S BP 34 EP 38 PG 5 WC Nursing SC Nursing GA 178IP UT WOS:000247214700008 PM 17563433 ER PT J AU Haas, L AF Haas, Linda TI Functional decline in older adults with diabetes - Self-care for older adults with disabilities related to aging, diabetes and its complications, or both. SO AMERICAN JOURNAL OF NURSING LA English DT Article ID VISUAL IMPAIRMENT; ELDERLY PEOPLE; INSULIN SENSITIVITY; GLYCEMIC CONTROL; EXERCISE; ASSOCIATION; POPULATION; PREVENTION; DYSFUNCTION; COMMUNITY C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Haas, L (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. EM linda.haas@med.va.gov NR 32 TC 1 Z9 1 U1 1 U2 1 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 JUN PY 2007 VL 107 IS 6 SU S BP 50 EP 54 PG 5 WC Nursing SC Nursing GA 178IP UT WOS:000247214700011 PM 17563439 ER PT J AU Seley, JJ Weinger, K AF Seley, Jane Jeffrie Weinger, Katie TI The state of the science on nursing best practices for diabetes self-management SO AMERICAN JOURNAL OF NURSING LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; GLYCEMIC CONTROL; EDUCATIONAL INTERVENTIONS; GLUCOSE CONTROL; DEPRESSION; ADULTS; CARE; COMPLICATIONS; METAANALYSIS; POPULATION C1 New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. Joslin Diabet Ctr, Ctr Innovat Diabet Educ, Boston, MA 02215 USA. Joslin Diabet Ctr, Off Res Fellow Affairs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Seley, JJ (reprint author), New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. EM diabetesnp@gmail.com RI Seley, Jane/D-1708-2013 FU NIDDK NIH HHS [DK60115] NR 22 TC 4 Z9 4 U1 0 U2 3 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 JUN PY 2007 VL 107 IS 6 BP 73 EP 78 PG 6 WC Nursing SC Nursing GA 176YS UT WOS:000247121400035 PM 17519615 ER PT J AU da Cunha, IT Henson, H Protas, EJ AF da Cunha-Filho, Inacio Teixeira Henson, Helene Protas, Elizabeth J. TI Reliability of a portable gas analyzer during a 5-min walk test SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE oxygen consumption; gait; reliability; walking ID OXYGEN-UPTAKE; COSMED K2; ENERGY-EXPENDITURE; TELEMETRY SYSTEM; VALIDITY; EXERCISE; CONSUMPTION; TREADMILL; DEVICE; GAIT AB Objective: To determine the reliability of a gas analyzer while assessing oxygen consumption (VO2) during a 5-min walking test. Design: Forty healthy participants were connected to the KB 1 -C and walked for 5 mins on a 5-m walkway. TotalVO(2) or energy expenditure (EE) was obtained by averaging the samples for each minute for 5 mins of walking. Walk distance (D), gait speed (S), and gait energy cost (C) were also evaluated. Results: The ICC2,1 for EE, D, S, and C were 0.88, 0.92, 0.92, and 0.67, respectively. The coefficient of variation across trials for each variable was 7.4, 3.6, 3.2, and 9%, respectively. Conclusion: All but C generated high coefficients of reliability. All variables demonstrated acceptable test-retest variability. There was low variability between participants for C. C1 Ctr Univ Belo Horizonte, Belo Horizonte, MG, Brazil. Michael E Debakey Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Houston, TX USA. Michael E Debakey Vet Affairs Med Ctr, Rehabil Res & Dev Ctr Excellence Healthy Aging Di, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Phys Therapy, Galveston, TX 77550 USA. RP da Cunha, IT (reprint author), Rua Ernani Agr 50-302, BR-30455760 Belo Horizonte, MG, Brazil. FU NIA NIH HHS [P30 AG024832] NR 25 TC 2 Z9 2 U1 0 U2 3 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 JUN PY 2007 VL 86 IS 6 BP 469 EP 473 DI 10.1097/PHM.0b013e31805b9505 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 172UJ UT WOS:000246829600007 PM 17515686 ER PT J AU Cusi, K Kashyap, S Gastaldelli, A Bajaj, M Cersosimo, E AF Cusi, Kenneth Kashyap, Sangeeta Gastaldelli, Amalia Bajaj, Mandeep Cersosimo, Eugenio TI Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; lipotoxicity; beta-cell; family history of T2DM ID BETA-CELL FUNCTION; NICOTINIC-ACID; GLUCOSE-TOLERANCE; HEALTHY-SUBJECTS; MOLECULAR-IDENTIFICATION; CONTROLLED-TRIAL; FUEL SELECTION; RESISTANCE; MELLITUS; PATHOGENESIS AB Elevated plasma FFA cause beta-cell lipotoxicity and impair insulin secretion in nondiabetic subjects predisposed to type 2 diabetes mellitus [ T2DM; i. e., with a strong family history of T2DM ( FH+)] but not in nondiabetic subjects without a family history of T2DM. To determine whether lowering plasma FFA with acipimox, an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine FH+ volunteers were admitted twice and received in random order either acipimox or placebo ( double- blind) for 48 h. Plasma glucose/ insulin/ C- peptide concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates ( ISRs) were assessed during a + 125 mg/ dl hyperglycemic clamp. Acipimox reduced 48- h plasma FFA by 36% ( P < 0.001) and increased the plasma C- peptide relative to the plasma glucose concentration or Delta C- peptide/ Delta glucose AUC ( + 177%, P = 0.02), an index of improved beta-cell function. Acipimox improved insulin sensitivity ( M/I) 26.1 +/- 5% ( P < 0.04). First- (+ 19 +/- 6%, P = 0.1) and second- phase ( + 31 +/- 6%, P = 0.05) ISRs during the hyperglycemic clamp also improved. This was particularly evident when examined relative to the prevailing insulin resistance [ 1/( M/I)], as both first- and second- phase ISR markedly increased by 29 +/- 7 ( P < 0.05) and 41 +/- 8% ( P = 0.02). There was an inverse correlation between fasting FFA and first- phase ISR ( r(2) = 0.31, P < 0.02) and acute ( 2 - 4 min) glucose- induced insulin release after acipimox ( r(2) = 0.52, P < 0.04). In this proof-of-concept study in FH + individuals predisposed to T2DM, a 48-h reduction of plasma FFA improves day- long meal and glucose- stimulated insulin secretion. These results provide additional evidence for the important role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed to T2DM. C1 Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, 7703 Floyd Curl Dr,Rm 3-380S, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu RI Bajaj, Mandeep/B-6060-2009; Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCRR NIH HHS [KL2 RR024990, M01-RR-01346] NR 54 TC 52 Z9 54 U1 2 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2007 VL 292 IS 6 BP E1775 EP E1781 DI 10.1152/ajpendo.00624.2006 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 188SH UT WOS:000247939100031 PM 17299078 ER PT J AU Fleischman, A Johnsen, S Systrom, DM Hrovat, M Farrar, CT Frontera, W Fitch, K Thomas, BJ Torriani, M Cote, HCF Grinspoon, SK AF Fleischman, Amy Johnsen, Stine Systrom, David M. Hrovat, Mirko Farrar, Christian T. Frontera, Walter Fitch, Kathleen Thomas, Bijoy J. Torriani, Martin Cote, Helene C. F. Grinspoon, Steven K. TI Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE human immunodeficiency virus; insulin resistance; magnetic resonance spectroscopy ID HIV-INFECTED PATIENTS; SKELETAL-MUSCLE; MAGNETIC-RESONANCE; DNA; LIPODYSTROPHY; THERAPY; SENSITIVITY; EXPRESSION; HYPOTHESIS; HUMANS AB Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors ( NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus ( HIV)- infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short- term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA ( mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30 - 40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1- mo exposure in the stavudine- treated subjects compared with placebo ( -0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg . kg(-1) . min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine- treated group showed significant reduction in mtDNA/ nuclear DNA (- 52%, P = 0.005), with no change in placebo- treated subjects ( + 8%, P = 0.9). P-31 magnetic resonance spectroscopy ( MRS) studies of mitochondrial function correlated with insulin sensitivity measures ( r(2) = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity. C1 Harvard Univ, Program Nutr Metab, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. Spaulding Rehabil Hosp, Boston, MA 02115 USA. Skejby Hosp, Dept Infect Dis, Aarhus, Denmark. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. RP Grinspoon, SK (reprint author), Harvard Univ, Program Nutr Metab, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org RI Cote, Helene/K-7896-2012; OI Systrom, David/0000-0002-9610-6330 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NIDDK NIH HHS [P30 DK040561-12, P30 DK040561, R01 DK059535, R01-DK-59535] NR 23 TC 83 Z9 87 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2007 VL 292 IS 6 BP E1666 EP E1673 DI 10.1152/ajpendo.00550.2006 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 188SH UT WOS:000247939100020 PM 17284576 ER PT J AU Shibolet, O Podolsky, DK AF Shibolet, Oren Podolsky, Daniel K. TI TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE toll-like receptors; innate immunity; inflammation; ligand inhibition ID NF-KAPPA-B; CROHNS-DISEASE; ULCERATIVE-COLITIS; EPITHELIAL-CELLS; PPAR-GAMMA; RESPONSES; INFLAMMATION; BACTERIA; INNATE; NOD2 AB Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-kappa B, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPAR gamma. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens. C1 Massachusetts Gen Hosp, Gastroenterol Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Ctr Study Inflammatory Bowel Dis, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK-069344, DK-43351, DK-60049] NR 29 TC 130 Z9 135 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2007 VL 292 IS 6 BP G1469 EP G1473 DI 10.1152/ajpgi.00531.2006 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 188RB UT WOS:000247935900002 PM 17554134 ER PT J AU Nahrendorf, M Badea, C Hedlund, LW Figueiredo, JL Sosnovik, DE Johnson, GA Weissleder, R AF Nahrendorf, Matthias Badea, Cristian Hedlund, Laurence W. Figueiredo, Jose-Luiz Sosnovik, David E. Johnson, G. Allan Weissleder, Ralph TI High-resolution imaging of murine myocardial infarction with delayed-enhancement cine micro-CT SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE remodeling; computed tomography ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; VISUALIZATION; DYSFUNCTION; MRI AB The objective of this study was to determine the feasibility of delayed-enhancement micro-computed tomography (mu CT) imaging to quantify myocardial infarct size in experimental mouse models. A total of 20 mice were ima ed 5 or 35 days after surgical ligation of the left coronary artery or sham Surgery (n = 6 or 7 per group). We utilized a prototype mu CT that covers a three-dimensional (3D) volume with an isotropic spatial resolution of 100 mu m. A series of image acquisitions were started after a 200 mu l bolus of a high-molecular-weight blood pool CT agent to outline the ventricles. CT imaging was continuously performed over 60 min, while an intravenous constant infusion with iopamidol 370 was started at a dosage of 1 ml/h. Thirty minutes after the initiation of this infusion, signal intensity in Hounsfield units was significantly higher in the infarct than in the remote, uninjured myocardium. Cardiac morphology and motion were visualized with excellent contrast and in fine detail. In vivo CT determination of infarct size at the midventricular level was in good agreement with ex vivo staining with triphenyltetrazolium chloride 15 days post-myocardial infarction (MI): r(2) = 0.86, P < 0.01; 35 days post-M 1: 12 = 0.92, P < 0.01]. In addition, we detected significant left ventricular remodeling consisting of left ventricular dilation and decreased ejection fraction. 3D cine mu CT reliably and rapidly quantifies infarct size and assesses murine anatomy and physiology after coronary ligation, despite the small size and fast movement of he mouse heart. This efficient imaging tool is a Valuable addition to the current phenotyping armamentarium and will allow rapid testing of novel drugs and cell-based interventions in murine models. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Duke Univ, Med Ctr, Ctr Vivo Microscopy, Durham, NC USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Boston, MA 02129 USA. EM mnahrendorf@partners.org RI Badea, Cristian/B-6681-2011; OI Badea, Cristian/0000-0002-1850-2522; Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NCI NIH HHS [R24 CA092656, R24 CA092656-06, R24 CA092782, R24 CA092782-06, R24-CA092656, R24-CA92782]; NCRR NIH HHS [P41-RR005959, P41 RR005959, P41 RR005959-17]; NHLBI NIH HHS [5R01-HL055348, R01 HL055348, R01 HL055348-07, R01 HL078641, R01 HL078641-04, R01-HL078641, U01 HL080731, U01 HL080731-04, U01-HL080731] NR 31 TC 37 Z9 37 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2007 VL 292 IS 6 BP H3172 EP H3178 DI 10.1152/ajpheart.01307.2006 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 186KJ UT WOS:000247777300074 PM 17322414 ER PT J AU Sanchez-Hidalgo, M Lu, Z Tan, DA Maldonado, MD Reiter, RJ Gregerman, RI AF Sanchez-Hidalgo, M. Lu, Z. Tan, D. A. Maldonado, M. D. Reiter, R. J. Gregerman, R. I. TI Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: implications for osteoblast differentiation and osteoporosis SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE fatty acids; oleic acid; osteogenesis; luzindole; S20928 ID MESENCHYMAL STEM-CELLS; RAT VISCERAL FAT; ADIPOSE-TISSUE; BONE-MARROW; BODY-WEIGHT; LIPOPROTEIN-LIPASE; SYRIAN-HAMSTERS; PLASMA LEPTIN; MIDDLE-AGE; RECEPTORS AB Melatonin is produced not only by the pineal gland but by cells of the bone marrow. Moreover, melatonin is known to promote osteogenic differentiation in several cell line models and in multipotential bone marrow mesenchymal stem cells. Fatty acids have been independently shown to direct such cells to acquire the phenotype and molecular characteristics of adipocytes. To examine the effect of melatonin on intracellular triglyceride accumulation, an indicator of adipogenic differentiation in the rat osteoblastlike ROS17/2.8 cell line, cells were incubated with added oleic acid (100 mu M), fixed and stained with Oil Red O. Cellular lipid accumulation was quantitated by an Oil Red O method highly specific for triglycerides and expressed as a triglyceride accumulation index (TGAI, triglyceride per cell). Melatonin in nanomolar concentrations inhibited oleic acid-induced triglyceride accumulation. To identify the mechanism by which melatonin reduces triglyceride accumulation, cells were incubated with the two melatonin receptor antagonists, luzindole and S20928, or forskolin, a stimulator of adenylyl cyclase and cAMP production. These compounds prevented the inhibitory effect of melatonin on triglyceride accumulation, indicating that melatonin acts through known melatonin receptor-mediated mechanisms. In view of the previously demonstrated positive effects of melatonin in promoting osteoblastic differentiation in ROS17/2.8 cells and their reciprocal adipocytic differentiation induced by fatty acids, our observations may serve to relate the known age-related decreases of melatonin production, the shift in the bone marrow toward an adipocytic line of cell development, and the development of osteoporosis during aging. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriat & Gerontol,Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Div, S Texas Vet Hlth Care Syst,Geriatr Res Educ & Cli, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX USA. RP Gregerman, RI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriat & Gerontol,Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM reiter@uthscsa.edu; gregerman@uthscsa.edu RI Maldonado, MD/A-3847-2008; tan, dun-xian/E-3610-2010; Sanchez-Hidalgo, Marina/E-9231-2010; OI Maldonado, MD/0000-0003-1375-447X; Sanchez Hidalgo, Marina/0000-0002-9210-2404 NR 45 TC 36 Z9 38 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 2007 VL 292 IS 6 BP R2208 EP R2215 DI 10.1152/ajpregu.00013.2007 PG 8 WC Physiology SC Physiology GA 185QK UT WOS:000247725300015 PM 17379847 ER PT J AU Strawn, JR Keck, PE Caroff, SN AF Strawn, Jeffrey R. Keck, Paul E. Caroff, Stanley N. TI Neuroleptic malignant syndrome SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID SERUM IRON; CATATONIA; HYPERACTIVITY; PROGRESSION; DRUGS C1 Univ Cincinnati, Dept Psychiat, Coll Med, Cincinnati, OH 45267 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Strawn, JR (reprint author), Univ Cincinnati, Dept Psychiat, Coll Med, Box 670559, Cincinnati, OH 45267 USA. EM strawnjr@uc.edu NR 33 TC 150 Z9 162 U1 1 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2007 VL 164 IS 6 BP 870 EP 876 DI 10.1176/appi.ajp.164.6.870 PG 7 WC Psychiatry SC Psychiatry GA 176ZE UT WOS:000247122600009 PM 17541044 ER PT J AU Polanczyk, G de Lima, MS Horta, BL Biederman, J Rohde, LA AF Polanczyk, Guilherme de Lima, Mauricio Silva Horta, Bernardo Lessa Biederman, Joseph Rohde, Luis Augusto TI The worldwide prevalence of ADHD: A systematic review and metaregression analysis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CULTURAL CONSTRUCT; MENTAL-HEALTH; CHILD; EPIDEMIOLOGY AB Objective: The worldwide prevalence estimates of attention deficit hyperactivity disorder (ADHD)/hyperkinetic disorder (HD) are highly heterogeneous. Presently, the reasons for this discrepancy remain poorly understood. The purpose of this study was to determine the possible causes of the varied worldwide estimates of the disorder and to compute its worldwide-pooled prevalence. Method: The authors searched MEDLINE and PsycINFO databases from January 1978 to December 2005 and reviewed textbooks and reference lists of the studies selected. Authors of relevant articles from North America, South America, Europe, Africa, Asia, Oceania, and the Middle East and ADHD/HD experts were contacted. Surveys were included if they reported point prevalence of ADHD/HD for subjects 18 years of age or younger from the general population or schools according to DSM or ICD criteria. Results: The literature search generated 9,105 records, and 303 full-text articles were reviewed. One hundred and two studies comprising 171,756 subjects from all world regions were included. The ADHD/HD worldwide-pooled prevalence was 5.29%. This estimate was associated with significant variability. In the multivariate metaregression model, diagnostic criteria, source of information, requirement of impairment for diagnosis, and geographic origin of the studies were significantly associated with ADHD/HD prevalence rates. Geographic location was associated with significant variability only between estimates from North America and both Africa and the Middle East. No significant differences were found between Europe and North America. Conclusions: Our findings suggest that geographic location plays a limited role in the reasons for the large variability of ADHD/HD prevalence estimates worldwide. Instead, this variability seems to be explained primarily by the methodological characteristics of studies. C1 Univ Fed Rio Grande do Sul, Hosp Cin Porto Alegre, Child & Adolescent Psychiat Div, ADHD Outpatient Program, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Univ Fed Pelotas, Pelotas, Brazil. Univ Catolica Pelotas, Pelotas, Brazil. Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil. RP Polanczyk, G (reprint author), Univ Fed Rio Grande do Sul, Hosp Cin Porto Alegre, Child & Adolescent Psychiat Div, ADHD Outpatient Program, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM gvp.ez@terra.com.br; lrohde@terra.com.br RI Rohde, Luis Augusto/A-6426-2008; Horta, Bernardo/A-7604-2008; Polanczyk, Guilherme/C-2345-2012; Epidemiologicas, Centro de pesquisas /D-4561-2013 OI Rohde, Luis Augusto/0000-0002-4552-4188; Polanczyk, Guilherme/0000-0003-2311-3289; NR 26 TC 1624 Z9 1686 U1 66 U2 427 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2007 VL 164 IS 6 BP 942 EP 948 DI 10.1176/appi.ajp.164.6.942 PG 7 WC Psychiatry SC Psychiatry GA 176ZE UT WOS:000247122600020 PM 17541055 ER PT J AU Abbara, S Nikolic, B Pelage, JP Banovac, F Spies, JB AF Abbara, Suhny Nikolic, Boris Pelage, Jean-Pierre Banovac, Filip Spies, James B. TI Frequency and extent of uterine perfusion via ovarian arteries observed during uterine artery embolization for leiomyomas SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hemodynamics; leiomyoma; oncologic imaging; pelvic imaging; uterine artery embolization; women's imaging ID FIBROIDS; COLLATERALS AB OBJECTIVE. The objective of our study was to evaluate the frequency and extent of residual uterine perfusion via the ovarian arteries after bilateral uterine artery embolization ( UAE) for the treatment of symptomatic uterine leiomyomas. MATERIALS AND METHODS. One hundred forty-five consecutive patients who underwent UAE were retrospectively evaluated for blood supply to the uterus via the ovarian arteries after UAE. After completion of UAE, uterine supply from the ovarian arteries was assessed by performing abdominal aortography in all patients. Selective ovarian arteriography, in addition, was performed in some patients. The criteria used to characterize ovarian artery perfusion as seen on the aortograms were vessel size compared with a 5-French catheter and visualization and extent of flow. When the ovarian arteries visibly supplied uterine tissue, a quantification system was applied as follows: the uterus was divided in 24 segments on the basis of a clock model that was superimposed over the uterine territory in the anteroposterior projection. Depending on its distance from the midpoint of the clock, perfusion segments were labeled as central, middle, distal, or peripheral for each hour of the clock resulting in a total of 24 ( 12 x 2) potential segments of residually perfused uterine tissue via the ovarian arteries. RESULTS. Two hundred ninety ovarian arteries were evaluated on aortography; of these, 202 ( 70%) were not seen during aortography. Of the visualized ovarian arteries ( n = 88), 52% ( 46/88) were smaller than, 25% ( 22/88) were equal to, and 23% ( 20/88) were larger than the diameter of a 5-French catheter. The aortogram revealed that 61% ( 54/88) of the ovarian arteries extended into the pelvis, whereas 38% ( 33/88 [one missing data point]) did not. Selective injections were performed in 54 ovarian arteries. Of these, 69% ( 37/54) of the ovarian arteries had residual fibroid perfusion from the ovarian arteries after UAE ( 10 left-sided, 15 right-sided, six bilateral = 37 ovarian arteries). Residual fibroid perfusion was more likely in large ovarian arteries, particularly those with rapid flow visualized extending into the pelvis. The perfusion scores ranged from one to 18 segments (< 6 segments, n = 21 ovarian arteries; 6-12 segments, n = 12; > 12 segments, n = 4). Direct communication with the uterine arteries was seen in 20 ovarian arteries, 40% ( 8/20) of which did not show any uterine or fibroid perfusion, suggesting that fibroid flow had been occluded by UAE. CONCLUSION. Based on aortography, the presence of residual fibroid perfusion is more likely if the ovarian arteries are large, have rapid flow, or have flow that extends into the pelvis. Selective ovarian artery evaluation may be indicated in these cases to determine the extent of residual fibroid perfusion. C1 Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Hop Lariboisiere, Dept Vasc & Body Imaging, F-75475 Paris, France. RP Spies, JB (reprint author), Georgetown Univ, Med Ctr, Dept Radiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. RI Pelage, Jean-Pierre/L-2488-2015 NR 9 TC 11 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 JUN PY 2007 VL 188 IS 6 BP 1558 EP 1563 DI 10.2214/AJR.05.1383 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170LV UT WOS:000246665800018 PM 17515376 ER PT J AU Dodd, JD Aquino, SL Holmvang, G Cury, RC Hoffmann, U Brady, TJ Abbara, S AF Dodd, Jonathan D. Aquino, Suzanne L. Holmvang, Godtfred Cury, Ricardo C. Hoffmann, Udo Brady, Thomas J. Abbara, Suhny TI Cardiac septal aneurysm mimicking pseudomass: Appearance on ECG-gated cardiac MRI and MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aneurysm; cardiopulmonary imaging; CT; CT technique; heart; MRI ID PATENT FORAMEN-OVALE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CT AB OBJECTIVE. Cardiac septal aneurysms in adults are diagnosed when the interatrial or interventricular septal membrane deviates more than 10-15 mm to either side in the cardiac chamber. Routine non-ECG-gated chest CT does not have sufficient temporal and spatial resolution for adequate characterization of such an entity. We report the imaging findings of cardiac septal aneurysms depicted in two patients with ECG-gated cardiac MRI and in a third with ECG-gated cardiac 64-MDCT. Each aneurysm was initially believed to be a cardiac tumor on the basis of the appearance on non-ECG-gated chest CT or MRI. CONCLUSION. Nonopacified blood can fill a cardiac septal aneurysm and mimic a pseudomass. It is important that radiologists recognize such an entity on chest CT and MRI because of the association with intracardiac shunting and stroke and to avoid misdiagnosis of an aneurysm as a cardiac tumor. C1 Massachusetts Gen Hosp, Dept Radiol, Cardiac CT MRI PET Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dodd, JD (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac CT MRI PET Program, 55 Fruit St, Boston, MA 02114 USA. EM jddodd@partners.org NR 14 TC 9 Z9 9 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2007 VL 188 IS 6 BP W550 EP W553 DI 10.2214/AJR.06.0996 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170LV UT WOS:000246665800051 PM 17515346 ER PT J AU Gomoll, AH O'Toole, RV Czarnecki, J Warner, JJP AF Gomoll, Andreas H. O'Toole, Robert V. Czarnecki, Joseph Warner, Jon J. P. TI Surgical experience correlates with performance on a virtual reality simulator for shoulder arthroscopy SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE surgical education; shoulder arthroscopy; arthroscopy simulator ID ORTHOPEDIC RESIDENTS; LAPAROSCOPIC SKILLS; CONSTRUCT-VALIDITY; PSYCHOMOTOR-SKILLS; TECHNICAL SKILLS; TRAINER; WORK; RESECTION; SURGEONS; PROSTATE AB Background: The traditional process of surgical education is being increasingly challenged by economic constraints and concerns about patient safety. Sophisticated computer-based devices have become available to simulate the surgical experience in a protected environment. As with any new educational tool, these devices have generated controversy about the validity of the training experience. Hypothesis: Performance on a virtual reality simulator correlates with actual surgical experience. Study Design: Controlled laboratory study. Methods: Forty-three test subjects of various experience levels in shoulder arthroscopy were tested on an arthroscopy simulator according to a standardized protocol. Subjects were evaluated for time to completion, distance traveled with the tip of the simulated probe compared with a computer-determined optimal distance, average probe velocity, and number of probe collisions with the tissues. Results: Subjects were grouped according to prior experience with shoulder arthroscopy. Comparing the least experienced with most experienced groups, the average time to completion decreased by 62% from 128.8 seconds to 49.2 seconds; path length and hook collisions were more than halved from 8.2 to 3.8 and 34.1 to 16.8, respectively; and average probe velocity more than doubled from 0.18 to 0.4 cm/second. There were no significant differences for any parameter tested between subjects with video game experience compared to those without. Conclusions: The study demonstrated a close and statistically significant correlation between simulator results and surgical experience, thus confirming the hypothesis. Conversely, experience with video games was not associated with improved simulator performance. This indicates that the skill set tested may be similar to the one developed in the operating room, thus suggesting its use as a potential tool for future evaluation of surgical trainees. Clinical Relevance: The results have implications for the future of orthopaedic surgical training programs, the majority of which have not embraced virtual reality technology for physician education. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Shoulder Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Univ Maryland, Med Ctr, R Adams Cowley Shock Trauma Ctr, Div Orthopaed Traumatol, Baltimore, MD 21201 USA. Excel Orthopaed Specialists, Woburn, MA USA. RP Warner, JJP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Shoulder Serv,Dept Orthopaed Surg, 55 Fruit St,YAW-3, Boston, MA 02114 USA. EM jwarner@partners.org NR 36 TC 40 Z9 41 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUN PY 2007 VL 35 IS 6 BP 883 EP 888 DI 10.1177/036354650629521 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 172KA UT WOS:000246802000002 PM 17261572 ER PT J AU Santagata, S Ligon, KL Hornick, JL AF Santagata, Sandro Ligon, Keith L. Hornick, Jason L. TI Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE germ cell tumor; immunohistochemistry; stem cell; transcription factor; seminoma; embryonal carcinoma ID ALKALINE-PHOSPHATASE; OCT4 IMMUNOHISTOCHEMISTRY; TESTICULAR CANCER; EXPRESSION; NANOG; PLURIPOTENCY; CARCINOMA; SEMINOMA; MARKER; CD30 AB The core embryonic stem cell transcription factors (TFs) OCT3/4 (OCT4), NANOG, and SOX2 have shared as well as nonoverlapping roles in stem cell growth and differentiation. These same TFs are also expressed in various types of human germ cell tumors (GCTs), implicating them in regulation of tumor growth and differentiation. Although NANOG and OCT3/4 are sensitive and specific markers for seminoma and embryonal carcinoma, neither factor aids in the clinically important distinction of seminomatous from nonseminomatous tumors. In contrast, expression profiling data suggest that SOX2 may help with this distinction. To determine if a panel of embryonic stem cell TFs (NANOG, OCT3/4, and SOX2) can facilitate the identification and distinction of seminomatous from nonseminomatous GCTs, we evaluated their expression by immunohistochemistry in primary testicular (n = 41) and metastatic retroperitoneal (n = 43) GCTs. Our results confirm NANOG and OCT3/4 as sensitive and specific markers for primary seminoma and embryonal carcinoma and demonstrate the novel finding that NANOG is a marker for metastatic GCTs. In addition, SOX2 is expressed in embryonal carcinoma but not pure seminoma and is therefore a useful diagnostic marker for distinguishing seminomatous and nonseminomatous GCTs. In summary, we find that the embryonic stem cell TF signature of seminoma is NANOG +, OCT3/4 +, and SOX2 - , whereas embryonal carcinoma is NANOG+, OCT3/4+, and SOX2+, and expect these immunohistochemical profiles will facilitate the diagnosis of both primary and metastatic GCTs. C1 Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Hornick, JL (reprint author), Harvard Univ, Dept Pathol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org RI Santagata, Sandro/A-7714-2009 NR 35 TC 102 Z9 108 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2007 VL 31 IS 6 BP 836 EP 845 DI 10.1097/PAS.0b013e31802e708a PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 173KS UT WOS:000246872500003 PM 17527070 ER PT J AU Perner, S Mosquera, JM Demichelis, F Hofer, MD Paris, PL Simko, J Collins, C Bismar, TA Chinnaiyan, AM De Marzo, AM Rubin, MA AF Perner, Sven Mosquera, Juan-Miguel Demichelis, Francesca Hofer, Matthias D. Paris, Pamela L. Simko, Jeff Collins, Colin Bismar, Tarek A. Chinnaiyan, Arul M. De Marzo, Angelo M. Rubin, Mark A. TI TMPRSS2-ERG fusion prostate cancer: An early molecular event associated with invasion SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE prostate cancer; TMPRSS2-ERG gene rearrangement; fluorescence in situ hybridization; PIN ID PROLIFERATIVE INFLAMMATORY ATROPHY; METHYLACYL-COA RACEMASE; SURVIVAL; OVEREXPRESSION; SWEDEN; DEATH AB Prostate cancer (PCA) is one of the most prevalent cancers and a major leading cause of morbidity and mortality in the Western world. The TMPRSS2-ERG fusion was recently identified as a common recurrent chromosomal aberration in this malignancy. In our study, we interrogated a broad spectrum of benign, precursor, and malignant prostatic lesions to assess the TMPRSS2-ERG fusion status using a multicolor interphase fluorescence in situ hybridization assay. Samples from hospital-based cohorts consisted of 237 clinically localized PCA, 34 hormone naive metastases, 9 hormone refractory metastases, 26 high grade prostatic intraepithelial neoplasia lesions, 15 samples of benign prostatic hyperplasia, 38 of proliferative inflammatory atrophy, and 47 of benign prostatic tissue. The TMPRSS2-ERG fusion was present in 48.5% of clinically localized PCA, 30% of hormone naive metastases, 33% of hormone refractory metastases, and in 19% of high grade prostatic intraepithelial neoplasia lesions in intermingling to cancer foci. Almost all these fusion positive cases show a homogenous distribution of the fusion pattern. In contrast, none of the other samples harbored this genetic aberration. If we consider the high incidence of PCA and the high frequency of this gene fusion, TMPRSS2-ERG is the most common genetic aberration so far described in human malignancies. Furthermore, its clinical application as a biomarker and ancillary diagnostic test is promising given its high specificity. C1 Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Univ Ulm, Dept Pathol, D-89069 Ulm, Germany. ITC Irst, SRA Div, Bioinformat Grp, Povo, Trento, Italy. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA USA. McGill Univ, Fac Med, Dept Pathol & Oncol, Montreal, PQ H3A 2T5, Canada. Johns Hopkins Univ, Dept Pathol Urol & Oncol, Sch Med, John Hopkins Bloomberg Sch Med, Baltimore, MD USA. Univ Michigan, Sch Med, Comprehens Canc Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Comprehens Canc Ctr, Dept Urol, Ann Arbor, MI 48109 USA. RP Rubin, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. EM marubin@partners.org OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50 CA090381, P50CA58236, P50CA89520]; NIA NIH HHS [R01AG21404] NR 27 TC 235 Z9 246 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2007 VL 31 IS 6 BP 882 EP 888 DI 10.1097/01.pas.0000213424.38503.aa PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 173KS UT WOS:000246872500008 PM 17527075 ER PT J AU Kirk, AD Baldwin, WM Cascalho, MI Chong, AS Sykes, M West, LJ AF Kirk, A. D. Baldwin, W. M. Cascalho, M. I. Chong, A. S. Sykes, M. West, L. J. TI American Society of Transplantation Symposium on B cells in Transplantation: Harnessing humoral immunity from rodent models to clinical practice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE antibody; immunosuppression; tolerance; transplantation ID RENAL-ALLOGRAFT REJECTION; NONLETHAL PREPARATIVE REGIMEN; INFANT HEART-TRANSPLANTATION; ANTIBODY-PRODUCING CELLS; MIXED CHIMERISM; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; GAL-ALPHA-1,3GAL EPITOPES; LYMPHOID NEOGENESIS; ORGAN ALLOGRAFTS; T-CELL AB There is growing awareness that B cells and alloantibodies are important mediators of both acute and chronic allograft injury. Unfortunately, few therapies are clinically available to mitigate the function of B cells or the effects of established alloantibody. As a result, many sensitized people await transplantation without a suitable donor, and several rejection syndromes are emerging that appear to involve B cells either as antibody producers or as antigen-presenting cells. In recognition of this unmet need in transplantation, the American Society of Transplantation organized a Symposium on B cells in Organ Transplantation to foster interest in this topic amongst basic researchers attending the annual meeting of the American Association of Immunologists. This manuscript will give an overview of the presentations from this symposium including the current risks of allosensitization, adaptive accommodation, approaches toward B-cell tolerance for allo- and xenoantigens and clinical application of these concepts in ABO incompatible neonatal cardiac transplantation. C1 NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Mayo Clin Coll Med, Dept Immunol, Rochester, MN USA. Mayo Clin Coll Med, Dept Surg, Rochester, MN USA. Mayo Clin Coll Med, Dept Pediat, Rochester, MN USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Boston, MA USA. Univ Alberta, Dept Pediat, Edmonton, AB, Canada. Univ Alberta, Dept Surg, Edmonton, AB, Canada. Univ Alberta, Dept Immunol, Edmonton, AB, Canada. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM AllanK@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012; OI Cascalho, Marilia/0000-0002-2695-3921 FU Intramural NIH HHS; NHLBI NIH HHS [HL79067, P01 HL18646, P01 HL70295, P01-HL079067, P01-HL56091]; NIAID NIH HHS [AI 052464, AI43631, AI53733, R01 AI42387] NR 40 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2007 VL 7 IS 6 BP 1464 EP 1470 DI 10.1111/j.1600-6143.2007.01815.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 169EY UT WOS:000246576700007 PM 17511676 ER PT J AU Fujitani, S Liu, CX Finegold, SM Song, YL Mathisen, GE AF Fujitani, Shigeki Liu, Chengxu X. Finegold, Sydney M. Song, Yuli L. Mathisen, Glenn E. TI Clostridium tertium isolated from gas gangrene wound; misidentified as Lactobacillus spp initially due to aerotolerant feature SO ANAEROBE LA English DT Article DE myonecrosis; aerotolerance; Clostridium tertium; gas gangrene; Lactobacillus ID BACTEREMIA AB Clostridium tertium has been increasingly reported as a human pathogen. This organism is an aerotolerant Gram-positive rod that is often mistaken for other organisms, such as Lactobacillus or Bacillus species. We describe a case of a patient with a history of intravenous drug use presenting to UCLA-Olive View Medical Center with gas gangrene of both upper extremities. The organism was initially misidentified as a Lactobacillus species on aerobic culture plates. However, terminal spore formation was detected in this isolate on a sub-cultured anaerobic culture plate and this isolate was confirmed as C tertium biochemically and genetically by 16S rDNA sequencing. Additional DNA cloning libraries made from the formalin-fixed specimen revealed Peptoniphilus species and an uncultured Clostridium clone, but not C tertium. C tertium might be a causative organism of gas-producing myonecrosis but such an association has never been described. Clinicians should be aware of the phenomenon of aerotolerance of some anaerobes and need to clarify the identification of organisms if the clinical picture does not fit the isolated organism. (c) 2007 Elsevier Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Olive View UCLA Med Ctr, Infect Dis Serv, Sylmar, CA 91342 USA. RP Fujitani, S (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shigekifujitani@hotmail.com; chengxu66@yahoo.com; sidfinegol@aol.com; yulisl@yahoo.com; gmatliisen@ladhs.org NR 10 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN-AUG PY 2007 VL 13 IS 3-4 BP 161 EP 165 DI 10.1016/j.anaerobe.2007.03.002 PG 5 WC Microbiology SC Microbiology GA 209DG UT WOS:000249368600010 PM 17446094 ER PT J AU Driscoll, WD Columbia, MA Peterfreund, RA AF Driscoll, William D. Columbia, Mary Ann Peterfreund, Robert A. TI An observational study of anesthesia record completeness using an anesthesia information management system SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 22-26, 2005 CL Atlanta, GA SP Amer Soc Anesthesiologists ID AUTOMATED DOCUMENTATION; ADVERSE EVENTS; QUALITY; AIMS; SURGERY AB BACKGROUND: Studies of the accuracy and completeness of handwritten anesthesia records demonstrate deficiencies in documentation, suggesting that the quality of anesthesia records can be improved. METHODS: We reviewed all electronic anesthesia records generated during a 1-month period at our institution to ascertain completion rates for six clinical documentation elements: allergies, IV access, electrocardiogram rhythm, ease of mask ventilation, laryngoscopic grade of view, and insertion depth of the endotracheal tube. RESULTS: Of 2838 records, 64% had the necessary free text remark in the allergy element. The free text required to complete endotracheal tube depth documentation appeared in 538 of 918 cases in which the patient was tracheally intubated (59%). Free text documentation of the electrocardiogram rhythm diagnosis appeared at least once in 86% of records. Documentation of mask ventilation characteristics was entered by touch screen from a pick list and was expected in 781 records but appeared in 664 records (85%). Laryngoscopic grade of view documentation was also selected by touch screen and expected in 883 records but present in 811 cases (92%). Any notation of IV access appeared in 84% of records. CONCLUSIONS: We found that electronic clinical anesthesia documentation was often incomplete. Dependence on free text remarks and the record keeping system's inability to automatically present entries in logical sequences consistent with workflow were associated with incomplete data entry. Our results suggest that the user interface for data entry, and the logic that an electronic system uses for preventing omissions and inconsistencies, merit further study and development in order to facilitate clinically useful documentation. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM rpeterfreund@partners.org NR 16 TC 24 Z9 24 U1 0 U2 2 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 JUN PY 2007 VL 104 IS 6 BP 1454 EP 1461 DI 10.1213/01.ane.0000264082.54561.d8 PG 8 WC Anesthesiology SC Anesthesiology GA 172GB UT WOS:000246791000024 PM 17513641 ER PT J AU Gandhi, SD Weiskopf, RB Jungheinrich, C Koorn, R Miller, D Shangraw, RE Prough, DS Baus, D Bepperling, F Warltier, DC AF Gandhi, Sweeta D. Weiskopf, Richard B. Jungheinrich, Cornelius Koorn, Robert Miller, Diane Shangraw, Robert E. Prough, Donald S. Baus, Daniela Bepperling, Frank Warltier, David C. TI Volume replacement therapy during major orthopedic surgery using Voluven (R) (hydroxyethyl starch 130/0.4) or hetastarch SO ANESTHESIOLOGY LA English DT Article ID HYDROXYETHYL STARCH HES; INCREASE BLOOD-LOSS; PLASMA-VOLUME; TRANSFUSION REQUIREMENTS; CARDIAC-SURGERY; DOSE INFUSION; COAGULATION; SUBSTITUTION; VOLUNTEERS; 6-PERCENT AB Background: The purpose of this study was to test the equivalence of efficacy and compare the safety of the 6% hydroxyethyl starches (HES) Voluven (R) (HES 130/0.4; Fresenius Kabi, Bad Homburg, Germany) and hetastarch (HES 670/0.75 in saline) for intravascular volume replacement therapy during major orthopedic surgery. Methods: In a prospective, controlled, randomized, double-blind, multicenter trial of patients undergoing major orthopedic surgery, 49 patients were treated with HES 130/0.4 and 51 patients were treated with hetastarch. infusion of colloids was guided by central venous and arterial blood pressures. The primary efficacy endpoint was the volume of colloid solution infused; the primary safety endpoints were calculated total erythrocyte loss, the nadir factor VIII activity, and the nadir von Willebrand factor concentration within 2 h of completion of surgery. Results: The total volume of colloid solution required for intraoperative volume replacement did not differ between HES 130/0.4 and hetastarch (1,613 +/- 778 [SD] ml for HES 130/0.4 and 1,584 +/- 958 ml for hetastarch). The nadir factor VIII activity within 2 h of the end of surgery was lower for hetastarch than for HES 130/0.4 (P = 0.0499); for those who received greater than 1,000 ml colloid, the nadir factor VIII activity and von Willebrand factor concentration within 2 h of end of surgery were lower for hetastarch than for HES 130/0.4 (P = 0.0487 and P = 0.008, respectively). Conclusion: Voluven (R) (HES 130/0.4) and hetastarch are equally efficacious plasma volume substitutes; however, HES 130/0.4 has a lesser effect on coagulation. C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Clermont J Zablocki Vet Affairs Med Ctr, Dept Anesthesiol, Milwaukee, WI USA. Clermont J Zablocki Vet Affairs Med Ctr, Dept Anesthesiol Pharmacol & Toxicol, Div Cardiovasc Dis, Milwaukee, WI USA. Clermont J Zablocki Vet Affairs Med Ctr, Dept Anesthesiol Pharmacol & Toxicol, Div Cardiovasc Dis, Milwaukee, WI USA. Clermont J Zablocki Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Milwaukee, WI USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Fresenius Kabi, Bad Homburg, Germany. Anesthesia Assoc So Connecticut, Norwalk, CT USA. Portland VA Med Ctr, Dept Anesthesiol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR USA. Univ Texas, Med Branch, Dept Anesthesiol, Galveston, TX USA. RP Gandhi, SD (reprint author), Med Coll Wisconsin, MEB M4280,8701 Watertown Plank RD, Milwaukee, WI 53226 USA. EM sdgandhi@mcw.edu RI Prough, Donald/G-5793-2013 OI Prough, Donald/0000-0001-7994-532X NR 33 TC 56 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2007 VL 106 IS 6 BP 1120 EP 1127 DI 10.1097/01.anes.0000265422.07864.37 PG 8 WC Anesthesiology SC Anesthesiology GA 172IM UT WOS:000246797500010 PM 17525586 ER PT J AU Frick, CG Richtsfeld, M Sahani, ND Kaneki, M Blobner, M Martyn, JAJ AF Frick, Christiane G. Richtsfeld, Martina Sahani, Nita D. Kaneki, Masao Blobner, Manfred Martyn, J. A. Jeevendra TI Long-term effects of botulinum toxin on neuromuscular function SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-18, 2006 CL Chicago, IL SP Amer Soc Anesthesiologists ID SUCCINYLCHOLINE-INDUCED HYPERKALEMIA; MUSCULOSKELETAL-TISSUE ALLOGRAFTS; ACETYLCHOLINE-RECEPTORS; D-TUBOCURARINE; CLOSTRIDIUM-SORDELLII; DRUG-USERS; NEUROTOXINS; INFECTIONS; RESISTANCE; JUNCTION AB Background: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium. Methods: Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated. Results: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups. Conclusion: Botulinum toxin causes dose-dependent long-term neuromuscular changes. The loss of tension generating capacity is almost exclusively related to muscle atrophy because the specific tension did not change. The decreased ED10, unaltered ED50, and increased ED90 to atracurium suggest its interactions with different isoforms of receptors having varying sensitivity to atracurium. The absence of fade, despite the persistent botulinum toxin-induced denervation (increased nAChRs), suggests that the up-regulated nAChRs may have compensated for the prejunctional effects of botulinum toxin. C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Tech Univ Munich, Res Klin Anesthesiol, Klinikum Rechts Isar, D-8000 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Clin & Biochem Pharmacol Lab, Boston, MA 02114 USA. RP Frick, CG (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, 51 Blossom St, Boston, MA 02114 USA. EM christiane_frick@web.de FU NIGMS NIH HHS [GM 21500, GM 31569, GM 55082, R01 GM055082] NR 39 TC 10 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2007 VL 106 IS 6 BP 1139 EP 1146 DI 10.1097/01.anes.0000267597.65120.16 PG 8 WC Anesthesiology SC Anesthesiology GA 172IM UT WOS:000246797500013 PM 17525589 ER PT J AU Bussey-Smith, KL Rossen, RD AF Bussey-Smith, Kristin L. Rossen, Roger D. TI A systematic review of randomized control trials evaluating the effectiveness of interactive computerized asthma patient education programs SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID INNER-CITY CHILDREN; SELF-MANAGEMENT; INTERVENTION; INSTRUCTION; OUTCOMES; ADULTS AB Background: Educating patients with asthma about the pathophysiology and treatment of their disease is recommended. In recent years, several computer programs have been developed to provide this education. These programs take advantage of the population's increasing skill with computers and the growth of the Internet as a source of health care information. Objective: To evaluate the effectiveness of published interactive computerized asthma patient education programs (CAPEPs) that have been subjected to randomized controlled trials (RCTs). Data Sources: The PubMed, ERIC, CINAHL, Psychinfo, and Clinicaltrials.gov databases were searched (through October 3, 2005) using the following terms: asthma, patient, education, interactive, and computer. Study Selection: RCTs in English that evaluated the effect of an interactive CAPEP on the following primary end points were included in the study: hospitalizations, acute care visits, rescue inhaler use, or lung function. Secondary end points included asthma knowledge and symptoms. Trials were screened by title and abstract before full text review. Two independent investigators used a standardized data extraction form to identify the articles chosen for full review. Results: Nine of 406 citations met inclusion criteria. Four CAPEPs were computer games, 7 only studied children, and 4 focused on urban populations. One study each showed that the intervention reduced the number of hospitalizations, acute care visits, or rescue inhaler use. Two studies reported lung function improvements. Four studies showed improvement in asthma knowledge, and 5 studies reported improvements in symptoms. Conclusions: Although interactive CAPEPs may improve patient asthma knowledge and symptoms, their effect on objective clinical outcomes is less consistent. C1 Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Bussey-Smith, KL (reprint author), 1 Baylor Plaza,BCM 285,Suite 672E, Houston, TX 77030 USA. EM kristinb@bcm.edu NR 25 TC 40 Z9 40 U1 0 U2 6 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 JUN PY 2007 VL 98 IS 6 BP 507 EP 516 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 178BK UT WOS:000247196000003 PM 17601262 ER PT J AU Lieberman, P Decker, W Camargo, CA O'Connor, R Oppenheimer, J Simons, FE AF Lieberman, Philip Decker, Wyatt Camargo, Carlos A., Jr. O'Connor, Robert Oppenheimer, John Simons, F. Estelle TI SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID EPINEPHRINE; EPIDEMIOLOGY; MANAGEMENT; ALLERGY; FOOD; MULTICENTER; POPULATION; COMMUNITY; OUTCOMES; VISITS AB Background: Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Allergists and emergency department (ED) physicians recognize the need for multidisciplinary efforts to increase public awareness of anaphylaxis, improve patient education, and enhance emergency and long-term management for the millions of Americans at risk for anaphylactic reactions. Objectives: To provide an overview of the scientific literature documenting inconsistencies and limitations in the management of anaphylaxis in the ED, to highlight the need to enhance ED discharge instructions and patient education materials, and to introduce the SAFE system, an aid to improve the ongoing management and avoidance of factors that contribute to anaphylaxis. Methods: An expert panel of allergists and ED physicians was convened by the American College of Allergy, Asthma and Immunology and the American College of Emergency Physicians to develop recommendations for educational materials on anaphylaxis for ED personnel and patients. Results: The panel developed the acronym SAFE, a mnemonic device to remind physicians of the 4 basic action steps suggested for the care of a patient with anaphylaxis: (1) Seek support, (2) Allergen identification and avoidance, (3) Follow-up for specialty care, and (4) Epinephrine for emergencies. Conclusion: The SAFE system is designed as a tool to raise awareness of anaphylaxis and its treatments among individuals at risk and the ED personnel charged with their care. Future studies need to examine the impact of the SAFE system in decreasing the morbidity and mortality rates associated with anaphylaxis and other severe allergic reactions. C1 Univ Tennessee, Coll Med, Div Allergy & Immunol, Dept Internal Med, Memphis, TN USA. Univ Tennessee, Coll Med, Div Allergy & Immunol, Dept Pediat, Memphis, TN USA. Mayo Clin, Coll Med, Dept Emergency Med, Rochester, MN USA. Mayo Clin, Coll Med, Dept Emergency Med, Jacksonville, FL USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Christiana Care Hlth Syst, Dept Emergency Med, Newark, DE USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada. RP Lieberman, P (reprint author), 7205 Wolf River Blvd 200, Germantown, TN 38138 USA. EM aac@allergymemphis.com NR 37 TC 28 Z9 29 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 JUN PY 2007 VL 98 IS 6 BP 519 EP 523 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 178BK UT WOS:000247196000004 PM 17601263 ER PT J AU Nagrath, D Avila-Elchiver, M Berthiaume, F Tilles, AW Messac, A Yarmush, ML AF Nagrath, Deepak Avila-Elchiver, Marco Berthiaume, Francois Tilles, Arno W. Messac, Achille Yarmush, Martin L. TI Integrated energy and flux balance based multiobjective framework for large-scale metabolic networks SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article; Proceedings Paper CT Annual Meeting of the Biomedical-Engineering-Society CY OCT 22, 2006 CL Chicago, IL SP Biomed Engn Soc DE metabolic networks; energy balance analysis; flux balance analysis; multi-objective optimization; Pareto optimality; hepatocytes; bioartificial liver ID CULTURED-HEPATOCYTES; PLASMA; OPTIMIZATION; INSULIN; MODEL AB Flux balance analysis (FBA) provides a framework for the estimation of intracellular fluxes and energy balance analysis (EBA) ensures the thermodynamic feasibility of the computed optimal fluxes. Previously, these techniques have been used to obtain optimal fluxes that maximize a single objective. Because mammalian systems perform various functions, a multi-objective approach is needed when seeking optimal flux distributions in such systems. For example, hepatocytes perform several metabolic functions at various levels depending on environmental conditions; furthermore, there is a potential benefit to enhance some of these functions for applications such as bioartificial liver (BAL) support devices. Herein we developed a multi-objective optimization approach that couples the normalized Normal Constraint (NC) with both FBA and EBA to obtain multi-objective Pareto-optimal solutions. We investigated the Pareto frontiers in gluconeogenic and glycolytic hepatocytes for various combinations of liver-specific objectives (albumin synthesis, glutathione synthesis, NADPH synthesis, ATP generation, and urea secretion). Next, we evaluated the impact of experimental flux measurements on the Pareto frontiers. We found that measurements induce dramatic changes in Pareto frontiers and further constrain the network fluxes. This multi-objective optimality analysis may help explain certain features of the metabolic control of hepatocytes, which is relevant to the response to hepatocytes and liver to various physiological stimuli and disease states. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Sci, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. Rensselaer Polytech Inst, Dept Mech Engn, Troy, NY USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org OI Nagrath, Deepak/0000-0002-8999-2282 FU NIDDK NIH HHS [DK 059766, DK 043371] NR 25 TC 31 Z9 33 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUN PY 2007 VL 35 IS 6 BP 863 EP 885 DI 10.1007/s10439-007-9283-0 PG 23 WC Engineering, Biomedical SC Engineering GA 171WA UT WOS:000246764900002 PM 17393337 ER PT J AU Lovasi, GS Lemaitre, RN Siscovick, DS Dublin, S Bis, JC Lumley, T Heckbert, SR Smith, NL Psaty, BM AF Lovasi, Gina S. Lemaitre, Rozenn N. Siscovick, David S. Dublin, Sascha Bis, Joshua C. Lumley, Thomas Heckbert, Susan R. Smith, Nicholas L. Psaty, Bruce M. TI Amount of leisure-time physical activity and risk of nonfatal myocardial infarction SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE case-control studies; epidemiology; exercise; leisure activities; myocardial infarction ID CARDIOVASCULAR-DISEASE; DOSE-RESPONSE; OLDER-ADULTS; EXERCISE; WOMEN; MORTALITY; HEALTH; INFLAMMATION; PREVENTION; INTENSITY AB Purpose: To investigate the shape of the relation between amount of leisure-time physical activity (LTPA) and myocardial infarction (MI) risk. Methods: Data were from a case-control study in a Washington State health maintenance organization, 1986 to 2002. Participants had no prior cardiovascular disease and good self-reported health before selection. Telephone interviews asked 697 nonfatal MI cases and 3,397 control subjects about 26 types of LTPA. Models adjusted for age, sex, year, treated hypertension, family history of heart disease, smoking, alcohol, aspirin, race, retirement, income, and education. Results: Some LTPA was reported by 90% of control subjects and 84% of cases. Compared with no LTPA, participation in LTPA was associated with lower risk of MI (adjusted odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.52, 0.86). Among active participants, LTPA time was associated with risk of MI (OR = 0.66 for high versus low quartile, 95% CI: 0.51, 0.86). Risk of MI decreased with increasing total or nonstrenuous LTPA time up to the median, beyond which we could not detect an association between LTPA time and MI risk. Conclusions: Time engaged in LTPA, even nonstrenuous LTPA, was associated with lower risk of MI, and the shape of this relationship was nonlinear. C1 Columbia Univ, Inst Social & Econ Res & Policy, New York, NY 10027 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lovasi, GS (reprint author), Columbia Univ, Inst Social & Econ Res & Policy, 820 Int Affairs Bldg,Mail Code 3355,420 W 118th S, New York, NY 10027 USA. EM gl2225@columbia.edu RI Lovasi, Gina/C-2781-2009 OI Lovasi, Gina/0000-0003-2613-9599 FU NHLBI NIH HHS [R01-HL043201, T32 HL007902, T32-HL07902, R01-HL068639]; NIA NIH HHS [R01-AG09556] NR 31 TC 12 Z9 13 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUN PY 2007 VL 17 IS 6 BP 410 EP 416 DI 10.1016/j.annepidem.2006.10.012 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178YU UT WOS:000247257100002 PM 17321755 ER PT J AU Bartlett, NL Niedzwiecki, D Johnson, JL Friedberg, JW Johnson, KB van Besien, K Zelenetz, AD Cheson, BD Canellos, GP AF Bartlett, N. L. Niedzwiecki, D. Johnson, J. L. Friedberg, J. W. Johnson, K. B. van Besien, K. Zelenetz, A. D. Cheson, B. D. Canellos, G. P. CA Canc Leukemia Grp B TI Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804 SO ANNALS OF ONCOLOGY LA English DT Article DE gemcitabine; Hodgkin's lymphoma; liposomal doxorubicin; recurrent; salvage therapy; vinorelbine ID CELL LUNG-CANCER; PHASE-II; RANDOMIZED TRIAL; DISEASE; TRANSPLANTATION; CHEMOTHERAPY; THERAPY; CISPLATIN; RECURRENT; ABVD AB Background: Because of high single-agent activity and modest toxicity, we hypothesized the combination of gemcitabine (G), vinorelbine M, and pegylated liposomal doxorubicin (D) would be an effective salvage therapy for Hodgkin's lymphoma (HL). Patients and methods: A total of 91 patients participated. GVD was administered on days 1 and 8 every 21 days at doses of G 1000 mg/m2, V 20 mg/m2, and D 15 mg/m2 for transplant-naive patients, and G 800 mg/m2, V 15 mg/m2, and D 10 mg/m2 for post-transplant patients. Results: The dose-limiting toxicity was mucositis for the transplant-naive patients and febrile neutropenia for posttransplant patients. The overall response rate (RR) for all patients was 70% [95% confidence interval (CI) 59.8, 79.7], with 19% complete remissions. The 4-year event-free and overall survival rates in transplant-naive patients treated with GVD followed by autologous transplant were 52% (95% CI 0.34, 0.68) and 70% (95% CI 0.49, 0.84), and in the patients in whom prior transplant failed, these were 10% (95% CI 0.03, 0.22) and 34% (95% CI 0.17, 0.52), respectively. Conclusions: GVD is a well-tolerated, active regimen for relapsed HL with results similar to those reported for more toxic regimens. High RRs in patients in whom prior transplant failed confirms this regimen's activity even in heavily pretreated patients. C1 Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Dana Farber Partners, Boston, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Chicago, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Bartlett, NL (reprint author), Washington Univ, Sch Med, Siteman Canc Ctr, 660 S Euclid,Box 8056, St Louis, MO 63110 USA. EM nbartlet@im.wustl.edu RI van Besien, Koen/G-4221-2012 OI van Besien, Koen/0000-0002-8164-6211 FU NCI NIH HHS [CA04326, CA07968, CA03927, CA11789, CA12046, CA12449, CA26806, CA31946, CA32291, CA33601, CA35113, CA41287, CA45389, CA45808, CA47642, CA77440, CA77597, CA77651, CA77658] NR 30 TC 99 Z9 109 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2007 VL 18 IS 6 BP 1071 EP 1079 DI 10.1093/annonc/mdm090 PG 9 WC Oncology SC Oncology GA 204NU UT WOS:000249052100016 PM 17426059 ER PT J AU Liao, EC Kish, JB Hertl, MC AF Liao, Eric C. Kish, Joshua B. Hertl, M. Catherine TI Incidental discovery of bilateral breast cancer in a 24-year-old man presenting with gynecomastia SO ANNALS OF PLASTIC SURGERY LA English DT Article DE gynecomastia; gynecomastia reduction; male breast cancer ID CARCINOMA IN-SITU; RISK-FACTORS; SUCTION LIPECTOMY; REDUCTION MAMMAPLASTY; PROGNOSTIC FACTORS; PULL-THROUGH; MEN; CLASSIFICATION; LIPOSUCTION; CHILDREN AB We present a case of a 24-year-old man who was treated for gynecomastia with bilateral mastectomy and free nipple grafts with subsequent discovery of bilateral breast cancer in the submitted specimens. Surgical treatment of gynecomastia is becoming more popular with over 16,000 procedures of gynecomastia reduction performed in 2005, air increase of 17% compared with the previous year. This case underscores the rare but real possibility of detecting breast cancer in men who present with gynecomastia to plastic surgeons. We caution that male breast tissue should be regarded with the same oncologic principle as female breast tissue. In cases in which ultrasound-assisted suction lipectomy is used, the inability to analyze the breast tissue should be disclosed to the patient. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hertl, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Profess Off Bldg,502, Boston, MA 02114 USA. EM chertl@partners.org NR 48 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 2007 VL 58 IS 6 BP 673 EP 676 DI 10.1097/01.sap.0000245118.98550.cf PG 4 WC Surgery SC Surgery GA 173GW UT WOS:000246862500015 PM 17522493 ER PT J AU Yoon, SS Tanabe, KK AF Yoon, Sam S. Tanabe, Kenneth K. TI Should surgical resection be combined with imatinib therapy for locally advanced or metastatic gastrointestinal stromal tumors? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID INTERSTITIAL-CELLS; MESYLATE; SURGERY; CAJAL; GIST; ERA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA USA. RP Tanabe, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA USA. EM ktanabe@partners.org NR 15 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2007 VL 14 IS 6 BP 1784 EP 1786 DI 10.1245/s10434-006-9344-x PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 181XS UT WOS:000247470300002 PM 17356951 ER PT J AU Abraham, JA Hornicek, FJ Kaufman, AM Harmon, DC Springfield, DS Raskin, KA Mankin, HJ Kirsch, DG Rosenberg, AE Nielsen, GP Desphpande, V Suit, HD DeLancy, TF Yoon, SS AF Abraham, John A. Hornicek, Francis J. Kaufman, Adam M. Harmon, David C. Springfield, Dempsey S. Raskin, Kevin A. Mankin, Henry J. Kirsch, David G. Rosenberg, Andrew E. Nielsen, G. Petur Desphpande, Vikram Suit, Herman D. DeLancy, Thomas F. Yoon, Sam S. TI Treatment and outcome of 82 patients with angiosarcoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE sarcoma; angiosarcoma; outcome; radiotherapy ID SOFT-TISSUE SARCOMAS; OF-THE-LITERATURE; EPITHELIOID ANGIOSARCOMA; PROGNOSTIC-FACTORS; HEPATIC ANGIOSARCOMA; BREAST; BONE; SERIES; SCALP; LYMPHANGIOSARCOMA AB Background: Angiosarcomas are an uncommon type of malignancy that are generally thought to behave usually in a locally aggressive fashion; they often metastasize to distant sites. Methods: Patients with a diagnosis of angiosarcoma treated at our institution between 1980 and 2006 were analyzed for patient demographics, tumor characteristics, multimodality treatment, and outcomes. Results: A total of 82 patients were divided into those with primary and advanced disease. Overall, the median age was 65 (range, 22 91) years, and 44% of patients were women. Median size of tumors was 3.8 cm, and 76% of tumors were intermediate or high grade. Tumors were located throughout the body: 32 cutaneous, 22 deep soft tissues or organs, 10 radiation or lymphedema field, 8 bone, and 7 nonirradiated breast. Of 46 patients with primary disease, all patients underwent surgical resection, 67% received radiotherapy, and 27% received chemotherapy. Five-year disease-specific survival was 60%, and negative prognostic factors included intermediate or high grade, and tumors arising in a radiated or lymphedema field. Of 36 patients with advanced disease, 36% underwent a palliative operation, 78% received radiation, and 58% received chemotherapy. Median survival was just 7.3 months, and cutaneous tumors predicted a better prognosis compared with other sites. Conclusions: Primary angiosarcomas treated with aggressive surgical resection and the addition of radiation for close margins or worrisome pathologic features can result in long-term survival in most patients. The role of adjuvant chemotherapy is unclear. Patients with advanced disease have a poor prognosis, but there can be dramatic responses to chemotherapy in a minority of patients. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7B-7926,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org FU NCI NIH HHS [5K12CA87723-03] NR 38 TC 100 Z9 106 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2007 VL 14 IS 6 BP 1953 EP 1967 DI 10.1245/s10434-006-9335-y PG 15 WC Oncology; Surgery SC Oncology; Surgery GA 181XS UT WOS:000247470300023 PM 17356953 ER PT J AU Gaissert, HA Honings, J Grillo, HC Donahue, DM Wain, JC Wright, CD Mathisen, DJ AF Gaissert, Henning A. Honings, Jimmie Grillo, Hermes C. Donahue, Dean M. Wain, John C. Wright, Cameron D. Mathisen, Douglas J. TI Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 29-31, 2007 CL San Diego, CA SP Soc Thorac Surg ID AIRWAY INVASION; SURGICAL-MANAGEMENT; CANCER; RECONSTRUCTION; INVOLVEMENT; SURGERY AB Background. Laryngotracheal invasion worsens prognosis in patients with thyroid carcinoma. The extent of resection is controversial. Methods. We performed a retrospective study of patients with thyroid carcinoma and invasion of the larynx or trachea between 1964 and 2005. Results. Eighty-two patients, mean age 64 years and 50% female, underwent segmental airway resection. Differentiated carcinoma was present in 76% ( 62 of 82 patients), prior tracheal "shave" procedures in 40% ( 33 of 82 patients), transmural invasion in 58% ( 48 of 82 patients), and preoperative vocal cord paralysis in 35% ( 29 of 82 patients). There were 29 tracheal and 40 laryngotracheal resections ( reconstruction group: 69 patients); 5 underwent laryngectomy, 7 cervical exenteration, and 1 tracheal resection after exenteration ( salvage group: 13 patients). Operative mortality was 1.2% ( 1 of 82 patients) and anastomotic dehiscence 4.3% ( 3 of 69 patients). Tracheostomy was permanent in 4.3% ( 3 of 69 patients). Mean follow-up was 6.1 years. After reconstruction, mean survival was 9.4 years and 10-year survival was 40%; after salvage, these were 5.6 years and 15%, respectively. In differentiated carcinoma, thyroidectomy, immediate shave procedure, and delayed ( mean, 67 months) resection of airway recurrence in 15 patients resulted in overall and disease-free survival of 13.1 and 5.1 years, respectively, compared with 17.9 and 14.6 years, respectively, after thyroidectomy and early airway resection in 11 patients. Airway symptoms, metastases at presentation, recurrent disease, and salvage operation were associated with decreased survival; airway resection early after thyroidectomy, complete resection, and well-differentiated tumors were associated with improved prognosis. Conclusions. Segmental airway resection for invasive thyroid cancer is safe, preserves the voice, and relieves airway obstruction. Complete resection of laryngeal and tracheal invasion during or early after thyroidectomy is associated with improved survival. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org RI Honings, Jimmie/B-3639-2016 OI Honings, Jimmie/0000-0001-5077-3472 NR 19 TC 48 Z9 56 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 JUN PY 2007 VL 83 IS 6 BP 1952 EP 1959 DI 10.1016/j.athoracsur.2007.01.056 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 172GD UT WOS:000246791200005 PM 17532377 ER PT J AU Slater, MS Komanapalli, CB Tripathy, U Ravichandran, PS Ungerleider, RM AF Slater, Matthew S. Komanapalli, Christopher B. Tripathy, Uttam Ravichandran, Pasala S. Ungerleider, Ross M. TI Treatment of endocarditis: a decade of experience SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 08-11, 2006 CL Tucson, AZ SP SE Thorac Surg Assoc ID PROSTHETIC VALVE ENDOCARDITIS; INFECTIVE ENDOCARDITIS; SURGICAL-MANAGEMENT; CLINICAL-FEATURES; EARLY PREDICTORS; MORTALITY; DIAGNOSIS; SURGERY; DEATH AB Background. Endocarditis represents a small proportion of cardiovascular disease but is associated with high mortality. Previous studies have reported a range of outcomes, and determinants of mortality remain poorly defined. Methods. The goal of this retrospective study was to identify independent variables for early and late mortality in 364 consecutive patients with endocarditis over a 10-year period. Results. The mean age of patients was 48.2 years, 35% had a history intravenous drug use, 19.8% were reoperative, and 93% had native valve endocarditis. Fever (68%) and fatigue (36%) were the most common presenting symptoms, and congestive heart failure (52%), embolization (45%), and uncontrolled sepsis (36%) were the most common indications for surgery. Overall survival at discharge, 1, 5, and 10 years was 87%, 76%, 55%, and 31%, respectively. Survival at discharge, 5, and 10 years was 91%, 69%, and 41% for surgical patients and 85%, 60%, and 31% for medically treated patients, respectively. Surgery was associated with improved short-term and long-term survival ( p < 0.0.01). Independent predictors of early death were hemodynamic instability ( p = 0.013) and age older than 55 years ( p < 0.025). Medical treatment ( p = 0.005), age older than 55 years ( p = 0.032), institution ( p < 0.001), New York Heart Association functional class III or IV ( p = 0.002), and hemodynamic instability ( p = 0.044) were predictive of late death. Conclusions. Short-term and long-term mortality from endocarditis remains high, although surgically treated patients had improved survival. Differing outcomes from two geographically similar institutions highlight the limitations of extrapolating risk factors between disparate patient populations. C1 Oregon Hlth & Sci Univ, Div Cardiothorac Surg, Dept Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Dept Surg, Div Cardiothorac Surg, Portland, OR USA. RP Slater, MS (reprint author), Oregon Hlth & Sci Univ, Div Cardiothorac Surg, Dept Surg, 3181 SW Sam Jackson Pk Rd L353, Portland, OR 97239 USA. EM slaterm@ohsu.edu NR 15 TC 8 Z9 9 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 JUN PY 2007 VL 83 IS 6 BP 2074 EP 2080 DI 10.1016/j.athoracsur.2007.01.051 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 172GD UT WOS:000246791200023 PM 17532400 ER PT J AU Ikonomidis, JS Hilton, EJ Payne, K Harrell, A Finklea, L Clark, L Reeves, S Stroud, RE Leonardi, A Crawford, FA Spinale, FG AF Ikonomidis, John S. Hilton, Ebony J. Payne, Kimberly Harrell, April Finklea, Laura Clark, Leslie Reeves, Scott Stroud, Robert E. Leonardi, Amy Crawford, Fred A., Jr. Spinale, Francis G. TI Selective endothelin-A receptor inhibition after cardiac surgery: A safety and feasibility study SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 08-11, 2006 CL Tucson, AZ SP SE Thorac Surg Assoc ID CONGESTIVE-HEART-FAILURE; CARDIOPULMONARY BYPASS; POSTOPERATIVE RECOVERY; ANTAGONIST; BLOCKADE; REPERFUSION; PROGRESSION; TEZOSENTAN; ISCHEMIA; MYOCYTES AB Background. Increased synthesis and release of the bioactive peptide endothelin has been shown to change hemodynamics and postoperative recovery after cardiac surgery. However, the clinical effects of selective interruption of endothelin signaling have not been studied. Because the endothelin-A (ET-A) receptor subtype is the primary cardiovascular effector for endothelin, this study used the ET-A receptor antagonist sitaxsentan sodium (TBC11251Na) to evaluate: (1) dose-dependent changes in pulmonary artery pressure (PAP) and pulmonary (PVRI) and systemic (SVRI) vascular resistance index in patients undergoing on-pump coronary revascularization; and (2) whether ET-RA administration was associated with increased adverse events. Methods. Patients (n = 44, age, 62 +/- 1 years) were randomized to receive vehicle (n = 9) or different bolus infusions of ET-A receptor antagonist: 0.1 (n = 9), 0.5 (n = 9) 1.0 (n = 9), and 2.0 mg/kg (n = 8) at separation from cardiopulmonary bypass (CPB). Adverse events were tabulated until hospital discharge. Results were expressed as changes from a composite baseline value, or from time 0 due to a high degree of intrapatient measurement variability in the postoperative period. Results. PAP increased by 27% +/- 13% from baseline (19 +/- 1 mm Hg) in the vehicle group at 6 hours post-CPB (p < 0.05). PAP fell from this post-CPB vehicle value in a dose-dependent manner with the ET-A receptor antagonist; with a significant reduction observed at 2 mg/kg (7% +/- 8% increase from baseline, p < 0.05). PVRI was reduced by 28.6% +/- 16% from baseline (249 +/- 22 dyn.s.cm(-5).m(-2)) in the 2 mg/kg ET-A receptor antagonist group at 30 minutes post-CPB and remained reduced up to 6 hours post-CPB (p < 0.05). SVRI was reduced from baseline (2770 +/- 106 dyn.s.cm(-5).m(-2)) by 51% +/- 6% in the 2.0 mg/kg ET-A receptor antagonist group at 30 minutes post-CPB (p < 0.05) and remained reduced up to 6 hours post-CPB. A total of 203 adverse events were tabulated in the postoperative period and were equally distributed across the five treatment groups, with no direct attributions to ET-A receptor antagonist treatment. Conclusions. This unique study demonstrates that heightened endothelin-A receptor activation contributes to hemodynamic changes in patients after CPB. Selective inhibition of the endothelin receptor system can be successfully and safely performed in patients undergoing cardiac surgery and thereby reveals a potential, and clinically relevant therapeutic target. C1 Med Univ S Carolina, Div Cardiothorac Surg, Cardiothorac Surg Lab, Charleston, SC 29425 USA. Ralph J Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Cardiothorac Surg Lab, Suite 409CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NHLBI NIH HHS [HL056603, HL057952] NR 26 TC 13 Z9 15 U1 0 U2 1 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 JUN PY 2007 VL 83 IS 6 BP 2153 EP 2161 DI 10.1016/j.athoracsur.2007.02.087 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 172GD UT WOS:000246791200036 PM 17532415 ER PT J AU Yan, X Shen, H Feng, Y Wang, J Lou, SW Wang, LP Wong, GL Yang, ZX Jiang, HJ Wu, XQ Hu, D Guan, Y Smaill, F Zhang, CS AF Yan, Xin Shen, Hua Feng, Yan Wang, Jun Lou, Shi-Wen Wang, Liping Wong, Gillian Yang, Zhaoxiong Jiang, Hongjian Wu, Xinqi Hu, Dan Guan, Yi Smaill, Fiona Zhang, Chengsheng TI Potent inhibition of viral entry and replication of SARS-CoV by siRNAs targeting the genes encoding the cellular ACE2 receptor or the viral nucleocapsid protein SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4L8, Canada. New Med Sci Res Inst, New York, NY USA. Inst Chongqing Tradit Chinese Med, Chongqing, Peoples R China. Univ Hong Kong, Hong Kong, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 10 BP A30 EP A31 DI 10.1016/j.antiviral.2007.01.018 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600011 ER PT J AU Zhang, C Feng, Y Wong, GL Wang, LP Cechetto, J Blanchard, J Brown, E Mahony, J AF Zhang, Chengsheng Feng, Yan Wong, Gillian Wang, Liping Cechetto, Jonathan Blanchard, Jan Brown, Eric Mahony, James TI Development of a cell-based assay for identification of viral entry inhibitors against SARS-CoV by high throughput screening (HTS) SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4L8, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. McMaster Univ, Dept Biochem, High Throughput Screening Lab, Hamilton, ON L8S 4L8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 135 BP A82 EP A82 DI 10.1016/j.antiviral.2007.01.143 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600135 ER PT J AU McNeil, MR Sung, JE Yang, D Pratt, SR Fossett, TRD Doyle, PJ Pavelko, S AF McNeil, Malcolm R. Sung, Jee Eun Yang, Dorothy Pratt, Sheila R. Fossett, Tepanta R. D. Doyle, Patrick J. Pavelko, Stacey TI Comparing connected language elicitation procedures in persons with aphasia: Concurrent validation of the Story Retell Procedure SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 36th Clinical Aphasiology Conference CY 2006 CL Ghent, BELGIUM ID LEXICAL DIVERSITY; RELIABILITY; ADULTS AB Background: The Story Retell Procedure (SRP) (Doyle et al., 1998) is a well-described method for eliciting connected language samples in persons with aphasia (PWA). However, the stimuli and task demands of the SRP are fundamentally different from commonly employed picture description, narrative, and procedural description tasks reported in the aphasia literature. As such, the extent to which measures of linguistic performance derived from the SRP may be associated with those obtained from picture description, narrative, and procedural description tasks is unknown. Aims: To assess the concurrent validity of linguistic performance measures obtained from the SRP with those obtained from picture description, narrative, and procedural description tasks by examining the correlations and the magnitude differences across the linguistic variables among the elicitation tasks. Secondarily, we examined the relationship of the percentage of information units per minute (%IU/Min) to other linguistic variables within the SRP and across the other elicitation tasks. Methods and Procedures: This study compared the SRP to six different, frequently used sampling procedures (three sets of picture descriptions, one fairytale generation, one set of narratives, and one set of procedural description tasks) from which the same five verbal productivity, four information content, two grammatical, and two verbal disruption measures were computed. Language samples were elicited from 20 PWA, spanning the aphasia comprehension severity range. Tests of association and difference were calculated for each measure between the SRP and the other sampling methods. Outcomes & Results: Significant and strong associations were obtained between the SRP and the other elicitation tasks for most linguistic measures. The SRP produced either no significant or significantly greater instances of the dependent variable except for the type-token ratio, which yielded a significantly lower value than the other sampling procedures. Conclusions: The findings are interpreted as support for the concurrent validity of the SRP and as evidence that a single form of the SRP will yield a language sample that is generally equivalent in distribution to other sampling procedures, and one that is generally greater in quantity to those typically used to assess connected spoken language in PWA. Additionally, it was found that the %IU/Min metric predicted highly the information content linguistic measures on the SRP as well as on the other elicitation procedures. However, it did not predict well measures of verbal productivity, grammaticality, or verbal disruptions. C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM mcneil@pitt.edu RI Pratt, Sheila/H-7139-2013 NR 19 TC 13 Z9 13 U1 1 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD JUN-AUG PY 2007 VL 21 IS 6-8 BP 775 EP 790 DI 10.1080/02687030701189980 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 179XN UT WOS:000247323900020 ER PT J AU Utikal, J Ugurel, S Kurzen, H Erben, P Reiter, A Hochhaus, A Nebe, T Hildenbrand, R Haberkorn, U Goerdt, S Schadendorf, D AF Utikal, Jochen Ugurel, Selma Kurzen, Hjalmar Erben, Philipp Reiter, Andreas Hochhaus, Andreas Nebe, Thomas Hildenbrand, Ralf Haberkorn, Uwe Goerdt, Sergij Schadendorf, Dirk TI Imatinib as a treatment option for systemic non-Langerhans cell histiocytoses SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ROSAI-DORFMAN-DISEASE; GASTROINTESTINAL STROMAL TUMORS; POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; RESIDUAL DISEASE; DISORDERS; FUSION; PCR; RECEPTOR; PDGFRA AB Background: Systemic non-Langerhans cell histiocytoses are disorders characterized by the accumulation of histiocytes that do not meet the criteria for Langerhans cells in various organs. So far, no causative treatment is known. Observations: Herein, we report the case of a 41-year-old man with Rosai-Dorfman disease, a form of systemic non-Langerhans cell histiocytoses, with histiocytic infiltrations in the skin, bone marrow, liver, and spleen. Histiocytes were positive for the imatinib target proteins platelet-derived growth factor receptor 0 and KIT. The disease completely responded to treatment with 400 to 600 mg daily of imatimb for more than 7 months. Conclusion: This case shows that imatimb is a powerful treatment option for patients with non-Langerhans cell histiocytoses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. Univ Heidelberg, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, D-6800 Mannheim, Germany. Univ Heidelberg, Univ Med Ctr Mannheim, Dept Internal Med 3, D-6800 Mannheim, Germany. Univ Heidelberg, Univ Med Ctr Mannheim, Cent Lab, D-6800 Mannheim, Germany. Univ Heidelberg, Univ Med Ctr Mannheim, Dept Pathol, D-6800 Mannheim, Germany. German Canc Res Ctr, Skin Canc Unit, D-6900 Heidelberg, Germany. Univ Heidelberg, Dept Nucl Med, Heidelberg, Germany. RP Utikal, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM jutikal@mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241; Hochhaus, Andreas/0000-0003-0626-0834 NR 20 TC 28 Z9 31 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2007 VL 143 IS 6 BP 736 EP 740 DI 10.1001/archderm.143.6.736 PG 5 WC Dermatology SC Dermatology GA 178FU UT WOS:000247207400008 PM 17576939 ER PT J AU Chamlin, SL Lai, JS Cella, D Frieden, IJ Williams, ML Mancini, AJ Chren, MM AF Chamlin, Sarah L. Lai, Jin-Shei Cella, David Frieden, Ilona J. Williams, Mary L. Mancini, Anthony J. Chren, Mary-Margaret TI Childhood Atopic Dermatitis Impact Scale - Reliability, discriminative and concurrent validity, and responsiveness SO ARCHIVES OF DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; EUROPEAN TASK-FORCE; INITIAL VALIDATION; SLEEP DISTURBANCE; CONSENSUS REPORT; SCORAD INDEX; CHILDREN; ECZEMA; FAMILIES AB Objective: To evaluate the test-retest reliability, discriminative and concurrent validity, and responsiveness of the Childhood Atopic Dermatitis Impact Scale (CADIS), a quality-of-life scale with 5 domains. Design: Prospective, longitudinal study. Setting: Two academic pediatric dermatology practices. Patients: A total of 301 parents of children younger than 6 years with atopic dermatitis. Main Outcome Measures: Participants completed the CADIS, sociodemographic items, and other clinical questions at enrollment and at a 4-week follow-up. In addition, 41 participants completed the CADIS again 48 hours after baseline. Disease severity was measured using the Severity Scoring of Atopic Dermatitis (SCORAD) index for all children. Results: Of 301 enrolled participants, 270 (90%) completed the enrollment materials and 228 (84%) of these completed the 4-week follow-up materials. Thirty-four (83%) of the 41 participants completed the 48-hour materials. Intraclass correlation coefficients of CADIS scores at enrollment and at 48 hours ranged from 0.89 to 0.95. Correlations between CADIS scores and the SCORAD index scores (range, 0.42-0.72) demonstrated that more severe atopic dermatitis is associated with worse quality of life. Scores from all 5 domains of the CADIS significantly differentiated patients at each severity level as measured by the SCORAD index (P <.001). Participants who rated their children as "improved" at the 4-week follow-up had significantly better CADIS scores than those who rated their children as having the "same" or "worse" skin disease (P <.05). Conclusions: These data confirm the test-retest reliability, concurrent validity, and discriminative validity of the CADIS. In addition, responsiveness evaluation demonstrates that the CADIS accurately measures change in patients whose disease improves. C1 Childrens Mem Hosp, Div Pediat Dermatol, Chicago, IL 60614 USA. Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. NW Feinberg Sch Med, Evanston, IL USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Serv Dermatol, San Francisco, CA USA. RP Chamlin, SL (reprint author), 2300 Childrens Plaza,Box 107, Chicago, IL 60614 USA. EM schamlin@childrensmemorial.org OI Frieden, Ilona/0000-0001-7305-5940 NR 17 TC 20 Z9 21 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2007 VL 143 IS 6 BP 768 EP 772 DI 10.1001/archderm.143.6.768 PG 5 WC Dermatology SC Dermatology GA 178FU UT WOS:000247207400013 PM 17576944 ER PT J AU Perlis, RH Purcell, S Fava, M Fagerness, J Rush, AJ Trivedi, MH Smoller, JW AF Perlis, Roy H. Purcell, Shaun Fava, Maurizio Fagerness, Jesen Rush, A. John Trivedi, Madhukar H. Smoller, Jordan W. TI Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; TRYPTOPHAN-HYDROXYLASE GENE; MAJOR DEPRESSIVE DISORDER; SINGLE NUCLEOTIDE POLYMORPHISM; SEROTONIN 2A RECEPTOR; WIDE LINKAGE SURVEY; REPORT QIDS-SR; RELIEVE DEPRESSION; ANTIDEPRESSANT TREATMENT; FLUOXETINE TREATMENT AB Context: A small subset of patients with depression exhibit new or worsening suicidal thoughts or behavior during short-term treatment with antidepressants. Because cyclic adenosine monophosphate response element binding (CREB) protein has been implicated in both antidepressant mechanisms and suicide, the CREB1 gene represents a gene that possibly influences the risk for treatment-emergent suicidality. Objective: To examine polymorphisms that span CREB1, which was previously associated with anger expression in men with major depressive disorder, for association with new or worsening suicidality. Design: Nested case-control study derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter, prospective, open, 12-week effectiveness trial from July 1, 2001, to September 30, 2006. Setting: Outpatient primary care and psychiatric clinics. Patients: Individuals with nonpsychotic major depressive disorder for whom DNA was available and who did not report suicidal ideation at study entry were subsequently treated with citalopram hydrobromide for up to 12 weeks. Main Outcome Measure: Emergent suicidal ideation, defined as a score of 2 or higher on any postbase-line visit for participants whose baseline score was 0 or 1 on the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated suicide item. Results: Of 1447 participants, 124 (8.6%) subsequently reported suicidality on at least 1 visit; these individuals were compared with the remaining 1324 participants. Of 5 single nucleotide polymorphisms (SNPs) examined, none were significantly associated with treatment-emergent suicidality overall. However, 2 SNPs revealed a gene-by-sex interaction with suicidality. Among the 539 men, these 2 SNPs and 2 of the 5 SNP haplotypes; were significantly associated with new-onset suicidality. Conclusions: Polymorphisms that span CREB1 were associated with treatment-emergent suicidality among men with depression, extending an observation of association with male anger expression in a prior independent cohort. If replicated, this finding would suggest that pharmacogenetic testing could facilitate the identification of the small subset of individuals at greater risk during short-term antidepressant treatment. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75230 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [K23MH67060, N01 MH-90003] NR 79 TC 93 Z9 97 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2007 VL 64 IS 6 BP 689 EP 697 DI 10.1001/archpsyc.64.6.689 PG 9 WC Psychiatry SC Psychiatry GA 175HQ UT WOS:000247005100007 PM 17548750 ER PT J AU White-Bateman, SR Schumacher, HC Sacco, RL Appelbaum, PS AF White-Bateman, Stephanie R. Schumacher, H. Christian Sacco, Ralph L. Appelbaum, Paul S. TI Consent for intravenous thrombolysis in acute stroke - Review and future directions SO ARCHIVES OF NEUROLOGY LA English DT Review ID ACUTE ISCHEMIC-STROKE; ACUTE MYOCARDIAL-INFARCTION; DECISION-MAKING CAPACITY; RT-PA STROKE; INFORMED-CONSENT; COMMUNITY CONSULTATION; SUBSTITUTED JUDGMENT; COGNITIVE IMPAIRMENT; PRESTROKE DEMENTIA; CLINICAL EMERGENCY AB Intravenous thrombolysis with recombinant tissue plasminogen activator is the standard of care for the treatment of acute ischemic stroke within 3 hours after stroke onset. Randomized clinical studies have demonstrated that intravenous thrombolysis improves functional outcomes but is not lifesaving. Complications of intravenous thrombolysis include severe intracranial hemorrhage that may be lethal. As with any therapy, consent cannot be assumed in the decision to use intravenous thrombolysis. Currently, there is no standardized method to estimate the capacity of patients with acute stroke, and empirical data for this patient population are limited. It is our position that candidates for intravenous thrombolysis should be properly assessed for their capacity to give direct consent before another form of consent is sought. We believe this would best be achieved by the development and standardization of a procedure for capacity assessment specifically for use in patients with acute stroke. To this end, we review the elements of informed consent, the legal standards for competence that a candidate for intravenous thrombolysis must meet to consent to treatment, recommendations for assessing capacity to give direct informed consent with attention to difficulties presented by the acute stroke setting, alternatives to direct consent with their inherent moral difficulties, and potential directions for research and discourse on capacity assessment in acute stroke. C1 New York Presbyterian Hosp, Doris & Stanley Tananbaum Stroke Ctr, Neurol Inst, Coll Phys & Surg, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. Columbia Univ, Coll Phys & Surg, Div Psychiat Law & Eth, Dept Psychiat, New York, NY USA. RP Schumacher, HC (reprint author), New York Presbyterian Hosp, Doris & Stanley Tananbaum Stroke Ctr, Neurol Inst, Coll Phys & Surg, 710 W 168th St,Box 163, New York, NY 10032 USA. EM hs775@columbia.edu FU NINDS NIH HHS [5-T32-NS007155-26] NR 87 TC 25 Z9 26 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2007 VL 64 IS 6 BP 785 EP 792 DI 10.1001/archneur.64.6.785 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 177HF UT WOS:000247143500002 PM 17562926 ER PT J AU Mendez, MF Shapira, JS McMurtray, A Licht, E Miller, BL AF Mendez, Mario F. Shapira, Jill S. McMurtray, Aaron Licht, Eliot Miller, Bruce L. TI Accuracy of the clinical evaluation for frontotemporal dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID FRONTAL-LOBE DEMENTIA; ALZHEIMERS-DISEASE; PICKS-DISEASE; WORK GROUP; DEGENERATION; DIAGNOSIS; FEATURES; CRITERIA; PREVALENCE; CONSENSUS AB Background: Without a definitive clinical test, the early diagnosis of frontotemporal dementia ( FTD) can be difficult. Objective: To evaluate the accuracy of the clinical evaluation for FTD. Design: Retrospective assessment of consensus criteria for FTD, neuropsychological measures, magnetic resonance images, and single- photon emission computed tomography/ positron emission tomography ( SPECT/ PET) scans at baseline compared with a standard of subsequent clinical diagnosis after follow- up and reevaluation to year 2. Setting: University hospital. Patients: A total of 134 patients referred for clinical evaluation of suspected FTD. These patients had 1 or more core or supportive features of FTD in the absence of another etiology on initial assessment. Main Outcome Measures: Sensitivities, specificities, and predictive values of consensus criteria for FTD, magnetic resonance images, and SPECT/ PET scans at initial assessment. Results: The sensitivities and specificities for the diagnosis of FTD were 36.5% and 100.0% for consensus criteria, 63.5% and 70.4% formagneticresonanceimages, and 90.5% and 74.6% for SPECT/ PET scans, respectively. With a previous prevalence of nearly 50% for FTD, the positive predictive value was greatest for consensus criteria ( 100.0%), and the negative predictive value was greatest for SPECT/ PET ( 89.8%). The initial neuropsychological results did not distinguish FTD, but the pattern of progression ( worse naming and executive functions and preserved constructional ability) helped establish the diagnosis at year 2. Conclusions: Consensus criteria for FTD and neuropsychological measures lacked sensitivity for FTD; however, neuroimaging, particularly functional brain studies, greatly increased the sensitivity of detecting FTD. The clinical diagnosis of FTD needs to combine neuropsychiatric features with SPECT or PET findings while following the changes on neuropsychological tests. C1 VA Greater Los Angeles Healthcare, Neurobev Unit 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Hawaii, Dept Neurol, Honolulu, HI 96822 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare, Neurobev Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU NIA NIH HHS [AG19724-01, P01 AG019724] NR 36 TC 91 Z9 98 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2007 VL 64 IS 6 BP 830 EP 835 DI 10.1001/archneur.64.6.830 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 177HF UT WOS:000247143500007 PM 17562930 ER PT J AU Blacker, D Lee, H Muzikansky, A Martin, EC Tanzi, R McArdle, JJ Moss, M Albert, M AF Blacker, Deborah Lee, Hang Muzikansky, Alona Martin, Emily C. Tanzi, Rudolph McArdle, John J. Moss, Mark Albert, Marilyn TI Neuropsychological measures in normal individuals that predict subsequent cognitive decline SO ARCHIVES OF NEUROLOGY LA English DT Article ID PRECLINICAL ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; OLDER-ADULTS; WORK GROUP; DEMENTIA; IMPAIRMENT; MEMORY; NEUROPATHOLOGY; ASSOCIATION; ONSET AB Objective: To examine neuropsychological measures among normal individuals that predict time to subsequent cognitive decline. Design: Cognitive performance, as measured by 6 neuropsychological tests, was examined at baseline. Participants were followed up for approximately 5 years. Cox proportional hazards models were used to evaluate the neuropsychological measures at baseline that predicted time to progression from normal cognition to mild impairment. Comparable data also examined time to progression from mild impairment to a diagnosis of Alzheimer disease. Setting: Community volunteer- based sample examined at a medical institution. Participants: One hundred and seven individuals who were cognitively normal and 235 individuals with mild cognitive impairment at baseline. Main Outcome Measures: Time to progression from normal cognition to mild impairment and time to progression from mild impairment to a diagnosis of Alzheimer disease. Results: The risk of progressing from normal to mild impairment was considerably greater among those with lower scores on tests of episodic memory ( eg, hazard ratio for a 1-SD decrease in the California Verbal Learning Test, 0.55; P<. 001). Normal individuals who carried at least 1 copy of the apolipoprotein E epsilon 2 allele were less likely to develop cognitive impairments over time than individuals with no epsilon 2 allele ( hazard ratio for presence of allele, 0.13; P=. 006). Measures of both episodic memory and executive function were significant predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease ( eg, hazard ratio for a 1-SD decrease in California Verbal Learning Test score, 0.67; P=. 005; hazard ratio for a 1-SD increase in the time to complete part B of the Trail Making test, 1.40; P=. 007). Among individuals with mild impairments, the apolipoprotein E epsilon 4 allele increased risk for Alzheimer disease in a dose- dependent manner; however, this effect was not significant within the context of multivariable models. Conclusions: Episodic memory performance among normal individuals predicts time to progression to mild impairment while apolipoprotein E e2 status is associated with lower risk of cognitive decline among normal individuals. Tests of both episodic memory and executive function are predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Boston Univ, Dept Anat & Neurobiol, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Albert, M (reprint author), 1620 McElderry St,Reed Hall E 2, Baltimore, MD 21205 USA. EM malbert9@jhmi.edu FU NIA NIH HHS [P50 AG05146, P01 AG04953] NR 53 TC 126 Z9 131 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2007 VL 64 IS 6 BP 862 EP 871 DI 10.1001/archneur.64.6.862 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 177HF UT WOS:000247143500012 PM 17562935 ER PT J AU Khan, BF Harissi-Dagher, M Pavan-Langston, D Aquavella, JV Dohlman, CH AF Khan, Bilal F. Harissi-Dagher, Mona Pavan-Langston, Deborah Aquavella, James V. Dohlman, Claes H. TI The Boston keratoprosthesis in herpetic keratitis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 04, 2006 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID REPEAT PENETRATING KERATOPLASTY; CORNEAL TRANSPLANTATION; SIMPLEX KERATITIS; SURVIVAL; OUTCOMES; MANAGEMENT; PROGNOSIS; GLAUCOMA AB Objective: To evaluate the role of an artificial cornea ( Boston Keratoprosthesis [ KPro]) in herpetic corneal graft failures. Methods: A series of 17 herpetic eyes of 14 patients with failed transplantations, treated with implantation of a corneal graft with a KPro, was reviewed. Outcomes measured were retention of the device, visual acuity at 1 week, best visual acuity, last assessed visual acuity, time of follow-up, and complications. Results: Follow-up ranged between 6 and 72 months ( median, 14 months). All patients had improvement in postoperative visual acuity, with 16 ( 94%) of 17 eyes getting better than preoperative visual acuity within 1 week. Of the 17 eyes, 15 ( 88%) achieved a best visual acuity of 20/25 to 20/70 and, at the last examination, 11 eyes ( 73%) were still in that range. Four patients with prolonged preoperative inflammation and ulceration at KPro placement had resolution of inflammation within days. The KPro had no extrusions. Complications included retroprosthesis membrane in 3 eyes and 1 tissue melt in an early case. Conclusions: The KPro can be of value in patients with graft failure from herpetic keratitis, even in the inflamed stage. We believe that herpetic keratitis is not a contraindication for KPro use. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Cornea & Refract Surg, Boston, MA 02115 USA. Univ Rochester, Inst Eye, Rochester, NY USA. RP Dohlman, CH (reprint author), 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu NR 24 TC 20 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2007 VL 125 IS 6 BP 745 EP 749 DI 10.1001/archopht.125.6.745 PG 5 WC Ophthalmology SC Ophthalmology GA 177HG UT WOS:000247143600003 PM 17562983 ER PT J AU Chen, L Huq, S Gardner, H de Fougerolles, AR Barabino, S Dana, MR AF Chen, Lu Huq, Syed Gardner, Humphrey de Fougerolles, Antonin R. Barabino, Stefano Dana, M. Reza TI Very late antigen 1 blockade markedly promotes survival of corneal allografts SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTEGRIN ALPHA-1; LYMPHATIC-SYSTEM; LYMPHANGIOGENESIS; REJECTION; NEOVASCULARIZATION; TRANSPLANTATION; HEMANGIOGENESIS; ANGIOGENESIS; INFLAMMATION; IMMUNOLOGY AB Objective: To investigate the role of very late antigen 1 ( VLA-1) ( also known as integrin receptor alpha(1)beta(1)) in corneal transplantation inflammation and allograft survival. Methods: Cell infiltration and vasculogenesis ( both angiogenesis and lymphangiogenesis) associated with allodisparate corneal transplantation were assessed in VLA-1-deficient conditions and controls by immunofluorescent microscopic studies. Corneal allograft survival was also assessed after anti-VLA-1 antibody treatment and in VLA-1 knockout recipient mice. Results: Anti-VLA-1 antibody treatment leads to a profound reduction in the granulocytic, monocytic, and T-cell infiltration after corneal transplantation. In addition, corneal angiogenesis and lymphangiogenesis were both significantly suppressed in VLA-1 knockout mice. Remarkably, universal graft survival was observed in both anti VLA-1 antibody treatment and knockout mice. Conclusions: Very late antigen 1 blockade markedly reduces inflammation and inflammation-induced tissue responses, including vasculogenic responses, associated with corneal transplantation and promotes allograft survival. Clinical Relevance: These studies offer insights into important integrin-mediated mechanisms of corneal transplant - related inflammation and provide possible new integrin-based immunotherapies for transplant rejection. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lan Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Biogen Inc, Res Pathol, Cambridge, MA USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lan Immunol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu FU NEI NIH HHS [EY014786, EY12963, F32 EY014786, R01 EY012963, R01 EY012963-07] NR 29 TC 28 Z9 28 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2007 VL 125 IS 6 BP 783 EP 788 DI 10.1001/archopht.125.6.783 PG 6 WC Ophthalmology SC Ophthalmology GA 177HG UT WOS:000247143600008 PM 17562989 ER PT J AU Loewenstein, JI Warden, SM Pachydaki, SI Christoforidis, JB D'Amico, DJ AF Loewenstein, John I. Warden, Scott M. Pachydaki, Sophia I. Christoforidis, John B. D'Amico, Donald J. TI Choroidal neovascularization following macular surgery - Reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM john_loewenstein@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2007 VL 125 IS 6 BP 857 EP 857 DI 10.1001/archopht.125.6.857 PG 1 WC Ophthalmology SC Ophthalmology GA 177HG UT WOS:000247143600035 ER PT J AU Teruya, J Van Cott, EM AF Teruya, Jun Van Cott, Elizabeth M. TI Questions and perspective on laboratory hypercoagulation testing SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material C1 Texas Childrens Hosp, Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Boston, MA 02114 USA. RP Teruya, J (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pathol, MC 1-2261,6621 Fannin St, Houston, TX 77030 USA. EM jteruya@bcm.edu NR 1 TC 0 Z9 0 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 JUN PY 2007 VL 131 IS 6 BP 864 EP 865 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 178RO UT WOS:000247238000004 ER PT J AU Rahemtullah, A Van Cott, EM AF Rahemtullah, Aliyah Van Cott, Elizabeth M. TI Hypercoagulation testing in ischemic stroke SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID C-REACTIVE PROTEIN; FACTOR-V-LEIDEN; CEREBRAL VENOUS THROMBOSIS; CORONARY-HEART-DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; DENSITY-LIPOPROTEIN CHOLESTEROL; INHERITED PROTHROMBOTIC CONDITIONS; INDEPENDENT RISK-FACTOR; APPARENTLY HEALTHY-MEN; ANTICARDIOLIPIN ANTIBODIES AB Context. - The utility of laboratory testing for hypercoagulability in the setting of stroke is uncertain. Objective. - To review the current literature and to make recommendations with regard to laboratory testing for various hypercoagulability risk factors for ischemic stroke. Data Sources. - Published articles studying the utility of various hypercoagulation tests in predicting initial and/or recurrent stroke or transient ischemic attack as well as cerebral vein thrombosis were collected and reviewed, with an emphasis on prospective studies. Conclusions. - Certain tests, such as C-reactive protein, homocysteine, antiphospholipid antibodies, and lipoprotein(a), may be useful in patients with a history of stroke or at high risk for stroke, as evidenced by prospective data. Factor V Leiden, prothrombin G20210A, protein C, protein S, and antithrombin are not recommended for routine testing but may be useful in certain populations, such as in pediatric patients or in patients with cerebral vein thrombosis. C1 Massachusetts Gen Hosp, Coagulat Lab, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Coagulat Lab, Div Lab Med, Dept Pathol, Jackson 235,55 Fruit St, Boston, MA 02114 USA. NR 142 TC 27 Z9 27 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 JUN PY 2007 VL 131 IS 6 BP 890 EP 901 PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 178RO UT WOS:000247238000008 PM 17550316 ER PT J AU Dicianno, BE Tovey, E AF Dicianno, Brad E. Tovey, Elyn TI Power mobility device provision: Understanding medicare guidelines and advocating for clients SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE insurance; medicare; public policy; rehabilitation; wheelchairs AB The Centers for Medicare and Medicaid (CMS) issued a new national coverage determination (NCD) for mobility assistive equipment (MAE) including wheelchairs in May 2005. CMS then issued a Final Rule in April 2006 that outlined significant changes required for documentation for prescribing MAE. Other insurance providers have since adopted and sometimes modified the NCD criteria and have begun to apply these criteria according to their own interpretations because some of the criteria are vague. In this report, we introduce a case example to show the components of the CMS NCD criteria, what was intended but poorly described in the language, how insurance providers may misinterpret or alter the criteria, and how clinicians can act as advocates. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Lab, Ctr Excellence Wheelchairs & Asocciated Rehabil E, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Med Phys, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Rehabil Inst Rehabil & Res, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Assist Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Phys Therapy, Pittsburgh, PA 15260 USA. RP Dicianno, BE (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Lab, Ctr Excellence Wheelchairs & Asocciated Rehabil E, 7180 Highland Dr,Bldg 4,2nd Fl E,151R1-H, Pittsburgh, PA 15206 USA. EM diciannob@herlpitt.org OI Dicianno, Brad/0000-0003-0738-0192 NR 26 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2007 VL 88 IS 6 BP 807 EP 816 DI 10.1016/j.apmr.2007.03.024 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 177AK UT WOS:000247125800021 PM 17532908 ER PT J AU Qiao, M Kisgati, M Cholewa, JM Zhu, WF Smart, EJ Sulistio, MS Asmis, R AF Qiao, Mu Kisgati, Marta Cholewa, Jill M. Zhu, Weifei Smart, Eric J. Sulistio, Melanie S. Asmis, Reto TI Increased expression of glutathione reductase in macrophages decreases atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; glutathione; macrophage; oxidized low-density lipoprotein; oxidative stress ID OXIDATIVE MODIFICATION HYPOTHESIS; INDUCED CELL INJURY; ATHEROGENESIS; CDNA; GENE; GLUTAREDOXIN; DYSFUNCTION; MECHANISMS; APOPTOSIS; SEQUENCE AB Objective-Thiol oxidative stress leads to macrophage dysfunction and cell injury, and has been implicated in the development of atherosclerotic lesions. We investigated if strengthening the glutathione-dependent antioxidant system in macrophages by overexpressing glutathione reductase (GR) decreases the severity of atherosclerosis. Methods and Results-Bone marrow cells infected with retroviral vectors expressing either enhanced green fluorescent protein (EGFP) or an EGFP-fusion protein of cytosolic GR (GR(cyto)-EGFP) or mitochondrial GR (GR(mito)-EGFP) were transplanted into low-density lipoprotein receptor-deficient mice. Five weeks after bone marrow transplantation, animals were challenged with a Western diet for 10 weeks. No differences in either plasma cholesterol and triglyceride levels or peritoneal macrophage content were observed. However, mice reconstituted with either GR(cyto)-EGFP or GR(mito)-EGFP-expressing bone marrow had lesion areas (P<0.009) that were 32% smaller than recipients of EGFP-expressing bone marrow. In cultured macrophages, adenovirus-mediated overexpression of GR(cyto)-EGFP or GR(mito)-EGFP protected cells from mitochondrial hyperpolarization induced by oxidized low-density lipoprotein. Conclusion-This study provides direct evidence that the glutathione-dependent antioxidant system in macrophages plays a critical role in atherogenesis, and suggests that thiol oxidative stress-induced mitochondrial dysfunction contributes to macrophage injury in atherosclerotic lesions. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Kenezy Gyula Hosp, Dept Lab Med, Debrecen, Hungary. Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA. Univ Kentucky, Dept Pediat, Lexington, KY USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX USA. RP Asmis, R (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM asmis@uthscsa.edu FU NHLBI NIH HHS [HL-70963] NR 32 TC 31 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP 1375 EP 1382 DI 10.1161/ATVBAHA.107.142109 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600022 PM 17363688 ER PT J AU Sugita, M Sugita, H Kaneki, M AF Sugita, Michiko Sugita, Hiroki Kaneki, Masao TI Farnesyltransferase inhibitor, manumycin A, prevents atherosclerosis development and reduces oxidative stress in apolipoprotein E-deficient mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apoE-deficient mice; atherosclerosis; farnesyltransferase; oxidative stress; Ras ID VASCULAR SMOOTH-MUSCLE; COA REDUCTASE INHIBITOR; ACUTE CORONARY SYNDROMES; NITRIC-OXIDE SYNTHASE; CHLAMYDIA-PNEUMONIAE; IN-VIVO; VITAMIN-E; ENDOTHELIAL DYSFUNCTION; CELL-PROLIFERATION; INSULIN-RESISTANCE AB Objective-Statins are presumed to exert their antiatherogenic effects in part via lipid-lowering-independent mechanisms. Inhibition of protein farnesylation and/or geranylgeranylation by statins has been postulated to contribute to the lipid-lowering-independent effects. However, a role for protein farnesylation in atherogenesis has not yet been studied. Therefore, we examined the effects of farnesyltransferase inhibitor, manumycin A, on the development of atherosclerosis in apolipoprotein E (apoE)-deficient mice fed a high-fat diet. Methods and Results-Manumycin A treatment for 22 weeks decreased Ras activity, and reduced fatty streak lesion size at the aortic sinus to 43% of that in vehicle-treated apoE-deficient mice (P<0.05), while plasma total cholesterol was unaltered. Moreover, manumycin A reduced a-smooth muscle actin-positive area to 29% of that in vehicle-treated apoE-deficient mice (P<0.01). The prevention of atherogenesis by manumycin A was accompanied by amelioration of oxidative stress, as judged by reduced ex vivo superoxide production and nitrotyrosine immunoreactivity. Conclusions-These results indicate that the inhibition of farnesyltransferase prevents the development of mature atherosclerosis with concomitant alleviation of oxidative stress in apoE-deficient mice. The present data highlight farnesyltransferase as a potential molecular target for preventive and/or therapeutic intervention against atherosclerosis. C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp,Shriners Hosp Children, Charlestown, MA 02129 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp,Shriners Hosp Children, 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@partners.org FU NIDDK NIH HHS [R01DK058127] NR 50 TC 25 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP 1390 EP 1395 DI 10.1161/ATVBAHA.107.140673 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600024 PM 17363690 ER PT J AU Dai, QY Xu, MD Yao, M Sun, BG AF Dai, Qiuyan Xu, Mengdan Yao, Min Sun, Baogui TI MCP-1/CCR2 involves AT1 receptor antagonism induced anti-inflammation via PI3K/Akt in SHR SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arteriosclerosis, Thrombos & Vasc Biol, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Shanghai First Peoples Hosp, Shanghai, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E88 EP E88 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600315 ER PT J AU Hong, CC Peterson, QP Hong, JY Peterson, RT AF Hong, Charles C. Peterson, Quinn P. Hong, Ji-Young Peterson, Randall T. TI Chemical genetic analysis reveals the central role of phosphatidylinositol-3 kinase and MAP kinase/ERK signaling pathways in artery/vein specification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Massachusetts Gen Hosp, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E42 EP E42 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600074 ER PT J AU Iftilkhar, IH Blankfield, RP Harris, S AF Iftilkhar, Imran H. Blankfield, Robert P. Harris, Stuart TI Temperature and blood pressure following amlodipine overdose: A test of the thermoregulatory-vascular remodeling hypothesis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Fairview Hosp, Cleveland Clin, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E134 EP E134 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600551 ER PT J AU Maree, AO Dicker, P Curtin, RJ Jneid, H Crean, P Cox, D Palacios, IF Rosenfield, KA Fitzgerald, DJ AF Maree, Andrew O. Dicker, Patrick Curtin, Ronan J. Jneid, Hani Crean, Peter Cox, Dermot Palacios, Igor F. Rosenfield, Kenneth A. Fitzgerald, Desmond J. TI Platelet thromboxane assay is a good predictor of aspirin response SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Cleveland Clin, Cleveland, OH 44106 USA. St James Hosp, Dublin 8, Ireland. Univ Coll Dublin, Dublin 2, Ireland. 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E109 EP E109 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600427 ER PT J AU Chen, NC Martin, SD Gill, TJ AF Chen, Neal C. Martin, Scott D. Gill, Thomas J. TI Risk to the lateral geniculate artery during arthroscopic lateral meniscal suture passage SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE meniscal repair; inside out; outside in; lateral geniculate artery; arthroscopy ID 2ND-LOOK ARTHROSCOPY; HEALING RATE; REPAIR; COMPLICATIONS; ANEURYSM; TEARS; KNEE AB Purpose: The purpose of this study was to evaluate the risk of lateral geniculate artery injury during suture passage through the lateral meniscus. Methods: Sutures were passed via inside-out and outside-in techniques in 11 embalmed cadaveric knees. The number of punctures of the lateral geniculate artery and quantitative distances of needle penetrations were measured. Results: The lateral geniculate artery was punctured 7 times during inside-out passes through the junction of the middle and anterior third of the meniscus and 8 times during passes through the body of the middle third of the meniscus. During outside-in passes, there were 5 punctures when passing anterior to the lateral collateral ligament and 4 punctures when posterior to the ligament. Conclusions: The lateral geniculate artery is in close proximity to the lateral meniscus and is punctured often during in vitro inside-out meniscal repair in the embalmed cadaver model. Clinical Relevance: Methods of meniscal repair that do not violate the lateral geniculate artery may offer improved rates of healing and should be further evaluated. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Chen, NC (reprint author), Massachusetts Gen Hosp, Hand & Upper Extremity Serv, 55 Fruit St,Yawkey,Suite 2100, Boston, MA 02114 USA. NR 29 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD JUN PY 2007 VL 23 IS 6 BP 642 EP 646 DI 10.1016/j.arthro.2007.01.003 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 181BX UT WOS:000247412900010 PM 17560479 ER PT J AU Simpson, R Koester, H LoPresti, E AF Simpson, Richard Koester, Heidi LoPresti, Ed TI Selecting an appropriate scan rate: The ".65 rule" SO ASSISTIVE TECHNOLOGY LA English DT Article DE assessment; row-column scanning; physical impairment; assistive technology; computer access AB Investigators have discovered that the ratio between a user's reaction time and an appropriate scan rate for that user is approximately.65, which we refer to as "the.65 rule." As part of a larger effort to develop software that automatically adapts the configuration of switch access software, data were collected comparing subject performance with a scan rate chosen using the .65 rule and a scan rate chosen by the user. Analysis of the data indicates that for many people, the .65 rule produces a scan rate that is approximately the same as the average switch press time plus 2 standard deviations. Further analysis demonstrates a relationship between the coefficient of variation (the standard deviation divided by the mean) and error rate. If accurate information is available about the mean, standard deviation, and distribution of a client's switch press time, a scan rate can be chosen that will yield a specific error level. If a rigorous statistical approach is impractical, the .65 rule will generally yield a usable scan rate based on mean press time alone. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. Koester Performance Res, Ann Arbor, MI USA. AT Sci, Pittsburgh, PA USA. RP Simpson, R (reprint author), Forbes Tower,Suite 5044,Sennott & Atwoods St, Pittsburgh, PA 15260 USA. EM ris20@pitt.edu RI Simpson, Richard/G-5683-2015 OI Simpson, Richard/0000-0002-6306-9393 FU NICHD NIH HHS [1 R43 HD045015-01] NR 7 TC 4 Z9 4 U1 0 U2 0 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SUM PY 2007 VL 19 IS 2 BP 51 EP 58 PG 8 WC Rehabilitation SC Rehabilitation GA 190PR UT WOS:000248071800001 PM 17727073 ER PT J AU Chaves, ES Cooper, RA Collins, DM Karmarkar, A Cooper, R AF Chaves, Eliana S. Cooper, Rory A. Collins, Diane M. Karmarkar, Amol Cooper, Rosemarie TI Review of the use of physical restraints and lap belts with wheelchair users SO ASSISTIVE TECHNOLOGY LA English DT Review DE seat belts; lap belts; restraints; wheelchair falls; wheelchair transportation ID NURSING-HOME RESIDENTS; UNITED-STATES; SEAT-BELT; FALLS; ACCIDENTS; PREDICTORS; FACILITIES; LEGRESTS; INJURIES; TIPS AB Wheelchair-related physical restraints, lap belts, and other alternatives are intended to provide safe and adequate seating and mobility for individuals using wheelchairs. Physical restraints and lap belts are also helpful for positioning people in their wheelchairs to reduce the risk of injury during wheelchair tips and falls. However, when used improperly or in ways other than intended, injury or even death can result. Although widely prescribed, little evidence is available to direct professionals on the appropriate use of these restraints and lap belts and for whom these restraints are indicated. The purpose of this study was to conduct a review of available literature from 1966-2006 to identify the risks and benefits associated with lap belts while seated in wheelchairs. Twenty-five studies that met the inclusion criteria were reviewed. Nine studies reported the frequency of asphyxial deaths caused by physical restraints, nine studies reported the long-term complication and indirect adverse effects of physical restraints and lap-belt use, and seven studies reported the benefits of physical restraints and lap belts with individuals using wheelchairs. Despite the weak evidence, the results suggest a considerable number of deaths from asphyxia caused by the use of physical restraints occurred each year in the U.S. The majority of the deaths occurred in nursing homes, followed by hospitals, and then the home of the person. Most deaths occurred while persons were restrained in wheelchairs or beds. Based on that, caution needs to be exercised when using restraints or positioning belts. In addition, other seating and environment alternatives should be explored prior to using restraints or positioning belts, such as power wheelchair seating options. Positioning belts may reduce risk of falls from wheelchairs and should be given careful consideration, but caution should be exercised if the individual cannot open the latch independently. Also, the duration of use of the physical restraint should be limited. Therefore, several factors should be considered when devising a better quality of physical-restraint services provided by health care professionals. These efforts can lead to improved safety and quality of life for individuals who use wheelchairs. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rahabil Sci & Technol, Pittsburgh, PA 15260 USA. RP Cooper, R (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, HD 151 R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Karmarkar, Amol/E-6030-2011 OI Karmarkar, Amol/0000-0001-8355-1585 NR 45 TC 7 Z9 7 U1 1 U2 7 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SUM PY 2007 VL 19 IS 2 BP 94 EP 107 PG 14 WC Rehabilitation SC Rehabilitation GA 190PR UT WOS:000248071800004 PM 17727076 ER PT J AU Ardehali, R Nasir, K Kolandaivelu, A Budoff, MJ Blumenthal, RS AF Ardehali, Reza Nasir, Khurram Kolandaivelu, Aravindan Budoff, Matthew J. Blumenthal, Roger S. TI Screening patients for subclinical atherosclerosis with non-contrast cardiac CT SO ATHEROSCLEROSIS LA English DT Review DE coronary calcification; asymptomatic coronary artery disease; subclinical atherosclerosis; coronary artery disease risk assessment; electron beam computed tomography (EBCT) ID CORONARY-ARTERY CALCIUM; BEAM COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; ASYMPTOMATIC LOW-RISK; DISEASE EVENTS; CARDIOVASCULAR-RADIOLOGY; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; CLINICAL-CARDIOLOGY; NONINVASIVE TESTS AB Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. Traditional risk assessment may be refined with the selective use of coronary artery calcium score (CACS) or other methods of subclinical atherosclerosis measurement. This article reviews information pertaining to the clinical use of CACS for assessing coronary atherosclerosis as a useful predictor of coronary artery disease (CAD) in certain population of patients. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CACS for the presence of coronary artery disease but a much lower specificity for obstructive CAD depending on the magnitude of the CACS. Several large clinical trials have found clear, incremental predictive value of CACS over the Framingham risk score when used in asymptomatic patients. However, early detection of CAD by Electron Beam Tomography (EBT) screening has not convincingly demonstrated a reduction in mortality and morbidity. Nevertheless, relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of existing atherosclerotic vascular disease. Current data suggest intermediate-risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is effective at identifying increased risk and in one study motivating effective behavioral changes. Randomized clinical trials will help determine if selective use of cardiac CT in the intermediate-risk patient would lead to more appropriate use of pharmacologic therapy and improved clinical outcomes. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp Cardiac MRI, PET, CT Program, Boston, MA USA. Johns Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. Univ Calif Los Angeles, Div Cardiol, Torrance, CA USA. RP Ardehali, R (reprint author), Stanford Univ, Sch Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA. EM rardehali@cvmed.stanford.edu NR 54 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUN PY 2007 VL 192 IS 2 BP 235 EP 242 DI 10.1016/j.atherosclerosis.2007.03.022 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178MX UT WOS:000247225900001 PM 17467714 ER PT J AU Bacci, S Zhang, YY Boonyasrisawat, W Nolan, D Duffy, J Morini, E Turchi, F Salvemini, L Mangiacotti, D Mastroianno, S Menzaghi, C Prudente, S Doria, A Trischitta, V AF Bacci, S. Zhang, Y. Y. Boonyasrisawat, W. Nolan, D. Duffy, J. Morini, E. Turchi, F. Salvemini, L. Mangiacotti, D. Mastroianno, S. Menzaghi, C. Prudente, S. Doria, A. Trischitta, V. TI Combined effect of K121Q of ENPP1 (PC-1) and Q84R of TRIB3 on age at myocardial infarction in type 2 diabetic patients SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 IRCCS, Diabet & Endocrine Unit, San Giovanni Rotondo, Italy. Harvard Med Sch, Joslin Diabet Ctr, Div Res, Boston, MA USA. Univ Rome, Rome, Italy. CSS Mendel Inst, Rome, Italy. RI Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016 OI Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 48 EP 49 DI 10.1016/S1567-5688(07)71136-4 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100190 ER PT J AU Erbay, SH O'Callaghan, MG Shah, P Kini, J Basset-Midle, J AF Erbay, S. H. O'Callaghan, M. G. Shah, P. Kini, J. Basset-Midle, J. TI Prospective evaluation of the role of the atherosclerosis on cerebral atrophy: Pilot study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Univ Washington, Dept Radiol, Harborview Med Ctr, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Biostat, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 146 EP 146 DI 10.1016/S1567-5688(07)71534-9 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100585 ER PT J AU Raal, FJ Marais, AD Gagne, C Gaudet, D Viljoen, J Hemphill, L Durham, K Thuren, T Shears, C AF Raal, F. J. Marais, A. D. Gagne, C. Gaudet, D. Viljoen, J. Hemphill, L. Durham, K. Thuren, T. Shears, C. TI Torcetrapibiatorvastatin substantially raises HDL-C and markedly lowers LDL-C in patients with homozygous familial hypercholesterolemia SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society/15th Paavo Nurmi Symposium CY JUN 10-13, 2007 CL Univ Helsinki, Helsinki, FINLAND SP European Atherosclerosis Soc HO Univ Helsinki C1 Univ Witwatersrand, Johannesburg Hosp, Dept Med, Div Endocrinol & Metab, Johannesburg, South Africa. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Cape Town, ZA-7925 Cape Town, South Africa. CHUQ, Dept Med, Clin Malad Lipid Quebec, Quebec City, PQ, Canada. Communautaire Complexe Hosp Sagamie, Ctr Med Gen, Clin Lipides, Chicoutimi, PQ, Canada. Genclin Corp, Bloemfontein, South Africa. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, Pfizer Global Res & Dev, New London, CT USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 EI 1878-5050 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 204 EP 204 DI 10.1016/S1567-5688(07)71774-9 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100822 ER PT J AU Sloan, DM Marx, BP Epstein, EM Lexington, JM AF Sloan, Denise M. Marx, Brian P. Epstein, Eva M. Lexington, Jennifer M. TI Does altering the writing instructions influence outcome associated with written disclosure? SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; BREAST-CANCER PATIENTS; EMOTIONAL EXPRESSION; PROLONGED EXPOSURE; PHYSICAL HEALTH; HEART-RATE; EVENTS; BEREAVEMENT; EXPERIENCES; VALIDATION AB This study examined the effect of changing the instructional set for written disclosure on psychological and physical health reports among traumatized college students with current posttraumatic stress symptoms. Eighty-two participants were randomly assigned to one of three writing conditions that focused on emotional expression (EE), insight and cognitive assimilation, or to a control condition. Participants assigned to the EE condition reported significant improvements in psychological and physical health 1 month following the writing sessions relative to the other two conditions. The EE participants also reported and displayed significantly greater initial psychophysiological reactivity and subsequent habituation compared with the other two conditions. These findings suggest the importance of emphasizing emotional expression during written disclosure and underscore the importance of examining how modifying the written disclosure protocol can affect outcome. C1 [Sloan, Denise M.; Marx, Brian P.; Epstein, Eva M.; Lexington, Jennifer M.] Temple Univ, Philadelphia, PA 19122 USA. RP Sloan, DM (reprint author), VA Boston Healthcare System, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov FU NIMH NIH HHS [R03 MH068223, MH068223] NR 47 TC 39 Z9 40 U1 0 U2 5 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2007 VL 38 IS 2 BP 155 EP 168 DI 10.1016/j.beth.2006.06.005 PG 14 WC Psychology, Clinical SC Psychology GA 323BH UT WOS:000257418500005 PM 17499082 ER PT J AU Bar, M AF Bar, Moshe TI The continuum of "looking forward," and paradoxical requirements from memory SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID EPISODIC MEMORY; FUTURE; MECHANISMS; IMAGINE; AMNESIA; BRAIN AB The claim that nonhuman animals lack foresight is common and intuitive. I propose an alternative whereby foresight is a gradual continuum in that it is present in animals to the extent that it is needed. A second aspect of this commentary points out that the requirements that the memory that mediates foresight be both specific yet flexible seem contradictory. C1 [Bar, Moshe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. RP Bar, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. EM bar@nmr.mgh.harvard.edu OI Suddendorf, Thomas/0000-0003-3328-7442 NR 14 TC 5 Z9 5 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2007 VL 30 IS 3 BP 315 EP + DI 10.1017/S0140525X07002002 PG 9 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 286LQ UT WOS:000254847800036 ER PT J AU Buckner, RL AF Buckner, Randy L. TI Prospection and the brain SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID FUTURE; MEMORY; EVOLUTION; STATE AB Suddendorf & Corballis (S&C) propose that the capacity to flexibly forsee the future was a critical step in human evolution and is accomplished by a set of component processes that can be likened to a theater production. Understanding the brain-bases of these functions may help to clarify the hypothesized component processes, inform us of how and when they are used adaptively, and also provide empirical ways of exploring to what degree these abilities exist and are implemented similarly (or differently) across species. C1 [Buckner, Randy L.] Harvard Univ, Athinoula A Martinos Ctr, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Psychol,Ctr Brain Sci, Cambridge, MA 02138 USA. RP Buckner, RL (reprint author), Harvard Univ, Athinoula A Martinos Ctr, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Psychol,Ctr Brain Sci, Cambridge, MA 02138 USA. EM rbuckner@wjh.harvard.edu NR 14 TC 1 Z9 1 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2007 VL 30 IS 3 BP 318 EP + DI 10.1017/S0140525X07002038 PG 9 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 286LQ UT WOS:000254847800039 ER PT J AU Zhang, HM Qin, GJ Liang, G Li, JN Barrington, RA Liu, DX AF Zhang, Haimou Qin, Gangjian Liang, Gang Li, Jinan Barrington, Robert A. Liu, Dong-xu TI C5aR-mediated myocardial ischemia/reperfusion injury SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE complement; C5aR; myocardial cell; ischemia/reperfusion; signaling ID C5A RECEPTOR ANTAGONIST; ISCHEMIA-REPERFUSION INJURY; ENDOTHELIAL-CELLS; G-PROTEIN; COMPLEMENT; ANAPHYLATOXIN; INFLAMMATION; NEUTROPHILS; APOPTOSIS; INHIBITION AB The complement system activation can mediate myocardial ischemia and reperfusion (I/R). Inhibition of C5a activity reveals attenuation of I/R-induced myocardial infarct size. However, the contribution of C5a receptor (C5aR) to I/R injury remains to be unknown. Here, we reported that both mRNA and protein for the C5aR were constitutively expressed on cardiomyocytes and upregulated as a function of time after I/R-induced myocardial cell injury in mice. Blockade of C5aR markedly decreased microvascular permeability in ischemic myocardial area and leukocyte adherence to coronary artery endothelium. Importantly, the blocking of C5aR with an anti-C5aR antibody was associated with inhibition in activation of protein kinase C delta (PKC-delta) and induction of PKC-mediated mitogen-activated protein kinase phosphatases-1 (MKP-1) leading to the increased activity of p42/p44 mitogen-activated protein (MAP) kinase cascade. These data provide evidence that C5aR-mediated myocardial cell injury is an important pathogenic factor, and that C5aR blockade may be useful therapeutic targets for the prevention of myocardial I/R injury. (c) 2007 Elsevier Inc. All rights reserved. C1 Hubei Univ, Ctr Infect & Immun Res, Sch Life Sci, Wuhan, Peoples R China. Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. Harvard Univ, Childrens Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, CBR Inst Biomed Res, Sch Med, Cambridge, MA 02138 USA. RP Liu, DX (reprint author), Hubei Univ, Ctr Infect & Immun Res, Sch Life Sci, 11 XueYuan Rd, Wuhan, Peoples R China. EM dxliu001@yahoo.com NR 34 TC 27 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 1 PY 2007 VL 357 IS 2 BP 446 EP 452 DI 10.1016/j.bbrc.2007.03.152 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 164SE UT WOS:000246253700020 PM 17416341 ER PT J AU Riese, DJ Gallo, RM Settleman, J AF Riese, David J., II Gallo, Richard M. Settleman, Jeffrey TI Mutational activation of ErbB family receptor tyrosine kinases: insights into mechanisms of signal transduction and tumorigenesis SO BIOESSAYS LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; CONSTITUTIVELY ACTIVE ERBB4; CELL LUNG-CANCER; TRANSMEMBRANE DOMAIN; POINT MUTATION; EGF RECEPTORS; EXTRACELLULAR REGION; SOMATIC MUTATIONS; COLONY FORMATION; DIMER INTERFACE AB Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations. C1 Purdue Canc Res Ctr, W Lafayette, IN 47907 USA. Purdue Univ, Sch Pharm, W Lafayette, IN 47907 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Riese, DJ (reprint author), Purdue Canc Res Ctr, HANS 114,201 S Univ St, W Lafayette, IN 47907 USA. EM driese@purdue.edu FU NCI NIH HHS [R01 CA115830-04, R01 CA114209-01A2, R01 CA114209-02, R01 CA114209-03, R01 CA114209-04, R01 CA115830-01, R01 CA115830-02, R01 CA115830-03, R01 CA115830-05] NR 65 TC 50 Z9 54 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUN PY 2007 VL 29 IS 6 BP 558 EP 565 DI 10.1002/bies.20582 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 173JC UT WOS:000246868300007 PM 17508401 ER PT J AU Glahn, DC Lovallo, WR Fox, PT AF Glahn, David C. Lovallo, William R. Fox, Peter T. TI Reduced amygdala activation in young adults at high risk of alcoholism: Studies from the Oklahoma family health patterns project SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; amygdala; behavioral disinhibition; fMRI; risk factors ID DECISION-MAKING; USE DISORDERS; SUBSTANCE USE; HISTORY; CORTEX; ABUSE; RECOGNITION; POPULATION; ALLOSTASIS; CORTISOL AB Background: Risk of alcoholism is higher in those with a positive family history (FH+) and in those showing behavioral disinhibition, possibly reflecting altered limbic system function. Methods: We performed functional magnetic resonance imaging (fMRI) in 17 nonabusing young adults, 9 with FH+ and high in disinhibition versus 8 with a negative family history (FH-) and low in disinhibition. We probed limbic system reactivity with a recognition task using faces expressing fear versus geometric objects. Results: Subjects with FH- had robust activation to the faces in the region of the right and left amygdalar complexes (p's <.05), while subjects with FH+ had no such activation (p's >.46). The blood oxygenation level-dependent (BOLD) signal in the region of the amygdala was correlated with scores on the self-report measure of temperament in the combined groups (r =.51, p <.04). Conclusions: Behaviorally disinhibited temperament, found in many with FH+, may be associated with amygdalar hyporesponsiveness and a failure to avoid risky decisions, increasing the person's liability for alcohol abuse. C1 Vet Affairs Med Ctr, Behav Sci Labs, Oklahoma City, OK 73104 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78285 USA. RP Lovallo, WR (reprint author), Vet Affairs Med Ctr, Behav Sci Labs, 151A,921 NE 13th St, Oklahoma City, OK 73104 USA. EM bill@mindbody1.org RI Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [M01 RR001346, RR14467, M01 RR014467, M01-RR-01346]; NIAAA NIH HHS [R01 AA012207, R01 AA012207-03, AA12207] NR 31 TC 67 Z9 67 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2007 VL 61 IS 11 BP 1306 EP 1309 DI 10.1016/j.biopsych.2006.09.041 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 172UK UT WOS:000246829700011 PM 17306772 ER PT J AU Armand, P Kim, HT DeAngelo, DJ Ho, VT Cutler, CS Stone, RM Ritz, J Alyea, EP Antin, JH Soiffer, RJ AF Armand, Philippe Kim, Haesook T. DeAngelo, Daniel J. Ho, Vincent T. Cutler, Corey S. Stone, Richard M. Ritz, Jerome Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. TI Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE allogeneic stem cell transplantation; cytogenetics; acute myelogenous leukemia; myelodysplastic syndrome; secondary leukemia; therapy-related disease ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MYELODYSPLASTIC SYNDROME; GROUP-B; PROGNOSTIC-SIGNIFICANCE; HODGKINS-LYMPHOMA; ADULT PATIENTS; ABNORMALITIES; MUTATIONS AB Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). However, it is unclear whether currently accepted cytogenetic risk groups, which were established for patients treated mostly with standard therapy, are optimally discriminating for patients undergoing HSCT. Also, the impact of cytogenetics in the growing population of patients with therapy-related disease has not been completely elucidated. In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution. We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and nonrelapse mortality for the 476 patients with de novo disease. We used these results to establish an optimal cytogenetic grouping scheme. We then applied this grouping scheme to the 80 patients with therapy-related disease. Our proposed 3-group cytogenetic classification outperformed the established grouping schemes for both de novo, and therapy-related disease. When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on nonrelapse mortality). After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo, disease. This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database. (C) 2007 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM rsoiffer@partners.org FU NCI NIH HHS [T32 CA009172]; NHLBI NIH HHS [P01 HL070149, P01 HL 070149]; NIAID NIH HHS [U19 AI 29530, U19 AI029530, U19 AI029530-14] NR 39 TC 78 Z9 78 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2007 VL 13 IS 6 BP 655 EP 664 DI 10.1016/j.bbmt.2007.01.079 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 181GQ UT WOS:000247425600004 PM 17531775 ER PT J AU Pennell, NA Sequist, LV AF Pennell, Nathan A. Sequist, Lecia V. TI Assessing the roles of EGFR gene copy number, protein expression and mutation in predicting,outcomes in non-small-cell lung cancer after treatment with EGFR inhibitors SO BIOMARKERS IN MEDICINE LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PREVIOUSLY TREATED PATIENTS; SOUTHWEST-ONCOLOGY-GROUP; PHASE-III TRIAL; BRONCHIOLOALVEOLAR-CARCINOMA; MOLECULAR PREDICTORS; GEFITINIB THERAPY; IN-SITU; ERLOTINIB; CARBOPLATIN AB In this article, we critically evaluate a recent publication that assessed molecular predictors of clinical benefit from treatment with gefitinib, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), in patients with advanced non-small-cell lung cancer. EGFR inhibitors, such as gefitinib, have previously been shown to preferentially benefit distinct subgroups of advanced non-small-cell lung cancer patients, and strategies to prospectively identify these subgroups are under active investigation. In this study, the authors analyzed tissue from a randomized Phase III trial to examine the association of clinical benefit after gefitinib treatment with EGFR protein expression, EGFR gene copy number, EGFR mutations and other potential predictive markers. The paper by Hirsch and colleagues will be discussed and compared with other studies of potentially useful EGFR biomarkers. C1 [Pennell, Nathan A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pennell, Nathan A.; Sequist, Lecia V.] Harvard Univ, Sch Med, MGH Canc Ctr, Boston, MA USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 28 TC 0 Z9 0 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD JUN PY 2007 VL 1 IS 1 BP 203 EP 207 DI 10.2217/17520363.1.1.203 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 248AN UT WOS:000252123800023 PM 20477469 ER PT J AU Cook, AJ Gold, DR Li, Y AF Cook, Andrea J. Gold, Diane R. Li, Yi TI Spatial cluster detection for censored outcome data SO BIOMETRICS LA English DT Article DE asthma; cluster detection; cumulative residuals; martingales; spatial scan statistic ID UNITED-STATES; PREVALENCE; CHILDREN; ASTHMA; MODEL; RESIDUALS AB While numerous methods have been proposed to test for spatial cluster detection, in particular for discrete outcome data (e.g., disease incidence), few have been available for continuous data that are subject to censoring. This article provides an extension of the spatial scan statistic (Kulldorff, 1997, Communications in Statistics 26, 1481-1496) for censored outcome data and further proposes a simple spatial cluster detection method by utilizing cumulative martingale residuals within the framework of the Cox's proportional hazards models. Simulations have indicated good performance of the proposed methods, with the practical applicability illustrated by an ongoing epidemiology study which investigates the relationship of environmental exposures to asthma, allergic rhinitis/hayfever, and eczema. C1 Univ Washington, Dept Biostat, Seattle, WA 98105 USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98101 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cook, AJ (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98105 USA. EM acook@u.washington.edu FU NCI NIH HHS [R01 CA95747]; NIAID NIH HHS [R01 AI/EHS 35786] NR 19 TC 16 Z9 16 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2007 VL 63 IS 2 BP 540 EP 549 DI 10.1111/j.1541-0420.2006.00714.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 172ZS UT WOS:000246843900026 PM 17688506 ER PT J AU Ostacher, MJ Perlis, RS Nierenberg, AA Calabrese, JR Salloum, IM Fossey, MD Thase, ME Sachs, GS Weiss, RD AF Ostacher, M. J. Perlis, R. S. Nierenberg, A. A. Calabrese, J. R. Salloum, I. M. Fossey, M. D. Thase, M. E. Sachs, G. S. Weiss, R. D. TI Recovery from depression in patients with bipolar disorder and comorbid substance and alcohol use disorders: prospective findings from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE major depressive episode; substance use disorders; alcohol use disorders; comorbidity; recovery C1 [Ostacher, M. J.; Perlis, R. S.; Nierenberg, A. A.; Sachs, G. S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ostacher, M. J.; Perlis, R. S.; Nierenberg, A. A.; Sachs, G. S.; Weiss, R. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calabrese, J. R.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. [Calabrese, J. R.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Salloum, I. M.; Thase, M. E.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Fossey, M. D.] Univ Oklahoma, Tulsa Med Coll, Dept Psychiat, Tulsa, OK USA. [Weiss, R. D.] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 10 EP 10 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000028 ER PT J AU Zeber, JE Copeland, LA McCarthy, JF Bauer, MS Kilbourne, AM AF Zeber, J. E. Copeland, L. A. McCarthy, J. F. Bauer, M. S. Kilbourne, A. M. TI Self-reported access to medical and psychiatric care in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE access; treatment barriers; veterans C1 [Zeber, J. E.; Copeland, L. A.] S Texas Vet Hlth Care Syst Verdict, San Antonio, TX USA. [Zeber, J. E.; Copeland, L. A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [McCarthy, J. F.; Kilbourne, A. M.] Univ Michigan, Va Ann Arbor Healthcare Syst, Serious Menatal Illness Treatment Res & Educ Ctr, Ann Arbor, MI USA. [McCarthy, J. F.; Kilbourne, A. M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI USA. [Bauer, M. S.] Brown Univ, Dept Psychiat, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 12 EP 12 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000033 ER PT J AU Abulseoud, OA Hellemann, G Frye, MA Altshuler, LL Keck, PE Mcelroy, SL Suppes, T Nolen, WA Kupka, RW Grunze, H Leverich, GS Post, RM AF Abulseoud, O. A. Hellemann, G. Frye, M. A. Altshuler, L. L. Keck, P. E., Jr. Mcelroy, S. L. Suppes, T. Nolen, W. A. Kupka, R. W. Grunze, H. Leverich, G. S. Post, R. M. TI Mood stabilizer and subsequent need for adjunctive antidepressant: naturalistic follow up of the SFBN SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar; depression; antidepressant; mood stabilizer C1 [Abulseoud, O. A.; Hellemann, G.; Frye, M. A.; Altshuler, L. L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Abulseoud, O. A.; Hellemann, G.; Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Frye, M. A.] Mayo Coll Med, Rochester, MN USA. [Mcelroy, S. L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Suppes, T.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kupka, R. W.] Altrech Inst Mental Hlth Care, Utrecht, Netherlands. [Grunze, H.] LMU Munioh, Munich, Germany. [Leverich, G. S.; Post, R. M.] Natl Inst Hlth, NIMH, Bethesda, MD USA. [Post, R. M.] Penn State Coll Med, Hershey, PA USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 13 EP 13 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000034 ER PT J AU Centorrino, F Talamo, A Lee, HB Ujkaj, M Cincotta, SL Baldessarini, RJ AF Centorrino, F. Talamo, A. Lee, H. B. Ujkaj, M. Cincotta, S. L. Baldessarini, R. J. TI Valproate vs. lamotrigine in outpatients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; mood stabilizer; outpatient C1 [Centorrino, F.; Talamo, A.; Lee, H. B.; Ujkaj, M.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. [Centorrino, F.; Talamo, A.; Lee, H. B.; Ujkaj, M.; Baldessarini, R. J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. [Centorrino, F.; Talamo, A.; Lee, H. B.; Ujkaj, M.; Cincotta, S. L.; Baldessarini, R. J.] Massachusetts Gen Hosp, McLean Div, Schizophrenia Bipolar Disorder & Psychopharmacol, Belmont, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 27 EP 27 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000075 ER PT J AU Copeland, LA Zeber, JE Salloum, IM Pincus, HA Fine, MJ Kilbourne, AM AF Copeland, L. A. Zeber, J. E. Salloum, I. M. Pincus, H. A. Fine, M. J. Kilbourne, A. M. TI Treatment adherence and illness insight in veterans with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; illness insight; patient acceptance of healthcare; patient non-adherence; veterans C1 [Copeland, L. A.; Zeber, J. E.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Salloum, I. M.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT, San Antonio, TX 78229 USA. [Salloum, I. M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Pincus, H. A.] Columbia Univ, Dept Psychiat, New York Presbyterian Hosp, New York, NY USA. [Fine, M. J.] Ctr Hlth Equ Res & Promot, VA Pittsburg Hlthcare Syst, Pittsburgh, PA USA. [Fine, M. J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. [Kilbourne, A. M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kilbourne, A. M.] Serious Mental Illness Treatment Res & Educ Ctr, VA Ann Arbor Hlthcare Syst, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 29 EP 30 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000081 ER PT J AU Deckersbach, T Nierenberg, A Buhlmann, U Ostacher, M Dougherty, D Loh, R Rauch, S Sachs, G AF Deckersbach, T. Nierenberg, A. Buhlmann, U. Ostacher, M. Dougherty, D. Loh, R. Rauch, S. L. Sachs, G. TI Negative affect and working memory in bipolar disorder: an fMRI investigation SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE neuroimaging; fMRI; depression; negative affect; cognitive impairment C1 [Deckersbach, T.; Nierenberg, A.; Ostacher, M.; Rauch, S. L.; Sachs, G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA USA. [Deckersbach, T.; Buhlmann, U.; Dougherty, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Psychiat Neurosci Res & Neurotherapeut, Boston, MA USA. [Loh, R.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 31 EP 31 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000086 ER PT J AU Deckersbach, T Nierenberg, AA Buhlmann, U Ostacher, M Dougherty, D Loh, R Rauch, SL Sachs, GS AF Deckersbach, T. Nierenberg, A. A. Buhlmann, U. Ostacher, M. Dougherty, D. Loh, R. Rauch, S. L. Sachs, G. S. TI The influence of sadness on working memory in bipolar disorder: an fMRI investigation SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE neuroimaging; fMRI; depression; sadness; cognitive impairment C1 [Deckersbach, T.; Nierenberg, A. A.; Ostacher, M.; Rauch, S. L.; Sachs, G. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. [Deckersbach, T.; Buhlmann, U.; Dougherty, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Psychiat Neurosci Res & Neurotherapeut, Boston, MA USA. [Loh, R.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 31 EP 32 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000087 ER PT J AU Del Debbio, A Blais, MA Dias, R Nierenberg, AA Sachs, GS AF Del Debbio, A. Blais, M. A. Dias, R. Nierenberg, A. A. Sachs, G. S. TI Use of factor analysis to type bipolar disorder by correspondence to classic phenotype: bipolarity index SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; factor analysis; bipolarity index (bpx); episode characteristics; age of onset; illness course/associated features; treatment response; family history; phenotypes C1 [Del Debbio, A.; Blais, M. A.; Dias, R.; Nierenberg, A. A.; Sachs, G. S.] Massachusetts Gen Hosp, Harvard Bipolar Program, Boston, MA 02114 USA. [Del Debbio, A.] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. [Blais, M. A.] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab, Boston, MA 02114 USA. [Dias, R.] Univ Sao Paulo, Inst Psychiat, PROMAN, Bipolar Res Program, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 32 EP 33 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000089 ER PT J AU Del Debbio, A Blais, MA Dias, R Nierenberg, AA Sachs, GS AF Del Debbio, A. Blais, M. A. Dias, R. Nierenberg, A. A. Sachs, G. S. TI Psychometric properties of the Bipolarity Index Rating System SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; factor analysis; rasch analysis; bipolarity index (bpx); episode characteristics; age of onset; illness course/associated features; treatment response; family history; phenotypes C1 [Del Debbio, A.; Blais, M. A.; Dias, R.; Nierenberg, A. A.; Sachs, G. S.] Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02114 USA. [Del Debbio, A.] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. [Blais, M. A.] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab, Boston, MA 02114 USA. [Dias, R.] Univ Sao Paulo, Inst Psychiat, PROMAN, Bipolar Res Program, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 32 EP 32 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000088 ER PT J AU Dias, RS Joffe, H DelDebbio, A Nierenberg, AA Sachs, GS AF Dias, R. S. Joffe, H. DelDebbio, A. Nierenberg, A. A. Sachs, G. S. TI Clinical correlates of premenstrual worsening of mood in women with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE women; premenstrual worsening; comorbidity; clinical phenotype C1 [Dias, R. S.] Univ Sao Paulo, Inst Psychiat, Bipolar Res Program, Sao Paulo, Brazil. [Joffe, H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal Psychiat Res Unit, Boston, MA 02115 USA. [DelDebbio, A.] Univ Pisa, Postdoctoral Fellowship Program, Neurobiol & Clin Affect Disorders, I-56100 Pisa, Italy. RI Dias, Rodrigo/N-8985-2013 OI Dias, Rodrigo/0000-0002-1315-7205 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 33 EP 34 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000092 ER PT J AU El-Mallakh, RS Ghaemi, SN Sagduyu, K Thase, ME Wisniewski, SR Nierenberg, AA Zhang, HW Pardo, TA Sachs, G AF El-Mallakh, R. S. Ghaemi, S. N. Sagduyu, K. Thase, M. E. Wisniewski, S. R. Nierenberg, A. A. Zhang, H. W. Pardo, T. A. Sachs, G. CA Step-BD Investigators TI Antidepressant-associated chronic irritable dysphoria (ACID) in STEP-BD patients SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar depression; antidepressants; ACID; antidepressant-associated chronic irritable dysphoria; treatment resistance C1 [Ghaemi, S. N.; Pardo, T. A.] Emory Univ, Sch Med, Bipolar Disorder Res Program, Atlanta, GA 30322 USA. [Sagduyu, K.] Univ Missouri, Kansas City, MO 64110 USA. [Thase, M. E.] Mercer Univ, Macon, GA 31207 USA. [Thase, M. E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Thase, M. E.] Univ Penn, Philadelphia, PA 19104 USA. [Wisniewski, S. R.; Zhang, H. W.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Nierenberg, A. A.; Sachs, G.] Massachusetts Gen Hosp, Harvard Bipolar Disorder Res Program, Boston, MA 02114 USA. [El-Mallakh, R. S.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Mood Disorders Res Program, Louisville, KY 40292 USA. RI Ghaemi, Nassir/J-4934-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 35 EP 35 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000097 ER PT J AU Filkowski, MM Ghaemi, SN Stan, V Borrelli, D Ostacher, MJ El-Mallakh, RS Baldassano, CF Sachs, GS Baldessarini, RJ AF Filkowski, M. M. Ghaemi, S. N. Stan, V. Borrelli, D. Ostacher, M. J. El-Mallakh, R. S. Baldassano, C. F. Sachs, G. S. Baldessarini, R. J. TI Effect of antidepressant treatment on depressive relapse in bipolar disorder: a randomized study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD C1 [Filkowski, M. M.; Ghaemi, S. N.] Emory Univ, Sch Med, Dept Psychiat, Bipolar Disorder Res Program, Atlanta, GA 30322 USA. [Stan, V.] Cambridge Hlth Alliance, Bipolar Disorder Res Program, Cambridge, MA USA. [Stan, V.; Borrelli, D.; Ostacher, M. J.; Sachs, G. S.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Borrelli, D.; Ostacher, M. J.; Sachs, G. S.] Massachusetts Gen Hosp Bipolar, Clin & Res Program, Boston, MA USA. [El-Mallakh, R. S.] Univ Louisville, Sch Med, Mood Disorders Program, Louisville, KY 40292 USA. [Baldassano, C. F.] Univ Penn, Sch Med, Mood Disorders Program, Philadelphia, PA 19104 USA. [Baldessarini, R. J.] Massachusetts Gen Hosp Bipolar, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. RI Ghaemi, Nassir/J-4934-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 38 EP 38 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000105 ER PT J AU Ghaemi, SN El-Mallakh, RS Baldassano, CF Ostacher, MJ Filkowski, MM Stan, VA Sachs, GS Baldessarini, RJ AF Ghaemi, S. N. El-Mallakh, R. S. Baldassano, C. F. Ostacher, M. J. Filkowski, M. M. Stan, V. A. Sachs, G. S. Baldessarini, R. J. TI Antidepressant effect on long-term mood morbidity in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD C1 [Ghaemi, S. N.; Filkowski, M. M.] Emory Univ, Sch Med, Dept Psychiat, Bipolar Disorder Res Program, Atlanta, GA 30322 USA. [El-Mallakh, R. S.] Univ Louisville, Sch Med, Mood Disorders Program, Louisville, KY 40292 USA. [Baldassano, C. F.] Univ Penn, Sch Med, Mood Disorders Program, Philadelphia, PA 19104 USA. [Ostacher, M. J.; Sachs, G. S.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ostacher, M. J.; Sachs, G. S.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA USA. [Stan, V. A.] Cambridge Hlth Alliance, Bipolar Disorder Res Program, Cambridge, MA USA. [Baldessarini, R. J.] Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. RI Ghaemi, Nassir/J-4934-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 44 EP 44 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000121 ER PT J AU Kelly, DI Suppes, T Keck, PE McElroy, SL Altshuler, LL Frye, MA Nolen, WA Kupka, RW Grunze, H Leverich, GS Mintz, J Luckenbaugh, DA Fischer, EG Post, RM AF Kelly, D. I. Suppes, T. Keck, P. E., Jr. McElroy, S. L. Altshuler, L. L. Frye, M. A. Nolen, W. A. Kupka, R. W. Grunze, H. Leverich, G. S. Mintz, J. Luckenbaugh, D. A. Fischer, E. G. Post, R. M. TI Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; bipolar depression; cycling; quetiapine C1 [Kelly, D. I.; Suppes, T.; Fischer, E. G.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Keck, P. E., Jr.; McElroy, S. L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Keck, P. E., Jr.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Altshuler, L. L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Frye, M. A.] Mayo Coll Med, Rochester, MN USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kupka, R. W.] Altrech Inst Med Hlth Care, Utrecht, Netherlands. [Grunze, H.] Ludwig Maximilians Univ Munchen, Munich, Germany. [Leverich, G. S.; Luckenbaugh, D. A.] NIMH, NIH, Bethesda, MD 20892 USA. [Post, R. M.] Penn State Coll Med, Hershey, PA USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000157 ER PT J AU Kilbourne, AM Bauer, MS Nossek, A Drill, L Cooley, S Post, EP AF Kilbourne, A. M. Bauer, M. S. Nossek, A. Drill, L. Cooley, S. Post, E. P. TI Improving medical outcomes in patients with bipolar disorder: a randomized, controlled trial SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE general medical comorbidity; cardiovascular disease; metabolic syndrome; chronic care model C1 [Kilbourne, A. M.; Post, E. P.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kilbourne, A. M.; Post, E. P.] VA Ann Arbor Serious Mental Illness Treatment Res, Ann Arbor, MI USA. [Bauer, M. S.] VA Providence Med Ctr, Providence, RI USA. [Bauer, M. S.] Brown Univ, Providence, RI 02912 USA. [Nossek, A.; Drill, L.; Cooley, S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Cooley, S.] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Post, E. P.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 59 EP 59 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000162 ER PT J AU Mansour, HA Chowdari, KV Wood, J Pless, L McClendon, TB King, AJ Allen, M Bowden, CL Calabrese, J El-Mallakh, RS Fagiolini, A Faraone, SV Fossey, MD Friedman, ES Gyulai, L Hauser, P Ketter, TA Laird, N Loftis, JM Marangell, LB Miklowitz, DJ McQueen, MB Nierenberg, AA Patel, J Sachs, GS Sklar, P Smoller, JW Thase, ME Frank, E Kupfer, DJ Devlin, B Nimgaonkar, VL AF Mansour, H. A. Chowdari, K. V. Wood, J. Pless, L. McClendon, T. B. King, A. J. Allen, M. Bowden, C. L. Calabrese, J. El-Mallakh, R. S. Fagiolini, A. Faraone, S. V. Fossey, M. D. Friedman, E. S. Gyulai, L. Hauser, P. Ketter, T. A. Laird, N. Loftis, J. M. Marangell, L. B. Miklowitz, D. J. McQueen, M. B. Nierenberg, A. A. Patel, J. Sachs, G. S. Sklar, P. Smoller, J. W. Thase, M. E. Frank, E. Kupfer, D. J. Devlin, B. Nimgaonkar, V. L. TI Circadian gene polymorphisms and liability to bipolar I disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE circadian; bipolar; association C1 [Mansour, H. A.; Chowdari, K. V.; Wood, J.; Pless, L.; McClendon, T. B.; King, A. J.; Fagiolini, A.; Friedman, E. S.; Thase, M. E.; Frank, E.; Kupfer, D. J.; Devlin, B.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 80202 USA. [Allen, M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Bowden, C. L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 44106 USA. [Calabrese, J.] Case Western Reserve Univ, Univ Hosp Cleveland, Hlth Sci Ctr, Cleveland, OH 40292 USA. [El-Mallakh, R. S.] Univ Louisville, Sch Med, Louisville, KY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY 74136 USA. [Fossey, M. D.] Univ Oklahoma, Tulsa Med Coll, Div Neonatol, Tulsa, OK 19104 USA. [Gyulai, L.] Univ Penn, Med Ctr, Philadelphia, PA USA. [Hauser, P.; Loftis, J. M.] Portland VA Med Ctr, Portland, OR USA. [Hauser, P.; Loftis, J. M.] Oregon Hlth & Sci OUniv, Portland, OR 94305 USA. [Ketter, T. A.] Stanford Univ, Sch Med, Stanford, CA 02115 USA. [Laird, N.] Harvard Univ, Sch Publ Hlth, Boston, MA 77030 USA. [Marangell, L. B.; Miklowitz, D. J.] Baylor Coll Med, Dept Vet Affairs, Houston, TX 80309 USA. [McQueen, M. B.] Univ Colorado, Boulder, CO USA. [Nierenberg, A. A.; Sachs, G. S.] Harvard Univ, Sch Med, Massachusetts Med Sch, Bipolar Clin & Res Program, Worcester, MA 02114 USA. [Sklar, P.] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sklar, P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sklar, P.] Harvard Univ, Ctr Human Genet Res, Boston, MA 02114 USA. [Smoller, J. W.] Massachusetts Gen Hosp, Psychiat Genet Program Mood Anxiety & Disorders, Boston, MA 15260 USA. [Devlin, B.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA USA. RI Allen, Michael/A-8776-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 73 EP 74 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000204 ER PT J AU Nery, FG Stanley, JA Chen, HH Hatch, JP Nicoletti, MA Monkul, ES Lafer, B Soares, JC AF Nery, F. G. Stanley, J. A. Chen, H. H. Hatch, J. P. Nicoletti, M. A. Monkul, E. S. Lafer, B. Soares, J. C. TI Glutamatergic abnormalities in the left dorsolateral prefrontal cortex of patients with bipolar disorder and comorbid alcohol/drug use disorders: a proton spectroscopy study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; substance-related disorders; magnetic resonance spectroscopy C1 [Nery, F. G.; Nicoletti, M. A.; Monkul, E. S.; Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, F. G.; Nicoletti, M. A.; Monkul, E. S.; Soares, J. C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Nery, F. G.; Lafer, B.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Stanley, J. A.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Chen, H. H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Hatch, J. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 82 EP 83 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000230 ER PT J AU Nierenberg, AA Marangell, LB Calabrese, JR Ketter, TA Bowden, CL Reilly-Harrington, N Freedman, ES Ostacher, MJ Dennehy, EB Thase, ME AF Nierenberg, A. A. Marangell, L. B. Calabrese, J. R. Ketter, T. A. Bowden, C. L. Reilly-Harrington, N. Freedman, E. S. Ostacher, M. J. Dennehy, E. B. Thase, M. E. TI NIMH bipolar trials network: an infrastructure for collaboration SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE NIMH; bipolar; trials; network C1 [Nierenberg, A. A.; Reilly-Harrington, N.; Ostacher, M. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Marangell, L. B.] Baylor Coll Med, Houston, TX 77030 USA. [Calabrese, J. R.] Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH USA. [Ketter, T. A.] Stanford Univ, Sch Med, Stanford, CA USA. [Bowden, C. L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Freedman, E. S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Dennehy, E. B.] Purdue Univ, W Lafayette, IN 47907 USA. [Thase, M. E.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 83 EP 84 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000232 ER PT J AU Perlis, RH Purcell, S Fagerness, J Kirby, A Petryshen, T Fan, J Sklar, P AF Perlis, R. H. Purcell, S. Fagerness, J. Kirby, A. Petryshen, T. Fan, J. Sklar, P. TI Family-based association study of candidate genes for lithium mechanism of action in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE genetic association; lithium; pharmacogenetic C1 [Perlis, R. H.; Purcell, S.; Fagerness, J.; Petryshen, T.; Fan, J.; Sklar, P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perlis, R. H.; Purcell, S.; Fagerness, J.; Kirby, A.; Petryshen, T.; Fan, J.; Sklar, P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet, Boston, MA USA. [Perlis, R. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin Res Program, Boston, MA USA. [Petryshen, T.; Fan, J.; Sklar, P.] Harvard Univ, MIT, Broad Inst, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 86 EP 86 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000238 ER PT J AU Quinones, MP Ahmadi, S Nery, FG Torres, V Estrada, C Olvera, R Hatch, JP Vipraio, G Pliszka, S Soares, JC AF Quinones, M. P. Ahmadi, S. Nery, F. G. Torres, V. Estrada, C. Olvera, R. Hatch, J. P. Vipraio, G. Pliszka, S. Soares, J. C. TI Reduction in the availability of the neurotrophic factor Insulin Growth Factor (IGF)-1, but not brain derived neurotrophic factor (BDNF), in individuals with mood disorder may result from synergistic effects of disease-specific processes and normal age-associated reduction in circulating levels SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE growth factors; biomarkers; children and adult bipolar disorder C1 [Quinones, M. P.; Ahmadi, S.; Estrada, C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Quinones, M. P.; Nery, F. G.; Estrada, C.; Olvera, R.; Pliszka, S.; Soares, J. C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Quinones, M. P.; Torres, V.; Olvera, R.; Pliszka, S.; Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, F. G.; Olvera, R.; Hatch, J. P.; Vipraio, G.; Pliszka, S.; Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX 78229 USA. [Nery, F. G.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Hatch, J. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 87 EP 88 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000243 ER PT J AU Quinones, MP Torres, V Nery, FG Ahmadi, S Estrada, C Olvera, R Hatch, JP Vipraio, G Pliszka, S Soares, JC AF Quinones, M. P. Torres, V. Nery, F. G. Ahmadi, S. Estrada, C. Olvera, R. Hatch, J. P. Vipraio, G. Pliszka, S. Soares, J. C. TI Differential involvement of inflammatory markers in adult and pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE inflammation; biomarkers; children and adult bipolar disorder C1 [Quinones, M. P.; Ahmadi, S.; Estrada, C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Quinones, M. P.; Nery, F. G.; Estrada, C.; Olvera, R.; Pliszka, S.; Soares, J. C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Quinones, M. P.; Torres, V.; Nery, F. G.; Olvera, R.; Pliszka, S.; Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. [Soares, J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Hatch, J. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 87 EP 87 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000242 ER PT J AU Zeber, JE Copeland, LA Good, CB Fine, MJ Bauer, MS Kilbourne, AM AF Zeber, J. E. Copeland, L. A. Good, C. B. Fine, M. J. Bauer, M. S. Kilbourne, A. M. TI Therapeutic alliance perceptions and medication adherence in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE therapeutic alliance; medication adherence; treatment barriers; ethnicity; veterans C1 [Zeber, J. E.; Copeland, L. A.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Zeber, J. E.; Copeland, L. A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Good, C. B.; Fine, M. J.] Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Good, C. B.; Fine, M. J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Bauer, M. S.] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Kilbourne, A. M.] Univ Michigan, Serious Mental Illness Treatment Res & Educ Ctr, VA Ann ARbor Healthcare Syst, Ann Arbor, MI 48109 USA. [Kilbourne, A. M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 113 EP 113 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000314 ER PT J AU Frey, BN Stanley, JA Nery, FG Monkul, ES Nicoletti, MA Chen, HH Hatch, JP Caetano, SC Ortiz, O Kapczinski, F Soares, JC AF Frey, Benicio N. Stanley, Jeffrey A. Nery, Fabiano G. Monkul, E. Serap Nicoletti, Mark A. Chen, Hua-Hsuan Hatch, John P. Caetano, Sheila C. Ortiz, Oswaldo Kapczinski, Flavio Soares, Jair C. TI Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo H-1 MRS study SO BIPOLAR DISORDERS LA English DT Article; Proceedings Paper CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; brain imaging dorsolateral; prefrontal cortex; magnetic resonance spectroscopy ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYL-ASPARTATE; BRAIN PHOSPHORUS-METABOLISM; MITOCHONDRIAL DYSFUNCTION; ACUTE MANIA; NEUROPSYCHIATRIC DISORDERS; CREATINE-KINASE; FRONTAL LOBES; RATING-SCALE; LITHIUM AB Objectives: While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy (H-1 MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr). Methods: Thirty-two medication-free BD subjects (33.8 +/- 10.2 years) and 32 matched controls ( 33.8 +/- 9.0 years) underwent a short echo-time (TE 30 ms) H-1 MRS. An 8-cm(3) single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate were obtained, using the water signal as an internal reference. Results: BD subjects had lower Cr + PCr [F-(1,F-62) 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [F-(1,F-62) 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites. Conclusions: These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD. C1 [Frey, Benicio N.; Nery, Fabiano G.; Monkul, E. Serap; Nicoletti, Mark A.; Hatch, John P.; Caetano, Sheila C.; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, MOOD CNS Program, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. [Frey, Benicio N.; Kapczinski, Flavio] Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, BR-90046900 Porto Alegre, RS, Brazil. [Frey, Benicio N.; Kapczinski, Flavio] Hosp Clin Porto Alegre, Bipolar Disorders Program, Porto Alegre, RS, Brazil. [Stanley, Jeffrey A.; Caetano, Sheila C.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. [Monkul, E. Serap] Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. [Nicoletti, Mark A.; Ortiz, Oswaldo; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Div, S Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX 78229 USA. [Chen, Hua-Hsuan; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. RP Frey, BN (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, MOOD CNS Program, Div Mood & Anxiety Disorders, 3939 Med Dr,Suite 100, San Antonio, TX 78229 USA. EM benicio.frey@gmail.com RI Kapczinski, Flavio/D-3175-2013; Caetano, Sheila/H-5010-2012; Kapczinski, Flavio/J-5803-2014 OI Caetano, Sheila/0000-0001-8403-7078; FU NCRR NIH HHS [M01-RR-01346, RR020571]; NIMH NIH HHS [MH 01736, MH 068662, MH 068766] NR 60 TC 60 Z9 63 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 119 EP 127 DI 10.1111/j.1399-5618.2007.00454.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000324 PM 17543030 ER PT J AU Bearden, CE Glahn, DC Caetano, S Olvera, RL Fonseca, M Najt, P Hunter, K Pliszka, SR Soares, JC AF Bearden, Carrie E. Glahn, David C. Caetano, Sheila Olvera, Rene L. Fonseca, Manoela Najt, Pablo Hunter, Kristina Pliszka, Steve R. Soares, Jair C. TI Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder SO BIPOLAR DISORDERS LA English DT Article; Proceedings Paper CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE ADHD; cognition; development; executive function; juvenile mania; pediatric mood disorder; working memory ID WORKING-MEMORY; ADOLESCENT BIPOLARITY; EUTHYMIC PATIENTS; COMORBID ANXIETY; RATING-SCALE; I DISORDER; CHILDREN; MANIA; ADHD; SCHIZOPHRENIA AB Objectives: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). Methods: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 +/- 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 +/- 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). Results: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. Conclusions: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies. C1 [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Glahn, David C.; Caetano, Sheila; Fonseca, Manoela; Najt, Pablo; Hunter, Kristina; Soares, Jair C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. [Caetano, Sheila] Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. [Olvera, Rene L.; Pliszka, Steve R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Child & Adolescent Psychiat, San Antonio, TX 78229 USA. [Fonseca, Manoela] Univ Fed Rio Grande do Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. [Najt, Pablo; Soares, Jair C.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 300 Bldg Med Plaza,Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [M01-RR-01346, RR-020571]; NIMH NIH HHS [MH-68662, K23 MH068280, MH-01736, K23 MH074644, K23 MH 074644-01, K23 MH074644-01, MH-69774] NR 55 TC 32 Z9 33 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 145 EP 159 DI 10.1111/j.1399-5618.2007.00453.x PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000327 PM 17543033 ER PT J AU Baldessarini, RJ Tondo, L Baethge, CJ Lepri, B Bratti, IM AF Baldessarini, Ross J. Tondo, Leonardo Baethge, Christopher J. Lepri, Beatrice Bratti, Irene M. TI Effects of treatment latency on response to maintenance treatment in manic-depressive disorders SO BIPOLAR DISORDERS LA English DT Article; Proceedings Paper CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE anticonvulsants; antipsychotics; bipolar disorder; episode counts; lithium; manic-depressive illness; treatment latency; treatment response ID BIPOLAR DISORDER; LONG-TERM; LITHIUM PROPHYLAXIS; FOLLOW-UP; ILLNESS; EPISODES; PREDICTORS; RECURRENCE; RISK AB Objectives: To further test the hypothesis that past illness episodes and delay of long-term treatment do not limit maintenance treatment response among patients with manic-depressive illnesses (MDI). Methods: In a sample of 764 MDI patients in Cagliari and Berlin, 77% of whom had bipolar disorder (BPD), we: (i) correlated treatment latency or pretreatment episode counts versus hospitalized morbidity during treatment; (ii) correlated treatment duration versus pretreatment morbidity; (iii) correlated treatment latency versus pretreatment or treated morbidity; (iv) modeled factors associated with longer treatment latency; (v) compared treatment latencies at extremes of treatment outcomes, and (vi) compared pretreatment morbidity within 2 years of the longest versus shortest treatment latency quartiles. Results: Pretreatment morbidity was strongly correlated with shorter treatment latency, but morbidity during treatment was unrelated to treatment latency, pretreatment episode counts, sex, diagnosis, treatment type or treatment duration. In multivariate modeling, treatment latency was longer among patients who had experienced an early onset of illness, mainly in depressive disorders (BPD II and major depression) and among women, but was unrelated to morbidity during treatment. Patients with no illness recurrences during treatment and those who were ill at least 50% of the time had similar treatment latencies. Pretreatment morbidity occurring just prior to the initiation of long-term treatment was very similar at the highest and lowest treatment latencies. Conclusions: These findings support the therapeutically favorable conclusion that prior episode counts and treatment delay have little association with morbidity during prophylaxis with mood-stabilizing agents. Comparisons of morbidity during versus before treatment in episodic disorders are misleading because overall morbidity becomes diluted with longer time-at-risk, whereas therapeutic intervention is typically determined by immediately preceding illness. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. Lucio Bini Mood Disorders Ctr, Cagliari, Sardinia, Italy. Univ Cologne, Dept Psychiat, Cologne, Germany. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, Psychopharmacol Program, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org FU NIMH NIH HHS [MH-073049] NR 35 TC 28 Z9 31 U1 3 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 IS 4 BP 386 EP 393 DI 10.1111/j.1399-5618.2007.00385.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 176UO UT WOS:000247110600009 PM 17547585 ER PT J AU Kuter, DJ AF Kuter, David J. TI New thrombopoietic growth factors SO BLOOD LA English DT Review ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; ACUTE MYELOID-LEUKEMIA; FACTOR PEG-RHUMGDF; BONE-MARROW-TRANSPLANTATION; BREAST-CANCER PATIENTS; PHASE-I TRIAL; PLATELET PRODUCTION; C-MPL; RECEPTOR AGONIST AB Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions of Fab (Fab 59), attached to the IgG Fc region (AMG 531), or pegylated (Peg-TPOmp). Orally available, TPO nonpeptide mimetics (eltrombopag, AKR-501) bind and activate the TPO receptor by a mechanism different from TPO and may have an additive effect to TPO. TPO agonist antibodies are monoclonal antibodies activating the TPO receptor but modified in size [TPO minibodies; ie, VB22B sc(FV)(2)] or immunoglobuin type (domain subclass-converted TPO agonist antibodies; ie, MA01 G4G344). All second-generation thrombopoietic growth factors stimulate growth of TPO-dependent cell lines via JAK2/STAT signaling pathways and increase platelet counts in animals. When tested in healthy humans, TPO peptide and nonpeptide mimetics produced a dose-dependent rise in platelet count. AMG 531 and eltrombopag markedly increase platelet counts in patients with immune thrombocytopenic purpura, without significant adverse effects. One or more second-generation thrombopoietic growth factors should soon be clinically available for treating thrombocytopenic disorders. C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Div Hematol, Yawkey 7940,55 Fruit St, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu FU NHLBI NIH HHS [HL 72299, HL 82889, R01 HL082889, U01 HL072299] NR 82 TC 160 Z9 176 U1 1 U2 7 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 JUN 1 PY 2007 VL 109 IS 11 BP 4607 EP 4616 DI 10.1182/blood-2006-10-019315 PG 10 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100010 PM 17289815 ER PT J AU Moreau, AS Jia, XY Ngo, HT Leleu, X O'Sullivan, G Alsayed, Y Leontovich, A Podar, K Kutok, J Daley, J Lazo-Kallanian, S Hatjiharissi, E Raab, MS Xu, L Treon, SP Hideshima, T Anderson, KC Ghobrial, IM AF Moreau, Anne-Sophie Jia, Xiaoying Ngo, Hai T. Leleu, Xavier O'Sullivan, Garrett Alsayed, Yazan Leontovich, Alexey Podar, Klaus Kutok, Jeffrey Daley, John Lazo-Kallanian, Suzan Hatjiharissi, Evdoxia Raab, Marc S. Xu, Lian Treon, Steven P. Hideshima, Teru Anderson, Kenneth C. Ghobrial, Irene M. TI Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; B-CELL LYMPHOMA; AKT PATHWAY; BETA; GROWTH; MODEL; MICE; EXPRESSION AB Waldenstrom macroglobulinernia (WM) is an incurable lymphoplasmacytic lymphoma with limited options of therapy. Protein kinase C beta (PKC beta) regulates cell survival and growth in many B-cell malignancies. In this study, we demonstrate up-regulation of PKC beta protein in WM using protein array techniques and immunohistochemistry. Enzastaurin, a PKC beta inhibitor, blocked PKC beta activity and induced a significant decrease of proliferation at 48 hours in WM cell lines (IC50, 2.5-10 mu M). Similar effects were demonstrated in primary CD19(+) WM cells, without cytotoxicity on peripheral blood mononuclear cells. In addition, enzastaurin overcame tumor cell growth induced by coculture of WM cells with bone marrow stromal cells. Enzastaurin induced dose-dependent apoptosis at 48 hours mediated via induction of caspase-3, caspase-8, caspase-9, and PARP cleavage. Enzastaurin inhibited Akt phosphorylation and Akt kinase activity, as well as downstream p-MARCKS and ribosomal p-S6. Furthermore, enzastaurin demonstrated additive cytotoxicity in combination with bortezomib, and synergistic cytotoxicity in combination with fludarabine. Finally, in an in vivo xenograft model of human WM, significant inhibition of tumor growth was observed in the enzastaurin-treated mice (P = .028). Our studies therefore show that enzastaurin has significant antitumor activity in WM both in vitro and in vivo, providing the framework for clinical trials to improve patient outcome in WM. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Hosp Reg & Univ Lille, Fac Med Lille, Serv Malad Sang, F-59037 Lille, France. Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. Mayo Clin, Coll Med, Rochester, MN USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 25 TC 75 Z9 76 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2007 VL 109 IS 11 BP 4964 EP 4972 DI 10.1182/blood-2006-10-054577 PG 9 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100057 PM 17284528 ER PT J AU Ray, A Cowan-Jacob, SW Manley, PW Mestan, J Griffin, JD AF Ray, Arghya Cowan-Jacob, Sandra W. Manley, Paul W. Mestan, Juergen Griffin, James D. TI Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; IMATINIB STI571 RESISTANCE; TYROSINE KINASE; CLINICAL RESISTANCE; CHRONIC-PHASE; CELL-LINES; C-ABL; DOMAIN; CML AB Patients with advanced stages of chronic myeloid leukemia (CML) often manifest imatinib mesylate resistance associated with point mutations in BCR-ABL. AMN107 is a new higher-potency inhibitor of BCR-ABL. To identify mutations in BCR-ABL that could result in resistance to AMN107, a cDNA library of BCR-ABL mutants was introduced into Ba/F3 cells followed by selection in AMN107 (0.125-0.5 mu M). A total of 86 individual, drug-resistant colonies were recovered, and the SH3, SH2, and kinase domains of BCR-ABL were sequenced. A total of 46 colonies had single point mutations in BCR-ABL, with a total of 17 different mutations, all within the kinase domain. The other 40 colonies had multiple point mutations and were not analyzed further. Each of the 17 single point mutants were reconstructed by site-directed mutagenesis of native BCR-ABL and found to be approximately 2.5- to 800-fold more resistant to AMN107 than native BCR-ABL. The mutations included 6 known imatinib mesylate-resistant mutations, including T3151, which showed complete resistance to AMN107. Interestingly, most AMN107-resistant mutants were also resistant to imatinib mesylate. These results may predict some of the resistance mutations that will be detected in clinical trials with this kinase inhibitor. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Novartis Inst BioMed Res, Basel, Switzerland. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu FU NCI NIH HHS [CA 66996] NR 31 TC 92 Z9 93 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 JUN 1 PY 2007 VL 109 IS 11 BP 5011 EP 5015 DI 10.1182/blood-2006-01-015347 PG 5 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100063 PM 17303698 ER PT J AU Yang, D Singh, R Diviet, P Guo, J Bouxsein, ML Bringhurst, FR AF Yang, D. Singh, R. Diviet, P. Guo, J. Bouxsein, M. L. Bringhurst, F. R. TI Contributions of parathyroid hormone (PTH)/PTH-related peptide receptor signaling pathways to the anabolic effect of PTH on bone SO BONE LA English DT Article DE bone formation; PTH/PTHrP receptor; blood cAMP; bone densitometry; bone QCT ID FEMORAL TRABECULAR BONE; KINASE-C ACTIVATION; OVARIECTOMIZED RATS; IN-VIVO; OSTEOBLASTIC CELLS; PHOSPHOLIPASE-C; CANCELLOUS BONE; PROTEIN; STIMULATION; FRAGMENTS AB PTH regulates ostcoblastic function by activating PTH/PTHrP receptors (PTHLRs), which trigger several signaling pathways in parallel, including cAMP/protein kinase A (PKA) and, via both phospholipase-C (PLC)-dependent and PLC-independent mechanisms, protein kinase C (PKC). These signaling functions have been mapped to distinct domains within PTH(1-34), but their roles in mediating the anabolic effect of intenuittent PTH in vivo are unclear. We compared the anabolic effects in mice of hPTH(1-34) with those of two analogs having restricted patterns of PTH1R signaling. [G(1),R-19]hPTH(1-28) lacks the 29-34 domain of hPTH(1-34) needed for PLC-independent PKC activation, incorporates a Gly(1) mutation that prevents PLC activation, and stimulates only cAMP/PKA signaling. [G(1),R-19]hPTH(1-34) retains the 29-34 domain and activates both cAMP/PKA and PLC-independent PKC. Human PTH(1-34) (40 mu g/kg), [G(1),R-19]hPTH(1-34) (120 mu g/kg), and [G(1),R-19]hPTH(1-28) (800 mu g/kg), at doses equipotent in elevating blood cAMP at 10 min and cAMP-dependent gene expression in bone at 6 h after s.c. injection, were administered to 10-week-old female C57BL/6.1 mice 5 days/week for 4 weeks. Acute blood cAMP responses, retested after 4 weeks, were not reduced by the preceding PTH treatment. The three PTH peptides induced equivalent increases in distal femoral bone mineral density (BMD), and, by microCT analysis, distal femoral and vertebral bone volume and trabecular thickness and mid-femoral cortical endosteal apposition. [G(1),R-19]hPTH(1-34) and hPTH(1-34) increased distal femoral BMD more rapidly and augmented total-body BMD and bone volume of proximal tibial trabeculi to a greater extent than did [G(1),R-19]hPTH(1-28). We conclude that cAMP/PKA signaling is the dominant mechanism for the anabolic actions of PTH in trabecular bone and that PLCindependent PKC signaling, attributable to the PTH(29-34) sequence, appears to accelerate the trabecular response and augment BMD at some skeletal sites. PTH1R PLC signaling pathway is not required for an anabolic effect of intermittent PTH(1-34) on bone. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Beth Israel Hosp, Harvard Med Sch, Orthoped Biomech Lab, Boston, MA USA. RP Bringhurst, FR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM rbringhurst@partners.org FU NCRR NIH HHS [S10 RR017868, S10-RR17868]; NIDDK NIH HHS [K08 DK002889, DK02889, DK11794, DK65032, P01 DK011794, P01 DK011794-300006, R03 DK065032] NR 31 TC 40 Z9 53 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 BP 1453 EP 1461 DI 10.1016/j.bone.2007.02.001 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181FX UT WOS:000247423600003 PM 17376756 ER PT J AU Bianchi, G Orsi, A Cascio, P Chauhan, D Anderson, KC Sitia, R Cenci, S AF Bianchi, G. Orsi, A. Cascio, P. Chauhan, D. Anderson, K. C. Sitia, R. Cenci, S. TI Assessing proteasome workload to predict response and overcome resistance to proteasome inhibitors in multiple myeloma SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Univ Vita Salute San Raffaele, San Raffaele Sci Inst, DiBit, Milan, Italy. Univ Turin, Dept Vet Morphophysiol, Turin, Italy. Jerome Lipper Multiple Myeloma Ctr, Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 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 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S153 EP S154 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100103 ER PT J AU Huang, AJ Ettinger, B Ensrud, K Vittinghoff, E Cummings, SR AF Huang, A. J. Ettinger, B. Ensrud, K. Vittinghoff, E. Cummings, S. R. TI The effect of ultra low-dose transdermal estradiol on bone turnover depends on endogenous estradiol levels SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 San Francisco VA Med Ctr, San Francisco, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. Vet Affairs Med Ctr, Minneapolis, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S134 EP S135 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100067 ER PT J AU Juppner, H AF Jueppner, H. TI Novel regulators of phosphate homeostasis and bone metabolism SO BONE LA English DT Meeting Abstract CT 4th International Conference on Childrens Bone Health CY JUN 21-24, 2007 CL Montreal, CANADA C1 Massachusetts Gen Hosp, Harvard Med Sch, Pediat Nephrol Unit, Endocrine Unit, Boston, MA 02114 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 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 1 BP S13 EP S14 DI 10.1016/j.bone.2007.04.148 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GU UT WOS:000247426000015 ER PT J AU Juppner, H AF Jueppner, H. TI Gs-alpha, genetic imprinting, and pseudohypoparathyroidism SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S131 EP S132 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100062 ER PT J AU Krum, SA Miranda-Carboni, GA Carroll, JS Lane, TF Freedman, LP Brown, M AF Krum, S. A. Miranda-Carboni, G. A. Carroll, J. S. Lane, T. F. Freedman, L. P. Brown, M. TI Estrogen induces apoptosis in osteoclasts via upregulation of FasL in osteoblasts SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Canc Res UK, Cambridge, England. Wyeth Res, Collegeville, PA USA. RI krum, susan/D-7282-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S179 EP S179 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100156 ER PT J AU Sitara, D Bergwitz, C Razzaque, MS Taguchi, T Erben, RG Juppner, H Lanske, B AF Sitara, D. Bergwitz, C. Razzaque, M. S. Taguchi, T. Erben, R. G. Jueppner, H. Lanske, B. TI Genetic evidence of pathologic role of NaPi2a in regulating altered phosphate homeostasis and skeletogenesis in Fgf-23(-/-) mice SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Nagasaki Univ, Sch Biomed Sci, Dept Pathol, Nagasaki 852, Japan. Univ Vet Med, Dept Nat Sci, Vienna, Austria. 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 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S128 EP S129 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100056 ER PT J AU Ballen, K AF Ballen, K. TI Targeting the stem cell niche: squeezing blood from bones SO BONE MARROW TRANSPLANTATION LA English DT Review DE stem cell niche; parathyroid hormone; osteoblasts ID HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; PARATHYROID-HORMONE; CORD BLOOD; AUTOLOGOUS TRANSPLANTATION; SELF-RENEWAL; IN-VIVO; OSTEOPOROSIS; DIFFERENTIATION AB During human development, stem cells establish themselves in specific anatomic locations or niches. The niche harbors the stem cells, and regulates how stem cells proliferate. The interaction between stem cells and their niche affects stem cell function, and offers an opportunity to improve the marrow microenvironment. Osteoblasts produce hematopoietic growth factors and are activated by parathyroid hormone (PTH). A calcium sensing receptor, expressed by hematopoietic stem cells, regulates the niche and can be targeted to increase stem cell numbers. Therefore, drugs that affect osteoblast function or target calcium receptors may be useful for stem cell mobilization and engraftment. In this review, the biology of the stem cell niche and the potential therapeutic manipulations of the stem cell niche are reviewed. PTH is in clinical trials for patients who have not mobilized autologous stem cells well. The limiting cell numbers for adult cord blood transplantation increase the risk of infection, and PTH is currently in a clinical trial following cord blood transplantation in an effort to improve engraftment and immune reconstitution. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Zero Emerson Pl,Suite 118,Room 134, Boston, MA 02214 USA. EM kballen@partners.org NR 39 TC 25 Z9 25 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2007 VL 39 IS 11 BP 655 EP 660 DI 10.1038/sj.bmt.1705651 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 168YV UT WOS:000246560800001 PM 17401397 ER PT J AU Thannickal, TC Lai, YY Siegel, JM AF Thannickal, Thomas C. Lai, Yuan-Yang Siegel, Jerome M. TI Hypocretin (orexin) cell loss in Parkinson's disease SO BRAIN LA English DT Article DE Parkinson; narcolepsy; sleep; hypocretin; orexin; melanin concentrating hormone ID EXCESSIVE DAYTIME SLEEPINESS; BEHAVIOR DISORDER; REM-SLEEP; HUMAN NARCOLEPSY; KNOCKOUT MICE; LEWY BODIES; NEURONS; HYPOTHALAMUS; WAKEFULNESS; PATHOLOGY AB It has recently been reported that Parkinson's disease (PD) is preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep behaviour disorder, hallucinations and depression, symptoms which are frequently as troublesome as the motor symptoms of PD. All these symptoms are present in narcolepsy, which is linked to a selective loss of hypocretin (Hcrt) neurons. In this study, the Hcrt system was examined to determine if Hcrt cells are damaged in PD. The hypothalamus of I I PD (mean age 79 +/- 4) and 5 normal (mean age 77 3) brains was examined. Sections were immunostained for H crt- 1, melanin concentrating hormone (MCH) and alpha synuclein and glial fibrillary acidic protein (GFAP).The substantia nigra of 10 PD brains and 7 normal brains were used for a study of neuromelanin pigmented cell loss. The severity of PD was assessed using the Hoehn and Yahr scale and the level of neuropathology was assessed using the Braak staging criteria. Cell number, distribution and size were determined with stereologic techniques on a one in eight series. We found an increasing loss of hypocretin cells with disease progression. Similarly, there was an increased loss of MCH cells with disease severity. Hcrt and MCH cells were lost throughout the anterior to posterior extent of their hypothalamic distributions. The percentage loss of Hcrt cells was minimal in stage 1 (23%) and was maximal in stage V (62%). Similarly, the percentage loss of MCH cells was lowest in stage 1 (12%) and was highest in stage V (74%). There was a significant increase (P = 0.0006, t = 4.25, df = 15) in the size of neuromelanin containing cells in PD patients, but no difference in the size of surviving Hcrt (P = 0.18, t = 1.39, df = 14) and MCH (P = 0.28, t = 1.39, df = 14) cells relative to controls. In summary, we found that PD is characterized by a massive loss of Hcrt neurons.Thus, the loss of Hcrt cells may be a cause of the narcolepsy-like symptoms of PD and may be ameliorated by treatments aimed at reversing the Hcrt deficit. We also saw a substantial loss of hypothalamic MCH neurons. The losses of Hcrt and MCH neurons are significantly correlated with the clinical stage of PD, not disease duration, whereas the loss of neuromelanin cells is significantly correlated only with disease duration. The significant correlations that we found between the loss of Hcrt and MCH neurons and the clinical stage of PD, in contrast to the lack of a relationship of similar strength between loss of neuromelanin containing cells and the clinical symptoms of PD, suggests a previously unappreciated relationship between hypothalamic dysfunction and the time course of the overall clinical picture of PD. C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, VAGLAHS, Neurobiol Res 151A3, 16111 Plummer St, Sepulveda, CA 91343 USA. EM jsiegel@ucla.edu FU NHLBI NIH HHS [HL41370]; NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610, NS42566] NR 59 TC 216 Z9 224 U1 5 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2007 VL 130 BP 1586 EP 1595 DI 10.1093/brain/awm097 PN 6 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 183IA UT WOS:000247565300015 PM 17491094 ER PT J AU Shin, HK Dunn, AK Jones, PB Boas, DA Lo, EH Moskowitz, MA Ayata, C AF Shin, Hwa Kyoung Dunn, Andrew K. Jones, Phillip B. Boas, David A. Lo, Eng H. Moskowitz, Michael A. Ayata, Cenk TI Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia SO BRAIN LA English DT Article DE neuroprotection; laser speckle flowmetry; multispectral reflectance imaging; middle cerebral artery occlusion; acute stroke ID LASER SPECKLE FLOWMETRY; EXPERIMENTAL STROKE; SPREADING ISCHEMIA; SUBARACHNOID SPACE; BRAIN ISCHEMIA; RAT MODEL; PERFUSION; THERAPY; CORTEX; REPERFUSION AB Normobaric hyperoxia is under investigation as a treatment for acute ischaemic stroke. In experimental models, normobaric hyperoxia reduces cerebral ischaemic injury and improves functional outcome. The mechanisms of neuroprotection are still debated because, (i) inhalation of 100% O-2 does not significantly increase total blood O-2 content; (ii) it is not known whether normobaric hyperoxia increases O-2 delivery to the severely ischaemic cortex because of its short diffusion distance; and (iii) hyperoxia may reduce collateral cerebral blood flow (CBF) to ischaemic penumbra because it can cause vasoconstriction. We addressed these issues using real-time two-dimensional multispectral reflectance imaging and laser speckle flowmetry to simultaneously and non-invasively determine the impact of normobaric hyperoxia on CBF and oxygenation in ischaemic cortex. Ischaemia was induced by distal middle cerebral artery occlusion (dMCAO) in normoxic (30% inhaled O-2, arterial pO(2) 134 +/- 9 mm Hg), or hyperoxic mice (100% inhaled 02 starting 15 min after dMCAO, arterial pO(2) 312 +/- 10 mm Hg). Post-ischaemic normobaric hyperoxia caused an immediate and progressive increase in oxyhaemoglobin (oxyHb) concentration, nearly doubling it in ischaernic core within 60 min. In addition, hyperoxia improved CBF so that the area of cortex with <= 20% residual CBF was decreased by 45% 60 min after dMCAO. Furthermore, hyperoxia reduced the frequency of peri-infarct depolarizations (PIDs) by more than 60%, and diminished their deleterious effects on CBF and metabolic load. Consistent with these findings, infarct size was reduced by 45% in the hyperoxia group 2 days after 7S min transient dMCAO. Our data show that normobaric hyperoxia increases tissue 02 delivery, and that novel mechanisms such as CBF augmentation, and suppression of PlDs may afford neuroprotection during hyperoxia. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Stroke Serv & Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014; OI Jones, Phillip/0000-0003-0525-6323 FU NIBIB NIH HHS [R01 EB000790, R01 EB000790-05, R01EB00790-01A2]; NINDS NIH HHS [P01 NS035611, K25 NS041291, K25 NS041291-06, K25NS041291, P01 NS035611-14, P01 NS055104, P01 NS35611, P50 NS010828, P50 NS010828-32, P50 NS10828, R01 NS037074, R01 NS037074-08, R01 NS056458, R01 NS056458-05, R01 NS061505, R01-NS37074, R01-NS56458] NR 39 TC 98 Z9 102 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2007 VL 130 BP 1631 EP 1642 DI 10.1093/brain/awm071 PN 6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 183IA UT WOS:000247565300019 PM 17468117 ER PT J AU Griffith, HR Okonkwo, OC den Hollander, JA Belue, K Lanza, S Harrell, LE Brockington, JC Clark, DG Marson, DC AF Griffith, H. Randall Okonkwo, Ozioma C. den Hollander, Jan A. Belue, Katherine Lanza, Sara Harrell, Lindy E. Brockington, John C. Clark, David G. Marson, Daniel C. TI Brain Proton MRS is Correlated with Financial Abilities in Patients with Alzheimer's Disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Financial abilities; Alzheimer's disease; Cingulate gyrus; Brain metabolism; Magnetic resonance spectroscopy AB Persons with Alzheimer's disease (AD) demonstrate frank impairments in the performance of everyday functional abilities. However, the neuroanatomic and neuro-metabolic correlates of these functional deficits in mild AD are largely unknown. Using 3-Tesla proton magnetic resonance spectroscopy ((1)H-MRS) of the posterior cingulate gyrus in 14 patients with mild AD and 14 healthy adult controls, we sought to determine the brain metabolic correlates of financial impairments in mild AD. Both N-acetylaspartate (NAA) and choline-containing compounds (Cho) were found to be abnormal in mild AD. In AD patients, NAA showed a positive correlation with financial abilities, while Cho showed a possible negative correlation with financial abilities. These findings suggest that metabolic abnormalities of posterior cortical paralimbic regions may reflect the underlying neuropathological processes that are instrumental in the degradation of financial abilities in mild AD. Proton MRS could offer a means to track brain changes associated with functional change in mild AD. C1 [Griffith, H. Randall; Okonkwo, Ozioma C.] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Belue, Katherine; Lanza, Sara; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [den Hollander, Jan A.] Univ Alabama, Dept Med Cardiol, Birmingham, AL USA. [Harrell, Lindy E.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Griffith, HR (reprint author), Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. EM rlgriffith@uabmc.edu FU National Institute on Aging [1P50 AG16582-01]; Alzheimer's of Central Alabama [1R01 AG021927-01] FX This research was supported by grants from the National Institute on Aging (Alzheimer's Disease Research Center; 1P50 AG16582-01: Harrell, PI), (1R01 AG021927-01: Marson, PI) and grants from Alzheimer's of Central Alabama. NR 34 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2007 VL 1 IS 1-2 BP 23 EP 29 DI 10.1007/s11682-007-9002-3 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA V07KX UT WOS:000207261200004 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Aromatase inhibitor-associated arthralgia syndrome SO BREAST LA English DT Review DE adjuvant therapy; hormonal therapy; aromatase inhibitors; arthralgia; postmenopausal ID QUALITY-OF-LIFE; EARLY BREAST-CANCER; PLACEBO-CONTROLLED TRIAL; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; RHEUMATOID-ARTHRITIS; ADJUVANT TREATMENT; DOUBLE-BLIND; CONTINUED TAMOXIFEN; HORMONAL-THERAPY AB Aromatase inhibitors (Als) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. Clinical trials have assessed 5 years of At therapy, either as an alternative to tamoxifen for primary adjuvant therapy of breast cancer, or after 5 years of adjuvant tamoxifen. Treatment of 2-3 years' duration after 2-3 years of tamoxifen has also been studied. Al therapy brings side effects related to estrogen deprivation, and this side effect profile differs in clinically relevant ways from that seen with tamoxifen. In particular, the selective estrogen receptor modulatory effects of tamoxifen contribute to menopausal symptoms, vaginal discharge, and the rare but worrisome risks of thromboembolism and uterine carcinoma. By contrast, the low levels of estrogen achieved with aromatase inhibition contribute to menopausal symptoms, vaginal dryness and sexual dysfunction, and accelerated bone demineralization with risk of osteoporosis and osteoporotic fracture. Clinical experience also suggests that Al therapy is associated with a novel musculoskeletal side effect consisting of an arthralgia syndrome. The actual incidence of Al-associated arthralgias or musculoskeletal symptoms is not known, though such symptoms are quite prevalent and appear more commonly with Al use than with tamoxifen. Arthralgias can be a reason for discontinuation of Al treatment. The possible mechanisms of Al-associated arthralgia are unclear. Estrogen deficiency causes bone toss, which in turn contributes to arthralgia. Less well-studied functions of estrogen include regulating immune cells and cytokines involved in bone remodeling, and modulating pain sensitivity at the level of the central nervous system. Arthralgia and arthritis have seldom been rigorously differentiated in clinical trials of Als. Assessment of inflammatory and rheumatologic markers, as well as detailed evaluation of patient symptoms using appropriate quality-of-life instruments, may be warranted in order to understand both the symptoms and the etiology of the arthralgia syndrome. Treatment options for arthralgia (primarily non-steroidal anti-inflammatory drugs) are currently inadequate, but areas of active research include high-dose vitamin D and new-targeted therapies to inhibit bone loss. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 79 TC 82 Z9 83 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD JUN PY 2007 VL 16 IS 3 BP 223 EP 234 DI 10.1016/j.breast.2007.01.011 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZN UT WOS:000257273900003 PM 17368903 ER PT J AU Richardson, PG Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S San Miguel, JF Cavenagh, JD Anderson, KC AF Richardson, Paul G. Sonneveld, Pieter Schuster, Michael W. Irwin, David Stadtmauer, Edward A. Facon, Thierry Harousseau, Jean-Luc Ben-Yehuda, Dina Lonial, Sagar San Miguel, Jesus-F. Cavenagh, Jamie D. Anderson, Kenneth C. TI Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE multiple myeloma; bortezomib; high-risk; elderly; ISS staging ID ADVERSE PROGNOSTIC IMPACT; SOUTHWEST-ONCOLOGY-GROUP; HIGH-DOSE DEXAMETHASONE; STAGING SYSTEM; REFRACTORY MYELOMA; ADVANCED AGE; PHASE-2; THERAPY; TRIAL AB Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age >= 65 years) and high-risk (> 1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34-40% vs. 13-19%), including complete response rate (5-8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged >= 65 years and with > 1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. New York Presbyterian Hosp, New York, NY USA. Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Hosp Univ Salamanca, Salamanca, Spain. St Bartholomews Hosp, London, England. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI 2007, Secribsal/A-1556-2012; FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 19 TC 75 Z9 79 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2007 VL 137 IS 5 BP 429 EP 435 DI 10.1111/j.1365-2141.2007.06585.x PG 7 WC Hematology SC Hematology GA 163TT UT WOS:000246186800006 PM 17451408 ER PT J AU Vivanco, I Palaskas, N Tran, C Finn, SP Getz, G Kennedy, NJ Jiao, J Rose, J Xie, WL Loda, M Golub, T Mellinghoff, IK Davis, RJ Wu, H Sawyers, CL AF Vivanco, Igor Palaskas, Nicolaos Tran, Chris Finn, Stephen P. Getz, Gad Kennedy, Norman J. Jiao, Jing Rose, Joshua Xie, Wanling Loda, Massimo Golub, Todd Mellinghoff, Ingo K. Davis, Roger J. Wu, Hong Sawyers, Charles L. TI Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN SO CANCER CELL LA English DT Article ID PROSTATE INTRAEPITHELIAL NEOPLASIA; INSULIN-RECEPTOR SUBSTRATE-1; JUN NH2-TERMINAL KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; GLIOBLASTOMA-MULTIFORME; TRANSDUCTION PATHWAY; CELL-PROLIFERATION; MAMMALIAN TARGET; UP-REGULATION AB Although most oncogenic phenotypes of PTEN loss are attributed to AKT activation, AKT alone is not sufficient to induce all of the biological activities associated with PTEN inactivation. We searched for additional PTEN-regulated pathways through gene set enrichment analysis (GSEA) and identified genes associated with JNK activation. PTEN null cells exhibit higher JNK activity, and genetic studies demonstrate that JNK functions parallel to and independently of AKT. Furthermore, PTEN deficiency sensitizes cells to JNK inhibition and negative feedback regulation of PI3K was impaired in PTEN null cells. Akt and JNK activation are highly correlated in human prostate cancer. These findings implicate JNK in PI3K-driven cancers and demonstrate the utility of GSEA to identify functional pathways using genetically defined systems. C1 Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. MIT, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, Howard Hughes Med Inst, Worcester, MA 01605 USA. RP Sawyers, CL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. EM sawyersc@mskcc.org RI Jiao, Jing/F-5354-2015; Sawyers, Charles/G-5327-2016; OI Vivanco, Igor/0000-0001-6347-9416; Finn, Stephen/0000-0002-8628-5814 FU NIGMS NIH HHS [5F31GM067600] NR 61 TC 135 Z9 140 U1 5 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2007 VL 11 IS 6 BP 555 EP 569 DI 10.1016/j.ccr.2007.04.021 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 179MB UT WOS:000247292800009 PM 17560336 ER PT J AU Schwarzberg, AB Stover, EH Sengupta, T Michelini, A Vincitore, M Baden, LR Kulke, MH AF Schwarzberg, Abraham B. Stover, Elizabeth H. Sengupta, Tanya Michelini, Ann Vincitore, Michele Baden, Lindsey R. Kulke, Matthew H. TI Selective lymphopenia and opportunistic infections in neuroendocrine tumor patients receiving temozolomide SO CANCER INVESTIGATION LA English DT Article DE temozolomide; neuroendocrine tumor; carcinoid; lymphopenia; opportunistic infection; pneumocystis jiroveci; pneumonia ID PNEUMOCYSTIS-CARINII-PNEUMONIA; VARICELLA-ZOSTER-VIRUS; PHASE-II; MARROW-TRANSPLANTATION; ANTIVIRAL THERAPY; HIV-INFECTION; CYTOMEGALOVIRUS; MELANOMA; CANCER; CHEMOTHERAPY AB Temozolomide is utilized as a treatment for a variety of solid tumors and has been associated with the development of selective lymphopenia. We evaluated the incidence of lymphopenia and opportunistic infections during treatment and up to 12 months following treatment discontinuation in a cohort of 39 patients receiving temozolomide for advanced neuroendocrine tumors. The incidence of Grade 3-4 lymphopenia was 46 percent after 4 months of therapy and remained at 30 percent or greater for 12 months following treatment discontinuation. The overall incidence of opportunistic infections was 10 percent, while among patients receiving therapy for >= 7 months, the incidence was 20 percent. Prophylaxis for Pneumocystis jiroveci pneumonia and varicella-zoster, as well as cytomegalovirus monitoring, should be considered in patients receiving temozolomide-based treatment. C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. RP Schwarzberg, AB (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, 44 Binney St, Boston, MA 02115 USA. EM aschwarzberg@partners.org FU NCI NIH HHS [K23 CA093401]; NHLBI NIH HHS [K30 HL04095]; NIGMS NIH HHS [T32 GM007753, T32GM07753-24] NR 30 TC 37 Z9 37 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD JUN PY 2007 VL 25 IS 4 BP 249 EP 255 DI 10.1080/07357900701206380 PG 7 WC Oncology SC Oncology GA 186MD UT WOS:000247781900005 PM 17612935 ER PT J AU Kozin, SV Winkler, F Garkavtsev, I Hicklin, DJ Jain, RK Boucher, Y AF Kozin, Sergey V. Winkler, Frank Garkavtsev, Igor Hicklin, Daniel J. Jain, Rakesh K. Boucher, Yves TI Human tumor xenografts recurring after radiotherapy are more sensitive to anti-vascular endothelial growth factor receptor-2 treatment than treatment-naive tumors SO CANCER RESEARCH LA English DT Article ID FIBRILLAR COLLAGEN; VASCULAR FUNCTION; IN-VIVO; ANGIOGENESIS; ANTIBODY; THERAPY; IRRADIATION; MOUSE; MICE; BED AB The effects of antiangiogenic therapy on tumors relapsing after irradiation are not known. To this end, we irradiated human tumors growing s.c. in nude mice with a single dose of 20 or 30 Gy. Compared with primary (treatment-naive) xenografts, the growth rate of recurrent tumors was 1.6-fold slower, which is consistent with the known "tumor bed effect." For similar size tumors, recurrences had fewer functional vessels, a reduced vessel coverage by perivascular cells, and were more necrotic. Placenta growth factor concentration was significantly lower in relapses, whereas vascular endothelial growth factor (VEGF) levels were similar between primary and recurrent tumors. On the other hand, fibrillar collagen deposition was significantly increased in recurrent tumors. This radiation-induced fibrosis was partially responsible for the slower growth of recurrences; the i.t. injection of collagenase increased the growth rate of tumor relapses without affecting primary tumor growth. The mouse-specific VEGF receptor 2-blocking antibody DC101 induced a 2.2-fold longer growth delay in recurrent tumors compared with treatment-naive tumors. DC101 significantly decreased the interstitial fluid pressure and did not change the functional vessel density and perivascular cell coverage in both tumor variants. Interestingly, DC101 induced a rapid (2 days after treatment initiation) and significant decrease in tumor cell proliferation in recurrent but not in primary tumors. Thus, our results show that the stromal compartment and the response to antiangionenic therapy of primary and in-field recurrent tumors are significantly different. Our findings suggest that antiangiogenic agents could be effective in the treatment of patients with relapses after radiotherapy. C1 Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol Radiat Oncol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. ImClone Syst Inc, New York, NY USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol Radiat Oncol, Dept Radiat Oncol, Cox 7,1800 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01-CA98706, P01-CA80124, R01-CA115767] NR 33 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5076 EP 5082 DI 10.1158/0008-5472.CAN-06-3664 PG 7 WC Oncology SC Oncology GA 175NS UT WOS:000247020900005 PM 17545583 ER PT J AU Daikoku, T Tranguch, S Chakrabarty, A Wang, DZ Khabele, D Orsulic, S Morrow, JD DuBois, RN Dey, SK AF Daikoku, Takiko Tranguch, Susanne Chakrabarty, Anindita Wang, Dingzhi Khabele, Dineo Orsulic, Sandra Morrow, Jason D. DuBois, Raymond N. Dey, Sudhansu K. TI Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer SO CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTESTINAL ADENOMA GROWTH; PPAR-DELTA; COLORECTAL-CANCER; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); TRANSCRIPTIONAL REPRESSION; CELL-PROLIFERATION; CARCINOMA CELLS; EXPRESSION; GAMMA AB The underlying causes of epithelial ovarian cancer (EOC) are unclear, and treatment options for patients with advanced disease are limited. There is evidence that the use of nonsteroidal anti-inflammatory drugs is associated with decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We previously showed that mouse and human EOCs have increased levels of COX-1, but not COX-2, and a COX-1-selective inhibitor, SC-560, attenuates prostaglandin production and tumor growth. However, the downstream targets of COX-1 signaling in EOC are not yet known. To address this question, we evaluated peroxisome proliferator-activated receptor 6 (PPAR delta) expression and function in EOC. We found that EOC cells express high levels of PPAR delta, and neutralizing PPAR delta function reduces tumor growth in vivo. More interestingly, aspirin, a nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1, compromises PPAR delta function and cell growth by inhibiting extracellular signal-regulated kinases 1/2, members of the mitogen-activated protein kinase family. Our study, for the first time, shows that whereas PPAR delta can he a target of COX-1, extracellular signal-regulated kinase is a potential target of PPAR delta. The ability of aspirin to inhibit EOC growth in vivo is an exciting finding because of its low cost, lack of cardiovascular side effects, and availability. C1 Vanderbilt Univ, Div Reprod & Dev Biol, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Div Reprod & Dev Biol, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Div Reprod & Dev Biol, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Div Reprod & Dev Biol, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Meharry Med Coll, Dept Obstet & Gynecol, Nashville, TN 37208 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. RP Dey, SK (reprint author), Vanderbilt Univ, Div Reprod & Dev Biol, Med Ctr, Dept Pediat, 221 Kirkland Hall, Nashville, TN 37232 USA. EM sk.dey@vanderbilt.edu OI Tranguch, Susanne/0000-0001-9496-7260 FU NCI NIH HHS [P01-CA-77839, U54CA091405-06]; NICHD NIH HHS [R37 HD12304]; NIDA NIH HHS [F31 DA0212062] NR 47 TC 27 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5285 EP 5292 DI 10.1158/0008-5472.CAN-07-0828 PG 8 WC Oncology SC Oncology GA 175NS UT WOS:000247020900031 PM 17545608 ER PT J AU Qiao, M Iglehart, JD Pardee, AB AF Qiao, Meng Iglehart, J. Dirk Pardee, Arthur B. TI Metastatic potential of 21T human breast cancer cells depends on Akt/protein kinase B activation SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; INTEGRIN-LINKED KINASE; RICTOR-MTOR COMPLEX; PROTEIN-KINASE; SIGNALING PATHWAY; TUMOR PROGRESSION; GROWTH-FACTOR; PHOSPHORYLATION; BINDING; B/AKT AB Most cancer lethality is caused by metastasis. To gain insight into the molecular basis of tumor progression to metastasis, we used the 21T series of human mammary epithelial cells obtained by successive biopsies from one breast cancer patient. The c-erbB2 gene is amplified and overexpressed in each of three 21T tumor lines. The erbB receptor tyrosine kinase-activated phosphatidylinositol 3-kinase/Akt signaling cascade is crucial for the development and maintenance of epithelial cells, and dysregulation of this pathway is frequently associated with cellular transformation and cancer. For Akt to be fully activated, Ser(473) on its COOH terminus needs to be phosphorylated. We detected more Ser(473) Akt phosphorylation in MT cells, derived from a pleural effusion, compared with cells from the primary tumor. This phosphorylation has recently been shown to be catalyzed by mammalian target of rapamycin (mTOR)/rictor kinase. By using genetic and pharmacologic activators and inhibitors, we showed that Ser(473) Akt phosphorylation is more sensitive to mTOR/rictor inhibition in metastatic tumor cells than normal mammary epithelial and primary tumor cells. The mTOR/rictor kinase activity was indispensable for both Ser(473) Akt phosphorylation and migration of metastatic MT2 cells. In addition, a large decrease of protein phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP) was found, which could be responsible for the overexpression of Ser 473 Akt in MT cells. Our data indicate that these breast cancer cells acquire new vulnerabilities, rictor and PHLPP, which might provide an Achilles' heel for therapeutic intervention of breast cancer metastasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02135 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Qiao, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith Bldg 928,44 Binney St, Boston, MA 02135 USA. EM arthur_pardee@dfci.harvard.edu NR 50 TC 48 Z9 59 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5293 EP 5299 DI 10.1158/0008-5472.CAN-07-0877 PG 7 WC Oncology SC Oncology GA 175NS UT WOS:000247020900032 PM 17545609 ER PT J AU Schernhammer, E Wolpin, B Rifai, N Cochrane, B Manson, JA Ma, J Giovannucci, E Thomson, C Stampfer, MJ Fuchs, C AF Schernhammer, Eva Wolpin, Brian Rifai, Nader Cochrane, Barbara Manson, Jo Ann Ma, Jing Giovannucci, Ed Thomson, Cynthia Stampfer, Meir J. Fuchs, Charles TI Plasma folate, vitamin B-6, vitamin B-12, and homocysteine and pancreatic cancer risk in four large cohorts SO CANCER RESEARCH LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE; COLORECTAL ADENOMA; PHYSICAL-ACTIVITY; MALE SMOKERS; OBESITY; POLYMORPHISMS; EPIDEMIOLOGY; METHIONINE; SYNTHASE; WOMEN AB Folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. Few studies have examined the influence of one-carbon nutrients on pancreatic cancer risk, although recent studies suggest a potential protective effect for one-carbon nutrients from food sources, but not from supplements. We conducted a prospective nested case-control study to examine plasma concentrations of folate, vitamin B-6 [whose main circulating form is pyridoxal-5'-phosphate (PLP)], vitamin B-12, and homocysteine in relationship to pancreatic cancer, using four large prospective cohorts. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. All statistical tests were two sided. Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B-12 or homocysteine and pancreatic cancer risk. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% Cl, 0.76-1.91) for folate, 0.80 (95% Cl, 0.51-1.25) for B-6, 0-91 (95% Cl, 0.57-1.46) for B-12, and 1.43 (95% Cl, 0.90-2.28) for homocysteine. In analyses restricted to nonusers of multivitamins, we observe a modest inverse trend between folate, PLP, and B-12 and pancreatic cancer risk. In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Among all participants, plasma levels of folate, B-6, B-12, and homocysteine were not associated with a significant reduction in the risk of pancreatic cancer. Among participants who obtain these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B-6, and B-12 and risk. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. ACR ITR VIEnna, Vienna, Austria. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ Arizona, Dept Nutr, Coll Agr & Life Sci, Tucson, AZ USA. RP Schernhammer, E (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu FU NCI NIH HHS [CA70817, CA42812, CA55075, CA58684, CA87969, CA90598, R01 CA124908, T32 CA009172] NR 25 TC 36 Z9 41 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5553 EP 5560 DI 10.1158/0008-5472.CAN-06-4463 PG 8 WC Oncology SC Oncology GA 175NS UT WOS:000247020900062 PM 17545639 ER PT J AU Michaelson, MD AF Michaelson, M. Dror TI ASCO 2006 highlights: Targeted therapy for renal cell carcinoma SO CANCER TREATMENT REVIEWS LA English DT Review DE ASCO 2006; RCC; renal cell carcinoma; sorafenib; sunitinib; SU11248; targeted therapy; ternsirolimus ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; RANDOMIZED PHASE-II; FACTOR RECEPTOR; IN-VIVO; INTERFERON-ALPHA; MAMMALIAN TARGET; KIDNEY CANCER; PATIENTS PTS; SU11248 AB In the past few years, advances in the understanding of the pathogenesis of renal cell carcinoma (RCC) have resulted in the identification of new therapeutic targets, and ultimately, the development of new targeted agents for the treatment of the disease. This paper reviews latest data in RCC for the recently approved agents sunitinib and sorafenib, as welt as other molecularly targeted drugs, presented at the annual meeting of the American Society for Clinical Oncology, held in Atlanta, Georgia, in June 2006. Clinical findings to date show that these new agents are challenging the role of cytokines in this setting, and for some (e.g. sunitinib) a substantially improved efficacy profile (progression -free survival and response) over conventional cytokine therapy has been reported. While challenges remain with regard to optimal use of these agents, the outlook for patients with advanced RCC has improved considerably and there is great hope for continuing progress. (C) 2007 Elsevier Ltd. All. rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaetsonl@partners.org OI Michaelson, Dror/0000-0001-9249-6338 NR 57 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD JUN PY 2007 VL 33 IS 4 BP 381 EP 390 DI 10.1016/j.ctrv.2007.01.002 PG 10 WC Oncology SC Oncology GA 176PW UT WOS:000247098400007 PM 17367939 ER PT J AU Liu, G Zhou, W Yeap, BY Su, L Wain, JC Poneros, JM Nishioka, NS Lynch, TJ Christiani, DC AF Liu, Geoffrey Zhou, Wei Yeap, Beow Y. Su, Li Wain, John C. Poneros, John M. Nishioka, Norman S. Lynch, Thomas J. Christiani, David C. TI XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR GENES; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER RISK; BARRETTS-ESOPHAGUS; CHINESE POPULATION; UNITED-STATES; ASSOCIATIONS; CAPACITY; SMOKING; DAMAGE AB DNA damage is important in the pathogenesis of esophageal adenocarcinoma (EA). Polymorphic variants in DNA repair genes may be modifiers of the risk of EA through their role in altering human host response to gastroesophageal acid reflux, a well-described risk factor for EA. We studied the role of genetic polymorphisms of two key DNA repair genes, xeroderma pigmentosum group D (XPD) (Asp312Asn and Lys751Gln) in the nucleotide excision repair (NER) pathway and X-ray repair cross-complementing gene 1 (XRCC1) (Arg399Gln) in the base excision repair (BER) pathway, in the development of EA in 183 cases and 336 frequency-matched controls for age, gender and race. Genomic DNA was extracted from blood samples. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from logistic regression models, adjusted for body mass index at 18 years of age, smoking and alcohol exposure. The variant genotypes of XPD Lys751Gln polymorphism were associated with a higher risk of EA; the adjusted OR comparing Gln/Gln + Lys/Gln with Lys/Lys was 1.49 (95% CI: 1.02-2.14). Although no significant relationships were found for the XRCC1 Arg399Gln polymorphism alone, this polymorphism did modify the relationship between XPD Lys751Gln and EA risk; when both polymorphisms were evaluated together, adding the number of variant alleles of the two polymorphisms resulted in a significant trend (trend test, P = 0.008); compared with individuals with no variant alleles (n = 88), the adjusted ORs of developing EA are 1.49 (95% CI: 0.88-2.59), 1.69 (95% CI: 0.98-2.96) and 2.58 (95% CI: 1.315.06) for one (n = 195), two (n = 166) and three or four variant alleles (n = 70), respectively. No relationships were found for the XPD Asp312Asn polymorphism. We conclude that combined NER and BER pathways are important to the development of EA. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Liu, G (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM geoffrey.liu@uhn.on.ca RI Mendez, Pedro /J-8955-2016; Liu, Geoffrey/N-4421-2016 OI Mendez, Pedro /0000-0001-6713-7907; FU NCI NIH HHS [ES/CA06409, CA109193, CA110822, CA74386] NR 41 TC 44 Z9 46 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2007 VL 28 IS 6 BP 1254 EP 1258 DI 10.1093/carcin/bgm020 PG 5 WC Oncology SC Oncology GA 189OZ UT WOS:000247999700018 PM 17264068 ER PT J AU Chopra, V Choksi, PU Cavusoglu, E AF Chopra, Vineet Choksi, Palak U. Cavusoglu, Erdal TI Beyond lipid lowering: The anti-hypertensive role of statins SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE cholesterol; blood pressure lowering; endothelium; statins; pleiotropic; review ID ENDOTHELIAL NITRIC-OXIDE; COA REDUCTASE INHIBITORS; ACUTE CORONARY SYNDROMES; SMOOTH-MUSCLE-CELLS; BLOOD-PRESSURE; ATHEROSCLEROTIC PLAQUES; CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; CHOLESTEROL LEVELS; SUPEROXIDE ANION AB Introduction The management of the hypercholesterolemic patient has evolved tremendously with the introduction of the HMG-CoA Reductase inhibitors, a class of drugs better known as the statins. Statins modify cholesterol metabolism by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, producing greater decreases in plasma cholesterol levels than previously realized with hypolipidemic therapy. With the advent of the classic statin-megatrials such as the Scandinavian Simvastatin Survival Study (4S), WOSCOPS, CARE, and the more recent Heart Protection Study (HPS), the role of statins in both the primary and secondary prevention and ultimate risk reduction of patients with coronary disease has been firmly established. Discussion With an increase in use and popularity, a number of beneficial actions of the statins unrelated to their cholesterol-lowering ability have been reported. These effects have generated greater interest in the possible additional roles and indications for the use of these drugs. Of central focus in this paper is the cholesterol-independent benefit of this group of agents on the cardiovascular system, particularly on the lowering of systemic blood pressure. A number of hypotheses have been proposed for this action and these shall be reviewed within this paper. Conclusion We explore recent data that suggests that statins may provide substantial reduction of blood pressure in the hypertensive, hypercholesterolemic patient independent of their lipid-lowering effect. In addition, we review several notable publications that postulate unique mechanisms for this action and benefit. We also present plausible explanations as to why some of the larger statin trials did not report similar such findings. C1 Bronx Vet Affairs Med Ctr, Div Internal Med, Bronx, NY USA. SUNY, Downstate Med Ctr, Div Cardiol, Brooklyn, NY USA. Mt Sinai Sch Med, Bronx, NY USA. RP Chopra, V (reprint author), Bronx Vet Affairs Med Ctr, Div Internal Med, Bronx, NY USA. EM vineet.chopra@sbcglobal.net NR 51 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 EI 1573-7241 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD JUN PY 2007 VL 21 IS 3 BP 161 EP 169 DI 10.1007/s10557-007-6025-3 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 171WE UT WOS:000246765300005 PM 17468937 ER PT J AU Bates, MC Campbell, JE Stone, PA Jaff, MR Broce, M Lavigne, PS AF Bates, Mark C. Campbell, John E. Stone, Patrick A. Jaff, Michael R. Broce, Mike Lavigne, Philip S. TI Factors affecting long-term survival following renal artery stenting SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE renal stent; angioplasty; outcomes and mortality ID CORONARY-HEART-DISEASE; ATHEROSCLEROTIC RENOVASCULAR DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; PERIPHERAL VASCULAR-DISEASE; BLOOD-PRESSURE CONTROL; CHRONIC KIDNEY-DISEASE; CARDIAC-CATHETERIZATION; NATURAL-HISTORY; CARDIOVASCULAR EVENTS; CHOLESTEROL LEVELS AB Introduction: This study defines clinical variables at the time of renal artery stenting that may be predictors of long-term all-cause mortality. Methods: The data are derived from the single operator, single center, renal stent retrospective study (SOCRATES) and includes a review of 748 (336 men, 412 women) consecutive symptomatic patients with de novo atherosclerotic renal artery stenosis treated over an 11-year period. All patients had clinical indications for renal revascularization, including, but not limited to; suboptimal control of hypertension, chronic kidney disease, and cardiac disturbance syndromes. Clinical variables at the time of the index procedure were evaluated as predictors of all-cause mortality using multivariate analysis. Mortality data were derived from hospital records and formal queries of the State Department of Health and Human Services, Health and Vital Statistics Division database. Results: In-hospital, 30-day and 6-month mortality rates were 0.5, 2.0, and 6.3%, respectively. Overall patient survival at years 1, 5, and 10 was 91.2, 66.6, and 40.9%, respectively. Comorbid conditions, including chronic obstructive pulmonary disease and congestive heart failure, were independently associated with increased mortality. There were incremental changes in mortality in patients with baseline azotemia, [preprocedure serum creatinine (sCr) 1.5-2.09 mg/dL hazard ratio 1.52; sCr >2.5 mg/dL hazard ratio 3.39]. Therapy with lipid lowering agents offered a survival advantage (hazard ratio 0.69, P = 0.0.049); however, this study was not designed to evaluate a "protective effect" of lipid lowering medications. Conclusions: Patients with chronic obstructive pulmonary disease and congestive heart failure undergoing renal artery stent revascularization have a poor long-term prognosis. Baseline azotemia is the strongest independent predictor of all cause mortality, with more than 70% of patients with marked azotemia (sCr > 2.5) dead at 5 years. (C) 2007 Wiley-Liss, Inc. C1 Charleston Area Med Ctr, Vasc Ctr Excellence, Charleston, WV USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Sch Med, Charleston Div, Charleston, WV 25304 USA. W Virginia Univ, Sch Med, Charleston Div, Charleston, WV USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Charleston Area Med Ctr, Res Inst, Outcomes Res Div, Charleston, WV USA. Charleston Area Med Ctr, Res Inst, Ctr Clin Sci Res, Charleston, WV USA. RP Bates, MC (reprint author), Dept Surg, 3100 MacCorkle Ave SE, Charleston, WV 25304 USA. EM markbates@charter.net NR 48 TC 35 Z9 37 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2007 VL 69 IS 7 BP 1037 EP 1043 DI 10.1002/ccd.21121 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 175DT UT WOS:000246993600022 PM 17525962 ER PT J AU Jaff, MR AF Jaff, Michael R. TI Renal artery stenosis: What we don't know won't hurt us....right? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID STENT REVASCULARIZATION; MANAGEMENT; DISEASE C1 Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Dept Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM mjaff@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2007 VL 69 IS 7 BP 1044 EP 1045 DI 10.1002/ccd.21234 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 175DT UT WOS:000246993600023 PM 17525995 ER PT J AU Shetty, SV Kwolek, CJ Garasic, JM AF Shetty, Sharad V. Kwolek, Christopher J. Garasic, Joseph M. TI Percutaneous closure after inadvertent subclavian artery cannulation SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE central venous catheterization; complications; angioseal ID VEIN CATHETERIZATION; DEVICE; PUNCTURE; COMPLICATIONS; PLACEMENT AB Accidental insertion of an arterial sheath is an uncommon but potentially serious complication of jugular venous catheterization. When the subclavian artery is inadvertently cannulated, sheath removal can be complicated by significant hemorrhage due to its incompressible location. We report a case of inadvertent insertion of an 8 French sheath into the subclavian artery, which was successfully removed and the puncture site sealed with a collagen-based vascular closure device (Angio-Seal STS Plus). This averted an otherwise emergent open surgical procedure to remove the sheath and repair the subclavian artery in a high-risk patient. (C) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Shetty, SV (reprint author), Royal Perth Hosp, Dept Cardiol, Wellington St, Perth, WA 6000, Australia. EM Sharad.Shetty@health.wa.gov.au NR 11 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2007 VL 69 IS 7 BP 1050 EP 1052 DI 10.1002/ccd.21143 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 175DT UT WOS:000246993600026 PM 17421015 ER PT J AU Sablina, AA Chen, W Arroyo, JD Corral, L Hector, M Bulmer, SE DeCaprio, JA Hahn, WC AF Sablina, Anna A. Chen, Wen Arroyo, Jason D. Corral, Laura Hector, Melissa Bulmer, Sara E. DeCaprio, James A. Hahn, William C. TI The tumor suppressor PP2A A beta regulates the RaIA GTPase SO CELL LA English DT Article ID PROTEIN PHOSPHATASE 2A; HUMAN CELL-TRANSFORMATION; SMALL-T-ANTIGEN; RAL-GTPASES; SUBUNIT INTERACTION; SIGNALING PATHWAY; PPP2R1B GENE; CANCER-CELLS; ACTIVATION; ALPHA AB The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that regulates numerous signaling pathways. Biallelic mutations of the structural PP2A A beta subunit occur in several types of human tumors; however, the functional consequences of these cancer-associated PP2A A beta mutations in cell transformation remain undefined. Here we show that suppression of PP2A A beta expression permits immortalized human cells to achieve a tumorigenic state. Cancer-associated A beta mutants fail to reverse tumorigenic phenotype induced by PP2A A beta suppression, indicating that these mutants function as null alleles. Wild-type PP2A A beta but not cancer-derived A beta mutants form a complex with the small GTPase RalA. PP2A A beta-containing complexes dephosphorylate RalA at Ser183 and Ser194, inactivating RalA and abolishing its transforming function. These observations identify PP2A A beta as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA. C1 Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Sun Yat Sen Univ, Sch Publ Hlth, Dept Toxicol, Guangzhou 510080, Peoples R China. Dana Farber Canc Inst, DF HCC Monoclonal Antibody Core, Boston, MA 02215 USA. RP Hahn, WC (reprint author), Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [P01 CA050661, P01 CA050661-190009, P01 CA50661] NR 58 TC 121 Z9 128 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 1 PY 2007 VL 129 IS 5 BP 969 EP 982 DI 10.1016/j.cell.2007.03.047 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 176KT UT WOS:000247084600016 PM 17540176 ER PT J AU Konner, AC Janoschek, R Plum, L Jordan, SD Rother, E Ma, XS Xu, C Enriori, P Hampel, B Barsh, GS Kahn, CR Cowley, MA Ashcroft, FM Bruning, JC AF Koenner, A. Christine Janoschek, Ruth Plum, Leona Jordan, Sabine D. Rother, Eva Ma, Xiaosong Xu, Chun Enriori, Pablo Hampel, Brigitte Barsh, Gregory S. Kahn, C. Ronald Cowley, Michael A. Ashcroft, Frances M. Bruening, Jens C. TI Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production SO CELL METABOLISM LA English DT Article ID ARCUATE NUCLEUS; HYPOTHALAMIC NEURONS; WEIGHT HOMEOSTASIS; GENE-EXPRESSION; POMC NEURONS; BODY-WEIGHT; FOOD-INTAKE; LEPTIN; BRAIN; RECEPTOR AB Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-iR knockout (IR AAgRP) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRIP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes. C1 Univ Cologne, Inst Genet, Ctr Mol Med, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. Univ Cologne, Klin & Poliklin Innere Med 2, Ctr Mol Med, D-50931 Cologne, Germany. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. RP Bruning, JC (reprint author), Univ Cologne, Inst Genet, Ctr Mol Med, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. EM jens.bruening@uni-koeln.de RI Cowley, Michael/B-9428-2008 OI Cowley, Michael/0000-0001-7811-134X FU NCRR NIH HHS [RR 0163]; NIDDK NIH HHS [DK 62202] NR 35 TC 270 Z9 279 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUN PY 2007 VL 5 IS 6 BP 438 EP 449 DI 10.1016/j.cmet.2007.05.004 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 176WK UT WOS:000247115400007 PM 17550779 ER PT J AU He, P Shan, L Sheen, J AF He, Ping Shan, Libo Sheen, Jen TI Elicitation and suppression of microbe-associated molecular pattern-triggered immunity in plant-microbe interactions SO CELLULAR MICROBIOLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASES; ELONGATION-FACTOR TU; PATHOGEN PSEUDOMONAS-SYRINGAE; BACTERIAL ELICITOR FLAGELLIN; ARABIDOPSIS INNATE IMMUNITY; ETHYLENE-INDUCING XYLANASE; DISEASE-RESISTANCE; DEFENSE RESPONSES; III EFFECTORS; MAP KINASE AB Recent studies have uncovered fascinating molecular mechanisms underlying plant-microbe interactions that coevolved dynamically. As in animals, the primary plant innate immunity is immediately triggered by the detection of common pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs). Different MAMPs are often perceived by distinct cell-surface pattern-recognition receptors (PRRs) and activate convergent intracellular signalling pathways in plant cells for broad-spectrum immunity. Successful pathogens, however, have evolved multiple virulence factors to suppress MAMP-triggered immunity. Specifically, diverse pathogenic bacteria have employed the type III secretion system to deliver a repertoire of virulence effector proteins to interfere with host immunity and promote pathogenesis. Plants challenged by pathogens have evolved the secondary plant innate immunity. In particular, some plants possess the specific intracellular disease resistance (R) proteins to effectively counteract virulence effectors of pathogens for effector-triggered immunity. This potent but cultivar-specific effector-triggered immunity occurs rapidly with localized programmed cell death/hypersensitive response to limit pathogen proliferation and disease development. Remarkably, bacteria have further acquired virulence effectors to block effector-triggered immunity. This review covers the latest findings in the dynamics of MAMP-triggered immunity and its interception by virulence factors of pathogenic bacteria. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU PHS HHS [R01 G70567] NR 110 TC 93 Z9 98 U1 2 U2 33 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2007 VL 9 IS 6 BP 1385 EP 1396 DI 10.1111/j.1462-5822.2007.00944.x PG 12 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 169FF UT WOS:000246577400003 PM 17451411 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI Cortical spreading depression - a critical link in migraine pathogenesis SO CEPHALALGIA LA English DT Meeting Abstract CT 13th Congress of the International-Headache-Society CY JUN 28-JUL 01, 2007 CL Stockholm, SWEDEN SP Int Headache Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2007 VL 27 IS 6 BP 575 EP 575 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176VU UT WOS:000247113800020 ER PT J AU Duffy, KR Murphy, KM Frosch, MP Livingstone, MS AF Duffy, Kevin R. Murphy, Kathryn M. Frosch, Matthew P. Livingstone, Margaret S. TI Cytochrome oxidase and neurofilament reactivity in monocularly deprived human primary visual cortex SO CEREBRAL CORTEX LA English DT Article DE CO blobs; deprivation; human; neurofilament; ocular dominance columns; primary visual cortex ID OCULAR DOMINANCE COLUMNS; STRIATE CORTEX; MACAQUE MONKEY; COMPARTMENTAL ORGANIZATION; FUNCTIONAL ARCHITECTURE; RECEPTIVE FIELDS; SQUIRREL-MONKEY; CATS; PLASTICITY; NEURONS AB Previous studies of human primary visual cortex (V1) have demonstrated a significant eye-specific decrease in cytochrome oxidase (CO) staining following monocular enucleation. We have extended these results by examining CO staining and neurofilament labeling in V1 from a patient with long-standing monocular blindness. A pattern of reduced neurofilament reactivity was found to align with pale CO-stained ocular dominance columns. Neurons located within deprived ocular dominance columns were significantly smaller compared with those in nondeprived columns. A spatial analysis of the relationship between CO blobs and ocular dominance columns revealed that both deprived and nondeprived blobs tended to align with the centers of ocular dominance columns. C1 Dalhousie Univ, Life Sci Ctr, Dept Psychol, Halifax, NS B3H 4J1, Canada. McMaster Univ, Dept Psychol, Hamilton, ON L8S 4K1, Canada. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Duffy, KR (reprint author), Dalhousie Univ, Life Sci Ctr, Dept Psychol, Halifax, NS B3H 4J1, Canada. EM kevin.duffy@dal.ca FU NEI NIH HHS [R01 EY016187-01A2, EY 13135, EY 16187, R01 EY013135, R01 EY016187] NR 30 TC 12 Z9 12 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2007 VL 17 IS 6 BP 1283 EP 1291 DI 10.1093/cercor/bhl038 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 169VO UT WOS:000246620400004 PM 16831856 ER PT J AU Makris, N Biederman, J Valera, EM Bush, G Kaiser, J Kennedy, DN Caviness, VS Faraone, SV Seidman, LJ AF Makris, Nikos Biederman, Joseph Valera, Eve M. Bush, George Kaiser, Jonathan Kennedy, David N. Caviness, Verne S. Faraone, Stephen V. Seidman, Larry J. TI Cortical thinning of the attention and executive function networks in adults with Attention-Deficit/Hyperactivity disorder SO CEREBRAL CORTEX LA English DT Review DE ADHD; attention; cerebral cortex; cortical thickness; executive function ID ANTERIOR CINGULATE CORTEX; DEFICIT HYPERACTIVITY DISORDER; RIGHT-HEMISPHERE DOMINANCE; HUMAN CEREBRAL-CORTEX; DISCONNEXION SYNDROMES; SUSTAINED ATTENTION; RHESUS-MONKEY; MOTOR CONTROL; HUMAN BRAIN; MRI AB Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that AND in adults is associated with thinner cortex in the cortical networks that modulate attention and EF. C1 Harvard Univ, Massachusetts Gen Hosp, Med Sch,Ctr Morphometr Anal Hlth Sci & Technol, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Med Sch,Ctr Morphometr Anal Hlth Sci & Technol, Radiol Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Hlth Sci & Technol Athinoula A Martinos Ctr Biome, Boston, MA 02129 USA. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Med Sch, Massachusetts Mental Hlth Ctr Publ Psychiat Div,D, Boston, MA 02115 USA. RP Makris, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Med Sch,Ctr Morphometr Anal Hlth Sci & Technol, Dept Neurol, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41 RR 14075]; NICHD NIH HHS [MH/HD 62152]; NIMH NIH HHS [MH 16259, MH 57934, F32 MH 0605040-01A1] NR 108 TC 227 Z9 230 U1 6 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2007 VL 17 IS 6 BP 1364 EP 1375 DI 10.1093/cercor/bhl047 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 169VO UT WOS:000246620400012 PM 16920883 ER PT J AU Hariharan, S Welsh, CH AF Hariharan, Sujatha Welsh, Carolyn H. TI Shortness of breath and hypoxemia after chemotherapy with carboplatin and gemcitabine SO CHEST LA English DT Editorial Material ID OBLITERANS ORGANIZING PNEUMONIA; PULMONARY TOXICITY C1 Denver Vet Affairs Med Ctr, Div Pulm Sci & Crit Care Med, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Med Oncol, Aurora, CO USA. RP Welsh, CH (reprint author), Denver Vet Affairs Med Ctr, Div Pulm Sci & Crit Care Med, Dept Med, 1055 Clermont St, Denver, CO 80220 USA. EM Carolyn.Welsh@med.va.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2007 VL 131 IS 6 BP 1978 EP 1981 DI 10.1378/chest.06-1464 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 180CD UT WOS:000247336600056 PM 17565034 ER PT J AU Baggish, AL van Kimmenade, R Bayes-Genis, A Davis, M Lainchbury, JG Frampton, C Pinto, Y Richards, MA Januzzi, JL AF Baggish, Aaron L. van Kimmenade, Roland Bayes-Genis, Antoni Davis, Mark Lainchbury, John G. Frampton, Chris Pinto, Yigal Richards, Mark A. Januzzi, James L. TI Hemoglobin and N-terminal pro-brain natriuretic peptide: Independent and synergistic predictors of mortality in patients with acute heart failure Results from the International Collaborative of NT-proBNP (ICON) Study SO CLINICA CHIMICA ACTA LA English DT Article DE anemia; heart failure; natriuretic peptides; prognosis ID ERYTHROPOIETIN LEVELS; EMERGENCY DIAGNOSIS; ANEMIA; DYSFUNCTION; CYTOKINES; PROGNOSIS; SURVIVAL; DYSPNEA; COMMON; TRIAL AB Background: Hemoglobin and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are both independent predictors of mortality in patients with chronic HE Their combined predictive power for mortality in the setting of acute HF is uncertain. Methods: In an international prospective cohort design, we evaluated the relationships between hemoglobin, NT-proBNP, and 60-day mortality in 690 patients with acute HF. Results: The median hemoglobin for the entire cohort was 13.0 g/dL (interquartile range 11.6-14.3). The WHO criterion for anemia was met by 44% (n = 05). The 60-day mortality rate for anemic patients was 16.4% vs. 8.8% in non-anemic patients (p < 0.001). Anemia was an independent predictor of short-term mortality (OR = 1.72, 95% CI = 1.05-2.80, p = 0.03), as was a NT-proBNP concentration > 5180 pg/mL (OR = 2.32,95% CI = 1.36-3.94 p = 0.002). Consideration of four risk groups: not anemic/low NT-proBNP (reference group, n = 220), anemic/low NT-proBNP (n = 152), not anemic/ high NT-proBNP (n = 165), and anemic/high NT-proBNP (n = 153) revealed respective 60-day mortality rates of 5.0% (referent), 9.2% (OR = 1.93, 95% CI = 0.85-4.36; p = 0.12), 13.9% (OR = 3.07, 95% CI = 1.45-6.50, p = 0.003), and 23.5% (OR = 5.84, 95% CI = 2.87-11.89, p < 0.001). Conclusions: Anemia was common in this cohort of subjects with acute HF and was related to adverse short-term outcome. Integrated use of hemoglobin and NT-proBNP measurements provides powerful additive information and is superior to the use of either in isolation. (c) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, PRIDE Study Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Hosp, Dept Cardiol, Maastricht, Netherlands. Hosp Santa Creu & Sant Pau, Dept Cardiol, E-08025 Barcelona, Spain. Christchurch Sch Med & Hlth Sci, Dept Med, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, PRIDE Study Grp, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 31 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUN PY 2007 VL 381 IS 2 BP 145 EP 150 DI 10.1016/j.cca.2007.03.010 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 182OK UT WOS:000247513700008 PM 17445789 ER PT J AU Nogueira, RD Alves, AC King, WF Goncalves, RB Hofling, JF Smith, DJ Mattos-Graner, RO AF Nogueira, Ruchele D. Alves, Alessandra C. King, William F. Goncalves, Reginaldo B. Hofling, Jose F. Smith, Daniel J. Mattos-Graner, Renata O. TI Age-specific salivary immunoglobulin A response to Streptococcus mutans GbpB SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID GLUCAN-BINDING-PROTEIN; DENTAL-CARIES; INFANTS; INFECTION; IMMUNITY; CHILDREN AB In a follow-up study of children infected with Streptococcus mutans at an early age (children previously shown to respond poorly to S. mutans GbpB), there was a delay in their immune response, rather than a complete inability to respond to this antigen. Epitopes in the N-terminal third of GbpB were identified as targets for naturally induced immunoglobulin A antibody in children at an early age. C1 Univ Estadual Campinas, Fac Odontol Piracicaba, Area Microbiol & Imunol, Dept Oral Diag,Piracicaba Sch Dent, BR-13414903 Piracicaba, SP, Brazil. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Mattos-Graner, RO (reprint author), Univ Estadual Campinas, Fac Odontol Piracicaba, Area Microbiol & Imunol, Dept Oral Diag,Piracicaba Sch Dent, Av Limeira 901, BR-13414903 Piracicaba, SP, Brazil. EM rmgraner@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012; OI Mattos-Graner, Renata/0000-0001-8309-8135; Nogueira, Ruchele Dias/0000-0002-7706-1376 FU FIC NIH HHS [R03 TW006324, TW-06324]; NIDCR NIH HHS [DE-01653] NR 13 TC 10 Z9 11 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2007 VL 14 IS 6 BP 804 EP 807 DI 10.1128/CVI.00098-07 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186HK UT WOS:000247769500027 PM 17475767 ER PT J AU Tchou, J Ward, MR Volpe, P Palma, MD Medina, CA Sargen, M Sonnad, SS Godwin, AK Daly, M Winchester, DJ Garber, J Weber, BL Domchek, S Nathanson, KL AF Tchou, Julia Renee Ward, M. Volpe, Patricia Palma, Maurizia Dalla Angelina Medina, C. Sargen, Michael Sonnad, Seema S. Godwin, Andrew K. Daly, Mary Winchester, David J. Garber, Judy Weber, Barbara L. Domchek, Susan Nathanson, Katherine L. TI Large genomic rearrangement in BRCA1 and BRCA2 and clinical characteristics of men with breast cancer in the United States SO CLINICAL BREAST CANCER LA English DT Article DE ashkenazi jewish mutation; estrogen receptor; mutation ID GERMLINE MUTATIONS; TUMOR CHARACTERISTICS; SUSCEPTIBILITY GENE; FAMILIES; POPULATION; RISK; IDENTIFICATION; FREQUENCY; DELETIONS; CARRIERS AB Purpose: Male breast cancer has been linked extensively to mutations of BRCA2 and, to a lesser extent, BRCA1. The aim of this study was to perform a comprehensive analysis of point mutations and genomic rearrangements in the BRCA1 and BRCA2 genes in 41 men with breast cancer. Patients and Methods: Deleterious point mutations were identified in 15 men (37%): 4 (10%) and 11 (27%) in BRCA1 and BRCA2, respectively. In the remaining 26 men, we screened for large genomic rearrangements in BRCA1 and BRCA2 using mutiplex ligation-dependent probe amplification. Results: We did not detect any large genomic rearrangements. Men with BRCA1 or BRCA2 mutations were more likely to have a family history of prostate cancer (P = 0.025). Three of 4 male breast tumors with BRCA1 mutations (75%) were estrogen receptor positive. Whereas some studies have reported an 8%-0 rate of large BRCA2 genomic rearrangement in familial male breast cancer cases, we did not detect any such genomic rearrangements in BRCA1 or BRCA2 for our cohort. Conclusion: Despite this negative finding, our study, to the best of our knowledge, is one of the first to comprehensively screen for mutations, including large genomic rearrangement mutations, in BRCA1 and BRCA2 in men with breast cancer in the United States. C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Abramson Canc Ctr, Dept Surg, San Francisco, CA USA. Pharmion Corp, San Francisco, CA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. GlaxoSmithKline, Collegeville, PA USA. RP Nathanson, KL (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, 513 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM knathans@mail.med.upenn.edu NR 28 TC 3 Z9 3 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2007 VL 7 IS 8 BP 627 EP 633 DI 10.3816/CBC.2007.n.021 PG 7 WC Oncology SC Oncology GA 182KF UT WOS:000247502800006 PM 17592676 ER PT J AU Motiwala, T Majumder, S Kutay, H Smith, DS Neuberg, DS Lucas, DM Byrd, JC Grever, M Jacob, ST AF Motiwala, Tasneem Majumder, Sarmila Kutay, Huban Smith, David Spencer Neuberg, Donna S. Lucas, David M. Byrd, John C. Grever, Michael Jacob, Samson T. TI Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELLS; ZAP-70 EXPRESSION; CLL CELLS; GENE; APOPTOSIS; CANCER; SUPPRESSION; BCL-2; PTPRO; HYPOMETHYLATION AB Purpose: Previous studies in our laboratory have shown the progressive methylation and suppression of the gene encoding protein tyrosine phosphatase, PTPRO, in the livers of rats fed a methyl-deficient diet that induces hepatocarcinogenesis. Subsequently, we observed the methylation of PTPRO in primary human lung tumors and also showed its potential tumor suppressor characteristics. The present study was undertaken to investigate whether the truncated form of PTPRO (PTPROt), specifically expressed in naive B lymphocytes, was also methylated and suppressed in chronic lymphocytic leukemia (CLL), a disease generally affecting B lymphocytes. Experimental Design and Results: Initial screening showed that 60% of the 52 CLL samples analyzed using methylation-specific PCR assay were methylated compared with B lymphocytes from normal individuals, which were not methylated. The expression of PTPROt, as measured by semiquantitative reverse transcription-PCR, inversely correlated with methylation in the few samples tested. Analysis of additional samples (n = 50) by combined bisulfite restriction analysis showed that the PTPRO CpG island was methylated in 82% of patients with CLL compared with B lymphocytes from normal individuals. Furthermore, overall expression of PTPRO was reduced in CLL relative to normal lymphocytes. The PTPRO gene was also suppressed by methylation in the CLL cell line WaC3CD5, where it could be reactivated upon treatment with the DNA hypomethylating agent 5-AzaC. Ectopic expression of PTPROt in a nonexpressing cell line increased growth inhibition with fludarabine treatment, a therapy commonly used for CLL. Conclusion: This study reveals the potential role of PTPRO methylation and Silencing in CLL tumorigenesis and also provides a novel molecular target in the pigenetic therapy. C1 Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Div Hematol Oncol, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Jacob, ST (reprint author), Ohio State Univ, Dept Mol & Cellular Biochem, 333 Hamilton Hall,1645 Neil Ave, Columbus, OH 43210 USA. EM Jacob.42@osu.edu RI Lucas, David/E-3555-2011 FU NCI NIH HHS [R01 CA086978, CA 86978, CA101956, P01 CA101956, P01 CA101956-01A2, R01 CA086978-01A2, R21 CA110496, R21CA110496] NR 37 TC 41 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2007 VL 13 IS 11 BP 3174 EP 3181 DI 10.1158/1078-0432.CCR-06-1720 PG 8 WC Oncology SC Oncology GA 172FE UT WOS:000246788700011 PM 17545520 ER PT J AU Treon, SP Hunter, ZR Matous, J Joyce, RM Mannion, B Advani, R Cook, D Songer, J Hill, J Kaden, BR Sharon, D Steiss, R Leleu, X Branagan, AR Badros, A AF Treon, Steven P. Hunter, Zachary R. Matous, Jeffrey Joyce, Robin M. Mannion, Brian Advani, Ranjana Cook, David Songer, Joseph Hill, John Kaden, Bruce R. Sharon, David Steiss, Ronald Leleu, Xavier Branagan, Andrew R. Badros, Ashraf TI Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's macroglobulinemia: Results of WMCTG trial 03-248 SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; UNFOLDED PROTEIN RESPONSE; 3RD INTERNATIONAL WORKSHOP; MANTLE CELL LYMPHOMA; MULTIPLE-MYELOMA; PHASE-II; DEXAMETHASONE; RITUXIMAB; RECOMMENDATIONS AB Purpose: Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite advances in the therapy, WM remains incurable. As such, novel therapeutic agents are needed for the treatment of WM. Experimental Design: In this multicenter study, 27 patients with WM received up to eight cycles of bortezomib at 1.3 mg/m(2) on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory disease. Results: Following therapy, median serum IgM levels declined from 4,660 to 2,092 mg/dL (P < 0.0001). The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. Responses were prompt and occurred at median of 1.4 months. The median time to progression for all responding patients was 7.9 (range, 3 -21.4+) months. The most common grade III/IV toxicities occurring in >= 5% of patients were sensory neuropathies (22.2%), leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia (7.4%). Sensory neuropathies resolved or improved in nearly all patients following cessation of therapy. Conclusions: The results of these studies show that bortezomib is an active agent in relapsed and refractory WM. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Rocky Mt Canc Ctr, Denver, CO USA. St Elizabeths Med Ctr, Crestview Hills, KY USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Bay Reg Med Ctr, Bay City, MI USA. Ball Canc Ctr, Muncie, IN USA. Hendersonville Hematol & Oncol, Hendersonville, NC USA. NW Med Specialists, Niles, IL USA. Monmouth Hematol & Oncol Associates, Long Branch, NJ USA. Atlanta Canc Care, Rosewell, GA USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [K23CA087977-03] NR 33 TC 95 Z9 100 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2007 VL 13 IS 11 BP 3320 EP 3325 DI 10.1158/1078-0432.CCR-06-2511 PG 6 WC Oncology SC Oncology GA 172FE UT WOS:000246788700030 PM 17545538 ER PT J AU Lotsch, J Belfer, I Kirchhof, A Mishra, BK Max, MB Doehring, A Costigan, M Woolf, CJ Geisslinger, G Tegeder, I AF Loetsch, Joern Belfer, Inna Kirchhof, Anja Mishra, Bikash K. Max, Mitchell B. Doehring, Alexandrea Costigan, Michael Woolf, Clifford J. Geisslinger, Gerd Tegeder, Irmgard TI Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms SO CLINICAL CHEMISTRY LA English DT Article ID RECONSTRUCTION; MUTATIONS AB Background: A haplotype in the GTP cyclohydrolase 1 (dopa-responsive dystonia) gene (GCH1) is associated with decreased persistent pain. The aim of the present study was to develop a screening method for the pain-protective haplotype. Methods: Complete genetic information for all 15 GCH1 DNA positions constituting the pain-protective GCH1 haplotype was available from 278 patients. In silico analyses, including discriminant analysis of the most frequent haplotypes, identified distinctive DNA positions that allow detection of the pain-protective haplotype at high sensitivity and specificity with the smallest possible number of DNA positions. Pyrosequencing((TM)) assays were subsequently developed for these DNA positions, established with 662 DNA samples from healthy volunteers, and prospectively validated with a random selection of DNA samples genotyped for all 15 DNA positions. Results: Diagnosis of the pain-protective GCH1 haplotype was possible with 100% sensitivity and specificity by screening for just 3 GCH1 genetic variants that span the entire DNA range of the haplotype: c.-9610G>A (dbSNP rs8007267G>A) in the 5 ' untranslated region, c.343 + 8900A>T (dbSNP rs3783641A>T) in intron 1, and c.*4279 (dbSNP rs10483639C>G) in the 3 ' untranslated region. Test sensitivity and specificity were still >95% with 2 or even just 1 of these GCH1 DNA positions. Conclusions: In silico analysis of complex GCH1 gene haplotypes reduced the requisite number of tested DNA positions from 15 to 3 while maintaining the reliability, specificity, and sensitivity of the genetic diagnosis. This screening method could reduce laboratory diagnostic efforts and facilitate investigations of the pain-protective GCH1 haplotype. (C) 2007 American Association for Clinical Chemistry. C1 Univ Frankfurt, Inst Clin Pharmacol, ZAFES, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany. Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Lotsch, J (reprint author), Univ Frankfurt, Inst Clin Pharmacol, ZAFES, Pharmazentrum Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM j.loetsch@em.uni OI Lotsch, Jorn/0000-0002-5818-6958; Tegeder, Irmgard/0000-0001-7524-8025 FU Intramural NIH HHS NR 10 TC 32 Z9 36 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 BP 1010 EP 1015 DI 10.1373/clinchem.2006.082883 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172UP UT WOS:000246830300005 PM 17363416 ER PT J AU Flood, JG Long, WH Nixon, AL Ng, K AF Flood, J. G. Long, W. H. Nixon, A. L. Ng, K. TI Performance and Workflow Analysis of the cobas (R) 6000 analyzer series (c 501, e 601) analyzers SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Roche Diagnost Operat Inc, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA E44 BP A227 EP A228 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000710 ER PT J AU Khoury, RH Gudaitis, P Sluss, PM Gudaitis, D Salmon, BP Gandhi, A Gudaitis, AV AF Khoury, R. H. Gudaitis, P. Sluss, P. M. Gudaitis, D. Salmon, B. P. Gandhi, A. Gudaitis, A. V. TI Establishment of TSH Reference ranges in geriatric population: relevance to thyroid pathophysiology. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Aculabs Inc, E Brunswick, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA D132 BP A201 EP A201 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000630 ER PT J AU Khoury, RH Gandhi, AH Salmon, BP Gudaitis, P Patel, DN Gudaitis, D Sluss, PM Gudaitis, AV AF Khoury, R. H. Gandhi, A. H. Salmon, B. P. Gudaitis, P. Patel, D. N. Gudaitis, D. Sluss, P. M. Gudaitis, A. V. TI Performance characteristics of the OC-Auto Micro 80 for the determination of fecal Occult blood. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Aculabs Inc, E Brunswick, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA C-8 BP A107 EP A107 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000335 ER PT J AU Price, C Ali, S Harris, L Brault, D Kostler, W Luftner, D Fornier, M Leitzel, K Lotz, JP Pichon, M Lipton, A Thiel, RP Esteva, F Tse, C Carney, WP AF Price, C. Ali, S. Harris, L. Brault, D. Kostler, W. Luftner, D. Fornier, M. Leitzel, K. Lotz, J. P. Pichon, M. Lipton, A. Thiel, R. P. Esteva, F. Tse, C. Carney, W. P. TI Changes in serum HER-2/neu levels of > 20% from baseline is associated with favorable clinical outcomes to Trastuzumab-based therapy SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Univ Oxford, Oxford, England. Lebanon VA Med Ctr, Lebanon, NH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Tenon Hosp, Paris, France. Univ Hosp Vienna, Vienna, Austria. Hosp Charite, Berlin, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Rene Huguenin Canc Ctr, Paris, France. Thiel Assoc, Groton, CT USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Siemens Med Solut Diagnost, Oncogene Sci Biomaker Grp, Cambridge, MA USA. RI Fornier, Monica/F-5899-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA C37 BP A115 EP A115 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000363 ER PT J AU Wong, A Smith, A Wu, AH Jaffe, A Miller, WL Hartman, K Januzzi, J Lewandrowski, EL Green, S Tannous, B Murakami, MM Kaczmarek, J Apple, FS AF Wong, A. Smith, A. Wu, A. H. Jaffe, A. Miller, W. L. Hartman, K. Januzzi, J. Lewandrowski, E. L. Green, S. Tannous, B. Murakami, M. M. Kaczmarek, J. Apple, F. S. TI Multi-center comparison of the response biomedical corporation RAMP (R) NT-proBNP assay against the roche diagnostics GmbH Elecsy (R) proBNP assay SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA A-21 BP A8 EP A8 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000022 ER PT J AU El-Serag, HB Richardson, P Pilgrim, P Gilger, MA AF El-Serag, Hashem B. Richardson, Peter Pilgrim, Petra Gilger, Mark A. TI Determinants of gastroesophageal reflux disease in adults with a history of childhood gastroesophageal reflux disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FOLLOW-UP; HIATAL-HERNIA; SYMPTOMS; CHILDREN; RISK; OBESITY; WOMEN AB Background & Aims: We conducted a nested case-control study to examine the prevalence and risk factors for current gastroesophageal reflux disease (GERD) symptoms in young adults with a history of childhood GERD. Methods: We identified a cohort of individuals diagnosed with GERD in childhood during 1995-1996, and controls without childhood GERD. Patients with neurodevelopmental disorders, tracheoesophageal anomalies, or cystic fibrosis were excluded. A computer-assisted telephone interview was conducted during 2004-2005. We calculated the prevalence of GERD symptoms, and examined the potential determinants of symptoms in unadjusted and adjusted logistic regression analyses. Results: A total of 113 cases completed the questionnaires (participation rate, 70.6%). The mean age of participants was 18 years, and their mean age at the time of childhood GERD diagnosis was 10 years. At least weekly heartburn or regurgitation was reported in 52 (46%) participants, 94% of whom were taking proton pump inhibitors, H2RA, or antacids. On the other hand, 33 controls were identified (44% participation rate) in whom weekly heartburn or regurgitation was reported in 30%. GERD was significantly more frequent in females using oral contraceptive pills (76.5%) as compared with females not on oral contraceptive pills (47.9%), or males (33.3%) (P = .008). Weight, height, nonsteroidal anti-inflammatory drug use, race, family history of GERD, education level, employment status, tobacco smoking, alcohol, or coffee drinking were not associated significantly with adulthood GERD. Conclusions: Frequent GERD symptoms requiring antisecretory therapy are present in approximately half of young adults with a history of childhood GERD. The use of oral contraceptives is a risk factor for GERD symptoms in these individuals. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU NIDDK NIH HHS [DK 56338] NR 15 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2007 VL 5 IS 6 BP 696 EP 701 DI 10.1016/j.cgh.2007.02.033 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 176JR UT WOS:000247081500013 PM 17544996 ER PT J AU Weinreb, N Barranger, J Packman, S Prakash-Cheng, A Rosenbloom, B Sims, K Angell, J Skrinar, A Pastores, GM AF Weinreb, N. Barranger, J. Packman, S. Prakash-Cheng, A. Rosenbloom, B. Sims, K. Angell, J. Skrinar, A. Pastores, G. M. TI Imiglucerase (Cerezyme((R))) improves quality of life in patients with skeletal manifestations of Gaucher disease SO CLINICAL GENETICS LA English DT Article DE cerezyme; enzyme replacement therapy; Gaucher disease; imiglucerase; quality of life; SF-36 ID ENZYME REPLACEMENT THERAPY; HEALTH SURVEY SF-36; PHENOTYPE; ADULTS AB Health-related quality of life (HRQOL) can be diminished in patients with type 1 Gaucher disease (GD) owing to the debilitating clinical manifestations of this chronic disease. This study investigates the impact of imiglucerase treatment on HRQOL of patients with type 1 GD and bone involvement. Thirty-two previously untreated type 1 GD patients with skeletal manifestations including bone pain, medullary infarctions, avascular necrosis, and lytic lesions received biweekly imiglucerase (at 60 U/kg). The Short Form-36 Health Survey (SF-36) was administered at regular intervals to assess HRQOL. Mean baseline SF-36 physical component summary (PCS) scores were diminished relative to US general population norms. Low PCS scores were more common in patients with medullary infarction, lytic lesions, and higher bone pain severity scores. Statistically significant improvements were observed for all eight SF-36 subscales after 2 years of treatment. Mean PCS and mental component summary (MCS) scores increased to within the normal range after 2 years of treatment and were maintained through year 4. Large HRQOL gains were observed even in patients with the most advanced disease and lowest baseline PCS scores. Imiglucerase treatment has a significant positive impact on HRQOL of type 1 GD patients with skeletal disease, including those with bone infarctions, lytic lesions, and avascular necrosis. C1 Lysosomal Storage Dis Inc, Res Fdn, Coral Springs, FL 33065 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA USA. Mt Sinai Med Ctr, Dept Human Genet, New York, NY USA. Tower Hematol, Los Angeles, CA USA. Massachusetts Gen Hosp, Div Neurogenet, Dept Neurol, Boston, MA USA. Genzyme Corp, Dept Clin Res, Cambridge, MA USA. NYU, Sch Med, Dept Neurol & Pediat, Neurogenet Unit, New York, NY USA. RP Weinreb, N (reprint author), Lysosomal Storage Dis Inc, Res Fdn, 8170 Royal Palm Blvd, Coral Springs, FL 33065 USA. EM boneal@winning.com NR 20 TC 53 Z9 55 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 2007 VL 71 IS 6 BP 576 EP 588 DI 10.1111/j.1399-0004-2007.00811.x PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 174CE UT WOS:000246918000012 PM 17539908 ER PT J AU Sartor, O AF Sartor, Oliver TI Chemotherapy in prostate cancer: An update SO CLINICAL GENITOURINARY CANCER LA English DT Editorial Material ID MITOXANTRONE; PREDNISONE; DOCETAXEL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Sartor, O (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2007 VL 5 IS 5 BP 304 EP 305 DI 10.3816/CGC.2007.n.008 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 194KU UT WOS:000248344100001 PM 17645826 ER PT J AU Geller, DS Hornicek, FJ Mankin, HJ Raskin, KA AF Geller, David S. Hornicek, Francis J. Mankin, Henry J. Raskin, Kevin A. TI Soft tissue sarcoma resection volume associated with wound-healing complications SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY JUN 08-10, 2006 CL Key West, FL SP Musculoskeletal Tumor Soc ID VACUUM-ASSISTED CLOSURE; EXTREMITY SARCOMAS; RADIOTHERAPY; SURGERY; THERAPY; SALVAGE; RECONSTRUCTION; NEOPLASMS; FLAP AB Limb-salvage surgery has become the standard of care for most soft tissue sarcomas. While primary closure is often possible, it is frequently complicated by wound-healing complications in the setting of previously irradiated tissue and surgical wounds closed under tension. We sought to identify a relationship between the volume of resected soft tissue and the rate of wound-healing complications. We retrospectively reviewed 108 patients who were treated over a 17-month period for soft-tissue sarcomas using limb-salvage methods. Of these, 87 patients were treated with primary wound closure and 21 patients underwent primary muscle flap closure at the time of wide surgical excision. Of the 87 patients treated with primary wound closure, the mean volume of resected tissue in the group with wound-healing complications was greater than that the group that healed without complications. The mean volume of resected tissue in the group with wound-healing complications was 919 cm(3) +/- 1173 cm(3) and the mean volume of resected tissue in the group without wound-healing complications was 456 cm(3) +/- 704 cm(3). Mean volume of resected tissue in the group of patients treated with primary flap coverage was 1908 cm(3), over twice as large as the mean volume of resected tissue in the group of patients treated with primary closure. C1 Montefiore Med Ctr, Albert Einstein Coll Med, Orthopaed Oncol Serv, Bronx, NY 10467 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02115 USA. RP Geller, DS (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Orthopaed Oncol Serv, 3400 Bainbridge Ave,6th Floor, Bronx, NY 10467 USA. EM gellerdavid@aol.com NR 23 TC 19 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2007 IS 459 BP 182 EP 185 DI 10.1097/BLO.0b013e3180514c50 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 176KZ UT WOS:000247085300030 PM 17452922 ER PT J AU Williams, PH Cobb, BL Namjou, B Scofield, RH Sawalha, AH Harley, JB AF Williams, Pamela H. Cobb, Beth L. Namjou, Bahram Scofield, R. Hal Sawalha, Amr H. Harley, John B. TI Horizons in Sjogren's syndrome genetics SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE Sjogren's syndrome; genetics; HLA; histocompatibility ID VASOACTIVE-INTESTINAL-PEPTIDE; BINDING LECTIN GENE; NOD MOUSE MODEL; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEPATITIS-C VIRUS; SALIVARY-GLANDS; AUTOANTIBODY PRODUCTION; AUTOIMMUNE-DISEASES; JAPANESE PATIENTS; CLASS-II AB Sjogren's syndrome (SS) is a complex polygenic autoimmune disorder. A few major genetic effects have been identified. Historically, HLA and non-HLA genetic associations have been reported. Recently, the HLA region continued to reveal association findings. A new susceptibility region has been suggested by a study of a D6S349 microsatellite marker. Among non-HLA studies, recent association of immunoglobulin K chain allotype KM1 with anti-La autoantibodies in primary Sjogren's syndrome confirms findings in a study from two decades ago. Meanwhile, mouse models have been employed to study the genetic contribution to salivary lymphadenitis or dry eyes and mouth. Gene transfer exploration in mouse models shows promise. The authors review the HLA and non-HLA association studies and the mouse model work that has been reported. Newly developed genomic capacity will provide, in the future, a much closer approximation of the true picture of the genetic architecture of Sjogren's syndrome. C1 Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, Arthritis & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM john-harley@omrf.ouhsc.edu FU NCRR NIH HHS [P20-RR015577, P20 RR015577, RR020143, P20 RR020143]; NIAID NIH HHS [AI24717, R01 AI031584, R37 AI024717, R01 AI024717, AI31584]; NIAMS NIH HHS [N01AR12253, P01 AR049084, P30 AR053483, R01 AR042460, P50 AR048940, AR048940, AR049084, AR42460]; NIDCR NIH HHS [R01 DE015223, DE015223] NR 76 TC 10 Z9 10 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD JUN PY 2007 VL 32 IS 3 BP 201 EP 209 DI 10.1007/s12016-007-8002-9 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 234HF UT WOS:000251150600002 PM 17963047 ER PT J AU Yang, M Barner, JC Worchel, J AF Yang, Min Barner, Jamie C. Worchel, Jason TI Factors related to antipsychotic oversupply among central Texas veterans SO CLINICAL THERAPEUTICS LA English DT Article DE adherence; oversupply; medication possession ratio; antipsychotic; medication utilization ID MEDICATION COMPLIANCE; ELDERLY-PATIENTS; HOSPITAL DISCHARGE; SUBSTANCE-ABUSE; DRUG ADHERENCE; MENTALLY-ILL; SCHIZOPHRENIA; NONCOMPLIANCE; PRESCRIPTION; POPULATION AB Background: There have been many studies of underadherence to antipsychotics, but antipsychotic overadherence, or medication oversupply, in which patients receive more prescription medications than are needed, has been overlooked. Both underadherence and oversupply can have an important impact on clinical outcomes. Objectives: This study examined adherence (based on the medication possession ratio [MPR]) among patients treated with antipsychotics in the Central Texas Veterans Health Care System (CTVHCS) and investigated factors associated with their adherence status. Methods: Data from September 1995 to October 2002 were extracted from the computerized patient record system of the CTVHCS for continuously enrolled adult outpatients receiving antipsychotic monotherapy and filling at least 2 prescriptions within a year of the index date. Patients' prescription records were tracked for up to 12 months. Underadherence was defined as an MPR <0.8, good adherence as an MPR from 0.8 to 1.2, and oversupply as an MPR >1.2. Results: Of 3268 eligible patients, 49.9% had good adherence, 42.6% were underadherent, and 7.6% had medication oversupply. The overall mean (SD) MPR was 0.83 (0.33). Multinomial logistic regression analysis revealed that compared with patients with good adherence, underadherent patients were significantly more likely to be nonwhite (P < 0.001), younger (P < 0.01), and receiving chlorpromazine therapy (P < 0.05), and were less likely to be receiving fluphenazine (P < 0.01), olanzapine (P < 0.05), or risperidone (P < 0.05). Patients with medication oversupply were significantly more likely to be receiving olanzapine (P < 0.001), quetiapine (P < 0.01), or risperidone (P < 0.05) than those with good adherence. Conclusions: Although half of adult outpatients receiving antipsychotic monotherapy in the CTVHCS were adherent to their treatment regimens, a large proportion were underadherent, and a small proportion had medication oversupply. Patients receiving second-generation antipsychotics were more likely to be adherent and were more likely to have medication oversupply than patients receiving first-generation antipsychotics. C1 Univ Texas, Coll Pharm, Austin, TX 78712 USA. US Dept Vet Affairs, Cent Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Yang, M (reprint author), QualityMetric Inc, 640 George Washington Highway,Suite 201, Lincoln, RI 02865 USA. EM myang@qualitymetric.com NR 50 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD JUN PY 2007 VL 29 IS 6 BP 1214 EP 1225 DI 10.1016/j.clinthera.2007.06.013 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 193SF UT WOS:000248293900020 PM 17692735 ER PT J AU Alexander, JA Copeland, LA Metzger, ME AF Alexander, Jeffrey A. Copeland, Laurel A. Metzger, Maureen E. TI Explaining differences in operating costs among poison control centers: An exploratory study SO CLINICAL TOXICOLOGY LA English DT Article DE poison control centers; costs and cost analyses; health resources AB Objectives. To explore the effects of population, staffing, location, and funding on cost per human poison exposure call; and organizational characteristics differentiating higher- and lower-cost centers. Methods. Data from 65 poison control centers (2001) were analyzed with linear multiple regression; qualitative data from 10 centers were compared. Results. The most important predictor of expenses per call was 24-hour coverage by Specialists in Poison Information ($15.70 of $40.53/call). Other factors increasing total expenses included northeast location and more health educator FTEs. Qualitative information revealed that more complex organizational forms, including multiple reporting and accountability relationships, characterized higher-cost centers. Surprisingly, having a wider range of reported activities (less specialization) was more common among lower-cost centers. Conclusions. Wide variability in cost per call suggests that inefficiencies exist. While elimination of inefficient poison control centers could reduce costs, the loss of training and collaborative opportunities, and preparedness for public health emergencies and bio-terrorism events, might mitigate against such restructuring. C1 Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Dept Vet Affairs,VERDICT Program, San Antonio, TX 78284 USA. RP Alexander, JA (reprint author), Univ Michigan, Sch Publ Hlth, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM jalexand@sph.umich.edu OI Copeland, Laurel/0000-0002-9478-0209 NR 13 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1556-3650 EI 1556-9519 J9 CLIN TOXICOL JI Clin. Toxicol. PD JUN-AUG PY 2007 VL 45 IS 5 BP 440 EP 450 DI 10.1080/15563650601117921 PG 11 WC Toxicology SC Toxicology GA 185SV UT WOS:000247731600002 PM 17503241 ER PT J AU Peerschke, EIB Agrawal, Y Alexander, CB Bovill, E Laposata, M AF Peerschke, Ellinor I. B. Agrawal, Yashpal Alexander, C. Bruce Bovill, Edwin Laposata, Michael TI Proposed research training guidelines for residents in laboratory medicine SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID EDUCATION AB It is expected that the role of the clinical pathologist will evolve from the more passive role of managing testing facilities to one of active service provider, using powerful molecular, cell biologic, and biochemical tools. The scope of knowledge required to be an effective physician scientist or an accomplished practicing clinical pathologist, however, cannot be acquired through clinical trainingalone and requires dedicated, structured research learning time. The goal of this article is to consider mechanisms that effectively integrate research training and scholarly activity into residency education in laboratory medicine/clinical pathology The proposed curricula are purposely unstructured to allow maximum flexibility for training programs to meet the needs and career goals of individual residents. C1 Cornell Univ, Dept Pathol & Lab Med, Weill Med Coll, New York, NY 10021 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35249 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Peerschke, EIB (reprint author), Cornell Univ, Dept Pathol & Lab Med, Weill Med Coll, 525 E 68th St, New York, NY 10021 USA. EM epeersch@med.cornell.edu NR 10 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2007 VL 27 IS 2 BP 241 EP + DI 10.1016/j.cll.2007.03.002 PG 15 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 185CP UT WOS:000247689200003 PM 17556083 ER PT J AU Yovel, I Safren, SA AF Yovel, Iftah Safren, Steven A. TI Measuring homework utility in psychotherapy: Cognitive-behavioral therapy for adult attention-deficit hyperactivity disorder as an example SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE cognitive behavioral therapy; homework; adherence; adult attention-deficit hyperactivity disorder; psychotherapy process ID OUTCOME RESEARCH; CLIENT IMPLEMENTATION; SUDDEN GAINS; RATING-SCALE; DOUBLE-BLIND; DEPRESSION; RECOMMENDATIONS; ASSIGNMENTS; DIFFICULTY; SYMPTOMS AB Homework, or practice of skills learned in treatment, is a critical component of cognitive-behavioral therapy (CBT). However, no matter how much effort clients put into their therapy homework, this effort can only be useful if adherence to homework is related to improvement in symptoms. Although homework adherence (the extent to which clients practice skills learned in therapy outside of sessions) has been studied with respect to psychotherapy outcomes, 'homework utility', a potentially important mechanism of action in cognitive behavioral treatments, has yet to be operationally defined as a distinct construct, and it has yet to be studied with respect to psychotherapy outcome. We therefore propose an operational definition of therapy homework utility: the extent to which homework adherence is associated with parallel symptom improvement across time throughout treatment for each individual client. In this capacity, an indicator of homework utility is operationalized as the within subject correlation of session-by-session homework adherence with session-by-session symptom change. We used a sample of clients who underwent CBT for attention-deficit hyperactivity disorder in adulthood as an example to quantify homework utility and examine its association to treatment outcome. Consistent with our hypotheses, homework utility was significantly associated with overall therapy outcome. Homework utility may be an important construct relevant to the mechanism of action of structured psychotherapies, and examining within subject sessions-by-session correlations with symptomatic change may be a useful way to examine other psychotherapy process variables. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hebrew Univ Jerusalem, Div Psychol, IL-91905 Jerusalem, Israel. RP Yovel, I (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM voveli@mscc.juji.ac.il; ssafren@partners.org NR 26 TC 11 Z9 12 U1 3 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD JUN PY 2007 VL 31 IS 3 BP 385 EP 399 DI 10.1007/s10608-006-9065-2 PG 15 WC Psychology, Clinical SC Psychology GA 179UR UT WOS:000247316100009 ER PT J AU Yoshida, H Nappi, J AF Yoshida, Hiroyuki Nappi, Janne TI CAD in CT colonography without and with oral contrast agents: Progress and challenges SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Review DE CAD; computer-aided detection; CT colonography; virtual colonoscopy; oral contrast ID COMPUTER-AIDED DETECTION; TOMOGRAPHIC VIRTUAL COLONOSCOPY; ASSISTED READER SOFTWARE; POLYP DETECTION; COLONIC POLYPS; FALSE POSITIVES; COLORECTAL-CANCER; BARIUM ENEMA; VOLUMETRIC FEATURES; DIAGNOSIS SCHEME AB Computed tomographic colonography (CTC), also known as virtual colonoscopy, is an emerging alternative technique for screening of colon cancers. CTC uses CT to provide a series of cross-sectional images of the colon for detection of polyps and masses. Fecal tagging is a means of labeling of residual feces by an oral contrast agent for improving the accuracy in the detection of polyps. Computer-aided diagnosis (CAD) for CTC automatically determines the locations of suspicious polyps and masses in CTC and presents them to radiologists, typically as a second opinion. Despite its relatively short history, CAD has become one of the mainstream techniques that could make CTC prime time for screening of colorectal cancer. Rapid technical developments have advanced CAD substantially during the last several years, and a fundamental scheme for the detection of polyps has been established, in which sophisticated 3D image processing, analysis, and display techniques play a pivotal role. The latest CAD systems indicate a clinically acceptable high sensitivity and a low false-positive rate, and observer studies have demonstrated the benefits of these systems in improving radiologists' detection performance. Some technical and clinical challenges, however, remain unresolved before CAD can become a truly useful tool for clinical practice. Also, new challenges are facing CAD as the methods for bowel preparation and image acquisition, such as tagging of fecal residue with oral contrast agents, and interpretation of CTC images evolve. This article reviews the current status and future challenges in CAD for CTC without and with fecal tagging. (c) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 75 Blossom Court,Suite 220, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu NR 120 TC 31 Z9 33 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUN-JUL PY 2007 VL 31 IS 4-5 BP 267 EP 284 DI 10.1016/j.compmedimag.2007.02.011 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 183ET UT WOS:000247556200008 PM 17376650 ER PT J AU Harissi-Dagher, M Khan, BF Schaumberg, DA Dohlman, CH AF Harissi-Dagher, Mona Khan, Bilal F. Schaumberg, Debra A. Dohlman, Claes H. TI Importance of nutrition to corneal grafts when used as a carrier of the Boston keratoprosthesis SO CORNEA LA English DT Article DE boston keratoprosthesis; corneal nutrition; corneal melt ID GLUCOSE; LENSES; EPITHELIUM; BARRIER; FLUID AB Purpose: Necrosis, melt, and perforation have historically been frequent around a Keratoprosthesis (KPro), even resulting in extrusion or endophthalmitis. Autoimmune diseases such as Stevens-Johnson Syndrome (SJS) and Ocular Cicatricial Pemphigoid (OCP) have been notorious in this respect. The purpose of this study was to compare the frequency of tissue melt after implantation of two designs of the Boston KPro, one allowing much better access of nutrition from the aqueous humor to the carrier graft. Methods: We retrospectively reviewed charts of 157 eyes implanted since 1990 with a poly (methylmethacrylate) Boston KPro, including 79 eyes implanted with the model having 8 small (1.3-mm diameter) holes in the back plate, and 78 eyes implanted with the older solid back plate. We compared the frequency of tissue melts between the two KPro designs, for all implants as well as for subgroups based on preoperative diagnosis. Results: In total, 48/157 eyes (31%) developed some degree of tissue melt around the stem, including 8/79 eyes (10%) in the back plate with holes group and 40/78 eyes (51%) in the solid back plate group (P < 0.0001). Among the melts in the back plate with holes group, 4/8 (50%) suffered from an underlying autoimmune disease such as SJS or OCP. Conclusions: The Boston KPro design with a back plate containing holes protects the overlying corneal tissue from necrosis and melts. This improved situation is likely due to increased aqueous access and better nutrition to the corneal graft cells. In addition, this study confirms earlier work regarding the particular corneal fragility of patients with autoimmune diseases. C1 Massachusetts Eye & Ear Infirm, Dept Cornea & External Dis, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Dohlman, CH (reprint author), 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu NR 22 TC 48 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2007 VL 26 IS 5 BP 564 EP 568 PG 5 WC Ophthalmology SC Ophthalmology GA 169QU UT WOS:000246607500012 PM 17525653 ER PT J AU Kojima, T Chung, TY Chang, JH Sayegh, R Casanova, TH Azar, DT AF Kojima, Takashi Chung, Tae-Young Chang, Jin-Hong Sayegh, Rony Casanova, Tabio H. Azar, Dimitri T. TI Comparison of EphA receptor tyrosine kinases and ephrinA ligand expression to EphB-ephrinB in vascularized corneas SO CORNEA LA English DT Article DE immunohistochemistry; cornea; corneal neovascularization; ephrin; Eph ID FIBROBLAST-GROWTH-FACTOR; ENDOTHELIAL-CELLS; CARDIOVASCULAR DEVELOPMENT; MELANOMA PROGRESSION; NEURAL DEVELOPMENT; ANGIOGENESIS; NEOVASCULARIZATION; MORPHOGENESIS; MIGRATION; ROLES AB Purpose: Eph cell surface receptors and their ligands, ephrins, are involved in neuronal patterning and neovascularization. Our purpose is to compare and characterize the expression of ephrinA ligands and EphA receptors to ephrinB; ligands and EphB receptors in excised mouse corneal tissue, in corneal epithelial and keratocyte cell lines, and during corneal angiogenesis. Methods: Mouse corneal epithelial cells and keratocytes were immortalized using SV40T antigen viral infection of primary cultures. The immortalized epithelial cells and keratocytes were cloned and characterized using antibodies to keratin, vimentin, integrin alpha 5 beta 1, and alpha-smooth muscle actin. Basic fibroblast growth factor pellets were implanted to induce corneal neovascularization. The eyes of wild-type, ephrinB2(tlacZ/+), and EphB4(tlacZ/+) heterozygous mice were harvested and sectioned 7 days after pellet implantation. Confocal immunohistochemistry was performed to compare the expression of the Eph/ephrinA family (EphA1-8, ephrinA1-5) and Eph/ephrinB family (EphB1-4, EphB6 ephrinB1-3). Results: EphA1, EphA3, ephrinA1, ephrinA2, EphB1, EphB4, ephrinB1, and ephrinB2 were detected in wild-type mouse corneal epithelial cells and keratocytes. EphA2 was immunolocalized only in epithelial cells. Also, EphA3, ephrinA1, EphB1, EphB4, and ephrinB1 were immunolocalized to the comeal epithelium and stroma. In the vascularized corneas, ephrinB1 was immunolocalized mainly to the keratocytes around the vessels, and ephrinB2, EphB 1, and EphB4 were colocalized mainly with CD31 to the vascular endothelial cells. Conclusions: The characterization of ephrin ligand and Eph receptor expression during cornea angiogensis in this study suggests that the Eph/ephrin family of receptor tyrosine kinases and their ligands may play a role in the regulation of corneal angiogenesis. C1 Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Fed Sao Paulo, Paulista Sch Med, Dept Ophthalmol, Sao Paulo, Brazil. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 FU NEI NIH HHS [EY14048] NR 47 TC 13 Z9 15 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2007 VL 26 IS 5 BP 569 EP 578 PG 10 WC Ophthalmology SC Ophthalmology GA 169QU UT WOS:000246607500013 PM 17525654 ER PT J AU Deans, KJ Minneci, PC Suffredini, AF Danner, RL Hoffman, WD Ciu, XZ Klein, HG Schechter, AN Banks, SM Eichacker, PQ Natanson, C AF Deans, Katherine J. Minneci, Peter C. Suffredini, Anthony F. Danner, Robert L. Hoffman, William D. Ciu, Xizhong Klein, Harvey G. Schechter, Alan N. Banks, Steven M. Eichacker, Peter Q. Natanson, Charles TI Randomization in clinical trials of titrated therapies: Unintended consequences of using fixed treatment protocols SO CRITICAL CARE MEDICINE LA English DT Article DE treatment dose; randomization; practice misalignment ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; ACUTE LUNG INJURY; TIDAL VOLUMES; MECHANICAL VENTILATION; COVARIATE INTERACTIONS; TRANSFUSION PRACTICES; BLOOD-TRANSFUSION; SEPTIC SHOCK; MANAGEMENT AB Objective: Clinical trial designs that randomize patients to fixed treatment regimens may disrupt preexisting relationships between illness severity and level of therapy. The practice misalignments created by such designs may have unintended effects on trial results and safety. Methods. To illustrate this problem, the Transfusion Requirements in Critical Care (TRICC) trial and the Acute Respiratory Distress Syndrome Network low tidal volume (ARMA) trial were analyzed. Results: Publications before TRICC indicated that clinicians used higher transfusion thresholds in patients with ischemic heart disease compared with younger, healthier patients (p = .001). The trial, however, randomized patients (n = 838) to liberal (10 g/dL hemoglobin) or restrictive (7 g/dL) transfusion thresholds. Thirty-day mortality was different and opposite in the liberal compared with the restrictive arm depending on presence (21 vs. 26%) or absence (25 vs. 16%) of ischemic heart disease (p = .03). At baseline in ARMA, consistent with prior publications, physicians set ventilator volumes lower in patients with high airway pressures and poor compliance (8.4-10.6 mL/kg interquartile range) than patients with less severe abnormalities (9.6-12 mL/kg) (p = .0001). In the trial, however, patients (n = 861) were randomized to low (6 mL/kg) or high (12 mL/kg) tidal volumes. In patients with low compliance (< 0.6 mL/kg), 28-day mortality was higher when tidal volumes were raised rather than lowered (42 vs. 29%), but this effect was reversed in patients with higher compliance (21 vs. 37%; p = .003). Conclusions: In TRICC and ARMA, randomization to fixed treatment regimens disrupted preexisting relationships between illness severity and therapy level. This created noncomparable subgroups in both study arms that received care different and opposite from titrated care, that is, practice misalignments. These subgroups reduced the interpretability and safety of each trial. Characterizing current practice, incorporating current practice controls, and using alternative trial designs to minimize practice misalignments should improve trial safety and interpretability. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Eichacker, PQ (reprint author), NIH, Crit Care Med Dept, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 33 TC 88 Z9 91 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2007 VL 35 IS 6 BP 1509 EP 1516 DI 10.1097/01.CCM.0000266584.40715.A6 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 170QO UT WOS:000246679200008 PM 17440420 ER PT J AU Stubbs, MC Annstrong, SA AF Stubbs, Matthew C. Annstrong, Scott A. TI FLT3 as a therapeutic target in childhood acute leukemia SO CURRENT DRUG TARGETS LA English DT Review ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; ENDOTHELIAL GROWTH-FACTOR; ABL-POSITIVE CELLS; HUMAN BONE-MARROW AB During the past few years, a major focus of leukemia research has centered on tyrosine kinases as potential therapeutic targets. This is due in large part to the success of imatinib mesylate (STI571, Gleevec), which has proven effective as a therapy for chronic myeloid leukemias bearing the t(9;22) encoding the BCR-ABL kinase. It has become increasingly evident that mutations producing constitutively active tyrosine kinases play a role in leukemogenesis. Another kinase that has drawn significant attention is the FMS-like tyrosine kinase 3 (FLT3). FLT3 is expressed in most childhood acute leukemias. Select genetic subgroups possess particularly high-level expression, with a significant percentage therein harboring activating mutations. In this review we will discuss FLT3 as a potential therapeutic target in childhood acute leukemias. We will highlight the role of FLT3 in hematopoiesis, and how when activated, it may play a role in the development of acute myeloid or acute lymphoblastic leukemia. We will examine the successes in elucidating FLT3 function in acute leukemias, highlight current FLT3 targeted therapeutics, and discuss how FLT3 inhibitors might be used in combination therapies in the future. C1 Childrens Hosp, Div Hematol Oncol, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Annstrong, SA (reprint author), Childrens Hosp, Karp Family Res Labs, 1 Blackfan Circle, Boston, MA 02215 USA. EM Scott.Armstrong@childrens.harvard.edu NR 149 TC 16 Z9 17 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD JUN PY 2007 VL 8 IS 6 BP 703 EP 714 DI 10.2174/138945007780830782 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 186JF UT WOS:000247774300003 PM 17584026 ER PT J AU Berman, JN Look, AT AF Berman, Jason N. Look, A. Thomas TI Targeting transcription factors in acute leukemia in children SO CURRENT DRUG TARGETS LA English DT Review DE transcription factors; ALL; AML; promyelocytic leukemia; HDAC inhibitors; all-trans retinoic acid (ATRA); targeted therapy; NOTCH ID ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; BINDING-PROTEIN-ALPHA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ARSENIC TRIOXIDE AS2O3; HISTONE DEACETYLASE INHIBITION; T-CELL LEUKEMIA; PLZF-RAR-ALPHA; THYROID-HORMONE AB Transcription factors play essential roles in controlling normal blood development and their alteration leads to abnormalities in cell proliferation, differentiation and survival. In many childhood acute leukemias, transcription factors are altered through chromosomal translocations that change their functional properties resulting in repressed activity or inappropriate activation. The development of therapies that specifically target these molecular abnormalities holds promise for improving the outcome in diseases that remain challenging to treat, such as childhood T-cell acute lymphoblastic leukemia and acute myeloid leukemia, with improved toxicity profiles. All trans-retinoic acid and arsenic trioxide have already demonstrated efficacy in acute promyelocytic leukemia in both adults and children. Newer agents, such as histone deacetylase inhibitors, drugs targeting the NOTCH pathway, and short interfering RNAs have shown encouraging results in pre-clinical studies and are likely to enter the clinical arena in the near future. Through an improved understanding of the pathways and mechanisms underlying the malignant transformation induced by altered transcription factors, new targeted therapies will be designed that should greatly enhance current available treatments. C1 Dana Farber Canc Inst, Pediat Oncol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Pediat Oncol Dept, 44 Binney St,Mayer 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu NR 113 TC 13 Z9 13 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD JUN PY 2007 VL 8 IS 6 BP 727 EP 737 DI 10.2174/138945007780830818 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 186JF UT WOS:000247774300005 PM 17584028 ER PT J AU McLaughlin, T Leibman, C Patel, P Camargo, CA AF McLaughlin, Trent Leibman, Christopher Patel, Pankaj Camargo, Carlos A., Jr. TI Risk of recurrent emergency department visits or hospitalizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE asthma; child; cohort studies; emergency service; hospitalization; nebulized budesonide inhalation suspension ID INHALED CORTICOSTEROIDS; RANDOMIZED-TRIALS; PERSISTENT ASTHMA; PEDIATRIC ASTHMA; YOUNG-CHILDREN; OUTCOMES; READMISSION; CHILDHOOD; THERAPY; IMPACT AB Objective: To examine whether nebulized budesonide inhalation suspension treatment reduces asthma-related emergency department visit/hospitalization recurrence risk in children compared with other asthma medications, particularly non-nebulized inhaled corticosteroids. Research design and methods: Longitudinal, retrospective claims analysis of data from a managed care organization database in the United States (July 1, 2000-June 30, 2002). Participants were children aged <= 8 years with an asthma diagnosis and asthma-related emergency department visit or hospitalization (index event). Asthma medication use, evaluated by asthma-related prescriptions <= 30 days after the index event, determined treatment groups. Main outcome measure: Emergency department visit/hospitalization recurrence risk from post-index day 31-180 across treatment groups. Results: Of 10176 patients with an index event, 13% experienced a post-index recurrence. For patients receiving asthma prescriptions <= 30 days after the index event, those receiving budesonicle inhalation suspension showed a significant reduction in emergency department visit/hospitalization recurrence risk compared with those not prescribed this treatment (adjusted hazard ratio, 0.71; 95% confidence interval, 0.57-0.89). For patients receiving asthma controller medication in the post-index period, those receiving budesonide inhalation suspension had a significantly lower recurrence risk than patients receiving prescriptions for other controller medications (hazard ratio, 0.71; 95% confidence interval, 0.52-0.97). Recurrence C1 NDCHlth, Phoenix, AZ USA. AstraZeneca, Wilmington, DE USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP McLaughlin, T (reprint author), Elan Pharmaceut, Pharmacoecon, 700 Gateway Blvd, San Francisco, CA 94080 USA. EM Trent.McLaughlin@elan.com NR 33 TC 6 Z9 11 U1 0 U2 1 PU LIBRAPHARM PI NEWBURY PA 29-35 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUN PY 2007 VL 23 IS 6 BP 1319 EP 1328 DI 10.1185/030079907X188170 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 188PE UT WOS:000247931000014 PM 17559731 ER PT J AU Newton-Cheh, C Shah, R AF Newton-Cheh, Christopher Shah, Ripal TI Genetic determinants of QT interval variation and sudden cardiac death SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID FAMILIAL ATRIAL-FIBRILLATION; OF-FUNCTION MUTATION; POTASSIUM CHANNEL GENE; ST-SEGMENT ELEVATION; TORSADES-DE-POINTES; LATE SODIUM CURRENT; INFANT-DEATH; COMMON POLYMORPHISM; UNEXPLAINED DEATH; LANGE-NIELSEN AB Electrocardiographic QT interval prolongation or shortening is a risk factor for sudden cardiac death. The study of Mendelian syndromes in families with extreme long and short QT interval duration and ventricular arrhythmias has led to the identification of genes encoding ion channel proteins important in myocardial repolarization. Rare mutations in such ion channel genes do not individually contribute substantially to the population burden of ventricular arrhythmias and sudden cardiac death. Only now are studies systematically testing the relationship between common variants in these genes - or elsewhere in the genome - and QT interval variation and sudden cardiac death. Identification of genetic variation underlying myocardial repolarization could have important implications for the prevention of both sporadic and drug-induced arrhythmias. C1 Massachusetts Gen Hosp, Div Cardiol, NHLBIs Framingham Heart Study, Broad Inst Harvard & MIT,Prog Med & Populat Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Div Cardiol, NHLBIs Framingham Heart Study, Broad Inst Harvard & MIT,Prog Med & Populat Genet, 32 Fruit St,GRB 847, Boston, MA 02114 USA. EM cnewtoncheh@partners.org FU NHLBI NIH HHS [HL080025] NR 75 TC 17 Z9 19 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2007 VL 17 IS 3 BP 213 EP 221 DI 10.1016/j.gde.2007.04.001 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 183FA UT WOS:000247556900007 PM 17467978 ER PT J AU Sundrud, MS Rao, A AF Sundrud, Mark S. Rao, Anjana TI New twists of T cell fate: control of T cell activation and tolerance by TGF-beta and NFAT SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID GROWTH-FACTOR-BETA; IN-VIVO; SIGNAL-TRANSDUCTION; REGULATORY CELLS; UBIQUITIN LIGASE; FOXP3 EXPRESSION; CUTTING EDGE; MECHANISMS; DIFFERENTIATION; INTERLEUKIN-2 AB Protective and pathogenic immune responses were initially thought to be determined by the differentiation of naive T cells into Th1 and Th2 effector subsets and the immunosuppressive activity of thymic-derived regulatory T cells. It is now clear that naive T cells can also differentiate into 'induced' regulatory T cells or inflammatory T cells that secrete IL-17. These divergent T-cell subsets have opposing functions in imparting inflammation or tolerance, yet both developmental programs are controlled by the pluripotent cytokine transforming growth factor beta and the transcription factor NFAT. Recent findings have begun to shed light on the mechanisms by which TGF-beta and NFAT integrate multiple signaling inputs to determine the direction of naive T-cell differentiation. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res Inc, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI48213] NR 51 TC 30 Z9 31 U1 0 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 JUN PY 2007 VL 19 IS 3 BP 287 EP 293 DI 10.1016/j.coi.2007.04.014 PG 7 WC Immunology SC Immunology GA 173YH UT WOS:000246907900007 PM 17433870 ER PT J AU Pipkin, ME Lieberman, J AF Pipkin, Matthew E. Lieberman, Judy TI Delivering the kiss of death: progress on understanding how perforin works SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TARGET-CELL DEATH; FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; GRANULE-MEDIATED CYTOTOXICITY; CYTOSOLIC PHOSPHOLIPASE A(2); PLASMA-MEMBRANE DISRUPTION; GRANZYME-B; C2 DOMAIN; DEFICIENT MICE; LYTIC GRANULES; T-LYMPHOCYTES AB Killer lymphocytes release perforin and granzymes from cytotoxic granules into the immunological synapse to destroy target cells as a critical mechanism. in the defense against viruses and cancer. Perforin, a Ca2+-dependent pore-forming protein that multimerizes in membranes, delivers granzymes into the target cell cytosol. The original model for perforin (acting by forming a cell membrane channel through which granzymes pass) does not fit the experimental data. Recently, an alternative model has been proposed that involves active target cell collaboration with perforin to deliver granzymes and direct the target cell to an apoptotic, rather than necrotic, death. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI040127, AI044432] NR 85 TC 141 Z9 147 U1 1 U2 13 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 JUN PY 2007 VL 19 IS 3 BP 301 EP 308 DI 10.1016/j.coi.2007.04.011 PG 8 WC Immunology SC Immunology GA 173YH UT WOS:000246907900009 PM 17433871 ER PT J AU Lara-Castro, C Fu, Y Chung, BH Garvey, WT AF Lara-Castro, Cristina Fu, Yuchang Chung, B. Hong Garvey, W. Timothy TI Adiponectin and the metabolic syndrome: mechanisms med ating risk for metabolic and cardiovascular disease SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE adipocytes; adiponectin; cardiovascular disease; insulin resistance; lipids ID MOLECULAR-WEIGHT ADIPONECTIN; CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; TYPE-2 DIABETES-MELLITUS; PROMOTES ADIPOCYTE DIFFERENTIATION; MONOCYTE-DERIVED MACROPHAGES; PLASMA-PROTEIN ADIPONECTIN; ADIPOSE-SPECIFIC PROTEIN; RECEPTOR-GAMMA AGONISTS; INSULIN-RESISTANCE AB Purpose of review Adiponectin is secreted exclusively by adipocytes, aggregates in multimeric forms, and circulates at high concentrations in blood. This review summarizes recent studies highlighting cellular effects of adiponectin and its role in human lipid metabolism and atherosclerosis. Recent findings Adiponectin is an important autocrine/paracrine factor in adipose tissue that modulates differentiation of preadipocytes and favors formation of mature adipocytes. It also functions as an endocrine factor, influencing whole-body metabolism via effects on target organs. Adiponectin multimers exert differential biologic effects, with the high-molecular-weight multimer associated with favorable metabolic effects (i.e. greater insulin sensitivity, reduced visceral adipose mass, reduced plasma triglycerides, and increased HDL-cholesterol). Adiponectin influences plasma lipoprotein levels by altering the levels and activity of key enzymes (lipoprotein lipase and hepatic lipase) responsible for the catabolism of triglyceride-rich lipoproteins and HDL. It thus influences atherosclerosis by affecting the balance of atherogenic and antiatherogenic lipoproteins in plasma, and by modulating cellular processes involved in foam cell formation. Summary Recent studies emphasize the role played by adiponectin in the homeostasis of adipose tissue and in the pathogenesis of the metabolic syndrome, type 2 diabetes, and atherosclerosis. These pleiotropic effects make it an attractive therapeutic target for obesity-related conditions. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Lara-Castro, C (reprint author), Univ Alabama, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. EM garveyt@uab.edu NR 99 TC 145 Z9 158 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD JUN PY 2007 VL 18 IS 3 BP 263 EP 270 DI 10.1097/MOL.0b013e32814a645f PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 176LJ UT WOS:000247086300006 PM 17495599 ER PT J AU Sherman, M AF Sherman, Mindy TI The new American Heart Association cardiopulmonary resuscitation guidelines: should children and adults have to share? SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE cardiopulmonary resuscitation; compression : ventilation ratio; hyperventilation ID PEDIATRIC CARDIAC-ARREST; BASIC LIFE-SUPPORT; CHEST COMPRESSIONS; VENTRICULAR-FIBRILLATION; EPIDEMIOLOGY; VENTILATION; CPR AB Purpose of review The latest American Heart Association guidelines for pediatric cardiopulmonary resuscitation (CPR) were published in December 2005. Changes from the 2000 guidelines were directed toward simplifying CPR. Infants, children, and adults now share the same recommendation for the initial compression:ventilation ratio. This is a significant change for the respiratory etiology of pediatric cardiopulmonary arrest. The present review will focus on the rationale behind these guideline changes. Recent findings The new guidelines for single rescuer CPR include a compression:ventilation ratio of 30:2 for both adult and pediatric victims. The impetus for this recommendation is based on recent appreciation for the deleterious effects of hyperventilation as well as an attempt to uncrease bystander delivery of CPR. The physiologic results of hyperventilation are discussed. The new pediatric basic life support guideline changes are underscored. Research representing the spectrum of opinions on the optimal compression:ventilation ratio, including copression-only CPR, is presented. Summary Although based primarily on adult, animal, and computational models, the new compression:ventilation ratio, recommended for both initial pediatric and adult CPR, is a reasonable recommendation. The simplified CPR guidelines released in 2005 will hopefully contribute to improved bystander in 2005 wiill hopefully contribute to improved bystander delivery of CPR ind improved outcome. C1 Massachusetts Gen Hosp, Pediat Emergency Med Unit, Pediat Emergency Dept, Boston, MA 02138 USA. RP Sherman, M (reprint author), Massachusetts Gen Hosp, Pediat Emergency Med Unit, Pediat Emergency Dept, Fruit St,Ellison One, Boston, MA 02138 USA. EM msherman1@partners.org NR 32 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD JUN PY 2007 VL 19 IS 3 BP 253 EP 257 DI 10.1097/MOP.0b013e3280fb270c PG 5 WC Pediatrics SC Pediatrics GA 174FI UT WOS:000246926900003 PM 17505182 ER PT J AU Hirschmann, JV AF Hirschmann, Jan V. TI Antimicrobial therapy for skin infections SO CUTIS LA English DT Article ID SOFT-TISSUE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; FINE-NEEDLE ASPIRATION; LONG-TERM EFFICACY; VENOUS LEG ULCERS; ATOPIC-DERMATITIS; DOUBLE-BLIND; CUTANEOUS CELLULITIS; ANAEROBIC BACTERIOLOGY; RECURRENT ERYSIPELAS AB The most common skin infections are caused by Staphylococcus aureus, group A streptococci (Streptococcus pyogenes), or the normal skin flora. An antistaphylococcal oral antibiotic is the preferred treatment for nonbullous and bullous impetigo, and a therapeutic agent that is effective against both S aureus and streptococci is appropriate for most cases of cellulitis. For furuncles, carbuncles, cutaneous abscesses, and inflamed epidermal cysts, the most important therapy is incision and drainage, and in most cases there is no need for antimicrobial therapy. Patients with venous ulcers and atopic eczema do not benefit from systemic antimicrobial therapy unless obvious infection is present, as indicated by clinical features such as fever, cellulitis, and lymphangitis. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Hirschmann, JV (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 86 TC 7 Z9 7 U1 2 U2 3 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD JUN PY 2007 VL 79 IS 6 SU S BP 26 EP 36 PG 11 WC Dermatology SC Dermatology GA 187XR UT WOS:000247883100003 PM 17649855 ER PT J AU Hirschmann, JV AF Hirschmann, Jan V. TI Antimicrobial prophylaxis in Dermatologic surgery SO CUTIS LA English DT Article ID ELECTIVE COLORECTAL SURGERY; INFECTIVE ENDOCARDITIS; SKIN SURGERY; ANTIBIOTIC-PROPHYLAXIS; CUTANEOUS ABSCESSES; BACTERIAL-ENDOCARDITIS; TRANSIENT BACTEREMIA; DENTAL EXTRACTIONS; DOUBLE-BLIND; PREVENTION AB Antimicrobial prophylaxis is rarely appropriate for dermatologic surgery. Dermatologic procedures seldom cause bacteremia, and they have been implicated as a cause in only an extremely small number of cases of endocarditis or infections of vascular grafts or orthopedic prostheses. Accordingly, systemic prophylactic antibiotics are not indicated in patients undergoing dermatologic surgery who have valvular heart disease, vascular grafts, or orthopedic prostheses. Because wound infections following dermatologic surgery are uncommon, usually mild, and generally easily treatable, systemic antimicrobial prophylaxis is not indicated to prevent postoperative wound infections either. Topical antibiotic ointments for that purpose are ineffective. Whether prophylactic antivirals are helpful in preventing herpes simplex infections after facial resurfacing is uncertain. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Hirschmann, JV (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 55 TC 6 Z9 7 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD JUN PY 2007 VL 79 IS 6 SU S BP 43 EP 51 PG 9 WC Dermatology SC Dermatology GA 187XR UT WOS:000247883100005 PM 17649857 ER PT J AU Chen, YC Ferracane, JL Prahl, SA AF Chen, Yin-Chu Ferracane, Jack L. Prahl, Scott A. TI Quantum yield of conversion of the photoinitiator camphorquinone SO DENTAL MATERIALS LA English DT Article DE dynamic absorption coefficient; light-activated polymerization; molar extinction coefficient; curing threshold; reciprocity; radiant exposure ID PHOTOPOLYMERIZATION KINETICS; POLYMERIZATION; COMPOSITES; EXPOSURE; SYSTEMS AB The primary absorber in dental resins is the photoinitiator, which starts the photo polymerization process. We studied the quantum yield of conversion of camphorquinone (CQ), a blue light photoinitiator, in dental resin composites using a LED lamp (3M FreeLight) and a Quartz Tungsten Halogen (QTH) lamp (VIP) as the light curing units at five different irradiances. The molar extinction coefficient, 6469, of CQ was 46 +/- 2 cm(-1)/(mol/L) at 469 nm. The reciprocity of irradiance and exposure time holds for changes of CQ absorption coefficient, that is irradiance x exposure time (=radiant exposure) = constant Both LED and QTH lamsp yielded the same curing threshold (the radiant exposure when CQ absorption drops to 1/e) and the same quantum yield conversion under different irradiances. In our dental resin formulation (0.7 wt.% CQ with reducing agents 0.35 wt.% dimethylaminoethyl methacrylate (DMAEMA) and 0.05 wt.% butylated hydroxytoluene (BHT)) the quantum yield was measured as 0.07 +/- 0.01 CQ conversion per absorbed photon. (C) 2006 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97225 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. Oregon Hlth & Sci Univ, Div Biomat & Biomech, Portland, OR USA. RP Prahl, SA (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, 9205 SW Barnes Rd, Portland, OR 97225 USA. EM prahl@bme.ogi.edu OI Ferracane, Jack/0000-0002-6511-5488 FU NCI NIH HHS [CI-R24-CA84587-04]; NIDCR NIH HHS [DE07079] NR 16 TC 41 Z9 43 U1 2 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD JUN PY 2007 VL 23 IS 6 BP 655 EP 664 DI 10.1016/j.dental.2006.06.005 PG 10 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA 170AG UT WOS:000246632600001 PM 16859741 ER PT J AU Wood, AW Sang, XP AF Wood, Antony W. Sang, Xianpeng TI IGF signaling cell-autonomously promotes primordial germ cell migration in zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reproduct Biol, Boston, MA USA. Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 255 BP 384 EP 384 DI 10.1016/j.ydbio.2007.03.364 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500271 ER PT J AU Enshell-Seijffers, D Linden, C Morgan, BA AF Enshell-Seijffers, David Linden, Catherine Morgan, Bruce A. TI Epithelial-mesenchymal interactions in hair follicle morphogenesis and regeneration SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 442 BP 448 EP 448 DI 10.1016/j.ydbio.2007.03.514 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500454 ER PT J AU Xu, G Kaneto, H Laybutt, DR Duvivier-Kali, VF Trivedi, N Suzuma, K King, GL Weir, GC Bonner-Weir, S AF Xu, Gang Kaneto, Hideaki Laybutt, D. Ross Duvivier-Kali, Valerie F. Trivedi, Nitin Suzuma, Kiyoshi King, George L. Weir, Gordon C. Bonner-Weir, Susan TI Downregulation of GLP-1 and GIP receptor expression by hyperglycemia - Possible contribution to impaired incretin effects in diabetes SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; BETA-CELL MASS; DEPENDENT INSULINOTROPIC PEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; C-MYC EXPRESSION; GLUCOSE-TOLERANCE; ORAL GLUCOSE; SECRETION; RAT; PROTEIN AB Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. We hypothesized that this impairment is due to a defect at the receptor level induced by the diabetic state, particularly hyperglycemia. Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-l receptor expression but increase in GIP receptor expression. Similar findings were found when islets were cultured at high glucose concentrations for 48 h. The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKC alpha overexpression. Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. St Vincents Hosp, Diabet & Obes Res Program, Garvan Inst Med Res, Sydney, NSW 2010, Australia. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu FU NIDDK NIH HHS [DK-44523, DK36836] NR 38 TC 157 Z9 165 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1551 EP 1558 DI 10.2337/db06-1033 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000008 PM 17360984 ER PT J AU Qi, L Doria, A Giorgi, E Hu, FB AF Qi, Lu Doria, Alessandro Giorgi, Elena Hu, Frank B. TI Variations in adiponection receptor genes and susceptibility to type 2 diabetes in women - A tagging-single nucleotide polymorphism haplotype analysis SO DIABETES LA English DT Article ID HUMAN SKELETAL-MUSCLE; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; ENCODING ADIPONECTIN-RECEPTOR-1; CARDIOVASCULAR RISK; PLASMA ADIPONECTIN; PROTEIN ACRP30; ASSOCIATION; EXPRESSION; GLUCOSE AB Adiponectin has been associated with low diabetes risk. The metabolic effects of adiponectin are mediated by adiponectin receptors 1 (ADIPOR1) and 2 (ADIPOR2). We conducted a prospective, nested case-control study of 714 cases of type 2 diabetes and 1,120 control subjects. Six polymorphisms in ADIPOR1 and 16 polymorphisms in ADIPOR2 were determined. Haplotypes inferred from ADIPOR1 polymorphisms were significantly associated with diabetes risk (overall test, -2log-likelihood = 15.1 on 5 df; P = 0.0098). A single copy of haplotype 001100 (0, common allele; and 1, minor allele) was associated with 24% decreased risk (odds ratio [OR] 0.76 [95% CI 0.61-0.961, P = 0.02) compared with the most common haplotype, 110000, adjusting for age, BMI, and other covariates. A 3' untranslated region (UTR) polymorphism, rs1139646, showed the strongest and nominally significant association with greater diabetes risk (unadjusted OR 1.26 [1.03-1.53] and adjusted OR 1.36 [1.10-1.701). However, such an association became marginal after controlling for multiple comparisons by permutation test (P = 0.08 on the basis of 10,000 permutations). There were not significant associations between ADIPOR2 polymorphisms, individually or in haplotypes, and the risk of type 2 diabetes. In conclusion, our data indicate significant associations between ADIPOR1 haplotypes and diabetes risk but do not support a relation between ADIPOR2 variability and the disease. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02115 USA. Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845] NR 37 TC 12 Z9 13 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1586 EP 1591 DI 10.2337/db06-1447 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000012 PM 17416799 ER PT J AU Ingelsson, E Sullivan, LM Murabito, JM Fox, CS Benjamin, EJ Polak, JF Meigs, JB Keyes, MJ O'Donnell, CJ Wang, TJ D'Agostino, RB Wolf, PA Vasan, RS AF Ingelsson, Erik Sullivan, Lisa M. Murabito, Joanne M. Fox, Caroline S. Benjamin, Emelia J. Polak, Joseph F. Meigs, James B. Keyes, Michelle J. O'Donnell, Christopher J. Wang, Thomas J. D'Agostino, Ralph B., Sr. Wolf, Philip A. Vasan, Ramachandran S. TI Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst ID CORONARY-HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; RISK-FACTORS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; MEDIA THICKNESS; OLDER-ADULTS; ASSOCIATION; DIAGNOSIS; STROKE AB Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and uriary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than individuals without MetS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67-2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12-2.33]). Participants with MetS and subclinical. disease experienced increased risk of overt CVD (2.67 [1.62-4.41] compared with those without MetS, diabetes, or subclinical diseease), whereas the association of MetS with CVD risk was tenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87-2.90]). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition. C1 Natl Heart Lund & Blood Inst Framingham Study, Framingham, MA USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), FACC, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195, 1R01HL080124, 2K24HL04334] NR 43 TC 54 Z9 56 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1718 EP 1726 DI 10.2337/db07-0078 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000029 PM 17369522 ER PT J AU Grant, RW Wexler, DJ Watson, AJ Lester, WT Cagliero, E Campbell, EG Nathan, DM AF Grant, Richard W. Wexler, Deborah J. Watson, Alice J. Lester, William T. Cagliero, Enrico Campbell, Eric G. Nathan, David M. TI How doctors choose medications to treat type 2 diabetes - A national survey of specialists and academic generalists SO DIABETES CARE LA English DT Article ID PRIMARY-CARE PHYSICIANS; INSULIN THERAPY; UNITED-STATES; QUALITY; PEOPLE; INTERVENTION; PREVENTION; MANAGEMENT; INITIATION; ADHERENCE AB OBJECTIVE- Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients. RESEARCH DESIGN AND METHODS - We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second-line oral agents, and insulin). RESULTS - Respondents reported using a median of five major considerations (interquartile range 4-6) at each stage. Frequently cited major considerations included overall assessment of the patient's heal th/comorbidity, AlC level, and patient's adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P < 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A I C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0-10, P < 0.001. CONCLUSIONS - The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Telemed Program, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM rgrant@partners.org OI Lester, William/0000-0003-4086-9280; Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452-05, K23 DK080228, K23 DK067452] NR 30 TC 40 Z9 41 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2007 VL 30 IS 6 BP 1448 EP 1453 DI 10.2337/dc06-2499 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175ES UT WOS:000246996400019 PM 17337497 ER PT J AU Funnell, MM Brown, TL Childs, BP Haas, LB Hosey, GM Jensen, B Maryniuk, M Peyrot, M Piette, JD Reader, D Siminerio, LM Weinger, K Weiss, MA AF Funnell, Martha M. Brown, Tammy L. Childs, Belinda P. Haas, Linda B. Hosey, Gwen M. Jensen, Brian Maryniuk, Melinda Peyrot, Mark Piette, John D. Reader, Diane Siminerio, Linda M. Weinger, Katie Weiss, Michael A. TI National standards for diabetes self-management education SO DIABETES CARE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; IMPROVE GLYCEMIC CONTROL; PRIMARY-CARE PATIENTS; HEALTH-CARE; COMPLICATIONS TRIAL; PATIENT EDUCATION; AFRICAN-AMERICAN; COMMUNITY-HEALTH; CHRONIC ILLNESS C1 Univ Michigan, Dept Med Educ, Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. Indian Hlth Serv, Albuquerque, NM USA. MidAmer Diabet Associates, Wichita, KS USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Lakeshore Apothacare, Two Rivers, WI USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Loyola Coll, Baltimore, MD 21210 USA. VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. Int Diabet Ctr, Minneapolis, MN USA. Univ Pittsburgh, Med Ctr, Inst Diabet, Pittsburgh, PA USA. Patient Centered Solut, Pittsburgh, PA USA. RP Funnell, MM (reprint author), Univ Michigan, Dept Med Educ, Diabet Res & Training Ctr, 300 N Ingalls,3D06,Box 0489, Ann Arbor, MI 48109 USA. EM mfunnell@umich.edu FU NIDDK NIH HHS [5P60 DK20572]; PHS HHS [1 R18 0K062323] NR 164 TC 72 Z9 75 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2007 VL 30 IS 6 BP 1630 EP 1637 DI 10.2337/dc07-9923 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175ES UT WOS:000246996400060 PM 17526822 ER PT J AU Laffel, LMB Hsu, WC McGill, JB Meneghini, L Volkening, LK AF Laffel, Lori M. B. Hsu, William C. McGill, Janet B. Meneghini, Luigi Volkening, Lisa K. CA Monitoring Blood Glucose TI Continued use of an integrated meter with electronic logbook maintains improvements in glycemic control beyond a randomized, controlled trial SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the American-Diabetes-Association CY JUN 09-13, 2006 CL Washington, DC SP Amer Diabet Assoc ID DEPENDENT DIABETES-MELLITUS; BLOOD-GLUCOSE; MONITORING ADHERENCE; METABOLIC-CONTROL; ADULTS; COMPLICATIONS; THERAPY; PREDICTORS; DIFFERENCE; OUTCOMES AB Background: Blood glucose monitoring is an important component of diabetes self-management for individuals with insulin-treated diabetes. Although patient-maintained logbooks are routinely used, glucose values may be inaccurately recorded or not recorded at all. Electronic logbooks may help overcome such problems. We conducted a randomized, controlled trial (RCT) to compare glycemic control in insulin-treated participants using integrated glucose meters and electronic logbooks (Electronic Group) with participants using conventional meters and paper logbooks (Paper Group), and to determine persistence of glycemic improvements during longterm observational follow-up. Methods: After a 4-week run-in, adult and pediatric participants (n = 205) with stable hemoglobin A(1C) (A1C) >= 8.0% were randomized, and their logbook data and A1C were monitored every 4 weeks for 16 weeks. After the RCT, patients selected their monitoring systems and resumed usual care. The four resulting subgroups, defined by whether patients continued or changed monitoring systems, were reassessed after 26-65 weeks. Results: During the RCT, mean A1C decreased -0.27% in the Paper Group and -0.35% in the Electronic Group. Repeated-measures analysis revealed that the mean decrease was significantly greater in the Electronic than the Paper Group (P = 0.022). From randomization through observational follow-up, participants consistently using integrated meters/logbooks had an A1C decrease of -0.36% (P = 0.008), whereas participants using conventional meters/logbooks throughout or switching meters returned to pre-enrollment A1C levels. Conclusions: Compared to conventional monitoring systems, use of an integrated meter and electronic logbook resulted in modest, but significant and sustained, improvement in A1C in insulin-treated patients with suboptimal glycemic control during an RCT and observational follow-up. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Miami, Miller Sch Med, Miami, FL 33152 USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Place, Boston, MA 02115 USA. EM lori.laffel@joslin.harvard.edu NR 28 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2007 VL 9 IS 3 BP 254 EP 264 DI 10.1089/dia.2006.0021 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180CO UT WOS:000247337800007 PM 17561796 ER PT J AU Wanic, K Malecki, MT Klupa, T Warram, JH Sieradzki, J Krolewski, AS AF Wanic, K. Malecki, M. T. Klupa, T. Warram, J. H. Sieradzki, J. Krolewski, A. S. TI Lack of association between polymorphisms in the gene encoding protein tyrosine phosphatase 1B (PTPN1) and risk of Type 2 diabetes SO DIABETIC MEDICINE LA English DT Article DE association; genetics; polymorphism; Type 2 diabetes mellitus ID SUSCEPTIBILITY LOCUS; FLUORESCENCE POLARIZATION; INSULIN SENSITIVITY; POPULATION; RESISTANCE; RECEPTOR; OBESITY; EXPRESSION; MELLITUS; PTP-1B AB Aims Recently, an association of Type 2 diabetes (T2DM) with polymorphisms in PTPN1 located on chromosome 20q was reported. We attempted to replicate this finding in an ethnically homogeneous Polish population. Methods The study groups comprised 474 cases with T2DM and 411 control subjects with normal fasting glucose. All individuals were genotyped for the five previously reported PTPN1 polymorphisms using a fluorescence polarization method. HAPLO.STAT software was used to infer and compare haplotype distributions. Results The distributions of alleles and genotypes for the five genotyped PTPN1 polymorphisms did not differ between the T2DM cases and control subjects (lowest P = 0.6). Similarly, the frequency of the common haplotype reported to be associated with T2DM did not differ in cases and control subjects. We also failed to find such an association in Whites by performing a meta-analysis of all the available data on the association of those five SNPs with T2DM. Conclusions This case-control study in a Polish population did not confirm the reported association between polymorphisms in PTPN1 and T2DM. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU FIC NIH HHS [TW 1351]; NIDDK NIH HHS [DK 47475] NR 30 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JUN PY 2007 VL 24 IS 6 BP 650 EP 655 DI 10.1111/j.1464-5491.2007.02132.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 171AS UT WOS:000246707900012 PM 17403124 ER PT J AU Tong, J Boyko, EJ Utzschneider, KM McNeely, MJ Hayashi, T Carr, DB Wallace, TM Zraika, S Gerchman, F Leonetti, DL Fujimoto, WY Kahn, SE AF Tong, J. Boyko, E. J. Utzschneider, K. M. McNeely, M. J. Hayashi, T. Carr, D. B. Wallace, T. M. Zraika, S. Gerchman, F. Leonetti, D. L. Fujimoto, W. Y. Kahn, S. E. TI Intra-abdominal fat accumulation predicts the development of the metabolic syndrome in non-diabetic Japanese-Americans SO DIABETOLOGIA LA English DT Article DE Asians; epidemiology; insulin resistance; metabolic syndrome; visceral adiposity ID VISCERAL ADIPOSITY; HYPERINSULINEMIA; DISEASE; RISK AB Aims/hypothesis Intra-abdominal fat (IAF) is an important risk factor for CHD and type 2 diabetes, and in cross-sectional studies is associated with the metabolic syndrome (MetS). Our aim was to determine whether IAF accumulation predicts the future development of MetS in non-diabetic Japanese-Americans. Subjects and methods We conducted a prospective study of 457 Japanese-American men and women (mean +/- SD: age 51.5 +/- 12.0 years, BMI 23.9 +/- 3.1 kg/m(2)) without diabetes or MetS at baseline. Of these, 408 completed a 5-year follow-up and 366 completed a 10-year follow-up. BMI, waist circumference, IAF and subcutaneous fat (SCF) areas by computed tomography, blood pressure, fasting plasma glucose, insulin, triacylglycerol and HDL-cholesterol were measured at baseline and at 5- and 10-year follow-up. MetS was defined using National Cholesterol Education Program Adult Treatment Panel III criteria. Results Incidence of MetS was 15.3% at 5 years and 17.8% at 10 years. A change of 1 SD in IAF area was associated with a 2.1-fold increase in the odds of MetS at 10 years (odds ratio = 2.08, 95% CI 1.41-3.07) after adjusting for age, sex, baseline IAF and the presence of each individual MetS criteria at baseline. This association was independent of changes in fasting insulin and SCF areas. Conclusion We conclude that IAF accumulation over time independently predicts the development of MetS and thus may play an important role in the development of MetS in Japanese-Americans. C1 VA Puget Sound Hlth Care Syst 151, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst 151, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Osaka City Univ, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Tong, J (reprint author), VA Puget Sound Hlth Care Syst 151, Div Metab Endocrinol & Nutr, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tongj@u.washington.edu RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK 02860, DK 55460] NR 12 TC 38 Z9 42 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2007 VL 50 IS 6 BP 1156 EP 1160 DI 10.1007/s00125-007-0651-y PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164YT UT WOS:000246271600006 PM 17387445 ER PT J AU Florez, JC Sjogren, M Agapakis, CM Burtt, NP Almgren, P Lindblad, U Berglund, G Tuomi, T Gaudet, D Daly, MJ Ardlie, KG Hirschhorn, JN Altshuler, D Groop, L AF Florez, J. C. Sjogren, M. Agapakis, C. M. Burtt, N. P. Almgren, P. Lindblad, U. Berglund, G. Tuomi, T. Gaudet, D. Daly, M. J. Ardlie, K. G. Hirschhorn, J. N. Altshuler, D. Groop, L. TI Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes SO DIABETOLOGIA LA English DT Article DE common variants; genetic association; insulin resistance; IRS1; linkage disequilibrium; single nucleotide polymorphism; SNP; type 2 diabetes ID HAPLOTYPE STRUCTURE; GLUCOSE-TOLERANCE; FAMILY-HISTORY; HUMAN GENOME; RESISTANCE; PROTEIN; PEOPLE; POLYMORPHISMS; METAANALYSIS; MELLITUS AB Aims/hypothesis Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal. Subjects and methods We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects. Results In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p=0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p=0.059). The combined OR was 1.20 (p=0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits. Conclusion/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent. C1 Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, England. MIT, Cambridge, MA 02139 USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Lund Univ, Univ Hosp MAS, Dept Clin Sci, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Folkhalsan Res Ctr, Folkhalsan Genet Inst, Helsinki, Finland. Univ Montreal, Community Genom Ctr, Chicoutimi Hosp, Chicoutimi, PQ, Canada. SeraCare Life Sci, Genom Collaborat Div, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Simches Res Bldg CPZN 6820, Boston, MA 02114 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202 FU NIDDK NIH HHS [K23 DK 65978-03] NR 30 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2007 VL 50 IS 6 BP 1209 EP 1217 DI 10.1007/s00125-007-0657-5 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164YT UT WOS:000246271600013 PM 17443311 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Gastrointestinal neuroendocrine tumors: a role for targeted therapies? SO ENDOCRINE-RELATED CANCER LA English DT Review ID PHASE-II TRIAL; METASTATIC CARCINOID-TUMORS; ENDOTHELIAL GROWTH-FACTOR; RADIOLABELED SOMATOSTATIN ANALOG; ISLET-CELL-CARCINOMA; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; TYROSINE KINASE INHIBITOR; SOUTHWEST-ONCOLOGY-GROUP; LIVER METASTASES AB Traditional therapies have offered patients with advanced gastrointestinal neuroenclocrine tumors limited benefit. Selected patients with hepatic metastases may benefit from surgical debulking, embolization, or other ablative therapies. While somatostatin analogs are highly effective in controlling symptoms of hormonal secretion, they are only rarely associated with tumor regression. The clinical benefit associated with the administration of systemic agents such as interferon-a or cytotoxic chemotherapy is less clear, and the widespread use of such regimens has been limited by their relatively modest anti-tumor activity, as well as concerns regarding their potential toxicity. The mixed clinical results seen with these agents in neuroendocrine tumors have led to great interest in the development of novel treatment approaches for patients with advanced disease. Recent clinical studies of novel agents, particularly those targeting the vascular endothelial growth factor pathway and mammalian target of rapamycin, have demonstrated promising activity in patients with advanced neuroendocrine tumors. Ongoing randomized studies should help better define the role these and other targeted agents will play in the future treatment of patients with this disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 102 TC 22 Z9 26 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2007 VL 14 IS 2 BP 207 EP 219 DI 10.1677/ERC-06-0061 PG 13 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 199UI UT WOS:000248720300003 PM 17639038 ER PT J AU Frohlich, LF Bastepe, M Ozturk, D Abu-Zahra, H Juppner, H AF Frohlich, Leopold F. Bastepe, Murat Ozturk, Defne Abu-Zahra, Hilal Juppner, Harald TI Lack of Gnas epigenetic changes and pseudohypoparathyroidism type Ib in mice with targeted disruption of syntaxin-16 SO ENDOCRINOLOGY LA English DT Article ID STIMULATORY G-PROTEIN; ALBRIGHT HEREDITARY OSTEODYSTROPHY; BECKWITH-WIEDEMANN-SYNDROME; IMPRINTING CONTROL ELEMENT; ALPHA-SUBUNIT; ANTISENSE RNA; X-INACTIVATION; CHROMOSOME 20Q; HUMAN GENOME; GENE AB Pseudohypoparathyroidism type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to proximal renal tubular resistance to PTH but without evidence for Albright's hereditary osteodystrophy. The disorder is paternally imprinted and affected individuals, but not unaffected carriers, show loss of GNAS exon A/B methylation, a differentially methylated region upstream of the exons encoding Gs alpha. Affected individuals of numerous unrelated kindreds with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) have an identical 3-kb microdeletion removing exons 4-6 of syntaxin-16 (STX16) (STX16de14- 6), which is thought to disrupt a cis-acting element required for exon A/B methylation. To explore the mechanisms underlying the regulation of exon A/B methylation, we generated mice genetically altered to carry the equivalent of STX16de14-6 (Stx16(Delta 4-6)). Although the human GNAS locus shows a similar organization as the murine Gnas ortholog and although the human and mouse STX16/Stx16 regions show no major structural differences, no phenotypic or epigenotypic abnormalities were detected in mice with Stx16 Delta 4-6 on one or both parental alleles. Furthermore, calcium and PTH levels in Stx16 Delta 4-6 mice were indistinguishable from those in wild-type animals, indicating that ablation of the murine equivalent of human STX16de14-6 does not contribute to the development of PTH resistance. The identification of a novel intragenic transcript from within the STX16/Stx16 locus in total RNA from kidneys of Stx16 Delta 4-6 mice and lymphoblastoid cell-derived RNA of a patient with ADPHP-Ib raises the question whether this transcript contributes, if deleted or altered, to the development of AD-PHP-Ib in humans. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK 46718-10] NR 57 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2007 VL 148 IS 6 BP 2925 EP 2935 DI 10.1210/en.2006-1298 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169DH UT WOS:000246572400044 PM 17317779 ER PT J AU Wu, Y Zhao, WD Zhao, JB Pan, JP Wu, QQ Zhang, YF Bauman, WA Cardozo, CP AF Wu, Yong Zhao, Weidong Zhao, Jingbo Pan, Jiangping Wu, Qiaqia Zhang, Yuanfei Bauman, William A. Cardozo, Christopher P. TI Identification of androgen response elements in the insulin-like growth factor I upstream promoter SO ENDOCRINOLOGY LA English DT Article ID STEROID-HORMONE RECEPTORS; IGF-I; GENE-EXPRESSION; DNA-BINDING; GLUCOCORTICOID-RECEPTORS; DEOXYRIBONUCLEIC-ACID; ANABOLIC-STEROIDS; DEPENDENT MANNER; PROBASIN GENE; MESSENGER-RNA AB Testosterone stimulates the expression of IGF-I in cells and tissues that include prostate, muscle and muscle satellite cells, and the uterus. Here, the molecular mechanisms of this effect of testosterone were explored. Testosterone increased IGF-I mRNA levels in HepG2 and LNCaP cells and stimulated the activity of reporter genes controlled by 1.6 kb of the upstream promoter of the human IGF- I gene. An androgen-responsive region that was located between -1320 and -1420 bases upstream of the first codon was identified by truncation studies. The androgen- responsive region was found to contain two sequences resembling known androgen receptor (AR)binding sites from the Pem1 gene. Reporter genes incorporating these sequences were strongly stimulated by androgens. Each of the androgen-responsive elements (AREs) bound recombinant AR-DNA-binding domain in gel-shift experiments; binding was greatly enhanced by sequences flanking the apparent AR-binding half-sites. Testosterone induced recruitment of AR to sequences of genomic DNA containing these AREs. The two AREs were activated 5-fold more by AR than glucocorticoid receptor. Collectively, these findings indicate the presence of two AREs within the IGF-I upstream promoter that act in cis to activate IGF-I expression. These AREs seem likely to contribute to the up-regulation of the IGF-I gene in prostate tissues, HepG2 cells, and potentially other tissues. C1 James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Room 1E-02, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU NIDDK NIH HHS [DK 60598] NR 48 TC 51 Z9 52 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2007 VL 148 IS 6 BP 2984 EP 2993 DI 10.1210/en.2006-1653 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169DH UT WOS:000246572400050 PM 17363459 ER PT J AU Meeker, JD Altshul, L Hauser, R AF Meeker, John D. Altshul, Larisa Hauser, Russ TI Serum PCBs, p,p'-DDE and HCB predict thyroid hormone levels in men SO ENVIRONMENTAL RESEARCH LA English DT Article DE DDE; hexachlorobenzene; hormone; PCB; thyroid ID POLYCHLORINATED-BIPHENYLS; ENVIRONMENTAL EXPOSURE; ORGANOCHLORINES; HEALTH; HEXACHLOROBENZENE; ASSOCIATIONS; P,P'-DDE; RECEPTOR; DISEASE; HUMANS AB Polychlorinated biphenyls (PCBs) and some organochlorine pesticides, which continue to be measurable in a high proportion of blood samples from the general population, have been found to alter thyroid hormone levels in animals and humans. However, studies of these relationships in adult men are limited and results across studies have been inconsistent. In the present study, we measured serum levels of 57 PCB congeners, dichlorodiphenyldichloroethylene (p,p '-DDE, a stable metabolite of DDT), and hexachlorobenzene (HCB), as well as free T-4, total T-3, and TSH, in 341 adult men recruited from an infertility clinic from 2000 to 2003. In multivariate linear regression, there were positive associations between p,p '-DDE and both free T4 and total T3, and an inverse association between p,p '-DDE and TSH. Conversely, for PCBs there was only a suggestive inverse association between PCB 153 and total T3 when potential confounding variables were considered. However, when results were additionally adjusted for p,p '-DDE, inverse associations with T3 were significant for PCB 138, PCB 153, sum of PCBs and three different PCB groupings, and HCB, while the positive associations between p,p '-DDE and T3 also remained. In conclusion, serum concentrations of PCBs, p,p '-DDE, and HCB were associated with circulating thyroid hormone levels in adult men. Abbreviations: BMI, body mass index; CYP, cytochrome P450; DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; HCB, hexachlorobenzene; MDL, method detection limit; NHANES, national health and nutrition examination survey: p,p '-DDE, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; PCB, polychlorinated biphenyl; T3, triiodothyronine; T4, thryoxine; TSH, thyroid stimulating hormone (thyrotrophin); US, United States. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Dept Environm Hlth Sci, M6226 SPH 2,109 S Observatory St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [P30 ES000002, R01 ES009718, ES09718, P30 ES000002-43, R01 ES009718-08, ES00002] NR 34 TC 71 Z9 75 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUN PY 2007 VL 104 IS 2 BP 296 EP 304 DI 10.1016/j.envres.2007.11.007 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 176CP UT WOS:000247060700013 PM 17189629 ER PT J AU Co, JPT Elia, M Engel, J Guerrini, R Mizrahi, EM Moshe, SL Plouin, P AF Co, John Patrick T. Elia, Maurizio Engel, Jerome Guerrini, Renzo Mizrahi, Eli M. Moshe, Solomon L. Plouin, Perrine TI Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries SO EPILEPSIA LA English DT Article DE algorithm; neonatal seizures; developing countries AB Seizures in the neonatal period are common. They can be caused by a variety of conditions, ranging from benign, self-limited illnesses to severe, life-threatening disorders. They are often the first sign of neurologic dysfunction in neonates, and may be used as one factor in considering long-term prognosis. An important mission of the International League Against Epilepsy (ILAE) is to improve the care of patients with epilepsy. Most recently, as part of the Global Campaign against Epilepsy, ILAE, in conjunction with the World Health Organization (WHO), established a new initiative to create clinical guidelines and diagnostic and management algorithms for the care of patients with seizures that can be applied worldwide, including in developing countries with limited or varied medical resources. Created by an international panel of experts in seizure management and guideline development, this document proposes guidelines for the diagnosis and management of the most common and important conditions that cause seizures in the neonatal period. The publication of these clinical pathways for neonatal seizures will be followed by a period of field testing and comment by WHO clinicians and officials before finalization. C1 WHO, Collaborating Ctr Res & Training Neurosci, Oasi Inst Res Mental Retardat & Brain Aging, IRCCS,Dept Neurol, I-94018 Troina, EN, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy,Dept Pediat, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90024 USA. Univ Pisa, Div Child Neurol & Psychiat, Epilepsy Neurophysiol & Neurogenet Unit, I-56100 Pisa, Italy. Stella Maris Fdn, Inst Res, Pisa, Italy. Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Sect Pediat Neurol, Houston, TX 77030 USA. Albert Einstein Coll Med, Einstein Montefiore Med Ctr, Saul R Korey Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Einstein Montefiore Med Ctr, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA. Albert Einstein Coll Med, Einstein Montefiore Med Ctr, Dept Pediat, Bronx, NY 10467 USA. Hop Necker Enfants Malad, INSERM, Dept Clin Neurophysiol, U663, Paris, France. RP Elia, M (reprint author), WHO, Collaborating Ctr Res & Training Neurosci, Oasi Inst Res Mental Retardat & Brain Aging, IRCCS,Dept Neurol, Via Conte Ruggero 73, I-94018 Troina, EN, Italy. EM melia@oasi.en.it RI Elia, Maurizio/K-3285-2016 OI Elia, Maurizio/0000-0002-0414-1359 NR 7 TC 8 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2007 VL 48 IS 6 BP 1158 EP 1164 DI 10.1111/j.1528-1167.2007.01008.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 176ZZ UT WOS:000247124700019 PM 17442012 ER PT J AU Niquet, J Auvin, S Archie, M Seo, DW Allen, S Sankar, R Wasterlain, CG AF Niquet, Jerome Auvin, Stephane Archie, Mark Seo, Dae-Won Allen, Suni Sankar, Raman Wasterlain, Claude G. TI Status epilepticus triggers caspase-3 activation and necrosis in the immature rat brain SO EPILEPSIA LA English DT Article DE hippocampus; electron microscopy; programmed cell death ID PILOCARPINE STATUS EPILEPTICUS; NEURONAL NECROSIS; NEURODEGENERATION AB The mode and mechanism of neuronal death induced by status epilepticus (SE) in the immature brain have not been fully characterized. In this study, we analyzed the contribution of neuronal necrosis and caspase-3 activation to CA1 damage following lithium-pilocarpine SE in P14 rat pups. By electron microscopy, many CA1 neurons displayed evidence of early necrosis 6 hours following SE, and the full ultrastructural features of necrosis at 24-72 hours. Caspase-3 was activated in injured (acidophilic) neurons 24 hours following SE, raising the possibility that they died by caspase-dependent "programmed" necrosis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Lille Univ Hosp, Pediat Neurol Dept, Lille, France. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu OI Auvin, Stephane/0000-0003-3874-9749 FU NINDS NIH HHS [NS046516, R01 NS13515] NR 13 TC 26 Z9 28 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2007 VL 48 IS 6 BP 1203 EP 1206 DI 10.1111/j.1528-1167.2007.01102.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 176ZZ UT WOS:000247124700024 PM 17441993 ER PT J AU Zeber, JE Copeland, LA Amuan, M Cramer, JA Pugh, MJV AF Zeber, John E. Copeland, Laurel A. Amuan, Megan Cramer, Joyce A. Pugh, Mary Jo V. TI The role of comorbid psychiatric conditions in health status in epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE epilepsy; comorbid psychiatric conditions; health status; veterans ID QUALITY-OF-LIFE; PSYCHOGENIC NONEPILEPTIC SEIZURES; VETERANS-AFFAIRS; OLDER-ADULTS; ADMINISTRATIVE DATA; RESISTANT EPILEPSY; MENTAL-ILLNESS; DISORDERS; DEPRESSION; PREVALENCE AB Comorbid psychiatric conditions are highly prevalent in patients with epilepsy, yet the long-term implications across multiple mental health conditions are poorly understood. We examined the association between psychiatric diagnoses and self-reported health status in veterans with epilepsy. ANCOVA models were used to derive adjusted SF-36V scores for individuals with epilepsy alone (N = 7379) or with additional psychiatric conditions (N = 6320): depression, schizophrenia, bipolar disorder, anxiety disorder, substance abuse, and posttraumatic stress disorder (PTSD). Compared with patients with epilepsy alone, scores of veterans with comorbid psychiatric diagnoses averaged 21% lower across all domains. Role Limitation scales exhibited the greatest decrement across domains. A PTSD diagnosis consistently corresponded to lower scores, followed by depression. Schizophrenia contributed the least detriment to perceived health status. Comorbid psychiatric conditions impart significant emotional and physical burdens, requiring timely recognition and treatment of these disorders. Patients with epilepsy are uniquely at risk for high physical-psychiatric comorbidity profiles, with concomitant losses in perceived health status. Published by Elsevier Inc. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT Ctr 11C6, HSR&D Verdict, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Edith Nourse Rogers Mem Vet Adm Hosp, CHQOER, Bedford, MA 01730 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Texas, Hlth Sci Ctr, Dept Internal Med, San Antonio, TX USA. RP Zeber, JE (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT Ctr 11C6, HSR&D Verdict, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM zeber@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 NR 67 TC 30 Z9 31 U1 4 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUN PY 2007 VL 10 IS 4 BP 539 EP 546 DI 10.1016/j.yebeh.2007.02.008 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 178JL UT WOS:000247216900004 PM 17416208 ER PT J AU Artinian, NT Warnecke, RB Kelly, KM Weiner, J Lurie, N Flack, JM Mattei, J Eschbach, K Long, JA Furumoto-Dawson, A Hankin, JR DeGraffinreid, C AF Artinian, Nancy T. Warnecke, Richard B. Kelly, Kimberly M. Weiner, Janet Lurie, Nicole Flack, John M. Mattei, Josiemer Eschbach, Karl Long, Judith A. Furumoto-Dawson, Alice Hankin, Janet R. DeGraffinreid, Cecilia TI Advancing the science of health disparities research SO ETHNICITY & DISEASE LA English DT Article DE Centers for Population Health and Health Disparities; health policy; population health; community-based participatory research; underserved populations ID RESIDENTIAL SEGREGATION; SOCIAL-ISOLATION; HEART-DISEASE; UNITED-STATES; CANCER; ENVIRONMENTS; MULTILEVEL; MECHANISMS; MORTALITY; PARADOX AB Research to eliminate health disparities in the United States is best approached from the perspective of population health. The objectives of this paper are to: a) describe how ongoing research at the eight national Centers for Population Health and Health Disparities (CPHHD) is using a population health perspective and a community-based approach to advance the field of health disparities research; and b) to discuss potential implications of such research for health policies that target some of the determinants of population health. C1 Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA. Wayne State Univ, Natl Ctr Populat Hlth & Hlth Dispar, Detroit, MI 48202 USA. Univ Illinois, Ctr Canc, Chicago, IL USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RAND, Ctr Publ Hlth, Ctr Domest & Int Hlth Secur, Philadelphia, PA USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48202 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Medford, MA 02155 USA. Univ Texas, Med Branch, Dept Internal Med Geriatr, Galveston, TX 77550 USA. Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Dept Internal Med, Philadelphia, PA 19104 USA. Univ Chicago, Ctr Interdisciplinary Hlth Dispar Res, Inst Mind & Biol, Chicago, IL 60637 USA. Wayne State Univ, Dept Sociol, Detroit, MI 48202 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Artinian, NT (reprint author), Wayne State Univ, Coll Nursing, 5557 Cass Ave, Detroit, MI 48202 USA. EM n.artinian@wayne.edu RI Mattei, Josiemer/H-1800-2016; OI Mattei, Josiemer/0000-0001-5424-8245; Weiner, Janet/0000-0001-5810-5807 FU NCI NIH HHS [1P50 CA 106743-01, 1P50 CA195641, 1P59 CA105632, 5P50 CA105631, P50 CA105631, P50 CA105632, P50 CA106743]; NHLBI NIH HHS [T32 HL069772]; NIA NIH HHS [5P01 AG023394-3, P01 AG023394]; NIEHS NIH HHS [5P50 ES012382, 5P50 ES12383, P50 ES012382, P50 ES012383, P50 ES012395] NR 31 TC 4 Z9 4 U1 0 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2007 VL 17 IS 3 BP 427 EP 433 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204TI UT WOS:000249066500002 PM 17985493 ER PT J AU Calkins, H Brugada, J Packer, DL Cappato, R Chen, SA Crijns, HJG Damiano, RJ Davies, DW Haines, DE Haissaguerre, M Lesaka, Y Jackman, W Jais, P Kottkamp, H Kuck, KH Lindsay, BD Marchlinski, FE McCarthy, PM Mont, JL Morady, F Nademanee, K Natale, A Pappone, C Prystowsky, E Raviele, A Ruskin, JN Shemin, RJ AF Calkins, Hugh Brugada, Josep Packer, Douglas L. Cappato, Riccardo Chen, Shih-Ann Crijns, Harry J. G. Damiano, Ralph J., Jr. Davies, D. Wyn Haines, David E. Haissaguerre, Michel Lesaka, Yoshito Jackman, Warren Jais, Pierre Kottkamp, Hans Kuck, Karl Heinz Lindsay, Bruce D. Marchlinski, Francis E. McCarthy, Patrick M. Mont, J. Lluis Morady, Fred Nademanee, Koonlawee Natale, Andrea Pappone, Carlo Prystowsky, Eric Raviele, Antonio Ruskin, Jeremy N. Shemin, Richard J. TI HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for personnel, policy, procedures and follow-up SO EUROPACE LA English DT Review ID PULMONARY VEIN ISOLATION; MITRAL-VALVE DISEASE; COX-MAZE PROCEDURE; PHRENIC-NERVE INJURY; ISOLATED SHEEP HEART; BIPOLAR RADIOFREQUENCY ABLATION; MAGNETIC-RESONANCE ANGIOGRAPHY; ACCESSORY ATRIOVENTRICULAR CONNECTIONS; ARRAY INTRACARDIAC ECHOCARDIOGRAPHY; EPICARDIAL MICROWAVE ABLATION C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. Taipei Vet Gen Hosp, Taipei, Taiwan. Allgemeines Krankenhaus St Georg, Hamburg, Germany. Cleveland Clin Fdn, Cleveland, OH 44195 USA. William Beaumont Hosp, Beaumont, TX USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Arrhythmia & EP Ctr, Milan, Italy. Univ Hosp Maastricht, Maastricht, Netherlands. Washington Univ, Sch Med, St Louis, MO 63130 USA. Univ Bordeaux, Hop Cardiol, Bordeaux, France. Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan. Clin Hirslanden Zurich, Zurich, Switzerland. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Hosp San Raffaele, Milan, Italy. Umberto I Hosp, Venice, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Calkins, H (reprint author), Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RI Pappone, Carlo/J-9853-2016 OI Pappone, Carlo/0000-0002-0901-6135 NR 351 TC 370 Z9 385 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD JUN PY 2007 VL 9 IS 6 BP 335 EP 379 DI 10.1093/europace/eum120 PG 45 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 202MA UT WOS:000248904600001 PM 17599941 ER PT J AU Pjrek, E Winkler, D Abramson, DW Konstantinidis, A Stastny, J Willeit, M Praschak-Rieder, N Kasper, S AF Pjrek, Edda Winkler, Dietmar Abramson, David W. Konstantinidis, Anastasios Stastny, Juergen Willeit, Matthaeus Praschak-Rieder, Nicole Kasper, Siegfried TI Serum lipid levels in seasonal affective disorder SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE serum lipids; cholesterol; triglycerides; seasonal affective disorder ID NORMOLIPIDEMIC POSTMENOPAUSAL WOMEN; MAJOR DEPRESSIVE DISORDER; CHOLESTEROL LEVELS; PLASMA-CHOLESTEROL; WINTER DEPRESSION; SUICIDE ATTEMPT; MELATONIN; LIGHT; MEN; STATE AB Previous research has assessed the relationship between blood lipid levels and depression with contradictory results. Several studies have linked low cholesterol levels with impulsive, aggressive and suicidal behaviours. The aim of this pilot study was to examine serum lipids in a sample of patients suffering from seasonal affective disorder (SAD). We conducted a retrospective analysis of data on total serum cholesterol and serum triglycerides in 39 SAD patients and 40 non-seasonally depressed or schizophrenic control subjects. Study subjects had to be free of psychotropic drugs for at least 2 weeks. Analysis of covariance (ANCOVA) was performed to assess group differences. After adjustment for significant covariates SAD patients had significantly lower total cholesterol levels (5.21 +/- 1.14 mmol/l) than control subjects (5.94 +/- 1.11 mmol/l; p = 0.013). Moreover, hypercholesterolemia (total cholesterol > 5.20 mmol/l) was significantly less frequent in the SAD group (46.2%) than in the control group (75.0%; p = 0.012). Total serum triglycerides did not differ significantly between SAD patients (1.54 +/- 1.07 mmol/l) and controls (1.56 +/- 0.96 mmol/l; p = 0.126). The results of this study support the idea that low cholesterol levels may be of pathogenetic importance in SAD. Further study in larger clinical samples is warranted to clarify our findings. C1 Med Univ Vienna, Dept Gen Psychiat, A-1090 Vienna, Austria. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pjrek, E (reprint author), Med Univ Vienna, Dept Gen Psychiat, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM edda.pjrek@meduniwien.ac.at NR 60 TC 3 Z9 3 U1 0 U2 4 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUN PY 2007 VL 257 IS 4 BP 197 EP 202 DI 10.1007/s00406-006-0706-y PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 184YU UT WOS:000247679300003 PM 17149538 ER PT J AU Pott, GB Sailer, CA Porat, R Peskind, RL Fuchs, AC Angel, JB Skolnik, PR Jacobson, MA Giordano, MF LeBeaut, A Grint, PC Dinarello, CA Shapiro, L AF Pott, Gregory B. Sailer, Carrie A. Porat, Reuven Peskind, Robert L. Fuchs, Amy C. Angel, Jonathan B. Skolnik, Paul R. Jacobson, Mark A. Giordano, Michael F. LeBeaut, Alexandre Grint, Paul C. Dinarello, Charles A. Shapiro, Leland TI Effect of a four-week course of interleukin-10 on cytokine production in a placebo-controlled study of HIV-1-infected subjects SO EUROPEAN CYTOKINE NETWORK LA English DT Article DE HIV-1; interleukin-10; pro-inflammatory cytokines; whole blood; ex vivo ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; BLOOD MONONUCLEAR-CELLS; INFECTED U1 CELLS; IN-VITRO; CONTROLLED-TRIAL; TNF-ALPHA; MONOCYTE/MACROPHAGE LINEAGE; RECEPTOR ANTAGONIST; HIV-1 EXPRESSION AB Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)alpha, IL-1 beta, and interferon (IFN)gamma. Since pro-inflammatory cytokines have been implicated in the production of human immunodeficiency virus type I (HIV-1), cytokine synthesis in whole blood cultures were determined during a 4-week course of subcutaneous IL-10 injections in 33 HIV-1-infected patients. Patients were randomized into four groups: placebo (nine), IL-10 at 1 mu g/kg/day (nine), IL-10 at 4 mu g/kg/day (six) and IL-10 at 8 mu g/kg three times per week (nine). Whole blood was obtained at the beginning and conclusion of the study and was stimulated for 24 hours with the combination of IL-18 plus lipopolysaccharide. TNF alpha production in stimulated whole blood was reduced three and six hours after the first injection of IL-10 compared to subjects injected with the placebo. After four weeks of treatment, production of IFN gamma was suppressed in a greater number of patients in the IL-10 treatment groups compared to subjects in the placebo group. Similarly, IL-1 beta production was lower in the IL-10 treatment groups compared to subjects receiving placebo. In contrast, after four weeks of IL-10, circulating levels of the anti-inflammatory TNF soluble receptor p55 increased dose-dependently compared to placebo subjects. Patient heterogeneity and small sample size presented difficulties in establishing statistical significance. Although the cytokine changes in our study did not demonstrate statistically significant changes, the data nevertheless reveal that four weeks of IL-10 therapy in HIV-1 infected subjects produced the anticipated suppression of pro-inflammatory cytokines. C1 Univ Colorado, Div Infect Dis, Dept Med, Denver, CO 80262 USA. Hlth Sci Ctr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Ischlov Hosp, Tel Aviv Soursky Med, Dept Med, Tel Aviv, Israel. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Ottawa, Ottawa, ON, Canada. Boston Univ, Med Ctr, Ctr HIV AIDS Care & Res, Boston, MA 02215 USA. Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA USA. San Francisco Gen Hosp, Med Serv, San Francisco, CA 94110 USA. Cornell Univ, Coll Med, New York, NY USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Shapiro, L (reprint author), Univ Colorado, Div Infect Dis, Dept Med, 4200 E 9th Ave,Box B168, Denver, CO 80262 USA. EM leland.shapiro@uchsc.edu FU NCRR NIH HHS [M01RR00083]; NIAID NIH HHS [AI 15614] NR 38 TC 4 Z9 5 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD JUN PY 2007 VL 18 IS 2 BP 49 EP 58 DI 10.1684/ecn.2007.0094 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 199RV UT WOS:000248713800001 PM 17594937 ER PT J AU Pai, JK Manson, JE Rexrode, KM Albert, CM Hunter, DJ Rimm, EB AF Pai, Jennifer K. Manson, Joann E. Rexrode, Kathryn M. Albert, Christine M. Hunter, David J. Rimm, Eric B. TI Complement factor H (Y402H) polymorphism and risk of coronary heart disease in US men and women SO EUROPEAN HEART JOURNAL LA English DT Article DE inflammation; coronary heart disease; genetics; epidemiology; complement factor H ID C-REACTIVE PROTEIN; MACULAR DEGENERATION; ATHEROSCLEROTIC LESIONS; MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; ACTIVATION; GENE; HAPLOTYPE AB Aims Complement factor H (CFH) Y402H polymorphism is located in a region that binds C-reactive protein and may affect inflammatory processes and risk of coronary heart disease (CHD). We assessed the association between Y402H and risk of CHD in nested case-controi studies among two large prospective cohorts of US mate health professionals and female nurses. Methods and results Among participants who were disease-free at baseline, we confirmed 266 (men) and 249 (women) incident CHD deaths and non-fatal myocardial infarctions (Mis) over 6 and 8 years of follow-up, respectively. Using risk-set sampling, controls were matched 2:1 on the basis of age, smoking, and date of blood draw. Comparing homozygous HH with Yy, the relative risk (RR) of CHD was 0.94 [95% confidence interval (CI) 0.59-1.49] among men and 0.51 (95% CI 0.29-0.89) among women (pooled RR 0.73, 95% CI 0.51-1.04). The HH genotype was inversely associated with CHD among those <65 years at onset (men: RR 0.39, 95% CI 0.16-0.95; women: 0.21, 95% CI 0.07-0.65; pooled: 0.30, 95% CI 0.15-0.61), but not among those >= 65 years (pooled RR 1.09, 95% CI 0.71-1.68). Conclusion CFH Y402H was inversely associated with CHD among women, but not men. This inverse association was observed in both populations with earlier age of CHD. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Pai, JK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 9th Floor, Boston, MA 02115 USA. EM jpai@hsph.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA 55075]; NHLBI NIH HHS [HL 34594, HL 35464] NR 27 TC 13 Z9 16 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2007 VL 28 IS 11 BP 1297 EP 1303 DI 10.1093/eurheartj/ehm090 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191GX UT WOS:000248120700009 PM 17483111 ER PT J AU Moukarbel, G Ennis, S Moore, S Macgillivray, T AF Moukarbel, G. Ennis, S. Moore, S. Macgillivray, T. TI Alterations of pulmonary artery pressure in patients with a new axial flow left ventricular device SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2007 VL 6 SU 1 BP 2 EP 2 DI 10.1016/S1567-4215(07)60005-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 185QW UT WOS:000247726500008 ER PT J AU Alexander, JJ Jacob, A Vezina, P Sekine, H Gilkeson, GS Quigg, RJ AF Alexander, Jessy J. Jacob, Alexander Vezina, Paul Sekine, Hideharu Gilkeson, Gary S. Quigg, Richard J. TI Absence of functional alternative complement pathway alleviates lupus cerebritis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE apoptosis; brain; complement factor B; extracellular matrix; MRL/lpr mice ID CENTRAL-NERVOUS-SYSTEM; INTERCELLULAR-ADHESION MOLECULE-1; ANTIGEN-SPECIFIC LYMPHOCYTES; ENDOTHELIAL GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; FACTOR-B; NEUROPSYCHIATRIC LUPUS; MEDIATED APOPTOSIS; AUTOIMMUNE MICE; GENE-EXPRESSION AB The complement inhibitor, Crry, which blocks both the classical and alternative pathways, alleviates CNS disease in the lupus model, MRLIMpJ-Tnfrsf6lpr (MRL/Ipr) mice. To understand the role of the alternative pathway, we studied mice deficient in a key alternative pathway protein, complement factor B (M). Immune deposits (IgG and C3) were reduced in the brains of MRL/lpr fB-deficient (fB(-/-)MRL/lpr) compared to fBsufficient (MRL/Ipr) mice, indicating reduced complement activation. Reduced neutrophil infiltration (22% of MRL/1pr mice) and apoptosis (caspase-3 activity was reduced to 33% of MRL/Ipr mice) in these mice indicates that the absence of the alternative pathway was neuroprotective. Furthermore, expression of phospho (p)-Akt (0.16 +/- 0.02 vs. 0.35 +/- 0.13, p < 0.03) was increased, while expression of p-PTEN (0.40 +/- 0.06 vs. 0.11 +/- 0.07, p < 0.05) was decreased in fB(-/-)MRL/lpr mice compared to their MRL/1pr counterparts. The expression of fibronectin, laminin and collagen I-V was significantly decreased in fB(-/-)MRL/Ipr mice compared to MRL/lpr mice, indicating that in the lupus setting, tissue integrity was maintained in the absence of the alternative pathway. Absence of fB reduced behavioral alterations in MRL/lpr mice. Our results suggest that in lupus, the alternative pathway may be the key mechanism through which complement activation occurs in brain, and therefore it might serve as a therapeutic target for lupus cerebritis. C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Med Univ SC, Ralph H Johnson VA Med Ctr, Dept Med, Med Res Serv, Charleston, SC USA. RP Alexander, JJ (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave,MC5100, Chicago, IL 60637 USA. EM jalexand@medicine.bsd.uchicago.edu FU NIDDK NIH HHS [R01DK055357] NR 55 TC 25 Z9 27 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 2007 VL 37 IS 6 BP 1691 EP 1701 DI 10.1002/eji.2006366381 PG 11 WC Immunology SC Immunology GA 179HF UT WOS:000247279600028 PM 17523212 ER PT J AU Alavi, A Mavi, A Basu, S Fischman, A AF Alavi, Abass Mavi, Ayse Basu, Sandip Fischman, Alan TI Is PET-CT the only option? SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; ATTENUATION CORRECTION; RESPIRATORY MOTION; CLINICAL ONCOLOGY; TRACER UPTAKE; ARTIFACTS; CONTRAST; REGISTRATION C1 Hosp Univ Penn, Div Nucl Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Yeditepe Univ, Div Nucl Med, Istanbul, Turkey. RP Alavi, A (reprint author), Hosp Univ Penn, Div Nucl Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM alavi@oasis.rad.upenn.edu NR 29 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUN PY 2007 VL 34 IS 6 BP 819 EP 821 DI 10.1007/s00259-006-0340-y PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169KY UT WOS:000246592300002 PM 17216469 ER PT J AU Kalva, SP Athanasoulis, CA Greenfield, AJ Fan, CM Curvelo, M Waltman, AC Wicky, S AF Kalva, S. P. Athanasoulis, C. A. Greenfield, A. J. Fan, C.-M. Curvelo, M. Waltman, A. C. Wicky, S. TI Inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Review DE inferior pancreatico-duodenal artery aneurysm; celiac stenosis; celiac occlusion; aneuryms of pancreaticoduodenal arcades ID MEDIAN ARCUATE LIGAMENT; MANAGEMENT; EMBOLIZATION AB Purpose. To describe the pathophysiology, identification and management of inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion has been reported. Review findings. These aneurysms are thought to arise due to increased flow through the pancreaticoduodenal arcades. The arcades first enlarge, and then form focal aneurysms which may rupture. The aneurysms can be treated through endovascular techniques or by surgery, though the former is a preferred approach. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM skalva@partners.org NR 21 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD JUN PY 2007 VL 33 IS 6 BP 670 EP 675 DI 10.1016/j.ejvs.2006.12.021 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 178JR UT WOS:000247217500006 PM 17276102 ER PT J AU Tgavalekos, NT Musch, G Harris, RS Melo, MFV Winkler, T Schroeder, T Callahan, R Lutchen, KR Venegas, JG AF Tgavalekos, N. T. Musch, G. Harris, R. S. Melo, M. F. Vidal Winkler, T. Schroeder, T. Callahan, R. Lutchen, K. R. Venegas, J. G. TI Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE airway obstruction; constriction; elastance; heterogeneous; oscillatory; resistance ID PULMONARY PERFUSION; EXERCISE CHALLENGE; METHACHOLINE; BRONCHOCONSTRICTION; INFLATION; IMPEDANCE; DISEASE; HUMANS; PET AB Bronchoconstriction in asthma results in patchy ventilation forming ventilation defects (VDefs). Patchy ventilation is clinically important because it affects obstructive symptoms and impairs both gas exchange and the distribution of inhaled medications. The current study combined functional imaging, oscillatory mechanics and theoretical modelling to test whether the degrees of constriction of airways feeding those units outside VDefs were related to the extent of VDefs in bronchoconstricted asthmatic subjects. Positron emission tomography was used to quantify the regional distribution of ventilation and oscillatory mechanics were measured in asthmatic subjects before and after bronchoconstriction. For each subject, ventilation data was mapped into an anatomically based lung model that was used to evaluate whether airway constriction patterns, consistent with the imaging data, were capable of matching the measured changes in airflow obstruction. The degree and heterogeneity of constriction of the airways feeding alveolar units outside VDefs was similar among the subjects studied despite large inter-subject variability in airflow obstruction and the extent of the ventilation defects. Analysis of the data amongst the subjects showed an inverse relationship between the reduction in mean airway conductance, measured in the breathing frequency range during bronchoconstriction, and the fraction of lung involved in ventilation defects. The current data supports the concept that patchy ventilation is an expression of the integrated system and not just the sum of independent responses of individual airways. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Dept Pulm & Crit Care Unit, Clin Epidemiol Unit, Boston, MA 02114 USA. Boston Univ, Harvard Med Sch, Dept Biomed Engn, Boston, MA 02215 USA. RP Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-237F, Boston, MA 02114 USA. EM jvenegas@partners.org RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [HL-68011] NR 25 TC 44 Z9 47 U1 0 U2 3 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 JUN PY 2007 VL 29 IS 6 BP 1174 EP 1181 DI 10.1183/09031936.00113606 PG 8 WC Respiratory System SC Respiratory System GA 179HN UT WOS:000247280500015 PM 17360726 ER PT J AU Cook-Easterwood, J Middaugh, LD Griffin, WC Khan, I Tyor, WR AF Cook-Easterwood, Jennifer Middaugh, Lawrence D. Griffin, William C., III Khan, Irfan Tyor, William R. TI Highly active antiretroviral therapy of cognitive dysfunction and neuronal abnormalities in SCID mice with HIV encephalitis SO EXPERIMENTAL NEUROLOGY LA English DT Article DE HIV; encephalitis; highly active antiretroviral therapy; cognition; neuronal abnormalities; TNF-alpha; SCID mice ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; DEMENTIA COMPLEX; ALPHA PRODUCTION; MURINE MODEL; MOUSE MODEL; BRAIN; NEUROPATHOGENESIS; QUANTITATION AB Our objective was to determine if highly active antiretroviral therapy (HAART), previously shown to ameliorate several pathological features of HIV encephalitis (HIVE) in a SCID mouse model, would also reduce additional established pathological features of HIV. cognitive dysfunction, TNF-alpha, production, and reduced MAP-2 expression. SCID mice with HIVE and control mice inoculated with uninfected monocytes were administered HAART or saline. The HIV pathological features evaluated included astrogliosis, viral load, neuronal apoptosis, MAP-2 expression, mouse TNF-alpha mRNA production and learning acquisition and retention. HAART reduced the HIV-induced viral load, and the astro- and microgliosis as previously observed-, this effect was extended to HIV-induced increases in TNF-alpha mRNA production. In contrast, although HIV produced the cognitive deficits previously observed and also decreased MAP-2 expression in the area surrounding the injected HIV-infected human monocytes, HAART did not attenuate these effects. Interestingly, there was no neuronal apoptosis evident at the time point reflecting the above pathology. The results of this study combined with previous reports indicate that HAART reduces TNF-alpha. mRNA, viral load and astrogliosis; however, HAART does not improve HIV-induced cognitive dysfunction or MAP-2 decreases. These results suggest that viral load, astrogliosis, TNF-alpha and apoptosis are not prominent in the pathogenesis of early functional deficits related to decreased MAP-2 expression or cognitive dysfunction in HIVE in SCID mice. (c) 2007 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Serv Neurol, Charleston, SC 29401 USA. RP Tyor, WR (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St,Suite 309, Charleston, SC 29425 USA. FU BLRD VA [I01 BX001506]; NIMH NIH HHS [R01 MH62697-05, R01 MH062697-04, R01 MH062697] NR 34 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2007 VL 205 IS 2 BP 506 EP 512 DI 10.1016/j.expneurol.2007.03.007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 176TQ UT WOS:000247108200020 PM 17442303 ER PT J AU Hezel, AF Ryan, DP AF Hezel, Aram F. Ryan, David P. TI Emerging therapies for colorectal cancer SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE APC/WNT; aurora kinase; colon cancer; colorectal cancer; EGFR; erbB/EGFR; Met; Notch; PI3K ID GROWTH-FACTOR RECEPTOR; TYROSINE-KINASE-INHIBITOR; METASTATIC BREAST-CANCER; HUMAN-COLON-CARCINOMA; C-SRC; PHASE-II; IN-VIVO; AURORA KINASES; BETA-CATENIN; TUMOR-GROWTH AB Colorectal carcinoma is a leading cause of cancer mortality worldwide. Survival for patients with metastatic disease is similar to 2 years on average and there is an ongoing need for the identification of new therapeutic agents. As the cancer research community has appreciated, newly discovered pathways governing cancer cell growth, survival, apoptosis, invasion and angiogenesis - all a host of potential therapeutic targets - have come into view. Basic research, preclinical data and observations arising from early stage trials have pointed towards possible roles for many of these agents in the future treatment of colorectal cancer. In this review, the authors summarize agents in development, modulating several of the most promising molecules and pathways that are thought to be relevant to colorectal cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. RP Hezel, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. EM ahezel@partners.org NR 96 TC 3 Z9 4 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2007 VL 16 IS 6 BP 867 EP 876 DI 10.1517/13543784.16.6.867 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 176JF UT WOS:000247080300011 PM 17501698 ER PT J AU Barry, E Alvarez, JA Scully, RE Miller, TL Lipshultz, SE AF Barry, Elly Alvarez, Jorge A. Scully, Rebecca E. Miller, Tracie L. Lipshultz, Steven E. TI Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE ACE inhibitors; anthracyclines; beta-blockers; cardiotoxicity; dexrazoxane; doxorubicin; epirubicin; heart failure; idarubicin; liposomal doxorubicin; mitoxantrone ID PEGYLATED-LIPOSOMAL DOXORUBICIN; ADVANCED BREAST-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; CARDIAC TROPONIN-T; CONGESTIVE-HEART-FAILURE; RANDOMIZED PHASE-III; VENTRICULAR SYSTOLIC DYSFUNCTION; SIGNIFICANT CLINICAL ACTIVITY; PRESERVED EJECTION FRACTION AB Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL 33101 USA. Univ Miami, Jackson Mem Med Ctr, Holtz Childrens Hosp, Miami, FL USA. Miami Univ, Sylvester Comprehens Canc Ctr, Miami, FL USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL 33136 USA. RP Lipshultz, SE (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp, 44 Binney St,3rd Foor, Boston, MA 02115 USA. EM slipshultz@med.miami.edu OI Scully, Rebecca/0000-0002-6887-9600 FU NCI NIH HHS [CA06516-SL, CA34183-SL, CA68484-SL, CA79060-SL]; NHLBI NIH HHS [HL53392-SL, HL59837-SL, HL69800-SL] NR 189 TC 138 Z9 150 U1 5 U2 24 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUN PY 2007 VL 8 IS 8 BP 1039 EP 1058 DI 10.1517/14656566.8.8.1039 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 178VP UT WOS:000247248500002 PM 17516870 ER PT J AU Kwon, DS Mylonakis, E AF Kwon, Douglas S. Mylonakis, Eleftherios TI Posaconazole: a new broad-spectrum antifungal agent SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE aspergillosis; Aspergillus spp; Candida spp; candidiasis; coccidioidomycosis; cryptococcal meningitis; fusariosis; histoplasmosis; posaconazole; scedosporiasis; SCH-56592; zygomycosis ID IN-VITRO ACTIVITIES; INVASIVE FUNGAL-INFECTIONS; AMPHOTERICIN-B; CANDIDA-ALBICANS; SALVAGE THERAPY; PULMONARY ASPERGILLOSIS; FILAMENTOUS FUNGI; VIVO ACTIVITIES; SCH 56592; OROPHARYNGEAL CANDIDIASIS AB The rising incidence of invasive fungal infections and the emergence of broader fungal resistance have led to the need for novel antifungal agents. Posaconazole is a new member of the triazole class of antifungals. it is available as an oral suspension and has a favorable toxicity profile, has demonstrated clinical efficacy in the treatment of oropharyngeal candidiasis and has shown promise as salvage therapy for invasive aspergillosis, zygomycosis, cryptococcal meningitis and a variety of other fungal infections. In addition, data from randomized controlled studies support its efficacy for use in prophylaxis of invasive fungal infections in patients who are severely immunocompromised. The wide spectrum activity of posaconazole in in vitro studies, animal models and preliminary clinical studies suggest that posaconazole represents an important addition to the antifungal armamentarium. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org NR 86 TC 25 Z9 27 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUN PY 2007 VL 8 IS 8 BP 1167 EP 1178 DI 10.1517/14656566.8.8.1167 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 178VP UT WOS:000247248500013 PM 17516880 ER PT J AU Jordan, KW Cheng, LL AF Jordan, Kate W. Cheng, Leo L. TI NMR-based metabolomics approach to target biomarkers for human prostate cancer SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE magnetic resonance spectroscopy; magnetic resonance spectroscopic imaging; metabolite; metabolite; metabolomics; nuclear magnetic resonance; prostate cancer ID MAGNETIC-RESONANCE-SPECTROSCOPY; HR-MAS SPECTROSCOPY; HUMAN SEMINAL FLUID; RADICAL PROSTATECTOMY; MR SPECTROSCOPY; ENDORECTAL MR; PRETREATMENT NOMOGRAM; QUANTITATIVE-ANALYSIS; FUNCTIONAL GENOMICS; RADIATION-THERAPY AB In the era of genomics and proteomics, metabolornics offers a unique way to probe the underlying biochemistry of malignant transformations. In the context of oncological metabolornics, the study of the global variation of metabolites involved in the development and progression of cancers, few existing techniques offer as much potential to discover biomarkers as nuclear magnetic resonance techniques. The most fundamental magnetic resonance methodologies with regard to human prostate cancer are magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging. Recent in vivo explorations have examined crucial metabolites that may indicate cancerous lesions and have the potential to direct treatment; while ex vivo studies of prostatic fluids and tissues have defined novel diagnostic parameters and indicated that magnetic resonance methodologies will be paramount in future prostate cancer management. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Cheng, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNY 149 13th St, Charlestown, MA 02129 USA. EM kcrocker@nmr.mgh.harvard.edu; cheng@nmr.mgh.harvard.edu OI Jordan, Kate/0000-0002-3089-2543 NR 65 TC 35 Z9 39 U1 1 U2 12 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JUN PY 2007 VL 4 IS 3 BP 389 EP 400 DI 10.1586/14789450.4.3.389 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 180QF UT WOS:000247379900018 PM 17552923 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time trends of ulcer mortality in Europe SO GASTROENTEROLOGY LA English DT Article ID PERFORATED PEPTIC-ULCER; LAST 150 YEARS; HELICOBACTER-PYLORI; SEX-DISTRIBUTION; DUODENAL-ULCER; AGE-INCIDENCE; DISEASE; ENGLAND; ADMISSIONS; INFECTION AB Background & Aims: The aim of the present study was to follow the time trends of ulcer disease in a representative sample of European countries and assess whether the most recent behavior of peptic ulcer still fits the overall pattern governed by an underlying birth-cohort phenomenon. Methods: Mortality data from 6 countries between 1921 and 2004 were analyzed, including Denmark, France, Germany, The Netherlands, Spain, and Switzerland. The age-specific death rates of gastric and duodenal ulcers from each individual country were plotted as period-age and cohort-age contours. Results: The data from the past 50-80 years show striking similarities among the 6 European countries. In all countries alike, the risk of dying from gastric and duodenal ulcer increased among consecutive generations born during the second half of the 19th century until shortly before the turn of the century, and then decreased in all subsequent generations. The time trends of gastric ulcer preceded those of duodenal ulcer by 10-30 years. The increase in nonsteroidal anti-inflammatory drug consumption or introduction of potent antisecretory medications have not affected the long-term downward trends of ulcer mortality. The birth-cohort pattern has continued to influence the temporal variations of peptic ulcer until most recently. Conclusions: The unique shape of the birth-cohort patterns of gastric and duodenal ulcers and their identical appearance in countries with different health care systems and varying political and socioeconomic histories reflect the overriding influence of Helicobacter pylori infection. C1 Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. EM sonnenbe@ohsu.edu NR 31 TC 47 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2007 VL 132 IS 7 BP 2320 EP 2327 DI 10.1053/j.gastro.2007.03.108 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 177IN UT WOS:000247146900013 PM 17570207 ER PT J AU El-Serag, HB Rudolph, L AF El-Serag, Hashem B. Rudolph, Lenhard TI Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis SO GASTROENTEROLOGY LA English DT Review ID CHRONIC HEPATITIS-C; NONALCOHOLIC FATTY LIVER; VIRUS-RELATED CIRRHOSIS; NF-KAPPA-B; POPULATION-BASED COHORT; ORAL-CONTRACEPTIVE USE; HFE C282Y MUTATIONS; UNITED-STATES; GENETIC EPIDEMIOLOGY; TELOMERE DYSFUNCTION AB Primary liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC has several interesting epidemiologic features including dynamic temporal trends; marked variations among geographic regions, racial and ethnic groups, and between men and women; and the presence of several well-documented environmental potentially preventable risk factors. Moreover, there is a growing understanding on the molecular mechanisms inducing hepatocarcinogenesis, which almost never occurs in healthy liver, but the cancer risk increases sharply in response to chronic liver injury at the cirrhosis stage. A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve our current concepts for screening and treatment of this disease. C1 Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Ctr Qual Care & Utilizat Studies, Houston, TX USA. Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. EM Rudolph.Lenhard@MH-Hannover.de OI Rudolph, Karl Lenhard/0000-0002-4839-2862 NR 183 TC 2490 Z9 2643 U1 61 U2 387 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2007 VL 132 IS 7 BP 2557 EP 2576 DI 10.1053/j.gastro.2007.04.061 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 177IN UT WOS:000247146900032 PM 17570226 ER PT J AU Lewis, JD Lichtenstein, GR Deren, JJ Chuai, S Ellenberg, JH Nessel, L Wu, GD Sands, BE Hanauer, SB Katz, JA Lashne, B Present, DH AF Lewis, J. D. Lichtenstein, G. R. Deren, J. J. Chuai, S. Ellenberg, J. H. Nessel, L. Wu, G. D. Sands, B. E. Hanauer, S. B. Katz, J. A. Lashne, B. Present, D. H. TI A randomized, placebo-controlled trial of the PPAR gamma ligand rosiglitazone for active ulcerative colitis SO GASTROENTEROLOGY LA English DT Meeting Abstract CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2007 CL Washington, DC C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Cleveland Clin, Cleveland, OH 44106 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2007 VL 132 IS 7 BP 2585 EP 2585 DI 10.1053/j.gastro.2007.04.017 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 177IN UT WOS:000247146900035 ER PT J AU Lieberman, D AF Lieberman, David TI Colorectal cancer screening in primary care SO GASTROENTEROLOGY LA English DT Editorial Material ID FECAL OCCULT BLOOD; ASYMPTOMATIC ADULTS; COLONOSCOPY; NEOPLASIA; SIGMOIDOSCOPY; POPULATION; RISK C1 Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA. EM lieberma@ohsu.edu NR 16 TC 11 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2007 VL 132 IS 7 BP 2591 EP 2594 DI 10.1016/j.gastro.2007.04.026 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 177IN UT WOS:000247146900042 PM 17570229 ER PT J AU Krasinskas, AM Raina, A Khalid, A Tublin, M Yadav, D AF Krasinskas, Alyssa M. Raina, Amit Khalid, Asif Tublin, Mitchell Yadav, Dhiraj TI Autoimmune pancreatitis SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; IDIOPATHIC CHRONIC-PANCREATITIS; SERUM IGG4 CONCENTRATIONS; FINE-NEEDLE-ASPIRATION; DIAGNOSTIC-CRITERIA; RETROPERITONEAL FIBROSIS; SJOGRENS-SYNDROME; STEROID-THERAPY; CLINICOPATHOLOGICAL FEATURES; EXTRAPANCREATIC LESIONS AB Autoimmune pancreatitis (AIP) is a benign, IgG4-related, fibroinflammatory form of chronic pancreatitis that can mimic pancreatic ductal adenocarcinoma both clinically and radiographically. Laboratory studies typically demonstrate elevated serum IgG4 levels and imaging studies reveal a diffusely or focally enlarged pancreas with associated diffuse or focal narrowing of the pancreatic duct. The pathologic features include periductal lymphoplasmacytic inflammation, obliterative phlebitis, and abundant IgG4-positive plasma cells. The treatment of choice for AIP is steroid therapy. Diagnostic criteria for All? have been proposed that incorporate histologic, radiographic, serologic, and clinical information. C1 Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, UPMC Shadyside, Dept Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, UPMC, Dept Radiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, UPMC, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15237 USA. RP Krasinskas, AM (reprint author), Univ Pittsburgh, Med Ctr, Dept Pathol, 200 Lothrop St,A610, Pittsburgh, PA 15213 USA. EM krasinskasam@upmc.edu NR 88 TC 19 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2007 VL 36 IS 2 BP 239 EP + DI 10.1016/j.gtc.2007.03.015 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 182WS UT WOS:000247535300003 PM 17533077 ER PT J AU Jani, N Moser, AJ Khalid, A AF Jani, Niraj Moser, A. James Khalid, Asif TI Pancreatic endocrine tumors SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ISLET-CELL TUMORS; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ZOLLINGER-ELLISON-SYNDROME; PHASE HELICAL CT; NEUROENDOCRINE TUMORS; INTRAOPERATIVE ULTRASONOGRAPHY; PREOPERATIVE LOCALIZATION; ENDOSCOPIC ULTRASOUND; PROGNOSTIC-FACTORS; NEOPLASIA TYPE-1 AB Incidental, nonfunctional pancreatic endocrine tumors (PET) are observed with increasing frequency. Most are insulinomas. Endoscopic ultrasound with fine-needle aspiration plays a significant role in the localization and tissue diagnosis of PET. Establishing PET behavior as aggressive or indolent remains challenging especially preoperatively. Newer techniques including DNA and micro-RNA analysis may play a role in this arena. Small benign PET may be enucleated or removed laparascopically. Surgery is the mainstay of treating advanced disease including those with metastases and Zollinger-Ellison syndrome. The management of multiple endocrine neoplasia type I continues to be a challenge, including treating symptoms, targeted resections, and close observation. Diagnosis, management, and prognostication of PET are under evolution and a number of changes in these fronts are anticipated. C1 Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Khalid, A (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 68 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2007 VL 36 IS 2 BP 431 EP + DI 10.1016/i.gtc.2007.03.002 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 182WS UT WOS:000247535300014 PM 17533088 ER PT J AU Leung, JW Lee, JG Rojany, M Wilson, R Leung, FW AF Leung, Joseph W. Lee, John G. Rojany, Micha Wilson, Robert Leung, Felix W. TI Development of a novel ERCP mechanical simulator SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROENTEROLOGY FELLOWS; TRAINER AB Background: There is a paucity of objective methods for evaluating trainee performance and comparing ERCP accessories. Objective: Use of a mechanical ERCP simulator to evaluate trainee performance and to compare ERCP accessories via procedure time. Design: Pilot study using a mechanical simulator. Setting: Hands-on ERCP practice workshops. Subjects: Endoscopists at various levels of ERCP experience. Method: Validation studies are described to show that the simulator permits participants with varying ERCP experience to demonstrate their skill levels and offers novel training applications in ERCP courses. The time required for completing a simulated stent placement procedure, simulated fluoroscopy time, and participant expectations were recorded in different settings. Participants' expectations were compared before and after training to determine whether the simulator was a credible adjunct to ERCP training. Results: Significantly shorter procedure times were recorded for the same accessories used by participants with more ERCP experience than those with less experience and for the same group of participants when using accessories with I design compared with another. The mean total credibility score showed a significant increase after simulator practice. Limitations: In vitro practice by using a mechanical simulator, results may not translate directly to the clinical setting. How the objective procedure times measured during practice can complement assessment of trainee competence or define usefulness of different accessories is unknown but deserves to be explored in future studies. Conclusions: The procedure times can categorize participants according to their ERCP experience and separate accessories according to their ease of use. An increase in credibility score validates participants' endorsement of such practice as a credible adjunct to ERCP training. C1 Sacramento VA Med Ctr, Gastroenterol Sect, Vet Affairs No Calif Healthcare Syst, Mather, CA 95655 USA. Univ Calif Davis, Davis Med Ctr, Div Gastroenterol, Sacramento, CA USA. Univ Calif Irvine, Med Ctr, Comprehens Digest Dis Ctr, Irvine, CA USA. Sepulveda Ambulatory Care Ctr & Nursing Home, Res & Med Serv, Sepulveda, CA USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Leung, JW (reprint author), Sacramento VA Med Ctr, Gastroenterol Sect, Vet Affairs No Calif Healthcare Syst, 10535 Hosp Way, Mather, CA 95655 USA. NR 14 TC 19 Z9 19 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2007 VL 65 IS 7 BP 1056 EP 1062 DI 10.1016/j.gie.2006.11.018 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 178JF UT WOS:000247216300021 PM 17531642 ER PT J AU Takahashi, H Prunet, P Kitahashi, T Kajimura, S Hirano, T Grau, EG Sakamoto, T AF Takahashi, Hideya Prunet, Patrick Kitahashi, Takashi Kajimura, Shingo Hirano, Tetsuya Grau, E. Gordon Sakamoto, Tatsuya TI Prolactin receptor and proliferating/apoptotic cells in esophagus of the Mozambique tilapia (Oreochromis mossambicus) in fresh water and in seawater SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 23rd Biennial Conference of European Comparative Endocrinologists CY AUG 29-SEP 02, 2006 CL Univ Sheffield, Sheffield, ENGLAND SP European Soc Comparat Endocrinol, City Manchester, Univ Manchester, Astra Zeneca HO Univ Sheffield DE prolactin; prolactin receptor; glucocorticoid receptor; esophagus; cell proliferation; apoptosis; fish; teleost; osmoregulation ID MUDSKIPPER PERIOPHTHALMUS-MODESTUS; TISSUE DISTRIBUTION; ANTERIOR INTESTINE; TAKIFUGU-RUBRIPES; CORTISOL RECEPTOR; GROWTH-HORMONE; EXPRESSION; NILOTICUS; TELEOST; PROLIFERATION AB We have previously shown that esophageal epithelium of a euryhaline goby displays elevated cell proliferation in freshwater (FW) fish, but undergo apoptosis during seawater (SW) acclimation. Prolactin (PRL) injection into the goby induced the cell proliferation, whereas cortisol treatment stimulated the cell proliferation and apoptosis [Takahashi, H., Sakamoto, T., Narita, K., 2006a. Cell proliferation and apoptosis in the anterior intestine of an amphibious, euryhaline mudskipper (Periophthalmus modestus). J. Comp. Physiol. B 176, 463-468, 2006). In the euryhaline tilapia (Oreochromis mossambicus), the dynamics of changes in cortisol-glucccorticoid receptors (GR) during acclimation to different salinities also suggests a role for glucocorticoid signaling in the esophageal cell turnover, but the mode of PRL action remains largely unclear. In the present study, we report on effects in the tilapia esophagus that result from changes in environmental salinity. Specifically, we assessed: (1) mRNA expression of PRL receptor (PRLR) using quantitative real-time RTPCR; (2) esophageal cell proliferation and apoptosis, using immunohistochemistry of proliferating cells nuclear antigen (PCNA) and in situ nick end-labeling of genomic DNA (TUNEL); (3) the possible localization of immunoreactive PRLR on proliferating/apoptotic cells. Plasma PRL increased after FW acclimation; PRLR mRNA levels in the esophagus of FW fish were significantly higher than those in SW-acclimated fish. Cell proliferation was induced randomly throughout the esophageal epithelium after FW acclimation, while cell division and increased apoptosis were concentrated at the tips of esopliageal epithelial folds in SW-acclimated fish. Immunoreactive PRLR appeared to be localized at proliferating cells and at certain apoptotic cells, whereas immunoreactive GR was observed over the whole epithelium including the apoptotic/proliferating cells. Thus, PRL appears to affect cell turnover directly in the esophageal epithelium of the eurylialine tilapia. (c) 2007 Elsevier Inc. All rights reserved. C1 Okayama Univ, Grad Sch Nat Sci & Technol, Ushimado Marine Lab, Ushimado, Setouchi 7014303, Japan. INRA, SCRIBE, IFR 140, F-35042 Rennes, France. Monash Univ, Sch Med & Hlth Sci, Petaling Jaya 46150, Selangor Darul, Malaysia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hawaii, Hawaii Inst Marine Biol, Kaneohe, HI 96744 USA. RP Takahashi, H (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Ushimado Marine Lab, Ushimado, Setouchi 7014303, Japan. EM dns18408@cc.okayama-u.ac.jp RI Scribe, Lab/B-3676-2009; OI Kitahashi, Takashi/0000-0003-0512-7548 NR 23 TC 12 Z9 12 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD JUN-JUL PY 2007 VL 152 IS 2-3 BP 326 EP 331 DI 10.1016/j.ygcen.2007.02.021 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187CD UT WOS:000247824000033 PM 17418192 ER PT J AU Langenau, DM Keefe, MD Storer, NY Guyon, JR Kutok, JL Le, XN Goessling, W Neuberg, DS Kunkel, LM Zon, LI AF Langenau, David M. Keefe, Matthew D. Storer, Narie Y. Guyon, Jeffrey R. Kutok, Jeffery L. Le, Xiuning Goessling, Wolfram Neuberg, Donna S. Kunkel, Louis M. Zon, Leonard I. TI Effects of RAS on the genesis of embryonal rhabdomyosarcoma SO GENES & DEVELOPMENT LA English DT Article DE zebrafish; rhabdomyosarcoma; RAS; p53; transgenic ID MUSCLE SATELLITE CELLS; TRANSGENIC ZEBRAFISH; SKELETAL-MUSCLE; EXPRESSION SIGNATURES; IN-VIVO; K-RAS; MYOBLAST DIFFERENTIATION; POSTNATAL MYOGENESIS; N-RAS; MUTATIONS AB Embryonal rhabdomyosarcoma (ERMS) is a devastating cancer with specific features of muscle differentiation that can result from mutational activation of RAS family members. However, to date, RAS pathway activation has not been reported in a majority of ERMS patients. Here, we have created a zebrafish model of RAS- induced ERMS, in which animals develop externally visible tumors by 10 d of life. Microarray analysis and cross- species comparisons identified two conserved gene signatures found in both zebrafish and human ERMS, one associated with tumor-specific and tissue-restricted gene expression in rhabdomyosarcoma and a second comprising a novel RAS-induced gene signature. Remarkably, our analysis uncovered that RAS pathway activation is exceedingly common in human RMS. We also created a new transgenic coinjection methodology to fluorescently label distinct subpopulations of tumor cells based on muscle differentiation status. In conjunction with fluorescent activated cell sorting, cell transplantation, and limiting dilution analysis, we were able to identify the cancer stem cell in zebrafish ERMS. When coupled with gene expression studies of this cell population, we propose that the zebrafish RMS cancer stem cell shares similar self- renewal programs as those found in activated satellite cells. C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU NCI NIH HHS [5R01 CA103846-02, R01 CA103846]; NICHD NIH HHS [P30 HD018655, P30HD018655]; NIGMS NIH HHS [T32 GM007753] NR 54 TC 178 Z9 180 U1 1 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2007 VL 21 IS 11 BP 1382 EP 1395 DI 10.1101/gad.1545007 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 174NH UT WOS:000246948500011 PM 17510286 ER PT J AU Dennis, JH Fan, HY Reynolds, SM Yuan, GC Meldrim, JC Richter, DJ Peterson, DG Rando, OJ Noble, WS Kingston, RE AF Dennis, Jonathan H. Fan, Hua-Ying Reynolds, Sheila M. Yuan, Guocheng Meldrim, James C. Richter, Daniel J. Peterson, Daniel G. Rando, Oliver J. Noble, William S. Kingston, Robert E. TI Independent and complementary methods for large-scale structural analysis of mammalian chromatin SO GENOME RESEARCH LA English DT Article ID IN-VIVO; NUCLEOSOME POSITIONS; MICROCOCCAL NUCLEASE; MMTV PROMOTER; TRANSCRIPTION; DNA; SEQUENCES; CLONING AB The fundamental building block of chromatin, the nucleosome, occupies 150 bp of DNA in a spaced arrangement that is a primary determinant in regulation of the genome. The nucleosomal organization of some regions of the human genome has been described, but mapping of these regions has been limited to a few kilobases. We have explored two independent and complementary methods for the high-throughput analysis of mammalian chromatin structure. Through adaptations to a protocol used to map yeast chromatin structure, we determined sites of nucleosomal protection over large regions of the mammalian genome using a tiling microarray. By modifying classical primer extension methods, we localized specific internucleosomally cleaved mammalian genomic sequences using a capillary electrophoresis sequencer in a manner that allows high-throughput nucleotide-resolution characterization of nucleosome protection patterns. We developed algorithms for the automated and unbiased analysis of the resulting data, a necessary step toward large-scale analysis. We validated these assays using the known positions of nucleosomes on the mouse mammary tumor virus LTR, and additionally, we characterized the previously unreported chromatin structure of the LCMT2 gene. These results demonstrate the effectiveness of the combined methods for reliable analysis of mammalian chromatin structure in a high-throughput manner. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. Broad Inst, Cambridge, MA 02141 USA. Mississippi State Univ, Dept Plant & Soil Sci, Mississippi State, MS 39762 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM kingston@frodo.mgh.harvard.edu OI Peterson, Daniel/0000-0002-0274-5968 FU NCI NIH HHS [CA-093660, K01 CA093660]; NHGRI NIH HHS [HG003141, HG003161, R01 HG003141, U01 HG003161]; NIGMS NIH HHS [R01 GM071923, GM071923] NR 25 TC 34 Z9 35 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 2007 VL 17 IS 6 BP 928 EP 939 DI 10.1101/gr.5636607 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 178NH UT WOS:000247226900024 PM 17568008 ER PT J AU Yu, CE Seltman, H Peskind, ER Galloway, N Zhou, PX Rosenthal, E Wijsman, EM Tsuang, DW Devlin, B Schellenberg, GD AF Yu, Chang-En Seltman, Howard Peskind, Elaine R. Galloway, Nichole Zhou, Peter X. Rosenthal, Elisabeth Wijsman, Ellen M. Tsuang, Debby W. Devlin, Bernie Schellenberg, Gerard D. TI Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: Patterns of linkage disequilibrium and disease/marker association SO GENOMICS LA English DT Article DE molecular haplotyping; apolipoprotein E; selection; linkage disequilibrium; genetic association; Alzheimer disease ID APOLIPOPROTEIN-E GENE; REGULATORY REGION; PHENOTYPIC ASSOCIATIONS; PROMOTER POLYMORPHISMS; CLADISTIC-ANALYSIS; LIPID-METABOLISM; RISK; EXPRESSION; HAPLOTYPES; GENOTYPE AB The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecularly haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4) allele and was strongly associated with the risk for developing LOAD. However, when all the SNPs were entered into a logit model, only the effect of APOE epsilon(4) remained significant. These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians. (c) 2007 Elsevier Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. Vet Affairs Puget Sound Hlth care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Washington, Sch Med, Dept Neurol, Div Neurogenet, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Yu, CE (reprint author), Vet Affairs Puget Sound Hlth care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. EM changeyu@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Seltman, Howard/0000-0002-7543-3578; Wijsman, Ellen/0000-0002-2725-6669 FU NIA NIH HHS [P50 AG005136-23, AG05136, AG21544, AG24486, P50 AG005136, P50 AG005136-21, R01 AG021544, R01 AG021544-05, R21 AG024486, R21 AG024486-01, R21 AG024486-02, U24 AG021886]; NIMH NIH HHS [MH57881, R01 MH057881, R37 MH057881] NR 50 TC 75 Z9 78 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2007 VL 89 IS 6 BP 655 EP 665 DI 10.1016/j.ygeno.2007.02.002 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 171YC UT WOS:000246770300001 PM 17434289 ER PT J AU Kraus, CA Kunik, ME Stanley, MA AF Kraus, Cynthia A. Kunik, Mark E. Stanley, Melinda A. TI Use of cognitive behavioral therapy in late-life psychiatric disorders SO GERIATRICS LA English DT Article DE cognitive behavioral therapy; anxiety; depression; psychosocial interventions ID CHRONIC BREATHING DISORDERS; OLDER-ADULTS; ANXIETY DISORDERS; PRIMARY-CARE; DEPRESSION; PREVALENCE; HEALTH AB With prevalence rates approaching 10% for anxiety disorders and 6% for major depression, anxiety and depression have a significant impact on adults in later life. Cognitive behavioral therapy (CBT) is a psychosocial intervention for anxiety and depression that can serve as a useful alternative or adjunct to pharmacologic intervention for older adults. Older adults often prefer nonmedical treatment and need to limit use of medications in conjunction with serious medical illness. This article presents a basic description of CBT in light of special considerations for older patients. The principles of CBT can be integrated into primary care interactions. Assessment instruments for anxiety and depressive disorders are mentioned, in addition to referral sources. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77211 USA. Baylor Coll Med, Div Psychol, Houston, TX 77030 USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, McIngvale Family Chair Obsess Compuls Disorder Re, Houston, TX 77030 USA. RP Kraus, CA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 152 MED-VAMC 152, Houston, TX 77211 USA. NR 21 TC 10 Z9 10 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUN PY 2007 VL 62 IS 6 BP 21 EP 26 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 182XP UT WOS:000247537600009 PM 17547480 ER PT J AU Wieland, D Hedrick, S AF Wieland, Darryl Hedrick, Susan TI Leading the way to quality long-term care: Lessons from the past, strategies for the future SO GERONTOLOGIST LA English DT Editorial Material C1 [Wieland, Darryl] Palmetto Hlth Richland Hosp, Geriatr Serv, Columbia, SC USA. [Hedrick, Susan] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. RP Wieland, D (reprint author), Palmetto Hlth Richland Hosp, Geriatr Serv, Columbia, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2007 VL 47 IS 3 BP 355 EP 355 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 272CR UT WOS:000253837100008 ER PT J AU Kinosian, B Stallard, E Wieland, D AF Kinosian, Bruce Stallard, Eric Wieland, Darryl TI Projected use of long-term-care services by enrolled veterans SO GERONTOLOGIST LA English DT Article DE projection models; nursing home utilization; home- and community-based service utilization; Veterans Health Administration; National Long-Term Care Survey AB Purpose: The purpose of this article is to describe the projected use for long-term-care services through 2012. Design and Methods: We constructed a static-component projection model using age, function, and other covariates. We obtained enrollee projections from the Veterans Health Administration (VHA) and combined these with nursing home and community long-term-care service use rates from the 1999 National Long-Term Care Survey and the 2000 National Health Interview Survey. Results: Over the next decade, the number of oldest veterans (aged 85+) will double, and VHA-enrolled veterans aged 85 and older will increase sevenfold. This will result in a 20-25% increase in use for both nursing home and home- and community-based services. VHA currently concentrates 90% of its long-term-care resources on nursing home care. However, among those who receive long-term care from all formal sources, 56% receive care in the community. Age and marital status are significant predictors of use of either type of formal long-term-care service for any given level of disability. VHA's experience with the mandatory nursing home benefit suggests that even when the cost to the veteran is near zero, only 60-65% of eligibles will choose VHA-provided care. Assisted living represents nearly 15% of care provided during the past decade to individuals in nursing homes, and approximately 19% of veterans using nursing homes have disability levels comparable to those of men supported in assisted living. Implications: As most of the increased projected use for long-term care will be for home- and community-based services, VHA will need to expand those resources. Use of VHA resources to leverage community services may offer new opportunities to enhance community-based long-term care. C1 [Kinosian, Bruce] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Univ Penn, Philadelphia, PA 19104 USA. [Wieland, Darryl] Univ S Carolina, Columbia, SC 29208 USA. [Stallard, Eric] Duke Univ, Ctr Demog Studies, Durham, NC 27706 USA. RP Kinosian, B (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 38th & Woodland Ave, Philadelphia, PA 19104 USA. EM brucek@mail.med.upenn.edu FU NIA NIH HHS [P01AG17937, U01AG07198] NR 9 TC 17 Z9 17 U1 3 U2 7 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2007 VL 47 IS 3 BP 356 EP 364 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 272CR UT WOS:000253837100009 PM 17565100 ER PT J AU Hedrick, S Guihan, M Chapko, M Manheim, L Sullivan, J Thomas, M Barry, S Zhou, A AF Hedrick, Susan Guihan, Marylou Chapko, Michael Manheim, Larry Sullivan, Jean Thomas, Mark Barry, Sarah Zhou, Andrew TI Characteristics of residents and providers in the assisted living pilot program SO GERONTOLOGIST LA English DT Article DE assisted living facilities; group homes; long-term care; Department of Veterans Affairs ID NURSING-HOMES; CARE; FACILITIES; SERVICES; OREGON AB Purpose: The number of residents in assisted living has rapidly increased, although these facilities still primarily serve people who can pay out of pocket. The U.S. Department of Veterans Affairs was authorized to provide this level of care for the first time in the Assisted Living Pilot Program (ALPP). We describe the residents and providers, comparing them across three facility types and other populations, to assess the characteristics and feasibility of this new approach. Design and Methods: We assessed ALPP residents and providers across seven Veterans Affairs Medical Centers. We obtained information from medical records, assessment tools, and a provider survey. Results: We report here on 743 residents placed from 2002 to 2004. The Department of Veterans Affairs contracted with 58 adult family homes, 56 assisted living facilities, and 46 residential care facilities. The average ALPP resident was a 70-year-old unmarried White man referred from an inpatient hospital and living in a private residence prior to placement. Adult family homes enrolled residents requiring greater levels of assistance with activities of daily living than other facility types Assisted living facilities were less likely than adult family homes to admit residents with functional disabilities and less likely than either adult family homes or adult residential care facilities to admit residents with certain care needs. Implications: ALPP placed residents with a wide range of characteristics in community facilities that varied widely in size and services. This information can help determine the role of this type of care in and outside of the Department of Veterans Affairs. C1 [Hedrick, Susan; Chapko, Michael; Sullivan, Jean; Barry, Sarah; Zhou, Andrew] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. [Guihan, Marylou; Manheim, Larry; Thomas, Mark] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. RP Hedrick, S (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM susan.hedrick@med.va.gov NR 30 TC 12 Z9 12 U1 2 U2 5 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2007 VL 47 IS 3 BP 365 EP 377 PG 13 WC Gerontology SC Geriatrics & Gerontology GA 272CR UT WOS:000253837100010 PM 17565101 ER PT J AU Hawes, C Fries, BE James, ML Guihan, M AF Hawes, Catherine Fries, Brant E. James, Mary L. Guihan, Marylou TI Prospects and pitfalls: Use of the RAI-HIC assessment by the Department of Veterans Affairs for home care clients SO GERONTOLOGIST LA English DT Article DE Minimum Data Set; MDS-HC; home health ID MINIMUM DATA SET; RESIDENT ASSESSMENT INSTRUMENT; LIVING ELDERLY-PATIENTS; ART. NO. 7; NURSING-HOMES; OLDER-PEOPLE; MDS-HC; RUG-III; COMMUNITY; SYSTEM AB Purpose: The U.S. Department of Veterans Affairs has adopted two functional assessment systems that guide care planning: one for nursing home residents (the Resident Assessment Instrument [RAI]) and a compatible one for home care clients (RAI-HC). The purpose of this article is to describe the RAI-HC (often referred to as the Minimum Data Set-Home Care or MDS-HC) and its uses and offer lessons learned from implementation experiences in other settings. Design and Methods: We reviewed implementation challenges associated both with the RAI and the RAI-HC in the United States, Canada, and other adopter countries, and drew on these to suggest lessons for the Department of Veterans Affairs as well as other entities implementing the RAI-HC. Results: Beyond its clinical utility, there are a number of evidence-based uses for the assessment system. The resident-level data can be aggregated and analyzed, and scales identify clinical conditions and risk for various types of negative outcomes. In addition, the data can be used for other programmatic and research purposes, such as determining eligibility, setting payment rates for contract care, and evaluating clinical interventions. At the same time, there are a number of implementation challenges the Department of Veterans Affairs and other organizations may face. Implications: Policy makers and program managers in any setting, including state long-term-care programs, who wish to implement an assessment system must anticipate and address a variety of implementation problems with a clear and consistent message from key leadership, adequate training and clinical support for assessors, and appropriate planning and resources for data systems. C1 [Hawes, Catherine] Texas A&M Univ Syst, Hlth Sci Ctr, Dept Hlth Policy & Management, Sch Rural Publ Hlth, College Stn, TX 77843 USA. [Fries, Brant E.; James, Mary L.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Fries, Brant E.] Ann Arbor Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Ann Arbor, MI USA. [Guihan, Marylou] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Guihan, Marylou] Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. RP Hawes, C (reprint author), Texas A&M Univ Syst, Hlth Sci Ctr, Dept Hlth Policy & Management, Sch Rural Publ Hlth, Mail Stop 1266, College Stn, TX 77843 USA. EM hawes@srph.tamhsc.edu NR 56 TC 12 Z9 13 U1 3 U2 9 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2007 VL 47 IS 3 BP 378 EP 387 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 272CR UT WOS:000253837100011 PM 17565102 ER PT J AU El-Serag, HB Ergun, GA Pandolfino, J Fitzgerald, S Tran, T Kramer, JR AF El-Serag, Hashem B. Ergun, Gulchin A. Pandolfino, John Fitzgerald, Stephanie Tran, Thomas Kramer, Jennifer R. TI Obesity increases oesophageal acid exposure SO GUT LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; PH-METRY; INTRAABDOMINAL PRESSURE; INTRAGASTRIC PRESSURE; SPHINCTER PRESSURE; RISK; RESISTANCE; DIAGNOSIS; ASCITES AB Background: Obesity has been associated with gastro-oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear. Aim: To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures. Methods: A cross-sectional study of consecutive patients undergoing 24 h pH-metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses. Results: 206 patients (63% women) with a mean age of 51.4 years who were not on acid-suppressing drugs were enrolled. A body mass index (BMI) of > 30 kg/m(2) (compared with BMI, 25 kg/m(2)) was associated with a significant increase in acid reflux episodes, long reflux episodes (> 5 min), time with pH < 4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI > 30 kg/m(2) and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure. Conclusions: Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure. C1 Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 28 TC 135 Z9 141 U1 2 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2007 VL 56 IS 6 BP 749 EP 755 DI 10.1136/gut.2006.100263 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 170WI UT WOS:000246696500005 PM 17127706 ER PT J AU Malfertheiner, P Megraud, F O'Morain, C Bazzoli, F El-Omar, E Graham, D Hunt, R Rokkas, T Vakil, N Kuipers, EJ AF Malfertheiner, P. Megraud, F. O'Morain, C. Bazzoli, F. El-Omar, E. Graham, D. Hunt, R. Rokkas, T. Vakil, N. Kuipers, E. J. CA EHSG Study Grp TI Current concepts in the management of Helicobacter pylori infection: the maastricht III consensus report SO GUT LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; RANDOMIZED CONTROLLED-TRIAL; C-13-UREA BREATH TEST; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IDIOPATHIC THROMBOCYTOPENIC PURPURA; PREVENT GASTRIC-CANCER; IRON-DEFICIENCY ANEMIA; PROTON PUMP INHIBITORS; LOW-DOSE ASPIRIN; B-CELL LYMPHOMA AB Background: Guidelines on the management of Helicobacter pylori, which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in (a) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; (b) patients with atrophic gastritis; (c) first degree relatives of patients with gastric cancer; (d) patients with unexplained iron deficiency anaemia; and (e) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a "test and treat'' strategy if other causes are excluded. Eradication of H pylori infection (a) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and (b) may prevent peptic ulcer in patients who are naive users of non-steroidal antiinflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development. C1 Univ Magdeburg, Fak Med, Zentrum Innere Med, Klin Gastroenterol Hepatol & Infektiol, D-39120 Magdeburg, Germany. INSERM, U853, Bordeaux, France. Univ Dublin Trinity Coll, Adelaide & Meath Hosp, Dublin, Ireland. Univ Bologna, Bologna, Italy. Univ Aberdeen, Aberdeen AB9 1FX, Scotland. VA Med Ctr, Houston, TX USA. McMaster Univ, Hamilton, ON, Canada. Henry Dunant Hosp, Athens, Greece. Univ Wisconsin, Sch Med, Milwaukee, WI 53201 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RP Malfertheiner, P (reprint author), Univ Magdeburg, Fak Med, Zentrum Innere Med, Klin Gastroenterol Hepatol & Infektiol, Leipziger Str 44, D-39120 Magdeburg, Germany. EM peter.malfertheiner@medizin.uni-magdeburg.de RI Machado, Jose Carlos/C-5907-2009 OI Machado, Jose Carlos/0000-0003-4741-8415 NR 100 TC 1112 Z9 1259 U1 9 U2 92 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2007 VL 56 IS 6 BP 772 EP 781 DI 10.1136/gut.2006.101634 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 170WI UT WOS:000246696500010 PM 17170018 ER PT J AU Carrasco, RD AF Carrasco, R. D. TI Genetic model of multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID MICE; PLASMACYTOMA C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 12 EP 13 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800014 ER PT J AU Tonon, G AF Tonon, G. TI From oncogenome mining to functional validation of multiple myeloma cancer genes SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID RESOLUTION GENOMIC PROFILES C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 13 EP 14 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800015 ER PT J AU Faber, J Krivtsov, A Stubbs, M Wright, R Van den Heuvel-Eibrink, M Zwaan, C Kung, A Armstrong, SA AF Faber, J. Krivtsov, A. Stubbs, M. Wright, R. Van den Heuvel-Eibrink, M. Zwaan, C. Kung, A. Armstrong, S. A. TI The homeobox A9 gene (HOXA9) is required for survival of human MLL-rearranged acute leukemias SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sophia Childrens Univ Hosp, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0045 BP 16 EP 16 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900047 ER PT J AU Roodman, GD Kurihara, N Hiruma, Y AF Roodman, G. D. Kurihara, N. Hiruma, Y. TI New agents targeting myeloma bone disease SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 20 EP 20 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800020 ER PT J AU Richardson, P Schlossman, R Ghobrial, I Mitsiades, C Hicleshima, T Chauhan, D Munshi, N Anderson, K AF Richardson, P. Schlossman, R. Ghobrial, I. Mitsiades, C. Hicleshima, T. Chauhan, D. Munshi, N. Anderson, K. TI The treatment of relapsed and refractory myeloma: Focus on bortezomib and bortezomib-based combinations SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID RELAPSED/REFRACTORY MULTIPLE-MYELOMA; HIGH-DOSE DEXAMETHASONE; PHASE-I/II TRIAL; LIPOSOMAL DOXORUBICIN; ORAL CYCLOPHOSPHAMIDE; II TRIAL; MELPHALAN; THERAPY; TIME C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 21 EP 22 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800023 ER PT J AU Chauhan, D Hideshima, T Mitsiades, C Richardson, F Munshi, N Anderson, K AF Chauhan, D. Hideshima, T. Mitsiades, C. Richardson, F. Munshi, N. Anderson, K. TI Novel proteasome inhibitors as therapy in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID BORTEZOMIB; APOPTOSIS; NPI-0052 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 25 EP 26 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800026 ER PT J AU Mitsiades, CS Richardson, PG Munshi, NC Anderson, KC AF Mitsiades, C. S. Richardson, P. G. Munshi, N. C. Anderson, K. C. TI Inhibition of heat shock proteins: Therapeutic perspectives SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID MULTIPLE-MYELOMA CELLS; HSP90 INHIBITOR; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; IPI-504 C1 Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 26 EP 27 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800027 ER PT J AU Kiziltepe, T Anderson', ,HCRYVYOIISCK Catley, L Raje, N Yasui, H Vallet, S Okawa, Y Ikeda, H Ishitsuka, K Shiraishi, N Chauhan, D Anderson, KC AF Kiziltepe, T. Hideshima, T. Catley, L. Raje, N. Yasui, H. Vallet, S. Okawa, Y. Ikeda, H. Ishitsuka, K. Shiraishi, N. Chauhan, D. Anderson, K. C. TI 5-azacytidine induces DNA damage responses and apoptosis in MM cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 39 EP 39 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800039 ER PT J AU Hideshima, T Raje, N AF Hideshima, T. Raje, N. TI Akt as a therapeutic target in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID SYNERGISTIC ACTIVITY; INHIBITOR RAPAMYCIN; IN-VITRO; COMBINATION C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 44 EP 45 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800051 ER PT J AU Munshi, NC AF Munshi, N. C. TI Novel immunotherapy strategies in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID DENDRITIC CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Hlthcare Syst, Boston, MA 02115 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 46 EP 47 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800053 ER PT J AU McMillin, D Negri, J Hayden, P Weisberg, E Klippel, S Zurawska, J Mitsiades, N Anderson, KC Mitsiades, CS AF McMillin, D. W. Negri, J. Hayden, P. Weisberg, E. Klippel, S. Zurawska, J. Mitsiades, N. Anderson, K. C. Mitsiades, C. S. TI Compartment-specific bioluminescence imaging (CS-BLI): A high-throughput approach to identify novel anti-myeloma therapies that overcome the protection of stromal cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 65 EP 65 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800073 ER PT J AU Klippel, S Tesmenitsky, Y McMillin, D Negri, J Selliah, R Robbins, P Mitsiades, N Richardson, P Sahasrabudhe, S Anderson, KC Mitsiades, CS AF Klippel, S. Tesmenitsky, Y. McMillin, D. Negri, J. Selliah, R. Robbins, P. Mitsiades, N. Richardson, P. G. Sahasrabudhe, S. Anderson, K. C. Mitsiades, C. S. TI In vitro and in vivo anti-myeloma activity of PRLX, an orally-bioavailable agent against mutant Ras-transformed cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Prolexys Phramaceut Inc, Salt Lake City, UT 84116 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 66 EP 66 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800074 ER PT J AU Anderson, KC AF Anderson, K. C. TI Future perspectives in the management of myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID HUMAN MULTIPLE-MYELOMA; CYTOTOXICITY; INHIBITION; CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 73 EP 74 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800082 ER PT J AU Pilarski, LM Adamia, S Reichert, A Ghosh, A Mant, MF Reiman, T Treon, SP Belch, AR AF Pilarski, L. M. Adamia, S. Reichert, A. Ghosh, A. Mant, M. F. Reiman, T. Treon, S. P. Belch, A. R. TI Inherited and acquired mutations in Waldenstrom's macroglobulinemia (WM): WM and MM have close genetic relationships not shared with B-CLL SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID MULTIPLE-MYELOMA; EXPRESSION C1 Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB, Canada. Univ Alberta, Cross Canc Inst, Dept Med, Edmonton, AB, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 80 EP 81 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800086 ER PT J AU Treon, SP Soumerai, JD Hunter, ZR Patterson, CJ Branagan, AR O'Connor, K Ghobrial, IM AF Treon, S. P. Soumerai, J. D. Hunter, Z. R. Patterson, C. J. Branagan, A. R. O'Connor, K. Ghobrial, I. M. CA WMCTG TI Novel agents in the treatment of Waldenstrom's macroglobulinemia: Update of WMCTG clinical trials SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 91 EP 91 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800095 ER PT J AU Ghobrial, I AF Ghobrial, I. TI Proteomic analysis in Waldenstrom macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID MYELOMA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 92 EP 93 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800096 ER PT J AU Hatjiharissi, E Adamia, S Cao, Y Ciccarelli, BT Xu, L Treon, SP AF Hatjiharissi, E. Adamia, S. Cao, Y. Ciccarelli, B. T. Xu, L. Treon, S. P. TI Novel splice variant transcript of SIVA in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Res, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 93 EP 93 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800099 ER PT J AU Hatjiharissi, E Zhan, F Adamia, S Cicarelli, BT Cao, Y Xu, L Hu, H Hunter, ZR Patterson, JR Ghobrial, IM Barlogie, B Shaughnessy, JD Treon, SP AF Hatjiharissi, E. Zhan, F. Adamia, S. Cicarelli, B. T. Cao, Y. Xu, L. Hu, H. Hunter, Z. R. Patterson, J. R. Ghobrial, I. M. Barlogie, B. Shaughnessy, J. D., Jr. Treon, S. P. TI Gene expression profiling of Waldenstrom's macroglobulinemia reveals genes that may be related to disease pathogenesis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Marcroglobulinemia, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 93 EP 93 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800098 ER PT J AU Adamia, S Xu, L Hatjiharissi, E Ciccarelli, BT Cao, Y Sacco, A Hunter, ZR Patterson, CJ Treon, SP AF Adamia, S. Xu, L. Hatjiharissi, E. Ciccarelli, B. T. Cao, Y. Sacco, A. Hunter, Z. R. Patterson, C. J. Treon, S. P. TI Aberrant post-transcriptional regulation of TNF family members and their adaptor molecules essential to B-cell growth and survival in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 94 EP 94 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800100 ER PT J AU Ciccarelli, BT Hatjiharissi, E Ho, AW Branagan, AR Hunter, ZR Adamia, S Leleu, X Xu, L O'Connor, KE Manning, RJ Santos, DD Patterson, CJ Soumerai, JD Munshi, NC McEarchern, JA Grewal, IS Treon, SP AF Ciccarelli, B. T. Hatjiharissi, E. Ho, A. W. Branagan, A. R. Hunter, Z. R. Adamia, S. Leleu, X. Xu, L. O'Connor, K. E. Manning, R. J. Santos, D. D. Patterson, C. J. Soumerai, J. D. Munshi, N. C. McEarchern, J. A. Grewal, I. S. Treon, S. P. TI The functional role of CD27-CD70 interactions in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Res, Boston, MA 02115 USA. Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. W Roxbury Vet Adm Med Ctr, Boston, MA USA. Seattle Genet Inc, Bothell, WA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 94 EP 94 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800101 ER PT J AU Palumbo, A Larocca, A Rus, C Gay, E Rossi, D Pregno, P Falco, P Avonto, I Magarotto, V D'Agostino, F Iacobelli, M Gaidano, G Mitsiades, C Richardson, PG Anderson, K Boccadoro, M AF Palumbo, A. Larocca, A. Rus, C. Gay, E. Rossi, D. Pregno, P. Falco, P. Avonto, I. Magarotto, V. D'Agostino, F. Iacobelli, M. Gaidano, G. Mitsiades, C. Richardson, P. G. Anderson, K. Boccadoro, M. TI Efficacy and safety of melphalan, prednisone,thalidomide and defibrotide in relapsed and refractory multiple myeloma patients: Results of a multicenter phase I/II trial SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Az Osp S Giovanni Battista, Turin, Italy. Univ Studi Piemonte Orientale, Novara, Italy. Gentium SpA, Como, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0258 BP 94 EP 94 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900260 ER PT J AU Leleu, X Manning, R Soumerai, J Hunter, ZR Moreau, AS Hatjiharissi, E Roccaro, A Sacco, A Adamia, S Patterson, CJ Ghobrial, IM Treon, SP AF Leleu, X. Manning, R. Soumerai, J. Hunter, Z. R. Moreau, A. S. Hatjiharissi, E. Roccaro, A. Sacco, A. Adamia, S. Patterson, C. J. Ghobrial, I. M. Treon, S. P. TI Increased incidence of disease transformation and development of MDS/AML in Waldenstrom's macroglobulinemia (WM) patients treated with nucleoside analogues SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. CHRU, Immunol Lab, Serv Malad Sang, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 95 EP 96 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800105 ER PT J AU Soumerai, J Branagan, A Hunter, Z Patterson, C Hatjiharissi, E Treon, S AF Soumerai, J. Branagan, A. Hunter, Z. Patterson, C. Hatjiharissi, E. Treon, S. TI Use of the immunomodulators thalidomide and lenalidomide to augment rituximab clinical activity in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 3 Z9 3 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 95 EP 95 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800103 ER PT J AU Podar, K Tonon, G Sattler, M Tai, YT Le Gouill, S Yasui, H Ishitsuka, K Kumar, S Kumar, R Pandite, LN Hideshima, T Chauhan, D Anderson, KC AF Podar, K. Tonon, G. Sattler, M. Tai, Y.-T. Le Gouill, S. Yasui, H. Ishitsuka, K. Kumar, S. Kumar, R. Pandite, L. N. Hideshima, T. Chauhan, D. Anderson, K. C. TI In vitro and in vivo activity of the VEGF inhibitor pazopanib in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Hosp Univ, Hotel Dieu, Nantes, France. Mayo Clin, Rochester, MN USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0269 BP 98 EP 98 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900271 ER PT J AU Gastinne, T Sebti, Y Moreau, AS Duhamel, A Le Friec, G Coiteux, V Amiot, L Poulain, S Hennache, B Morel, P Ghobrial, IM Treon, SP Facon, T Zorn, E Leleu, X AF Gastinne, Th. Sebti, Y. Moreau, A.-S. Duhamel, A. Le Friec, G. Coiteux, V. Amiot, L. Poulain, S. Hennache, B. Morel, P. Ghobrial, I. M. Treon, S. P. Facon, T. Zorn, E. Leleu, X. TI Clinical relevance of soluble HLA class I in Waldenstroms Macroglobulinemia and IgM MGUS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 CHU Nantes, F-44035 Nantes 01, France. UPRES 38 89, Hematol Lab, Rennes, France. Dana Farber Canc Inst, Boston, MA 02115 USA. CHRU, Lab Biostat, Lille, France. CHRU Lille, Biochim Lab, Lille, France. Serv Hematol, Lens, France. CHU Nantes, Serv Hematol Clin, F-44035 Nantes 01, France. RI Duhamel, Alain/B-8624-2011; FACON, THIERRY/M-9736-2014; Duhamel, Alain/A-4899-2013; Amiot, laurence/J-5955-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0272 BP 99 EP 99 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900274 ER PT J AU Adamia, S Van Ness, B Ramos, C Reiman, T Belch, AR Pilarski, LM AF Adamia, S. Van Ness, B. Ramos, C. Reiman, T. Belch, A. R. Pilarski, L. M. TI HAS1 gene polymorphisms may contribute to myelomagenesis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 104 EP 104 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800133 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Breitktreutz, I Kiziltepe, T Yasui, H Pozzi, S Cirstea, D Ocio, E Shiraishi, N Ladettoz, M Boccadoro, M Anderson, K AF Vallet, S. Raje, N. Ishitsuka, K. Hideshima, T. Breitktreutz, I. Kiziltepe, T. Yasui, H. Pozzi, S. Cirstea, D. Ocio, E. Shiraishi, N. Ladettoz, M. Boccadoro, M. Anderson, K. TI MLN3897, a novel CCR1 inhibitor, impairs osteoclast formation and function associated with downregulation of c-fos SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Studi Torino, Turin, Italy. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0312 BP 112 EP 113 PG 2 WC Hematology SC Hematology GA 177UB UT WOS:000247176900314 ER PT J AU Prabhala, RH Therrien, VA Pelluru, D Neri, P Fulciniti, M Driscoll, JJ Song, W Daley, JF Anderson, KC Munshi, NC AF Prabhala, R. H. Therrien, V. A. Pelluru, D. Neri, P. Fulciniti, M. Driscoll, J. J. Song, W. Daley, J. F. Anderson, K. C. Munshi, N. C. TI Myeloma microenvironment creates abnormal APC function and may favor generation of TH17 cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 VA Boston Healthcare Syst HMS, W Roxbury, MA USA. Harvard Univ, Sch Med, DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 120 EP 121 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800189 ER PT J AU Runnels, J Pitsillides, C Spencer, J Fujisaki, J Ngo, H Leleu, X Moreau, AS Jial, X Roccaro, A Sacco, A Hatjiharissi, E Hideshima, T Munshi, N Anderson, K Lin, C Ghobrial, I AF Runnels, J. Pitsillides, C. Spencer, J. Fujisaki, J. Ngo, H. Leleu, X. Moreau, A. S. Jial, X. Roccaro, A. Sacco, A. Hatjiharissi, E. Hideshima, T. Munshi, N. Anderson, K. Lin, C. Ghobrial, I. TI A novel real-time in vivo homing model of multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Care, Boston, MA 02115 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 123 EP 123 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800199 ER PT J AU Neri, P Tassone, P Shen, Z Patel, N Fajardo, R Fulciniti, M Prabhala, R Masood, S Blotta, S Hideshima, T Chauhan, D Muller, J Venuta, S Snyder, BD Goldring, SR Anderson, KC Munshi, NC AF Neri, P. Tassone, P. Shen, Z. Patel, N. Fajardo, R. Fulciniti, M. Prabhala, R. Masood, S. Blotta, S. Hideshima, T. Chauhan, D. Muller, J. Venuta, S. Snyder, B. D. Goldring, S. R. Anderson, K. C. Munshi, N. C. TI A murine model to study bone disease in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia, I-88100 Catanzaro, Italy. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 127 EP 127 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800211 ER PT J AU Breitkreutz, I Raab, MS Vallet, S Hideshima, T Raje, N Chauhan, D Munshi, N Richardson, P Anderson, KC AF Breitkreutz, I. Raab, M. S. Vallet, S. Hideshima, T. Raje, N. Chauhan, D. Munshi, N. Richardson, P. Anderson, K. C. TI Lenalidomide and bortezomib in multiple myeloma: Influence on osteoclast SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 131 EP 131 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800223 ER PT J AU Breitkreutz, I Raab, MS Vallet, S Hideshima, T Raje, N Chauhan, D Munshi, N Richardson, P Tai, YT Anderson, KC AF Breitkreutz, I. Raab, M. S. Vallet, S. Hideshima, T. Raje, N. Chauhan, D. Munshi, N. Richardson, P. Tai, Y. T. Anderson, K. C. TI AZD6244, a MEK1/2 inhibitor, inhibits osteoclast differentiation and activity in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 131 EP 131 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800222 ER PT J AU Tsimberidou, AM Wierda, WG Plunkett, WW O'Brien, S Kipps, TJ Brown, JR Lerner, S Kantarjian, HM Keating, MJ AF Tsimberidou, A. M. Wierda, W. G. Plunkett, W. W. O'Brien, S. Kipps, T. J. Brown, J. R. Lerner, S. Kantarjian, H. M. Keating, M. J. TI Clinical efficacy of oxaliplatin, fludarabine, cytarabine,and rituximab combination therapy inpatients with richters syndrome or fludarabine-refractory chronic lymphocytic leukemia: Results of a phase I-II clinical trial SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0364 BP 131 EP 131 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900366 ER PT J AU Pozzi, S Hideshima, T Vallet, S Mukherjee, S Chhetri, S Cirstea, D Thomas, C Rosen, E Ikeda, H Okawa, Y Kiziltepe, T Schipani, E Bouxsein, M Anderson, KC Raje, N AF Pozzi, S. Hideshima, T. Vallet, S. Mukherjee, S. Chhetri, S. Cirstea, D. Thomas, C. Rosen, E. Ikeda, H. Okawa, Y. Kiziltepe, T. Schipani, E. Bouxsein, M. Anderson, K. C. Raje, N. TI In vivo effects of zoledronic acid on bone remodelling SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 134 EP 134 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800231 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Breitkreutz, I Kiziltepe, T Yasui, H Ocio, EM Shiraishi, N Ladetto, M Boccadoro, M Anderson, KC AF Vallet, S. Raje, N. Ishitsuka, K. Hideshima, T. Breitkreutz, I. Kiziltepe, T. Yasui, H. Ocio, E. M. Shiraishi, N. Ladetto, M. Boccadoro, M. Anderson, K. C. TI MLN3897 impairs osteoclastogenesis by C-fos inhibition SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. Univ Turin, Dipartimento Med & Oncol Sperimentale, Cattedra Ematol, Turin, Italy. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 134 EP 135 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800233 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Breitkreutz, I Kiziltepe, T Chhetti, S Pozzi, S Okawa, Y Ikeda, H Boccadoro, M Anderson, KC AF Vallet, S. Raje, N. Ishitsuka, K. Hideshima, T. Breitkreutz, I. Kiziltepe, T. Chhetti, S. Pozzi, S. Okawa, Y. Ikeda, H. Boccadoro, M. Anderson, K. C. TI MLN3897 disrupts osteoclast-myeloma cells interaction SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA USA. Univ Turin, Dipartimento Med & Oncol Sperimentale, Cattedra Ematol, Turin, Italy. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 135 EP 135 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800234 ER PT J AU Kiziltepe, T Hideshima, T Raje, N Ishitsuka, K Ocio, EM Catley, L Li, CQ Trudel, L Yasui, H Shirashi, N Tai, YT Chauhan, D Mitsiades, C Saavedra, JE Wong, GN Keefer, LK Shami, PJ Anderson, KC AF Kiziltepe, T. Hideshima, T. Raje, N. Ishitsuka, K. Ocio, E. M. Catley, L. Li, C. Q. Trudel, L. Yasui, H. Shirashi, N. Tai, Y. T. Chauhan, D. Mitsiades, C. Saavedra, J. E. Wong, G. N. Keefer, L. K. Shami, P. J. Anderson, K. C. TI The in vitro and in vivo anti-tumor effects of JS-K in MM SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, MIT, Biol Engn Div, Cambridge, MA 02139 USA. SAIC, Frederick, MD USA. NCI, NIH, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. Univ Utah, Dept Med Oncol, Salt Lake City, UT 84112 USA. Salt Lake City Vet Adm Med Ctr, Salt Lake City, UT USA. RI Catley, Laurence/E-5313-2013; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 139 EP 140 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800249 ER PT J AU Liso, A Lenze, D Hasserjian, R Coupland, S Jaehne, D Soupir, C Martelli, MP Bolli, N Bacci, F Pettirossi, V Santucci, A Martelli, MF Pileri, S Stein, H Falini, B AF Liso, A. Lenze, D. Hasserjian, R. Coupland, S. Jaehne, D. Soupir, C. Martelli, M. P. Bolli, N. Bacci, F. Pettirossi, V. Santucci, A. Martelli, M. F. Pileri, S. Stein, H. Falini, B. TI Cytoplasmic mutated nucleophosmin defines the molecular status of a significant fraction of myeloid sarcomas SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Univ Med Berlin, Charite, Berlin, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Martelli, Maria Paola/I-5618-2012 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0385 BP 141 EP 141 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900387 ER PT J AU Podar, K Raab, MS Tonon, G Sattler, M Barila, D Tai, YT Yasui, H Raje, N Depinho, RA Hideshima, T Chauhan, D Anderson, KC AF Podar, K. Raab, M. S. Tonon, G. Sattler, M. Barila, D. Tai, Y. T. Yasui, H. Raje, N. Depinho, R. A. Hideshima, T. Chauhan, D. Anderson, K. C. TI C-jun and C-Abl in human multiple myeloma cell death SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Fdn Santa Lucia, Rome, Italy. RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 141 EP 141 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800254 ER PT J AU McMillin, DW Negri, J Hayden, P Zurawska, J Mitsiades, N Richardson, PG Anderson, KC Mitsiades, CS AF McMillin, D. W. Negri, J. Hayden, P. Zurawska, J. Mitsiades, N. Richardson, P. G. Anderson, K. C. Mitsiades, C. S. TI Mechanistic insight into anti-tumor effects of reversine in human myeloma and lymphoma cell lines SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 143 EP 144 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800264 ER PT J AU Neri, P Tassone, P Calimeri, T Rossi, M Tagliaferri, P Pietragalla, A Ventura, M Cucinotto, I Bulotta, A Di Martino, MT Blotta, S Fulciniti, MT Munshi, NC Anderson, KC Venuta, S AF Neri, P. Tassone, P. Calimeri, T. Rossi, M. Tagliaferri, P. Pietragalla, A. Ventura, M. Cucinotto, I. Bulotta, A. Di Martino, M. T. Blotta, S. Fulciniti, M. T. Munshi, N. C. Anderson, K. C. Venuta, S. TI In vitro and in vivo activity of valproic acid in myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Univ Magna Graecia, Catanzaro, Italy. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Univ Hartford, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 143 EP 143 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800262 ER PT J AU Negri, J Mitsiades, N McMullan, CJ Hayden, P McMillin, D Klippel, S Tesmenitsky, Y Haridas, V Munshi, N Richardson, P Gutterman, J Anderson, KC Mitsiades, CS AF Negri, J. Mitsiades, N. McMullan, C. J. Hayden, P. McMillin, D. Klippel, S. Tesmenitsky, Y. Haridas, V. Munshi, N. Richardson, P. Gutterman, J. Anderson, K. C. Mitsiades, C. S. TI Avicins: A novel class of anti-myeloma agents SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 144 EP 144 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800265 ER PT J AU Palladino, MA Chao, TH Barral, AM Macherla, V Potts, BC Neuteboom, STC Chauhan, D Anderson, KC AF Palladino, M. A. Chao, T. H. Barral, A. M. Macherla, Venkat Potts, B. C. Neuteboom, S. T. C. Chauhan, D. Anderson, K. C. TI NPI-1387 regulates IKK alpha and NF-kappa B: A target for myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Nereus Pharmaceut Inc, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 144 EP 144 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800266 ER PT J AU Raab, MS Podar, K Zhang, J Tonon, G McMillin, D Breitkreutz, I Tai, YT Lin, B Munshi, N Hideshima, T Chauhan, D Anderson, KC AF Raab, M. S. Podar, K. Zhang, J. Tonon, G. McMillin, D. Breitkreutz, I. Tai, Y.-T Lin, B. Munshi, N. Hideshima, T. Chauhan, D. Anderson, K. C. TI Targeting PKC informs in MM by enzastaurin (LY317615.HCL) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Univ Heidelberg, Dept Internal Med 5, D-6900 Heidelberg, Germany. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 145 EP 145 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800268 ER PT J AU Raje, N Hideshima, T Vallet, S Chhetri, S Mitsiades, C Rooney, M Kiziltepe, T Podar, K Okawa, Y Ikeda, H Schlossman, R Richardson, PG Chauhan, D Munshi, NC Sharma, S Parikh, H Anderson, KC AF Raje, N. Hideshima, T. Vallet, S. Chhetri, S. Mitsiades, C. Rooney, M. Kiziltepe, T. Podar, K. Okawa, Y. Ikeda, H. Schlossman, R. Richardson, P. G. Chauhan, D. Munshi, N. C. Sharma, S. Parikh, H. Anderson, K. C. TI Targeting cyclin D1 in the treatment of multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 145 EP 145 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800269 ER PT J AU Echart, C Distaso, M Ferro, L Palombo, A Mitsiades, C Richardson, P Anderson, K Lacobelli, M AF Echart, C. Distaso, M. Ferro, L. Palombo, A. Mitsiades, C. Richardson, P. Anderson, K. Lacobelli, M. TI Defibrotide induces downregulation of heparanase expression in multiple myeloma cell lines: a novel mechanism of action SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Ist Tumori, Turin, Italy. Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 146 EP 146 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800272 ER PT J AU Prabhala, RH Neri, P Fulciniti, M Pelluru, D Therrien, VA Driscoll, JJ Tai, YT Daley, JF Anderson, KC Munshi, NC AF Prabhala, R. H. Neri, P. Fulciniti, M. Pelluru, D. Therrien, V. A. Driscoll, J. J. Tai, Y. T. Daley, J. F. Anderson, K. C. Munshi, N. C. TI Lack of TLR ligand-mediated innate responses in myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 VA Boston Healthcare Syst HMS, W Roxbury, MA USA. Harvard Med Sch, DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 147 EP 148 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800278 ER PT J AU Tai, YT Hideshima, T Song, W Li, XE Rumizen, M Burger, P Morrison, A Podar, K Schlossman, R Richardson, P Munshi, NC Ghobrial, I Smith, P Anderson, KC AF Tai, Y. T. Hideshima, T. Song, W. Li, X. F. Rumizen, M. Burger, P. Morrison, A. Podar, K. Schlossman, R. Richardson, P. Munshi, N. C. Ghobrial, I. Smith, P. Anderson, K. C. TI Inhibition of extracellular signal-regulated kinase1/2 mitogen-activated protein kinase (MAPK/ERK1/2) activity by MEK1/2 inhibitor AZD6244 (ARRY-142886) induces human multiple myeloma (MM) cell apoptosis and inhibits osteoclasts within the bone marrow (BM) microenvironment SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. AstraZeneca, Macclesfield SK10 4TG, Cheshire, England. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 147 EP 147 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800275 ER PT J AU Leleu, X O'Sullivan, G Jia, X Ngo, H Moreau, AS Roccaro, A Hatjiharisi, F Hideshima, T Anderson, K Ghobrial, I AF Leleu, X. O'Sullivan, G. Jia, X. Ngo, H. Moreau, A. S. Roccaro, A. Hatjiharisi, F. Hideshima, T. Anderson, K. Ghobrial, I. TI The combination of the MTOR inhibitor rapamycin and proteasome inhibitor bortezomib is synergistic in vitro in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Immunol Lab, Serv Malad Sang, Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 148 EP 149 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800281 ER PT J AU Tai, YT Song, W Li, XF Burger, P Lee, A Leiba, M Podar, K Schlossman, R Rice, A van Abbema, A Richardson, P Munshi, NC DePinho, RA Afar, D Anderson, KC AF Tai, Y. T. Song, W. Li, X. F. Burger, P. Lee, A. Leiba, M. Podar, K. Schlossman, R. Rice, A. van Abbema, A. Richardson, P. Munshi, N. C. DePinho, R. A. Afar, D. Anderson, K. C. TI Targeting CS1, a newly identified human multiple myeloma antigen, by a novel humanized monoclonal antibody HuLuc63, blocks myeloma cell adhesion in the bone marrow microenvironment and induces potent cytotoxicity against myeloma cells even resistant to conventional and novel therapies SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. Ctr Appl Canc Sci, Dept Med Oncol, Fremont, CA USA. PDL Biopharma Inc, Dept Res, Fremont, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 148 EP 148 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800280 ER PT J AU Huston, A Leleu, X Jia, X Anderson, J Alsayed, Y Vallet, S Roccaro, A Moreau, AS Runnels, J Ngo, H Hatjiharissi, E Roodman, D Tai, YT Sportelli, P Hideshima, T Richardson, P Anderson, K Ghobrial, I AF Huston, A. Leleu, X. Jia, X. Anderson, J. Alsayed, Y. Vallet, S. Roccaro, A. Moreau, A. S. Runnels, J. Ngo, H. Hatjiharissi, E. Roodman, D. Tai, Y. T. Sportelli, P. Hideshima, T. Richardson, P. Anderson, K. Ghobrial, I. TI Combination of the AKT inhibitor perifosine with the HSP90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) has synergistic activity in tumor cell and its microenvironment in multiple myeloma (MM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 149 EP 150 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800284 ER PT J AU Podar, K Tonon, G Sattler, M Tai, YT LeGouill, S Yasui, H Ishitsuka, K Kumar, S Kumar, R Pandite, LN Hideshima, T Chauhan, D Anderson, KC AF Podar, K. Tonon, G. Sattler, M. Tai, Y. T. LeGouill, S. Yasui, H. Ishitsuka, K. Kumar, S. Kumar, R. Pandite, L. N. Hideshima, T. Chauhan, D. Anderson, K. C. TI In vitro and in vivo activity of the VEGF inhibitor pazopanib SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. CHU Nantes, Hotel Dieu, INSERM, Inst Biol,Serv Hematol Clin,U0601, F-44035 Nantes 01, France. Mayo Clin, Div Hematol, Rochester, MN USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 150 EP 150 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800285 ER PT J AU Atadja, P Shao, W Growney, J Wang, Y Pu, M Firestone, B Cheng, J Miller, C Eckman, J Yao, YM Fawell, S Anderson, K AF Atadja, P. Shao, W. Growney, J. Wang, Y. Pu, M. Firestone, B. Cheng, J. Miller, C. Eckman, J. Yao, Y. M. Fawell, S. Anderson, K. TI LBH589: Efficacy and protection of bone integrity in multiple myeloma as demonstrated in cell lines and in vivo mouse model SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Novartis Inst Biomed Res Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 151 EP 151 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800288 ER PT J AU Palladino, MA Barral, AM Chao, TH Neuteboom, STC Hannah, A Morgan, E Spear, M Lloyd, GK Chauhan, D Anderson, K AF Palladino, M. A. Barral, A. M. Chao, T. H. Neuteboom, S. T. C. Hannah, A. Morgan, E. Spear, M. Lloyd, G. K. Chauhan, D. Anderson, K. TI Cell specific proteasome inhibition profiles by NPI-0052 SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Nereus Pharmaceut Inc, San Diego, CA USA. Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 152 EP 152 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800292 ER PT J AU Mateos, MV Cibeira, MT Blade, J Prosper, F Lahuerta, JJ Garcia-Sanz, R Escalante, F Flores, LM Espinoza, J Mitsiades, C Richardson, PG Anderson, K San Miguel, JF AF Mateos, M. V. Cibeira, M. T. Blade, J. Prosper, F. Lahuerta, J. J. Garcia-Sanz, R. Escalante, F. Flores, L. M. Espinoza, J. Mitsiades, C. Richardson, P. G. Anderson, K. San Miguel, J. F. TI Phase II trial with plitidepsin (Aplidin) alone and in combination with dexamethasone (dex) in patients with relapsed/refractory multiple myeloma: Preliminary results SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Hosp Univ Salamanca, Salamanca, Spain. Hosp Clin Barcelona, Barcelona, Spain. Clin Univ Navarra, Navarra, Spain. PharmaMar SAU, Clin R&D, Madrid, Spain. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 153 EP 154 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800296 ER PT J AU Jakubowiak, A Richardson, P Zimmerman, T Alsina, M Lonial, S Kendall, T Hideshima, T Sportelli, P Birch, R Henderson, IC Giusti, K Anderson, K AF Jakubowiak, A. Richardson, P. Zimmerman, T. Alsina, M. Lonial, S. Kendall, T. Hideshima, T. Sportelli, P. Birch, R. Henderson, I. C. Giusti, K. Anderson, K. TI A multicenter phase I trial of perifosine (KRX-0401) in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma: Preliminary results. Multiple myeloma research consortium (MMRC) trial SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Emory Winship Canc Inst, Atlanta, GA USA. Keryx Biopharmaceut Inc, New York, NY USA. Multiple Myeloma Res Fdn, Norwalk, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 154 EP 155 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800299 ER PT J AU Richardson, PG Jakubowiak, A Wolf, J Krishnan, A Lonial, S Ghobrial, I Facon, T Colson, K Kendall, T Leister, C Martineau, B Hideshima, T Sportelli, P Birch, R Henderson, IC Anderson, K AF Richardson, P. G. Jakubowiak, A. Wolf, J. Krishnan, A. Lonial, S. Ghobrial, I. Facon, T. Colson, K. Kendall, T. Leister, C. Martineau, B. Hideshima, T. Sportelli, P. Birch, R. Henderson, I. C. Anderson, K. TI A multicenter phase I/II trial of perifosine (KRX-0401) + bortezomib in relapsed and refractory multiple myeloma patients previously treated wth bortezomib: Preliminary results SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Alte Bates Canc Ctr, Berkeley, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Emory Winship Canc Inst, Atlanta, GA USA. Huriez Hosp, Lille, France. Keryx Biopharmaceut, New York, NY USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 3 Z9 3 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 155 EP 156 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800301 ER PT J AU Richardson, PG Lonial, S Jakubowiak, A Krishnan, A Wolf, J Singhal, S Densmore, J Ghobrial, I Stephenson, J Colson, K Harris, J Kendall, T Obadike, N Martineau, B Vickrey, E Sullivan, K Hideshima, T Lai, L Sportelli, P Gardner, L Birch, R Henderson, IC Anderson, KC AF Richardson, P. G. Lonial, S. Jakubowiak, A. Krishnan, A. Wolf, J. Singhal, S. Densmore, J. Ghobrial, I. Stephenson, J. Colson, K. Harris, J. Kendall, T. Obadike, N. Martineau, B. Vickrey, E. Sullivan, K. Hideshima, T. Lai, L. Sportelli, P. Gardner, L. Birch, R. Henderson, I. C. Anderson, K. C. TI Perifosine (KRX-0401) plus low dose dexamethasone is active in patients with relapsed and refractory multiple myeloma (MM): Perifosine MM investigator group phase II multicenter study update SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA 22903 USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 3 Z9 3 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 155 EP 155 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800300 ER PT J AU Richardson, PG Chanan-Khan, A Lonial, S Krishnan, A Carroll, M Cropp, GF Albitar, M Johnson, RG Hannah, AL Anderson, KC AF Richardson, P. G. Chanan-Khan, A. Lonial, S. Krishnan, A. Carroll, M. Cropp, G. F. Albitar, M. Johnson, R. G. Hannah, A. L. Anderson, K. C. TI Tanespimycin (T) plus bortezomib (BZ) in multiple myeloma (MM): Pharmacology, safety and activity in relapsed/refractory patients SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Winship Canc Ctr, Atlanta, GA USA. City Hope Canc Ctr, Duarte, CA USA. Arizona Canc Ctr, Tucson, AZ USA. Quest Hematopathol, San Juan Capistrano, CA USA. Kosan Biosci, Hayward, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 156 EP 156 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800303 ER PT J AU Lonial, S Richardson, PG Miguel, JS Sonneveld, P Schuster, M Blade, J Cavenagh, J Rajkumar, V Jakubowiak, A Esseltine, D Anderson, KC Harousseau, J AF Lonial, S. Richardson, P. G. Miguel, J. San Sonneveld, P. Schuster, M. Blade, J. Cavenagh, J. Rajkumar, V. Jakubowiak, A. Esseltine, D. Anderson, K. C. Harousseau, J. TI Hematologic profiles with bortezomib in relapsed MM SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID MULTIPLE-MYELOMA; REFRACTORY MYELOMA; PHASE-2 C1 Emory Univ, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Univ Salamanca, Salamanca, Spain. Univ Rotterdam Hosp, Rotterdam, Netherlands. NY Presbyterian Hosp, New York, NY USA. Univ Barcelona, Barcelona, Spain. St Bartholomews Hosp, London, England. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Hop Hotel Dieu, Nantes, France. NR 6 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 159 EP 160 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800315 ER PT J AU Niesvizky, R Richardson, PG Rajkumar, SV Sonneveld, P Schuster, MW Coleman, M Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Blade, J Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D Miguel, JFS Boccadoro, M Cavenagh, J Dalton, WS Boral, A Esseltine, DL Neuwirth, R Anderson, KC AF Niesvizky, R. Richardson, P. G. Rajkumar, S. V. Sonneveld, P. Schuster, M. W. Coleman, M. Irwin, D. Stadtmauer, E. A. Facon, T. Harousseau, J. L. Blade, J. Ben-Yehuda, D. Lonial, S. Goldschmidt, H. Reece, D. Miguel, J. F. San Boccadoro, M. Cavenagh, J. Dalton, W. S. Boral, A. Esseltine, D. L. Neuwirth, R. Anderson, K. C. TI Quality of response with bortezomib in APEX SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID STEM-CELL TRANSPLANTATION; RELAPSED MULTIPLE-MYELOMA; HIGH-DOSE DEXAMETHASONE C1 Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Erasmus MC, Rotterdam, Netherlands. Alta Bates Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Hosp Caude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hosp Clin Barcelona, Barcelona, Spain. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Univ Heidelberg, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Hosp Univ Salamanca, Salamanca, Spain. Univ Turin, Turin, Italy. St Bartholomews Hosp, London, England. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 9 TC 4 Z9 4 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 161 EP 162 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800320 ER PT J AU Palumbo, A Gay, F Rus, C Pregno, P Larocca, A Bringhen, S Magarotto, V D'Agostino, F Iacobelli, M Gaidano, G Mitsiades, C Richardson, PG Anderson, KC Boccadoro, M AF Palumbo, A. Gay, F. Rus, C. Pregno, P. Larocca, A. Bringhen, S. Magarotto, V. D'Agostino, F. Iacobelli, M. Gaidano, G. Mitsiades, C. Richardson, P. G. Anderson, K. C. Boccadoro, M. CA Italian Multiple Myeloma Network GIMEMA TI Melphalan, prednisone, thalidomide and defibrotide in advanced myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Univ Turin, Osped Molinette, Azienda Osped S Giovanni Battista, Div Ematol, Turin, Italy. Univ Study Piemonte Orientale, Dept Oncol, Dipartimento Sci Med & IRCAD, Div Ematol, Novara, Italy. Azienda Osped San Giovanni Battista, Turin, Italy. Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 169 EP 169 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800345 ER PT J AU Richardson, PG Jagannath, S Raje, N Ghobrial, I Schlossman, RL Mazumder, A Munshi, NC VeSole, D Colson, K McKenney, ML Farrell, MG Lunde, WE Lunde, LE Giove, L Kaster, S Shea, K Jakubowiak, A Alsina, M Lonial, S Mitsiades, CS Hideshima, T Knight, R Myers, T Anderson, KC AF Richardson, P. G. Jagannath, S. Raje, N. Ghobrial, I. Schlossman, R. L. Mazumder, A. Munshi, N. C. VeSole, D. Colson, K. McKenney, M. L. Farrell, M. G. Warren, D. L. Lunde, L. E. Giove, L. Kaster, S. Shea, K. Jakubowiak, A. Alsina, M. Lonial, S. Mitsiades, C. S. Hideshima, T. Knight, R. Myers, T. Anderson, K. C. TI Phase 2 study of Rev/Vel/Dex in relapsed/refractory MM SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Winship Canc Inst, Atlanta, GA USA. Celgene Inc, Summit, NJ USA. Millennium Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 171 EP 171 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800353 ER PT J AU Richardson, RG Jagannath, S Raje, NS Ghobrial, IM Schlossman, RL Mazumder, A Munshi, NC Vesole, D Doss, D McKenney, ML Farrell, MG Warren, DL Hayes, SW Freeman, A Giove, L Kaster, S Shea, K Avigan, D Joyce, RM Delaney, C Lauria, M Jakubowiak, A Lonial, S Mitsiades, CS Hideshima, T Knight, R Myers, T Anderson, KC AF Richardson, R. G. Jagannath, S. Raje, N. S. Ghobrial, I. M. Schlossman, R. L. Mazumder, A. Munshi, N. C. Vesole, D. Doss, D. McKenney, M. L. Farrell, M. G. Warren, D. L. Hayes, S. W. Freeman, A. Giove, L. Kaster, S. Shea, K. Avigan, D. Joyce, R. M. Delaney, C. Lauria, M. Jakubowiak, A. Lonial, S. Mitsiades, C. S. Hideshima, T. Knight, R. Myers, T. Anderson, K. C. TI Phase 1/2 study of upfront Rev/Vel/Dex in MM: Early results SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Winship Canc Inst, Atlanta, GA 30322 USA. Elgene Inc, Summit, NJ USA. Millennium Pharmaceut Inc, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 179 EP 179 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800375 ER PT J AU Blotta, S Prabhala, R Bellucci, R Tassone, P Tai, YT Song, W Podar, K Neri, P Franco, B Venuta, S Ritz, J Anderson, KC Munshi, NC AF Blotta, S. Prabhala, R. Bellucci, R. Tassone, P. Tai, Y. T. Song, W. Podar, K. Neri, P. Franco, B. Venuta, S. Ritz, J. Anderson, K. C. Munshi, N. C. TI Identification of antigens with induced immune response in MGUS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Crocia, Ctr Canc, Catanzaro, Italy. Tigem Inst, Naples, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 197 EP 197 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800435 ER PT J AU Bertolotti, P Bilotti, E Colson, K Curran, K Doss, D Faiman, B Gavino, M Jenkins, B Lilleby, K Love, G Mangan, PA McCullagh, E Miceli, T Miller, K Rogers, K Rome, S Sandifer, S Smith, L Tariman, J Westphal, J Durie, BGM AF Bertolotti, P. Bilotti, E. Colson, K. Curran, K. Doss, D. Faiman, B. Gavino, M. Jenkins, B. Lilleby, K. Love, G. Mangan, P. A. McCullagh, E. Miceli, T. Miller, K. Rogers, K. Rome, S. Sandifer, S. Smith, L. Tariman, J. Westphal, J. Durie, B. G. M. TI Nursing guidelines for enhanced patient care SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Arkansas, Med Ctr, Myeloma Inst, Fayetteville, AR 72701 USA. H Lee Moffitt Canc Ctr & Res Inst, Res Inst, Tampa, FL 33612 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Rochester, MN 55905 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 211 EP 211 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800481 ER PT J AU Miguel, JFS Richardson, PG Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D Blade, J Boccadoro, M Neuwirth, R Boral, AL Esseltine, DL Anderson, KC AF Miguel, J. F. San Richardson, P. G. Sonneveld, P. Schuster, M. W. Irwin, D. Stadtmauer, E. A. Facon, T. Harousseau, J. L. Ben-Yehuda, D. Lonial, S. Goldschmidt, H. Reece, D. Blade, J. Boccadoro, M. Neuwirth, R. Boral, A. L. Esseltine, D. L. Anderson, K. C. TI Bortezomib in renally impaired multiple myeloma patients SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Univ Hosp, Salamanca, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus MC, Rotterdam, Netherlands. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Univ Heidelberg, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Barcelona, Barcelona, Spain. Univ Turin, I-10124 Turin, Italy. Millennium Pharmaceut Inc, Cambridge, MA USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 214 EP 215 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800493 ER PT J AU Raje, N Woo, SB Hande, K Vallet, R Richardson, PG Vallet, S Treister, N Hideshima, T Sheehy, N Chhetri, S Connell, B Xie, W Tai, YT Szot-Barnes, A Tian, M Schlossman, RL Weller, E Munshi, NC Abbeele, AD Anderson, KC AF Raje, N. Woo, S.-B. Hande, K. Yap, J. T. Richardson, P. G. Vallet, S. Treister, N. Hideshima, T. Sheehy, N. Chhetri, S. Connell, B. Xie, W. Tai, Y. T. Szot-Barnes, A. Tian, M. Schlossman, R. L. Weller, E. Munshi, N. C. Abbeele, A. D. Anderson, K. C. TI Osteonecrosis of the jaw in multiple myeloma patients. SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 216 EP 216 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800497 ER PT J AU Hunter, ZR Leleu, X Adamia, S Hatjiharissi, E Xu, L Ioakimidis, L Moreau, AS Moreau, AS Soumerai, O Soumerai, J Patterson, C Hamilton, S Verselis, S Fox, EA Treon, SP AF Hunter, Z. R. Leleu, X. Adamia, S. Hatjiharissi, E. Xu, L. Ioakimidis, L. Moreau, A. S. Moreau, A. S. O'Connor, K. E. Soumerai, J. Patterson, C. Hamilton, S. Verselis, S. Fox, E. A. Treon, S. P. TI Mutations the April/Taci/Traf pathway in Waldenstrom's macroglobulinemia (WM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Diagnost Core, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 220 EP 220 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800508 ER PT J AU Ngo, H Leleu, X Runnels, J Moreau, AS Jia, X Hatjiharissi, E Roccaro, A Sacco, A Treon, S Hideshima, T Anderson, K Ghobrial, I AF Ngo, H. Leleu, X. Runnels, J. Moreau, A. S. Jia, X. Hatjiharissi, E. Roccaro, A. Sacco, A. Treon, S. Hideshima, T. Anderson, K. Ghobrial, I. TI The CXCR4/SDF-1 axis regulates migration in Waldenstrom's macroglobuilinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Core, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 222 EP 222 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800517 ER PT J AU Ngo, H Leleu, X Runnels, J Moreau, AS Jia, X Roccaro, A Sacco, A Hatjiharissi, E Treon, S Hideshima, T Anderson, K Ghobrial, I AF Ngo, H. Leleu, X. Runnels, J. Moreau, A. S. Jia, X. Roccaro, A. Sacco, A. Hatjiharissi, E. Treon, S. Hideshima, T. Anderson, K. Ghobrial, I. TI CXCR4 and VLA-4 interaction promotes adhesion of Waldenstrom's macroglobuilinemia cells SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Core, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 222 EP 222 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800516 ER PT J AU Roccaro, AM Leleu, X Moreau, AS Patterson, CJ Xu, L Jia, X Ngo, H Sacco, A Cao, J Ciccarelli, B Manning, R Adamia, S Hatjiharissi, E Russo, D Vacca, A Dammacco, E Ghobrial, IM Treon, SP AF Roccaro, A. M. Leleu, X. Moreau, A. S. Patterson, C. J. Xu, L. Jia, X. Ngo, H. Sacco, A. Cao, J. Ciccarelli, B. Manning, R. Adamia, S. Hatjiharissi, E. Russo, D. Vacca, A. Dammacco, E. Ghobrial, I. M. Treon, S. P. TI Resveratrol exerts antiproliferative effect and induces apoptosis in Waldenstrom's macroglobuilinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, I-25121 Brescia, Italy. Univ Bari, Sch Med, Dept Internal Med & Clin Oncol, I-70121 Bari, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 224 EP 225 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800525 ER PT J AU Leleu, X Jia, X Moreau, AS Ngo, H Runnels, J Hatjiharisi, E Roccaro, A O'Sullivan, G Moreno, D Kiziltepe, T Facon, T Treon, S Hideshima, T Anderson, K Ghobrial, I AF Leleu, X. Jia, X. Moreau, A. S. Ngo, H. Runnels, J. Hatjiharisi, E. Roccaro, A. O'Sullivan, G. Moreno, D. Kiziltepe, T. Facon, T. Treon, S. Hideshima, T. Anderson, K. Ghobrial, I. TI Perifosine, an oral bioactive novel akt inhibitor, induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Immunol Lab, Serv Malad Sang, Lille, France. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 225 EP 226 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800528 ER PT J AU Moreau, AS Jia, X Ngo, H Leleu, X Daley, J Lalo, S O'Sullivan, G Roccaro, A Hatjiharisi, E Raab, MS Podar, K D'Halluim, JC Facon, T Treon, S Hideshima, T Anderson, K Ghobrial, I AF Moreau, A. S. Jia, X. Ngo, H. Leleu, X. Daley, J. Lalo, S. O'Sullivan, G. Roccaro, A. Hatjiharisi, E. Raab, M. S. Podar, K. D'Halluim, J. C. Facon, T. Treon, S. Hideshima, T. Anderson, K. Ghobrial, I. TI Protein kinase inhibitor, enzastaurin, induces in vitro and in vivo antitumor activity in Waldenstrom S macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. INSERM, CHRU, U837, Serv Malad Sang, Lille, France. RI Hunter, Zachary/H-3018-2013; FACON, THIERRY/M-9736-2014 OI Hunter, Zachary/0000-0002-1689-1691; FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 225 EP 225 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800527 ER PT J AU Moreau, AS Jia, X Leleu, X Patterson, CJ Hunter, ZR Roccaro, AM Sacco, A Soumerai, J O'Connor, K Ciccarelh, B Xu, L Manning, R Ghobrial, IM Treon, SP AF Moreau, A. S. Jia, X. Leleu, X. Patterson, C. J. Hunter, Z. R. Roccaro, A. M. Sacco, A. Soumerai, J. O'Connor, K. Ciccarelh, B. Xu, L. Manning, R. Ghobrial, I. M. Treon, S. P. TI Simvastatin, an HMG-COA inhibitor, induces in vitro antitumor activity in Waldenstrom's macroglosulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Bing Ctr waldenstrom MAcroglobulinemia, Boston, MA 02115 USA. INSERM, CHRU, U837, Serv Malad Sang, Lille, France. RI Hunter, Zachary/H-3018-2013; FACON, THIERRY/M-9736-2014 OI Hunter, Zachary/0000-0002-1689-1691; FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 225 EP 225 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800526 ER PT J AU Ghobrial, IM Leleu, X Treon, SP Nelson, MB Leduc, R Warren, D Soumerai, J Ngo, H Sportelli, P Birch, R Henderson, IC Richardson, P Anderson, K AF Ghobrial, I. M. Leleu, X. Treon, S. P. Nelson, M. B. Leduc, R. Warren, D. Soumerai, J. Ngo, H. Sportelli, P. Birch, R. Henderson, I. C. Richardson, P. Anderson, K. TI Phase II trial of perifosine (KRX-0401) in relapsed and/or refractory Waldenstrom's macroglobulinemia: Preliminary results SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Keryx Biopharmaceut Inc, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 226 EP 226 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800530 ER PT J AU Leleu, X Jia, X Moreau, AS Ngo, H Runnels, J Roccaro, A Kiziltepe, T Ciccarelli, B Hatjiharissi, E Hunter, Z Adamia, S Sportelli, P Treon, S Anderson, K Ghobrial, I AF Leleu, X. Jia, X. Moreau, A. S. Ngo, H. Runnels, J. Roccaro, A. Kiziltepe, T. Ciccarelli, B. Hatjiharissi, E. Hunter, Z. Adamia, S. Sportelli, P. Treon, S. Anderson, K. Ghobrial, I. TI The combination of perifosine with bortezomib and rituximab provides synergistic anti-tumor activity in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. CHRU, Fac Med, Immunol Lab, Serv Malad Sang, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 226 EP 226 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800529 ER PT J AU Leleu, X Moreau, AS Manning, R Coiteux, V Darre, S Nelson, M Leduc, R Poulain, S Faucompret, JL Hennache, B Treon, S Facon, T Ghobrial, IM AF Leleu, X. Moreau, A. S. Manning, R. Coiteux, V. Darre, S. Nelson, M. Leduc, R. Poulain, S. Faucompret, J. L. Hennache, B. Treon, S. Facon, T. Ghobrial, I. M. TI Serum free light chain is a marker of tumor burden and of prognostic impact in Waldenstrom's macroglobulinemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Serv Malad Sang, Immunol Lab, Lille, France. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 IS 6 SU 2 BP 229 EP 229 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800537 ER PT J AU Gastinne, T Leleu, X Moreau, AS Andrieux, J Lai, JL Coiteux, V Yacoub-Agha, I Bauters, F Moreau, P Harousseau, JL Facon, T Zandecki, M AF Gastinne, Th. Leleu, X. Moreau, A.-S. Andrieux, J. Lai, J.-L. Coiteux, V. Yacoub-Agha, I. Bauters, F. Moreau, P. Harousseau, J.-L. Facon, T. Zandecki, M. TI Plasma cell proliferation using KI67 antigen expression defines subgroups related to short survival in multiple myeloma especially with low B-2 microglobulin SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 CHU Nantes, F-44035 Nantes 01, France. Dana Farber Canc Inst, Boston, MA 02115 USA. CHU Lille, Gen Med Serv, F-59037 Lille, France. CHU Nantes, Serv Hematol Clin, F-44035 Nantes 01, France. CHU Angers, Hematol Lab, Angers, France. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0690 BP 257 EP 258 PG 2 WC Hematology SC Hematology GA 177UB UT WOS:000247176900692 ER PT J AU Podar, K Raab, MS Tonon, G Sattler, M Barila, D Zhang, J Tai, YT Yasui, H Raje, N DePinho, RA Hideshima, T Chauhan, D Anderson, KC AF Podar, K. Raab, M.-S. Tonon, G. Sattler, M. Barila, D. Zhang, J. Tai, Y.-T. Yasui, H. Raje, N. DePinho, R. A. Hideshima, T. Chauhan, D. Anderson, K. C. TI C-jun and C-ABL in human multiple myeloma cell death SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dulbecco Telethon Inst, Rome, Italy. RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0689 BP 257 EP 257 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900691 ER PT J AU Hawtin, E Cohen, R Haas, N Mendelson, D Gordon, M Eder, JP Dezube, BJ Adelman, DC Shapiro, GI Hoch, U Stockett, DE Conroy, A Fox, JA AF Hawtin, E. Cohen, R. Haas, N. Mendelson, D. Gordon, M. Eder, J. P. Dezube, B. J. Adelman, D. C. Shapiro, G. I. Hoch, U. Stockett, D. E. Conroy, A. Fox, J. A. TI SNS-032 exhibits dose-dependent mechanism-based inhibition of CDK7 and CDK9 in peripheral blood mononuclear cells from patients with advanced cancers treated in an ongoing phase 1 trial SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Sunesis Pharmaceut Inc, San Francisco, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Premiere Oncol Arizona, Scottsdale, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2007 VL 92 SU 1 MA 0742 BP 276 EP 277 PG 2 WC Hematology SC Hematology GA 177UB UT WOS:000247176900744 ER PT J AU Emerick, KS Deschler, DG AF Emerick, Kevin S. Deschler, Daniel G. TI Incidence of donor site skin graft loss requiring surgical intervention with the radial forearm free flap SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Head-and-Neck-Society CY MAY 15-16, 2005 CL Boca Raton, FL SP Amer Head & Neck Soc DE radial forearm; free flap; donor site; morbidity; complication ID FUNCTIONAL MORBIDITY; COVERAGE; HARVEST; HEAD AB Background. Many methods of managing the fasciocutaneous radial forearm free flap (RFFF) donor site have been described. Ideal management would be technically easy to perform, reliable, cost-effective, and prevent further complications. Methods. The clinical records of 54 consecutive patients undergoing RFFF surgery by the senior author were reviewed. Records were reviewed to identify donor sites with significant breakdown that required intervention. Results. Fifty-four patients were identified. Only 1 patient had significant tendon exposure. A V to Y closure was performed. The site healed well following this procedure and no further intervention was required. No other donor site complications were noted in this group. Conclusion. The incidence of wound breakdown requiring surgical intervention at the RFFF donor site is less than 2% utilizing a simple technique of split thickness skin grafting, bolster, and short-term splinting. This study demonstrates the low donor site morbidity of the RFFF. (c) 2007 Wiley Periodicals, Inc. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. EM Kevin_Emerick@meei.harvard.edu NR 18 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUN PY 2007 VL 29 IS 6 BP 573 EP 576 DI 10.1002/hed.20584 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 174QW UT WOS:000246958600008 PM 17252598 ER PT J AU Vincent, M Hadjikhani, N AF Vincent, Maurice Hadjikhani, Nouchine TI The cerebellum and migraine SO HEADACHE LA English DT Review DE migraine; familial hemiplegic migraine; cerebellum; progressive ataxia; episodic ataxia ID FAMILIAL HEMIPLEGIC MIGRAINE; EPISODIC ATAXIA TYPE-2; CORTICAL SPREADING DEPRESSION; BASILAR ARTERY MIGRAINE; ISOLATED CHICK RETINA; CACNA1A MISSENSE MUTATION; TRANSIENT GLOBAL AMNESIA; DELAYED CEREBRAL EDEMA; MINOR HEAD TRAUMA; CALCIUM-CHANNEL AB Clinical and pathophysiological evidences connect migraine and the cerebellum. Literature on documented cerebellar abnormalities in migraine, however, is relatively sparse. Cerebellar involvement may be observed in 4 types of migraines: in the widespread migraine with aura (MWA) and migraine without aura (MWoA) forms; in particular subtypes of migraine such as basilar-type migraine (BTM); and in the genetically driven autosomal dominant familial hemiplegic migraine (FHM) forms. Cerebellar dysfunction in migraineurs varies largely in severity, and may be subclinical. Purkinje cells express calcium channels that are related to the pathophysiology of both inherited forms of migraine and primary ataxias, mostly spinal cerebellar ataxia type 6 (SCA-6) and episodic ataxia type 2 (EA-2). Genetically driven ion channels dysfunction leads to hyperexcitability in the brain and cerebellum, possibly facilitating spreading depression waves in both locations. This review focuses on the cerebellar involvement in migraine, the relevant ataxias and their association with this primary headache, and discusses some of the pathophysiological processes putatively underlying these diseases. C1 Univ Fed Rio de Janeiro, Fac Med, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. RP Vincent, M (reprint author), Ave Amer 1155-504, BR-22631000 Rio De Janeiro, Brazil. RI Hadjikhani, Nouchine/C-2018-2008; Vincent, Maurice/B-1415-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NINDS NIH HHS [5P01 NS 35611-09, P01 NS035611] NR 154 TC 31 Z9 32 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD JUN PY 2007 VL 47 IS 6 BP 820 EP 833 DI 10.1111/j.1526-4610.2006.00715.x PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 177UM UT WOS:000247178000002 PM 17578530 ER EF