FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shah, SS Downes, KJ Elliott, MR Bell, LM McGowan, KL Metlay, JP AF Shah, Samir S. Downes, Kevin J. Elliott, Michael R. Bell, Louis M. McGowan, Karin L. Metlay, Joshua P. TI How long does it take to "Rule Out" bacteremia in children with central venous catheters? SO PEDIATRICS LA English DT Article DE child; bacteremia; sepsis; central venous catheterization; blood culture ID PEDIATRIC OBSERVATION UNIT; BLOOD-STREAM INFECTIONS; ANTIBIOTIC-TREATMENT; HOSPITAL CHARGES; TIME; CULTURES; POSITIVITY; TECHNOLOGY; EMERGENCY; FUNGEMIA AB BACKGROUND. Children with central venous catheters and suspected bloodstream infection are often hospitalized for 48 hours to receive empiric antibiotic therapy pending blood-culture results. Continuous monitoring blood-culture systems allow for more rapid detection of bloodstream infection than previous blood-culture systems, a feature that may facilitate earlier determination of the true presence or absence of bloodstream infection and shorten empiric antibiotic therapy and duration of hospitalization. METHODS. This retrospective cohort study included children with central venous catheters who were diagnosed with laboratory-confirmed bloodstream infection after evaluation in the ambulatory care setting. RESULTS. Two-hundred episodes of bloodstream infection were included. The median patient age was 5.5 years. Central venous catheters were in place for a median of 80.5 days. Gram-negative bacteria accounted for 51% of infections as part of either a monomicrobial (25%) or polymicrobial (26%) infection. The overall median time to blood-culture positivity was 14 hours. The predicted probability for a culture being positive at 36 hours was 99.2% for infections caused by Gram-negative bacteria and 96.6% for any infection after adjusting for age, catheter type, and recent antibiotic use. In a multivariate Cox proportional-hazards regression model, polymicrobial infections with >= 1 Gram-negative bacteria and monomicrobial infections caused by Gram-negative bacteria were independently associated with an earlier time to blood-culture positivity after adjusting for age, catheter type, and recent antibiotic use. CONCLUSIONS. The time to blood-culture positivity depends on bacterial category. Bloodstream infections caused by Gram-negative bacteria are detected most quickly. Our data suggest that discontinuation of empiric antibiotic coverage may be warranted in clinically stable children with central venous catheters if the blood-culture results remain negative 24 to 36 hours after collection. C1 [Shah, Samir S.; Downes, Kevin J.] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. [Bell, Louis M.] Childrens Hosp Philadelphia, Div Gen Pediat, Philadelphia, PA 19104 USA. [McGowan, Karin L.] Childrens Hosp Philadelphia, Dept Clin Microbiol Lab, Philadelphia, PA 19104 USA. [Shah, Samir S.; Metlay, Joshua P.] Univ Penn, Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USA. [Shah, Samir S.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [McGowan, Karin L.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Shah, Samir S.; Metlay, Joshua P.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Shah, Samir S.; Metlay, Joshua P.] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Elliott, Michael R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Elliott, Michael R.] Univ Michigan, Inst Social Res, Survey Methodol Program, Ann Arbor, MI 48109 USA. RP Shah, SS (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, Room 1526,North Campus,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM shahs@email.chop.edu OI Shah, Samir/0000-0001-7902-7000 NR 27 TC 13 Z9 14 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 JAN PY 2008 VL 121 IS 1 BP 135 EP 141 DI 10.1542/peds.2007-1387 PG 7 WC Pediatrics SC Pediatrics GA 247RC UT WOS:000252096300018 PM 18166567 ER PT J AU Benoit, MM Bhattacharyya, N Faquin, W Cunningham, M AF Benoit, Margo McKenna Bhattacharyya, Neil Faquin, William Cunningham, Michael TI Cancer of the nasal cavity in the pediatric population SO PEDIATRICS LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY APR 27-29, 2007 CL San Diego, CA SP Amer Soc Pediat Otolaryngol DE esthesioneuroblastoma; rhabdomyosarcoma; nasal obstruction; neoplasm ID CRANIOFACIAL RESECTION; ESTHESIONEUROBLASTOMA; PROGNOSIS; SURVIVAL; SARCOMA; RHABDOMYOSARCOMA; RADIOTHERAPY; CHILDHOOD; TUMORS; SINUS AB OBJECTIVE. The purpose of this work was to investigate the clinical manifestations and diagnostic range of malignant entities presenting as a nasal mass in the pediatric population. PATIENTS AND METHODS. A retrospective cohort analysis was conducted at a specialty hospital and a tertiary care university hospital. Patients aged between birth and 18 years and diagnosed with a malignancy that arose within the nasal cavity between the years 1991 and 2006 were included. This institution-specific patient group was compared with a similar cohort of patients extracted from the national Surveillance Epidemiology and End Results database. The main outcome measures were the incidence, presentation, and diagnoses of nasal cancer presenting in this population. RESULTS. Sixteen patients with nasal malignancies presented institutionally in the defined pediatric age group. Patient age at the time of diagnosis ranged from 7 months to 17 years, with a slight male predominance. The main presenting symptoms were unilateral nasal congestion and ophthalmologic complaints. The median time from presentation to diagnosis was 7 weeks; patients who presented with nonspecific complaints, such as nasal obstruction, headache, and fatigue, were given a diagnosis, on average, later than those who presented with focal manifestations. Nationwide, 47 patients were identified from the Surveillance Epidemiology and End Results database. In both subject groups, the most common diagnoses were rhabdomyosarcoma (37.5% institutionally and 23% in the Surveillance Epidemiology and End Results group) and esthesioneuroblastoma (25% institutionally and 28% Surveillance Epidemiology and End Results). In the Surveillance Epidemiology and End Results cohort, the overall mean survival rate was 188 months. CONCLUSIONS. Nasal cancer in the pediatric population often presents with nonspecific signs and symptoms, and a high index of suspicion is necessary for a timely diagnosis. Soft tissue sarcomas are expectedly common. The relative high frequency of esthesioneuroblastoma is particularly noteworthy. C1 [Benoit, Margo McKenna; Cunningham, Michael] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Benoit, Margo McKenna; Bhattacharyya, Neil; Cunningham, Michael] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. [Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Benoit, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 14 Z9 15 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 JAN PY 2008 VL 121 IS 1 BP E141 EP E145 DI 10.1542/peds.2007-1319 PG 5 WC Pediatrics SC Pediatrics GA 247RC UT WOS:000252096300056 PM 18086819 ER PT J AU Biederman, J Melmed, RD Patel, A McBurnett, K Konow, J Lyne, A Scherer, N AF Biederman, Joseph Melmed, Raun D. Patel, Anil McBurnett, Keith Konow, Jennifer Lyne, Andrew Scherer, Noreen CA SPD503 Study Grp TI A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder SO PEDIATRICS LA English DT Article DE attention-deficit/hyperactivity disorder; ADHD; alpha(2)-adrenoceptor agonist; guanfacine; SPD503; nonstimulant; stimulant ID DEFICIT-HYPERACTIVITY DISORDER; STIMULANT TREATMENT; TOURETTES-SYNDROME; TRIAL; CLONIDINE; METHYLPHENIDATE; ATOMOXETINE; PERFORMANCE; PREVALENCE; EFFICACY AB OBJECTIVE. With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder. METHODS. In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release ( 2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale Revised: Short Form, and Conners' Teacher Rating Scale-Revised: Short Form. RESULTS. A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg ( n = 87), 3 mg ( n = 86), or 4 mg ( n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: -16.18 in the 2-mg group, -16.43 in the 3-mg group, and -18.87 in the 4-mg group, compared with -8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale-Revised: Short Form, and Conners' Teacher Rating Scale Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful. CONCLUSIONS. Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Dept, Boston, MA 02114 USA. [Melmed, Raun D.] Melmed Ctr, Scottsdale, AZ USA. [Patel, Anil] Ctr Psychiat, San Marino, CA USA. [McBurnett, Keith] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Konow, Jennifer] Kendle Int Inc, Late Phase Res, Cincinnati, OH USA. [Lyne, Andrew] Shire Pharmaceut Dev Ltd, Basingstoke, Hants, England. [Scherer, Noreen] Shire Dev Inc, Wayne, NJ USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Dept, Boston, MA 02114 USA. NR 36 TC 145 Z9 148 U1 4 U2 13 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 JAN PY 2008 VL 121 IS 1 BP E73 EP E84 DI 10.1542/peds.2006-3695 PG 12 WC Pediatrics SC Pediatrics GA 247RC UT WOS:000252096300048 PM 18166547 ER PT J AU Keyhani, S Kleinman, LC Rothschild, M Bernstein, JM Anderson, R Simon, M Chassin, M AF Keyhani, Salomeh Kleinman, Lawrence C. Rothschild, Michael Bernstein, Joseph M. Anderson, Rebecca Simon, Melissa Chassin, Mark TI Clinical characteristics of New York City children who received tympanostomy tubes in 2002 SO PEDIATRICS LA English DT Article; Proceedings Paper CT AcademyHealth Annual Research Meeting CY JUN 03-05, 2007 CL Orlando, FL SP AcademyHealth DE tympanostomy tubes; epidemiology; physician's practice pattern; use ID ASSESSING FEBRILE CHILDREN; ACUTE PEDIATRIC ILLNESSES; PERSISTENT OTITIS-MEDIA; QUALITY-OF-LIFE; DEVELOPMENTAL OUTCOMES; OBSERVATION VARIABLES; DELAYED INSERTION; EFFUSION; HISTORY; PERFORMANCE AB OBJECTIVE. Tympanostomy tube insertion is the most common procedure that requires general anesthesia for children in the United States. We report on the clinical characteristics of a cohort of New York City children who received tympanostomy tubes in 2002. METHODS. This retrospective cohort study included all 1046 children who received tubes in 2002 in any of 5 New York City area hospitals. We analyzed clinical data for all 682 (65%) children for whom we were able to abstract data for the preceding year from all of 3 sources: hospital, pediatrician, and otolaryngologist medical charts. RESULTS. Mean age was 3.8 years, 57% were male, and 74% had private insurance. More than 25% of children had received tubes previously. The stated reason for surgery was otitis media with effusion for 60.4% of children, recurrent acute otitis media for 20.7%, and eustachian tube dysfunction for 10.6%. Children with recurrent acute otitis media averaged 3.1 +/- 0.2 episodes ( median: 3.0) in the previous year; those with otitis media with effusion averaged effusions that were 29 +/- 1.7 days long ( median: 16 days) at surgery. Twenty-five percent of children had bilateral effusions of > 42 days' duration at surgery. Despite a clinical practice guideline for otitis media with effusion that recommends withholding tympanostomy tubes for otherwise healthy children until a bilateral effusion is at least 3 to 4 months old, 50% of children had surgery without having had 3 months of effusion cumulatively during the year before surgery. CONCLUSIONS. The clinical characteristics of children who received tympanostomy tubes varied widely. Many children with otitis media with effusion had shorter durations of effusions than are generally recommended before surgery. The extent of variation in treating this familiar condition with limited treatment options suggests both the importance and the difficulty of managing common practice in accordance with clinical practice guidelines. C1 [Keyhani, Salomeh; Kleinman, Lawrence C.; Anderson, Rebecca; Chassin, Mark] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. [Keyhani, Salomeh] James J Peters VA Med Ctr, Bronx, NY USA. [Rothschild, Michael] Mt Sinai Sch Med, Dept Pediat & Otolaryngol, New York, NY USA. [Bernstein, Joseph M.] NYU, Sch Med, Dept Pediat & Otolaryngol, New York, NY USA. [Simon, Melissa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Keyhani, S (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. FU AHRQ HHS [R01 HS 10302] NR 36 TC 14 Z9 15 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2008 VL 121 IS 1 BP E24 EP E33 DI 10.1542/peds.2007-0623 PG 10 WC Pediatrics SC Pediatrics GA 247RC UT WOS:000252096300042 PM 18166541 ER PT J AU Blevins, JE Chelikani, PK Haver, AC Reidelberger, RD AF Blevins, J. E. Chelikani, P. K. Haver, A. C. Reidelberger, R. D. TI PYY(3-36) induces Fos in the arcuate nucleus and in both catecholaminergic and non-catecholaminergic neurons in the nucleus tractus solitarius of rats SO PEPTIDES LA English DT Article DE PYY(3-36); satiety; forebrain; hindbrain; Fos; tyrosine hydroxylase ID INHIBITS FOOD-INTAKE; BRAIN-STEM NUCLEI; PEPTIDE YY3-36; INTRAVENOUS-INFUSION; RECEPTOR SUBTYPES; BETA-ENDORPHIN; OBESE SUBJECTS; ALPHA-MSH; PYY3-36; EXPRESSION AB Peptide YY (3-36) [PYY(3-36)] inhibits feeding in rodents, nonhuman primates and humans, yet the neural circuits underlying this action remain to be determined. Here we assessed whether PYY(3-36) inhibits feeding by activating neurons in forebrain and hindbrain sites containing Y2 receptors and linked to control of food intake, or in hindbrain sites immediately downstream of vagal afferent neurons. Rats received an anorexigenic dose of PYY(3-36), and the number of neurons expressing Fos, an indicator of neuronal activation, was determined in anterior hypothalamus (AH), arcuate nucleus (ARC), dorsomedial hypothalamus (DMH), lateral hypothalamus (LH), ventromedial hypothalamus (VMH), central nucleus of the amygdala (CeA), area postrema (AP), and caudal medial nucleus tractus solitarius (cmNTS), commissural NTS (cNTS), and gelatinosus NTS (gNTS). Expression of tyrosine hydroxylase (TH), an indicator of catecholamine synthesis, was also measured in the cmNTS. PYY(3-36) increased Fos in ARC, cmNTS, gNTS and AP. Approximately 10% of Fos(+) neurons in the cmNTS were TH(+). These results suggest that PYY(3-36) inhibits feeding through direct activation of ARC neurons, and direct and/or indirect activation via vagal afferent nerves of cmNTS, gNTS and AP, including some catecholaminergic neurons in the cmNTS. (C) 2007 Elsevier Inc. All rights reserved. C1 [Blevins, J. E.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Blevins, J. E.] VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. [Chelikani, P. K.; Reidelberger, R. D.] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. [Haver, A. C.; Reidelberger, R. D.] VA Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68105 USA. RP Blevins, JE (reprint author), Vet Adm Med Ctr, Res-151,1660 S Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu; prasanth.chelikani@ucalgary.ca; ahaver@juno.com; roger.reidelberger@va.gov FU NCRR NIH HHS [P20 RR016469, RR-16469]; NIDDK NIH HHS [R01 DK055830, DK-41301, DK-56805, DK-73152, P30 DK017047, P30 DK017047-31, P30 DK017047-316819, P30 DK041301, R01 DK055830-05, R01 DK056805, R01 DK073152, R01 DK073152-02] NR 39 TC 35 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2008 VL 29 IS 1 BP 112 EP 119 DI 10.1016/j.peptides.2007.11.003 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 254LR UT WOS:000252588600015 PM 18082288 ER PT J AU Vanrullen, R Pascual-Leone, A Battelli, L AF Vanrullen, R. Pascual-Leone, A. Battelli, L. TI The continuous wagon wheel illusion and the 'WHEN' pathway of the right parietal lobe: a repetitive transcranial magnetic stimulation study SO PERCEPTION LA English DT Meeting Abstract C1 [Vanrullen, R.] Univ Toulouse 3, CNRS, CerCo, F-31062 Toulouse, France. [Pascual-Leone, A.; Battelli, L.] Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Beth, Israel. Harvard Univ, Sch Med, Deaconess Med Ctr, Boston, MA USA. EM rufin.vanrullen@cerco.ups-tlse.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2008 VL 37 BP 83 EP 83 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 406BL UT WOS:000263269900296 ER PT J AU Sekuler, R McLaughlin, C Yotsumoto, Y AF Sekuler, Robert McLaughlin, Chris Yotsumoto, Yuko TI Age-related changes in attentional tracking of multiple moving objects SO PERCEPTION LA English DT Article ID VISUAL RECOGNITION; OLDER-ADULTS; MEMORY; CONTRAST AB In a multiple-object tracking (MOT) task, young and older adults attentively tracked a Subset of 10 identical, randomly moving disks for several seconds, and then tried to identify those disks that had comprised the subset. Young adults who habitually played video games performed significantly better than those who did not. Compared to young subjects (mean age = 20.6 years) with whom they were matched for video game experience, older subjects (mean age = 75.3 years) showed much reduced ability to track multiple moving objects, particularly with faster movement or longer tracking times. Control measurements with stationary disks show that the age-related decline in MOT was not caused by a general change in memory per se. To generate an item-wise performance measure, we examined older subjects' proportion correct according to the serial order in which individual disks were identified. Correct identification of target disks declined with the order in which targets were reported, suggesting that attentional tracking produced graded, rather than all-or-none, outcomes. C1 [Sekuler, Robert; McLaughlin, Chris] Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02454 USA. [Yotsumoto, Yuko] Massachusetts Gen Hosp, Martinos Imaging Ctr, Boston, MA 02215 USA. RP Sekuler, R (reprint author), Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02454 USA. EM vision@brandeis.edu FU NIMH NIH HHS [MH068404, R01 MH068404] NR 34 TC 17 Z9 17 U1 0 U2 6 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2008 VL 37 IS 6 BP 867 EP 876 DI 10.1068/p5923 PG 10 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 329YN UT WOS:000257906600008 PM 18686706 ER PT J AU Vogt, DS Rizvi, SL Shipherd, JC Resick, PA AF Vogt, Dawne S. Rizvi, Shireen L. Shipherd, Jillian C. Resick, Patricia A. TI Longitudinal investigation of reciprocal relationship between stress reactions and hardiness SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article DE hardiness; stress reactions; gender; social support; longitudinal ID OPERATION DESERT-STORM; AFFECT SCHEDULE PANAS; PERSIAN-GULF-WAR; SOCIAL SUPPORT; NEGATIVE AFFECT; MENTAL-HEALTH; FACTORIAL INVARIANCE; GENDER-DIFFERENCES; FIT INDEXES; LIFE STRESS AB Although many studies have examined hardiness as a protective factor against stress reactions, to the authors' knowledge no studies have yet examined the impact of stress reactions on hardiness. However, there is theoretical support for this notion. In this longitudinal study of 1,571 Marine recruits who participated in a highly stressful training program, the authors applied regression-based cross-lagged analyses to examine associations between stress reactions and hardiness over time for both men and women, and they investigated social support as a moderator of these relationships. Men who were hardier at Time 1 (T1) reported lower stress reactions at Time 2 (T2), and men who experienced more stress reactions at T1 were less hardy at T2. Although the negative impact of stress reactions on hardiness was strongest when social support was low for both genders, stress reactions predicted enhanced hardiness when social support was high for women only. C1 [Vogt, Dawne S.; Rizvi, Shireen L.; Shipherd, Jillian C.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Vogt, Dawne S.; Rizvi, Shireen L.; Shipherd, Jillian C.; Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Vogt, DS (reprint author), Natl Ctr Posttraumat Stress Disorder 116B 5, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov NR 94 TC 23 Z9 25 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD JAN PY 2008 VL 34 IS 1 BP 61 EP 73 DI 10.1177/0146167207309197 PG 13 WC Psychology, Social SC Psychology GA 245OI UT WOS:000251944400005 PM 18162656 ER PT J AU Stahl, JE AF Stahl, James E. TI Modelling methods for pharmacoeconomics and health technology assessment - An overview and guide SO PHARMACOECONOMICS LA English DT Article ID COST-EFFECTIVENESS; INFLUENCE DIAGRAMS; SOCIAL NETWORKS; SIMULATION; SYSTEMS; CARE; UNCERTAINTY; VACCINATION; MANAGEMENT; PROGNOSIS AB This paper provides an overview of, and guidance as to when, why and how to choose and use, different simulation modelling methods as applied to healthcare. What simulation is and why it is necessary in addressing healthcare problems are discussed. In addition, key criteria for choosing an appropriate method (project type, population resolution, interactivity, treatment of time and space, resource constraints, autonomy and how knowledge is embedded) are covered. Key concepts for each method, moving from the simplest to most complex methods, are reviewed in some detail. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merimac St,10th Floor, Boston, MA 02114 USA. EM James@mgh-ita.org NR 70 TC 56 Z9 58 U1 1 U2 15 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2008 VL 26 IS 2 BP 131 EP 148 PG 18 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 265NM UT WOS:000253366300004 PM 18198933 ER PT J AU Arpino, PA Greer, DM AF Arpino, Paul A. Greer, David M. TI Practical Pharmacologic aspects of therapeutic hypothermia after cardiac arrest SO PHARMACOTHERAPY LA English DT Review DE therapeutic hypothermia; pharmacokinetics; pharmacology; physiology; cardiac arrest ID INTENSIVE INSULIN THERAPY; RANDOMIZED CLINICAL-TRIAL; CRITICALLY-ILL PATIENTS; CEREBRAL BLOOD-FLOW; SEVERE HEAD-INJURY; VENTRICULAR-FIBRILLATION; BRETYLIUM TOSYLATE; CARDIOPULMONARY BYPASS; MILD HYPOTHERMIA; CANINE MODEL AB Therapeutic hypothermia has emerged as an effective means of improving neurologic outcomes among cardiac arrest survivors. To achieve optimal results, clinicians must understand and anticipate potential adverse effects of cooling and provide rigorous monitoring and/or pharmacologic interventions as appropriate. Using pharmacotherapy to counter adverse effects of cooling or to treat an intrinsic process under hypothermic conditions requires understanding how hypothermia will influence the clinical effects of the drug, including the drug's pharmacokinetics and pharmacodynamics. The pharmacologic aspects of therapeutic hypothermia in relation to physiology and adverse effects are reviewed. C1 [Arpino, Paul A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Greer, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Arpino, PA (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. EM parpino@partners.org NR 91 TC 43 Z9 43 U1 2 U2 5 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2008 VL 28 IS 1 BP 102 EP 111 DI 10.1592/phco.28.1.102 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248CF UT WOS:000252128200013 PM 18154480 ER PT J AU Raffetto, JD Khalil, RA AF Raffetto, J. D. Khalil, R. A. TI Mechanisms of varicose vein formation: valve dysfunction and wall dilation SO PHLEBOLOGY LA English DT Review DE chronic venous disease; inflammation; matrix metalloproteinases; varicose veins; venous pressure ID CHRONIC VENOUS INSUFFICIENCY; SMOOTH-MUSCLE-CELLS; KLIPPEL-TRENAUNAY-SYNDROME; MATRIX METALLOPROTEINASES; EDINBURGH VEIN; HYPERPOLARIZING FACTOR; EXTRACELLULAR-MATRIX; LOWER-EXTREMITY; GENERAL-POPULATION; CLINICAL SEVERITY AB Varicose veins are a common venous disease of the lower extremity. Although the mechanisms and determinants in the development of varicosities are not clearly defined, recent clinical studies and basic science research have cast some light on possible mechanisms of the disease. In varicose veins, there are reflux and incompetent valves as well as vein wall dilation. Primary structural changes in the valves may make them 'leaky', with progressive reflux causing secondary changes in the vein wall. Alternatively, or concurrently, the valves may become incompetent secondary to structural abnormalities and focal dilation in vein wall segments near the valve junctions, and the reflux ensues as an epiphenomenon. The increase in venous pressure causes structural and functional changes in the vein wall that leads to further venous dilation. Increase in vein wall tension augments the expression/activity of matrix metalloproteinases (MMPs), which induces degradation of the extracellular matrix proteins and affect the structural integrity of the vein wall. Recent evidence also suggests an effect of MMPs on the endothelium and smooth muscle components of the vein wall and thereby causing changes in the venous constriction/relaxation properties. Endothelial cell injury also triggers leukocyte infiltration, activation and inflammation, which lead to further vein wall damage. Thus, vein wall dilation appears to precede valve dysfunction, and the MMP activation and superimposed inflammation and fibrosis would then lead to chronic and progressive venous insufficiency and varicose vein formation. C1 [Raffetto, J. D.] VA Boston Healthcare Syst, Div Vasc Surg, W Roxbury, MA 02132 USA. [Khalil, R. A.] Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. [Khalil, R. A.] Harvard Univ, Sch Med, Boston, MA USA. RP Raffetto, JD (reprint author), VA Boston Healthcare Syst, Div Vasc Surg, Surg 112,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov FU NHLBI NIH HHS [HL-70659, HL-65998] NR 80 TC 81 Z9 91 U1 0 U2 8 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0268-3555 J9 PHLEBOLOGY JI Phlebology PY 2008 VL 23 IS 2 BP 85 EP 98 DI 10.1258/phleb.2007.007027 PG 14 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 293YV UT WOS:000255372200007 PM 18453484 ER PT J AU Fan, CM Rox-Anderson, R AF Fan, C-M Rox-Anderson, R. TI Endovenous laser ablation: mechanism of action SO PHLEBOLOGY LA English DT Article DE endovenous laser treatment; varicose veins; endovenous technique ID GREAT SAPHENOUS-VEIN; DIODE-LASER; THERMAL-DAMAGE; OCCLUSION; REFLUX; BLOOD; MODEL; NM AB Objectives: The objective of this study is to review the basics of laser and established tissue response patterns to thermal injury, with specific reference to endovenous laser ablation (EVLA). This study also reviews the current theories and supporting aspects for the mechanism of action of EVLA in the treatment of superficial venous reflux. Methods: The method involves the review of published literature and original investigation of histological effects of 810 nm and 980 nm. wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro system. Results: The existing histological reports confirm that EVLA produces a transmural vein wall injury, typically associated with perforations and carbonization. The pattern of injury is eccentrically distributed, with maximum injury occurring along the path of laser contact. Intravenous temperature monitoring studies during EVLA have confirmed that the peak temperatures at the fibre tip exceed 1000 degrees C, and continuous temperatures of at least 300 degrees C are maintained in the firing zone for the majority of the procedure. Steam production during EVLA, which occurs early in the photothermolytic process when temperatures reach 100 degrees C, accounts for only 2% of applied energy dose, and is therefore unlikely to be the primary mechanism of action of thermal injury during the procedure. Conclusion: EVLA causes permanent vein closure through a high-temperature photothermolytic process at the point of contact between the vein and the laser. C1 [Fan, C-M] Brigham & Womens Hosp, Div Angiog & Intervent Radiol, Boston, MA 02115 USA. [Rox-Anderson, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Fan, CM (reprint author), Brigham & Womens Hosp, Div Angiog & Intervent Radiol, 75 Francis St,Midcampus 3, Boston, MA 02115 USA. EM cfan@partners.org NR 23 TC 55 Z9 58 U1 0 U2 5 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0268-3555 J9 PHLEBOLOGY JI Phlebology PY 2008 VL 23 IS 5 BP 206 EP 213 DI 10.1258/phleb.2008.008049 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 369TU UT WOS:000260717600002 PM 18806202 ER PT J AU Tawakol, A Castano, AP Gad, F Zahra, T Bashian, G Migrino, RQ Ahmadi, A Stern, J Anatelli, F Chirico, S Shirazi, A Syed, S Fischman, AJ Muller, JE Hamblin, MR AF Tawakol, Ahmed Castano, Ana P. Gad, Faten Zahra, Touqir Bashian, Gregory Migrino, Raymond Q. Ahmadi, Atosa Stern, Jeremy Anatelli, Florencia Chirico, Stephanie Shirazi, Azadeh Syed, Sakeenah Fischman, Alan J. Muller, James E. Hamblin, Michael R. TI Intravascular detection of inflamed atherosclerotic plaques using a fluorescent photosensitizer targeted to the scavenger receptor SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID MACROPHAGES IN-VIVO; PHOTODYNAMIC THERAPY; INTIMAL HYPERPLASIA; HOST-DEFENSE; EXPRESSION; RUPTURE; LESIONS; PHOTOANGIOPLASTY; DIFFERENTIATION; OPPORTUNITIES AB Inflammation plays an important role in the pathophysiology of atherosclerotic disease. We have previously shown that the targeted photosensitizer chlorin (e(6)) conjugated with maleylated albumin (MA-ce6) is taken up by macrophages via the scavenger receptor with high selectivity. In a rabbit model of inflamed plaque in New Zealand white rabbits via balloon injury of the aorto-iliac arteries and high cholesterol diet we showed that the targeted conjugate showed specificity towards plaques compared to free ce6. We now show that an intravascular fiber-based spectrofluorimeter advanced along the-iliac vessel through blood detects 24-fold higher fluorescence in atherosclerotic vessels compared to control rabbits (p < 0.001 ANOVA). Within the same animals, signal derived from the injured iliac artery was 16-fold higher than the contralateral uninjured iliac (p < 0.001). Arteries were removed and selective accumulation of MA-ce6 in plaques was confirmed using: (1) surface spectrofluorimetry, (2). fluorescence extraction of ce6 from aortic segments, and (3) confocal microscopy. Immunohistochemical analysis of the specimens showed a significant correlation between MA-ce6 uptake and RAM-11 macrophage staining (R = 0.83, p < 0.001) and an inverse correlation between MA-ce6 uptake and smooth muscle cell staining (R = -0.74, p < 0.001). MA-ce6 may function as a molecular imaging agent to detect and/ or photodynamically treat inflamed plaques. C1 [Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Anatelli, Florencia; Chirico, Stephanie; Shirazi, Azadeh; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tawakol, Ahmed; Bashian, Gregory; Muller, James E.] Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. [Castano, Ana P.; Gad, Faten; Zahra, Touqir; Anatelli, Florencia; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Migrino, Raymond Q.; Syed, Sakeenah; Fischman, Alan J.] Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, P01 CA084203, P01CA84203, R01 CA083882-02]; NCRR NIH HHS [K23 RR016046, RR16046]; NIAID NIH HHS [CA / AI838801] NR 43 TC 15 Z9 17 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2008 VL 7 IS 1 BP 33 EP 39 DI 10.1039/b710746c PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 247AE UT WOS:000252048700004 PM 18167594 ER PT S AU Burns, JA AF Burns, James A. BE Kollias, N Choi, B Zeng, H Malek, RS Wong, BJF Ilgner, JFR Gregory, KW Tearney, GJ Hirschberg, H Madsen, SJ TI Innovative laser based approaches to laryngeal cancer: what an engineer and physicist needs to know - art. no. 68421H SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics IV CY JAN 19, 2008 CL San Jose, CA SP SPIE DE larynx; thulium laser; KTP laser; vocal cord; dysphonia; glottic cancer; hoarseness; photoangiolysis; laser laryngeal surgery; laser thermal effects ID PULSED-DYE-LASER; CHORIOALLANTOIC MEMBRANE; CLINICAL EXPERIENCE; GLOTTAL DYSPLASIA; VOCAL FOLD; KTP LASER; SURGERY; PAPILLOMATOSIS; MANAGEMENT; PHOTOTHERMOLYSIS AB Innovative laser-based approaches to laryngeal cancer include the clinical applications of two new technologies, photoangiolysis using a 532nm wavelength pulsed-KTP laser and fiber-based cutting using a 2 mu m wavelength thulium laser. Photoangiolysis is well-suited for treatment of minimally invasive glottic cancer and allows maximum preservation of phonatory surfaces needed for optimal voicing. The thulium laser offers an alternative to the carbon dioxide laser as an endolaryngeal cutting tool due to its enhanced hemostatic properties and fiber-based delivery. Clinical examples of pulsed-KTP laser involution of early glottic cancer will be presented in order to highlight the concept of targeting tumor angiogenesis in treating laryngeal cancer. The surgical experience using the thulium laser for complex endoscopic endolaryngeal excisions of large laryngeal cancers is presented to demonstrate the expanded clinical applications of endolaryngeal cutting offered by this laser. The laryngeal tissue effects of various laser power and pulse width (PW) settings, mode of delivery, active cooling to reduce thermal trauma, and wavelength selection have been extensively studied for the KTP and thulium lasers in both ex-vivo and live-perfusing models. The results from these studies, included herein, determine the clinical efficacy and safety of these innovative laser-based approaches to laryngeal cancer. C1 Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Laryngeal Surg & Voice, Cambridge, MA 02138 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Laryngeal Surg & Voice, Cambridge, MA 02138 USA. NR 39 TC 0 Z9 0 U1 2 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7017-1 J9 P SOC PHOTO-OPT INS PY 2008 VL 6842 BP H8421 EP H8421 DI 10.1117/12.775864 PG 12 WC Biophysics; Engineering, Biomedical; Optics; Physics, Applied SC Biophysics; Engineering; Optics; Physics GA BHQ04 UT WOS:000255314100036 ER PT S AU Razansky, D Vinegoni, C Ntziachristos, V AF Razansky, Daniel Vinegoni, Claudio Ntziachristos, Vasilis BE Oraevsky, AA Wang, LV TI Multi-spectral photo-acoustic molecular tomography resolves fluorochrome distribution with high resolution and sensitivity in small animals - art. no. 685613 SO PHOTONS PLUS ULTRASOUND: IMAGING AND SENSING 2008: THE NINTH CONFERENCE ON BIOMEDICAL THERMOACOUSTICS, OPTOACOUSTICS, AND ACOUSTIC-OPTICS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 9th Conference on Biomedical Thermoacoustics, Optoacoustics and Acousto-optics CY JAN 20-23, 2008 CL San Jose, CA SP SPIE, Fairway Med Technol ID IN-VIVO; FLUORESCENCE; RECONSTRUCTION; CANCER AB Current non-invasive imaging methods of fluorescent molecular probes in the visible and near-infrared suffer from low spatial resolution as a result of rapid light diffusion in biological tissues. We show that three-dimensional distribution of fluorochromes deep in small animals can be resolved with below 25 femtomole sensitivity and 150 microns spatial resolution by means of multi-spectral photoacoustic molecular tomography. The low sensitivity limit of the method is enabled by using the highly resonant absorption spectrum of a commonly used near-infrared fluorescent molecular probe Alexa Fluor (R) 750 in order to acquire differential images at multiple wavelengths with tomographic topology suitable for whole-body small animal imaging. C1 [Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Massachusetts Gen Hosp East, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Razansky, D (reprint author), Massachusetts Gen Hosp East, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7031-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6856 BP 85613 EP 85613 DI 10.1117/12.764155 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BHR12 UT WOS:000255591000036 ER PT S AU Razansky, D Ntziachristos, V AF Razansky, Daniel Ntziachristos, Vasilis BE Oraevsky, AA Wang, LV TI Fluorescence molecular tomography using a-priori photoacoustic data - art. no. 685617 SO PHOTONS PLUS ULTRASOUND: IMAGING AND SENSING 2008: THE NINTH CONFERENCE ON BIOMEDICAL THERMOACOUSTICS, OPTOACOUSTICS, AND ACOUSTIC-OPTICS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 9th Conference on Biomedical Thermoacoustics, Optoacoustics and Acousto-optics CY JAN 20-23, 2008 CL San Jose, CA SP SPIE, Fairway Med Technol ID DIFFUSE OPTICAL TOMOGRAPHY AB We present the first hybrid photoacoutic fluorescence molecular tomography system, capable of three-dimensional imaging of both fluorochrome and chromophore distributions in highly scattering and absorbing tissues. Quantitative three-dimensional maps of optical absorption coefficient are acquired using photoacoustic tomography. The reconstructed absorption data is fed into the Fluorescence Molecular Tomography inversion scheme in order to improve its accuracy and quatification capabilities in the presence of strong and distributed absorbers that are expected to bias stand-alone fluorescence reconstructions. At all, having both techniques in one hybrid modality yields a system that combines high molecular specificity and targeting flexibility of fluorescent imaging and high spatial resolution functional information obtained via photo-acoustic images. C1 [Razansky, Daniel; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Lab Bio Opt & Mol Imaging, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Razansky, D (reprint author), Massachusetts Gen Hosp, Lab Bio Opt & Mol Imaging, Ctr Mol Imaging Res, Boston, MA 02129 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7031-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6856 BP 85617 EP 85617 DI 10.1117/12.764272 PG 9 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BHR12 UT WOS:000255591000040 ER PT J AU Rothman, MS Wierman, ME AF Rothman, Micol S. Wierman, Margaret E. TI Female hypogonadism: evaluation of the hypothalamic-pituitary-ovarian axis SO PITUITARY LA English DT Article DE female hypogonadism; amenorrhea; hypopituitarism; ovarian reserve testing ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; KALLMANN-SYNDROME; MUTATIONS; HORMONE; WOMEN; DEFICIENCY; PHENOTYPES; FAILURE; GPR54; GENE AB Female hypogonadism refers to deficient or abnormal function of the hypothalamic-pituitary-ovarian axis that clinically presents with menstrual cycle disturbances. Female hypogonadism can be due to a congenital or acquired cause, and the defect can be at the level of the hypothalamus, pituitary or ovary. A careful history, physical exam and selected laboratory testing can often determine the locus of the defect and whether it results from a structural or hormonal problem. Laboratory testing generally relies on basal hormone levels; however, timing of blood sampling in relation to menses is important to interpretation of the data. C1 [Rothman, Micol S.; Wierman, Margaret E.] Univ Colorado Denver, Dept Med, Div Endocrinol, Aurora, CO 80045 USA. [Rothman, Micol S.; Wierman, Margaret E.] Hlth Sci Ctr, Aurora, CO 80045 USA. [Wierman, Margaret E.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. RP Rothman, MS (reprint author), Univ Colorado Denver, Dept Med, Div Endocrinol, 1635 N Ursula St,MS F732, Aurora, CO 80045 USA. EM Micol.Rothman@uchsc.edu NR 31 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X J9 PITUITARY JI Pituitary PY 2008 VL 11 IS 2 BP 163 EP 169 DI 10.1007/s11102-008-0109-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 307HR UT WOS:000256310500008 PM 18404388 ER PT J AU Yuan, GC Liu, JS AF Yuan, Guo-Cheng Liu, Jun S. TI Genomic sequence is highly predictive of local nucleosome depletion SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CIS-REGULATORY MODULES; SACCHAROMYCES-CEREVISIAE; EUKARYOTIC GENOME; BINDING-SITES; DNA-SEQUENCE; YEAST; CHROMATIN; PROMOTER; WIDE; ELEMENTS AB The regulation of DNA accessibility through nucleosome positioning is important for transcription control. Computational models have been developed to predict genome-wide nucleosome positions from DNA sequences, but these models consider only nucleosome sequences, which may have limited their power. We developed a statistical multi-resolution approach to identify a sequence signature, called the N-score, that distinguishes nucleosome binding DNA from non-nucleosome DNA. This new approach has significantly improved the prediction accuracy. The sequence information is highly predictive for local nucleosome enrichment or depletion, whereas predictions of the exact positions are only modestly more accurate than a null model, suggesting the importance of other regulatory factors in fine-tuning the nucleosome positions. The N-score in promoter regions is negatively correlated with gene expression levels. Regulatory elements are enriched in low N-score regions. While our model is derived from yeast data, the N-score pattern computed from this model agrees well with recent high-resolution protein-binding data in human. C1 [Yuan, Guo-Cheng; Liu, Jun S.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yuan, Guo-Cheng] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Yuan, GC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM gcyuan@jimmy.harvard.edu; jliu@stat.harvard.edu FU NHGRI NIH HHS [R01 HG005085]; NIGMS NIH HHS [R01 GM078990, R01-GM078990] NR 44 TC 120 Z9 121 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2008 VL 4 IS 1 AR e13 DI 10.1371/journal.pcbi.0040013.eor PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 294LM UT WOS:000255407500004 PM 18225943 ER PT J AU Jain, RK Lahdenranta, J Fukumura, D AF Jain, Rakesh K. Lahdenranta, Johanna Fukumura, Dai TI Targeting PDGF signaling in carcinoma-associated fibroblasts controls cervical cancer in mouse model SO PLOS MEDICINE LA English DT Editorial Material ID GROWTH-FACTOR-RECEPTOR; ENDOTHELIAL-CELLS; TUMOR VASCULATURE; IMATINIB MESYLATE; PERICYTES; GLIOBLASTOMA; THERAPY; BETA C1 [Jain, Rakesh K.; Lahdenranta, Johanna; Fukumura, Dai] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. [Jain, Rakesh K.; Lahdenranta, Johanna; Fukumura, Dai] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. EM Jain@steele.mgh.harvard.edu FU NCI NIH HHS [CA80124, CA96915, P01 CA080124, R01 CA096915] NR 15 TC 13 Z9 14 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2008 VL 5 IS 1 BP 20 EP 21 AR e24 DI 10.1371/journal.pmed.0050024 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 287PJ UT WOS:000254928700008 PM 18232729 ER PT J AU Slagowski, NL Kramer, RW Morrison, MF LaBaer, J Lesser, CF AF Slagowski, Naomi L. Kramer, Roger W. Morrison, Monica F. LaBaer, Joshua Lesser, Cammie F. TI A functional genomic yeast screen to identify pathogenic bacterial proteins SO PLOS PATHOGENS LA English DT Article ID LARGE VIRULENCE PLASMID; III EFFECTOR FAMILY; SHIGELLA-FLEXNERI; HOST-CELLS; SACCHAROMYCES-CEREVISIAE; FRANCISELLA-TULARENSIS; ACTIN POLYMERIZATION; SECRETION PATHWAY; IV PILI; SYSTEM AB Many bacterial pathogens promote infection and cause disease by directly injecting into host cells proteins that manipulate eukaryotic cellular processes. Identification of these translocated proteins is essential to understanding pathogenesis. Yet, their identification remains limited. This, in part, is due to their general sequence uniqueness, which confounds homology-based identification by comparative genomic methods. In addition, their absence often does not result in phenotypes in virulence assays limiting functional genetic screens. Translocated proteins have been observed to confer toxic phenotypes when expressed in the yeast Saccharomyces cerevisiae. This observation suggests that yeast growth inhibition can be used as an indicator of protein translocation in functional genomic screens. However, limited information is available regarding the behavior of non-translocated proteins in yeast. We developed a semi-automated quantitative assay to monitor the growth of hundreds of yeast strains in parallel. We observed that expression of half of the 19 Shigella translocated proteins tested but almost none of the 20 non-translocated Shigella proteins nor; 1,000 Francisella tularensis proteins significantly inhibited yeast growth. Not only does this study establish that yeast growth inhibition is a sensitive and specific indicator of translocated proteins, but we also identified a new substrate of the Shigella type III secretion system (TTSS), IpaJ, previously missed by other experimental approaches. In those cases where the mechanisms of action of the translocated proteins are known, significant yeast growth inhibition correlated with the targeting of conserved cellular processes. By providing positive rather than negative indication of activity our assay complements existing approaches for identification of translocated proteins. In addition, because this assay only requires genomic DNA it is particularly valuable for studying pathogens that are difficult to genetically manipulate or dangerous to culture. C1 [Slagowski, Naomi L.; Kramer, Roger W.; Morrison, Monica F.; Lesser, Cammie F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, Cambridge, MA 02138 USA. [LaBaer, Joshua] Harvard Univ, Sch Med, Harvard Inst Proteom, Cambridge, MA 02138 USA. RP Lesser, CF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, Cambridge, MA 02138 USA. EM clesser@rics.bwh.harvard.edu FU NIAID NIH HHS [AI068924, R01 AI064285, U54 AI057159] NR 59 TC 9 Z9 10 U1 1 U2 7 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 JAN PY 2008 VL 4 IS 1 AR 9 DI 10.1371/journal.ppat.0040009 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294NH UT WOS:000255412300009 PM 18208325 ER PT J AU Rubins, JB Boulware, DR Janoff, EN AF Rubins, Jeffrey B. Boulware, David R. Janoff, Edward N. BE Siber, GR Klugman, KP Makela, PH TI Pneumococcal Pneumonia in Adults: Epidemiology, Clinical Features, Diagnosis, and Therapy SO PNEUMOCOCCAL VACCINES: THE IMPACT OF CONJUGATE VACCINE LA English DT Article; Book Chapter ID COMMUNITY-ACQUIRED PNEUMONIA; IMMUNODEFICIENCY-VIRUS-INFECTION; POLYMERASE-CHAIN-REACTION; SURFACE ADHESIN-A; SPUTUM GRAM STAIN; RAPID IMMUNOCHROMATOGRAPHIC ASSAY; VIRIDANS GROUP STREPTOCOCCI; LINKED-IMMUNOSORBENT-ASSAY; URINARY ANTIGEN TEST; INTENSIVE-CARE-UNIT C1 [Rubins, Jeffrey B.] Vet Adm Med Ctr, Div Pulm Med, Minneapolis, MN 55417 USA. [Rubins, Jeffrey B.] Univ Minnesota, Minneapolis, MN 55417 USA. [Boulware, David R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Janoff, Edward N.] Univ Colorado, Colorado Ctr AIDS Res, Div Infect Dis, Denver, CO 80220 USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Hlth Sci Ctr, Denver, CO 80220 USA. RP Rubins, JB (reprint author), Vet Adm Med Ctr, Div Pulm Med, Minneapolis, MN 55417 USA. RI Boulware, David/B-5516-2011; Boulware, David/I-4533-2013 NR 162 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-582-0 PY 2008 BP 117 EP 138 PG 22 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BOY53 UT WOS:000278065300010 ER PT J AU Panigrahy, D Kapainen, A Kieran, MW Huang, S AF Panigrahy, Dipak Kapainen, Arja Kieran, Mark W. Huang, Sui TI PPARs: A Double-Edged Sword in Cancer Therapy? SO PPAR RESEARCH LA English DT Editorial Material C1 [Panigrahy, Dipak; Kieran, Mark W.] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. [Panigrahy, Dipak; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kapainen, Arja] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Huang, Sui] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada. RP Panigrahy, D (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. EM dipak.panigrahy@childrens.harvard.edu NR 2 TC 9 Z9 9 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2008 AR 350351 DI 10.1155/2008/350351 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13TO UT WOS:000207689300001 ER PT J AU Hoey, P Eisenberg, M AF Hoey, Patty Eisenberg, Matt BE Payne, TH TI WORKING WITH THE USER COMMUNITY SO PRACTICAL GUIDE TO CLINICAL COMPUTING SYSTEMS: DESIGN, OPERATIONS, AND INFRASTRUCTURE LA English DT Article; Book Chapter C1 [Hoey, Patty] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Eisenberg, Matt] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. RP Hoey, P (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055792-2 PY 2008 BP 129 EP 155 DI 10.1016/B978-0-12-374002-1.00008-1 PG 27 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BFF43 UT WOS:000319660300009 ER PT J AU Abdullah, AR Smith, EE Biddinger, PD Kalenderian, D Schwamm, LH AF Abdullah, Abdul R. Smith, Eric E. Biddinger, Paul D. Kalenderian, Deidre Schwamm, Lee H. TI ADVANCE HOSPITAL NOTIFICATION BY EMS IN ACUTE STROKE IS ASSOCIATED WITH SHORTER DOOR-TO-COMPUTED TOMOGRAPHY TIME AND INCREASED LIKELIHOOD OF ADMINISTRATION OF TISSUE-PLASMINOGEN ACTIVATOR SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE advance notification; stroke; tissue-plasminogen activator; computer tomography ID RT-PA STROKE; DELAYS; CARE AB Background. Rapid brain imaging is a critical step in facilitating the use of intravenous (IV) tissue-plasminogen activator (tPA) or catheter-based thrombolysis. We hypothesized that advance notification by emergency medical services (EMS) would shorten emergency department (ED) arrival-to-computed tomography (CT) time and increase the use of IV and intra-arterial thrombolysis, even at a tertiary care stroke center with high baseline rates of tPA use. Methods. We analyzed data on all acute stroke patients transported from March 2004 to June 2005 by EMS from the scene to our facility arriving 6 hours from symptom onset. We reviewed digital voice recordings of all EMS communications to our hospital and in-hospital time intervals and outcomes from our stroke database. Results. Among the 118 patients who met criteria, there were no significant differences between those with notification (n = 44) and those without (n = 74) in terms of age, gender, history of prior stroke, median National Institutes of Health Stroke Scale (NIHSS) score in the ED, proportion with mild stroke (NIHSS score 4), or mean onset-to-ED arrival time. Door-to-CT time was 17% shorter (40 vs. 47 minutes, p = 0.01) in the advance-notification group, and thrombolysis occurred twice as often (41% vs. 21%, p = 0.04). Conclusion. Advance notification of patient arrival by EMS shortened time to CT and was associated with a modest increase in the use of thrombolysis at our hospital. This occurred even with protocols in place to shorten the time to CT for all acute stroke patients. Further research is needed to understand how to increase rates of advance notification by EMS in potential tPA candidates. C1 [Abdullah, Abdul R.; Smith, Eric E.; Kalenderian, Deidre; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Prehosp Care & Disaster Med, Dept Emergency Med, Boston, MA 02114 USA. [Abdullah, Abdul R.; Smith, Eric E.; Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. RP Abdullah, AR (reprint author), 1 City Pl,Apartment 2903, White Plains, NY USA. EM arabdullah@gmail.com OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 NR 19 TC 75 Z9 75 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2008 VL 12 IS 4 BP 426 EP 431 DI 10.1080/10903120802290828 PG 6 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 360RB UT WOS:000260074100003 PM 18924004 ER PT J AU Tiamfook-Morgan, TO Kociszewski, C Browne, C Barclay, D Wedel, SK Thomas, SH AF Tiamfook-Morgan, Tami O. Kociszewski, Christine Browne, Ciaran Barclay, Derek Wedel, Suzanne K. Thomas, Stephen H. TI HELICOPTER SCENE RESPONSE: REGIONAL VARIATION IN COMPLIANCE WITH AIR MEDICAL TRIAGE GUIDELINES SO PREHOSPITAL EMERGENCY CARE LA English DT Article; Proceedings Paper CT 14th Annual Scientific Assembly of the American-Academy-of-Emergency-Medicine CY FEB, 2008 CL Amelia Isl, FL SP Amer Acad Emergency Med DE helicopter EMS; prehospital; trauma triage; utilization review ID PEDIATRIC TRAUMA SCORE; FIELD TRIAGE; PREHOSPITAL TRIAGE; MAJOR TRAUMA; TRANSPORT; INJURY; CARE; SYSTEM; SEVERITY; CENTERS AB Background. Our state has consensus guides for helicopter emergency medical services (HEMS) scene dispatch, based on physiologic, anatomic, and special criteria (e.g., ejection from a vehicle, age < 10 or > 55 years). There has been much attention paid to improving HEMS triage criteria, but less focus on whether current HEMS uses meet existing criteria. Objectives. To assess a HEMS program's compliance with regional air medical dispatch guidelines and to identify factors associated with noncompliant flights. Methods. Using chart review and discussion with referring agencies, we conducted a consecutive case review of a HEMS program's initial 100 flights in one year (2005), collecting data pertinent to triage, prehospital times, and hospital course. Analysis (p = 0.05) of the outcome met triage criteria (MTC) used Kruskal-Wallis and Fisher's exact tests. Logistic regression, reporting odds ratios (ORs) with 95% confidence intervals (CIs), was used to adjust for covariates while assessing predictors of the dichotomous outcome MTC. The predictors assessed included demographics, advanced life support (ALS) scene presence, and whether transports occurred during rush hours (0700-1000 and 1600-1900). Results. The 100 patients (98 blunt trauma; 73% male) from four Massachusetts emergency medical services (EMS) regions (n = 94) and New Hampshire (n = 6) were classified as MTC in 73% of cases. Physiologic criteria were met in 19% of cases (they were the sole criterion met in one case), anatomic criteria in 49% (sole criterion n = 24), and special criteria in 67% (sole criterion n = 15). There was no association between MTC status and age (p = 0.98), gender (p = 0.39), rush-hour transport (p = 0.81), or ALS-trained ground EMS presence on scene (p = 0.98). Analysis adjusting for transport distance and injury mechanism identified an association between EMS region and MTC transport status (p = 0.006); regions' likelihoods of MTC proportions ranged from 50% to 94%. Conclusion. Despite promulgation of consensus guidelines, nearly a fourth of HEMS transports were non-MTC. Wide interregional variation in the likelihood of MTC HEMS use provides a focus for further research/education. Regional systems should strive not only for the refinement of, but also the compliance with, HEMS triage guidelines. C1 [Thomas, Stephen H.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Kociszewski, Christine; Wedel, Suzanne K.; Thomas, Stephen H.] Boston MedFlight Crit Care Transport Serv, Bedford, MA USA. [Wedel, Suzanne K.] Boston Univ, Sch Med, Dept Surg, Bedford, MA USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Zero Emerson Pl Suite 3B, Boston, MA 02114 USA. EM thomas.stephen@mgh.harvard.edu NR 35 TC 18 Z9 19 U1 3 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2008 VL 12 IS 4 BP 443 EP 450 DI 10.1080/10903120802290794 PG 8 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 360RB UT WOS:000260074100006 PM 18924007 ER PT J AU Horne, WC Duong, LT Sanjay, A Baron, R AF Horne, William C. Duong, Le T. Sanjay, Archana Baron, Roland BE Bilezikian, JP Raisz, LG Martin, TJ TI Regulating Bone Resorption: Targeting Integrins, Calcitonin Receptor, and Cathepsin K SO PRINCIPLES OF BONE BIOLOGY, VOL 1, 3RD EDITION LA English DT Article; Book Chapter ID FOCAL ADHESION KINASE; ACTIVATED PROTEIN-KINASE; MEDIATED EXTRACELLULAR ACIDIFICATION; AUTOSOMAL RECESSIVE OSTEOPETROSIS; LYSOSOMAL CYSTEINE PROTEASES; COLONY-STIMULATING-FACTOR; SYK TYROSINE KINASE; OSTEOCLAST FUNCTION; C-CBL; PARATHYROID-HORMONE C1 [Horne, William C.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immunol, Boston, MA 02115 USA. [Duong, Le T.] Merck Res Labs, Dept Bone Biol & Osteoporosis, West Point, PA 19486 USA. [Sanjay, Archana] Temple Univ, Sch Med, Dept Anat & Physiol, Philadelphia, PA 19140 USA. [Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Endocrine Unit, Boston, MA 02115 USA. RP Horne, WC (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immunol, 188 Longwood Ave, Boston, MA 02115 USA. NR 199 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1 PY 2008 BP 221 EP 236 DI 10.1016/B978-0-12-373884-4.00031-8 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS73 UT WOS:000311294700015 ER PT J AU Lee, M Shimizu, E Krane, SM Partridge, NC AF Lee, Minnkyoung Shimizu, Emi Krane, Stephen M. Partridge, Nicola C. BE Bilezikian, JP Raisz, LG Martin, TJ TI Bone Proteinases SO PRINCIPLES OF BONE BIOLOGY, VOL 1, 3RD EDITION LA English DT Article; Book Chapter ID MEMBRANE-TYPE MATRIX; OSTEOBLAST-LIKE CELLS; PLASMINOGEN-ACTIVATOR INHIBITOR; OSTEOGENIC-SARCOMA CELLS; GROWTH-FACTOR-BETA; K-DEFICIENT-MICE; PARATHYROID-HORMONE REGULATION; RABBIT SYNOVIAL FIBROBLASTS; RAT COLLAGENASE-3 PROMOTER; FACTOR-BINDING PROTEIN-3 C1 [Lee, Minnkyoung; Shimizu, Emi; Partridge, Nicola C.] Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ USA. [Krane, Stephen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Partridge, NC (reprint author), MDNJ RWJMS, Dept Physiol & Biophys, 683 Hoes Lane, Piscataway, NJ 08854 USA. EM partrinc@umdnj.edu NR 239 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1 PY 2008 BP 367 EP 384 DI 10.1016/B978-0-12-373884-4.00038-0 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS73 UT WOS:000311294700022 ER PT B AU Gardella, TJ Juppner, H Bringhurst, FR Potts, JT AF Gardella, Thomas J. Jueppner, H. Bringhurst, F. Richard Potts, John T., Jr. BE Bilezikian, JP Raisz, LG Martin, TJ TI Receptors for Parathyroid Hormone (PTH) and PTH-Related Protein SO PRINCIPLES OF BONE BIOLOGY, VOL 1, 3RD EDITION LA English DT Article; Book Chapter ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; CARBOXYL-TERMINAL REGION; UMR-106 OSTEOBLASTIC CELLS; MESSENGER-RIBONUCLEIC-ACID; INHIBITS BONE-RESORPTION; 1ST EXTRACELLULAR LOOP; OPOSSUM KIDNEY-CELLS; PTH/PTHRP RECEPTOR; COUPLED-RECEPTOR; MOLECULAR-CLONING C1 [Gardella, Thomas J.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Gardella, Thomas J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gardella, Thomas J.; Jueppner, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jueppner, H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Bringhurst, F. Richard; Potts, John T., Jr.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. [Bringhurst, F. Richard; Potts, John T., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Bringhurst, F. Richard; Potts, John T., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Potts, JT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 149 13th St,Room 4013, Charlestown, MA 02129 USA. EM jtpotts@partners.org NR 202 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1; 978-0-12-373884-4 PY 2008 BP 555 EP 576 DI 10.1016/B978-0-12-373884-4.00046-X PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS73 UT WOS:000311294700030 ER PT J AU Naveh-Many, T Silver, J Kronenberg, HM AF Naveh-Many, Tally Silver, Justin Kronenberg, Henry M. BE Bilezikian, JP Raisz, LG Martin, TJ TI Parathyroid Hormone Molecular Biology SO PRINCIPLES OF BONE BIOLOGY, VOL 1, 3RD EDITION LA English DT Article; Book Chapter ID PRE-PROPARATHYROID HORMONE; MESSENGER-RIBONUCLEIC-ACID; CHRONIC-RENAL-FAILURE; VITAMIN-D-RECEPTOR; FAMILIAL ISOLATED HYPOPARATHYROIDISM; RESTRICTION REVERSES HYPERPARATHYROIDISM; EXTRACELLULAR CA2+-SENSING RECEPTOR; CHICKEN PREPROPARATHYROID HORMONE; MEDIATES NEGATIVE REGULATION; CALCIUM-SENSING RECEPTOR C1 [Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Naveh-Many, Tally; Silver, Justin] Hadassah Hebrew Univ, Med Ctr, Serv Nephrol, Minerva Ctr Calcium & Bone Metab, Jerusalem, Israel. RP Kronenberg, HM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu NR 136 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1 PY 2008 BP 577 EP 593 DI 10.1016/B978-0-12-373884-4.00047-1 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS73 UT WOS:000311294700031 ER PT B AU Wiren, KM AF Wiren, Kristine M. BE Bilezikian, JP Raisz, LG Martin, TJ TI Androgens Receptor Expression and Steroid Action in Bone SO PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION LA English DT Article; Book Chapter ID OSTEOBLAST-LIKE CELLS; GROWTH-FACTOR-BETA; CAG-REPEAT POLYMORPHISM; MESSENGER-RIBONUCLEIC-ACID; THYROID-HORMONE RECEPTOR; GENITAL SKIN FIBROBLASTS; ADULT MALE-MICE; AGED MALE-RATS; MINERAL DENSITY; OVARIECTOMIZED RATS C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Wiren, KM (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. OI Wiren, Kristine/0000-0002-6159-4450 NR 231 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1; 978-0-12-373884-4 PY 2008 BP 1001 EP 1023 DI 10.1016/B978-0-12-373884-4.00062-8 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS75 UT WOS:000311296900005 ER PT B AU Juppner, H Schipani, E Silve, C AF Jueppner, Harald Schipani, Ernestina Silve, Caroline BE Bilezikian, JP Raisz, LG Martin, TJ TI Genetic Disorders Caused by PTH/PTHrP Receptor Mutations SO PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION LA English DT Article; Book Chapter ID HORMONE-RELATED PEPTIDE; JANSENS METAPHYSEAL CHONDRODYSPLASIA; MESSENGER RIBONUCLEIC-ACIDS; BLOMSTRAND LETHAL OSTEOCHONDRODYSPLASIA; EXTRACELLULAR CA2+-SENSING RECEPTOR; ENDOCHONDRAL BONE-FORMATION; CALCIUM-SENSING RECEPTOR; SMOOTH-MUSCLE-CELLS; HYPERFUNCTIONING THYROID ADENOMAS; OSTEOCLAST DIFFERENTIATION FACTOR C1 [Jueppner, Harald; Schipani, Ernestina] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. [Jueppner, Harald; Schipani, Ernestina] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Silve, Caroline] Univ Paris 07, INSERM, U773, F-75018 Paris, France. [Silve, Caroline] Hop Paris, Lab Biochim Hormonale & Genet, F-75018 Paris, France. [Silve, Caroline] Univ Paris 07, F-75018 Paris, France. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. NR 212 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1; 978-0-12-373884-4 PY 2008 BP 1431 EP 1452 DI 10.1016/B978-0-12-373884-4.00077-X PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS75 UT WOS:000311296900025 ER PT B AU Singer, FR Roodman, GD AF Singer, Frederick R. Roodman, G. David BE Bilezikian, JP Raisz, LG Martin, TJ TI Paget's Disease of Bone SO PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION LA English DT Article; Book Chapter ID CANINE-DISTEMPER VIRUS; RESPIRATORY SYNCYTIAL VIRUS; FAMILIAL EXPANSILE OSTEOLYSIS; POLYMERASE CHAIN-REACTION; MEASLES-VIRUS; CHROMOSOME 18Q; GENETIC-HETEROGENEITY; OSTEOCLAST PRECURSORS; OSTEITIS DEFORMANS; RIBONUCLEIC-ACID C1 [Singer, Frederick R.] St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA 90404 USA. [Roodman, G. David] Univ Pittsburgh, Dept Med, Div Hematol, Pittsburgh, PA USA. [Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Singer, FR (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA 90404 USA. EM singerf@yahoo.com NR 70 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1; 978-0-12-373884-4 PY 2008 BP 1599 EP 1609 DI 10.1016/B978-0-12-373884-4.00081-1 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS75 UT WOS:000311296900033 ER PT S AU Hamblin, MR Castano, AP Mroz, P AF Hamblin, Michael R. Castano, Ana P. Mroz, Pawel BA Tata, DB BF Tata, DB BE Waynant, R TI Combination Immunotherapy and Photodynamic Therapy for Cancer SO PROCEEDINGS OF LIGHT-ACTIVATED TISSUE REGENERATION AND THERAPY CONFERENCE SE Lecture Notes in Electrical Engineering LA English DT Proceedings Paper CT 2nd International Engineering Conference on Light-Activated Tissue Regeneration and Therapy CY JUN 24-29, 2007 CL Tomar, PORTUGAL DE Photodynamic therapy; anti-tumor immunity; toll-like receptors; T regulatory cells; dendritic cells; cytotoxic T-cells; antigen presentation ID TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; REGULATORY T-CELLS; CONTACT HYPERSENSITIVITY; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID; ADOPTIVE IMMUNOTHERAPY; LOCALIZED TREATMENT; MOUSE CARCINOMA; DENDRITIC CELLS; IMMUNE-SYSTEM AB Cancer is a leading cause of death among modern peoples largely clue to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with the minimal toxicity. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT Clue to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock protein,,,, while the three commonest cancer therapies (surgery, chemotherapy and radiotherapy) all tend to suppress the immune system. Like many other immunotherapies, the extent of the immune response after PDT tends to depend oil the antigenicity of the particular tumor. Combination regimens using PDT and immunostimulating treatments are likely to emerge in the future to even further enhance immunity. These are likely to include the so called biological response modifiers that generally consist of products obtained from pathogenic microorganisms against which mammals have evolved sophisticated defenses involving immune activation. A series of pattern recognition molecules including toll-like receptors have been identified that are activated by products derived from pathogens and lead to upregulation of transcription factors that induce expression of many cytokines and inflammatory mediators, which then cause activation of macrophages, dendritic and natural killer cells. There have been several reports of combinations of PDT with microbial derived products potentiating tumor response and leading to long-term anti-tumor immunity. In recent years the role of regulatory T-cells in suppressing anti-tumor immunity has been identified. Treatments such as low dose cyclophosphamide that selectively reduces T-regulatory cells can also be combined with PDT. Methods may be developed to increase the expression of particular tumor antigens before PDT. Although so far these combination therapies have only been used in animal models. their use in clinical trials should receive careful consideration. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR 414, Boston, MA 02114 USA. EM Hamblin@Helix.Mgh.Harvard.Edu OI Hamblin, Michael/0000-0001-6431-4605 NR 58 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1876-1100 BN 978-0-387-71808-8 J9 LECT NOT EL ENGR PY 2008 VL 12 BP 99 EP 113 PG 15 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BIK11 UT WOS:000260249400011 ER PT B AU MacLaughlin, DT Pieretti-Vanmarcke, R Chang, HL Preffer, FI Dombkowski, D Szotek, P Donahoe, PK AF MacLaughlin, D. T. Pieretti-Vanmarcke, R. Chang, H. L. Preffer, F. I. Dombkowski, D. Szotek, P. Donahoe, P. K. BE GodoyMatos, A Wass, J TI Mullerian Inhibiting Substance/Anti-Mullerian Hormone as a Cancer Treatment SO PROCEEDINGS OF THE 13TH INTERNATIONAL CONGRESS OF ENDOCRINOLOGY LA English DT Proceedings Paper CT 13th International Congress of Endocrinology CY NOV 08-12, 2008 CL Rio de Janeiro, BRAZIL ID OVARIAN-CANCER; IMMUNOASSAY; CELLS; GROWTH AB Mullerian Inhibiting Substance (MIS) also known as Anti-Mullerian Hormone (AMH) is a gonadal protein that causes. regression of the Mullerian ducts in male embryos. The MIS gene has a sexually dimorphic pattern of expression; males and females both produce MIS after birth. Serum MIS has been used to detect recurrences of granulosa cell tumors and to monitor response to therapy. We showed that human MIS is effective as a single agent for human ovarian, cervical, endometrial, breast, and prostate cancer cell lines that express MIS type II receptor. MIS could also be used with cytotoxic agents. The mouse ovarian carcinoma (MOVCAR) transgenic cell line that expresses MIS receptor was used as a model with MIS alone and in combination with doxorubicin, paclitaxel, rapamycin, or cisplatin. Paclitaxel resistant IGROV-1 cells and MOVCAR side population cells, which possess properties of tumor initiating cells, retain MIS responsiveness. Doxorubicin, and rapamycin were synergistic, whereas paclitaxel and cisplatin were additive with MIS. Combinations of MIS and cytotoxic agents may enhance clinical efficacy and reduce toxicity. C1 [MacLaughlin, D. T.; Pieretti-Vanmarcke, R.; Chang, H. L.; Preffer, F. I.; Dombkowski, D.; Szotek, P.; Donahoe, P. K.] Harvard Univ, Pediat Surg Res Lab, Massachusetts Gen Hosp, Sch Med,Dept Pathol,Clin Flow Cytometry Lab, Boston, MA 02114 USA. RP MacLaughlin, DT (reprint author), Harvard Univ, Pediat Surg Res Lab, Massachusetts Gen Hosp, Sch Med,Dept Pathol,Clin Flow Cytometry Lab, 185 Cambridge St,CPZN 6100, Boston, MA 02114 USA. EM maclaugh@helix.mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-472-8 PY 2008 BP 91 EP 99 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BIY34 UT WOS:000263685200017 ER PT S AU Halperin, D Clark, SS Fu, K Heydt-Benjamin, TS Defend, B Kohno, T Ransford, B Morgan, W Maisel, WH AF Halperin, Daniel Clark, Shane S. Fu, Kevin Heydt-Benjamin, Thomas S. Defend, Benessa Kohno, Tadayoshi Ransford, Benjamin Morgan, Will Maisel, William H. GP IEEE Computer Soc TI Pacemakers and implantable cardiac defibrillators: Software radio attacks and zero-power defenses SO PROCEEDINGS OF THE 2008 IEEE SYMPOSIUM ON SECURITY AND PRIVACY SE IEEE Symposium on Security and Privacy LA English DT Proceedings Paper CT IEEE Symposium on Security and Privacy CY MAY 18-21, 2008 CL Oakland, CA SP IEEE Comp Soc ID MALFUNCTIONS AB Our study analyzes the security and privacy properties of an implantable cardioverter defibrillator (ICD). Introduced to the U.S. market in 2003, this model of ICD includes pacemaker technology and is designed to communicate wirelessly with a nearby external programmer in the 175 kHz frequency range. After partially reverse-engineering the ICD's communications protocol with an oscilloscope and a software radio, we implemented several software radio-based attacks that could compromise patient safety and patient privacy. Motivated by our desire to improve patient safety, and mindful of conventional trade-offs between security and power consumption for resource-constrained devices, we introduce three new zero-power defenses based on RF power harvesting. Two of these defenses are human-centric, bringing patients into the loop with respect to the security and privacy of their implantable medical devices (IMDs). Our contributions provide a scientific baseline for understanding the potential security and privacy risks of current and future IMDs, and introduce human-perceptible and zero-power mitigation techniques that address those risks. To the best of our knowledge, this paper is the first in our community to use general-purpose software radios to analyze and attack previously unknown radio communications protocols. C1 [Clark, Shane S.; Fu, Kevin; Heydt-Benjamin, Thomas S.; Defend, Benessa; Ransford, Benjamin; Morgan, Will] Univ Massachusetts Amherst, Dept Comp Sci, Med Device Secur Ctr, 140 Governors Dr, Amherst, MA 01003 USA. [Halperin, Daniel; Kohno, Tadayoshi] Univ Washington, Seattle, WA 98195 USA. [Maisel, William H.] BIDMC, Boston, MA USA. [Maisel, William H.] Harvard Med Sch, Boston, MA USA. RP Fu, K (reprint author), Univ Massachusetts Amherst, Dept Comp Sci, Med Device Secur Ctr, 140 Governors Dr, Amherst, MA 01003 USA. EM kevinfu@cs.umass.edu; yoshi@cs.washington.edu; wmaisel@bidmc.harvard.edu OI Halperin, Daniel/0000-0003-0118-0931 FU National Science Foundation (NSF) [CNS-0435065, CNS-0520729, CNS-0627529] FX We thank Rick Adrion, Tom Anderson, Mark Corner, Matthew Garber, Robert W. Jackson, Barry Karas, Jim Kurose, Ed Lazowska, Mark McGovern, Jerry Saltzer, Stefan Savage, Prashant Shenoy, Joshua Smith, Bill Stasny, Paul van Oorschot, David Wagner, Matt Welsh, David Wetherall, Dan Yeager, Serge Zhilyaev, and the anonymous reviewers for their collective assistance, feedback, and generous support of this many-person, interdisciplinary project. This work was supported in part by National Science Foundation (NSF) grants CNS-0435065, CNS-0520729, CNS-0627529, and the NSF Research Experiences for Undergraduates (REU) program. Dr. Maisel is a U.S. Food and Drug Administration consultant. The opinions expressed in this paper are those of the authors and do not necessarily reflect the opinions, positions, practices, or policies of the FDA. NR 31 TC 104 Z9 106 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1081-6011 BN 978-0-7695-3168-7 J9 P IEEE S SECUR PRIV PY 2008 BP 129 EP + DI 10.1109/SP.2008.31 PG 2 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BHU82 UT WOS:000256560300009 ER PT S AU Martinvalet, D Thiery, J Chowdhury, D AF Martinvalet, Denis Thiery, Jerome Chowdhury, Dipanjan BE KhosraviFar, R Zakeri, Z Lockshin, RA Piacentini, M TI Granzymes and cell death SO PROGRAMMED CELL DEATH, GENERAL PRINCIPLES FOR STUDYING CELL DEATH, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID MEDIATED CYTOTOXICITY; APOPTOSIS; PURIFICATION; PERFORIN AB Granzymes are cell death-inducing serine proteases released from cytotoxic granules of cytotoxic T lymphocytes and natural killer cells during granule exocytosis in response to viral infection or against transformed cells marked for elimination. A critical cofactor for the granule exocytosis pathway is perforin, which mediates the entry of granzymes into target cells, where they cleave specific substrates that initiate DNA fragmentation and apoptosis. One of the biggest challenges in studying the biology of granzymes has been the functional redundancy of granzymes in animal models making an in vitro experimental system essential. This chapter discusses methods to study granzyme function in vitro under physiologically relevant experimental conditions. C1 [Martinvalet, Denis; Thiery, Jerome] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Martinvalet, Denis; Thiery, Jerome] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Martinvalet, D (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. NR 16 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374312-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 442 BP 213 EP 230 DI 10.1016/S0070-6879(08)01411-0 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIH30 UT WOS:000259483100011 PM 18662572 ER PT J AU Moore, VDG Letai, A AF Moore, Victoria Del Gaizo Letai, Anthony TI Rational design of therapeutics targeting the BCL-2 family - Are some cancer cells primed for death but waiting for a final push? SO PROGRAMMED CELL DEATH IN CANCER PROGRESSION AND THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article DE apoptosis; BCL-2; BH3; therapeutics; peptide ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CHEMOSENSITIZES HUMAN-MELANOMA; SMALL-MOLECULE INHIBITORS; DNA-DAMAGE RESPONSE; HUMAN MYELOMA CELLS; IN-VIVO; CYTOCHROME-C; BH3-ONLY PROTEINS AB A mechanism for circumventing apoptosis prevalent in many cancer cells is the overexpression of antiapoptotic BCL-2 family members. Upregulated expression of BCL-2 may be required to permit ongoing death signaling without a cellular response. Therefore, antagonizing BCL-2 function may cause death in many cancer cells. The selection for expression of BCL-2 or other antiapoptotic proteins during oncogenesis may derive from these proteins' ability to bind and sequester proapoptotic BH3-only proteins. This situation may be advantageous from a therapeutic viewpoint because cancer cells may be distinguished from normal cells by being primed with death signals. There are several strategies currently under investigation that may lead to improved treatment of many cancers by taking advantage of these differences. C1 [Moore, Victoria Del Gaizo; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 530B, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu NR 106 TC 11 Z9 11 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 615 BP 159 EP 175 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHN08 UT WOS:000254419500008 ER PT J AU Chauhan, D Hideshima, T Anderson, KC AF Chauhan, Dharminder Hideshima, Tern Anderson, Kenneth C. TI Targeting proteasomes as therapy in multiple myeloma SO PROGRAMMED CELL DEATH IN CANCER PROGRESSION AND THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article DE proteasomes; apoptosis; drug resistance; myeloma ID INHIBITOR PS-341; SALINOSPORAMIDE-A; KAPPA-B; CELLS; BORTEZOMIB; MECHANISMS; APOPTOSIS; CANCER; SURVIVAL; NPI-0052 AB The Ubiquitin-proteasome pathway (UPP) regulates normal intracellular protein degradation processes essential for cell cycle progression, inflammation, transcription, DNA replication, and apoptosis. Blockade of UPP using proteasome inhibitor Bortezomib (Velcade) is an effective therapy for relapsed/refractory multiple myeloma (MM). Both oligonucleotide microarrays and proteomic studies are delineating the molecular mechanisms mediating Bortezornib-induced cytotoxicity, defining targets of sensitivity vs resistance, allowing for the development of next generation therapies, and providing the rationale for combination therapies. C1 [Chauhan, Dharminder; Hideshima, Tern; Anderson, Kenneth C.] Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA 50947, CA 78373, CA100707-01] NR 29 TC 35 Z9 36 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 615 BP 251 EP 260 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHN08 UT WOS:000254419500012 PM 18437898 ER PT J AU Dykxhoorn, DM Chowdhury, D Lieberman, J AF Dykxhoorn, Derek M. Chowdhury, Dipanjan Lieberman, Judy TI RNA interference and cancer: Endogenous pathways and therapeutic approaches SO PROGRAMMED CELL DEATH IN CANCER PROGRESSION AND THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article DE RNA interference; microRNA; cancer; microarray; tumor profile; siRNA; therapy; prognosis ID CYTOPLASMIC PROCESSING BODIES; CHRONIC LYMPHOCYTIC-LEUKEMIA; MOUSE VASCULAR ENDOTHELIUM; SERUM RESPONSE FACTOR; HUMAN LUNG CANCERS; MESSENGER-RNA; MICRORNA EXPRESSION; MULTIDRUG-RESISTANCE; NUCLEAR EXPORT; IN-VIVO AB The endogenous RNA interference (RNAi) pathway regulates cellular differentiation and development using, small noncoding hairpin RNAs, called microRNAs. This chapter will review the link between mammalian microRNAs and genes involved in cellular proliferation, differentiation, and apoptosis. Some microRNAs act as oncogenes or tumor suppressor genes, but the target gene networks they regulate are just beginning to be described. Cancer cells have altered patterns of microRNA expression, which can be used to identify the cell of origin and to subtype cancers. RNAi has also been used to identify novel genes involved in cellular transformation using forward genetic screening methods previously only possible in invertebrates. Possible strategies and obstacles to harnessing RNAi for cancer therapy will also be discussed. C1 [Dykxhoorn, Derek M.; Chowdhury, Dipanjan; Lieberman, Judy] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Dykxhoorn, Derek M.; Chowdhury, Dipanjan; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 NR 176 TC 25 Z9 33 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 615 BP 299 EP 329 PG 31 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHN08 UT WOS:000254419500014 PM 18437900 ER PT S AU Zhang, XF Parangi, S AF Zhang, Xuefeng Parangi, Sareh BE KhosraviFar, R Zakeri, Z Lockshin, RA Piacentini, M TI Quantification of vascular endothelial cell apoptosis in vivo SO PROGRAMMED CELL DEATH, THE BIOLOGY AND THERAPEUTIC IMPLICATIONS OF CELL DEATH, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID ANGIOGENESIS; CANCER AB Regulation of vascular endothelial cell survival and apoptosis plays a crucial role during development and numerous physiologic and pathologic processes. Analyzing endothelial. apoptosis in vivo is necessary not only for the understanding of many physiologic and pathotogic processes but also for evaluating treatments that induce endothelial cell apoptosis. This chapter describes one of the more widely used protocols for detecting and quantifying vascular endothelial cell apoptosis by double-staining vascular endothelial cells with immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). C1 [Zhang, Xuefeng; Parangi, Sareh] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Zhang, Xuefeng; Parangi, Sareh] Harvard Univ, Sch Med, Boston, MA USA. [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Zhang, XF (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. NR 4 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374464-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 446 BP 287 EP 292 DI 10.1016/S0076-6879(08)01617-0 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIC04 UT WOS:000258322300017 PM 18603129 ER PT S AU Zhang, XP Li, WH Olumi, AF AF Zhang, Xiaoping Li, Wenhua Olumi, Aria F. BE KhosraviFar, R Zakeri, Z Lockshin, RA Piacentini, M TI Overcoming resistance to TRAIL-induced apoptosis in prostate cancer by regulation of c-FLIP SO PROGRAMMED CELL DEATH, THE BIOLOGY AND THERAPEUTIC IMPLICATIONS OF CELL DEATH, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID RECEPTOR-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; NF-KAPPA-B; CELLULAR FLIP; SIGNALING COMPLEX; CASPASE-8 ACTIVATION; DEATH; CELLS; EXPRESSION; PROTEIN AB Using Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL) for cancer therapy is attractive, because TRAIL is effective against cancer cells without inducing significant cytotoxicity, making it an ideal cancer drug. However, some cancer cells evade TRAIL-induced apoptosis and become resistant. We have been investigating the molecular mechanisms that differentiate between TRAIL-resistant and TRAIL-sensitive prostate cancer cells. We have found that transcriptional regulation of the anti-apoptotic molecule, c-FLIP(L), can regulate sensitivity of cancer cells to TRAIL. We have found that c-Fos, represses expression of c-FLIP(L), and promotes TRAIL-induced apoptosis. Identifying molecular mechanisms that differentiate between sensitive and resistant cancer cells will help improve pro-apoptotic cancer therapies. C1 [Zhang, Xiaoping; Li, Wenhua; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Zhang, XP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. FU Howard Hughes Medical Institute [53000234-0006]; NIDDK NIH HHS [DK64062] NR 43 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374464-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 446 BP 333 EP 349 DI 10.1016/S0076-6879(78)01620-0 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIC04 UT WOS:000258322300020 PM 18603132 ER PT S AU Bird, GH Bernal, F Pitter, K Walensky, LD AF Bird, Gregory H. Bernal, Federico Pitter, Kenneth Walensky, Loren D. BE KhosraviFar, R Zakeri, Z Lockshin, RA Piacentini, M TI Synthesis and biophysical characterization of stabilized alpha-helices of BCL-2 domains SO PROGRAMMED CELL DEATH, THE BIOLOGY AND THERAPEUTIC IMPLICATIONS OF CELL DEATH, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID CELL-PENETRATING PEPTIDES; PROTEIN TRANSDUCTION; NMR STRUCTURE; AMINO-ACIDS; BH3 HELIX; IN-VIVO; APOPTOSIS; DELIVERY; BINDING; ANTENNAPEDIA AB Rational design of compounds to mimic the functional domains of BCL-2 family proteins requires chemical reproduction of the biologic complexity afforded by the relatively large and folded surfaces of BCL-2 homology (BH) domain peptide a-helices. Because the intermolecular handshakes of BCL-2 proteins are so critical to controlling cellular fate, we undertook the development of a toolbox of peptidic ligands that harness the natural potency and specificity of BH a-helices to interrogate and potentially medicate the deregulated apoptotic pathways of human disease. To overcome the classic deficiencies of peptide reagents, including loss of bioactive structure in solution, rapid proteolytic degradation in vivo, and cellular impermeability, we developed a new class of compounds based on hydrocarbon stapling of BH3 death domain peptides. Here we describe the chemical synthesis of Stabilized Alpha-Helices of BCL-2 domains or SAHBs, and the analytical methods used to characterize their secondary structure, proteotytic stability, and cellular penetrance. C1 [Bird, Gregory H.] Dana Farber Canc Inst, Dept Pediat Oncol, Program Canc Chem Biol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Bird, GH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Program Canc Chem Biol, Boston, MA 02115 USA. FU NCI NIH HHS [5P01CA92625, 5R01CA50239]; NHLBI NIH HHS [K08HL074049] NR 36 TC 51 Z9 52 U1 1 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374464-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 446 BP 369 EP 386 DI 10.1016/S0076-6879(08)01622-4 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIC04 UT WOS:000258322300022 PM 18603134 ER PT S AU Pitter, K Bernal, F LaBelle, J Walensky, LD AF Pitter, Kenneth Bernal, Federico LaBelle, James Walensky, Loren D. BE KhosraviFar, R Zakeri, Z Lockshin, RA Piacentini, M TI Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains SO PROGRAMMED CELL DEATH, THE BIOLOGY AND THERAPEUTIC IMPLICATIONS OF CELL DEATH, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID OUTER MITOCHONDRIAL-MEMBRANE; CYTOCHROME-C RELEASE; CELL SURVIVAL; CHROMOSOMAL BREAKPOINT; BH3 DOMAINS; BAX; APOPTOSIS; DEATH; PROTEIN; DISTINCT AB The BCL-2 family of apoptotic proteins regulates the critical balance between cellular life and death and, thus, has become the focus of intensive basic science inquiry and a fundamental target for therapeutic development in oncology and other diseases. Classified based on the presence of conserved alpha-helical motifs and pro- and anti-apoptotic functionalities, BCL-2 proteins participate in a complex interaction network that determines cellular fate. The identification of BCL-2 homology domain 3 (BH3) as a critical death helix that engages and regulates BCL-2 family proteins has inspired the development of molecular tools to decode and drug the interaction network. Stabilized Alpha-Helices of BCL-2 domains (SAH Bs) are structurally reinforced, protease-resistant, and cell-permeable compounds that retain the specificity of native BH3 death ligands and, therefore, serve as ideal reagents to dissect BCL-2 family interactions in vitro and in vivo. Here, we describe the in vitro and cell-based methods that exploit SAHB compounds to determine the functional consequences of BH3 interactions in regulating apoptosis. C1 [Pitter, Kenneth] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Pitter, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [5R01CA50239, 5P01CA92625]; NHLBI NIH HHS [K08HL074049] NR 43 TC 26 Z9 26 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374464-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 446 BP 387 EP 408 DI 10.1016/S0076-6879(08)01623-6 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIC04 UT WOS:000258322300023 PM 18603135 ER PT J AU Dupin, MM Halliday, I Care, CM Munn, LL AF Dupin, M. M. Halliday, I. Care, C. M. Munn, L. L. TI Efficiency oriented, hybrid approach for modelling deformable particles in three dimensions SO PROGRESS IN COMPUTATIONAL FLUID DYNAMICS LA English DT Article DE blood flow; deformable particles; DPs; emulsion; hybrid model; lattice Boltzmann; suspension flow; vesicles ID RED-BLOOD-CELLS; LATTICE-BOLTZMANN SIMULATIONS; SHEAR-FLOW; BOUNDARY-CONDITION; OPTICAL TWEEZERS; POISEUILLE FLOW; ERYTHROCYTE; AGGREGATION; SUSPENSIONS; MIGRATION AB In this paper, we demonstrate a new, rigorous, accurate and efficient model for simulating the flow of a suspension of deformable particles. The model uses a hybrid system: an Eulerian approach is used for the Navier-Stokes solver and a Lagrangian approach for the evolution of the DPs mesh. We demonstrate in this manuscript the capabilities of the model by simulating more than 130 deformable RBC in a tube of 60 x 30 x 30 mu m the transverse migration of 20 vesicles at a low concentration (25% by volume) in a capillary tube of dimensions 150 x 40 x 40 mu m, in a matter of hours. C1 [Dupin, M. M.; Munn, L. L.] Massachusetts Gen Hosp, Steele Lab Canc Biol, Boston, MA 02114 USA. [Dupin, M. M.; Munn, L. L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Halliday, I.; Care, C. M.] Sheffield Hallam Univ, Mat & Engn Res Inst, Sheffield S1 1WB, S Yorkshire, England. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Steele Lab Canc Biol, Boston, MA 02114 USA. EM mdupin@steele.mgh.harvard.edu; i.halliday@shu.ac.uk; c.m.care@shu.ac.uk; lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Care, Christopher/0000-0003-2592-5280 NR 42 TC 4 Z9 4 U1 0 U2 5 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 1468-4349 J9 PROG COMPUT FLUID DY JI Prog. Comput. Fluid Dyn. PY 2008 VL 8 IS 1-4 BP 109 EP 120 DI 10.1504/PCFD.2008.018083 PG 12 WC Thermodynamics; Mechanics SC Thermodynamics; Mechanics GA 305FP UT WOS:000256163500011 ER PT J AU Freedland, SJ Mavropoulos, J Wang, A Darshan, M Demark-Wahnefried, W Aronson, WJ Cohen, P Hwang, D Peterson, B Fields, T Pizzo, SV Isaacs, WB AF Freedland, Stephen J. Mavropoulos, John Wang, Amy Darshan, Medha Demark-Wahnefried, Wendy Aronson, William J. Cohen, Pinchas Hwang, David Peterson, Bercedis Fields, Timothy Pizzo, Salvatore V. Isaacs, William B. TI Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis SO PROSTATE LA English DT Article DE prostatic neoplasms; diet; carbohydrate; fat; ketogenesis; insulin; IGF-1 ID LOW-FAT DIET; KETOGENIC DIET; WEIGHT-LOSS; RANDOMIZED-TRIAL; HEART-DISEASE; RISK-FACTORS; FACTOR-I; PATTERNS; WOMEN; MICE AB BACKGROUND. Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model. METHODS. Seventy-five male SCID mice were fed a NCKD (84% fat-0% carbohydrate-16% protein kcal), low-fat (12% fat-72% carbohydrate-16% protein kcal), or Western diet (40% fat-44% carbohydrate-16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm(3). RESULTS. Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms. CONCLUSIONS. In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet. C1 [Freedland, Stephen J.; Demark-Wahnefried, Wendy] Duke Univ, Med Ctr, Sch Nursing, Durham, NC 27710 USA. [Freedland, Stephen J.] Durham VA Med Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen J.; Demark-Wahnefried, Wendy] Duke Univ, Sch Med, Dept Surg, Div Urol,Duke Prostate Ctr, Durham, NC USA. [Wang, Amy; Darshan, Medha; Isaacs, William B.] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD USA. [Freedland, Stephen J.; Mavropoulos, John; Fields, Timothy; Pizzo, Salvatore V.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Aronson, William J.] Greater Los Angeles VA Med Ctr, Dept Surg, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Cohen, Pinchas; Hwang, David] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. [Peterson, Bercedis] Duke Univ, Sch Med, Dept Biostat, Durham, NC USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Sch Nursing, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu FU NCI NIH HHS [P50 CA092131, R01 CA085740, P50 CA092131-01A1, P50CA92131] NR 35 TC 69 Z9 71 U1 1 U2 8 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 JAN 1 PY 2008 VL 68 IS 1 BP 11 EP 19 DI 10.1002/pros.20683 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 245TD UT WOS:000251957800002 PM 17999389 ER PT B AU Rubin, MA AF Rubin, Mark A. BE Pestell, RG Nevalainen, MT TI New Perspectives in Prediction of Clinical Outcome of Prostate Cancer TMPRSS2-ETS Gene Fusion in Prostate Cancer SO PROSTATE CANCER: SIGNALING NETWORKS, GENETICS, AND NEW TREATMENT STATEGIES SE Current Clinical Oncology Series LA English DT Article; Book Chapter ID CHRONIC MYELOID-LEUKEMIA; RADICAL PROSTATECTOMY; NATURAL-HISTORY; SERINE-PROTEASE; POOR-PROGNOSIS; DELETIONS; TMPRSS2; EXPRESSION; FUSION; FAMILY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rubin, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 39 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-741-9 J9 CURR CLIN ONCOL PY 2008 BP 309 EP 321 DI 10.1007/978-1-60327-079-3_14 D2 10.1007/978-1-60327-079-3 PG 13 WC Oncology SC Oncology GA BJY12 UT WOS:000267393300014 ER PT B AU Hayes, JH Kantoff, P AF Hayes, Julia H. Kantoff, Philip BE Pestell, RG Nevalainen, MT TI New Perspectives on Chemotherapy in Prostate Cancer SO PROSTATE CANCER: SIGNALING NETWORKS, GENETICS, AND NEW TREATMENT STATEGIES SE Current Clinical Oncology Series LA English DT Article; Book Chapter ID PHASE-II TRIAL; ANALOG IXABEPILONE BMS-247550; MITOXANTRONE PLUS PREDNISONE; PALLIATIVE END-POINTS; HIGH-DOSE CALCITRIOL; LEUKEMIA GROUP-B; ESTRAMUSTINE PHOSPHATE; RADICAL PROSTATECTOMY; IN-VITRO; ORAL ESTRAMUSTINE C1 [Hayes, Julia H.] Harvard Univ, Sch Med,Prostate Canc Program, Dana Farber Canc Inst,Div Solid Tumor Oncol, Dept Med Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Kantoff, Philip] Harvard Univ, Sch Med, Prostate Canc SPORE Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. RP Hayes, JH (reprint author), Harvard Univ, Sch Med,Prostate Canc Program, Dana Farber Canc Inst,Div Solid Tumor Oncol, Dept Med Oncol,Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-741-9 J9 CURR CLIN ONCOL PY 2008 BP 401 EP 425 DI 10.1007/978-1-60327-079-3_19 D2 10.1007/978-1-60327-079-3 PG 25 WC Oncology SC Oncology GA BJY12 UT WOS:000267393300019 ER PT S AU Faull, KF Dooley, AN Halgand, F Shoemaker, LD Norris, AJ Ryan, CM Laganowsky, A Johnson, JV Katz, JE AF Faull, Kym F. Dooley, Alek N. Halgand, Frederic Shoemaker, Lorelei D. Norris, Andrew J. Ryan, Christopher M. Laganowsky, Arthur Johnson, Jodie V. Katz, Jonathan E. BE Whitelegge, JP TI An Introduction to the Basic Principles and Concepts of Mass Spectrometry SO PROTEIN MASS SPECTROMETRY SE Wilson and Wilsons Comprehensive Analytical Chemistry LA English DT Editorial Material; Book Chapter ID ELECTRON-CAPTURE DISSOCIATION; CYCLOTRON RESONANCE SPECTROSCOPY; COLLISION-INDUCED DISSOCIATION; FAST-ATOM-BOMBARDMENT; ION-SOURCE; B-IONS; IONIZATION; PEPTIDES; TRAP; NEUTRALIZATION C1 [Faull, Kym F.; Dooley, Alek N.; Norris, Andrew J.; Ryan, Christopher M.] Univ Calif Los Angeles, David Geffen Sch Med, Pasarow Mass Spectrometry Lab, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Faull, Kym F.; Dooley, Alek N.; Norris, Andrew J.; Ryan, Christopher M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Halgand, Frederic] Univ Tours, Reprod Physiol Lab, UMR INRA CNRS 6175, F-37380 Nouzilly, France. [Johnson, Jodie V.] Univ Florida, Dept Chem, Gainesville, FL USA. [Katz, Jonathan E.] Cedars Sinai Med Ctr, Spielberg Family Ctr Appl Prote, Los Angeles, CA 90048 USA. [Laganowsky, Arthur] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Shoemaker, Lorelei D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. RP Faull, KF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Pasarow Mass Spectrometry Lab, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. NR 65 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-526X BN 978-0-08-093203-3; 978-0-444-53055-4 J9 COMP ANAL C PY 2008 VL 52 BP 1 EP 46 DI 10.1016/S0166-526X(08)00201-8 PG 46 WC Chemistry, Analytical SC Chemistry GA BCM54 UT WOS:000310710400004 ER PT J AU Traum, AZ Schachter, AD AF Traum, Avram Z. Schachter, Asher D. TI Urinary proteome profiling to search for biomarkers in steroid-resistant nephrotic syndrome SO PROTEOMICS IN NEPHROLOGY - TOWARDS CLINICAL APPLICATIONS SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article ID AMINO-ACID OXIDATION; TANDEM MASS-SPECTROMETRY; PRIMARY CULTURES; PROTEINS; AMMONIA; PHOSPHORYLATION; ASTROCYTES; NEURONS; UREA; GLOMERULOSCLEROSIS AB Long-term outcomes for patients with nephrotic syndrome (NS) correlate closely with the degree of steroid responsiveness. There are currently no diagnostic tests that accurately predict steroid responsiveness in NS. In children in particular, a prolonged course of daily, high-dose corticosteroid therapy is as much a diagnostic maneuver as it is a treatment. Urine proteomics has been emerging as a potentially rich source of noninvasive yet informative biomarkers of drug responsiveness in NS. In this review, we discuss some of the initial studies of the nephrotic urinary proteome as well as some ongoing and future challenges, including defining the normal urinary proteome, and extracting valuable urinary protein data from an abundance of urinary albumin. Copyright (c) 2008 S. Karger AG, Basel. C1 [Traum, Avram Z.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Schachter, Asher D.] Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. [Schachter, Asher D.] Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Schachter, Asher D.] Harvard Univ, Sch Med, Boston, MA USA. RP Traum, AZ (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 55 Fruit St, Boston, MA 02114 USA. EM atraum@partners.org NR 27 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2008 VL 160 BP 29 EP 36 DI 10.1159/000125925 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA BHX13 UT WOS:000257140500003 PM 18401159 ER PT J AU Arthur, JM Janech, MG Varghese, SA Almeida, JS Powell, TB AF Arthur, John M. Janech, Michael G. Varghese, Sanju A. Almeida, Jonas S. Powell, T. Brian TI Diagnostic and prognostic biomarkers in acute renal failure SO PROTEOMICS IN NEPHROLOGY - TOWARDS CLINICAL APPLICATIONS SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; PROTEOMIC ANALYSIS; LEAD-EXPOSURE; GEL-ELECTROPHORESIS; PROTEIN ALTERATIONS; HOSPITAL MORTALITY; URINARY BIOMARKER; RIFLE CRITERIA; IDENTIFICATION; DISCOVERY AB Acute kidney injury (AKI) is a process that can lead to renal failure. No biological markers are available for predicting the cause or prognosis of AKI. Tests that can predict which patients will need renal replacement therapy (RRT) are needed. In this chapter, we review the recent literature for proteomic analysis in AKI and identify new candidate markers to predict the need for RRT. We also used artificial neural network (ANN) analysis of urine protein data obtained by two-dimensional gel electrophoresis from 19 patients with acute tubular necrosis to identify a set of proteins that can predict whether a patient will require RRT. Ten patients were randomly selected to train an ANN algorithm. The remaining 9 patients were withheld to serve as an independent validation set. The ANN algorithm correctly predicted the renal prognosis of all 10 patients in the training set. In the validation set, the test correctly predicted the future course of renal failure in 7 of the 9 patients (78% accuracy) including 3 of 4 patients who would require RRT (75% sensitivity) and 4 of 5 who L would not (80% specificity). Combinations of urine proteins can be used to predict which patients will require RRT. (c) Copyright (c) 2008 S. Karger AG, Basel. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Div Nephrol, 96 Jonathan Lucas St POB 250623, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU NHLBI NIH HHS [N01-HV-28181] NR 24 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2008 VL 160 BP 53 EP 64 DI 10.1159/000125929 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA BHX13 UT WOS:000257140500005 PM 18401161 ER PT J AU Cohen, AN Glynn, SM Murray-Swank, AB Barrio, C Fischer, EP McCutcheon, SJ Perlick, DA Rotondi, AJ Sayers, SL Sherman, MD Dixon, LB AF Cohen, Amy N. Glynn, Shirley M. Murray-Swank, Aaron B. Barrio, Concepcion Fischer, Ellen P. McCutcheon, Susan J. Perlick, Deborah A. Rotondi, Armando J. Sayers, Steven L. Sherman, Michelle D. Dixon, Lisa B. TI The family forum: Directions for the implementation of family psychoeducation for severe mental illness SO PSYCHIATRIC SERVICES LA English DT Article ID CONTROLLED-TRIAL; RATING-SCALE; TREATMENT RECOMMENDATIONS; SCHIZOPHRENIC-PATIENTS; MEASURING EMPOWERMENT; PATIENT OUTCOMES; PRIMARY-CARE; INTERVENTION; RELAPSE; MANAGEMENT AB It is well documented that family psychoeducation decreases relapse rates of individuals with schizophrenia. Despite the evidence, surveys indicate that families have minimal contact with their relative's treatment team, let alone participate in the evidence-based practice of family psychoeducation. The Department of Veterans Affairs (VA) sponsored a conference, the Family Forum, to assess the state of the art regarding family psychoeducation and to form a consensus regarding the next steps to increase family involvement. The forum reached consensus on these issues: family psychoeducation treatment models should be optimized by efforts to identify the factors mediating their success in order to maximize dissemination; leadership support, training in family psychoeducation models for managers and clinicians, and adequate resources are necessary to successfully implement family psychoeducation; because family psychoeducation may not be appropriate, indicated, or acceptable for all families, additional complementary strategies are needed that involve families in the mental health care of the patient; and work is required to develop and validate instruments that appropriately assess the intervention process and consumer and family outcomes. A treatment heuristic for working with families of persons with severe mental illness is also offered and provides a match of interventions at varying levels of intensity, tailored to family and consumer needs and circumstances. The article describes opportunities for the research and clinical communities to expand the proportion of families served. C1 [Cohen, Amy N.] Greater Los Angeles Vet Affairs Hlth Ctr, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Glynn, Shirley M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Glynn, Shirley M.] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst W Los Ange, Los Angeles, CA 90024 USA. [Murray-Swank, Aaron B.; Dixon, Lisa B.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Murray-Swank, Aaron B.; Dixon, Lisa B.] Univ Maryland, VA Capitol Network MIRECC, Baltimore, MD 21201 USA. [Barrio, Concepcion] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Fischer, Ellen P.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR USA. [Fischer, Ellen P.; Sherman, Michelle D.] VA S Cent MIRECC, N Little Rock, AR USA. [McCutcheon, Susan J.] VA Off Mental Hlth Serv, Dept Vet Affairs, Washington, DC USA. [Perlick, Deborah A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Perlick, Deborah A.] Mt Sinai Sch Med, Vet Integrated Serv Network 3 MIRECC, New York, NY USA. [Rotondi, Armando J.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA. [Rotondi, Armando J.] Univ Pittsburgh, VA Stars & Stripes MIRECC, Pittsburgh, PA 15260 USA. [Sayers, Steven L.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Sayers, Steven L.] Univ Penn, VA Stars & Stripes MIRECC, Philadelphia, PA 19104 USA. [Sherman, Michelle D.] VA Med Ctr, Oklahoma City, OK USA. RP Cohen, AN (reprint author), Greater Los Angeles Vet Affairs Hlth Ctr, Mental Illness Res Educ & Clin Ctr, 11301 Blvd,MIRECC 210A, Los Angeles, CA 90073 USA. EM ancohen@ucla.edu NR 70 TC 34 Z9 34 U1 6 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2008 VL 59 IS 1 BP 40 EP 48 DI 10.1176/appi.ps.59.1.40 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 266OA UT WOS:000253444400010 PM 18182538 ER PT J AU Henderson, C Swanson, JW Szmukler, G Thornicroft, G Zinkler, M AF Henderson, Claire Swanson, Jeffrey W. Szmukler, George Thornicroft, Graham Zinkler, Martin TI A typology of advance statements in mental health care SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; JOINT CRISIS PLANS; PSYCHIATRIC-TREATMENT; TREATMENT ORDERS; DECISION-MAKING; DIRECTIVES; COMMUNITY; SERVICE; USERS; HOSPITALIZATION AB Advance statements documenting mental health service consumers' preferences for treatment during a future mental health crisis or period of incapacity have gained currency in recent years in the United States and some European countries. Several kinds of advance statements have emerged-some as legal instruments, others as treatment planning methods-but no formal comparison has been made among them. This article reviews the literature in English and German to develop a comparative typology of advance statements: joint crisis plans, crisis cards, treatment plans, wellness recovery action plans, and psychiatric advance directives (with and without formal facilitation). The features that distinguish them are the extent to which they are legally binding, whether health care providers are involved in their production, and whether an independent facilitator assists in their production. The differing nature of advance statements is related to the diverse models of care upon which they are based and the legislative and service contexts in which they have been developed. However, there is recent convergence between the United Kingdom and the United States with respect to research interventions that facilitate the production of advance statements, as evidence emerges for the effectiveness of facilitated psychiatric advance directives and joint crisis plans. Different types of advance statements can coexist and in some cases may interact in complementary ways. However, the relationship of advance statements to involuntary treatment is more problematic, as is their effective implementation in many mental health service settings. C1 [Henderson, Claire] Vet Adm Med Ctr, James J Peters Dept, Mental Illness Res Educ & Clin Ctrs, Bronx, NY 10468 USA. [Swanson, Jeffrey W.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Szmukler, George; Thornicroft, Graham] Kings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, London WC2R 2LS, England. RP Henderson, C (reprint author), Vet Adm Med Ctr, James J Peters Dept, Mental Illness Res Educ & Clin Ctrs, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rosalind.henderson@va.gov RI Henderson, Claire/E-4664-2010; Thornicroft, Graham/B-4027-2010 OI Henderson, Claire/0000-0002-6998-5659; Thornicroft, Graham/0000-0003-0662-0879 NR 48 TC 43 Z9 44 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2008 VL 59 IS 1 BP 63 EP 71 DI 10.1176/appi.ps.59.1.63 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 266OA UT WOS:000253444400013 PM 18182541 ER PT J AU Dahlin, C Photopoulos, R AF Dahlin, Constance Photopoulos, Rhaea TI Stepping into Palliative Care 2: Care and Practice (2nd edn) SO PSYCHO-ONCOLOGY LA English DT Book Review C1 [Dahlin, Constance; Photopoulos, Rhaea] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dahlin, C (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2008 VL 17 IS 1 BP 101 EP 102 DI 10.1002/pon.1236 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 253RT UT WOS:000252536000014 ER PT J AU Pompili, M Rihmer, Z Akiskal, HS Innamorati, M Iliceto, P Akiskal, KK Lester, D Narciso, V Ferracuti, S Tatarelli, R De Pisa, E Girardi, P AF Pompili, Maurizio Rihmer, Zoltan Akiskal, Hagop S. Innamorati, Marco Iliceto, Paolo Akiskal, Kareen K. Lester, David Narciso, Valentina Ferracuti, Stefano Tatarelli, Roberto De Pisa, Eleonora Girardi, Paolo TI Temperament and personality dimensions in suicidal and nonsuicidal psychiatric inpatients SO PSYCHOPATHOLOGY LA English DT Article DE suicide; temperament; personality traits ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MAJOR DEPRESSIVE DISORDER; CLINICAL PREDICTORS; HOPELESSNESS SCALE; EVENTUAL SUICIDE; MOOD DISORDERS; RISK-FACTORS; BIPOLAR-II; DSM-IV; IDEATION AB Background: Suicide is a serious public health problem. In the international literature there is evidence to support the notion that certain temperaments and personality traits are often associated with suicidal behavior. Sampling and Methods: In this study, 150 psychiatric inpatients were investigated using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego autoquestionnaire, the Minnesota Multiphasic Personality Inventory, 2nd edition (MMPI-2) and the Beck Hopelessness Scale and evaluated for suicide risk by means of the critical items of the Mini International Neuropsychiatric Interview. Results: Statistical analysis, including logistic regression analysis and multiple regression analysis, showed that suicide risk contributed to the prediction of hopelessness. Among the temperaments, only the hyperthymic temperament, as a protective factor, and the dys thymic/cyclothymic/anxious temperament contributed significantly to the prediction of hopelessness. Irritable temperament and social introversion were predictive factors for suicidal risk. Hopelessness and depression were associated with higher suicidal behavior and ideation, but, unexpectedly, depression as measured by the MMPI did not contribute significantly to the multiple regressions. Conclusions: The present study indicated that, although suicidal psychiatric patients have MMPI-2 profiles in the pathological range, they exhibit several differences from nonsuicidal patients. Patients at risk of suicide have specific temperaments as well as personality and defense mechanism profiles. They are more socially introverted, depressed and psychasthenic, and use hysterical and schizoid mechanisms more often. Generalizability of the findings was limited by the small sample size and the mix of bipolar disorder I, bipolar disorder II, major depressive disorder and psychotic disorder patients. Copyright (C) 2008 S. Karger AG, Basel. C1 [Pompili, Maurizio; Iliceto, Paolo; Narciso, Valentina; Ferracuti, Stefano; Tatarelli, Roberto; De Pisa, Eleonora; Girardi, Paolo] Univ Roma La Sapienza, St Andreas Hosp, Dept Psychiat, IT-0189 Rome, Italy. [Innamorati, Marco] Univ Europea Roma, Rome, Italy. [Pompili, Maurizio] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Pompili, Maurizio] Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. [Akiskal, Hagop S.; Akiskal, Kareen K.] Int Mood Ctr, La Jolla, CA USA. [Akiskal, Hagop S.] San Diego Vet Adm Med Ctr, La Jolla, CA USA. [Lester, David] Richard Stockton Coll New Jersey, Pomona, NJ USA. [Rihmer, Zoltan] Semmelweis Univ, Natl Inst Psychiat & Neurol, H-1085 Budapest, Hungary. [Rihmer, Zoltan] Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Hungary. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andreas Hosp, Dept Psychiat, Vai Grottarossa 1035, IT-0189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; OI Innamorati, Marco/0000-0003-1389-2290; Tatarelli, Roberto/0000-0003-4396-2632; Pompili, Maurizio/0000-0003-1886-4977 NR 54 TC 52 Z9 56 U1 6 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PY 2008 VL 41 IS 5 BP 313 EP 321 DI 10.1159/000146069 PG 9 WC Psychiatry SC Psychiatry GA 335VF UT WOS:000258318900007 PM 18635934 ER PT J AU Trivedi, MH Kocsis, JH Thase, ME Morris, DW Wisniewski, SR Leon, AC Gelenberg, AJ Klein, DN Niederehe, G Schatzberg, AF Ninan, PT Keller, MB AF Trivedi, Madhukar H. Kocsis, James H. Thase, Michael E. Morris, David W. Wisniewski, Stephen R. Leon, Andrew C. Gelenberg, Alan J. Klein, Daniel N. Niederehe, George Schatzberg, Alan F. Ninan, Philip T. Keller, Martin B. TI REVAMP - Research Evaluating the Value of Augmenting Medication with Psychotherapy: Rationale and Design SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE antidepressant; algorithm; pharmacotherapy; psychotherapy; augmentation; remission; response; measurement-based care; personalized care AB This report presents the rationale, design, and baseline sample characteristics for the REVAMP study. This project is a multisite clinical trial designed to evaluate the efficacy of augmenting state-of-the-art pharmacotherapy with psychotherapy in chronically depressed patients who fail to respond or respond incompletely to an initial trial of antidepressant medication. Background: Chronic forms of major depression disorder (cMDD) are longitudinally continuous forms of major depressive disorder (MDD), and may account for a significant portion of the societal burden of disease associated with MDD. Antidepressant medications and depression-focused psychotherapies have been shown to be effective for cMDD, though the majority fail to achieve remission following an acute course of treatment. There is a pressing need to evaluate whether the outcomes obtained from a well implemented medication algorithm combined with depression-focused psychotherapy can significantly enhance outcomes for cMDD. Rationale: Although there is evidence for the effectiveness of depression-focused psychotherapy for the treatment of cMDD, this is the first prospective, randomized, controlled trial investigating psychotherapy as an augmentation strategy for patients with cMDD incompletely responsive to a trial of antidepressant medication. Specific Aims: The REVAMP study has three specific aims: first, to compare the efficacy of adding psychotherapy to a medication change versus changing medication alone in chronic depressives with partial response or nonresponse to an initial trial of antidepressant medication; second, to test efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) as an augmentation strategy by comparing it to Supportive Psychotherapy (SP); and third, to test a hypothesized mechanism of therapeutic action of CBASP by examining whether patients receiving CBASP exhibit significantly greater improvements in social problem solving than patients receiving adjunctive SP or continued medication alone. As a subsidiary aim, the study also compares the effects of the three randomized treatments on psychosocial outcomes. Design: The study involves two 12-week phases. During Phase 1, patients with cMDD receive antidepressant monotherapy selected according to an algorithm that takes into account their prior treatment history. Their pattern of response is evaluated, those with no response at 8 weeks or less than a full response at 12 weeks advance to Phase 2. At the beginning of Phase 2, patients who did not respond to the initial antidepressant monotherapy during Phase 1 are switched to the next medication in the pharmacotherapy algorithm and randomly assigned in a 2:2: ratio to one of three treatment cells: 16 sessions of either CBASP (40% of randomizations) or SP (40%) added to pharmacotherapy, or medication alone (20%) with no added psychotherapy. Similarly, patients achieving a partial response during Phase 1 have their initial medication augmented with a second antidepressant agent during Phase 2 and are randomly assigned to either CBASP, SP, or medication alone. Patients who achieve remission during Phase 1 are not randomized to Phase 2, but rather are monitored monthly for an additional 12 weeks. Comment: Recent sequential treatment studies have provided state-of-the-art knowledge about the need for multiple steps in order to achieve remission. The current study, therefore, provides an important next step in understanding the role of depression-focused psychotherapy in a treatment algorithm so essential in the management of difficul-to-treat depression such as chronic forms of major depression. Psychopharmacology Bulletin. 2008; 41(4): 5-33. C1 [Trivedi, Madhukar H.; Morris, David W.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Kocsis, James H.; Leon, Andrew C.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY USA. [Thase, Michael E.] Univ Penn Sch Med, Philadelphia, PA USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Dept Psychiat, Pittsburgh, PA USA. [Gelenberg, Alan J.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Klein, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Niederehe, George] NIMH, Geriatr Res Branch, Bethesda, MD 20892 USA. [Schatzberg, Alan F.] Stanford Univ Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Ninan, Philip T.] Emory Univ Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, Collegeville, PA USA. [Keller, Martin B.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU Cornell University [UO1 MH62475]; University of Pittsburgh [UO1 MH61587]; University of Stony Brook [UO1 MH62546]; University of Texas Southwestern Medical Center [UO1 MH61562]; Emory University School of Medicine [UO1 MH63481]; University of Arizona [UO1 MH62465]; Brown Medical School [UO1 MH61590]; Stanford University [UO1 MH61504]; Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research MedAvante, Inc.; Neuronetics, Inc.; Novartis; Organon Inc.; Sepracor, Inc.; Shire US, Inc.; Transcept; Wyeth Pharmaceuticals; AstraZeneca; Bristol-Myers Squibb; Eli Lilly Co.; GlaxoSmithKline; Sepracor; American Psychiatric Publishing, Inc; Guilford Publications and Herald House FX Cornell University (UO1 MH62475): James H. Kocsis, M.D.; John C. Markowitz, M.D.; Andrew C. Leon, Ph.D.; Richard A. Friedman, M.D.; University of Pittsburgh (UO1 MH61587): Michael E. Thase, M.D.; Edward S. Friedman, M.D.; Robert H. Howland, M.D.; Stephen R. Wisniewski, Ph.D.; Jennifer Barkin, M.S.; University of Stony Brook (UO1 MH62546): Daniel N. Klein, Ph.D.; Dina Vivian, Ph.D.; Frank Dowling, M. D.; Thomas D'Zurilla, Ph.D.; University of Texas Southwestern Medical Center (UO1 MH61562): Madhukar H. Trivedi, M. D.; Prabha Sunderajan, M.D.; David W. Morris, Ph.D.; Beverly Kleiber, Ph.D.; Emory University School of Medicine (UO1 MH63481): Barbara O. Rothbaum, Ph.D.; Broadie Dunlop, M.D.; Philip T. Ninan, M.D.; Steven J. Garlow, M.D., Ph.D.; University of Arizona (UO1 MH62465): Alan J. Gelenberg, M.D.; John Misiazek, M.D.; Brown Medical School (UO1 MH61590): Martin B. Keller, M. D.; Ivan Miller, M.D.; Gabor Keitner, M. D.; Susan Raffa, Ph.D.; Stanford University (UO1 MH61504): Alan Schatzberg, M.D.; Bruce Arnow, Ph.D.; Rachel Manber, Ph.D.; Brent Solvason, M.D., Ph.D.; NIMH collaborators: George Niederehe, Ph.D; Louise Ritz, M.B.A.; Elizabeth Zachariah, M.S.; Madhukar H. Trivedi, M. D. has been a consultant or served on speakers bureaus for Abbott Laboratories, Inc.; Abdi Brahim; Akzo (Organon Pharmaceuticals Inc.); AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc.; Fabre-Kramer Pharmaceuticals, Inc. Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Neuronetics; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Sepracor; VantagePoint; and Wyeth-Ayerst Laboratories. He has received research support from the Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research MedAvante, Inc., Neuronetics, Inc., Novartis, Organon Inc., Sepracor, Inc., Shire US, Inc., Transcept, and Wyeth Pharmaceuticals. Dr Thase has received honoraria for talks sponsored by: AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., and Wyeth Pharmaceuticals. Dr Thase has received grants from Eli Lilly & Co., GlaxoSmithKline, and Sepracor. He has equity holdings in MedAvante, Inc and receives income from royalties from American Psychiatric Publishing, Inc., Guilford Publications and Herald House. NR 105 TC 4 Z9 4 U1 1 U2 5 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 4 BP 5 EP 33 PG 29 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HJ UT WOS:000207792800001 PM 19015627 ER PT J AU Davis, L Ward, LC Rasmusson, A Newell, JM Frazier, E Southwick, SM AF Davis, Lori Ward, L. Charles Rasmusson, Ann Newell, Jason M. Frazier, Elizabeth Southwick, Steven M. TI A Placebo-Controlled Trial of Guanfacine for the Treatment of Posttraumatic Stress Disorder in Veterans SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE posttraumatic stress disorder; guanfacine; noradrenergic; norepinephrine; pharmacologic treatment AB Objective: Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). alpha(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the alpha(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD. Experimental Design: Patients with chronic PTSD were randomized (1: 1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2-month, open-label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report). Principal Observations: There were no significant differences in the drug versus placebo responses for the clinician-administered or patient self-report outcome measures in this small sample of predominantly male combat veterans with PTSD. However, the medication was well tolerated. Conclusion: Similar to previous findings, this small pilot study failed to show differences in the response to guanfacine versus placebo in a small sample of predominantly male combat veterans with PTSD. Psychopharmacology Bulletin. 2008; 41(1): 8-18. C1 [Davis, Lori; Ward, L. Charles; Newell, Jason M.] VA Med Ctr, Tuscaloosa, AL 35404 USA. [Davis, Lori] Univ Alabama, Sch Med, Dept Psychiat, Birmingham, AL USA. [Davis, Lori] Univ Alabama, Sch Med, Dept Psychiat, Tuscaloosa, AL 35401 USA. [Rasmusson, Ann] Boston VA Healthcare Syst, Boston, MA USA. [Rasmusson, Ann; Southwick, Steven M.] VA Connecticut Hlth Care Syst, West Haven, CT USA. [Rasmusson, Ann; Southwick, Steven M.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Newell, Jason M.] Univ Alabama, Sch Social Work, Tuscaloosa, AL USA. [Frazier, Elizabeth] VA Med Ctr, San Francisco, CA USA. RP Davis, L (reprint author), VA Med Ctr, 151,3701 Loop Rd E, Tuscaloosa, AL 35404 USA. EM lori.davis@med.va.gov FU VA Merit Award; VA Research and Development FX This study was funded by a VA Merit Award (Principal Investigator Steven Southwick, MD) The authors acknowledge financial support of VA Research and Development and the following research coordinators and clinical raters involved with the collection of this data: Elizabeth Frazier, MS; Elizabeth B. Waldrop, RN; Sheila Essary, LPN; Stephanie K. Wallace, MS; Sandra Ambrose, MSN; and Raela Williford, Pharm.D. NR 21 TC 20 Z9 22 U1 0 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 1 BP 8 EP 18 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HF UT WOS:000207792400001 PM 18362867 ER PT J AU Busch, AB Frank, RG Sachs, G AF Busch, Alisa B. Frank, Richard G. Sachs, Gary TI Bipolar-I Depression Outpatient Treatment Quality and Costs in Usual Care Practice SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE quality of care; bipolar disorder; bipolar depression AB Objective: To examine the longitudinal usual care quality and costs of bipolar-I depression treatment in adults. Experimental Design: Observational study of claims data from a privately insured population, ages 18-64, diagnosed with bipolar-I depression (N = 925), treated in 1999 and 2000, examining depressed phase specific and annualized treatment quality (receipt of antimanic medication and/or psychotherapy). Treatment costs were calculated and stratified by quality. Principal Observations: Little than half (56%) of the patients diagnosed with bipolar-I depression received both an antimanic agent and psychotherapy during their acute phase depression treatment, whereas 15% received an antimanic agent without psychotherapy. Eighteen to 28% of spending was accounted for by treatment that did not meet the standards of practice guidelines-and two-thirds to three-quarters of it was treatment that included an antidepressant without an antimanic agent (care that is advised against by guidelines). Conclusions: Considerable resources were spent in care inconsistent with guidelines-much of that was care that could worsen the course of bipolar illness. This provides an opportunity for policy makers to develop mechanisms of quality improvement that redirect a substantial proportion of resource dollars to care that is more efficacious. Further, when conducting quality assessment and examining outcomes using administrative data, hospital admissions alone are an inadequate measure of bipolar disorder affective instability in claims data. Psychopharmacology Bulletin. 2008; 41(2): 24-39. C1 [Busch, Alisa B.] McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02478 USA. [Busch, Alisa B.; Sachs, Gary] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Busch, Alisa B.; Frank, Richard G.] Harvard Univ, Dept Hlth Care Policy, Med School, Cambridge, MA 02138 USA. [Sachs, Gary] Massachusetts Gen Hosp, Bipolar Mood Disorder Program, Boston, MA 02114 USA. RP Busch, AB (reprint author), McLean Hosp, Alcohol & Drug Abuse Treatment Program, Proctor Bldg,115 Mill St, Belmont, MA 02478 USA. EM abusch@hcp.med.harvard.edu FU National Institute of Mental Health [98 DS 001, R01MH62028, R01 MH069721, K01MH071714]; Dr. Ralph and Marian Falk Medical Research Trust; National Center on Minority Health and Health Disparities; Abbott; GSK; Janssen; NIMH; Memory; Repligen; Pfizer; Wyeth FX The authors gratefully acknowledge funding from the National Institute of Mental Health: 98 DS 001 (Systematic Treatment Enhancement Program-Bipolar Disorder (STEP-BD), R01MH62028 and R01 MH069721 (Drs. Busch and Frank), and K01MH071714 (Dr. Busch). Also, additional funding for Dr. Busch by the Dr. Ralph and Marian Falk Medical Research Trust and the National Center on Minority Health and Health Disparities is acknowledged. They are also grateful for the statistical consultation of Sharon-Lise Normand, PhD, and the programming expertise of Al Belanger and Katya Zelevinsky. Drs. Busch and Frank report no competing interests. Dr. Sachs has received grant/research support from: Abbott, GSK, Janssen, NIMH, Memory, Repligen, Pfizer, Wyeth; he has served as a consultant for Abbott, AstraZeneca, BMS, GSK, Lilly, Janssen, JDS, Memory, Merck, Repligen, Pfizer, Solvay, Wyeth (each under $ 10,000) and on the speakers' bureau of AstraZeneca, BMS, GSK, Lilly (each under $ 10,000). His spouse holds proprietary interest in company which trains and monitors clinical raters (Concordant Rater Systems, Inc.). NR 50 TC 7 Z9 7 U1 2 U2 3 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 2 BP 24 EP 39 PG 16 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HG UT WOS:000207792500005 PM 18668015 ER PT J AU Petersen, T Perlis, RH Ticknor, C Lohr, J Solvason, HB O'Reardon, JP Wohlreich, MM Andreotti, C Wilson, M Fava, M AF Petersen, Timothy Perlis, Roy H. Ticknor, Chris Lohr, Jim Solvason, H. Brent O'Reardon, John P. Wohlreich, Madelaine M. Andreotti, Charissa Wilson, Michael Fava, Maurizio TI Efficacy of Duloxetine for the Treatment of Depression: Relationship to Most Recent Antidepressant Trial SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE treatment-resistant depression; duloxetine; antidepressants; switch treatments; depression AB Objectives: To describe and examine, in a sample of depressed outpatients, the relationship between level of response to a previous SSRI or SNRI antidepressant trial and subsequent response to duloxetine hydrochloride. Experimental Design: Data collected from a multicenter trial that evaluated the safety and efficacy of duloxetine for the treatment of major depressive disorder were analyzed to determine the relationship between response to previous antidepressant treatment and degree of response to duloxetine. Eighty-two patients, with documented antidepressant usage history, were included in the analysis. Participants were required, at baseline of the duloxetine treatment protocol, to be >= 18 years of age and meet criteria for major depressive disorder. Patients, whose data were included in these analyses, were classified as belonging to one of the three groups based on the most recent antidepressant treatment received: nonresponders, partial responders, and responders without remission. Time to first response, first remission, sustained response, and sustained remission during the first 12 weeks of duloxetine treatment were compared across patient groups. Principal Observations: Response and remission with duloxetine treatment ranged between 57 and 68% and 29 and 57%, respectively, and did not differ significantly across previous response levels. An additional analysis, collapsing the partial responder and responder without remission groups, indicated significantly lower rates of remission in those patients who demonstrated nonresponse to the most recent antidepressant treatment. Conclusions: Findings suggest that patient's response to duloxetine, when used as a switch treatment, may not be significantly influenced by degree of response to the most recent antidepressant treatment. Psychopharmacology Bulletin. 2008; 41(1): 34-45. C1 [Petersen, Timothy; Andreotti, Charissa] Massachusetts Gen Hosp, Div Postgrad Educ, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Ticknor, Chris] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Lohr, Jim] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Solvason, H. Brent] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [O'Reardon, John P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Wohlreich, Madelaine M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Wilson, Michael] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Div Postgrad Educ, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM tpetersen@partners.org FU Eli Lilly and Company, Indianapolis, IN, USA FX Supported by Eli Lilly and Company, Indianapolis, IN, USA. NR 30 TC 1 Z9 1 U1 0 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 1 BP 34 EP 45 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HF UT WOS:000207792400003 PM 18362869 ER PT J AU Lipkovich, I Mallinckrodt, CH Prakash, A Nierenberg, AA AF Lipkovich, Ilya Mallinckrodt, Craig H. Prakash, Apurva Nierenberg, Andrew A. TI Addressing Methodological Issues in Studying Antidepressant Onset Efficacy Using Prespecified Sensitivity Analyses SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE onset of action; antidepressant; onset efficacy; study design; study methodology; noninferiority ID MAJOR DEPRESSIVE DISORDER; TRUE DRUG RESPONSE; PATTERN-ANALYSIS; RAPID-ONSET; CONTROLLED TRIALS; MISSING DATA; STRATEGIES; SCALE; FLUOXETINE; PLACEBO AB Objectives: Assessing antidepressant onset efficacy presents substantial methodological challenges. Most assessments of onset efficacy are based on post hoc analyses. This article presents a case study of a prospectively designed trial to compare antidepressant onset efficacy. Experimental Design: The current study design was compared with previously published criteria for an ideal onset of action study. Prospectively defined sensitivity analyses were used to assess whether results of the present study were influenced by the assumptions and decisions necessary to implement this study. Principal Observations: The study achieved its primary objective of establishing noninferiority between SNRI and SSRI. Sensitivity analyses suggested that results from the primary analysis were not influenced by patient population, outcome measure, cut-off for defining clinically meaningful sustained improvement, or analytical method. Although not all limitations could be addressed, appropriate conclusions could be drawn. For example, the study tested only one fixed dose of each drug; hence, conclusions are limited to those dosages and cannot be extrapolated across the entire dose ranges, as would be possible in the ideal study. Conclusion: This article illustrates that prospectively designed studies (as opposed to retrospective comparisons) can be implemented and sensitivity analyses can be used to address concerns regarding assumptions and arbitrary decisions. Psychopharmacology Bulletin. 2008; 41(2): 40-54. C1 [Lipkovich, Ilya] Eli Lilly & Co, Lilly Corp Ctr DC 0734, Lilly Res Labs, Indianapolis, IN 46285 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Mallinckrodt, CH (reprint author), Eli Lilly & Co, Lilly Corp Ctr DC 0734, Lilly Res Labs, Indianapolis, IN 46285 USA. EM cmallinc@lilly.com FU Eli Lilly and Company; Wyeth; GSK; BMS; Cyberonics; Lichtwer; Pfizer; Cederroth; Forest; Janssen; NARSAD; NIMH FX The authors thank Andrew C. Leon, Ph.D., for reviewing drafts of this manuscript and for providing critical review and feedback. This study was sponsored by Eli Lilly and Company. Dr. Nierenberg is an employee of Massachusetts General Hospital, is a consultant for Eli Lilly and Company, Shire, GSK, Innapharma, Genaissance, Sepracor, Novartis, and Somerset, and has received grant support from Eli Lilly and Company, Wyeth, GSK, BMS, Cyberonics, Lichtwer, Pfizer, Cederroth, Forest, Janssen, NARSAD, and NIMH, and has also received honoraria from Eli Lilly and Company, Wyeth, GSK, and Cyberonics. Drs. Lipkovich and Mallinckrodt and Ms. Prakash are stock shareholders and full-time employees of Eli Lilly and Company. NR 45 TC 0 Z9 0 U1 0 U2 0 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 2 BP 40 EP 54 PG 15 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HG UT WOS:000207792500006 PM 18668016 ER PT J AU Gyulai, L Bauer, MS Marangell, LB Dennehy, EB Thase, ME Otto, MW Zhang, HW Wisniewski, SR Miklowitz, DJ Rapaport, MH Baldassano, CF Sachs, GS AF Gyulai, Laszlo Bauer, Mark S. Marangell, Lauren B. Dennehy, Ellen B. Thase, Michael E. Otto, Michael W. Zhang, Hongwei Wisniewski, Stephen R. Miklowitz, David J. Rapaport, Mark H. Baldassano, Claudia F. Sachs, Gary S. CA STEP-BD Investigators TI Correlates of Functioning in Bipolar Disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE bipolar disorder; depression; psychosocial function; personality AB Objectives: Our primary aim was to describe unique correlates of functioning in bipolar disorder (BD). Experimental Design: The study included the first 500 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Patients were 41.9 +/- 12.7 years old, and diagnosed with bipolar I, II or NOS, verified by structured interview. Overall functionality was determined by the Range of Impaired Function Tool (LIFE-RIFT). Stepwise multiple regression analysis tested the non-redundant-independent-association of 28 variables on functioning. Principal Observations: Severity of depression symptoms was significantly and uniquely correlated with impaired functioning in the context of a wide variety of demographic and clinical variables, contributing 60.9% to the total variance in overall functioning (beta = 0.254, p = 0.0001). Substantial variance in function remains unexplained. Conclusions: Intensity of depressive symptoms is the major determinant of impaired functioning in bipolar disorder, but longitudinal analyses may further explain the substantial variance in function not explained by this large and comprehensive model. Treatments and outcome assessment for patients with bipolar disorders should consider both functional and symptomatic change. Psychopharmacology Bulletin. 2008; 41(4):51-64. C1 [Gyulai, Laszlo; Thase, Michael E.; Baldassano, Claudia F.] Univ Penn, Dept Psychiat, Bipolar Disorders Program, Philadelphia, PA 19104 USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Boston, MA USA. [Bauer, Mark S.] Vet Affairs Hlth Syst, Boston, MA USA. [Marangell, Lauren B.] Baylor Coll Med, Mood Disorders Ctr, Dept Psychiat, Houston, TX 77030 USA. [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. [Otto, Michael W.; Sachs, Gary S.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Partners Bipolar Res Program, Boston, MA 02115 USA. [Zhang, Hongwei; Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. [Miklowitz, David J.] Univ Colorado, Boulder, CO 80309 USA. [Rapaport, Mark H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Cedars Sinai Med Ctr,Dept Psychiat, Los Angeles, CA 90095 USA. RP Gyulai, L (reprint author), Univ Penn, Dept Psychiat, Bipolar Disorders Program, 3535 Market St,6th Floor,Suite 670, Philadelphia, PA 19104 USA. EM gyulai@mail.med.upenn.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU National Institute of Mental Health (NIMH), National Institutes of Health [N01MH80001]; J. and J. Rooney Research Fund; P. Kind Research Funds FX STEP-BD was funded with Federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH80001. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NIMH. The contents of this article were reviewed and approved by the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Steering Committee.; Additional detail on STEP-BD can be located at http://www.nimh. nih.gov/health/trials/practical/step-bd/questions-and-answers-for-the-sy stematic- treatment-enhancement-program-for-bipolar-disorderstep- bd-study-background.shtml.; Additional support was provided to Laszlo Gyulai by the J. and J. Rooney Research Fund and P. Kind Research Funds.; Dr. Marrangell is currently working at the Ely Lilly Company. NR 44 TC 11 Z9 11 U1 0 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 4 BP 51 EP 64 PG 14 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HJ UT WOS:000207792800003 PM 19015629 ER PT J AU Thase, ME AF Thase, Michael E. TI Are SNRIs More Effective than SSRIs? A Review of the Current State of the Controversy SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE depression; meta-analysis; antidepressants; SSRIs; SNRIs ID MAJOR DEPRESSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; VENLAFAXINE EXTENDED-RELEASE; ANTIDEPRESSANT CLINICAL-TRIALS; DRUG-ADMINISTRATION DATABASE; DOSE-RESPONSE RELATIONSHIP; META-REGRESSION ANALYSIS; DOUBLE-BLIND; BIPOLAR DEPRESSION; REMISSION RATES AB The selective serotonin reuptake inhibitors (SSRI) are widely considered to be the first choice for antidepressant therapy. There is evidence from inpatient studies dating to 1986, however, suggesting that the tricyclic antidepressant clomipramine, which inhibits reuptake of both serotonin and norepinephrine, may have greater efficacy than some SSRIs for severe depression. There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlled trials (RCTs), including the factors that limit their sensitivity to detect differences between active antidepressants, and meta-analysis to examine results of large sets of RCTs. Next, the results of RCTs and meta-analyses are reviewed. Although few individual studies report significant differences, meta-analyses consistently suggest that venlafaxine may have greater efficacy than the SSRIs as a class. The magnitude of this advantage is modest (i.e., differences in remission rates of 5-10%) and no advantage has been demonstrated versus escitalopram. The advantage for duloxetine versus selected SSRIs is limited to patients with more severe depression and the RCTs are flawed by use of minimum therapeutic doses of SSRIs. No evidence of an advantage is found in RCTs of milnacipran versus SSRIs. Even a modest difference in antidepressant efficacy-if sustained-may have important public health implications for the common, disabling condition of depression. Nevertheless, differences in tolerability and cost also must be considered when choosing therapies. Psychopharmacology Bulletin. 2008; 41(2): 58-85. C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 113 TC 30 Z9 32 U1 1 U2 10 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 2 BP 58 EP 85 PG 28 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HG UT WOS:000207792500007 PM 18668017 ER PT J AU Dillon, DG Holmes, AJ Jahn, AL Bogdan, R Wald, LL Pizzagalli, DA AF Dillon, Daniel G. Holmes, Avram J. Jahn, Allison L. Bogdan, Ryan Wald, Lawrence L. Pizzagalli, Diego A. TI Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing SO PSYCHOPHYSIOLOGY LA English DT Article DE reward; motivation; anticipation; consumption; emotion; fMRI ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; HUMAN ORBITOFRONTAL CORTEX; MEDIAL FRONTAL-CORTEX; DECISION-MAKING; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; REWARD CIRCUITRY; EXPERIMENTAL-DESIGN; DOPAMINE NEURONS AB Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n = 13 and n = 8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed. C1 [Dillon, Daniel G.; Holmes, Avram J.; Bogdan, Ryan; Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Jahn, Allison L.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Pizzagalli, DA (reprint author), Harvard Univ, Dept Psychol, 1220 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM dap@wjh.harvard.edu RI Wald, Lawrence/D-4151-2009; OI Dillon, Daniel/0000-0002-1977-700X; Bogdan, Ryan/0000-0002-1430-1045 FU NIMH NIH HHS [R01 MH068376, R01 MH068376-01A1, R01 MH68376] NR 81 TC 61 Z9 64 U1 5 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2008 VL 45 IS 1 BP 36 EP 49 DI 10.1111/j.1469-8986.2007.00594.x PG 14 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 254NG UT WOS:000252592700005 PM 17850241 ER PT J AU Jones, NP Siegle, GJ Muelly, ER Haggerty, A Ghinassi, F Thase, ME AF Jones, Neil P. Siegle, Greg J. Muelly, Emilie R. Haggerty, Agnes Ghinassi, Frank Thase, Michael E. TI Pupillary correlates of rumination during a frustrating serial working memory task in unipolar depression SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 01-05, 2008 CL Austin, TX SP Soc Psychophysiol Res C1 [Jones, Neil P.; Siegle, Greg J.; Haggerty, Agnes; Ghinassi, Frank] Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Jones, Neil P.; Siegle, Greg J.; Haggerty, Agnes; Ghinassi, Frank] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Muelly, Emilie R.] Penn State Univ, University Pk, PA 16802 USA. [Thase, Michael E.] Univ Penn, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2008 VL 45 SU 1 BP S80 EP S80 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 347LX UT WOS:000259144200332 ER PT J AU Sandt, AR Sloan, DM AF Sandt, Arthur R. Sloan, Denise M. TI Affectively modulated postauricular responding and dysphoria SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 01-05, 2008 CL Austin, TX SP Soc Psychophysiol Res C1 [Sandt, Arthur R.] Temple Univ, Philadelphia, PA 19122 USA. [Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2008 VL 45 SU 1 BP S43 EP S43 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 347LX UT WOS:000259144200184 ER PT J AU Kinder, LS Bradley, KA Katon, WJ Ludman, E McDonell, MB Bryson, CL AF Kinder, Leslie S. Bradley, Katharine A. Katon, Wayne J. Ludman, Evette McDonell, Mary B. Bryson, Chris L. TI Depression, posttraumatic stress disorder, and mortality SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; posttraumatic stress disorder; mortality; veterans ID NATIONAL-COMORBIDITY-SURVEY; ALCOHOL-CONSUMPTION QUESTIONS; PRIMARY-CARE PATIENTS; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; COMMUNITY SAMPLE; VETERANS HEALTH; SCREENING-TEST; US VETERANS; EPIDEMIOLOGY AB Objective: To determine whether a history of depression and/or posttraumatic stress disorder (PTSD) is associated with all-cause mortality in primary care patients over an average of 2 years. Methods: Patients from seven Department of Veterans Affairs medical centers completed mailed questionnaires. Depression and PTSD status were determined from patient self-report of a prior diagnosis and/or electronic administrative data. Date of death was ascertained from Veterans Health Information Systems and Technology Architecture and the Department of Veterans Affairs' Beneficiary Identification and Records Locator System. Results: Among 35,715 primary care patients, those with a history of depression without a history of PTSD (n = 6876) were at increased risk of death over an average of 2 years compared with patients with neither depression nor PTSD after adjustment for demographic variables, health behaviors, and medical comorbidity (hazard ratio (HR) = 1.17; 95% Confidence Interval (CI) = 1.06-1.28). However, patients with a history of PTSD without a history of depression (n = 748) were not at increased risk of death compared with patients with neither depression nor PTSD (HR = 0.841; 95% CI = 0.63-1.13). Patients with a history of both (n = 3762) were at increased risk of death after adjustment for demographic factors, although not after additional adjustment for health behaviors and medical comorbidity (HR = 0.90; 95% CI = 0.78-1.04). Conclusions: In a large sample of veterans, a prior diagnosis of depression, but not PTSD, was associated with an increased risk of death over an average of 2 years after adjusting for age, demographic variables, health behaviors, and medical comorbidity. C1 [Kinder, Leslie S.; Bradley, Katharine A.; McDonell, Mary B.; Bryson, Chris L.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Kinder, Leslie S.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bradley, Katharine A.; Bryson, Chris L.] Univ Washington, Dept Med, Seattle, WA USA. [Katon, Wayne J.; Ludman, Evette] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Ludman, Evette] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Bradley, Katharine A.] VA Ctr Excellence Substance Abuse Treatment & Edu, Seattle, WA USA. [Bradley, Katharine A.] VA Med Ctr, Primary & Specialty Med Care, Seattle, WA USA. RP Kinder, LS (reprint author), 8506 SE 72nd St, Mercer Isl, WA 98040 USA. EM lskinder@stanfordalumni.org NR 33 TC 25 Z9 25 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2008 VL 70 IS 1 BP 20 EP 26 DI 10.1097/PSY.0b013e31815aac93 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 253GM UT WOS:000252506700004 PM 17991816 ER PT J AU Caplan, JP Epstein, LA Stern, TA AF Caplan, Jason P. Epstein, Lucy A. Stern, Theodore A. TI Consultants' conflicts: A case discussion of differences and their resolution SO PSYCHOSOMATICS LA English DT Review ID TEMPORAL-LOBE EPILEPSY; NEUROLOGY; PSYCHIATRY AB Conflicts among consultants are frequent in general hospitals. Unfortunately, such disputes are rarely resolved to the satisfaction of all concerned. The authors discuss the conflicts that may arise among consultants and review techniques that can lead to more effective collaboration. Authors review the literature on consultants' conflicts and discuss strategies for their resolution. They present the case of a man with neuropsychiatric symptoms and discuss how practitioners of psychiatry and neurology often approach differential diagnosis, work-up, and treatment of challenging cases. The consultants were able to find several points of agreement and generated a workable plan that led to improvement in the patient's symptoms. Conflict among medical consultants is poorly described in the literature. However, an understanding of conflict and strategies for its resolution can lead to improved patient care. Conflict is a common and virtually unavoidable aspect of multidisciplinary care. However effective tools exist that can help physicians embrace, rather than avoid, conflict, and lead to more effective collaboration. Effective management of interdisciplinary conflict improves communication, assists in medical decision-making, and, most importantly, improves the delivery of patient care. C1 Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Caplan, JP (reprint author), Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. EM jpcaplan@gmail.com NR 24 TC 5 Z9 5 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2008 VL 49 IS 1 BP 8 EP 13 DI 10.1176/appi.psy.49.1.8 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 248KC UT WOS:000252151200003 PM 18212170 ER PT J AU Nierenberg, AA Smoller, JW Eidelman, P Wu, YP Tilley, CA AF Nierenberg, Andrew A. Smoller, Jordan W. Eidelman, Polina Wu, Yelena P. Tilley, Claire A. TI Critical thinking about adverse drug effects: Lessons from the psychology of risk and medical decision-making for clinical psychopharmacology SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE adverse drug effects; psychology of risk; psychopharmacology ID RANDOMIZED CONTROLLED-TRIALS; CYTOCHROME-P450 SYSTEM; CHRONIC-SCHIZOPHRENIA; BUPROPION SR; ZIPRASIDONE; OLANZAPINE; PROBABILITY; INFORMATION; SERTRALINE; JUDGMENT AB Systematic biases in decision-making have been well characterized in medical and nonmedical fields but mostly ignored in clinical psychopharmacology. The purpose of this paper is to sensitize clinicians who prescribe psychiatric drugs to the issues of the psychology of risk, especially as they pertain to the risk of side effects. Specifically, the present analysis focuses on heuristic organization and framing effects that create cognitive biases in medical practice. Our purpose is to increase the awareness of how pharmaceutical companies may influence physicians by framing the risk of medication side effects to favor their products. Copyright (c) 2008 S. Karger AG, Basel. C1 [Nierenberg, Andrew A.; Eidelman, Polina; Wu, Yelena P.; Tilley, Claire A.] Harvard Univ, Depression Clin & Res Programs, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Eidelman, Polina; Wu, Yelena P.; Tilley, Claire A.] Harvard Univ, Bipolar Clin & Res Program, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smoller, Jordan W.] Harvard Univ, Psychiat Genet Program Mood & Anxiety Disorders, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Depression Clin & Res Programs, Sch Med, Massachusetts Gen Hosp, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM anierenberg@partners.org NR 60 TC 11 Z9 11 U1 4 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2008 VL 77 IS 4 BP 201 EP 208 DI 10.1159/000126071 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 297AC UT WOS:000255586300003 PM 18418026 ER PT J AU Howland, RH Schettler, PJ Rapaport, MH Mischoulon, D Schneider, T Fasiczka, A Delrahiem, K Maddux, R Lightfoot, M Nierenberg, AA AF Howland, Robert H. Schettler, Pamela J. Rapaport, Mark Hyman Mischoulon, David Schneider, Trisha Fasiczka, Amy Delrahiem, Katia Maddux, Rachel Lightfoot, Michael Nierenberg, Andrew A. TI Clinical features and functioning of patients with minor depression SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE minor depression; depressive disorders; psychosocial function; depressive symptoms ID OLDER MEDICAL INPATIENTS; QUALITY-OF-LIFE; MAJOR DEPRESSION; PRIMARY-CARE; SUBSYNDROMAL DEPRESSION; SUBTHRESHOLD DEPRESSION; SERVICE UTILIZATION; MENTAL-DISORDERS; ELDERLY-PATIENTS; CONTROLLED-TRIAL AB Background: The two essential features of minor depression are that it has fewer symptoms than major depression and that it is less chronic than dysthymia. This study describes the clinical features and functioning of outpatients with minor depression. Methods: Subjects with minor depression (with and without a prior history of major depression) were recruited through clinical referrals and community advertising. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the 17-item Hamilton Rating Scale for Depression (HAM-D), the Inventory of Depressive Symptom-atology-Self Report (IDS-SR) and Clinician Rated (IDS-C) scales, the Global Assessment of Functioning (GAF) scale, the Medical Outcomes Study 36-item Short-Form scale (MOS), and the Clinical Global Impressions Severity Scale (CGI). Data from previously published studies of major depression, minor depression, and normal controls were compared to our data set. Results: Minor depression is characterized primarily by mood and cognitive symptoms rather than vegetative symptoms; the functional impairment associated with minor depression is as severe as for major depression in several areas; minor depression occurs either independently of major depression or as a stage of illness during the long-term course of major depression, and minor depression patients with and without a history of major depression have similar levels of depressive severity and functional impairment. Conclusions: These findings support the notion that minor depression is an important clinical entity that fits within the larger spectrum of depressive disorders. Copyright (c) 2008 S. Karger AG, Basel. C1 [Howland, Robert H.; Schneider, Trisha; Fasiczka, Amy; Lightfoot, Michael] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Schettler, Pamela J.; Rapaport, Mark Hyman; Delrahiem, Katia; Maddux, Rachel] Cedars Sinai Med Ctr, Dept Psychiat, Los Angeles, CA 90048 USA. [Schettler, Pamela J.; Mischoulon, David; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Howland, RH (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM HowlandRH@upmc.edu RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU National Institute of Mental Health; National Center for Complementary and Alternative Medicine [MH-061394] FX This project was funded by the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine (Grant MH-061394). NR 47 TC 40 Z9 40 U1 3 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2008 VL 77 IS 6 BP 384 EP 389 DI 10.1159/000151519 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 351SI UT WOS:000259445800008 PM 18716424 ER PT J AU Biddinger, PD Cadigan, RO Auerbach, BS Burstein, JL Savoia, E Stoto, MA Koh, HK AF Biddinger, Paul D. Cadigan, Rebecca Orfaly Auerbach, Bruce S. Burstein, Jonathan L. Savoia, Elena Stoto, Michael A. Koh, Howard K. TI On linkages: Using exercises to identify systems-level preparedness challenges SO PUBLIC HEALTH REPORTS LA English DT Article ID PUBLIC-HEALTH PREPAREDNESS; EMERGENCY PREPAREDNESS; TABLETOP C1 [Biddinger, Paul D.; Cadigan, Rebecca Orfaly; Auerbach, Bruce S.; Burstein, Jonathan L.; Savoia, Elena; Stoto, Michael A.; Koh, Howard K.] Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, Div Publ Hlth Practice, Boston, MA 02115 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Auerbach, Bruce S.] Sturdy Mem Hosp, Emergency & Ambulatory Serv, Attleboro, MA USA. [Burstein, Jonathan L.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Burstein, Jonathan L.] Massachusetts Dept Publ Hlth, Off Emergency Med Serv, Boston, MA USA. [Stoto, Michael A.] Georgetown Univ, Sch Nursing & Hlth Studies, Hlth Serv Adm & Populat Hlth, Washington, DC USA. RP Cadigan, RO (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, Div Publ Hlth Practice, 677 Huntington Ave,Landmark Ctr,3rd Floor E, Boston, MA 02115 USA. EM rcadigan@hsph.harvard.edu FU ODCDC CDC HHS [U90/CCU124242-03] NR 17 TC 13 Z9 13 U1 0 U2 3 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2008 VL 123 IS 1 BP 96 EP 101 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 240FF UT WOS:000251571900017 PM 18348486 ER PT J AU Bresolin, L McLoud, TC Becker, GJ Kwakwa, F AF Bresolin, Linda McLoud, Theresa C. Becker, Gary J. Kwakwa, Francis TI Education techniques for lifelong learning - International variations in initial certification and maintenance of certification in radiology: A multinational survey SO RADIOGRAPHICS LA English DT Article AB A survey was sent to representatives of national and regional radiology societies around the world regarding the status of certification, maintenance of certification (MOC), and continuing medical education (CME) requirements. Data were forthcoming from 24 countries (response rate, 71%), including the United States. The survey results indicated that most responding countries now have a standardized process and requirements for initial certification of diagnostic and therapeutic radiologists. Similarly, most reporting countries now have some form of mandatory CME, although the degree to which compliance is tracked varies. There is considerable heterogeneity in what these countries require for recertification or MOC, and the development of such requirements is cited as a goal for many of the countries. The standardization and institutionalization of certification and recertification requirements is in rapid evolution globally. C1 [Bresolin, Linda] Johnson & Johnson, New Brunswick, NJ 08933 USA. [Bresolin, Linda] Edwards Lifesci, Irvine, CA USA. [Bresolin, Linda; Kwakwa, Francis] Radiol Soc N Amer, Oak Brook, IL 60523 USA. [McLoud, Theresa C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Becker, Gary J.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. RP Bresolin, L (reprint author), Johnson & Johnson, New Brunswick, NJ 08933 USA. EM bresolin@rsna.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2008 VL 28 IS 1 BP 13 EP 20 DI 10.1148/rg.281075176 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251VF UT WOS:000252402900004 PM 18203927 ER PT J AU Kalva, SP Thabet, A Wicky, S AF Kalva, Sanjeeva P. Thabet, Ashraf Wicky, Stephan TI Recent advances in transarterial therapy of primary and secondary liver malignancies SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; ART BRACHYTHERAPY TREATMENT; RANDOMIZED CONTROLLED TRIAL; Y-90 MICROSPHERE THERAPY; (90)YTTRIUM MICROSPHERES; HEPATIC MALIGNANCY; COLORECTAL-CANCER; TUMOR RESPONSE; CHEMOEMBOLIZATION; METASTASES AB The management of liver malignancies presents many challenges. Few patients with primary hepatocellular carcinoma or metastatic disease of the liver are eligible for surgery, which is the only curative therapeutic option. Because the hepatic tumor burden is often a determinant of eligibility for surgery and is a primary contributor to morbidity and mortality, an increasing number of innovative techniques based on the transarterial administration of liver-directed drug-eluting or radiationemitting microspheres are being tested for use in cytoreductive and palliative therapy. The delivery of therapy via a transarterial route takes advantage of the fact that hepatic malignancies are primarily supplied by the hepatic artery. The early results of clinical trials are promising; the clinical effectiveness and safety of drug-eluting and yttrium-90-bearing microspheres have been demonstrated; however, further clinical investigation is needed to verify a benefit in survival. Transarterially administered gene therapy holds promise but is still in the early stages of investigation. For all transarterial therapies, the outcome depends heavily on meticulous patient selection, careful preparation and administration of therapy, and early and regular follow-up evaluations by using an interdisciplinary approach. C1 [Kalva, Sanjeeva P.; Thabet, Ashraf; Wicky, Stephan] Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Intervent, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Intervent, Gray 2,55 Fruit St,GRB 290, Boston, MA 02114 USA. EM skalva@partners.org NR 60 TC 31 Z9 35 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2008 VL 28 IS 1 BP 101 EP 117 DI 10.1148/rg.281075115 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251VF UT WOS:000252402900012 PM 18203933 ER PT J AU Catalano, OA Sahani, DV Kalva, SP Cushing, MS Hahn, PF Brown, JJ Edelman, RR AF Catalano, Onofrio A. Sahani, Dushyant V. Kalva, Sanjeeva P. Cushing, Matthew S. Hahn, Peter F. Brown, Jeffery J. Edelman, Robert R. TI MR imaging of the gallbladder: A pictorial essay SO RADIOGRAPHICS 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 MAGNETIC-RESONANCE CHOLANGIOGRAPHY; BILIARY-ENTERIC ANASTOMOSES; BILE-DUCT STRICTURES; ACUTE CHOLECYSTITIS; XANTHOGRANULOMATOUS CHOLECYSTITIS; MIRIZZI-SYNDROME; MANGAFODIPIR TRISODIUM; 1.5 T; CARCINOMA; ADENOMYOMATOSIS AB The gallbladder serves as the repository for bile produced in the liver. However, bile within the gallbladder may become supersaturated with cholesterol, leading to crystal precipitation and subsequent gallstone formation. The most common disorders of the gallbladder are related to gallstones and include symptomatic cholelithiasis, acute and cholecystitis, and carcinoma of the gallbladder. Other conditions that can affect the gallbladder include biliary dyskinesia (functional), adenomyomatosis (hyperplastic), and postoperative changes or complications (iatrogenic). Ultrasonography (US) has been the traditional modality for evaluating gallbladder disease, primarily owing to its high sensitivity and specificity for both stone disease and gallbladder inflammation. US performed before and after ingestion of a fatty meal may also be useful for functional evaluation of the gallbladder. However, US is limited by patient body habitus, with degradation of image quality and anatomic detail in obese individuals. With the advent of faster an more efficient imaging techniques, magnetic resonance (MR) imaging has assumed an increasing role as an adjunct modality for gallbladder imaging, primarily in patients who are incompletely assessed with US. MR imaging allows simultaneous anatomic and physiologic assessment of the gallbladder and biliary tract in both initial evaluation of disease and examination of the postoperative patient. This assessment is accomplished chiefly through the use of MR imaging contrast agents excreted preferentially via the biliary system. C1 [Catalano, Onofrio A.; Sahani, Dushyant V.; Kalva, Sanjeeva P.; Cushing, Matthew S.; Hahn, Peter F.] Massachusetts Gen Hosp, Div Gastrointestinal Radiol, Dept Radiol, Boston, MA 02114 USA. [Brown, Jeffery J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Edelman, Robert R.] Northwestern Univ, Sch Med, Dept Radiol, Evanston, IL USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal Radiol, Dept Radiol, WHT 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 61 TC 36 Z9 40 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2008 VL 28 IS 1 BP 135 EP 155 DI 10.1148/rg.281065183 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251VF UT WOS:000252402900014 PM 18203935 ER PT J AU Viswanathan, AN Buttin, BM Kennedy, AM AF Viswanathan, Akila N. Buttin, Barbara M. Kennedy, Anne M. TI Oncodiagnosis Panel: 2006 - Ovarian, cervical, and endometrial cancer SO RADIOGRAPHICS LA English DT Editorial Material ID GYNECOLOGIC-ONCOLOGY-GROUP; STAGE-III OVARIAN; PELVIC RADIATION-THERAPY; DOSE-RATE BRACHYTHERAPY; INTRAPERITONEAL CHEMOTHERAPY; RANDOMIZED-TRIAL; RADICAL HYSTERECTOMY; VAGINAL RECURRENCE; CARCINOMA; CISPLATIN C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Buttin, Barbara M.] Northeastern Univ, Feinberg Sch Med, Div Gynecol Oncol, Chicago, IL USA. [Kennedy, Anne M.] Univ Utah, Hlth Sci Ctr, Dept Radiol, Salt Lake City, UT USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 46 TC 2 Z9 2 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2008 VL 28 IS 1 BP 289 EP 307 DI 10.1148/rg.281075134 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251VF UT WOS:000252402900026 PM 18444279 ER PT J AU Kalra, MK Singh, S Blake, MA AF Kalra, Mannudeep K. Singh, Sarabjeet Blake, Michael A. TI CT of the urinary tract: Turning attention to radiation dose SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID DUAL-ENERGY CT; NOISE-REDUCTION FILTERS; TUBE CURRENT MODULATION; COMPUTED-TOMOGRAPHY; RENAL DONORS; CANCER-RISK; IMAGES; ABDOMEN; STONES; MDCT AB Expanding applications and uses of CT have fueled concerns about possible increases in the risk of radiation-induced cancer. This article reviews several strategies for optimizing the radiation dose necessary for adequate CT imaging of the urinary tract. C1 [Kalra, Mannudeep K.; Singh, Sarabjeet; Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kalra, MK (reprint author), 25 New Chardon St,Suite 400, Boston, MA 02114 USA. EM mkalra@partners.org NR 47 TC 4 Z9 4 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 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP 1 EP + DI 10.1016/j.rcl.2008.01.002 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200002 PM 18328876 ER PT J AU Blake, MA Kalra, MK AF Blake, Michael A. Kalra, Mannudeep K. TI Genitourinary tract imaging - Preface SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Blake, Michael A.; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org; mkalra@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP XI EP XII DI 10.1016/j.rcl.2008.02.001 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200001 PM 18328875 ER PT J AU He, W Fischman, AJ AF He, Wei Fischman, Alan J. TI Nuclear Imaging in the Genitourinary tract: Recent advances and future directions SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID GLOMERULAR-FILTRATION-RATE; RENAL-ARTERY STENOSIS; CONGENITAL UNILATERAL HYDRONEPHROSIS; DIRECT RADIONUCLIDE CYSTOGRAPHY; MAGNETIC-RESONANCE UROGRAPHY; F+0 DIURESIS RENOGRAPHY; PATLAK PLOT TECHNIQUE; CONTRAST-ENHANCED CT; UPPER URINARY-TRACT; CAPTOPRIL RENOGRAPHY AB For almost three decades, noninvasive radionuclide procedures for the evaluation of renal disease have been important components of nuclear medicine practice. With the introduction of new imaging agents and procedures, these techniques can provide valuable data on perfusion and function of individual kidneys. In general, these procedures are easy to per-form and carry a low radiation burden and sedation is not required. Moreover, radionuclide imaging of the genitourinary tract has become an invaluable asset to clinicians in the evaluation of renal parenchyma and urologic abnormalities. C1 [He, Wei; Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu NR 141 TC 7 Z9 7 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP 25 EP + DI 10.1016/j.rcl.2008.01.006 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200004 PM 18328878 ER PT J AU Uppot, RN Gervais, DA Mueller, PR AF Uppot, Raul N. Gervais, Debra A. Mueller, Peter R. TI Interventional uroradiology SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID GUIDED PROSTATE BIOPSY; NEGATIVE PREDICTIVE-VALUE; RENAL-CELL-CARCINOMA; PERCUTANEOUS SUPRAPUBIC CYSTOSTOMY; TERM BLADDER DRAINAGE; ADRENAL BIOPSY; RADIOFREQUENCY ABLATION; NEEDLE-BIOPSY; COMPUTERIZED-TOMOGRAPHY; PATIENT-MANAGEMENT AB With advances in imaging capabilities and percutaneous instruments, many urologic diseases that were once managed surgically are now managed with minimally invasive image-guided techniques. Interventional uroradiology has evolved from simple renal biopsies for diagnostic confirmation, to percutaneous management of stones, to ablation of renal and adrenal tumors. Central to this evolution is the close cooperation with the urologist and nephrologist, each of whom provides specific skill sets and knowledge that can be used to successfully manage the patient. The purpose of this article is to detail the wide range of image-guided interventional techniques, including a discussion of indications, methods, success rates, and complications. C1 [Uppot, Raul N.; Gervais, Debra A.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Uppot, RN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM ruppot@partners.org NR 66 TC 7 Z9 7 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP 45 EP + DI 10.1016/j.rcl.2008.01.010 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200005 PM 18328879 ER PT J AU Blake, MA Holalkere, NS Boland, GW AF Blake, Michael A. Holalkere, Nagaraj-Setty Boland, Giles W. TI Imaging techniques for adrenal lesion characterization SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CONTRAST-ENHANCED CT; POSITRON-EMISSION-TOMOGRAPHY; CHEMICAL-SHIFT MR; DUAL-ENERGY CT; INITIAL-EXPERIENCE; HISTOGRAM ANALYSIS; F-18-FDG PET/CT; UNENHANCED CT; MASSES; ADENOMAS AB Imaging of the adrenal gland for characterization of adrenal lesions has made tremendous strides and new technologies continue to evolve. This article highlights the anatomic and physiologic imaging principles that underpin current major adrenal imaging modalities and the new techniques becoming available. This article focuses primarily on incidental adrenal lesions, which are encountered more frequently with increasing use of imaging. This article concludes with a brief discussion of the role of adrenal biopsy, performed less frequently because of the success of these noninvasive adrenal imaging advances. C1 [Blake, Michael A.; Holalkere, Nagaraj-Setty; Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Blake, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org NR 76 TC 12 Z9 16 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP 65 EP + DI 10.1016/j.rcl.2008.01.003 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200006 PM 18328880 ER PT J AU Singh, AK Sahani, DV AF Singh, Anand K. Sahani, Dushyant V. TI Imaging of the and transplant renal donor recipient SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID MULTIDETECTOR ROW CT; ARTERY STENOSIS; LAPAROSCOPIC NEPHRECTOMY; PREOPERATIVE EVALUATION; VEIN THROMBOSIS; MR-ANGIOGRAPHY; MDCT; ALLOGRAFTS; ULTRASOUND; SONOGRAPHY AB Renal transplant remains the mainstay of the treatment of end-stage renal disease. With improvement in management strategies and the diverse imaging options, the yearly survival of recipients with functional kidneys has improved significantly. This improved survival is attributed to factors such as immunosuppressive therapy planning in recipients, human leukocyte antigen matching, surgeon experience, and recipient's age. Transplantation offers the closest thing to a normal state if the transplanted kidney can replace the failed kidneys. Living-donor kidney transplants are playing a vital role in bridging the gap between decreased supply of, and increased demand for, kidneys for transplant. Early detection and characterization of complications in the recipient are of immense clinical relevance, allowing timely intervention to prevent graft failure. C1 [Singh, Anand K.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Singh, Anand K.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 2-270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 38 TC 8 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2008 VL 46 IS 1 BP 79 EP + DI 10.1016/j.rcl.2008.01.009 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285DT UT WOS:000254758200007 PM 18328881 ER PT J AU Thrall, JH AF Thrall, James H. TI Theresa C. McLoud, MD, President, Radiological Society of North America, 2008 SO RADIOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZFND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 9 EP 10 DI 10.1148/radiol.2461071699 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300003 ER PT J AU Lu, MT Cai, TX Ersoy, H Whitmore, AG Quiroz, R Goldhaber, SZ Rybicki, FJ AF Lu, Michael T. Cai, Tianxi Ersoy, Hale Whitmore, Amanda G. Quiroz, Rene Goldhaber, Samuel Z. Rybicki, Frank J. TI Interval increase in right-left ventricular diameter ratios at CT as a predictor of 30-day mortality after acute pulmonary embolism: Initial experience SO RADIOLOGY LA English DT Article; Proceedings Paper CT 92nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 2006 CL Chicago, IL SP Radiol Soc N Amer ID BRAIN NATRIURETIC PEPTIDE; HELICAL COMPUTED-TOMOGRAPHY; RISK STRATIFICATION; PROGNOSTIC ROLE; DYSFUNCTION SECONDARY; TROPONIN-T; ECHOCARDIOGRAPHY; ANGIOGRAPHY; THROMBOLYSIS; ENLARGEMENT AB Purpose: To retrospectively determine if the interval increase of right ventricular-left ventricular (RV/LV) diameter ratio from negative prior to positive current computed tomographic (CT) examination findings for pulmonary embolism (PE) is more accurate for predicting 30-day mortality than positive CT ratio alone, by using patient 30-day mortality as reference standard. Materials and Methods: This IRB-approved, HIPAA-compliant study had waiver of informed consent and retrospectively reviewed 50 patients (19 men, 31 women; mean age, 60 years) with negative prior and positive current CT findings for acute PE (median interval, 63 days). Interval increase was defined as percentage change in RV/LV diameter ratio by using reformatted four-chamber views. Receiver operating characteristic (ROC) analysis compared the interval increase with the RV/LV diameter ratio from the positive findings alone for PE-related and all-cause mortality. Results: Twelve (24%) patients died in 30 days; nine were PE-related. The interval increase was significantly more accurate overall than the ratio from the positive study alone for PE-related (area under the ROC curve [AUC] = 0.95 vs 0.73, P = .003) and all-cause (AUC = 0.81 vs 0.66, P = .05) mortality. The respective sensitivity, specificity, positive predictive value, and negative predictive value were 0.78 (seven of nine; 95% confidence interval [CI]: 0.43, 1.00), 0.93 (38 of 41; 95% CI: 0.83, 1.00), 0.70 (seven of 10; 95% CI: 0.38, 1.00), and 0.95 (38 of 40; 95% CI: 0.87, 1.00) for PE-related mortality (interval increase, > 18%) and 0.75 (nine of 12; 95% CI: 0.49, 1.00), 0.89 (34 of 38; 95% CI: 0.80, 0.99), 0.69 (nine of 13; 95% CI: 0.44, 0.95), and 0.92 (34 of 37; 95% CI: 0.83, 1.00) for all-cause mortality (interval increase, > 15%). At target sensitivity (0.75), specificity of interval increase was significantly higher than from positive scans alone for both PE-related (0.93 vs 0.59, P = .001) and all-cause (0.89 vs 0.58, P = .05) mortality. Conclusion: The interval increase in four-chamber RV/LV diameter ratio is more accurate than the diameter ratio of the CT examination with with positive findings for PE alone for mortality prediction after acute PE. (c) RSNA, 2008. C1 [Lu, Michael T.; Ersoy, Hale; Whitmore, Amanda G.; Rybicki, Frank J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Goldhaber, Samuel Z.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Lu, Michael T.; Cai, Tianxi; Ersoy, Hale; Whitmore, Amanda G.; Quiroz, Rene; Goldhaber, Samuel Z.; Rybicki, Frank J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cai, Tianxi] Harvard Univ, Dept Biostat, Boston, MA USA. [Quiroz, Rene] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Rybicki, FJ (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM frybicki@partners.org NR 32 TC 32 Z9 32 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 281 EP 287 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300036 PM 18096540 ER PT S AU Berson, EL AF Berson, Eliot L. BE Anderson, RE LaVail, MM Hollyfield, JG TI Retinal degenerations: Planning for the future SO RECENT ADVANCES IN RETINAL DEGENERATION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 12th International Symposium on Retinal Degeneration CY OCT, 2006 CL Bariloche, ARGENTINA ID VITAMIN-A SUPPLEMENTATION; FACTOR-H POLYMORPHISM; RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; DOCOSAHEXAENOIC ACID; GYRATE ATROPHY; CLINICAL-TRIAL; GENE; PREVALENCE; PROTEIN C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM Linda_Berard@meei.harvard.edu FU NEI NIH HHS [EY00169] NR 44 TC 6 Z9 7 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-74902-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 613 BP 21 EP 35 PG 15 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BHF26 UT WOS:000252649500002 PM 18188925 ER PT S AU Shields, AE McGinn-Shapiro, M Fronstin, P AF Shields, Alexandra E. McGinn-Shapiro, Mary Fronstin, Paul BE Kaler, SG Rennert, OM TI Trends in private insurance, Medicaid/State Children's Health Insurance Program, and the Healthcare safety net - Implications for vulnerable populations and health disparities SO REDUCING THE IMPACT OF POVERTY ON HEALTH AND HUMAN DEVELOPMENT: SCIENTIFIC APPROACHES SE Annals of the New York Academy of Sciences LA English DT Article DE disparities; health policy; uninsured; Medicaid; SCHIP; safety net providers ID COVERAGE AB This chapter examines trends in private and public health coverage, as well as implications for vulnerable populations and health disparities. We find that there has been erosion in employment-based health benefits. Both the percentage of employers offering coverage and the percentage of workers with coverage declined in recent years. Those with coverage face eroding benefits and increased cost sharing. Within the public sector, Medicaid enrollment has decreased, with benefits increasingly restricted. Although State Children's Health Insurance Program (SCHIP) enrollment has increased among low-income children, the future of SCHIP remains uncertain. Meeting the healthcare needs of Americans and reducing health disparities requires both the provision of health coverage to all and sufficient comprehensiveness of benefits within private and public programs to meet enrollees' healthcare needs. Our findings suggest that we have a long way to go in reaching these goals. C1 [Shields, Alexandra E.] Massachusetts Gen Hosp, Inst Hlth Policy, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02114 USA. [Shields, Alexandra E.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Shields, Alexandra E.] Massachusetts Gen Hosp Partners HealthCare, Inst Hlth Policy, Boston, MA USA. [McGinn-Shapiro, Mary] Georgetown Univ, Georgetown Publ Policy Inst, Washington, DC USA. [Fronstin, Paul] Employee Benefit Res Inst, Washington, DC USA. RP Shields, AE (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM ashields@partners.org NR 44 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-711-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1136 BP 137 EP 148 DI 10.1196/annals.1425.029 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHY28 UT WOS:000257430500016 PM 18579880 ER PT S AU Kelly, JF McCrady, BS AF Kelly, John F. McCrady, Barbara S. BE Galanter, M Kaskutas, LA TI Twelve-Step Facilitation in Non-specialty Settings SO RESEARCH ON ALCOHOLICS ANONYMOUS AND SPIRITUALITY IN ADDICTION RECOVERY SE Recent Developments in Alcoholism LA English DT Article; Book Chapter ID SELF-HELP GROUPS; SUBSTANCE-ABUSE PATIENTS; ALCOHOL-USE DISORDERS; GROUP INVOLVEMENT; OUTPATIENT TREATMENT; FRIENDSHIP NETWORKS; GROUP PARTICIPATION; SOCIAL NETWORKS; PROJECT MATCH; REDUCE DEMAND AB Participation in the twelve-step mutual-help organization, Alcoholics Anonymous, has proven to be an effective means of helping individuals with alcohol dependence achieve lasting sobriety. Although many patients choose to attend AA of their own accord, clinicians' facilitation of AA involvement ("Twelve-Step Facilitation" [TSF]) has shown to substantially increase the likelihood that patients will become engaged with these freely available resources. Importantly, many individuals with alcohol dependence never seek help from addiction specialists, yet often encounter other health professionals due to alcohol-related physical or psychological problems providing an opportunity for intervention. However, for clinicians who do not specialize in addiction treatment, knowledge about what AA actually is and does is often lacking, and confidence in implementing TSF strategies is low. This chapter provides essential information for clinicians working in non-specialty settings who have little knowledge of, or experience with, AA or TSF, but who may wish to utilize proven strategies to augment existing interventions by helping educate, link, and engage patients with A-A. Detailed information on the origins and specific elements of AA is provided along with recommended TSF approaches and strategies to aid the non-specialist in building effective interventions for patients with alcohol dependence. C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McCrady, Barbara S.] Univ New Mexico, CASAA, Albuquerque, NM 87106 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM Jkelly11@partners.org; bmccrady@unm.edu NR 82 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0738-422X BN 978-0-387-77724-5 J9 RECENT DEV ALCOHOL PY 2008 VL 18 BP 321 EP 346 DI 10.1007/978-0-387-77725-2_18 D2 10.1007/978-0-387-77725-2 PG 26 WC Substance Abuse; Religion SC Substance Abuse; Religion GA BKH63 UT WOS:000268129200018 PM 19115777 ER PT J AU Jordan, AS White, DP AF Jordan, Amy S. White, David P. TI Pharyngeal motor control and the pathogenesis of obstructive sleep apnea SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Review DE obstructive sleep apnea; upper airway dilator muscles; neurobiology; sleep; breathing ID POSITIVE AIRWAY PRESSURE; MUSCLE-ACTIVITY; GENIOGLOSSAL ELECTROMYOGRAM; CARDIOVASCULAR OUTCOMES; ANATOMIC DISORDER; BREATHING ROUTE; ONSET; ACTIVATION; REFLEX; ADULTS AB The upper airway in patients with obstructive sleep apnea (OSA) is thought to collapse during sleep at least in part, because of a sleep related reduction in upper airway dilator muscle activity. Therefore, a comprehensive understanding of the neural regulation of these muscles is warranted. The dilator muscles can be classified in two broad categories; those that have respiratory related activity and those that fire constantly throughout the respiratory cycle. The motor control of these two groups likely differs with the former receiving input from respiratory neurons and negative pressure reflex circuits. The activity of both muscle groups is reduced shortly after sleep onset, indicating that both receive input from brainstem neurons involved in sleep regulation. In the apnea patient, this may lead to pharyngeal airway collapse. This review briefly describes the currently proposed sleep and respiratory neural pathways and how these circuits interact with the upper airway dilator muscle motorneurones, including recent evidence from animal studies. Published by Elsevier B.V. C1 [Jordan, Amy S.; White, David P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jordan, Amy S.; White, David P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jordan, AS (reprint author), BIDMC, Sleep Disorders Program, Boston, MA 02115 USA. EM ajordan@rics.bwh.harvard.edu; dpwhite@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU NHLBI NIH HHS [R01 HL048531-14] NR 55 TC 48 Z9 51 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD JAN 1 PY 2008 VL 160 IS 1 BP 1 EP 7 DI 10.1016/j.resp.2007.07.009 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 260EZ UT WOS:000252994900001 PM 17869188 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Iodinated contrast media and the kidney SO REVIEWS IN CARDIOVASCULAR MEDICINE LA English DT Article DE contrast-induced acute kidney injury; lodinated contrast; Osmolality ID HIGH-RISK PATIENTS; INDUCED NEPHROPATHY; RAT-KIDNEY; RENAL-INSUFFICIENCY; DOUBLE-BLIND; RADIOCONTRAST AGENTS; CORONARY-ANGIOGRAPHY; BLOOD-FLOW; IODIXANOL; TRIAL AB One of the principal complications of radiographic procedures utilizing intravascular iodinated contrast media is acute kidney injury. Although several clinical and procedural factors impact a patient's risk for contrast-induced acute kidney injury (CIAKI), substantial attention has been focused on the relationship between the type of contrast agent used and renal injury. Multiple contrast agents are available for clinical use, each defined by a series of physicochemical properties. The evolution from high osmolal to low osmolal and, more recently, iso-osmolal contrast media has led to several clinical trials and meta-analyses comparing the nephrotoxicity of different contrast agents. This article summarizes the physicochemical properties that define and differentiate iodinated contrast media, discusses the purported relationship between these properties and kidney injury, and describes the salient findings of clinical trials and meta-analyses that have compared the nephrotoxic effects of contrast agents. Although ongoing and future studies will further elucidate our understanding of the relationship between iodinated contrast and risk for CIAKI, a sound understanding of the currently available data will help inform evidence-based decisions on the use of these agents in clinical practice. C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare, Renal Sect, Pittsburgh, PA USA. NR 28 TC 6 Z9 7 U1 0 U2 0 PU MEDREVIEWS PI NEW YORK PA 1333 BROADWAY, STE 400, NEW YORK, NY 10018 USA SN 1530-6550 J9 REV CARDIOVASC MED JI Rev. Cardiovasc. Med. PY 2008 VL 9 SU 1 BP S14 EP S23 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 283CS UT WOS:000254614800003 PM 18418313 ER PT J AU Bradberry, CW AF Bradberry, Charles W. TI Comparison of acute and chronic neurochemical effects of cocaine and cocaine cues in rhesus monkeys and rodents: Focus on striatal and cortical dopamine systems SO REVIEWS IN THE NEUROSCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Primate Models for Psychiatric Disorder held at the 16th International Behavioral Neuroscience Meeting CY JUN, 2007 CL Joao Pressoa, BRAZIL DE cocaine; rhesus monkey; rodent; extracellular dopamine; nucleus accumbens; cortex ID CORTICOTROPIN-RELEASING-FACTOR; SELF-ADMINISTERED COCAINE; NUCLEUS-ACCUMBENS DOPAMINE; MEDIAL PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; EXTRACELLULAR DOPAMINE; SEEKING BEHAVIOR; INTRAVENOUS COCAINE; NONHUMAN PRIMATE; DORSAL STRIATUM AB Preclinical work into the effects of cocaine on mesostriatal and mesocorticolimbic dopamine systems has rightly been dominated by studies in rodent models. From the wealth of data that has resulted from those studies, models of chronic neurobiological adaptations have been developed that might illuminate the cellular and systems bases for the compulsive and self-injurious aspects of addiction. Chronic adaptations of dopaminergic mechanisms often dominate these models. Our studies into the acute and chronic dopaminergic effects of cocaine in non-human primates are compared to important aspects of the larger rodent literature. In some ways there is good concordance, but in others the non-human primate results differ in ways that are more similar to the human literature. This is especially true in regard to sensitization of dopamine systems in response to chronic self-administration. To best evaluate potential models of addiction, it will be important to also consider data from non-human primates as a more proximal animal model to the human condition, particularly in the greater complexity of cortical development. C1 [Bradberry, Charles W.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15203 USA. [Bradberry, Charles W.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15203 USA. [Bradberry, Charles W.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Bradberry, CW (reprint author), Univ Pittsburgh, Dept Psychiat, 3025 E Carson St, Pittsburgh, PA 15203 USA. EM bradberrycw@upmc.edu RI bradberry, charles/M-2082-2015 OI bradberry, charles/0000-0003-2630-4144 FU PHS HHS [10331] NR 100 TC 14 Z9 14 U1 1 U2 3 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2008 VL 19 IS 2-3 BP 113 EP 128 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 334RX UT WOS:000258240000005 PM 18751519 ER PT J AU Offner, H Sinha, S Wang, CH Burrows, GG Vandenbark, AA AF Offner, Halina Sinha, Sushmita Wang, Chunhe Burrows, Gregory G. Vandenbark, Arthur A. TI Recombinant T Cell Receptor Ligands: Immunomodulatory, Neuroprotective and Neuroregenerative Effects Suggest Application as Therapy for Multiple Sclerosis SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE RTL; experimental autoimmune encephalomyelitis; multiple sclerosis; neuroprotection; immunomodulation ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MHC CLASS-II; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; STRUCTURAL BASIS; TRANSGENIC MICE; PEPTIDE LIGANDS; BINDING-SITE; MYELIN; TCR; ANTIGEN AB Recombinant T cell receptor (TCR) ligands (RTL) represent the minimal interactive surface with antigen-specific T cell receptors. These novel constructs fold similarly to native four-domain NIHC/peptide complexes but deliver suboptimal and qualitatively different signals that cause a 'cytokine switch' to anti-inflammatory factors in targeted encephalitogenic T cells. RTL treatment can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) and most dramatically can promote myelin and axonal recovery in the CNS of mice with chronic disease. These properties of RTL suggest that this novel antigen-specific approach may hold unusual promise as a therapy for multiple sclerosis. C1 [Offner, Halina; Sinha, Sushmita; Wang, Chunhe; Vandenbark, Arthur A.] VA Med Ctr, Portland, OR USA. [Offner, Halina; Sinha, Sushmita; Wang, Chunhe; Burrows, Gregory G.; Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU National Multiple Sclerosis Society [RG3794A, RG3468]; NIH [NS47661, A143960, NS41965, NS46877]; The Nancy Davis MS Center; Biomedical Laboratory RD Service; Department of Veterans Affairs FX This work was supported by the National Multiple Sclerosis Society Grants RG3794A and RG3468, NIH Grants NS47661, A143960, NS41965, and NS46877, The Nancy Davis MS Center Without Walls, and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. NR 52 TC 12 Z9 13 U1 0 U2 1 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2008 VL 19 IS 4-5 BP 327 EP 339 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 380OV UT WOS:000261475900006 PM 19145988 ER PT B AU Alloy, LB Abramson, LY Keyser, J Gerstein, RK Sylvia, LG AF Alloy, Lauren B. Abramson, Lyn Y. Keyser, Jessica Gerstein, Rachel K. Sylvia, Louisa G. BE Dobson, KS Dozois, DJA TI NEGATIVE COGNITIVE STYLE SO RISK FACTORS IN DEPRESSION LA English DT Article; Book Chapter ID CAUSAL MEDIATION COMPONENTS; SELF-ESTEEM THEORIES; ADAPTIVE INFERENTIAL FEEDBACK; DEPRESSIVE MOOD REACTIONS; DIATHESIS-STRESS MODEL; ATTRIBUTIONAL STYLE; HOPELESSNESS THEORY; DYSFUNCTIONAL ATTITUDES; LIFE EVENTS; CHILDHOOD MALTREATMENT C1 [Alloy, Lauren B.; Keyser, Jessica; Gerstein, Rachel K.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Abramson, Lyn Y.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Sylvia, Louisa G.] Massachussetts Gen Hosp, Boston, MA USA. RP Alloy, LB (reprint author), Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. NR 132 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-056056-4; 978-0-08-045078-0 PY 2008 BP 237 EP 262 DI 10.1016/B978-0-08-045078-0.00011-3 PG 26 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BID45 UT WOS:000327701500012 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Introduction to FNA and Salivary Gland Neoplasia SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Editorial Material; Book Chapter ID FINE-NEEDLE-ASPIRATION; PAROTID-GLAND; BIOPSY; DIAGNOSIS; LESIONS C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 1 EP 16 D2 10.1007/978-0-387-76623-2 PG 16 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700003 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Salivary Gland Cytopathology Foreword SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Editorial Material; Book Chapter C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP V EP VI D2 10.1007/978-0-387-76623-2 PG 2 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700001 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Salivary Gland Cytopathology Series Preface SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Editorial Material; Book Chapter C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP VII EP VIII D2 10.1007/978-0-387-76623-2 PG 2 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700002 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Salivary Gland FNA: Anatomic, Clinical, and Technical Considerations SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID NEEDLE-ASPIRATION-CYTOLOGY C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 17 EP 28 D2 10.1007/978-0-387-76623-2 PG 12 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700004 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Algorithmic Approach to Salivary Gland FNA: An Overview SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID NEEDLE-ASPIRATION-CYTOLOGY C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 29 EP 40 D2 10.1007/978-0-387-76623-2 PG 12 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700005 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI The Normal Salivary Gland Aspirate SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 41 EP 55 D2 10.1007/978-0-387-76623-2 PG 15 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700006 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Inflammatory Patterns and Lymphoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID SALIVARY-GLANDS; LESIONS; DISORDERS C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 57 EP 80 D2 10.1007/978-0-387-76623-2 PG 24 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700007 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Matrix-Containing Tumors: Pleomorphic Adenoma and Adenoid Cystic Carcinoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID KIT CD117; GRADE C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 81 EP 114 D2 10.1007/978-0-387-76623-2 PG 34 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700008 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Basaloid Tumors: Basal Cell Adenoma and Basal Cell Adenocarcinoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID SALIVARY-GLANDS C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 115 EP 130 D2 10.1007/978-0-387-76623-2 PG 16 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700009 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Oncocytic Tumors: Oncocytoma, Warthin Tumor, and Acinic Cell Carcinoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID MUCOEPIDERMOID CARCINOMA; SALIVARY-GLANDS; ASPIRATION; CYTOLOGY C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 131 EP 158 D2 10.1007/978-0-387-76623-2 PG 28 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700010 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Cystic and Mucinous Lesions: Mucocele and Low-Grade Mucoepidermoid Carcinoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID SALIVARY-GLANDS C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 159 EP 181 D2 10.1007/978-0-387-76623-2 PG 23 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700011 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI High-Grade Salivary Gland Tumors: Salivary Duct Carcinoma, High-Grade Mucoepidermoid Carcinoma, and Carcinoma ex Pleomorphic Adenoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID SMALL-CELL CARCINOMA; PAROTID-GLAND; EXPRESSION C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 183 EP 201 D2 10.1007/978-0-387-76623-2 PG 19 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700012 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Spindle Cell Tumors: Spindled Myoepithelioma, Myoepithelial-Predominant Pleomorphic Adenoma, and Schwannoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID FINE-NEEDLE-ASPIRATION; CYTOLOGIC FEATURES; SALIVARY-GLANDS; NEOPLASMS; DIAGNOSIS; PITFALL; LESIONS C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 203 EP 231 D2 10.1007/978-0-387-76623-2 PG 29 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700013 ER PT S AU Faquin, WC Powers, CN AF Faquin, William C. Powers, Celeste N. BA Faquin, WC Powers, C BF Faquin, WC Powers, C TI Clear Cell Neoplasms and Secondary Tumors: Epithelial-Myoepithelial Carcinoma SO SALIVARY GLAND CYTOPATHOLOGY SE Essentials in Cytopathology LA English DT Article; Book Chapter ID SALIVARY-GLANDS; PAROTID-GLAND; DISEASE C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Pathol, Richmond, VA 23298 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1574-9053 BN 978-0-387-76623-2 J9 ESSENT CYTOPATHOL PY 2008 BP 233 EP 253 D2 10.1007/978-0-387-76623-2 PG 21 WC Pathology SC Pathology GA BNQ18 UT WOS:000275223700014 ER PT J AU Matsuda, K Yamauchi, K Matsumoto, T Sano, K Yamaoka, Y Ota, H AF Matsuda, Kazuyuki Yamauchi, Kazuyoshi Matsumoto, Takehisa Sano, Kenji Yamaoka, Yoshio Ota, Hiroyoshi TI Quantitative analysis of the effect of Helicobacter pylori on the expressions of SOX2, CDX2, MUC2, MUC5AC, MUC6, TFF1, TFF2, and TFF3 mRNAs in human gastric carcinoma cells SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE CDX2; Helicobacter pylori; MUC; PDX1; real-time PCR; TFF ID HOMEODOMAIN PROTEIN CDX2; EPITHELIAL-CELLS; GENE-EXPRESSION; INTESTINAL METAPLASIA; TREFOIL FACTOR; ABERRANT EXPRESSION; ECTOPIC EXPRESSION; MUCOUS LAYER; CAGA PROTEIN; IV SECRETION AB Objective. To investigate the phenotypic characters of carcinoma cells and the response of gastric epithelial cells to Helicobacter pylori (H. pylori) infection using the gastric carcinoma cell lines. Material and methods. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the effect of H. pylori infection on mRNA levels of transcription factors (SOX2 and CDX2), mucin core proteins (MUC2, MUC5AC, and MUC6), and trefoil factor family peptides (TFF) (TFF1, TFF2, and TFF3) in gastric carcinoma cells (AGS, MKN45, and KATO III cells). H. pylori ATCC 43504 and its isogenic cag pathogenicity island (PAI) deleted mutant were used. Results. These cell lines expressed mixed gastric and intestinal phenotypes. The intestinal phenotype predominated in AGS cells and gastric phenotypes in MKN45 and KATO III cells. In all three cell lines, H. pylori infection inhibited SOX2 mRNA expression, but induced the three TFFs mRNAs. In AGS cells, H. pylori induced cag PAI-dependent mRNA expression of CDX2, MUC2, MUC5AC, and MUC6. mRNA expressions of CDX2, MUC5AC, and MUC6 were inhibited in KATO III cells, whereas MUC2 mRNA expression was unchanged. In MKN45 cells, H. pylori induced the three MUCs mRNAs but inhibited CDX2 mRNA expression. Conclusions. This study provides a useful platform for selecting appropriate cell lines to model H. pylori-related changes in the gastric epithelium that mirror the changes seen in vivo. The outcome of H. pylori infection may reflect changes in the mucus gel layer caused by altered expression of mucins and TFF peptides. C1 [Ota, Hiroyoshi] Shinshu Univ, Sch Med, Dept Biomed Lab Sci, Sch Hlth Sci, Matsumoto, Nagano 3908621, Japan. [Matsuda, Kazuyuki; Yamauchi, Kazuyoshi; Matsumoto, Takehisa; Sano, Kenji] Shinshu Univ Hosp, Dept Lab Med, Matsumoto, Nagano, Japan. [Yamaoka, Yoshio] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. RP Ota, H (reprint author), Shinshu Univ, Sch Med, Dept Biomed Lab Sci, Sch Hlth Sci, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM hohta@shinshu-u.ac.jp FU NIDDK NIH HHS [R01 DK062813-03, DK62813, R01 DK062813] NR 47 TC 19 Z9 21 U1 0 U2 4 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2008 VL 43 IS 1 BP 25 EP 33 DI 10.1080/00365520701579795 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 244CF UT WOS:000251842900004 PM 18938748 ER PT J AU Becher, A El-Serag, HB AF Becher, Anja El-Serag, Hashem B. TI Mortality associated with gastroesophageal reflux disease and its non-malignant complications: a systematic review SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Review DE GERD; epidemiology; esophagus ID AORTOESOPHAGEAL FISTULA SECONDARY; NATURAL-HISTORY; TEMPORAL TRENDS; TIME TRENDS; FOLLOW-UP; EPIDEMIOLOGY; ESOPHAGITIS; POPULATION; GERD; PREVALENCE AB Objective. The mortality associated with malignant complications of gastroesophageal reflux disease (GERD) is well recognized. The aim of this systematic review was to assess the less well-examined mortality associated with GERD and its non-malignant complications, including esophageal erosions, ulcers, bleeding, perforation and strictures. Material and methods. Studies reporting mortality in GERD and its non-malignant complications were identified via systematic PubMed searches, and previously unpublished population mortality statistics from public access databases. Results. Three countries were examined (USA, UK, Finland). Cohort studies (n=3) in the UK showed a 1.16- to 1.6-fold increase in risk of death in individuals with GERD compared with the general population, the majority of deaths being due to cardiac disease. Population data indicate that GERD and its likely esophageal complications were the cause of death in 685 and 521 cases, respectively, in the USA (year: 2003) (age-adjusted mortality: 2.3/million and 1.8/million, respectively), and in 36 and 349 cases, respectively, in England and Wales (2004) (0.6/million and 5.4/million, respectively). In Finland (2000), GERD-related mortality was 4.6/million. Mortality from GERD and its likely esophageal complications increased with age, and was between 1.2-fold and 1.8-fold higher in men than in women. Cohort studies in the USA are inconsistent on mortality risk associated with surgical therapy. Time-trend data suggest that mortality from GERD and its non-malignant complications has been increasing. Conclusions. Data from Europe and the USA show that GERD and its non-malignant complications can on rare occasions cause death. C1 [Becher, Anja] Oxford PharmaGenesis Ltd, Res Evaluat Unit, Oxford, England. [El-Serag, Hashem B.] Baylor Coll Med, Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. [El-Serag, Hashem B.] Baylor Coll Med, Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Sect Gastroenterol & Hlth Serv Res, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 29 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2008 VL 43 IS 6 BP 645 EP 653 DI 10.1080/00365520701785475 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 317NY UT WOS:000257028100002 PM 18569980 ER PT J AU Toracchio, S El-Zimaity, HMT Urmacher, C Katz, S Graham, DY AF Toracchio, Sonia El-Zimaity, Hala M. T. Urmacher, Carlos Katz, Seymour Graham, David Y. TI Mycobacterium avium subspecies paratuberculosis and Crohn's disease granulomas SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Crohn's disease; granuloma; IS900; Mycobacterium paratuberculosis; paraffin embedded ID INFLAMMATORY-BOWEL-DISEASE; POLYMERASE-CHAIN-REACTION; TISSUES; ABSENCE; DNA; INDIVIDUALS AB Objective. Chronic infection with Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) has been proposed as a cause of Crohn's disease. Although numerous investigators have examined the link between M. paratuberculosis and Crohn's disease, the evidence remains controversial. The aim of this study was to examine intestinal granuloma from Crohn's patients for M. paratuberculosis using a semi-nested M. paratuberculosis-specific IS900 polymerase chain reaction (PCR). Material and methods. Paraffin-embedded ileal or colonic tissues of patients with Crohn's disease were analyzed. Microdissection of this tissue into granulomas and not granulomas was performed. On the basis of sequences reported in GenBank alignments, we designed primer sets specific for M. paratuberculosis. The presence of the M. paratuberculosis was examined by semi-nested IS900-specific PCR with human -actin gene as a control for DNA quality. Results. Biopsies from 20 Crohn's patients were examined. Human -actin gene was amplified in all samples. M. paratuberculosis DNA was detected in the microdissected granuloma in 1 (5%) patient with Crohn's disease and in none of the not granuloma tissues. Conclusions. M. paratuberculosis DNA can rarely be detected within Crohn's granuloma. These results do not support M. paratuberculosis as the primary etiology of Crohn's disease. C1 [Toracchio, Sonia; El-Zimaity, Hala M. T.; Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Toracchio, Sonia; El-Zimaity, Hala M. T.; Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Toracchio, Sonia] Univ G dAnnunzio, Sect Mol Pathol, Dept Oncol & Neurosci, Chieti, Italy. [Toracchio, Sonia] G dAnnunzio Fdn, Ctr Excellence Aging, Chieti, Italy. [Urmacher, Carlos] CBLPath Inc, New York, NY USA. [Katz, Seymour] NYU, Sch Med, N Shore Univ Hosp Long Isl Jewish Syst, New York, NY USA. RP Graham, DY (reprint author), VA Med Ctr, 111-D,2002 Holcombe Blvd,RM 3A320, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu OI katz, seymour/0000-0002-3492-9200 FU Fondazione Italiana per la Ricerca sul Cancro (FIRC), Milan, Italy; Associazione Italiana per la Ricerca sul Cancro FX Sonia Toracchio was supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro (FIRC), Milan, Italy. NR 27 TC 10 Z9 10 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2008 VL 43 IS 9 BP 1108 EP 1111 DI 10.1080/00365520802116455 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 339PM UT WOS:000258589500013 PM 18609156 ER PT J AU Essa, AS Nouh, MAE Ghaniam, NM Graham, DY Sabry, HS AF Essa, Abdallah Said Nouh, Mohammed Alaa Eldeen Ghaniam, Naglaa Mohammed Graham, David Y. Sabry, Hany Said TI Prevalence of cagA in relation to clinical presentation of Helicobacter pylori infection in Egypt SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PEPTIC-ULCER DISEASE; CYTOTOXIN PRODUCTION; DYSPEPTIC PATIENTS; VACA GENOTYPES; ANTIBODIES; GASTRITIS; GENES; RISK AB Helicobacter pylori infection, peptic ulcer and gastric cancer are common problems in Egypt. We investigated the prevalence of cagA-positive Helicobacter pylori infections among Egyptian adults in relation to presentation (e.g. dyspepsia vs asymptomatic controls) in Minofyia, Egypt. Patients included men or women seeking care for at least 3 months of upper gastrointestinal symptoms. Helicobacter pylori status was determined by rapid urease test and gastric histopathology in patients and by anti-Helicobacter pylori IgG antibodies in controls. CagA status was determined using an anti-cag A ELISA. 99 Helicobacter pylori infected patients were entered including 90 dyspeptic patients (30 each with gastric cancer, peptic ulcer, and non-ulcer dyspepsia) and 9 non-dyspeptic healthy controls. Age ranged from 27 to 78 y (mean 49.5 y); 50% were men. Anti-cagA antibodies were present in 62.2% of dyspeptic patients compared with 11% of asymptomatic controls (p=0.004). Anti-cagA antibodies were more prevalent among dyspeptic patients with gastric cancer or peptic ulcer (73.3%) compared to those with non-ulcer dyspepsia (40%) (p=0.004). The prevalence of cagA in Egypt was related to the clinical presentation of Helicobacter pylori infection being lowest in asymptomatic controls (11.1%) and increasingly prevalent in non-ulcer dyspepsia (40%), peptic ulcer (66.7%), and gastric cancer (89%). C1 Minofyia Univ, Dept Trop Med, Minofyia, Egypt. Minofyia Univ, Dept Biochem, Minofyia, Egypt. Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Vet Affairs Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu NR 24 TC 6 Z9 7 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2008 VL 40 IS 9 BP 730 EP 733 DI 10.1080/00365540802023725 PG 4 WC Infectious Diseases SC Infectious Diseases GA 340CN UT WOS:000258623800007 ER PT J AU Frazier, JA Hodge, SM Breeze, JL Giuliano, AJ Terry, JE Moore, CM Kennedy, DN Lopez-Larson, MP Caviness, VS Seidman, LJ Zablotsky, B Makris, N AF Frazier, Jean A. Hodge, Steven M. Breeze, Janis L. Giuliano, Anthony J. Terry, Janine E. Moore, Constance M. Kennedy, David N. Lopez-Larson, Melissa P. Caviness, Verne S. Seidman, Larry J. Zablotsky, Benjamin Makris, Nikos TI Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE mood disorders; psychosis; brain imaging technique; child psychiatry ID ADULT HUMAN BRAIN; NEURAL CIRCUITRY; PUBERTAL CHANGES; CHILDHOOD; MRI; ADOLESCENCE; AMYGDALA; MATTER; NEURODEVELOPMENT; ABNORMALITIES AB Objective: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. Methods: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HQ, similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. Results: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. Conclusion: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression. C1 [Frazier, Jean A.; Breeze, Janis L.; Giuliano, Anthony J.; Moore, Constance M.; Lopez-Larson, Melissa P.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Frazier, Jean A.; Breeze, Janis L.; Giuliano, Anthony J.; Terry, Janine E.; Moore, Constance M.; Kennedy, David N.; Lopez-Larson, Melissa P.; Zablotsky, Benjamin] Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, Cambridge, MA USA. [Hodge, Steven M.; Kennedy, David N.; Caviness, Verne S.; Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Giuliano, Anthony J.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat, New York, NY 10003 USA. [Kennedy, David N.; Caviness, Verne S.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Caviness, Verne S.] Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Frazier, JA (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. EM JFrazier@challiance.org RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [K01 MH001978, K01 MH01798, K08 MH01573] NR 63 TC 61 Z9 62 U1 5 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2008 VL 34 IS 1 BP 37 EP 46 DI 10.1093/schbul/sbm120 PG 10 WC Psychiatry SC Psychiatry GA 248JE UT WOS:000252148800009 PM 18003631 ER PT J AU Stone, WS Seidman, LJ AF Stone, William S. Seidman, Larry J. TI Toward a model of memory enhancement in schizophrenia: Glucose administration and hippocampal function SO SCHIZOPHRENIA BULLETIN LA English DT Review DE cognitive enhancement; antipsychotic medication; medial temporal lobe ID SPONTANEOUS-ALTERNATION PERFORMANCE; SCHIZOTYPAL PERSONALITY-DISORDER; DEPENDENT DIABETES-MELLITUS; FRONTAL-LOBE DYSFUNCTION; PLACEBO-CONTROLLED TRIAL; HEALTHY-YOUNG ADULTS; CEREBRAL BLOOD-FLOW; COGNITIVE FUNCTION; DOUBLE-BLIND; NEUROPSYCHOLOGICAL FUNCTION AB Recognition of the need to treat cognitive deficits in schizophrenia is compelling and well established, with empirical findings and conceptual arguments related to cognitive enhancement appearing regularly in the literature. Cognitive enhancement itself, however, remains at an early stage. Biological approaches have centered on the development of antipsychotic medications that also improve cognition, but the results have so far remained modest. As a way to facilitate the development of cognitive enhancers in schizophrenia, this article focuses on adjunctive pharmacological approaches to antipsychotic medications and highlights the need for systematic explorations of relevant brain mechanisms. While numerous conceptual criteria might be employed to guide the search, we will focus on 4 points that are especially likely to be useful and which have not yet been considered together. First, the discussion will focus on deficits in a particular cognitive domain, verbal declarative memory. Second, we will review the current status of preclinical and clinical efforts to improve declarative memory using antipsychotic medications, which is the main, existing mode of treatment. Third, we will examine an example of an adjunctive intervention-glucose administration-that improves memory in animals and humans, modulates function in brain regions related to verbal declarative memory, and is highly amenable to translational research. Finally, a heuristic model will be outlined to explore how the intervention maps on to the underlying neurobiology of schizophrenia. More generally, the discussion underlines the promise of cognitive improvement in schizophrenia and the need to approach the issue in a programmatic manner. C1 [Stone, William S.; Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Psychiat, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Stone, William S.; Seidman, Larry J.] Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stone, WS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Psychiat, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. EM wstone@bidmc.harvard.edu FU NIMH NIH HHS [MH 43518, MH 63951, MH 65562, R01 MH043518, R01 MH065562, R37 MH043518, R01 MH063951] NR 249 TC 17 Z9 17 U1 5 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2008 VL 34 IS 1 BP 93 EP 108 DI 10.1093/schbul/sbm041 PG 16 WC Psychiatry SC Psychiatry GA 248JE UT WOS:000252148800014 PM 17504777 ER PT J AU Byne, W Dracheva, S Chin, B Schmeidler, JM Davis, KL Haroutunian, V AF Byne, William Dracheva, Stella Chin, Benjamin Schmeidler, James M. Davis, Kenneth L. Haroutunian, Vahram TI Schizophrenia and sex associated differences in the expression of neuronal and oligodendrocyte-specific genes in individual thalamic nuclei SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; thalamus; neurons; oligodendrocytes; gene expression ID MESSENGER-RNA EXPRESSION; NEVER-MEDICATED PATIENTS; PREFRONTAL CORTEX; MEDIODORSAL NUCLEUS; BIPOLAR DISORDER; ELDERLY-PATIENTS; PROTEIN EXPRESSION; MAJOR DEPRESSION; BINDING PROTEINS; POSTMORTEM AB Considerable evidence based on the study of postmortem brain tissue suggests deficits in both neuronal and myelin systems in schizophrenia (SZ), To date, the majority of the biochemical and molecular biological studies have focused on the cerebral cortex. Most information traveling to or from the cortex is relayed or synaptically gated through the thalamus, and numerous studies suggest structural and functional abnormalities in interconnected regions of the thalamus and cortex in SZ. The present study extends our gene expression studies of neuronal and myelin systems to the thalamus. Quantitative PCR was employed to assess the expression of 10 genes in 5 divisions of the thalamus which were precisely harvested using Laser Capture Microdissection. The divisions studied were present on coronal sections at the level of the centromedian nucleus (CMN) taken from 14 schizophrenic and 16 normal control postmortem brains. The genes examined were specific for oligodendrocytes (MAG, CNP MBP), neurons (ENO2), glutamatergic, neurons (VGlut1, VGlut2, PV, CB) or GABAergic neurons (GAD65, GAD67). Expression levels for each of these markers were quantitated and compared between diagnoses, between sexes, and across nuclei. CB was much more highly expressed in the CMN in SZs compared to NCs. No other diagnosis related differences in gene expression were observed. The expression levels of CNP and MAG, but not MBP, were highly correlated with one another and both, but not MBP, were much more highly expressed in females than in males in all thalamic divisions examined. All markers were differentially expressed across nuclei. Published by Elsevier B.V. C1 [Byne, William; Dracheva, Stella; Chin, Benjamin; Haroutunian, Vahram] Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Byne, William; Dracheva, Stella; Schmeidler, James M.; Davis, Kenneth L.; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, Psychiat Res 3F-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Vahram.Haroutunian@mssm.edu FU NIMH NIH HHS [P50 MH066392-05A19004, MH064673, MH066392, P50 MH066392, R01 MH064673, R01 MH064673-06] NR 65 TC 27 Z9 25 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 JAN PY 2008 VL 98 IS 1-3 BP 118 EP 128 DI 10.1016/j.schres.2007.09.034 PG 11 WC Psychiatry SC Psychiatry GA 253BQ UT WOS:000252494100015 PM 18029146 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Taming vessels to treat cancer SO SCIENTIFIC AMERICAN LA English DT Article ID ANTIANGIOGENIC THERAPY; NORMALIZATION; VASCULATURE AB Restoring order to the chaotic blood vessels inside a tumor opens a window of opportunity for attacking it. Surprisingly, drugs meant to destroy vasculature can make the repairs and may help reverse conditions that lead to cardiovascular disease and blindness C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA126642] NR 4 TC 58 Z9 58 U1 0 U2 7 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD JAN PY 2008 VL 298 IS 1 BP 56 EP 63 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248GN UT WOS:000252140800049 PM 18225696 ER PT J AU Spiegellman, B AF Spiegellman, Bruce TI The skinny fat SO SCIENTIST LA English DT Article AB Food is converted to energy within the mitochondrion and excess food is stored as lipid deposits in white fat in adults. The number of fat cells does not increase with morbid obesity. The master gene or aP2 gene is responsible for fat cell differentiation and it is also a receptor for some antidiabetic drugs. Brown fat is commonly found in infants, where the cell type helps generate enough heat for the child's survival. PGC-1 alpha is the key regulator of brown fat genes. C1 [Spiegellman, Bruce] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Spiegellman, Bruce] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegellman, B (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN PY 2008 VL 22 IS 1 BP 28 EP 34 PG 7 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 248GO UT WOS:000252140900020 ER PT J AU Chen, Y Inoue, Y Pauzenberger, R Junger, WG AF Chen, Yu Inoue, Yoshiaki Pauzenberger, Reinhard Junger, Wolfgang G. TI Neutrophil accumulation in the lungs requires P2Y2 and A3 adenosine receptors SO SHOCK LA English DT Meeting Abstract CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc C1 [Chen, Yu; Inoue, Yoshiaki; Pauzenberger, Reinhard; Junger, Wolfgang G.] Harvard Univ, Sch Med, BIDMC, Dept Surg Trauma & Surg Crit Care, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2008 VL 29 SU 1 MA P110B BP 40 EP 40 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 308SE UT WOS:000256409500130 ER PT J AU Inoue, Y Chen, Y Pauzenberger, R Hirsh, M Junger, WG AF Inoue, Yoshiaki Chen, Yu Pauzenberger, Reinhard Hirsh, Mark Junger, Wolfgang G. TI Hypertonic saline increases acute lung injury by up-regulating neutrophil A3 adenosine receptor expression SO SHOCK LA English DT Meeting Abstract CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc C1 [Inoue, Yoshiaki; Chen, Yu; Pauzenberger, Reinhard; Hirsh, Mark; Junger, Wolfgang G.] Harvard Univ, Sch Med, BIDMC, Dept Surg Trauma & Surg Crit Care, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2008 VL 29 SU 1 MA P110A BP 40 EP 40 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 308SE UT WOS:000256409500129 ER PT J AU Li, YH Liu, YJ Zhang, J Xiao, GZ Vodovotz, Y Billiar, T Wilson, M Fan, J AF Li, Yuehua Liu, Yujian Zhang, Jian Xiao, Guozhi Vodovotz, Yoram Billiar, Timothy Wilson, Mark Fan, Jie TI Role of TLR2 signaling in hemorrhagic shock-primed IL-1 beta processing SO SHOCK LA English DT Meeting Abstract CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc C1 [Wilson, Mark; Fan, Jie] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. [Vodovotz, Yoram; Billiar, Timothy; Wilson, Mark; Fan, Jie] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Zhang, Jian; Xiao, Guozhi] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 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 1073-2322 J9 SHOCK JI Shock PY 2008 VL 29 SU 1 MA P195 BP 66 EP 67 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 308SE UT WOS:000256409500214 ER PT J AU Corriden, R Chen, Y Inoue, Y Beldi, G Robson, S Junger, WG AF Corriden, Ross Chen, Yu Inoue, Yoshiaki Beldi, Guido Robson, Simon Junger, Wolfgang G. TI Generation of adenosine from released ATP, by the ectoenzymes CD39 and alkaline phosphatase, regulates chemotaxis SO SHOCK LA English DT Meeting Abstract CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc C1 Harvard Univ, Sch Med, BIDMC, Dept Surg & Med, Boston, MA 02215 USA. Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 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 1073-2322 J9 SHOCK JI Shock PY 2008 VL 29 SU 1 MA P197 BP 67 EP 67 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 308SE UT WOS:000256409500216 ER PT J AU Hirsh, MI Inoue, Y Chen, Y Pauzenberger, R Junger, WG AF Hirsh, Mark I. Inoue, Yoshiaki Chen, Yu Pauzenberger, Reinhard Junger, Wolfgang G. TI Hypertonic saline increases the clearance of inflamed neutrophils by T cells SO SHOCK LA English DT Meeting Abstract CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc C1 [Hirsh, Mark I.; Inoue, Yoshiaki; Chen, Yu; Pauzenberger, Reinhard; Junger, Wolfgang G.] Harvard Univ, Sch Med, BIDMC, Dept Surg Trauma & Surg Crit Care, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2008 VL 29 SU 1 MA P196 BP 67 EP 67 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 308SE UT WOS:000256409500215 ER PT J AU Morgenthaler, TI Aurora, N Brown, T Zak, R Alessi, C Boehlecke, B Chesson, AL Friedman, L Kapur, V Maganti, R Owens, J Pancer, J Swick, TJ AF Morgenthaler, Timothy I. Aurora, Nisha Brown, Terry Zak, Rochelle Alessi, Cathy Boehlecke, Brian Chesson, Andrew L., Jr. Friedman, Leah Kapur, Vishesh Maganti, Rama Owens, Judith Pancer, Jeffrey Swick, Todd J. CA Standards Practice Comm AASM TI Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: An update for 2007 SO SLEEP LA English DT Article DE obstructive sleep apnea; continuous positive airway pressure; CPAP; sleep disordered breathing; autotitrating; APAP ID AUTOMATIC CPAP TITRATION; NASAL CPAP; APNEA/HYPOPNEA SYNDROME; BREATHING DISORDERS; HYPOPNEA SYNDROME; AUTO-CPAP; HOME; THERAPY; TRIAL; POLYSOMNOGRAPHY AB These practice parameters are an update of the previously published recommendations regarding the use of autotitrating positive airway pressure (APAP) devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. Continuous positive airway pressure (CPAP) at an effective setting verified by attended polysomnography is a standard treatment for obstructive sleep apnea (OSA). APAP devices change the treatment pressure based on feedback from various patient measures such as airflow, pressure fluctuations, or measures of airway resistance. These devices may aid in the pressure titration process, address possible changes in pressure requirements throughout a given night and from night to night, aid in treatment of OSA when attended CPAP titration has not or cannot be accomplished, or improve patient comfort. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine has reviewed the literature published since the 2002 practice parameter on the use of APAP. Current recommendations follow: (1) APAP devices are not recommended to diagnose OSA; (2) patients with congestive heart failure, patients with significant lung disease such as chronic obstructive pulmonary disease; patients expected to have nocturnal arterial oxyhemoglobin desaturation due to conditions other than OSA (e.g., obesity hypoventilation syndrome); patients who do not snore (either naturally or as a result of palate surgery); and patients who have central sleep apnea syndromes are not currently candidates for APAP titration or treatment; (3) APAP devices are not currently recommended for splitnight titration; (4) certain APAP devices may be used during attended titration with polysomnography to identify a single pressure for use with standard CPAP for treatment of moderate to severe OSA; (5) certain APAP devices may be initiated and used in the self-adjusting mode for unattended treatment of patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (6) certain APAP devices may be used in an unattended way to determine a fixed CPAP treatment pressure for patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (7) patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must have close clinical follow-up to determine treatment effectiveness and safety; and (8) a reevaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the APAP treatment otherwise appears to lack efficacy. C1 [Aurora, Nisha; Zak, Rochelle] Mt Sinai Med Ctr, New York, NY 10029 USA. [Brown, Terry] St Joseph Mem Hosp, Murphysboro, IL USA. [Alessi, Cathy] VA Greater Los Angeles Healthcare Syst Sepulveda, Los Angeles, CA USA. [Boehlecke, Brian] Univ N Carolina, Chapel Hill, NC USA. [Chesson, Andrew L., Jr.] Louisiana State Univ, Shreveport, LA 71105 USA. [Friedman, Leah] Stanford Univ, Stanford, CA 94305 USA. [Kapur, Vishesh] Univ Washington, Seattle, WA 98195 USA. [Maganti, Rama] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Owens, Judith] Rhode Isl Hosp, Providence, RI 02903 USA. [Swick, Todd J.] Houston Sleep Ctr, Houston, TX USA. [Morgenthaler, Timothy I.] Mayo Clin, Rochester, MN 55905 USA. RP Morgenthaler, TI (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM aasm@aasmnet.org RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 40 TC 94 Z9 98 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2008 VL 31 IS 1 BP 141 EP 147 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 249XN UT WOS:000252264000018 PM 18220088 ER PT J AU Atwood, CW Shalaby, A Selzer, F Strollo, PJ Goresan, J Hickey, K AF Atwood, C. W. Shalaby, A. Selzer, F. Strollo, P. J. Goresan, J. Hickey, K. TI Periodic breathing in wakefulness is associated with severe sleep APNEA in heart failure patients who are candidates for cardiac resynchronization therapy SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Atwood, C. W.] VA Pittsburgh Healthcare Syst, Pulm Unit, Pittsburgh, PA USA. [Atwood, C. W.; Strollo, P. J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Shalaby, A.; Hickey, K.] VA Pittsburgh Healthcare Syst, Cardiol Sect, Pittsburgh, PA USA. [Shalaby, A.; Goresan, J.] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. [Selzer, F.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 0922 BP A303 EP A303 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001351 ER PT J AU Barilla, HE Cook, J Gehrman, P Ross, R AF Barilla, H. E. Cook, J. Gehrman, P. Ross, R. TI Changes in content of combat-related nightmares in Vietnam veterans with PTSD receiving Imagery Rehearsal therapy SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD SP Amer Acad Sleep Med, Sleep Res Soc C1 [Barilla, H. E.; Gehrman, P.] Univ Sci Philadelphia, Dept Psychol, Philadelphia, PA USA. [Cook, J.; Ross, R.] Philadelphia VA Med Ctr, Mental Hlth Clin, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1156 BP A381 EP A381 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001585 ER PT J AU Berka, C Johnson, R Morgan, T Levendowski, D Westbrook, P Olmstead, R Davis, G Leathers, R Whitmoyer, M AF Berka, C. Johnson, R. Morgan, T. Levendowski, D. Westbrook, P. Olmstead, R. Davis, G. Leathers, R. Whitmoyer, M. TI Influence of sleep-disordered breathing on neurocognitive functions pre- and post-treatment with oral appliance therapy SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD SP Amer Acad Sleep Med, Sleep Res Soc C1 [Berka, C.; Johnson, R.; Levendowski, D.; Westbrook, P.; Davis, G.; Leathers, R.; Whitmoyer, M.] Adv Brain Monitoring, Carlsbad, CA USA. [Morgan, T.] Scripps Mem Hosp, Encinitas, CA USA. [Olmstead, R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 457 BP A152 EP A153 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000457 ER PT J AU Buxton, OM Ebbeling, CB Stoddard, A Pereira, L Yang, M Quintiliani, L Sorensen, G AF Buxton, O. M. Ebbeling, C. B. Stoddard, A. Pereira, L. Yang, M. Quintiliani, L. Sorensen, G. TI Sleep adequacy associated with more healthful food choices and positive workplace experience in motor freight workers SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Buxton, O. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ebbeling, C. B.] Childrens Hosp, Boston, MA 02115 USA. [Stoddard, A.; Yang, M.] New England Res Inst, Boston, MA USA. [Pereira, L.; Quintiliani, L.; Sorensen, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sorensen, G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 340 BP A113 EP A113 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000340 ER PT J AU Chen, L Basheer, R Bolortuya, Y McKenna, JT Winston, S McCarley, RW AF Chen, L. Basheer, R. Bolortuya, Y. McKenna, J. T. Winston, S. McCarley, R. W. TI Sleep changes after repeated small interfering RNA injections targeting vesicular GABA transporter in the rat basal forebrain SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1093 BP A360 EP A360 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001522 ER PT J AU Christie, M Conelly, N Bolortuya, Y McCarley, R Strecker, R AF Christie, M. Conelly, N. Bolortuya, Y. McCarley, R. Strecker, R. TI Comparison of the effects of 24-hours of total sleep deprivation and sleep interruption on vigilance performance in the rat-psychomotor vigilance task SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Christie, M.; Conelly, N.; Bolortuya, Y.; McCarley, R.; Strecker, R.] VA Boston Healthcare Syst, Brockton, MA USA. [Christie, M.; Conelly, N.; Bolortuya, Y.; McCarley, R.; Strecker, R.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1121 BP A370 EP A370 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001550 ER PT J AU Dzierzewski, JM McCrae, CS Rowe, M Marsiske, M McCoy, K McNamara, J Dautovich, N AF Dzierzewski, J. M. McCrae, C. S. Rowe, M. Marsiske, M. McCoy, K. McNamara, J. Dautovich, N. TI Nightly sleep patterns in older adults: Night-to-night fluctuations in the sleep of older good-noncomplaining, good-complaining, poor-noncomplaining, poor-complaining/insomnia, and caregivers SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Dzierzewski, J. M.; McCrae, C. S.; Rowe, M.; Marsiske, M.; McNamara, J.; Dautovich, N.] Univ Florida, Gainesville, FL USA. [McCoy, K.] Vet Adm, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 315 BP A104 EP A104 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000315 ER PT J AU Ellenbogen, JM Jiang, Y Hulbert, JC Stickgold, R AF Ellenbogen, J. M. Jiang, Y. Hulbert, J. C. Stickgold, R. TI The memory-enhancing effects of sleep SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Ellenbogen, J. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Div Sleep, Boston, MA 02115 USA. [Jiang, Y.] Dartmouth Coll, Hanover, NH 03755 USA. [Hulbert, J. C.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Stickgold, R.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1120 BP A369 EP A370 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001549 ER PT J AU Fava, M Asnis, G Shrivastava, R Lydiard, RB Bastani, B Sheehan, D Roth, T AF Fava, M. Asnis, G. Shrivastava, R. Lydiard, R. B. Bastani, B. Sheehan, D. Roth, T. TI Improved insomnia symptoms and daily functioning in patients with comorbid major depressive disorder and insomnia following zolpidem extended-release 12.5mg and escitalopram co-treatment SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD SP Amer Acad Sleep Med, Sleep Res Soc C1 [Fava, M.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Asnis, G.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Shrivastava, R.] Eastside Comprehens Med, New York, NY USA. [Lydiard, R. B.] S E Hlth Consultants, Charleston, SC USA. [Bastani, B.] N Coast Clin Trials, Beachwood, OH USA. [Sheehan, D.] Univ S Florida, Coll Med, Tampa, FL USA. [Roth, T.] Henry Ford Hosp, Sleep Disorders Ctr, Detroit, MI 48202 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 984 BP A324 EP A324 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001413 ER PT J AU Franciosi, S Yanagawa, Y McCarley, RW Brown, RE AF Franciosi, S. Yanagawa, Y. McCarley, R. W. Brown, R. E. TI The putative sleep homeostatic factor adenosine selectively inhibits one type of basal forebrain GABA neurons SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Franciosi, S.; McCarley, R. W.; Brown, R. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Franciosi, S.] Univ Milan, Inst Human Physiol, Milan, Italy. [Yanagawa, Y.] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 371, Japan. [Yanagawa, Y.] SORST, Maebashi, Gumma 371, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 44 BP A14 EP A14 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000045 ER PT J AU Hanak, V Carr, L Moorman, D Howell, M Gilmartin, G AF Hanak, V Carr, L. Moorman, D. Howell, M. Gilmartin, G. TI Screening for undiagnosed and untreated obstructive sleep apnea in patients undergoing elective surgery SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Hanak, V; Moorman, D.; Howell, M.; Gilmartin, G.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Carr, L.] Harvard Univ, Sch Med, Silberman Inst Hlth Care Qual & Safety, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1083 BP A357 EP A357 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001512 ER PT J AU Kim, Y McKenna, JT Bolortuya, Y McCarley, RW Strecker, RE AF Kim, Y. McKenna, J. T. Bolortuya, Y. McCarley, R. W. Strecker, R. E. TI Rats experience sleepiness during chronic sleep restriction SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Kim, Y.; McKenna, J. T.; Bolortuya, Y.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Kim, Y.; McKenna, J. T.; Bolortuya, Y.; McCarley, R. W.; Strecker, R. E.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 364 BP A121 EP A121 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000364 ER PT J AU King, C Popovic, D Levendowski, DJ Guerrero, M Olmstead, R Andrada, T Velimirovic, V Yan, N Zavora, T Westbrook, P AF King, C. Popovic, D. Levendowski, D. J. Guerrero, M. Olmstead, R. Andrada, T. Velimirovic, V. Yan, N. Zavora, T. Westbrook, P. TI Validation of changes in forehead venous pressure as a measure of respiratory effort SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [King, C.; Guerrero, M.; Andrada, T.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Popovic, D.; Levendowski, D. J.; Velimirovic, V.; Yan, N.; Zavora, T.; Westbrook, P.] Adv Brain Monitoring Inc, Carlsbad, CA USA. [Olmstead, R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 1006 BP A332 EP A332 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001435 ER PT J AU Kumar, S Alam, M Rai, S McGinty, D Szymusiak, R AF Kumar, S. Alam, M. Rai, S. McGinty, D. Szymusiak, R. TI Microdialysis perfusion of eszopiclone into the rat perifornical-lateral hypothalamus suppresses waking c-Fos expression in hypocretin neurons SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Kumar, S.; Alam, M.; Rai, S.; McGinty, D.; Szymusiak, R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Alam, M.; McGinty, D.; Szymusiak, R.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 66 BP A21 EP A21 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000067 ER PT J AU Lyamin, O Kosenko, P Lapierre, J Pryaslova, J Vyssotski, A Lipp, H Siegel, J Mukhametov, L AF Lyamin, O. Kosenko, P. Lapierre, J. Pryaslova, J. Vyssotski, A. Lipp, H. Siegel, J. Mukhametov, L. TI Study of sleep in a walrus SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Lyamin, O.; Lapierre, J.; Siegel, J.] Univ Calif Los Angeles, Dept Psychiat, North Hills, CA USA. [Lyamin, O.; Lapierre, J.; Siegel, J.] Univ Calif Los Angeles, VA GLAHS Sepulveda, North Hills, CA USA. [Lyamin, O.; Kosenko, P.; Pryaslova, J.; Mukhametov, L.] Utrish Dolphinarium Ltd, Moscow, Russia. [Vyssotski, A.; Lipp, H.] Univ Zurich, Inst Anat, Zurich, Switzerland. NR 0 TC 2 Z9 2 U1 2 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 73 BP A24 EP A25 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000074 ER PT J AU Martin, J Josephson, KR Khan-Hudson, A Harker, JO Alessi, CA AF Martin, J. Josephson, K. R. Khan-Hudson, A. Harker, J. O. Alessi, C. A. TI Self-reported sleep quality predicts mortality within one year of post-acute rehabilitation among older people SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Martin, J.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Josephson, K. R.; Khan-Hudson, A.; Harker, J. O.; Alessi, C. A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 292 BP A96 EP A96 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000292 ER PT J AU McKenna, JT Christie, MA McCarley, RW Strecker, RE AF McKenna, J. T. Christie, M. A. McCarley, R. W. Strecker, R. E. TI Sleepiness and impairment of sustained attention produced by sleep deprivation SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [McKenna, J. T.; Christie, M. A.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 379 BP A126 EP A126 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000379 ER PT J AU Peterfi, Z McGinty, D Szymusiak, R AF Peterfi, Z. McGinty, D. Szymusiak, R. TI Growth hormone releasing hormone (GHRH) activates GABAergic neurons in the rat preoptic hypothalamus SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Peterfi, Z.; McGinty, D.; Szymusiak, R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Peterfi, Z.; McGinty, D.; Szymusiak, R.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 67 BP A21 EP A22 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000068 ER PT J AU Platt, A Field, SH Gupta, R Chen, Z Roche, D Patel, NP Gurubhagavatula, I Christie, JD Asch, DA Kuna, ST AF Platt, A. Field, S. H. Gupta, R. Chen, Z. Roche, D. Patel, N. P. Gurubhagavatula, I Christie, J. D. Asch, D. A. Kuna, S. T. TI Neighborhood socioeconomic factors predict initial CPAP adherence better than disease or patient-level characteristics SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Platt, A.; Field, S. H.; Patel, N. P.; Gurubhagavatula, I; Christie, J. D.; Asch, D. A.; Kuna, S. T.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Platt, A.; Chen, Z.; Patel, N. P.; Christie, J. D.; Asch, D. A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Platt, A.; Field, S. H.; Gupta, R.; Roche, D.; Asch, D. A.; Kuna, S. T.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 452 BP A151 EP A151 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000452 ER PT J AU Platt, A Field, SH Zhen, C Christie, JD Roche, D Gupta, R Asch, DA Kuna, ST AF Platt, A. Field, S. H. Zhen, C. Christie, J. D. Roche, D. Gupta, R. Asch, D. A. Kuna, S. T. TI Does adherence to lipid-lowering medications predict CPAP adherence? SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Platt, A.; Field, S. H.; Christie, J. D.; Asch, D. A.; Kuna, S. T.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Platt, A.; Zhen, C.; Christie, J. D.; Asch, D. A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Platt, A.; Field, S. H.; Roche, D.; Gupta, R.; Asch, D. A.; Kuna, S. T.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 451 BP A150 EP A151 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000451 ER PT J AU Ross, RJ Gellis, LA Stepanski, EJ Green, DB Woodward, SH AF Ross, R. J. Gellis, L. A. Stepanski, E. J. Green, D. B. Woodward, S. H. TI REM phasic activity in PTSD-discordant monozygotic twins SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Ross, R. J.; Green, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Ross, R. J.; Gellis, L. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Stepanski, E. J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Woodward, S. H.] Natl Ctr PTSD, Palo Alto, CA USA. [Woodward, S. H.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 953 BP A314 EP A315 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001382 ER PT J AU Sawyer, AM Deatrick, JA Kuna, ST Weaver, TE AF Sawyer, A. M. Deatrick, J. A. Kuna, S. T. Weaver, T. E. TI Adult perceptions of the diagnosis and treatment of obstructive sleep apnea: A mixed methods study examining the influence of patient experiences and beliefs on continuous positive airway pressure adherence outcomes SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Sawyer, A. M.; Kuna, S. T.; Weaver, T. E.] Univ Penn, Ctr Sleep Resp Neurobiol, Philadelphia, PA 19104 USA. [Deatrick, J. A.; Weaver, T. E.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Sawyer, A. M.; Kuna, S. T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Sawyer, A. M.; Kuna, S. T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Deatrick, J. A.] Univ Penn, Ctr Hlth Disparities Res, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 639 BP A210 EP A210 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001068 ER PT J AU Sheehan, D Asnis, G Shrivastava, R Lydiard, RB Bastani, B Roth, T Fava, M AF Sheehan, D. Asnis, G. Shrivastava, R. Lydiard, R. B. Bastani, B. Roth, T. Fava, M. TI Zolpidem extended-release 12.5 mg co-administered with escitalopram improves insomnia symptoms and next-day functioning in generalized anxiety disorder comorbid with chronic insomnia SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD SP Amer Acad Sleep Med, Sleep Res Soc C1 [Sheehan, D.] Univ S Florida, Coll Med, Tampa, FL USA. [Asnis, G.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Shrivastava, R.] Eastside Comprehens Med, New York, NY USA. [Lydiard, R. B.] S E Hlth Consultants, Charleston, SC USA. [Bastani, B.] N Coast Clin Trials, Beachwood, OH USA. [Roth, T.] Henry Ford Sleep Disorders Ctr, Detroit, MI USA. [Fava, M.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 985 BP A325 EP A325 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001414 ER PT J AU Ward, CP Connolly, NP Christie, MA McCarley, RW Strecker, RE AF Ward, C. P. Connolly, N. P. Christie, M. A. McCarley, R. W. Strecker, R. E. TI Spatial memory impairments due to sleep fragmentation depend on rat strain and task difficulty SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Ward, C. P.] Univ Florida, Gainesville, FL USA. [Connolly, N. P.; Christie, M. A.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Connolly, N. P.; Christie, M. A.; McCarley, R. W.; Strecker, R. E.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 394 BP A131 EP A131 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000394 ER PT J AU Winkelman, JW Gottlieb, DJ AF Winkelman, J. W. Gottlieb, D. J. TI Polysomnographic correlates of restless legs syndrome in the sleep heart health study SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Winkelman, J. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med, Brighton, MA USA. [Gottlieb, D. J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gottlieb, D. J.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 807 BP A265 EP A265 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001236 ER PT J AU Woodward, S Stepanski, EJ Ross, RJ AF Woodward, S. Stepanski, E. J. Ross, R. J. TI Twins sleep more alike on night 2 than on night 1 SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Woodward, S.] VA Palo Alto HCS, Palo Alto, CA USA. [Stepanski, E. J.] Accelerated Community Oncol Res Network Inc, Memphis, TN USA. [Ross, R. J.] Univ Penn, Philadelphia, PA 19104 USA. [Ross, R. J.] Vet Affairs Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 989 BP A326 EP A326 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001418 ER PT S AU Kirchhausen, T Macia, E Pelish, HE AF Kirchhausen, Tom Macia, Eric Pelish, Henry E. BE Balch, WE Der, CJ Hall, A TI Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis SO SMALL GTPASES IN DISEASE, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID CLATHRIN-MEDIATED ENDOCYTOSIS; ACTIN-BINDING PROTEIN; GTPASE ACTIVITY; GOLGI STRUCTURE; COATED PITS; MAMMALIAN-CELLS; LIVING CELLS; IN-VITRO; MEMBRANE; PATHWAY AB The large GTPase dynamin is essential for clathrin-dependent coated-vesicle formation. Dynasore is a cell-permeable small molecule that inhibits the GTPase activity of dynamin1, dynamin2 and Drp1, the mitochondrial dynamin. Dynasore was discovered in a screen of similar to 16,000 compounds for inhibitors of the dynamin2 GTPase. Dynasore is a noncompetitive inhibitor of dynamin GTPase activity and blocks dynamin-dependent endocytosis in cells, including neurons. It is fast acting (seconds) and its inhibitory effect in cells can be reversed by washout. Here we present a detailed synthesis protocol for dynasore, and describe a series of experiments used to analyze the inhibitory effects of dynasore on dynamin in vitro and to study the effects of dynasore on endocytosis in cells. C1 [Kirchhausen, Tom; Macia, Eric; Pelish, Henry E.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kirchhausen, Tom; Macia, Eric; Pelish, Henry E.] IDI Immune Res Inst, Boston, MA USA. [Pelish, Henry E.] Makoto Life Sci Inc, Boston, MA USA. [Macia, Eric] CNRS, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM62566, GM03548, GM075252, P01 GM062566, R01 GM036548, R01 GM075252, R01 GM075252-04] NR 59 TC 177 Z9 181 U1 3 U2 23 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373968-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 438 BP 77 EP 93 DI 10.1016/S0076-6879(07)38006-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHR78 UT WOS:000255834100006 PM 18413242 ER PT S AU McDermott, U Sharma, SV Settleman, J AF McDermott, Ultan Sharma, Sreenath V. Settleman, Jeffrey BE Balch, WE Der, CJ Hall, A TI High-throughput lung cancer cell line screening for genotype-correlated sensitivity to an EGFR kinase inhibitor SO SMALL GTPASES IN DISEASE, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID MUTATIONS; GEFITINIB; ERLOTINIB AB Human cancer cell lines that can be propagated and manipulated in culture have proven to be excellent models for studying many aspects of gene function in cancer. In addition, they can provide a powerful system for assessing the molecular determinants of sensitivity to anticancer drugs. They have also been used in recent studies to identify genomic alterations and gene expression patterns that provide important insights into the genetic features that distinguish the properties of tumor cells associated with similar histologies. We have established a large repository of human tumor cell lines (> 1000) corresponding to a wide variety of tumor types, and we have developed a methodology for profiling the collection for sensitivity to putative anticancer compounds. The rationale for examining tumor cell lines on this relatively large scale reflects accumulating evidence indicating that there is substantial genetic heterogeneity among human tumor cells-even those derived from tumors of similar histologies. Thus, to develop an accurate picture of the molecular determinants of tumorigenesis and response to therapy, it is essential to study the nature of such heterogeneity in a relatively large sample set. Here, we describe the methodologies used to conduct such screens and we describe a "proof-of-concept" screen using the EGFR kinase inhibitor, erlotinib (Tarceva), with a panel of lung cancer lines to demonstrate a correlation between EGFR mutations and drug sensitivity. C1 [McDermott, Ultan] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP McDermott, U (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. RI han, chao/B-6245-2011; OI McDermott, Ultan/0000-0001-9032-4700 NR 6 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373968-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 438 BP 331 EP 341 DI 10.1016/S0076-6879(07)38023-3 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHR78 UT WOS:000255834100023 PM 18413259 ER PT J AU Blue-Howells, J McGuire, J Nakashima, J AF Blue-Howells, Jessica McGuire, Jim Nakashima, John TI Co-location of health care services for homeless veterans: A case study of innovation in program implementation SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE program innovation; program implementation; homeless; veterans ID MEDICAL-CARE; LOS-ANGELES; ILLNESS; ADULTS AB This case study examines how the Veterans Affairs Greater Los Angeles Healthcare System (GLA) improved homeless veteran service utilization through program innovation that addressed service fragmentation. The new program offered same-day co-located mental health, medical, and homeless services with a coordinated intake system. The program is analyzed using a framework proposed by Rosenheck (2001) that has four phases: the decision to implement, initial implementation, sustained maintenance, and termination or transformation. GLA was able to successfully implement a new program that remains in the sustained maintenance phase five years after the initial decision to implement. Key factors from the Rosenheck innovation model in the program's success included coalition building, linking the project to legitimate goals, program monitoring, and developing communities of practicing clinicians. The key lesson from the case study is the need for a coalition to persistently problem solve and act as advocates for the program, even after successful initial implementation. Social work leadership was critical in all phases of program implementation. C1 [Blue-Howells, Jessica; Nakashima, John] W Los Angeles Healthcare Ctr, VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [McGuire, Jim] Univ Calif Los Angeles, Sch Publ Policy & Social Res, Los Angeles, CA USA. [McGuire, Jim] NEPEC, Dept Vet Affairs, CHALENG Evaluat, Los Angeles, CA USA. [McGuire, Jim] Homelessness Prevent & Incarcerated Vet Programs, Los Angeles, CA USA. RP Blue-Howells, J (reprint author), W Los Angeles Healthcare Ctr, VA Greater Angeles Healthcare Syst, 11301 Wilshire Blvd,Mail Code 10H-5,Bldg 206,Room, Los Angeles, CA USA. EM Jessica.Blue-Howells@va.gov NR 21 TC 11 Z9 11 U1 2 U2 8 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2008 VL 47 IS 3 BP 219 EP 231 DI 10.1080/00981380801985341 PG 13 WC Social Work SC Social Work GA 355BK UT WOS:000259683500001 PM 19042482 ER PT J AU Snow, A Warner, J Zilberfein, F AF Snow, Alison Warner, Jocelyn Zilberfein, Felice TI The Increase of Treatment Options at the End of Life: Impact on the Social Work Role in an Inpatient Hospital Setting SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE End of life; treatment options; social work role; decision making ID OF-LIFE; CARE; CANCER AB Treatment choices for cancer patients are becoming increasingly complex as medicine advances and doctors are able to offer more treatment options at the end of life. Research data shows that 22% of all Medicare patients start a new chemotherapy regimen in the last month of life. In a study released in 2004, data showed treatment within two weeks of death has increased from 13.8% to 18.5% over a period of three years. Treatment options should be presented to ensure that the final treatment decision made is optimal and encompasses the patient's wishes, prognosis, financial barriers, and familial Support. In this article we explore three case studies where patients and families were faced with the challenges of making treatment decisions at the end of life and the importance and impact of the social work role in the multidisciplinary team. An inpatient social worker can assume a leadership position to assist patients and families in navigating the health care system and with difficult treatment options. C1 [Snow, Alison; Zilberfein, Felice] Mt Sinai Sch Med, New York, NY 10029 USA. [Warner, Jocelyn] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Snow, A (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1252, New York, NY 10029 USA. EM Alison.Snow@mountsinai.org NR 15 TC 6 Z9 7 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2008 VL 47 IS 4 BP 376 EP 391 DI 10.1080/00981380802179191 PG 16 WC Social Work SC Social Work GA 380BE UT WOS:000261439700003 PM 19042492 ER PT J AU Bershteyn, A Chaparro, J Yau, R Kim, M Reinherz, E Ferreira-Moita, L Irvine, DJ AF Bershteyn, Anna Chaparro, Jose Yau, Richard Kim, Mikyung Reinherz, Ellis Ferreira-Moita, Luis Irvine, Darrell J. TI Polymer-supported lipid shells, onions, and flowers SO SOFT MATTER LA English DT Article ID LATERAL DIFFUSION; CRYOELECTRON MICROSCOPY; MEMBRANES; BILAYERS; SILICA; PEG; MICROSPHERES; ADSORPTION; DYNAMICS; PHOSPHATIDYLCHOLINE AB Phospholipid-enveloped biodegradable polymer microparticles and nanoparticles synthesized by an emulsion-solvent evaporation process were characterized by confocal and cryoelectron micros-copies to show that the lipid envelope exhibits two-dimensional fluidity and can be configured into 'shell', 'onion', or 'flower' nanostructures, depending on the quantity and composition of lipids employed in the synthesis. C1 [Bershteyn, Anna; Chaparro, Jose; Yau, Richard; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn & Biol Engn, Cambridge, MA 02139 USA. [Kim, Mikyung; Reinherz, Ellis] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ferreira-Moita, Luis] Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal. RP Irvine, DJ (reprint author), MIT, Dept Mat Sci & Engn & Biol Engn, Room 8-425,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ellis_reinherz@dfci.harvard.edu; lferreiramoita@gmail.com; djirvine@mit.edu RI Moita, Luis/L-1296-2013 OI Moita, Luis/0000-0003-0707-315X FU NIAID NIH HHS [R21 AI073165, R21 AI073165-02] NR 44 TC 40 Z9 40 U1 1 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2008 VL 4 IS 9 BP 1787 EP 1791 DI 10.1039/b804933e PG 5 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 364ZY UT WOS:000260376900007 PM 19756178 ER PT J AU Wright, DE Hunt, DP AF Wright, Douglas E. Hunt, Daniel P. TI Perioperative surveillance for adverse myocardial events SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE electrocardiography; myocardial ischemia; perioperative; troponin ID MAJOR VASCULAR-SURGERY; CARDIAC TROPONIN-T; NONCARDIAC SURGERY; PROGNOSTIC VALUE; CARDIOVASCULAR EVALUATION; CAROTID-ENDARTERECTOMY; GUIDELINE UPDATE; RISK; INFARCTION; ISCHEMIA AB Perioperative myocardial infarctions occur in 1 to 4% of unselected noncardiac surgical patients, and are associated with high mortality. Detection of these events can be challenging, because 'typical' symptoms of myocardial ischemia may not be present or may be masked in the perioperative period. Therefore, surveillance by means of intraoperative cardiac monitoring and postoperative serial electrocardiograms (ECGs) and troponins may be needed. Cardiac monitoring not infrequently detects ST-segment changes suggestive of ischemia during or shortly after surgery. To respond to these changes, the risk for coronary artery disease should be assessed before recommending additional interventions. For all vascular surgery patients, and for patients who have or are felt to be at risk for coronary artery disease, serial postoperative 12-lead ECGs and troponins should be considered. Among surgical patients not meeting these criteria, obtaining routine ECGs in the absence of signs or symptoms that suggest a cardiac event may be falsely reassuring and is not felt to be useful. The presence of elevated postoperative troponins predicts worsened prognosis, and argues for intensified risk factor modification. The need for noninvasive cardiac testing or cardiac catheterization should be made on an individual basis. C1 [Wright, Douglas E.; Hunt, Daniel P.] Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educator Serv, Boston, MA 02114 USA. [Wright, Douglas E.; Hunt, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Wright, DE (reprint author), Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educator Serv, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM dewright@partners.org NR 48 TC 4 Z9 6 U1 0 U2 0 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 JAN PY 2008 VL 101 IS 1 BP 52 EP 58 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 249XO UT WOS:000252264100020 PM 18176293 ER PT J AU Smith, DJ Mattos-Graner, RO AF Smith, D. J. Mattos-Graner, R. O. TI Secretory immunity following mutans streptococcal infection or immunization SO SPECIALIZATION AND COMPLEMENTATION OF HUMORAL IMMUNE RESPONSES TO INFECTION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID GLUCAN-BINDING-PROTEIN; BRAZILIAN NURSERY CHILDREN; SINGLE-CHAIN ANTIBODIES; DENTAL-CARIES VACCINES; AGE-RELATED-CHANGES; PASSIVE-IMMUNIZATION; PROTECTIVE IMMUNITY; ORAL STREPTOCOCCI; INTRANASAL IMMUNIZATION; CHOLERA-TOXIN AB Salivary IgA antibody responses to mutans streptococci can be observed in early childhood, sometimes even before permanent colonization of the oral biofilm occurs. Many of these early immune responses are directed to components thought to be essential for establishment and emergence of mutans streptococci in the oral biofilm. Initial responses are likely to be modulated by antigen dose, by immunological maturity, and by previous encounters with similar antigenic epitopes in the pioneer commensal flora. Our understanding of these modulating factors is modest and is an opportunity for continued investigation. Under controlled conditions of infection, experimental vaccine approaches have repeatedly shown that infection and disease can be modified in the presence of elevated levels of antibody in the oral cavity. Protection can be observed regardless of antibody isotype or method used to actively or passively provide the immune reagent. Limited clinical trials have supported the utility of both of these approaches in humans. Refinements in antigen formulation, delivery vehicles, enhancing agents and routes of application, coupled with approaches that are timed to intercept most vulnerable periods of infection of primary and permanent dentition may well provide the healthcare practitioner with an additional tool to maintain oral health. C1 [Smith, D. J.; Mattos-Graner, R. O.] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM dsmith@forsyth.org RI Mattos-Graner, Renata/C-9410-2012 OI Mattos-Graner, Renata/0000-0001-8309-8135 FU FIC NIH HHS [TW-06324]; NIDCR NIH HHS [DE-04733, DE-06133, DE/AI-12434] NR 100 TC 26 Z9 27 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2008 VL 319 BP 131 EP 156 PG 26 WC Immunology; Microbiology SC Immunology; Microbiology GA BHE08 UT WOS:000252396900006 PM 18080417 ER PT J AU Friedman, DJ Dunn, JC Higgins, LD Warner, JJP AF Friedman, Darren J. Dunn, John C. Higgins, Laurence D. Warner, Jon J. P. TI Proximal biceps tendon - Injuries and management SO SPORTS MEDICINE AND ARTHROSCOPY REVIEW LA English DT Review DE proximal biceps tendon; subluxation; instability; tenotomy; tenodesis; subpectoral ID ROTATOR CUFF TEARS; LONG HEAD; ELECTROMYOGRAPHIC ANALYSIS; SUBSCAPULARIS TEARS; BICIPITAL GROOVE; GLENOID LABRUM; SHOULDER; TENODESIS; BRACHII; LESIONS AB The long head of the biceps tendon is a known pain generator of the shoulder. There are numerous pathologic entities that may affect this tendon, including tendonitis, partial tearing, and subluxation. These conditions are often associated with rotator cuff tears, especially those involving the subscapularis. Operative interventions include tenotomy and tenodesis. Tenodesis can be preformed in a proximal or distal location. Subpectoral tenodesis may have a lower recurrence rate than proximal-based techniques. C1 [Warner, Jon J. P.] Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA. [Friedman, Darren J.; Higgins, Laurence D.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Dunn, John C.] Harvard Univ, Sch Med, Boston, MA USA. RP Warner, JJP (reprint author), Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Shoulder Serv, 55 Fruit St,YAW 3 3G, Boston, MA 02114 USA. EM jwarner@partners.org NR 52 TC 37 Z9 40 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-8592 J9 SPORTS MED ARTHROSC JI Sports Med. Arthrosc. Rev. PY 2008 VL 16 IS 3 BP 162 EP 169 DI 10.1097/JSA.0b013e318184f549 PG 8 WC Sport Sciences SC Sport Sciences GA 337VE UT WOS:000258462800009 PM 18703976 ER PT S AU Ntziachristos, V Hyde, D AF Ntziachristos, Vasilis Hyde, Damon BE ReschGenger, U TI In-vivo Fluorescence Imaging: Applications, Future Trends & Approaches to Standardization SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Diffusion imaging; Fluorescence; Fluorescence imaging; Scattering; Tissue optical properties ID DIFFUSE OPTICAL TOMOGRAPHY; STRUCTURAL INFORMATION; RECONSTRUCTION; MEDIA AB Standards are important for calibration procedures in fluorescence imaging and overall for enabling accurate quantification. However, due to the strong nonlinear dependence of the fluorescence signal on tissue scattering, tissue absorption and activity depth, the construction of standards becomes challenging. So far, most fluorescent standards for diffusive imaging have been based on laboratory solutions that mix scattering, absorbing and fluorescence materials to construct substances of known and stable optical properties. Herein we review the most common characteristics of diffusive imaging and outline strategies to produce materials that can serve as standards in whole body imaging applications. C1 [Ntziachristos, Vasilis; Hyde, Damon] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ntziachristos, Vasilis; Hyde, Damon] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5406, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 549 EP 560 DI 10.1007/4243_2008_052 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000022 ER PT J AU Strachan, LR Scalapino, KJ Lawrence, HJ Ghadially, R AF Strachan, Lauren R. Scalapino, Kenneth J. Lawrence, H. Jeffery Ghadially, Ruby TI Rapid adhesion to collagen isolates murine keratinocytes with limited long-term repopulating ability in vivo despite high clonogenicity in vitro SO STEM CELLS LA English DT Article DE keratinocyte; stem cell; collagen; epidermis; colony forming ID EPIDERMAL STEM-CELLS; TRANSIT-AMPLIFYING CELLS; HAIR FOLLICLE BULGE; MOUSE BONE-MARROW; HEMATOPOIETIC STEM; SIDE POPULATION; REGULATORY LOCI; IDENTIFICATION; EXPRESSION; ASSAY AB A prevalent belief in epidermal biology is that stem cells are highly clonogenic; that is, they have the ability to produce many large colonies in vitro. However, it has been well-established in hematology, and recently suggested in epithelial biology, that short-term in vitro clonogenic assays may not be reliable predictors of long-term in vivo repopulating ability. Numerous groups have shown that rapid adhesion to collagen selects for highly clonogenic keratinocytes, but it has not been demonstrated whether this subpopulation is enriched in stem cells as defined by long- term repopulating ability in vivo. We found that although rapid adhesion to collagen (within 5 minutes) selected for cells with increased short-term colony forming ability in vitro, these cells were not enriched in long-term proliferative ability in vitro or in repopulating ability in vivo after 9 weeks. Conversely, keratinocytes that did not adhere to collagen (after 20 minutes) were less clonogenic in short-term assays but possessed equivalent long-term proliferative ability in vitro and superior long-term repopulating ability in vivo. Both the rapidly adherent cell and not rapidly adherent cell populations contained small, noncomplex basaloid cells, expressed integrin alpha 2 (a collagen IV receptor), and expressed the putative epidermal stem cell phenotype integrin alpha 6(hi)CD71(lo). Our results indicate that the superior short-term colony forming ability of collagen-adherent murine keratinocytes does not correlate with long-term repopulating ability in vitro or in vivo and that proliferation in vitro is not a reliable surrogate for stem cell behavior in vivo. C1 [Strachan, Lauren R.; Ghadially, Ruby] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Scalapino, Kenneth J.] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA. [Lawrence, H. Jeffery] San Francisco VA Med Ctr, San Francisco, CA USA. RP Ghadially, R (reprint author), Vet Adm Med Ctr, Dept Dermatol 190, 4150 Clement St, San Francisco, CA 94121 USA. EM ghadiallyr@derm.ucsf.edu FU BLRD VA [I01 BX000794]; NIAMS NIH HHS [R01 AR053765, R01-AR020786] NR 48 TC 15 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2008 VL 26 IS 1 BP 235 EP 243 DI 10.1634/stemcells.2007-0534 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 250LV UT WOS:000252302500026 PM 17932419 ER PT J AU Parekkadan, B Tilles, AW Yarmush, ML AF Parekkadan, Biju Tilles, Arno W. Yarmush, Martin L. TI Bone marrow-derived mesenchymal stem cells ameliorate autoimmune enteropathy independently of regulatory T cells SO STEM CELLS LA English DT Article DE mesenchymal stem cell; bone marrow stromal cell; tolerance; enhanced green fluorescent protein; autoimmunity; inflammatory bowel disease; regulatory T cell ID VERSUS-HOST-DISEASE; IN-UTERO TRANSPLANTATION; LYMPHOCYTE-PROLIFERATION; STROMAL CELLS; PROGENITOR CELLS; IMMUNE-RESPONSE; DIFFERENTIATION; MICE; THERAPY; INHIBIT AB Cell-based tolerogenic therapy is a relatively new approach for the treatment of autoimmune diseases. Mesenchymal stem cells (MSCs) have been shown to be potent immunomodulatory agents in a number of experimental and clinical scenarios; however, their use in various autoimmune diseases is undefined. Herein, we report the efficacy of MSC transplantation in a multiorgan autoimmunity model. Mice with defective peripheral tolerance caused by a deficiency in regulatory T cells were used as a testbed for therapy. After screening multiple target tissues of autoimmune attack, we observed an MSC-specific improvement in the histopathology of the distal ileum of treated mice. We then showed that MSCs can reduce mesenteric lymph node (MLN) cellularity in autoimmune mice during active disease and decrease activated T-cell populations in the MLN. Trafficking studies using enhanced green fluorescent protein (eGFP)-reporter MSCs revealed no appreciable engraftment in the intestine, but it did reveal the presence of eGFP+ cells organized in clusters within the MLN, as well as ancillary nodes. Semiquantitative analysis showed no difference in the number of clusters; however, eGFP+ cells in MLNs compared with ancillary nodes had distinct fibroblastoid morphology and formed a network with neighboring eGFP+ cells. Finally, we show evidence that transplantation of MSCs caused global immunosuppression, as measured by increased CD4+ CD8+ thymocyte production and serum interleukin-10 and decreased serum interferon-gamma. These data implicate the intestine as a new site of MSC tolerance induction and should motivate additional studies evaluating the use of MSCs as a treatment for autoimmune enteropathies. C1 [Parekkadan, Biju; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA USA. [Parekkadan, Biju; Tilles, Arno W.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Parekkadan, Biju; Yarmush, Martin L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [K18 DK076819, K08 DK66040, R01 DK43371] NR 42 TC 90 Z9 96 U1 1 U2 9 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2008 VL 26 IS 7 BP 1913 EP 1919 DI 10.1634/stemcells.2007-0790 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 331HX UT WOS:000258004400027 PM 18420833 ER PT J AU Eminli, S Utikal, J Arnold, K Jaenisch, R Hochedlinger, K AF Eminli, Sarah Utikal, Jochen Arnold, Katrin Jaenisch, Rudolf Hochedlinger, Konrad TI Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression SO STEM CELLS LA English DT Article DE Reprogramming; Neural progenitor cells; Induced pluripotent stem cells; Sox2; Oct4 ID HUMAN SOMATIC-CELLS; HUMAN FIBROBLASTS; DEFINED FACTORS; MOUSE; DIFFERENTIATION; GENERATION; ADULT; STATE; MYC AB Expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and beta cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are equally amenable to reprogramming into iPS cells by the same combination of factors. To test this, we have isolated genetically marked neural progenitor cells (NPCs) from neonatal mouse brains and infected them with viral vectors expressing Oct4, Sox2, Klf4, and c-Myc. Infected NPCs gave rise to iPS cells that expressed markers of embryonic stem cells, showed demethylation of pluripotency genes, formed teratomas, and contributed to viable chimeras. In contrast to other somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did not require viral Sox2 expression for reprogramming into iPS cells. Our data show that in addition to mesoderm- and endoderm-derived cell types, neural progenitor cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting that in vitro reprogramming is a universal process. These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context. STEM CELLS 2008; 26: 2467-2474 C1 [Eminli, Sarah; Utikal, Jochen; Arnold, Katrin; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Eminli, Sarah; Utikal, Jochen; Arnold, Katrin; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Eminli, Sarah] Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, Germany. [Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA USA. [Jaenisch, Rudolf] MIT, Whitehead Inst, Cambridge, MA USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St,CPZN 4242, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241 FU NIH Director's Innovator Award; Harvard Stem Cell Institute; V Foundation; Kimmel Foundation; Dr. Mildred Scheel Foundation for Cancer Research FX We thank Jennifer Shay and members of the Hochedlinger laboratory for critical review of the manuscript. We also thank Laura Prickett, Kathryn E. Folz-Donahue, Adlen Foudi, and Matthias Stadtfeld for help with FACS analysis. K. H. was supported by the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the V Foundation, and the Kimmel Foundation. J.U. was supported by the Dr. Mildred Scheel Foundation for Cancer Research. This study has been approved by the Massachusetts General Hospital animal and biosafety committees. NR 21 TC 223 Z9 247 U1 6 U2 16 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2008 VL 26 IS 10 BP 2467 EP 2474 DI 10.1634/stemcells.2008-0317 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 362DH UT WOS:000260177900002 PM 18635867 ER PT J AU Shields, DC Cheng, ML Flaherty, AW Gale, JT Eskandar, EN AF Shields, Donald C. Cheng, Ming L. Flaherty, Alice W. Gale, John T. Eskandar, Emad N. TI Microelectrode-guided deep brain stimulation for Tourette syndrome: Within-subject comparison of different stimulation sites SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE deep brain stimulation; thalamus; Tourette syndrome; microelectrode recording; internal capsule ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA AB Background: As medical therapy for Tourette syndrome (TS) is ineffective in a small subset of patients, surgical interventions, including deep brain stimulation at various sites, have been developed in recent years. Case Description: We present the case of a 40-year-old woman with TS whose severe tics had caused unilateral blindness. Despite trials of more than 40 medications, her symptoms improved significantly only after placement of bilateral deep brain stimulators in the anterior inferior internal capsule. However, symptomatic improvement was not complete, and her electrode connections eventually became permanently damaged by the remaining retrocollic jerks. She underwent removal of the internal capsule electrodes and placement of centromedian nucleus thalamic stimulators with significantly improved tic control. Conclusion: Whereas the anterior internal capsule site had also produced psychiatric side effects such as altered mood and impulse control, the thalamic site has not done so to date. Thus, distinct surgical targets for TS may be appropriate for patients with specific comorbidities. Copyright (C) 2007 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Boston, MA USA. [Shields, Donald C.; Cheng, Ming L.; Gale, John T.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Wang Ambulatory Care Ctr, 15 Parkman St,331, Boston, MA 02114 USA. EM eeskandar@partners.org NR 19 TC 46 Z9 46 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2008 VL 86 IS 2 BP 87 EP 91 DI 10.1159/000112429 PG 5 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 263WN UT WOS:000253247300004 PM 18073521 ER PT S AU Tache, Y Brunnhuber, S AF Tache, Yvette Brunnhuber, Stefan BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI From Hans Selye's Discovery of Biological Stress to the Identification of Corticotropin-Releasing Factor Signaling Pathways SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE CRF; CRF receptors; CRF antagonists; colonic motor function; irritable bowel syndrome; stress ID IRRITABLE-BOWEL-SYNDROME; COLONIC MOTOR FUNCTION; HORMONE-RECEPTOR ANTAGONIST; WATER-AVOIDANCE STRESS; GASTRIC-ACID SECRETION; CENTRAL-NERVOUS-SYSTEM; FACTOR CRF ANTAGONIST; PARAVENTRICULAR NUCLEUS; GASTROINTESTINAL-TRACT; LOCUS-COERULEUS AB Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF(1) and CRF(2) receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF(1) receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF(1) receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF(1) receptor antagonists in blunting these stress-related components. The importance of CRF(1) signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients. C1 [Tache, Yvette] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Brunnhuber, Stefan] Univ Wurzburg, Wurzburg, Germany. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU National Institute of Arthritis, Metabolism and Digestive Diseases [R01 DK-33061, R01 DK-57236, DK-41301, P50 AR-049550]; VA Merit and Senior Scientist Awards; University of Wuerzburg/Germany; European Academy of Science and Arts FX The authors' work was supported by the National Institute of Arthritis, Metabolism and Digestive Diseases, Grants R01 DK-33061, R01 DK-57236, DK-41301 (Animal Core), P50 AR-049550, and VA Merit and Senior Scientist Awards. The authors thank Drs. J. Rivier (Salk Institute, La Jolla, CA), D. Grigoriadis (Neurocrine Biosciences Inc., La Jolla, CA), and E.D. Pagani (Center Research Division, Pfizer Inc., Groton, CT) for the generous supply of different CRF agonises and antagonists used in the studies. Dr. S. Brunnhuber is supported by the University of Wuerzburg/Germany and the European Academy of Science and Arts (F. Unger), which is gratefully acknowledged. NR 131 TC 39 Z9 43 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 29 EP 41 DI 10.1196/annals.1410.007 PG 13 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300002 PM 19120089 ER PT J AU Kelly, PJ Morrow, JD Ning, MM Koroshetz, W Lo, EH Terry, E Milne, GL Hubbard, J Lee, H Stevenson, E Lederer, M Furie, KL AF Kelly, Peter J. Morrow, Jason D. Ning, MingMing Koroshetz, Walter Lo, Eng H. Terry, Erin Milne, Ginger L. Hubbard, Jane Lee, Hang Stevenson, Elizabeth Lederer, Megan Furie, Karen L. TI Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke - The biomarker evaluation for antioxidant therapies in stroke (BEAT-stroke) study SO STROKE LA English DT Article DE cerebrovascular disorders; metalloproteinase; oxidative stress ID TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; MATRIX METALLOPROTEINASES; PLASMA-LEVELS; MARKERS; BRAIN; PRODUCTS; RADICALS; INJURY AB Background and Purpose-Experimental stroke studies indicate that oxidative stress is a major contributing factor to ischemic cerebral injury. Oxidative stress is also implicated in activation of matrix metalloproteinases (MMPs) and blood-brain barrier injury after ischemia-reperfusion. Plasma biomarkers of oxidative stress may have utility as early indicators of efficacy in Phase 2 trials of antioxidant therapies in human stroke. To date, a valid biomarker has been unavailable. We measured F2-isoprostanes (F2IPs), free-radical induced products of neuronal arachadonic acid peroxidation, in acute ischemic stroke. We aimed to determine the change in plasma F2IP levels over time and relationship with plasma MMP-9 in tPA-treated and tPA-untreated stroke patients. Methods-We performed a case-control study of consecutive ischemic stroke patients (25 tPA-treated and 27 tPA-untreated) presenting within 8 hours of stroke onset. Controls were individuals without prior stroke from a primary care clinic network serving the source population from which cases were derived. Infarct volume was determined on acute diffusion-weighted MRI (DWI) performed within 48 hours using a semi-automated computerized segmentation algorithm. Phlebotomy was performed at < 8 hours, 24 hours, 2 to 5 days, and 4 to 6 weeks. F2IPs were measured by gas chromatography/mass spectrometry and MMP-9 by ELISA. Prestroke antioxidant dietary intake was measured by the 24-hour recall method. Results-In 52 cases and 27 controls, early (median 6 hours postonset) F2IPs were elevated in stroke cases compared with controls (medians 0. 041 versus 0.0295pg/mL, P = 0.012). No difference in F2IPSs was present at later time points. Early plasma F2IPs correlated with MMP-9 in all patients (P = 0.01) and the tPA-treated subgroup (P = 0.02). No correlation was found with NIHSS, DWI infarct volume, 90-day Rankin score, or C-reactive protein (P > 0.05 for all). Conclusions-In early human stroke we found evidence of increased oxidative stress and a relationship with MMP-9 expression, supporting findings from experimental studies. C1 [Kelly, Peter J.] Mater Univ Hosp, Catherine McAuley Res Ctr, Neurovasc Clin Sci Unit, Dublin 7, Ireland. [Kelly, Peter J.; Ning, MingMing; Koroshetz, Walter; Stevenson, Elizabeth; Lederer, Megan; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv, Boston, MA 02115 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol & Radiol, Neuroprotect Res Lab, Boston, MA USA. [Hubbard, Jane] Harvard Univ, Sch Med, Mallinckrodt Gen Clin Resource Ctr, Bionutr Serv, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Morrow, Jason D.; Terry, Erin; Milne, Ginger L.] Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. RP Kelly, PJ (reprint author), Mater Univ Hosp, Catherine McAuley Res Ctr, Neurovasc Clin Sci Unit, Dublin 7, Ireland. EM pjkelly@partners.org RI Milne, Ginger/D-7648-2014 OI Milne, Ginger/0000-0003-3890-151X FU AHRQ HHS [R01-HS011392]; NCI NIH HHS [CA77839]; NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK48831]; NIEHS NIH HHS [ES13125]; NIGMS NIH HHS [GM15431]; NINDS NIH HHS [K23 NS42720, K23-NS051588, R01-NS37074, R01-NS38731, R01-NS40529, R21NS052498] NR 22 TC 107 Z9 119 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2008 VL 39 IS 1 BP 100 EP 104 DI 10.1161/STROKEAHA.107.488189 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 245HB UT WOS:000251924600018 PM 18063832 ER PT J AU Mays, KL Clark, DL Gordon, AJ AF Mays, Kara L. Clark, David L. Gordon, Adam J. TI Treating Addiction with Tunes: A Systematic Review of Music Therapy for the Treatment of Patients with Addictions SO SUBSTANCE ABUSE LA English DT Review DE Addictions; music therapy; treatment AB Music therapy is the use of musical interventions in a therapeutic setting to accomplish health-related goals. Descriptions of music therapy exist in the peer-reviewed literature and indicate potential use of music therapy in treatment of patients with addiction disorders. This systematic review describes and compares the types of music therapy demonstrated in the literature and evaluates the evidence that music therapy improves outcomes of patients with addictions. A search and critical review of all the existing published literature on music therapy for the treatment of addictions was conducted using online databases and secondary search strategies. Few studies quantitatively assess the use of music therapy in the treatment of patients with addictions. Music listening provided by music therapists is commonly studied. Music therapy sessions reported were additive, not independent, treatment modalities. In the literature, no consensus exists regarding of the efficacy of music therapy as treatment for patients with addictions. C1 [Mays, Kara L.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15206 USA. [Clark, David L.] First Aid Treatment Humanity, Monaca, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, VISN 4, Mailcode 151C-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov FU VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), VA Pittsburgh Healthcare System FX This project was funded by infrastructure support funding from the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC, Director: D. Oslin; Co-Director: G. Haas), VA Pittsburgh Healthcare System. NR 27 TC 11 Z9 11 U1 1 U2 19 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 4 BP 51 EP 59 DI 10.1080/08897070802418485 PG 9 WC Substance Abuse SC Substance Abuse GA V14AZ UT WOS:000207708600005 PM 19042198 ER PT J AU Kelly, JF Myers, MG Rodolico, J AF Kelly, John F. Myers, Mark G. Rodolico, John TI What Do Adolescents Exposed to Alcoholic Anonymous Think About 12-Step Groups? SO SUBSTANCE ABUSE LA English DT Article DE Mutual-help groups; self-help; adolescents; Alcoholics Anonymous; Narcotics Anonymous; addiction; substance abuse; treatment; substance use disorder AB Objectives: Referral to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) is a common continuing care recommendation. Evidence suggests some youth benefit, yet, despite referrals, youth participation is low. Little is known about adolescents' experiences of AA/NA. Greater knowledge would inform and help tailor aftercare recommendations. Method: Two clinical samples of youth (N = 74 and N = 377) were asked about their perceptions of, and experiences with, AA/NA with responses categorized by content into domains assessed for face validity and reliability. Results: The aspects of AA/NA youth liked best were general group dynamic processes related to universality, support, and instillation of hope. The most common reason for discontinuing was boredom/lack of fit. Conclusions: General group-therapeutic, and not 12-step-specific, factors are most valued by youth during early stages of recovery and/or degree of AA/NA exposure. Many youth discontinue due to a perceived lack of fit, suggesting a mismatch between some youth and aspects of AA/NA. doi:10.1080/08897070802093122 [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mailaddress: < docdelivery@haworthpress.com > Website: < http://www.HaworthPress.com > (C) 2008 by The Haworth Press. All rights reserved.] C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, MGH Addict Res Program, Boston, MA 02114 USA. [Kelly, John F.; Rodolico, John] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Myers, Mark G.] VA San Diego Healthcare Syst, San Diego, CA USA. [Myers, Mark G.] Univ Calif San Diego, San Diego, CA 92103 USA. [Rodolico, John] McLean Hosp, Belmont, MA USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, MGH Addict Res Program, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org RI Reis, Aline/G-9573-2012; OI Myers, Mark/0000-0003-4044-2914 FU NIAAA NIH HHS [R01 AA015526] NR 36 TC 15 Z9 16 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 2 BP 53 EP 62 DI 10.1080/08897070802093122 PG 10 WC Substance Abuse SC Substance Abuse GA V14AV UT WOS:000207708200006 PM 19042324 ER PT J AU Walley, AY Phillips, KA Gordon, AJ AF Walley, Alexander Y. Phillips, Karran A. Gordon, Adam J. TI The Patients in Recovery (PIR) Perspective: Teaching Physicians About Methamphetamine SO SUBSTANCE ABUSE LA English DT Article DE Methamphetamine abuse; physician education; substance abuse training AB Methamphetamine dependence is an emerging epidemic confronting physicians. In an effort to improve understanding of its impact, the authors presented an educational workshop at a national meeting for general internists featuring small group discussions with patients in recovery (PIR) from methamphetamine dependence. Participants rated the workshop highly, stating it would lead to concrete change in their teaching, research, or patient care practices and they would invite the workshop to their institution for presentation. Direct interaction with PIR was the most valued aspect of the workshop. Lessons learned included patient's fear of being "turned in" limits disclosure of methamphetamine use to physicians; active users have little insight into methamphetamine-related changes in physical appearance; and a sense of productivity reinforces ongoing methamphetamine use. Workshops that include small group discussions between physicians and PIR are an innovative, practical, and acceptable method to teach physicians about their role in helping patients with substance dependence. C1 [Walley, Alexander Y.] Boston Med Ctr, Gen Internal Med Sect, Clin Addict Res & Educ Unit, Boston, MA 02218 USA. [Phillips, Karran A.] Johns Hopkins Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, VISN 4, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Walley, AY (reprint author), Boston Med Ctr, Gen Internal Med Sect, Clin Addict Res & Educ Unit, 801 Massachusetts Ave,2nd Floor, Boston, MA 02218 USA. EM awalley@bu.edu OI Walley, Alexander/0000-0002-8158-4882 FU National Institute on Drug Abuse [R25-DA13582]; National Institute of Allergy and Infectious Diseases [T32-AI52074]; VA HSR&D Research Career Development Award [RCD-00038-2] FX The authors would like to acknowledge the assistance of Deborah Service of the Matrix Institute and the 10 volunteer small group leaders at the workshop. The authors would also like to acknowledge Maryann Amodeo, MSW, PhD, for guidance in developing the workshop. Dr. Walley was supported by the National Institute on Drug Abuse (R25-DA13582) and National Institute of Allergy and Infectious Diseases (T32-AI52074). Dr. Gordon was supported by a VA HSR&D Research Career Development Award (RCD-00038-2). The results of this paper were presented at the 2006 Association for Medical Education and Research in Substance Abuse (AMERSA) national conference, Washington, DC, November 2007. NR 12 TC 0 Z9 0 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 4 BP 61 EP 64 DI 10.1080/08897070802418493 PG 4 WC Substance Abuse SC Substance Abuse GA V14AZ UT WOS:000207708600006 PM 19042199 ER PT J AU Katzburg, JR Farmer, MM Poza, IV Sherman, SE AF Katzburg, Judith R. Farmer, Melissa M. Poza, Ines V. Sherman, Scott E. TI Listen to the consumer: Designing a tailored smoking-cessation program for women SO SUBSTANCE USE & MISUSE LA English DT Article DE women veterans; smoking cessation; tailored; consumer-focus ID VA HEALTH-CARE; FEMALE VETERANS; GENDER-DIFFERENCES; NICOTINE DEPENDENCE; CONTROLLED-TRIAL; SOCIAL SUPPORT; MEDICAL-CARE; TOBACCO; PREDICTORS; THERAPY AB We used a consumer-driven approach to develop a model smoking-cessation program for women. Four focus groups (N = 23 [5-7/group]), each lasting 2 hours, were led by a professional moderator and audiotaped in 2004. Researchers reviewed transcripts; key themes were identified using scrutiny techniques (Ryan and Bernard, 2003). Necessary elements of a smoking-cessation program for women included support and choice (i.e., control over the program components), suggesting the need for an individualized program. Identifying appropriate components is a critical step in the development of efficacious programs that target substance-abusing populations; focus group methodology is useful in this endeavor. The study's implications and limitations are noted. C1 [Katzburg, Judith R.] Univ Calif Los Angeles, Anderson Sch Management, Johnson & Johnson Healthcare Inst, Los Angeles, CA 90095 USA. [Farmer, Melissa M.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, North Hills, CA USA. [Poza, Ines V.] Poza Consulting Serv, Santa Monica, CA USA. [Sherman, Scott E.] VA New York Harbor Healthcare Syst, Dept Vet Affairs, New York, NY USA. [Sherman, Scott E.] NYU, Sch Med, New York, NY 10003 USA. RP Katzburg, JR (reprint author), Univ Calif Los Angeles, Anderson Sch Management, Johnson & Johnson Healthcare Inst, 110 Westwood Plaza,Gold Hall,Suite B307,Box 95148, Los Angeles, CA 90095 USA. EM Judith.Katzburg@anderson.ucla.edu OI Sherman, Scott/0000-0003-1752-7303 NR 58 TC 9 Z9 9 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2008 VL 43 IS 8-9 BP 1240 EP 1259 DI 10.1080/10826080801914204 PG 20 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 329DE UT WOS:000257846300018 PM 18649241 ER PT J AU Gianni, L Cole, BF Panzini, I Snyder, R Holmberg, SB Byrne, M Crivellari, D Colleoni, M Aebi, S Simoncini, E Pagani, O Castiglione-Gertsch, M Price, KN Goldhirsch, A Coates, AS Ravaioli, A AF Gianni, Lorenzo Cole, Bernard F. Panzini, Ilaria Snyder, Raymond Holmberg, Stig B. Byrne, Michael Crivellari, Diana Colleoni, Marco Aebi, Stefan Simoncini, Edda Pagani, Olivia Castiglione-Gertsch, Monica Price, Karen N. Goldhirsch, Aron Coates, Alan S. Ravaioli, Alberto TI Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group SO SUPPORTIVE CARE IN CANCER LA English DT Article DE adjuvant therapy; adverse event; anemia; breast cancer; chemotherapy ID QUALITY-OF-LIFE; PATIENTS RECEIVING CHEMOTHERAPY; EPOETIN-ALPHA; ERYTHROPOIETIN; WOMEN; TRANSFUSION; HEMOGLOBIN; PREDICTION; MANAGEMENT; TAMOXIFEN AB Goal of work Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. Materials and methods We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. Main results Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P=0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. Conclusions Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia. C1 [Gianni, Lorenzo; Panzini, Ilaria; Ravaioli, Alberto] Osped Infermi, Div Oncol & Ematol, I-47037 Rimini, Italy. [Gianni, Lorenzo; Panzini, Ilaria; Ravaioli, Alberto] Ist Sci Romagnolo Studio & Cura Tumori, I-47037 Rimini, Italy. [Cole, Bernard F.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Cole, Bernard F.] Dartmouth Med Sch, Lebanon, NH USA. [Snyder, Raymond] St Vincents Hosp, Melbourne, Vic, Australia. [Holmberg, Stig B.] Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden. [Byrne, Michael] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Crivellari, Diana] Ctr Riferimento Oncol, I-33081 Aviano, Italy. [Colleoni, Marco; Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Aebi, Stefan] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Aebi, Stefan; Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Simoncini, Edda] Oncol Med Spedali Civili, Brescia, Italy. [Pagani, Olivia; Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Castiglione-Gertsch, Monica; Coates, Alan S.] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA USA. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. RP Gianni, L (reprint author), Osped Infermi, Div Oncol & Ematol, Azienda USL Rimini Via Settembrini 2, I-47037 Rimini, Italy. EM lgianni@auslrn.net RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU NCI NIH HHS [CA 75362] NR 27 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JAN PY 2008 VL 16 IS 1 BP 67 EP 74 DI 10.1007/s00520-007-0295-y PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 240QC UT WOS:000251601100009 PM 17629752 ER PT J AU Stewart, L Grifiss, JM Jarvis, GA Way, LW AF Stewart, Lygia Grifiss, J. McLeod Jarvis, Gary A. Way, Lawrence W. TI Elderly patients have more severe biliary infections: Influence of complement-killing and induction of TNF alpha production SO SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Hepato-Pancreato-Biliary-Association CY APR 14-17, 2005 CL Ft Lauderdale, FL SP Amer Hepato Pancreato Biliary Assoc ID NECROSIS-FACTOR-ALPHA; ACTIVE ANTIRETROVIRAL THERAPY; GALLSTONE DISEASE; INFLAMMATORY CYTOKINES; PIGMENT GALLSTONES; MORTALITY; BACTERIA; INTERLEUKIN-6; SEPSIS; PATHOGENESIS AB Background. Biliary bacteria are more common in elderly patients and cause more serious illnesses. The reasons for this are unclear. We noted previously that bacterial serum-sensitivily and induction of TNF alpha production in sera (iTNFsera) were associated with severe biliary infections. We examined the influence of age and these factors on illness severity. Methods. Three-hundred and forty Patients were studied. Gallstones and bile were cultured. Illness was staged as none (no clinical infection or inflammation), SIRS (fever, leukocytosis), severe (cholangitis, abscess, empyema), or MODS (bacteremia, hypotension, organ dysfunction/failure). Bacterial serum-sensitivity and TNF alpha induction were measured. Younger (< 70 years) and elderly (>= 70 years) patients were compared. Results. Biliaiy bacteria were more common in elderly (64% vs 41%, P < .0001). Among patients with biliary bacteria, the elderly had more serious illnesses: none: 44% younger, 19% elderly; SIRS: 16% younger, 22% elderly; severe: 22% younger, 21 % elderly; MODS 18% younger, 38% elderly (P = .003). Bacteria from elderly patients induced more TNF alpha (580 vs 310 pg/ml, P = .023). In both groups, serum-sensitive bacteria caused infectious manifestations and induced abundant TNF alpha; however, serum-resistant bacteria from elderly usually (69%) caused infectious manifestations and abundant TNF alpha, while serum-resistant bacteria from younger patients rarely (8%) caused infectious manifestations and minimal TNF alpha. Elderly patients with high iTNFsera bacteria had more severe illnesses. Conclusions. Biliary bacteria were more common in elderly patients and produced more serious illnesses. Many younger patients with biliary bacteria displayed no infectious manifestations. Elderly patients harbored more virulent bacteria, and had a heightened response to high iTNFsera bacteria, as well as bacteria largely tolerated by younger patients. C1 [Stewart, Lygia; Way, Lawrence W.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Stewart, Lygia] San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. [Grifiss, J. McLeod; Jarvis, Gary A.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Immunochem, San Francisco, CA 94143 USA. [Grifiss, J. McLeod; Jarvis, Gary A.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Stewart, L (reprint author), Dept Surg 112, 4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@med.va.gov NR 39 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2008 VL 143 IS 1 BP 103 EP 112 DI 10.1016/j.surg.2007.06.035 PG 10 WC Surgery SC Surgery GA 245YB UT WOS:000251973600012 PM 18154938 ER PT J AU McCormack, MC Kwon, E Eberlin, KR Randolph, M Friend, DS Thomas, AC Watkins, MT Austen, WG AF McCormack, Michael C. Kwon, Edwin Eberlin, Kyle R. Randolph, Mark Friend, Dan S. Thomas, Andrew C. Watkins, Michael T. Austen, William G., Jr. TI Development of reproducible histologic injury severity scores: Skeletal muscle reperfusion injury SO SURGERY LA English DT Article ID ISCHEMIA-REPERFUSION; ISCHAEMIA/REPERFUSION INJURY; COMPLEMENT; PROTEIN; MODEL; MICE AB Background. Ischemia-reperfusion injury of skeletal muscle is a common clinical and experimental problem. To date, there has been no uniform and reproducible method to assess the extent of histologic injury. In this study, we developed a novel statistical methodology for evaluating injury in individual myocytes and 3 distinct methods for the interpretation of this data. Methods. C57/BL6 mice underwent 2 h of hindlimb ischemia followed by reperfusion for 3 (n = 11), 24 (n = 12), or 48 (n = 10) h. The gastrocnemius muscles were harvested, stained, and evaluated under microscopy. Standardized criteria were applied to score individual myocytes as healthy or injured., and injury score was expressed as injured fibers/total fibers %. Three methods of analyzing myocyte data were developed and evaluated with statistical Block-Random Sampling to determine the number of counted fibers required to represent accurately the total injury. The Full-Frame Counting, Fourfold Divided Counting, and Stratified Individual Counting methods differ in the random order in which fibers or microscopic fields are scored. Results. The 3 methods were found to be statistically sound at all experimental time points. Using the Full-Frame, Fourfold, and Stratified methods, the maximum number of required fibers at all time points was 600, 300, and 100, respectively, to obtain an estimation of injury with a 95 % confidence interval. Conclusions. These criteria and statistical methods for histologic evaluation of ischemia-reperfusion injury in skeletal muscle are accurate and reproducible. The Fourfold method is the most practical and technically efficient method of assessing injury. Such a quantitative, direct assessment of injury is important and will be useful for future studies. C1 [McCormack, Michael C.; Kwon, Edwin; Eberlin, Kyle R.; Randolph, Mark; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02144 USA. [Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02144 USA. [Thomas, Andrew C.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Friend, Dan S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pathol, Boston, MA 02115 USA. RP Austen, WG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC 453,15 Parkman St, Boston, MA 02144 USA. EM wausten@partners.org NR 20 TC 25 Z9 25 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2008 VL 143 IS 1 BP 126 EP 133 DI 10.1016/j.surg.2007.06.005 PG 8 WC Surgery SC Surgery GA 245YB UT WOS:000251973600014 PM 18154940 ER PT J AU Hayden, PJ Mitsiades, CS Anderson, KC Richardson, PG AF Hayden, Patrick J. Mitsiades, Constantine S. Anderson, Kenneth C. Richardson, Paul G. TI From the bench to the bedside: emerging new treatments in multiple myeloma SO TARGETED ONCOLOGY LA English DT Review DE Multiple myeloma; Thalidomide; Lenalidomide; Bortezomib; Targeted therapies ID PEGYLATED LIPOSOMAL DOXORUBICIN; STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; MULTICENTER PHASE-I/II; TUMOR-MICROENVIRONMENTAL INTERACTIONS; PROTEASOME INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; INDUCTION TREATMENT PRIOR; ACID COMBINATION THERAPY; HIGH-DOSE DEXAMETHASONE AB Several novel drug classes have been developed for multiple myeloma treatment within the last decade. The immunomodulatory drugs, thalidomide and lenalidomide, and the first-in-class proteasome inhibitor, bortezomib, target not only the malignant plasma cells but also key stromal cell support for the neoplastic clone. All three compounds have proven efficacy in advanced disease and increasing evidence for excellent response rates and clinical benefit in newly diagnosed patients. Attention is now focused on producing rational molecularly based drug combinations, incorporating both novel agents and conventional drugs, to further improve outcome. In the setting of autologous stem cell transplantation, the incorporation of these therapies into transplant-based treatment has recently been shown to result in superior overall survival, as have other combinations in relapsed disease, such as bortezomib with liposomally encapsulated doxorubicin. Several new agents are now in clinical trials or are at advanced stages of pre-clinical studies. These include second generation proteasome inhibitors, as well as inhibitors of heat shock proteins, histone deacetylases, receptor tyrosine kinases, and agents targeting the microenvironment of tumors, including defibrotide. C1 [Hayden, Patrick J.; Mitsiades, Constantine S.; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 98 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 J9 TARGET ONCOL JI Target. Oncol. PD JAN PY 2008 VL 3 IS 1 BP 19 EP 29 DI 10.1007/s11523-007-0072-3 PG 11 WC Oncology SC Oncology GA 451QY UT WOS:000266486200004 ER PT J AU Fisher, JM Fisher, DE AF Fisher, Jonathan M. Fisher, David E. TI From suntan to skin cancers: molecular pathways and prevention strategies SO TARGETED ONCOLOGY LA English DT Review DE Melanin; Pigment; Ultraviolet; Melanocyte; Keratinocytes ID SUNSCREEN USE; MELANOMA; RECEPTOR; CELL; PIGMENTATION; MELANOCORTIN; EXPRESSION; DEFICIENT; PEPTIDES; FRANCE AB The incidence of skin cancer is rising, and significantly linked to carcinogenic effects of ultraviolet radiation. While clashes in lifestyle and cancer risk have undoubtedly contributed to this health crisis, it is equally clear that certain human populations have a notably lower risk of skin cancer. This apparent natural protection, typically afforded by darker skin pigmentation or an easy ability to tan, has begun to reveal mechanistic insights of great relevance to skin cancer risk. An understanding of the genes that participate in pigmentation and the sun-tanning response has permitted greater understanding of the intracellular and intercellular signaling events that culminate in human skin pigmentation. Moreover the same observations have also suggested novel targeted approaches to mimic the pigmentary response using agents that spare the cell from carcinogenic effects of ultraviolet radiation. The application of such strategies is not yet at hand, but potentially promises to provide a complementary approach to prevention of cutaneous cancer. C1 [Fisher, Jonathan M.; Fisher, David E.] Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. RP Fisher, JM (reprint author), Dana Farber Canc Inst, Melanoma Program, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 19 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 J9 TARGET ONCOL JI Target. Oncol. PD JAN PY 2008 VL 3 IS 1 BP 41 EP 44 DI 10.1007/s11523-007-0066-1 PG 4 WC Oncology SC Oncology GA 451QY UT WOS:000266486200006 ER PT J AU Gaufberg, E Baumer, N Hinrichs, M Krupat, E AF Gaufberg, Elizabeth Baumer, Nicole Hinrichs, Margaret Krupat, Ed TI Professional Boundaries: The Perspective of the Third Year Medical Student in Negotiating Three Boundary Challenges SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID SELF-DISCLOSURE; EDUCATION; ETHICS; CURRICULUM; SCHOOL; ABUSE AB Background: The negotiation and maintenance of professional boundaries is a central developmental challenge for medical students in clinical training. The purpose of this study is to assess problem solving strategies, decisions made, level of confidence, and language used by beginning third year medical students when faced with professional boundary challenges. Description: Forty-two students in the first quarter of their third year at Harvard Medical School viewed three brief audiovisual trigger tapes, each depicting a medical student faced with a boundary challenge (the offer of a gift, a personal question from a patient, an errand request by a supervisor). Evaluation: There was a high degree of agreement and confidence among students about how to negotiate a monetary gift (reject) and how to respond to a patient's too personal question (not answer and/or redirect). However, the students were less confident and more divided on the issue of whether or not to run a personal errand for the team at the request of a superior. Conclusion: Our findings have implications for medical professionalism curricula, especially regarding the importance of mentorship and role modeling in medical education. Effective professional boundaries curricula allow the student to problem solve and practice communication skills in boundary challenging situations. C1 [Gaufberg, Elizabeth] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02139 USA. [Baumer, Nicole] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krupat, Ed] Harvard Univ, Sch Med, Ctr Evaluat, Cambridge, MA 02139 USA. RP Gaufberg, E (reprint author), Harvard Univ, Sch Med, Cambridge Hlth Alliance, 1493 Cambridge St, Cambridge, MA 02139 USA. EM Elizabeth.gaufberg@hms.harvard.edu NR 32 TC 3 Z9 3 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PY 2008 VL 20 IS 4 BP 334 EP 339 DI 10.1080/10401330802384862 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 366CL UT WOS:000260458100009 PM 18855238 ER PT J AU Peacock, WF Bhatt, DL Diercks, D Amsterdam, E Chandra, A Ohman, EM Brown, DFM Januzzi, J AF Peacock, W. Frank Bhatt, Deepak L. Diercks, Deborah Amsterdam, Ezra Chandra, Ablhinav Ohman, E. Magnus Brown, David F. M. Januzzi, James TI Cardiologists' and emergency physicians' perspectives on and knowledge of reperfusion guidelines pertaining to ST-segment-elevation myocardial infarction SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE angioplasty, transluminal, percutaneous coronary/standards/utilization cardiovascular diseases/epiderniology/mortality; chronology as topic; delivery of health care/standards; fibrinolysis; guideline adherence; hospitals/standards; practice guidelines as topic; quality assurance/health care; randomized controlled studies as topic; statistics & numerical data; statistics as topic; time factors; treatment outcome ID PERCUTANEOUS CORONARY INTERVENTION; HIGH-RISK PATIENTS; TO-BALLOON TIME; FIBRINOLYTIC THERAPY; PRIMARY ANGIOPLASTY; RANDOMIZED TRIALS; HEART-DISEASE; MORTALITY; MANAGEMENT; IMPROVEMENT AB We sought to determine U.S. physicians'knowledge and perspectives regarding the 2004 American College of Cardiology/American Heart Association guidelines for management of patients who have ST-segment-elevation myocardial infarction (STEMI). We invited 45,998 physicians from the American Medical Association's roster to take an Internet survey of U. S. cardiologists and emergency physicians who were hospital-based or who had hospital-admitting privileges. To represent individual and combined populations, data were weighted on the basis of years in practice, sex, and geographic region. Of 505 cardiologists and 509 emergency physicians who completed the survey, 90% worked in an urban or suburban setting and 82% at hospitals with a cardiac catheterization laboratory. Sampling error was 3.4%. Most respondents (61%) believed that overall myocardial infarction treatment needed a "great deal" or "fair amount" of improvement; 24% were,, somewhat" or "not at all" familiar with the guidelines. Although 84% knew the recommended STEMI treatments for a patient who presents within 3 hours of symptom onset without contraindications to reperfusion or delay to invasive treatment, only 11 % knew that there is no preferred approach. If percutaneous coronary intervention proved impossible within 90 minutes of presentation, 21 % reported that eligible patients-assuming early presentation, confirmed STEMI diagnosis, and no high-risk STEMI or contraindications to fibrinolysis-would "rarely" or "never" receive guideline-recommended fibrinolysis. Many cardiologists and emergency physicians are unfamiliar with the guidelines and with the uncertainty that surrounds therapeutic approaches, which suggests the need for increased education on effective treatments to expedite myocardial reperfusion in STEMI. C1 [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44195 USA. [Bhatt, Deepak L.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA. [Amsterdam, Ezra] Univ Calif Davis, Dept Cardiovasc Med, Davis, CA 95616 USA. [Diercks, Deborah] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Chandra, Ablhinav] Duke Univ, Dept Emergency Med, Durham, NC 27710 USA. [Ohman, E. Magnus] Duke Univ, Dept Cardiol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Januzzi, James] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Peacock, WF (reprint author), Cleveland Clin, Dept Emergency Med, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM Peacocw@ccf.org NR 24 TC 4 Z9 5 U1 0 U2 1 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 2008 VL 35 IS 2 BP 152 EP 161 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 318NC UT WOS:000257097700011 PM 18612446 ER PT J AU Sattler, M Abidoye, O Salgia, R AF Sattler, Martin Abidoye, Oyewale Salgia, Ravi TI EGFR-Targeted Therapeutics: Focus on SCCHN and NSCLC SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE cetuximab; epidermal growth factor receptor; Erbitux; head and neck cancer; lung cancer; targeted therapy ID CELL-LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; MULTICENTER PHASE-II; NECK-CANCER; C-MET; GEFITINIB; CETUXIMAB; HEAD; ERLOTINIB AB Cancers of the head and neck and of the lung are associated with high morbidity and mortality rates that have remained relatively unchanged for more than 3 decades, despite advances in radiation therapies and chemotherapies over the same time. It is generally believed that the efficacy of standard therapy regimens has reached a plateau for these cancers. The discovery of specific aberrant molecular signaling pathways in solid tumors has afforded promising new directions for newer "targeted" cancer therapeutics. Among these, the epidermal growth factor receptor (EGFR) shows promise as a therapeutic target. Clinical studies have demonstrated that this targeted approach provides clinically meaningful benefit. This article reviews EGFR-targeted therapies in use and in development, with a focus on the role of EGFR in the pathophysiology of head and neck and lung cancer, and new concepts being investigated to improve outcomes with these agents. C1 [Abidoye, Oyewale; Salgia, Ravi] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Sattler, Martin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sattler, Martin] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Dept Med, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu FU NIH/NCI [CA125541-02, CA129501]; American Lung Association; V-Foundation; Respiratory Health Association of Chicago; Kate McMullen Foundation; University of Chicago Cancer Research Center FX Funding to RS is from NIH/NCI R01 (CA125541-02 and CA129501), American Lung Association, V-Foundation (with the Geleerd Family), Respiratory Health Association of Chicago, Kate McMullen Foundation, and the University of Chicago Cancer Research Center. NR 58 TC 12 Z9 12 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2008 VL 8 BP 909 EP 919 DI 10.1100/tsw.2008.117 PG 11 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 380QE UT WOS:000261479500021 PM 18836658 ER PT J AU Becker, L Huang, Q Mashimo, H AF Becker, Laren Huang, Qin Mashimo, Hiroshi TI Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE Lgr5; stem cell; cancer; colon; small intestine; adenoma; Barrett's esophagus; CD133; tumorigenesis; stem cell niche ID PROTEIN-COUPLED RECEPTOR; BARRETTS-ESOPHAGUS; PROGENITOR CELLS; CANCER CELLS; BETA-CATENIN; IDENTIFICATION; EPITHELIUM; ORIGIN; COLON; OVEREXPRESSION AB Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barretta's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5(+) cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5(+) cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis. C1 [Becker, Laren; Huang, Qin; Mashimo, Hiroshi] VA Boston Healthcare Syst, Boston, MA USA. [Becker, Laren] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Becker, Laren; Huang, Qin; Mashimo, Hiroshi] Harvard Univ, Sch Med, Boston, MA USA. RP Mashimo, H (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM hmashimo@hms.harvard.edu FU VA Merit Research Award [T32 DK 07760]; Beth Israel Deaconess Medical Center FX Sources of support include the VA Merit Research Award and T32 DK 07760 "Research Training in Gastroenterology" institutional grant through Beth Israel Deaconess Medical Center (Program Director: J. Thomas Lamont, M.D.). NR 35 TC 66 Z9 68 U1 0 U2 5 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2008 VL 8 BP 1168 EP 1176 DI 10.1100/tsw.2008.148 PG 9 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 380QE UT WOS:000261479500052 PM 19030762 ER PT J AU Schulz, C Konrad, I Sauer, S Orschiedt, L Koellnberger, M Lorenz, R Walter, U Massberg, S AF Schulz, Christian Konrad, Ildiko Sauer, Susanne Orschiedt, Lena Koellnberger, Maria Lorenz, Reinhard Walter, Ulrich Massberg, Steffen TI Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE atherosclerosis; platelet pharmacology; anti platelet agents; atherothrombosis; animal models ID LOW-DOSE ASPIRIN; PLATELET-ADHESION; CARDIOVASCULAR-DISEASE; THROMBUS FORMATION; ATHEROSCLEROSIS; PREVENTION; TRIAL; ATHEROGENESIS; ACTIVATION; INITIATION AB Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by similar to 50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice. C1 [Schulz, Christian; Konrad, Ildiko; Sauer, Susanne; Orschiedt, Lena; Koellnberger, Maria; Massberg, Steffen] Tech Univ, Klinikum Rechts Isar, Deutsch Herzzentrum Muenchen, Munich, Germany. [Schulz, Christian; Konrad, Ildiko; Sauer, Susanne; Orschiedt, Lena; Koellnberger, Maria; Massberg, Steffen] Tech Univ, Klinikum Rechts Isar, Med Klin 1, Munich, Germany. [Lorenz, Reinhard] Univ Muenchen, Inst Prophylaxe & Epidemiol Kreislaufkrankheiten, Munich, Germany. [Walter, Ulrich] Julius Maximilians Univ, Inst Klin Biochem & Pathobiochem, Wurzburg, Germany. [Massberg, Steffen] Harvard Univ, Sch Med, CBR Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Schulz, C (reprint author), Deutsch Herzzentrum Cardiol, Lazarettstr 136, D-80636 Munich, Germany. EM schulz@dhm.mhn.de RI Schulz, Christian/J-8545-2012 OI Schulz, Christian/0000-0003-3878-7833 NR 28 TC 29 Z9 29 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JAN PY 2008 VL 99 IS 1 BP 190 EP 195 DI 10.1160/TH07-03-0235 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 255PR UT WOS:000252670400026 PM 18217153 ER PT J AU Nowak, J Kalinka-Warzocha, E Juszczynski, P Mika-Witkowska, R Zajko, M Graczyk-Pol, E Coiffier, B Salles, G Warzocha, K AF Nowak, J. Kalinka-Warzocha, E. Juszczynski, P. Mika-Witkowska, R. Zajko, M. Graczyk-Pol, E. Coiffier, B. Salles, G. Warzocha, K. TI Haplotype-specific pattern of association of human major histocompatibility complex with non-Hodgkin's lymphoma outcome SO TISSUE ANTIGENS LA English DT Article DE association; killer immunoglobulin-like receptor ligands; major histocompatibility complex haplotypes; non-Hodgkin's lymphoma; prognosis ID TUMOR-NECROSIS-FACTOR; B-CELL LYMPHOMAS; GENETIC POLYMORPHISMS; TNF RECEPTOR; T-CELLS; EXPRESSION; LINKAGE; REGION; ALPHA; ACTIVATION AB In the previous studies, some human major histocompatibility complex (MHC) genes such as TNF, LTA and human leukocyte antigen (HLA)-DR2 genes and A1-B8-TNF-308A haplotype were implied in non-Hodgkin's lymphoma (NHL) outcome. In the current study, we have assigned most probable six-locus haplotypes determined by HLA-A, -Cw, -B and -DRB1 highly polymorphic genes and non-HLA LTA(+252) and TNF-308 single nucleotide polymorphisms (SNPs) in 152 NHL Caucasian French patients. We have broadly mapped the MHC region by its component blocks and tagging alleles. Ten frequent (with haplotype frequency > 1%) six-locus extended haplotypes (EHs) were revealed in NHL patients. The only two adjacent locus fragment of 8.1 EH associated with shortened freedom from progression (FFP) was B*08-LTA(+252G) (P = 0.0084, RR = 2.45). Interestingly, 305-kbp-long, four-locus fragment of 8.1 EH, Cw*07-B*08-LTA(+252G)-TNF-308A block was much strongly associated with shortened FFP (P = 0.00045, RR = 3.26). The analysis of further extended haploblocks comprising five or six loci showed weaker association with outcome measures, suggesting linkage disequilibrium to be the cause of DRB1*03 and A*01 allele associations. In contrast, all fragments of 7.1 EH influenced FFP favorably with top association of TNF-308G allele. In multivariate analysis, only Cw*07-B*08-LTA(+252G)-TNF-308A and TNF-308G-DRB1*01 haplotypes remained predictive for shortened FFP (P = 0.024 and 0.027, respectively) and independent of International Prognostic Index (P = 0.00044). This study reveals that the block composition of EHs may cause important functional differences for NHL outcomes. Further study will be required in NHL patients by fine mapping with dense microsatellite or SNP tags to define susceptibility genes in associating regions. C1 [Warzocha, K.] Inst Haematol & Transfus Med, Dept Hematol, PL-02766 Warsaw, Poland. [Nowak, J.; Mika-Witkowska, R.; Zajko, M.; Graczyk-Pol, E.] Inst Haematol & Transfus Med, Immunogenet Lab, Warsaw, Poland. [Kalinka-Warzocha, E.] Reg Oncol Ctr, Dept Proliferat Dis, Lodz, Poland. [Juszczynski, P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coiffier, B.; Salles, G.] Univ Lyon 1, Serv Hematol, Hosp Civils Lyon, Pierre Benite, France. RP Warzocha, K (reprint author), Inst Haematol & Transfus Med, Dept Hematol, 14 Indira Gandhi St, PL-02766 Warsaw, Poland. EM warzocha@ihit.waw.pl RI Nowak, Jacek/B-8045-2009; OI Nowak, Jacek/0000-0002-3474-7597 NR 35 TC 9 Z9 10 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JAN PY 2008 VL 71 IS 1 BP 16 EP 26 DI 10.1111/j.1399-0039.2007.00954.x PG 11 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 239ZA UT WOS:000251555600002 PM 17971052 ER PT J AU Ivancic, PC Pearson, AM Tominaga, Y Simpson, AK Yue, JJ Panjabi, MM AF Ivancic, Paul C. Pearson, Adam M. Tominaga, Yasuhiro Simpson, Andrew K. Yue, James J. Panjabi, Manohar M. TI Biomechanics of Cervical Facet Dislocation SO TRAFFIC INJURY PREVENTION LA English DT Article DE Bilateral Facet Dislocation; Cervical Spine; Facet Joint; Neck Loads; Injury Mechanism ID FLEXION-DISTRACTION INJURIES; STRUCTURAL-PROPERTIES; SIMULATED WHIPLASH; JOINT KINEMATICS; SPINE; FRACTURES; MECHANICS; EXTENSION; STRENGTHS AB Objectives: The goal of this study was to compute the dynamic neck loads during simulated high-speed bilateral facet dislocation and investigate the injury mechanism. Methods: Ten osteoligamentous functional spinal units (C3/4, n = 4; C5/6, n = 3; C7/T1, n = 3) were prepared with muscle force replication, motion tracking flags, and a 3.3-kg mass rigidly attached to the upper vertebra. Frontal impacts of increasing severity were applied to the lower vertebra until dislocation was achieved. Inverse dynamics was used to calculate the dynamic neck loads during dislocation. Average peak impact acceleration required to cause dislocation ranged between 7.6 and 11.6 g. This resulted in dynamic neck loads applied at average peak rates of 906 Nm/s for flexion moment, 8017 N/s for anterior shear, and 8100 N/s for axial compression. To determine the temporal event patterns, the average occurrence times of the load and motion peaks were statistically compared (P < 0.05). Results: Among average peak loads, axial compression of 233.6 N was first to occur followed by anterior shear force of 73.1 N and flexion moment of 30.7 Nm. Among average peak motions, axial separation of 5.3 mm was first to occur followed by flexion rotation of 63.1 degrees and anterior shear of 21.5 mm. Subsequently, average peak posterior shear force of 110.3 N was observed as the upper facet became locked in the intervertebral foramina. Average peak axial compression of 6.6 mm occurred significantly later than all preceding events. Conclusions: During bilateral facet dislocation, the main loads included flexion moment and forces of axial compression and anterior shear. These loads caused flexion rotation, facet separation, and anterior translation of the upper facet relative to the lower. The present data help elucidate the injury mechanism of cervical facet dislocation. C1 [Ivancic, Paul C.; Yue, James J.; Panjabi, Manohar M.] Yale Univ, Sch Med, Biomech Res Lab, Dept Orthopaed & Rehabil, New Haven, CT 06520 USA. [Pearson, Adam M.] Dartmouth Hitchcock Med Ctr, Dept Orthopaed Surg, Lebanon, NH 03766 USA. [Tominaga, Yasuhiro] St Marianna Univ, Sch Med, Dept Orthopaed Surg, Kanagawa, Japan. [Simpson, Andrew K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. [Simpson, Andrew K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ivancic, PC (reprint author), Yale Univ, Sch Med, Biomech Res Lab, Dept Orthopaed & Rehabil, 333 Cedar St,POB 208071, New Haven, CT 06520 USA. EM paul.ivancic@yale.edu FU Cervical Spine Research Society FX This research was supported by a grant from the Cervical Spine Research Society. NR 29 TC 5 Z9 7 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1538-9588 J9 TRAFFIC INJ PREV JI Traffic Inj. Prev. PY 2008 VL 9 IS 6 BP 606 EP 611 DI 10.1080/15389580802344804 PG 6 WC Public, Environmental & Occupational Health; Transportation SC Public, Environmental & Occupational Health; Transportation GA 387DN UT WOS:000261932000015 PM 19058109 ER PT B AU Fang, QQ Carp, S Selb, J Boas, D AF Fang, Qianqian Carp, Stefan Selb, Juliette Boas, David BE Azar, FS Intes, X TI Optical Imaging and X-Ray Imaging SO TRANSLATIONAL MULTIMODALITY OPTICAL IMAGING SE Artech House Bioinformatics and Biomedical Imaging Series LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; NEAR-INFRARED TOMOGRAPHY; MONITORING NEOADJUVANT CHEMOTHERAPY; BREAST-CANCER; IN-VIVO; BLOOD-FLOW; SCREENING MAMMOGRAPHY; DIFFUSIVE LIGHT; SPECTROSCOPY; PET C1 [Fang, Qianqian; Carp, Stefan; Selb, Juliette; Boas, David] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Fang, QQ (reprint author), Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu; carp@nmr.mgh.harvard.edu; juliette@nmr.mgh.harvard.edu; dboas@nmr.mgh.harvard.edu NR 110 TC 0 Z9 0 U1 0 U2 0 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-307-1 J9 ARTECH HSE BIOINF BI JI Artech House Bioinform. Biomed. Imaging Ser. PY 2008 BP 185 EP 204 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BJL11 UT WOS:000266734600009 ER PT J AU Raab, MS Richardson, PG Anderson, KC AF Raab, Marc S. Richardson, Paul G. Anderson, Kenneth C. BE Rajkumar, SV Kyle, RA TI Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma SO TREATMENT OF MULTIPLE MYELOMA AND RELATED DISORDERS LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; LOW-DOSE THALIDOMIDE; LENALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW-TRANSPLANTATION; PREVIOUSLY TREATED PATIENTS; COOPERATIVE-ONCOLOGY-GROUP; PHASE-II; VAD CHEMOTHERAPY; HIGH-RISK C1 [Raab, Marc S.] Heidelberg Univ, Dept Med, D-69120 Heidelberg, Germany. [Raab, Marc S.] Natl Ctr Tumor Dis, Multiple Myeloma Res Ctr, D-69120 Heidelberg, Germany. [Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. RP Raab, MS (reprint author), Heidelberg Univ, Dept Med, INF 410, D-69120 Heidelberg, Germany. NR 125 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51503-0 PY 2008 BP 46 EP 63 DI 10.1017/CBO9780511551901.005 D2 10.1017/CBO9780511551901 PG 18 WC Oncology SC Oncology GA BDM18 UT WOS:000313789100005 ER PT J AU Treon, SP Merlini, G AF Treon, Steven P. Merlini, Giampaolo BE Rajkumar, SV Kyle, RA TI Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma SO TREATMENT OF MULTIPLE MYELOMA AND RELATED DISORDERS LA English DT Article; Book Chapter ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; IGM MONOCLONAL GAMMOPATHY; STEM-CELL TRANSPLANTATION; ANTIBODY-MEDIATED IMMUNOTHERAPY; PROTEASOME INHIBITOR BORTEZOMIB; COLD-REACTING AUTOANTIBODIES; COOPERATIVE-ONCOLOGY-GROUP; HIGH-DOSE THERAPY; MULTIPLE-MYELOMA C1 [Treon, Steven P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Merlini, Giampaolo] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Merlini, Giampaolo] Fdn IRCCS Policlin San Matteo, Ctr Res & Treatment Syst Amyloidosis, I-27100 Pavia, Italy. RP Treon, SP (reprint author), Harvard Univ, Sch Med, M547,44 Binney St, Boston, MA 02115 USA. OI Merlini, Giampaolo/0000-0001-7680-3254 NR 177 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51503-0 PY 2008 BP 129 EP 149 DI 10.1017/CBO9780511551901.011 D2 10.1017/CBO9780511551901 PG 21 WC Oncology SC Oncology GA BDM18 UT WOS:000313789100011 ER PT J AU Allard, WJ Moore, RG Miller, MC Somers, E Brown, AK Nilsson, O Skates, SJ Knapp, RC AF Allard, W. Jeffrey Moore, Richard G. Miller, M. Craig Somers, Elizabeth Brown, Amy K. Nilsson, Olle Skates, Steven J. Knapp, Robert C. TI Application of a Novel Dual Biomarker Algorithm for Differential Diagnosis in Patients with an Adnexal Mass SO TUMOR BIOLOGY LA English DT Meeting Abstract CT 36th Meeting of the International-Society-of-Oncology-and-BioMarkers CY OCT 05-09, 2008 CL Tokyo, JAPAN SP Int Soc Oncol & BioMarkers C1 [Allard, W. Jeffrey; Miller, M. Craig; Somers, Elizabeth; Nilsson, Olle] Fujirebio Diagnost Inc, Malvern, PA USA. [Moore, Richard G.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Brown, Amy K.] Univ Connecticut, Hartford Hosp, Hartford, CT 06112 USA. [Skates, Steven J.; Knapp, Robert C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2008 VL 29 BP 30 EP 30 PG 1 WC Oncology SC Oncology GA 355RA UT WOS:000259724800045 ER PT B AU Maryniuk, MD Christian, MJ AF Maryniuk, Melinda D. Christian, Mary Jean BE Feinglos, MN Bethel, MA TI Medical Nutrition Therapy in Type 2 Diabetes SO TYPE 2 DIABETES MELLITUS: AN EVIDENCE-BASED APPROACH TO PRACTICAL MANAGEMENT SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Nutrition; carbohydrate; meal planning; weight management; diet; dietitian; glycemic index; type 2 diabetes ID LOW-CARBOHYDRATE DIET; WEIGHT-LOSS; INSULIN-RESISTANCE; RANDOMIZED-TRIAL; GLYCEMIC INDEX; MANAGEMENT; PREVENTION; DISEASE; GLUCOSE; RISK AB Medical Nutrition Therapy is a cornerstone of diabetes management. While its effectiveness to reduce A1C by 1-2% has been demonstrated when delivered by registered dietitians. all members of the medical care team need to understand the basic elements of MNT to reinforce the care plan. Although an integral part of the treatment strategy, patients with type 2 diabetes are particularly challenged by the need for weight loss. However, there are other strategies besides a calorie-restricted diet that will improve metabolic measures. Patients and providers alike may be confused by the myriad messages related to level of carbohydrate recommended, glycemic index, fiber and the diet-of-the-day in the popular press. This chapter, divided in three sections, includes 1) an overview of popular messages, separating fact from fiction, 2) a summary of the evidence based nutrition recommendations for each nutrient and 3) guidelines for weight reduction. C1 [Maryniuk, Melinda D.] Joslin Diabet Ctr, Affiliated Programs, Boston, MA 02215 USA. [Christian, Mary Jean] Univ Calif Irvine, Joslin Diabet Ctr, Irvine, CA USA. RP Maryniuk, MD (reprint author), Joslin Diabet Ctr, Affiliated Programs, Boston, MA 02215 USA. NR 50 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-794-5 J9 CONTEMP ENDOCRINOL S PY 2008 BP 115 EP 133 DI 10.1007/978-1-60327-043-4_8 D2 10.1007/978-1-60327-043-4 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJQ60 UT WOS:000266995700008 ER PT J AU Singhal, AB Koroshetz, WJ Caplan, LR AF Singhal, Aneesh B. Koroshetz, Walter J. Caplan, Louis R. BE Caplan, LR TI REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROMES SO UNCOMMON CAUSES OF STROKE, 2ND EDITION LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; CALL-FLEMING-SYNDROME; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; GUILLAIN-BARRE-SYNDROME; THUNDERCLAP HEADACHE; INTRACRANIAL HEMORRHAGE; INTRACEREBRAL HEMORRHAGE; CAROTID-ENDARTERECTOMY; TRANSCRANIAL DOPPLER; MIGRAINOUS VASOSPASM C1 [Singhal, Aneesh B.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Singhal, AB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 121 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87437-3 PY 2008 BP 505 EP 514 DI 10.1017/CBO9780511544897.068 D2 10.1017/CBO9780511544897 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BDP59 UT WOS:000314314600068 ER PT J AU Feldman, AS McDougal, WS Harisinghani, MG AF Feldman, Adam S. McDougal, W. Scott Harisinghani, Mukesh G. TI The potential of nanoparticle-enhanced imaging SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE magnetic resonance imaging; lymph node; metastasis; prostate cancer; bladder cancer; testicular cancers; penile cancer ID SUPERPARAMAGNETIC IRON-OXIDE; LYMPH-NODE METASTASES; POSITRON-EMISSION-TOMOGRAPHY; PROSTATE-CANCER; MR LYMPHANGIOGRAPHY; CERVICAL-CARCINOMA; CONTRAST AGENTS; BLADDER-CANCER; NONINVASIVE DETECTION; C-11-CHOLINE PET AB Accurate lymph node staging in genitourinary malignancy is an important component in the diagnostic algorithm and therapeutic planning. A promising new method for lymph node staging is lymphotrophic nanoparticle enhanced magnetic resonance imaging. This novel technique uses ultrasmall Superparamagnetic iron oxide particles, which localize in lymph nodes and provide detailed characterization of these nodes independent of typically accepted size criteria. This review provides a brief overview of the presently accepted methods for noninvasive lymph node staging and thoroughly discusses lymphotrophic nanoparticle enhanced MR imaging: a technique that can be used for accurate detection of lymph node metastases and will likely play a major role in noninvasive lymph node staging in genitourinary cancer in the near future. (c) 2008 Elsevier Inc. All rights reserved. C1 [Feldman, Adam S.; McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Feldman, AS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM afeldman@partnners.org NR 52 TC 16 Z9 18 U1 1 U2 3 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 JAN-FEB PY 2008 VL 26 IS 1 BP 65 EP 73 DI 10.1016/j.urolonc.2007.03.016 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 255TK UT WOS:000252680100012 PM 18190834 ER PT J AU Lee, SWH Liong, ML Yuen, KH Leong, WS Cheah, PY Khan, NAK Krieger, JN AF Lee, Shaun Wen Huey Liong, Men Long Yuen, Kah Hay Leong, Wing Seng Cheah, Phaik Yeong Khan, Nurzalina Abdul Karim Krieger, John N. TI Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome SO UROLOGY LA English DT Article ID INSTITUTES-OF-HEALTH; ERECTILE FUNCTION IIEF; CLINICAL CHARACTERISTICS; INTERNATIONAL INDEX; SYMPTOM INDEX; MEN; TRIAL; DISTURBANCES; EPIDEMIOLOGY; POPULATION AB OBJECTIVES To examine the prevalence, characteristics, and impact of sexual dysfunction in our primary care referral population. METHODS Participants seeking treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited from general urology clinics. The subjects completed the National Institutes of Health-Chronic Prostatitis Symptom Index, International Index of Erectile Function-5, and selected questions from the University of Washington Symptom Score. Additional information on demographics and medical and treatment history were also obtained. Sexual dysfunction was defined as self-reported erectile dysfunction (ED) or ejaculatory difficulty, or both. RESULTS Of 296 participants with CP/CPPS, 214 (72.3%) reported sexual dysfunction. The National Institutes of Health-Chronic Prostatitis Symptom Index total score averaged 22.5 +/- 6.9 for participants with sexual dysfunction compared with 20.4 +/- 7.8 for participants who did not report sexual dysfunction (P = 0.03). Of the 214 participants with sexual dysfunction, 54 (25.0%) complained of ED only, 71 (33.4%) complained of ejaculatory difficulties only, and 89 (41.6%) complained of both ED and ejaculatory difficulties. Men reporting both ED and ejaculatory difficulty reported worse CP/CPPS symptoms (analysis of variance, P = 0.042) and worse quality of life (analysis of variance, P = 0.006) than men without sexual dysfunction. CONCLUSIONS Sexual dysfunction was reported by almost three quarters of patients with CP/CPPS. Patients with CP/CPPS and sexual dysfunction experienced substantially worse symptoms, particularly worse quality of life, than other patients with CP/CPPS. Sexual dysfunction merits consideration as an important aspect of CP/CPPS and a potential outcome measure. C1 [Krieger, John N.] Univ Washington, Sch Med, Dept Urol Surg, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Sci Malaysia, Sch Pharmaceut Sci, George Town, Malaysia. Lam Wah Ee Hosp, Dept Urol, George Town, Malaysia. RP Krieger, JN (reprint author), Univ Washington, Sch Med, Dept Urol Surg, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jkrieger@u.washington.edu RI Yuen, Kah Hay /F-9059-2010; Khan, Nurzalina/E-3875-2012; OI Lee, Shaun/0000-0001-7361-6576 FU NIDDK NIH HHS [DK065266, DK38955] NR 24 TC 36 Z9 47 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2008 VL 71 IS 1 BP 79 EP 84 DI 10.1016/j.urology.2007.08.043 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 263CH UT WOS:000253194700019 PM 18242370 ER PT J AU Chung, CS Chen, MH Cullen, J McLeod, D Carroll, P D'Amico, AV AF Chung, Christine S. Chen, Ming-Hui Cullen, Jennifer McLeod, David Carroll, Peter D'Amico, Anthony V. TI Time to prostate-specific antigen nadir after androgen suppression therapy for postoperative or postradiation PSA failure and risk of prostate dancer-specific mortality SO UROLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; NATURAL-HISTORY; MITOXANTRONE; PREDNISONE; DOCETAXEL AB OBJECTIVES To examine whether the time to the prostate-specific antigen (PSA) nadir was associated with prostate cancer-specific mortality (PCSM) in men with PSA failure after radical prostatectomy or radiotherapy who do not achieve an undetectable PSA level (PSA level of 0.2 ng/mL or less) after 8 months of androgen suppression therapy (AST). METHODS The cohort included 162 men with localized prostate cancer treated with AST for an increasing PSA level after radical prostatectomy or radiotherapy. Gray's analysis was used to evaluate for an association between the time to PSA nadir after 8 months of AST and the time to PCSM, adjusting for established prognostic factors. The median age and follow-up after 8 months of AST was 71.2 and 1.8 years, respectively. RESULTS After adjusting for Gleason score, pre-AST PSA doubling time, PSA at AST, PSA nadir value, time to PSA failure, initial treatment, and age, the time to PSA nadir was significantly associated with PCSM (adjusted hazard ratio 2.53, 95% confidence interval 1.24 to 5.14, P = 0.01). Men with a PSA nadir greater than the median value of 0.9 ng/mL and the time to PSA nadir longer than the median of 4 months had significantly greater PCSM estimates (P < 0.001) compared with men with a PSA nadir of 0.9 ng/mL or less. CONCLUSIONS The time to PSA nadir, combined with the PSA nadir level, can be used to identify men who are at high risk of PCSM after a short course of AST for entry onto clinical trials using novel systemic agents with AST. C1 [Chung, Christine S.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Storrs, CT USA. Ctr Prostate Dis Res, Bethesda, MD USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Chung, CS (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, L2,75 Francis St, Boston, MA 02115 USA. EM cchung1@partners.org NR 16 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2008 VL 71 IS 1 BP 136 EP 140 DI 10.1016/j.urology.2007.08.028 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 263CH UT WOS:000253194700031 PM 18242382 ER PT J AU Gonzalez, SF Kuligowski, M Pitcher, LA Carroll, MC AF Gonzalez, S. F. Kuligowski, M. Pitcher, L. A. Carroll, M. C. TI Intravital Microscopic Characterization of the Innate Immune Responses to Influenza SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE Intravital Microscopy; Influenza; Innate Immunity; Inflammation C1 [Gonzalez, S. F.; Kuligowski, M.; Pitcher, L. A.; Carroll, M. C.] Harvard Univ, Sch Med, IDI Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600143 ER PT J AU Burkitt, KH Larkin, GL AF Burkitt, Kelly H. Larkin, Gregory L. TI The Transtheoretical Model in Intimate Partner Violence Victimization: Stage Changes Over Time SO VIOLENCE AND VICTIMS LA English DT Article DE intimate partner violence; stages of change; transtheoretical model; medical advocacy; longitudinal studies AB The transtheoretical model of behavior change (TTM) has been extended to describe the process of change in victims of intimate partner violence (IPV); however, it has not been validated over time or in a population of women experiencing IPV who are not currently in shelter. This article examines the process of change in IPV victims longitudinally and identifies factors that may relate to staging and stage progression. Fifty-three women were enrolled on presentation to an emergency department for health care treatment and completed follow-up at 3 to 4 months. Measures of TTM staging, use of community resources, ongoing abuse, mental health, and social support were collected. Cluster analyses were conducted, and descriptive summaries of clusters and significant demographic, abuse, and outcome variables related to cluster membership are presented. A five-cluster solution was selected on the basis of parsimony, theory, and overall coherence with the data. Forward progression through the stages over time was related to both the use of community resources and ending the IPV relationship. C1 [Burkitt, Kelly H.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Larkin, Gregory L.] Yale Univ, Sch Med, Dept Surg, Sect Emergency Med, New Haven, CT 06510 USA. RP Burkitt, KH (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM Kelly.burkitt@va.gov NR 39 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2008 VL 23 IS 4 BP 411 EP 431 DI 10.1891/0886-6708.23.4.411 PG 21 WC Criminology & Penology SC Criminology & Penology GA V18EP UT WOS:000207988400001 PM 18788336 ER PT B AU Farooqi, MH Jabbour, SA AF Farooqi, M. Hamed Jabbour, Serge A. BE Clouse, AL Sherif, K TI Thyroid Disorders SO WOMEN'S HEALTH IN CLINICAL PRACTICE: A HANDBOOK FOR PRIMARY CARE SE Current Clinical Practice LA English DT Article; Book Chapter ID SUBCLINICAL HYPOTHYROIDISM; SUPPRESSIVE THERAPY; GRAVES-DISEASE; NODULES; OPHTHALMOPATHY; MANAGEMENT; ANTIBODIES; CARCINOMA; DIAGNOSIS; CYTOLOGY AB Thyroid disorders in women can be divided into two broad categories, disorders of thyroid function, such as hyperthyroidism or hypothyroidism; and disorders related to structural or morphological abnormalities. The major areas of concern here are thyroid nodules and thyroid cancer. C1 [Farooqi, M. Hamed] Mease Countryside Hosp, FACE Joslin Diabet Ctr, Safety Harbor, FL USA. [Jabbour, Serge A.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Div Endocrinol Diabet & Metab Dis, Philadelphia, PA 19107 USA. RP Farooqi, MH (reprint author), Mease Countryside Hosp, FACE Joslin Diabet Ctr, Safety Harbor, FL USA. NR 29 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-631-3 J9 CURR CLIN PRACT PY 2008 BP 251 EP 272 DI 10.1007/978-1-59745-469-8_13 D2 10.1007/978-1-59745-469-8 PG 22 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology GA BJO64 UT WOS:000266908000013 ER PT J AU Velmahos, GC Constantinou, C Kasotakis, G AF Velmahos, George C. Constantinou, Constantinos Kasotakis, George TI Safety of repair for severe duodenal injuries SO WORLD JOURNAL OF SURGERY LA English DT Article ID COMBINED PANCREATODUODENAL INJURIES; PYLORIC EXCLUSION; PANCREATICODUODENAL INJURIES; SURGICAL-MANAGEMENT; TRAUMA; GASTROJEJUNOSTOMY; REAPPRAISAL; PANCREAS; WOUNDS AB Background There is ongoing debate about the management of severe duodenal injuries (SDIs), and earlier studies have recommended pyloric exclusion. The objective of this study was to compare primary repair with pyloric exclusion to examine if primary repair can be safely used in SDIs. Methods The medical records of 193 consecutive patients who were admitted between August 1992 and January 2004 with duodenal injuries were reviewed. After excluding early deaths (n = 50), low-grade duodenal injuries ( n = 81), and pancreatoduodenectomies for catastrophic trauma ( n = 12), a total of 50 patients with SDIs ( grade III, IV, or V) were analyzed. Primary repair (PR-simple duodenorrhaphy or resection and primary anastomosis) was performed in 34 (68%) and pyloric exclusion ( PE) in 16 (32%). Characteristics and outcomes of these two groups were compared. Results PE and PR patients were similar for age, injury severity score, abdominal abbreviated injury score, physiologic status on admission, time to operation, and most abdominal organs injured. PE patients had more pancreatic injuries (63% vs. 24%, p < 0.01), a higher frequency of injuries to the first and second part of the duodenum (79% vs. 42%, p = 0.02), and a nonsignificant trend toward more grade IV and V injuries (37% vs. 18%, p = 0.11). There was no difference in morbidity (including complications specific to the duodenal repair), mortality, and intensive care unit and hospital length of stay between the two groups. Conclusions Pyloric exclusion is not necessary for all patients with SDIs, as previously suggested. Selected SDI patients can be safely managed by simple primary repair. C1 Univ So Calif, Med Ctr, Div Trauma & Crit Care, Dept Surg, Los Angeles, CA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI Kasotakis, George/0000-0002-7630-0742 NR 34 TC 13 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JAN PY 2008 VL 32 IS 1 BP 7 EP 12 DI 10.1007/s00268-007-9255-4 PG 6 WC Surgery SC Surgery GA 243LE UT WOS:000251797400002 PM 17952703 ER PT S AU Buckner, RL Andrews-Hanna, JR Schacter, DL AF Buckner, Randy L. Andrews-Hanna, Jessica R. Schacter, Daniel L. BE Kingstone, A Miller, MB TI The brain's default network - Anatomy, function, and relevance to disease SO YEAR IN COGNITIVE NEUROSCIENCE 2008 SE Annals of the New York Academy of Sciences LA English DT Article DE default mode; default system; default network; fMRI; PET; hippocampus; memory; schizophrenia; Alzheimer ID RESTING-STATE NETWORKS; STIMULUS-INDEPENDENT THOUGHT; MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; MONKEY RETROSPLENIAL CORTEX; MILD COGNITIVE IMPAIRMENT; POSTERIOR PARIETAL CORTEX; TASK-INDUCED DEACTIVATION; BOLD SIGNAL FLUCTUATIONS; MENTAL TIME-TRAVEL AB Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease. C1 [Buckner, Randy L.; Andrews-Hanna, Jessica R.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02148 USA. [Buckner, Randy L.; Andrews-Hanna, Jessica R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02148 USA. [Buckner, Randy L.; Andrews-Hanna, Jessica R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, William James Hall,33 Kirkland Dr, Cambridge, MA 02148 USA. EM rbuckner@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU Howard Hughes Medical Institute; NIA NIH HHS [AG021910]; NIMH NIH HHS [MH060941]; PHS HHS [JAG08441] NR 225 TC 3209 Z9 3306 U1 136 U2 906 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-726-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1124 BP 1 EP 38 DI 10.1196/annals.1440.011 PG 38 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BHX09 UT WOS:000257139500002 PM 18400922 ER PT S AU Schacter, DL Addis, DR Buckner, RL AF Schacter, Daniel L. Addis, Donna Rose Buckner, Randy L. BE Kingstone, A Miller, MB TI Episodic simulation of future events - Concepts, data, and applications SO YEAR IN COGNITIVE NEUROSCIENCE 2008 SE Annals of the New York Academy of Sciences LA English DT Article DE episodic memory; simulation of future events; neuroimaging; constructive memory; episodic future thinking; prospective memory; foresight; hippocampus; prefrontal cortex; mental time travel ID MENTAL TIME-TRAVEL; WESTERN SCRUB-JAYS; AUTOBIOGRAPHICAL MEMORY; IMPLEMENTATION INTENTIONS; COGNITIVE NEUROSCIENCE; MAJOR DEPRESSION; PHENOMENAL CHARACTERISTICS; TEMPORAL ORGANIZATION; NEGATIVE EVENTS; SPATIAL MEMORY AB This article focuses on the neural and cognitive processes that support imagining or simulating future events, a topic that has recently emerged in the forefront of cognitive neuroscience. We begin by considering concepts of simulation from a number of areas of psychology and cognitive neuroscience in order to place our use of the term in a broader context. We then review neuroimaging, neuropsychological, and cognitive studies that have examined future-event simulation and its relation to episodic memory. This research supports the idea that simulating possible future events depends on much of the same neural machinery, referred to here as a core network, as does remembering past events. After discussing several theoretical accounts of the data, we consider applications of work on episodic simulation for research concerning clinical populations suffering from anxiety or depression. Finally, we consider other aspects of future-oriented thinking that we think are related to episodic simulation, including planning, prediction, and remembering intentions. These processes together comprise what we have termed "the prospective brain," whose primary function is to use past experiences to anticipate future events. C1 [Schacter, Daniel L.; Addis, Donna Rose; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Schacter, Daniel L.; Addis, Donna Rose; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061; Addis, Donna Rose/0000-0002-6231-1491 FU Howard Hughes Medical Institute NR 169 TC 312 Z9 315 U1 16 U2 59 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-726-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1124 BP 39 EP 60 DI 10.1196/annals.1440.001 PG 22 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BHX09 UT WOS:000257139500003 PM 18400923 ER PT J AU Ruff, RL McKerracher, L Selzer, ME AF Ruff, Robert L. McKerracher, Lisa Selzer, Michael E. TI Repair and Neurorehabilitation Strategies for Spinal Cord Injury SO YEAR IN NEUROLOGY 2008 SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE spinal cord injury; neural repair; neural regeneration; neurorehabilitation; brain computer interface; functional electrical stimulation ID RETINAL GANGLION-CELLS; ENHANCES AXONAL REGENERATION; CENTRAL-NERVOUS-SYSTEM; CHONDROITIN SULFATE PROTEOGLYCAN; MYELIN-ASSOCIATED GLYCOPROTEIN; GROWTH-ASSOCIATED PROTEIN-43; INHIBITS NEURITE OUTGROWTH; FACTOR-KAPPA-B; FUNCTIONAL RECOVERY; NOGO RECEPTOR AB The failure of axons in the central nervous system (CNS) to regenerate has been considered the main factor limiting recovery from spinal cord injury (SCI). Impressive gains in identification of growth-inhibitory molecules in the CNS led to expectations that their neutralization would lead to functional regeneration. However, results of therapeutic approaches based on this assumption have been mixed. Recent data suggest that neurons differ in their ability to regenerate through similar extracellular environments, and moreover, they undergo a developmental loss of intrinsic regenerative ability. Factors mediating these intrinsic regenerative abilities include expression of (1) receptors for inhibitory molecules such as the myelin-associated growth inhibitors and developmental guidance molecules, (2) surface molecules that permit axon adhesion to cells in the path of growth, (3) cytoskeletal proteins that mediate the mechanics of axon growth, and (4) molecules in the intracellular signaling cascades that mediate responses to chemoattractive and chemorepulsive cues. In contrast to axon development, regeneration might involve internal protrusive forces generated by microtubules, either through their own elongation or by transporting other cytoskeletal elements such as neurofilaments into the axon tip. Because of the complexity of the regenerative program, one approach will probably be insufficient to achieve functional restoration of neuronal circuits. Combination treatments will be increasingly prominent. SCI is a debilitating and costly condition that compromises pursuit of activities usually associated with an independent and productive lifestyle. This article discusses recent advances in neurorehabilitation that can improve the life quality of individuals with SCI. C1 [Ruff, Robert L.] Vet Affairs Med Ctr, Louis Stokes Dept, Cleveland, OH USA. [Ruff, Robert L.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Ruff, Robert L.] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. [Selzer, Michael E.] Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Selzer, Michael E.] US Dept Vet Affairs, Off Res & Dev, Washington, DC USA. RP Ruff, RL (reprint author), Cleveland VA Med Ctr, Neurol Serv 127W, 10701 East Blvd, Cleveland, OH 44106 USA. EM robert.ruffl@va.gov NR 133 TC 32 Z9 33 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1142 BP 1 EP 20 DI 10.1196/annals.1444.004 PG 20 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIM55 UT WOS:000260858700001 PM 18990118 ER PT S AU Schmahmann, JD Smith, EE Eichler, FS Filley, CM AF Schmahmann, Jeremy D. Smith, Eric E. Eichler, Florian S. Filley, Christopher M. BE Johnson, RT TI Cerebral White Matter Neuroanatomy, Clinical Neurology, and Neurobehavioral Correlates SO YEAR IN NEUROLOGY 2008 SE Annals of the New York Academy of Sciences LA English DT Article DE fiber tracts; neuropsychiatry; cognition; demyelination; vascular dementia ID CENTRAL-NERVOUS-SYSTEM; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; X-LINKED-ADRENOLEUKODYSTROPHY; LANGERHANS CELL HISTIOCYTOSIS; NORMAL-PRESSURE HYDROCEPHALUS; AIDS DEMENTIA COMPLEX; COGNITIVE-AFFECTIVE SYNDROME; DELAYED POSTHYPOXIC LEUKOENCEPHALOPATHY; ACUTE DISSEMINATED ENCEPHALOMYELITIS; MAGNETIC-RESONANCE SPECTROSCOPY AB Lesions of the cerebral white matter (WM) result in focal neurobehavioral syndromes, neuropsychiatric phenomena, and dementia. The cerebral WM contains fiber pathways that convey axons linking cerebral cortical areas with each other and with subcortical structures, facilitating the distributed neural circuits that subserve sensorimotor function, intellect, and emotion. Recent neuroanatomical investigations reveal that these neural circuits are topographically linked by five groupings of fiber tracts emanating from every neocortical area: (1) cortico-cortical association fibers; (2) corticostriatal fibers; (3) commissural fibers; and cortico-subcortical pathways to (4) thalamus and (5) pontocerebellar system, brain stem, and/or spinal cord. Lesions of association fibers prevent communication between cortical areas engaged in different domains of behavior. Lesions of subcortical structures or projection/striatal fibers disrupt the contribution of subcortical nodes to behavior. Disconnection syndromes thus result from lesions of the cerebral cortex, subcortical structures, and WM tracts that link the nodes that make up the distributed circuits. The nature and the severity of the clinical manifestations of WM lesions are determined, in large part, by the location of the pathology: discrete neurological and neuropsychiatric symptoms result from focal WM lesions, whereas cognitive impairment across multiple domains-WM dementia-occurs in the setting of diffuse WM disease. We present a detailed review of the conditions affecting WM that produce these neurobehavioral syndromes, and consider the pathophysiology, clinical effects, and broad significance of the effects of aging and vascular compromise on cerebral WM, in an attempt to help further the understanding, diagnosis, and treatment of these disorders. C1 [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cognit Behav Neurol Unit, Boston, MA 02114 USA. [Schmahmann, Jeremy D.; Smith, Eric E.; Eichler, Florian S.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Eric E.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Leukodystrophy Clin, Boston, MA 02114 USA. [Filley, Christopher M.] Univ Colorado, Denver Sch Med, Dept Neurol, Aurora, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cognit Behav Neurol Unit, CPZS-340,55 Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU National Institute of Mental Health [IR01MH067980]; Birmingham Foundation FX Supported in part by National Institute of Mental Health grant IR01MH067980 and the Birmingham Foundation. The assistance of Jason MacMore, BA, is gratefully acknowledged. NR 308 TC 152 Z9 154 U1 3 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-730-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1142 BP 266 EP 309 DI 10.1196/annals.1444.017 PG 44 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIM55 UT WOS:000260858700015 PM 18990132 ER PT J AU Li, W Carroll, JS Brown, M Liu, XS AF Li, Wei Carroll, Jason S. Brown, Myles Liu, X. Shirley TI xMAN: extreme MApping of OligoNucleotides SO BMC GENOMICS LA English DT Article AB Background: The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies. Results: We propose an intuitive and efficient algorithm, titled extreme MApping of OligoNucleotide (xMAN), to rapidly map millions of oligonucleotide fragments to a genome of any length. By converting oligonucleotides to integers hashed in RAM, xMAN can scan through genomes using bit shifting operation and achieve at least one order of magnitude speed increase over existing tools. xMAN can map the 42 million 25-mer probes on the Affymetrix whole human genome tiling arrays to the entire genome in less than 6 CPU hours. Conclusions: In addition to the speed advantage, we found the probe mapping of xMAN to substantially improve the final analysis results in both a spike-in experiment on ENCODE tiling arrays and an estrogen receptor ChIP-chip experiment on whole human genome tiling arrays. Those improvements were confirmed by direct ChIP and real-time PCR assay. xMAN can be further extended for application to other high-throughput genomic technologies for oligonucleotide mapping. C1 [Li, Wei; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol,Dept Biostat, Boston, MA 02115 USA. [Carroll, Jason S.; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol,Dept Biostat, Boston, MA 02115 USA. EM weili@jimmy.harvard.edu; jason_carroll@dfci.harvard.edu; myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Li, Wei/A-8544-2009; OI Brown, Myles/0000-0002-8213-1658 FU NHGRI NIH HHS [R01 HG004069, 1R01 HG004069-01, R01 HG004069-01, R01 HG004069-02] NR 19 TC 14 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S20 DI 10.1186/1471-2164-9-S1-S20 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100021 PM 18366610 ER PT J AU Blower, MD Feric, E Weis, K Heald, R AF Blower, Michael D. Feric, Elma Weis, Karsten Heald, Rebecca TI Genome-wide analysis demonstrates conserved localization of messenger RNAs to mitotic microtubules SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSLATIONAL CONTROL; MASS-SPECTROMETRY; EGG EXTRACTS; SPINDLE; PROTEIN; RIBOSOMES; MECHANISMS; EMBRYOS; CPEB AB RNA localization is of critical importance in many fundamental cell biological and developmental processes by regulating the spatial control of gene expression. To investigate how spindle-localized RNAs might influence mitosis, we comprehensively surveyed all messenger RNAs (mRNAs) that bound to microtubules during metaphase in both Xenopus laevis egg extracts and mitotic human cell extracts. We identify conserved classes of mRNAs that are enriched on microtubules in both human and X. laevis. Active mitotic translation occurs on X. laevis meiotic spindles, and a subset of microtubule-bound mRNAs (MT-mRNAs) associate with polyribosomes. Although many MT-mRNAs associate with polyribosomes, we find that active translation is not required for mRNA localization to mitotic microtubules. Our results represent the first genome-wide survey of mRNAs localized to a specific cytoskeletal component and suggest that microtubule localization of specific mRNAs is likely to function in mitotic regulation and mRNA segregation during cell division. C1 [Blower, Michael D.; Weis, Karsten; Heald, Rebecca] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Blower, Michael D.; Feric, Elma] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Blower, Michael D.; Feric, Elma] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Blower, MD (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. EM blower@molbio.mgh.harvard.edu RI Weis, Karsten/F-5719-2011; OI Weis, Karsten/0000-0001-7224-925X; Heald, Rebecca/0000-0001-6671-6528 FU NIGMS NIH HHS [GM065232, R01 GM065232] NR 25 TC 86 Z9 88 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 31 PY 2007 VL 179 IS 7 BP 1365 EP 1373 DI 10.1083/jcb.200705163 PG 9 WC Cell Biology SC Cell Biology GA 246YV UT WOS:000252045200006 PM 18166649 ER PT J AU Howell, GR Libby, RT Jakobs, TC Smith, RS Phalan, FC Barter, JW Barbay, JM Marchant, JK Mahesh, N Porciatti, V Whitmore, AV Masland, RH John, SWM AF Howell, Gareth R. Libby, Richard T. Jakobs, Tatjana C. Smith, Richard S. Phalan, F. Campbell Barter, Joseph W. Barbay, Jessica M. Marchant, Jeffrey K. Mahesh, Nagaraju Porciatti, Vittorio Whitmore, Alan V. Masland, Richard H. John, Simon W. M. TI Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE ELEVATION; WALLERIAN DEGENERATION WLD(S); LATERAL GENICULATE-NUCLEUS; HUMAN LAMINA-CRIBROSA; OPEN-ANGLE GLAUCOMA; TRANSGENIC MICE; C57BL/OLA MICE; MOUSE MODEL; PATTERN ELECTRORETINOGRAM; NEUROMUSCULAR-JUNCTIONS AB Here, we use a mouse model (DBA/2J) to re address the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-defficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wld(s) allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve. C1 [Howell, Gareth R.; Libby, Richard T.; Smith, Richard S.; Phalan, F. Campbell; Barter, Joseph W.; Barbay, Jessica M.; Whitmore, Alan V.; John, Simon W. M.] Jackson Lab, Bar Harbor, ME 04609 USA. [Jakobs, Tatjana C.; Masland, Richard H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Smith, Richard S.; Phalan, F. Campbell; Barter, Joseph W.; John, Simon W. M.] Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. [Marchant, Jeffrey K.] Tufts Univ, Dept Anat & Cell Biol, Boston, MA 02111 USA. [Mahesh, Nagaraju; Porciatti, Vittorio] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [John, Simon W. M.] Tufts Univ Med, Dept Ophthalmol, Boston, MA 02111 USA. RP John, SWM (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM simon.john@jax.org OI Libby, Richard/0000-0003-2844-7632; Jakobs, Tatjana/0000-0002-8104-9206 FU NCI NIH HHS [P30 CA034196, CA34196]; NEI NIH HHS [EY017169, F32 EY014515, F32EY014515, P30 EY014801, P30-EY14801, R01 EY017169, R03 EY016322, R03 EY016322-03] NR 81 TC 253 Z9 261 U1 0 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 31 PY 2007 VL 179 IS 7 BP 1523 EP 1537 DI 10.1083/jcb.200706181 PG 15 WC Cell Biology SC Cell Biology GA 246YV UT WOS:000252045200018 PM 18158332 ER PT J AU Steyerberg, EW Balmana, J Stockwell, DH Syngal, S AF Steyerberg, Ewout W. Balmana, Judith Stockwell, David H. Syngal, Sapna TI Data reduction for prediction: A case study on robust coding of age and family history for the risk of having a genetic mutation SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Conference of the International-Society-for-Clinical-Biostatistics CY AUG 27-31, 2006 CL Geneva, SWITZERLAND SP Int Soc Clin Biostat DE statistical modeling; Lynch syndrome; HNPCC; family history; mutation ID NONPOLYPOSIS COLORECTAL-CANCER; LOGISTIC-REGRESSION MODELS; BETHESDA GUIDELINES; LYNCH-SYNDROME; VALIDATION; SURVIVAL AB Data reduction is often desired in the development of a prediction model, for example for effects of age and family history in the identification of subjects having a genetic mutation. We aimed to evaluate a strategy for model simplification by robust coding of related predictors. We considered 898 patients suspected of having Lynch syndrome, which is caused primarily by mutations in the mismatch repair genes, MLH1 or MSH2. The presence of colorectal cancer (CRC) and endometrial cancer in patients and their relatives was related to mutation prevalence with logistic regression analysis. The performances of simplified and more complex models were quantified with a concordance statistic (c), which was corrected for optimism by cross-validation and bootstrapping. External validation was performed in 1016 patients. The first challenge was the coding of age at diagnosis of CRC, where we forced effects to be identical in patients, in 1st degree and in 2nd degree relatives by taking the sum of the ages at diagnosis. As a further simplification, CRC diagnosis in 2nd degree relatives was weighted half that of 1st degree relatives. These data reduction approaches were also followed for endometrial cancer. The simplified model used 7 instead of 17 degrees of freedom (df) for a more complex model incorporating individual predictor effects. The optimism-corrected c was higher (0.79 instead of 0.77), but the external c was similar (0.78 for the simplified and more complex models). A stepwise selected model performed slightly worse (external c=0.77). In conclusion, a prediction model could be developed with relatively few df that captured effects of age at diagnosis across patients and relatives per type of cancer in the family. Such robust coding may especially be relevant for modeling in relatively small data sets. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Steyerberg, Ewout W.] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Balmana, Judith; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Balmana, Judith] Univ Autonoma Barcelona, Hosp Vall Hebron, Barcelona, Spain. [Stockwell, David H.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Steyerberg, EW (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM E.Steyerberg@ErasmusMC.nl OI Steyerberg, Ewout/0000-0002-7787-0122 NR 23 TC 5 Z9 6 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 30 PY 2007 VL 26 IS 30 BP 5545 EP 5556 DI 10.1002/sim.3119 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 254OJ UT WOS:000252595600016 PM 17948867 ER PT J AU Xie, AY Hartlerode, A Stucki, M Odate, S Puget, N Kwok, A Nagaraju, G Yan, C Alt, FW Chen, J Jackson, SP Scully, R AF Xie, Anyong Hartlerode, Andrea Stucki, Manuel Odate, Shobu Puget, Nadine Kwok, Amy Nagaraju, Ganesh Yan, Catherine Alt, Frederick W. Chen, Junjie Jackson, Stephen P. Scully, Ralph TI Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair SO MOLECULAR CELL LA English DT Article ID DNA-DAMAGE-RESPONSE; HISTONE H2AX; HOMOLOGOUS RECOMBINATION; GENOMIC INSTABILITY; GENE CONVERSION; BLM HELICASE; END; CHECKPOINT; PATHWAY; TRANSLOCATIONS AB Phosphorylated histone H2AX ("gamma-H2AX") recruits MDC1, 53BP1, and BRCA1 to chromatin near a double-strand break (DSB) and facilitates efficient repair of the break. It is unclear to what extent gamma-H2AX-associated proteins act in concert and to what extent their functions within gamma-H2AX chromatin are distinct. We addressed this question by comparing the mechanisms of action of MDC1 and 53BP1 in DSB repair (DSBR). We find that MDC1 functions primarily in homologous recombination/sister chromatid recombination, in a manner strictly dependent upon its ability to interact with gamma-H2AX but, unexpectedly, not requiring recruitment of 53BP1 or BRCA1 to gamma-H2AX chromatin. In contrast, 5313131 functions in XRCC4-dependent nonhomologous end-joining, likely mediated by its interaction with dimethylated lysine 20 of histone H4 but, surprisingly, independent of H2AX These results suggest a specialized adaptation of the "histone code" in which distinct histone tail-protein interactions promote engagement of distinct DSBR pathways. C1 [Xie, Anyong; Hartlerode, Andrea; Odate, Shobu; Puget, Nadine; Kwok, Amy; Nagaraju, Ganesh; Scully, Ralph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Xie, Anyong; Hartlerode, Andrea; Odate, Shobu; Puget, Nadine; Kwok, Amy; Nagaraju, Ganesh; Scully, Ralph] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stucki, Manuel; Jackson, Stephen P.] Univ Cambridge, Dept Zool, Cambridge CB2 1QN, England. [Alt, Frederick W.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Yan, Catherine; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Yan, Catherine; Alt, Frederick W.] Childrens Hosp, Boston, MA 02115 USA. [Yan, Catherine; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA. [Chen, Junjie] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. RP Scully, R (reprint author), Harvard Univ, Sch Med, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM rscully@bidmc.harvard.edu RI Scully, Ralph/F-5008-2013; Dry, Kate/I-2328-2014; OI Jackson, Stephen Philip/0000-0001-9317-7937 FU NCI NIH HHS [CA092312, CA109901, CA92625, CA95175, P01 CA092625, P01 CA109901, R01 CA092312, R01 CA095175, R01 CA095175-05]; NIGMS NIH HHS [GM73894, R01 GM073894, R01 GM073894-03] NR 48 TC 141 Z9 145 U1 1 U2 6 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 DEC 28 PY 2007 VL 28 IS 6 BP 1045 EP 1057 DI 10.1016/j.molcel.2007.12.005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 248QS UT WOS:000252170000011 PM 18158901 ER PT J AU Reddy, VY Reynolds, MR Neuzil, P Richardson, AW Taborsky, M Jongnarangsin, K Kralovec, S Sediva, L Ruskin, JN Josephson, ME AF Reddy, Vivek Y. Reynolds, Matthew R. Neuzil, Petr Richardson, Allison W. Taborsky, Milos Jongnarangsin, Krit Kralovec, Stepan Sediva, Lucie Ruskin, Jeremy N. Josephson, Mark E. TI Prophylactic catheter ablation for the prevention of defibrillator therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Scientific Session of the Heart-Rhythm-Society CY MAY 17-20, 2006 CL Boston, MA SP Heart Rhythm Soc ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; SINUS RHYTHM; DRUG-THERAPY; SOTALOL; SHOCKS; CARDIOMYOPATHY; ORIGIN; TRIAL AB Background: For patients who have a ventricular tachyarrhythmic event, implantable cardioverter-defibrillators (ICDs) are a mainstay of therapy to prevent sudden death. However, ICD shocks are painful, can result in clinical depression, and do not offer complete protection against death from arrhythmia. We designed this randomized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy. Methods: Eligible patients with a history of a myocardial infarction underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation. The patients did not receive antiarrhythmic drugs. Patients were randomly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation (64 patients in each group). Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary end point was survival free from any appropriate ICD therapy. Results: The mortality rate 30 days after ablation was zero, and there were no significant changes in ventricular function or functional class during the mean (+/-SD) follow-up period of 22.5+/-5.5 months. Twenty-one patients assigned to defibrillator implantation alone (33%) and eight patients assigned to defibrillator implantation plus ablation (12%) received appropriate ICD therapy (antitachycardia pacing or shocks) (hazard ratio in the ablation group, 0.35; 95% confidence interval, 0.15 to 0.78, P=0.007). Among these patients, 20 in the control group (31%) and 6 in the ablation group (9%) received shocks (P=0.003). Mortality was not increased in the group assigned to ablation as compared with the control group (9% vs. 17%, P=0.29). Conclusions: In this randomized trial, prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infarction who received ICDs for the secondary prevention of sudden death. (Current Controlled Trials number, ISRCTN62488166.). C1 Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Div Cardiovasc, Boston, MA 02215 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Arrhythmia Serv, Boston, MA 02215 USA. Homolka Hosp, Cardiac Arrhythmia Serv, Prague, Czech Republic. RP Josephson, ME (reprint author), Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Div Cardiovasc, 185 Pilgrim Rd, Boston, MA 02215 USA. EM mjoseph2@bidmc.harvard.edu FU NHLBI NIH HHS [K23 HL077171, K23 HL068064, K23 HL077171-04, K23 HL68064] NR 26 TC 296 Z9 306 U1 1 U2 19 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 DEC 27 PY 2007 VL 357 IS 26 BP 2657 EP 2665 DI 10.1056/NEJMoa065457 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 245UO UT WOS:000251964500004 PM 18160685 ER PT J AU Miller, K Wang, ML Gralow, J Dickler, M Cobleigh, M Perez, EA Shenkier, T Cella, D Davidson, NE AF Miller, Kathy Wang, Molin Gralow, Julie Dickler, Maura Cobleigh, Melody Perez, Edith A. Shenkier, Tamara Cella, David Davidson, Nancy E. TI Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; COMBINED BIOLOGICAL THERAPY; QUALITY-OF-LIFE; ANGIOGENESIS; RESISTANCE; TARGET; TRIALS; TUMORS; CELLS AB Background: In an open-label, randomized, phase 3 trial, we compared the efficacy and safety of paclitaxel with that of paclitaxel plus bevacizumab, a monoclonal antibody against vascular endothelial growth factor, as initial treatment for metastatic breast cancer. Methods: We randomly assigned patients to receive 90 mg of paclitaxel per square meter of body-surface area on days 1, 8, and 15 every 4 weeks, either alone or with 10 mg of bevacizumab per kilogram of body weight on days 1 and 15. The primary end point was progression-free survival; overall survival was a secondary end point. Results: From December 2001 through May 2004, a total of 722 patients were enrolled. Paclitaxel plus bevacizumab significantly prolonged progression-free survival as compared with paclitaxel alone (median, 11.8 vs. 5.9 months; hazard ratio for progression, 0.60; P<0.001) and increased the objective response rate (36.9% vs. 21.2%, P<0.001). The overall survival rate, however, was similar in the two groups (median, 26.7 vs. 25.2 months; hazard ratio, 0.88; P=0.16). Grade 3 or 4 hypertension (14.8% vs. 0.0%, P<0.001), proteinuria (3.6% vs. 0.0%, P<0.001), headache (2.2% vs. 0.0%, P=0.008), and cerebrovascular ischemia (1.9% vs. 0.0%, P=0.02) were more frequent in patients receiving paclitaxel plus bevacizumab. Infection was more common in patients receiving paclitaxel plus bevacizumab (9.3% vs. 2.9%, P<0.001), but febrile neutropenia was uncommon (<1% overall). Conclusions: Initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab prolongs progression-free survival, but not overall survival, as compared with paclitaxel alone. (ClinicalTrials.gov number, NCT00028990.). C1 Indiana Univ, Ctr Canc, Indiana Canc Pavil, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Puget Sound Oncol Consortium, Seattle, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Mayo Clin, Jacksonville, FL 32224 USA. British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. Evanston NW Healthcare, Evanston, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Miller, K (reprint author), Indiana Univ, Ctr Canc, Indiana Canc Pavil, 535 Barnhill Dr,RT473, Indianapolis, IN 46202 USA. EM kathmill@iupui.edu FU NCI NIH HHS [CA21115, CA16116, CA23318, CA49883, CA66636] NR 30 TC 1809 Z9 1874 U1 21 U2 125 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 DEC 27 PY 2007 VL 357 IS 26 BP 2666 EP 2676 DI 10.1056/NEJMoa072113 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 245UO UT WOS:000251964500005 PM 18160686 ER PT J AU Triggs, WJ Cros, D AF Triggs, William J. Cros, Didier TI A man with weakness in the hands - Multifocal motor neuropathy with conduction block SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; NEURON DISEASE; MUSCULAR-ATROPHY; ANTIBODIES; FEATURES; GANGLIOSIDE; FEDERATION; RITUXIMAB; DIAGNOSIS; CRITERIA C1 Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA. Univ Florida, Dept Neurol, Gainesville, FL USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Triggs, WJ (reprint author), Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA. NR 39 TC 2 Z9 2 U1 0 U2 1 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 DEC 27 PY 2007 VL 357 IS 26 BP 2707 EP 2715 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 245UO UT WOS:000251964500011 PM 18160691 ER PT J AU John, EM Miron, A Gong, G Phipps, AI Felberg, A Li, FP West, DW Whittemore, AS AF John, Esther M. Miron, Alexander Gong, Gail Phipps, Amanda I. Felberg, Anna Li, Frederick P. West, Dee W. Whittemore, Alice S. TI Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER PATIENTS; POPULATION-BASED SERIES; SENSITIVE GEL-ELECTROPHORESIS; AFRICAN-AMERICAN FAMILIES; SAN-LUIS VALLEY; BREAST/OVARIAN CANCER; OVARIAN-CANCER; GENETIC EPIDEMIOLOGY; HIGH PROPORTION; GERMLINE MUTATIONS AB Context Information on the prevalence of pathogenic BRCA1 mutation carriers in racial/ ethnic minority populations is limited. Objective To estimate BRCA1 carrier prevalence in Hispanic, African American, and Asian American female breast cancer patients compared with non- Hispanic white patients with and without Ashkenazi Jewish ancestry. Design, Setting, and Participants We estimated race/ ethnicity- specific prevalence of BRCA1 in a population- based, multiethnic series of female breast cancer patients younger than 65 years at diagnosis who were enrolled at the Northern California site of the Breast Cancer Family Registry during the period 1996- 2005. Race/ ethnicity and religious ancestry were based on self- report. Weighted estimates of prevalence and 95% confidence intervals ( CIs) were based on Horvitz- Thompson estimating equations. Main Outcome Measure Estimates of BRCA1 prevalence. Results Estimates of BRCA1 prevalence were 3.5% ( 95% CI, 2.1%- 5.8%) in Hispanic patients ( n = 393), 1.3% ( 95% CI, 0.6%- 2.6%) in African American patients ( n = 341), and 0.5% ( 95% CI, 0.1%- 2.0%) in Asian American patients ( n = 444), compared with 8.3% ( 95% CI, 3.1%- 20.1%) in Ashkenazi Jewish patients ( n= 41) and 2.2% ( 95% CI, 0.7%- 6.9%) in other non- Hispanic white patients ( n= 508). Prevalence was particularly high in young ( < 35 years) African American patients ( 5/30 patients [ 16.7%]; 95% CI, 7.1%- 34.3%). 185delAG was the most common mutation in Hispanics, found in 5 of 21 carriers ( 24%). Conclusions Among African American, Asian American, and Hispanic patients in the Northern California Breast Cancer Family Registry, the prevalence of BRCA1 mutation carriers was highest in Hispanics and lowest in Asian Americans. The higher carrier prevalence in Hispanics may reflect the presence of unrecognized Jewish ancestry in this population. C1 No Calif Canc Ctr, Fremont, CA 94538 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP John, EM (reprint author), No Calif Canc Ctr, 2201 Walnut Ave,Ste 300, Fremont, CA 94538 USA. EM ejohn@nccc.org FU NCI NIH HHS [U01 CA69417, CA-95-003, CA78564, CA94069, U01 CA069417, U01 CA069417-10] NR 60 TC 144 Z9 145 U1 0 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 DEC 26 PY 2007 VL 298 IS 24 BP 2869 EP 2876 DI 10.1001/jama.298.24.2869 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 243RW UT WOS:000251816000019 PM 18159056 ER PT J AU Unger, TJ Calderon, GA Bradley, LC Sena-Esteves, M Rios, M AF Unger, Thaddeus J. Calderon, German A. Bradley, Leila C. Sena-Esteves, Miguel Rios, Maribel TI Selective deletion of Bdnf in the ventromedial and Dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; VMH; DMH; satiety; obesity; adult ID NEUROTROPHIC FACTOR BDNF; RECEPTOR MESSENGER-RNA; LONG-TERM POTENTIATION; REDUCES ENERGY-INTAKE; BROWN ADIPOSE-TISSUE; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; DOPAMINE PATHWAY; WEIGHT-GAIN; MOUSE-BRAIN AB Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in several hypothalamic and hindbrain nuclei involved in regulating energy homeostasis, developmentally and in the adult animal. Their depletion during the fetal or early postnatal periods when developmental processes are still ongoing elicits hyperphagic behavior and obesity in mice. Whether BDNF is a chief element in appetite control in the mature brain remains controversial. The required sources of this neurotrophin are also unknown. We show that glucose administration rapidly induced BDNF mRNA expression, mediated by Bdnf promoter 1, and TrkB transcription in the ventromedial hypothalamus (VMH) of adult mice, consistent with a role of this pathway in satiety. Using viral-mediated selective knock-down of BDNF in the VMH and dorsomedial hypothalamus(DMH) of adult mice, we were able to elucidate the physiological relevance of BDNF in energy balance regulation. Site-specific mutants exhibited hyperphagic behavior and obesity but normal energy expenditure. Furthermore, intracerebroventricular administration of BDNF triggered an immediate neuronal response in multiple hypothalamic nuclei in wild-type mice, suggesting that its anorexigenic actions involve short-term mechanisms. Locomotor, aggressive, and depressive-like behaviors, all of which are associated with neural circuits involving the VMH, were not altered in VMH/DMH-specific BDNF mutants. These findings demonstrate that BDNF is an integral component of central mechanisms mediating satiety in the adult mouse and, moreover, that its synthesis in the VMH and/or DMH is required for the suppression of appetite. C1 [Calderon, German A.; Rios, Maribel] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Unger, Thaddeus J.] Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. [Bradley, Leila C.] Wyeth Pharmaceut, Cambridge, MA 02140 USA. [Sena-Esteves, Miguel] Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. [Sena-Esteves, Miguel] Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurosci, Charlestown, MA 02129 USA. [Sena-Esteves, Miguel] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rios, M (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02111 USA. EM maribel.rios@tufts.edu FU NIDDK NIH HHS [P30 DK34928, DK073311]; NIMH NIH HHS [MH67817]; NINDS NIH HHS [P30 NS047243] NR 64 TC 167 Z9 173 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 26 PY 2007 VL 27 IS 52 BP 14265 EP 14274 DI 10.1523/JNEUROSCI.3308-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 245CB UT WOS:000251911100006 PM 18160634 ER PT J AU Gao, X Arlotta, P Macklis, JD Chen, JH AF Gao, Xiang Arlotta, Paola Macklis, Jeffrey D. Chen, Jinhui TI Conditional knock-out of beta-catenin in postnatal-born dentate gyrus granule neurons results in dendritic malformation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE conditional knock-out; beta-catenin; dendritic development; newborns; dentate gyrus granule neurons; hippocampus ID ADULT HIPPOCAMPAL NEUROGENESIS; GENERATED NEURONS; STEM-CELLS; DOUBLECORTIN; EXPRESSION; PROJECTIONS; MATURATION; CADHERINS; BINDING; MARKER AB Neurons are continuously added to the brain throughout life, and these neurons must develop dendritic arbors and functional connections with existing neurons to be integrated into neuronal circuitry. The molecular mechanisms that regulate dendritic development of newborn neurons in the hippocampal dentate gyrus are still unclear. Here, we show that beta-catenin is expressed in newborn granule neurons and in neural progenitor cells in the hippocampal dentate gyrus. Specific knock-out of beta-catenin in newborn neurons, without affecting beta-catenin expression in neural progenitor cells, led to defects in dendritic morphology of these newborn neurons in vivo. Majority of newborn neurons that cannot extend dendrites survive < 1 month after they were born. Our results indicate that beta-catenin plays an important role in dendritic development of postnatal-born neurons in vivo, and is therefore essential for the neurogenesis in the postnatal brain. C1 [Gao, Xiang; Chen, Jinhui] Univ Kentucky, Spinal Cord & Brain Injury Res Ctr, Lexington, KY 40536 USA. [Chen, Jinhui] Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. [Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Program, Boston, MA 02114 USA. [Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Ctr Nervous Syst Repair, Boston, MA 02114 USA. RP Chen, JH (reprint author), Univ Kentucky, Spinal Cord & Brain Injury Res Ctr, Lexington, KY 40536 USA. EM jchen@uky.edu RI Chen, Jinhui/A-7138-2009 FU NINDS NIH HHS [NS 41590, NS 45523, NS 49553] NR 44 TC 52 Z9 53 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 26 PY 2007 VL 27 IS 52 BP 14317 EP 14325 DI 10.1523/JNEUROSCI.3206-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 245CB UT WOS:000251911100011 PM 18160639 ER PT J AU Apidianakis, Y Mindrinos, MN Xiao, WZ Tegos, GP Papisov, MI Hamblin, MR Davis, RW Tompkins, RG Rahme, LG AF Apidianakis, Yiorgos Mindrinos, Michael N. Xiao, Wenzhong Tegos, George P. Papisov, Michail I. Hamblin, Michael R. Davis, Ronald W. Tompkins, Ronald G. Rahme, Laurence G. TI Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma SO PLOS ONE LA English DT Article AB Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals. C1 [Apidianakis, Yiorgos; Tompkins, Ronald G.; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Apidianakis, Yiorgos; Tompkins, Ronald G.; Rahme, Laurence G.] Shriners Burn Inst, Boston, MA 02114 USA. [Mindrinos, Michael N.; Xiao, Wenzhong; Davis, Ronald W.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Papisov, Michail I.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Lab Mol Bioengn, Boston, MA 02114 USA. [Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM rahme@amber.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Papisov, Mikhail/0000-0003-4716-2122; Apidianakis, Yiorgos/0000-0002-7465-3560; xiao, wenzhong/0000-0003-4944-6380; Hamblin, Michael/0000-0001-6431-4605 FU Shriners Research [8892]; Shriners Post-doctoral Fellowship; NIH [AI050875]; [DK43351]; [DK57521] FX Funding: This work was supported by the Shriners Research grant #8892 to LGR. YA was supported by a Shriners Post-doctoral Fellowship, MRH by NIH Grant AI050875 and electron microscopy core by grants DK43351 and DK57521. NR 41 TC 22 Z9 23 U1 0 U2 1 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 DEC 26 PY 2007 VL 2 IS 12 AR e1356 DI 10.1371/journal.pone.0001356 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JG UT WOS:000207459700013 PM 18159239 ER PT J AU Yang, XH Zou, L AF Yang, Xiaohong H. Zou, Lee TI Launching a ubiquitination cascade at DNA breaks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; BRCA1; COMPLEX; REPAIR; UBC13 C1 [Yang, Xiaohong H.] Harvard Med Sch, Dept Pathol, Charlestown, MA 02129 USA. [Yang, Xiaohong H.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Zou, L (reprint author), Harvard Med Sch, Dept Pathol, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu NR 17 TC 4 Z9 4 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 DEC 26 PY 2007 VL 104 IS 52 BP 20645 EP 20646 DI 10.1073/pnas.0710916105 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247KJ UT WOS:000252077400004 PM 18093907 ER PT J AU Wang, J Theunissen, TW Orkin, SH AF Wang, Jianlong Theunissen, Thorold W. Orkin, Stuart H. TI Site-directed, virus-free, and inducible RNAi in embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microRNAs; Nanog; RNA interference; tetracycline ID MAMMALIAN-CELLS; SHRNA LIBRARIES; GENE KNOCKDOWN; ES CELLS; INTERFERENCE; MOUSE; NANOG; PLURIPOTENCY; EXPRESSION; SYSTEM AB RNAi is a powerful tool for interrogating gene function in ES cells. Combining the high penetrance of a microRNA-embedded shRNA (shRNA-mir) cassette with a locus-defined, inducible expression strategy, we developed a system for RNAi in mouse ES cells. An shRNA-mir cassette is targeted near the constitutively active HPRT locus under a tetracycline (tet)-regulatable promoter through Cremediated site-specific recombination. The major advantage of this system is that the shRNA-mir cassette can be targeted to a precise locus, allowing for control of shRNA-mir expression in an inducible fashion. Induction of an shRNA-mir directed against the pluripotency factor, Nanog, resulted in the loss of self-renewal and differentiation to parietal endoderm-like cells, which can be rescued by the introduction of an RNAi-immune version of Nanog cDNA. Knockdown efficiency can be enhanced by using multiple shRNA-mir hairpins against the target gene, which was further validated by knocking down two additional ES cell factors. This site-directed, virus-free, and tet-inducible RNAi system, designated as SDVFi RNAi in our study, presents an efficient option for controlled gene silencing in ES cells. C1 [Wang, Jianlong; Theunissen, Thorold W.; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Wang, Jianlong; Theunissen, Thorold W.; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Theunissen, Thorold/0000-0001-6943-7858 NR 25 TC 23 Z9 23 U1 0 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 DEC 26 PY 2007 VL 104 IS 52 BP 20850 EP 20855 DI 10.1073/pnas.0710565105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247KJ UT WOS:000252077400043 PM 18093939 ER PT J AU O'Neil, J Tchinda, J Gutierrez, A Moreau, L Maser, RS Wong, KK Li, W McKenna, K Liu, XS Bin, F Neuberg, D Sidverman, L DeAngelo, DJ Kutok, JL Rothstein, R DePinho, RA Chin, L Lee, C Look, AT AF O'Neil, Jennifer Tchinda, Joelle Gutierrez, Alejandro Moreau, Lisa Maser, Richard S. Wong, Kwok-Kin Li, Wei McKenna, Keith Liu, X. Shirley Feng, Bin Neuberg, Donna Sidverman, Lewis DeAngelo, Daniel J. Kutok, Jeffery L. Rothstein, Rodney DePinho, Ronald A. Chin, Lynda Lee, Charles Look, A. Thomas TI Alu elements mediate MYB gene tandem duplication in human T-ALL SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYB; CELL DEVELOPMENT; HOMOLOGOUS RECOMBINATION; GENOMIC ALTERATIONS; V-MYB; ONCOGENE; NOTCH1; TRANSLOCATION; EXPRESSION AB Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats and that the duplication is mediated somatically by homologous recombination between the flanking Alu elements on sister chromatids. Nested long-range PCR analysis indicated a low frequency of homologous recombination leading to MYB tandem duplication in the peripheral blood mononuclear cells of similar to 50% of healthy individuals, none of whom had a MYB duplication in the germline. We conclude that Alu-mediated MYB tandem duplication occurs at low frequency during normal thymocyte development and is clonally selected during the molecular pathogenesis of human T-ALL. C1 [O'Neil, Jennifer; Gutierrez, Alejandro; Moreau, Lisa; McKenna, Keith; Sidverman, Lewis; Look, A. Thomas] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Pediat Oncol, Boston, MA 02115 USA. [Maser, Richard S.; Wong, Kwok-Kin; DeAngelo, Daniel J.; DePinho, Ronald A.; Chin, Lynda] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [Li, Wei; Liu, X. Shirley; Neuberg, Donna] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Feng, Bin] Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA. [Tchinda, Joelle; Kutok, Jeffery L.; Lee, Charles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med Genet, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Li, Wei; Liu, X. Shirley; Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rothstein, Rodney] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Dept Pediat Oncol, Boston, MA 02115 USA. EM clee@rics.boh.harvard.edu; Thomas_Look@dfci.harvard.edu RI Li, Wei/A-8544-2009; Maser, Richard/B-2970-2012 FU NCI NIH HHS [CA109901, CA11560, CA115853, CA68484-11, P01 CA068484, P01 CA109901, R01 CA111560, R21 CA115853]; NIGMS NIH HHS [R37 GM050237, GM050237, GM067055, R01 GM050237, R01 GM067055] NR 33 TC 46 Z9 47 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 24 PY 2007 VL 204 IS 13 BP 3059 EP 3066 DI 10.1084/jem.20071637 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 248KV UT WOS:000252153100003 PM 18070937 ER PT J AU Kim, KH Park, BH Maguluri, GN Lee, TW Rogomentich, FJ Bancu, MG Bouma, BE de Boer, JF Bernstein, JJ AF Kim, Ki Hean Park, B. Hyle Maguluri, Gopi N. Lee, Tom W. Rogomentich, Fran J. Bancu, Mirela G. Bouma, Brett E. de Boer, Johannes F. Bernstein, Jonathan J. TI Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID IN-VIVO; BARRETTS-ESOPHAGUS; DYNAMIC-RANGE; SWEPT SOURCE; MIRROR; REFLECTOMETRY; DERMATOLOGY; TRACT AB A two-axis scanning catheter was developed for 3D endoscopic imaging with spectral domain optical coherence tomography (SD-OCT). The catheter incorporates a micro-mirror scanner implemented with microelectromechanical systems (MEMS) technology: the micro-mirror is mounted on a two-axis gimbal comprised of folded flexure hinges and is actuated by magnetic field. The scanner can run either statically in both axes or at the resonant frequency (<= 350Hz) for the fast axis. The assembled catheter has an outer diameter of 2.8 mm and a rigid part of 12 mm in length. Its scanning range is +/- 20 degrees in optical angle in both axes with low voltages (1 similar to 3V), resulting in a scannable length of approximately 1 mm at the surface in both axes, even with the small catheter size. The catheter was incorporated with a multi-functional SD-OCT system for 3D endoscopic imaging. Both intensity and polarization-sensitive images could be acquired simultaneously at 18.5K axial scans/s. In vivo 3D images of human fingertips and oral cavity tissue are presented as a demonstration. (c) 2007 Optical Society of America. C1 [Lee, Tom W.; Rogomentich, Fran J.; Bancu, Mirela G.; Bernstein, Jonathan J.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Kim, Ki Hean; Park, B. Hyle; Maguluri, Gopi N.; Bouma, Brett E.; de Boer, Johannes F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Bernstein, JJ (reprint author), Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. EM jbernstein@draper.com RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU PHS HHS [19768] NR 51 TC 97 Z9 98 U1 2 U2 30 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 24 PY 2007 VL 15 IS 26 BP 18130 EP 18140 DI 10.1364/OE.15.018130 PG 11 WC Optics SC Optics GA 246YX UT WOS:000252045400073 PM 19551111 ER PT J AU Martin, BC Bortfeld, TR Castanon, DA AF Martin, Benjamin C. Bortfeld, Thomas R. Castanon, David A. TI Accelerating IMRT optimization by voxel sampling SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; CONVERGENCE AB This paper presents a new method for accelerating intensity-modulated radiation therapy (IMRT) optimization using voxel sampling. Rather than calculating the dose to the entire patient at each step in the optimization, the dose is only calculated for some randomly selected voxels. Those voxels are then used to calculate estimates of the objective and gradient which are used in a randomized version of a steepest descent algorithm. By selecting different voxels on each step, we are able to find an optimal solution to the full problem. We also present an algorithm to automatically choose the best sampling rate for each structure within the patient during the optimization. Seeking further improvements, we experimented with several other gradient-based optimization algorithms and found that the delta-bar-delta algorithm performs well despite the randomness. Overall, we were able to achieve approximately an order of magnitude speedup on our test case as compared to steepest descent. C1 [Martin, Benjamin C.; Castanon, David A.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Bortfeld, Thomas R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bortfeld, Thomas R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Martin, BC (reprint author), Boston Univ, Dept Elect & Comp Engn, 8 St Marys St, Boston, MA 02215 USA. EM bcmartin@bu.edu; tbortfeld@partners.org; dac@bu.edu FU NCI NIH HHS [R01-CA103904, R01-CA118200] NR 15 TC 6 Z9 6 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 DEC 21 PY 2007 VL 52 IS 24 BP 7211 EP 7228 DI 10.1088/0031-9155/52/24/002 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 288UM UT WOS:000255011300002 PM 18065835 ER PT J AU Mouridsen, H Keshaviah, A Coates, AS Rabaglio, M Castiglione-Gertsch, M Sun, Z Thurlimann, B Mauriac, L Forbes, JF Paridaens, R Gelber, RD Colleoni, M Smith, I Price, KN Goldhirsch, A AF Mouridsen, Henning Keshaviah, Aparna Coates, Alan S. Rabaglio, Manuela Castiglione-Gertsch, Monica Sun, Zhuoxin Thuerlimann, Beat Mauriac, Louis Forbes, John F. Paridaens, Robert Gelber, Richard D. Colleoni, Marco Smith, Ian Price, Karen N. Goldhirsch, Aron TI Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: Safety analysis of BIG 1-98 trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; AROMATASE INHIBITORS; CLINICAL-TRIALS; ANASTROZOLE; COMBINATION AB Purpose Previous analyses of adjuvant studies of aromatase inhibitors versus tamoxifen, including the Breast International Group (BIG) 1-98 study, have suggested a small numerical excess of cardiac adverse events (AEs) on aromatase inhibitors, a reduction in the incidence of hypercholesterolemia on tamoxifen, and significantly higher incidence of thromboembolic AEs on tamoxifen. The purpose of the present study is to provide detailed updated information on these AEs in BIG 1-98. Patients and Methods Eight thousand twenty-eight postmenopausal women with receptor-positive early breast cancer were randomly assigned (double-blind) between March 1998 and May 2003 to receive 5 years of adjuvant endocrine therapy with letrozole, tamoxifen, or a sequence of these agents. Seven thousand nine hundred sixty-three patients who actually received therapy are included in this safety analysis, which focuses on cardiovascular events. AE recording ceased 30 days after therapy completion (or after switch on the sequential arms). Results Baseline comorbidities were balanced. At a median follow-up time of 30.1 months, we observed similar overall incidence of cardiac AEs (letrozole, 4.8%; tamoxifen, 4.7%), more grade 3 to 5 cardiac AEs on letrozole (letrozole, 2.4%; tamoxifen, 1.4%; P=.001) - an excess only partially attributable to prior hypercholesterolemia - and more overall (tamoxifen, 3.9%; letrozole, 1.7%; P <.001) and grade 3 to 5 thromboembolic AEs on tamoxifen (tamoxifen, 2.3%; letrozole, 0.9%; P <.001). There was no significant difference between tamoxifen and letrozole in incidence of hypertension or cerebrovascular events. Conclusion The present safety analysis, limited to cardiovascular AEs in BIG 1-98, documents a low overall incidence of cardiovascular AEs, which differed between treatment arms. C1 [Mouridsen, Henning] Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen O, Denmark. Dana Farber Canc Inst, IBCSG, Ctr Stat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. IBCSG Coordinating Ctr, Bern, Switzerland. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. Inst Bergonie, French Breast Canc Grp, Bordeaux, France. Catholic Univ Leuven, Univ Hosp Gasthuisberg, Dept Med Oncol, Louvain, Belgium. European Inst Oncol, Milan, Italy. Royal Marsden Hosp, London SW3 6JJ, England. RP Mouridsen, H (reprint author), Rigshosp, Danish Breast Canc Cooperat Grp, Dept 2501,Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM henning.mouridsen@rh.hosp.dk FU NCI NIH HHS [CA-75362] NR 20 TC 64 Z9 66 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2007 VL 25 IS 36 BP 5715 EP 5722 DI 10.1200/JCO.2007.12.1665 PG 8 WC Oncology SC Oncology GA 272UT UT WOS:000253886600007 PM 17998546 ER PT J AU Pollak, KI Arnold, RM Jeffreys, AS Alexander, SC Olsen, MK Abernethy, AP Skinner, CS Rodriguez, KL Tulsky, JA AF Pollak, Kathryn I. Arnold, Robert M. Jeffreys, Amy S. Alexander, Stewart C. Olsen, Maren K. Abernethy, Amy P. Skinner, Celette Sugg Rodriguez, Keri L. Tulsky, James A. TI Oncologist communication about emotion during visits with patients with advanced cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY-CARE; TRAINING MODEL; BAD-NEWS; PHYSICIAN; CONSULTATION; ENCOUNTERS; EFFICACY; SKILLS; TRIAL; SCALE AB Introduction Cancer care involves addressing patient emotion. When patients express negative emotions, empathic opportunities emerge. When oncologists respond with a continuer statement, which is one that offers empathy and allows patients to continue expressing emotions, rather than with a terminator statement, which is one that discourages disclosure, patients have less anxiety and depression and report greater satisfaction and adherence to therapy. We studied whether oncologist traits were associated with empathic opportunities and empathic responses. Patients and Methods We audio-recorded 398 clinic conversations between 51 oncologists and 270 patients with advanced cancer; oncologists also completed surveys. Conversations were coded for the presence of empathic opportunities and oncologist responses. Analyses examined the relationship with oncologists' demographics, self-reported confidence, outcome expectancies, and comfort to address social versus technical aspects of care. Results In 398 conversations, 37% contained at least one empathic opportunity; the range was 0 to 10, and the total empathic opportunities was 292. When they occurred, oncologists responded with continuers 22% of the time. Oncologist sex was related to the number of empathic opportunities; female patients seen by female oncologists had the most empathic opportunities (P = .03). Younger oncologists (P = .02) and those who rated their orientation as more socioemotional than technical (P = .03) were more likely to respond with empathic statements. Conclusion Oncologists encountered few empathic opportunities and responded with empathic statements infrequently. Empathic responses were more prevalent among younger oncologists and among those who were self-rated as socioemotional. To reduce patient anxiety and increase patient satisfaction and adherence, oncologists may need training to encourage patients to express emotions and to respond empathically to patients' emotions. C1 [Pollak, Kathryn I.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27705 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27710 USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res, Durham, NC 27710 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Inst Doctor Patient Commun, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Inst Enhance Palliat Care, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Pollak, KI (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, 2424 Erwin Rd,Suite 602, Durham, NC 27705 USA. EM polla007@mc.duke.edu FU NCI NIH HHS [R01 CA100387, R01CA100387] NR 30 TC 151 Z9 152 U1 2 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2007 VL 25 IS 36 BP 5748 EP 5752 DI 10.1200/JCO.2007.12.4180 PG 5 WC Oncology SC Oncology GA 272UT UT WOS:000253886600012 PM 18089870 ER PT J AU Klausner, EA Peer, D Chapman, RL Multack, RF Andurkar, SV AF Klausner, Eytan A. Peer, Dan Chapman, Robert L. Multack, Richard F. Andurkar, Shridhar V. TI Corneal gene therapy SO JOURNAL OF CONTROLLED RELEASE LA English DT Review DE cornea; eye; gene therapy; corneal graft rejection; herpetic stromal keratitis; corneal neovascularization ID HERPETIC STROMAL KERATITIS; DNA ENCODING IFN-ALPHA-1; OCULAR HSV-1 INFECTION; RECOMBINANT ADENOASSOCIATED VIRUS; IN-VIVO TRANSFER; ENDOTHELIAL-CELLS; EX-VIVO; ALLOGRAFT SURVIVAL; MUCOPOLYSACCHARIDOSIS-VII; DELIVERY-SYSTEMS AB Gene therapy to the cornea can potentially correct inherited and acquired diseases of the cornea. Factors that facilitate corneal gene delivery are the accessibility and transparency of the cornea, its stability ex vivo and the immune privilege of the eye. Initial corneal gene delivery studies characterized the relationship between intraocular modes of administration and location of reporter gene expression. The challenge of achieving effective topical gene transfer, presumably due to tear flow, blinking and low penetration of the vector through epithlelial tight junctions left no alternative but invasive administration to the anterior chamber and corneal stroma. DNA vaccination, RNA interference and gene transfer of cytokines, growth factors and enzymes modulated the corneal microenvironment. Positive results were obtained in preclinical studies for prevention and treatment of corneal graft rejection, neovascularization, haze and herpetic stromal keratitis. These studies, corneal gene delivery systems and modes of administration, and considerations regarding the choice of animal species used are the focus of this review. Opportunities in the field of corneal gene therapy lie in expanding the array of corneal diseases investigated and in the implementation of recent designs of safer vectors with reduced immunogenicity and longer duration of gene expression. (c) 2007 Elsevier B.V. All rights reserved. C1 [Klausner, Eytan A.; Chapman, Robert L.; Andurkar, Shridhar V.] Midwestern Univ, Chicago Coll Pharm, Downers Grove, IL 60515 USA. [Peer, Dan] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Peer, Dan] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Multack, Richard F.] Midwestern Univ, Chicago Coll Osteopath Med, Downers Grove, IL 60515 USA. RP Klausner, EA (reprint author), Midwestern Univ, Chicago Coll Pharm, 533 31st St, Downers Grove, IL 60515 USA. EM eklaus@niidwestem.edu RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 NR 224 TC 43 Z9 45 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD DEC 20 PY 2007 VL 124 IS 3 BP 107 EP 133 DI 10.1016/j.jconrel.2007.05.041 PG 27 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 246NW UT WOS:000252014700001 PM 17707107 ER PT J AU Nagrath, S Sequist, LV Maheswaran, S Bell, DW Irimia, D Ulkus, L Smith, MR Kwak, EL Digumarthy, S Muzikansky, A Ryan, P Balis, UJ Tompkins, RG Haber, DA Toner, M AF Nagrath, Sunitha Sequist, Lecia V. Maheswaran, Shyamala Bell, Daphne W. Irimia, Daniel Ulkus, Lindsey Smith, Matthew R. Kwak, Eunice L. Digumarthy, Subba Muzikansky, Alona Ryan, Paula Balis, Ulysses J. Tompkins, Ronald G. Haber, Daniel A. Toner, Mehmet TI Isolation of rare circulating tumour cells in cancer patients by microchip technology SO NATURE LA English DT Article ID METASTATIC BREAST-CANCER; ON-A-CHIP; PERIPHERAL-BLOOD; CARCINOMA-CELLS; EXPRESSION; FLOW; MICROFLUIDICS; ENUMERATION; SEPARATION AB Viable tumour- derived epithelial cells ( circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease(1-4). Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers(5-8). The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity(9). Here we describe the development of a unique microfluidic platform ( the 'CTC-chip') capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody ( EpCAM)- coated microposts under precisely controlled laminar flow conditions, and without requisite pre- labelling or processing of samples. The CTC- chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 ( 99%) samples, with a range of 5-1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early- stage prostate cancer. Given the high sensitivity and specificity of the CTC- chip, we tested its potential utility in monitoring response to anti- cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC- chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer(10). C1 Harvard Univ, Sch Med, Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, BioMEMS Resource Ctr, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NCI NIH HHS [K24 CA121990-02, K24 CA121990]; NIBIB NIH HHS [P41 EB002503] NR 32 TC 1608 Z9 1674 U1 138 U2 1026 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 20 PY 2007 VL 450 IS 7173 BP 1235 EP U10 DI 10.1038/nature06385 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 243HA UT WOS:000251786200051 PM 18097410 ER PT J AU Poeta, ML Manola, J Goldwasser, MA Forastiere, A Benoit, N Califano, JA Ridge, JA Goodwin, J Kenady, D Saunders, J Westra, W Sidransky, D Koch, WM AF Poeta, M. Luana Manola, Judith Goldwasser, Meredith A. Forastiere, Arlene Benoit, Nicole Califano, Joseph A. Ridge, John A. Goodwin, Jarrard Kenady, Daniel Saunders, John Westra, William Sidransky, David Koch, Wayne M. TI TP53 mutations and survival in squamous-cell carcinoma of the head and neck SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-PAPILLOMAVIRUS; P53 NETWORK; BREAST-CANCER; GENE; SMOKING; ASSOCIATION; PROGNOSIS; ALCOHOL; TOBACCO; MODEL AB Background: The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck. Methods: A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53-DNA complexes. TP53 mutational status was compared with clinical outcome. Results: TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P=0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P=0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P=0.003). Conclusions: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck. C1 Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21287 USA. Greater Baltimore Med Ctr, Baltimore, MD USA. Univ Campus Biomed Rome, Ctr Integrated Res, Lab Mol Med & Biotechnol, Rome, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. Univ Kentucky, Lexington, KY USA. RP Koch, WM (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol, 601 N Caroline St,JHOC 6221, Baltimore, MD 21287 USA. EM wkoch@jhmi.edu FU NCI NIH HHS [U10 CA023318]; NIDCR NIH HHS [R01 DE013152, R01 DE013152-09] NR 36 TC 310 Z9 314 U1 3 U2 12 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 DEC 20 PY 2007 VL 357 IS 25 BP 2552 EP 2561 DI 10.1056/NEJMoa073770 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 242MJ UT WOS:000251728900006 PM 18094376 ER PT J AU Fishman, JA AF Fishman, Jay A. TI Medical progress: Infection in solid-organ transplant recipients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; HEPATITIS-C VIRUS; RESISTANT CYTOMEGALOVIRUS-INFECTION; ORTHOTOPIC LIVER-TRANSPLANTATION; HUMAN-IMMUNODEFICIENCY-VIRUS; VISCERAL LEISHMANIASIS; RISK-FACTORS; RENAL-TRANSPLANTATION; LUNG TRANSPLANTATION; FUNGAL-INFECTIONS C1 Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 110 TC 641 Z9 676 U1 2 U2 32 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 DEC 20 PY 2007 VL 357 IS 25 BP 2601 EP 2614 DI 10.1056/NEJMra064928 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 242MJ UT WOS:000251728900010 PM 18094380 ER PT J AU Burnett, MM Huang, MS Seliem, RM AF Burnett, Melissa M. Huang, Mary S. Seliem, Rania M. TI A 5-month-old girl with skin lesions - Acute myeloid leukemia with a t(11q23) translocation, with involvement of the skin (leukemia cutis) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENERALIZED ERUPTIVE HISTIOCYTOMA; CONGENITAL LEUKEMIA; MUTATIONS; CHILDREN; NEONATE; INFANT C1 Massachusetts Gen Hosp, Dept Pediat Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cambridge Hosp, Cambridge Hlth Alliance, Dept Pediat Dermatol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Burnett, MM (reprint author), Massachusetts Gen Hosp, Dept Pediat Dermatol, Boston, MA 02114 USA. NR 30 TC 2 Z9 2 U1 0 U2 1 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 DEC 20 PY 2007 VL 357 IS 25 BP 2616 EP 2623 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 242MJ UT WOS:000251728900013 PM 18094382 ER PT J AU Diaz-Griffero, F Kar, A Lee, M Stremlau, M Poeschla, E Sodroski, J AF Diaz-Griffero, Felipe Kar, Alak Lee, Mark Stremlau, Matthew Poeschla, Eric Sodroski, Josedh TI Comparative requirements for the restriction of retrovirus infection by TRIM5 alpha and TRIMCyp SO VIROLOGY LA English DT Article DE restriction factors; retrovirus; uncoating; human immunodeficiency virus ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEW-WORLD PRIMATES; CYCLOPHILIN-A; REVERSE TRANSCRIPTION; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; CAPSID-BINDING; OLD-WORLD; HIV-1; CELLS AB The restriction factors, TRIM5 alpha in most primates and TRIMCyp in owl monkeys, block infection of various retroviruses soon after virus entry into the host cell. Rhesus monkey TRIN15 alpha (TRIM5 alpha(rh)) inhibits human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV) more potently than human TRIM5a (TRIM5 alpha(hu)). TRIMCyp restricts infection of HIV-1, simian immunodeficiency virus of African green monkeys (SIVagm) and FIV. Early after infection, TRIMCyp, like TRIM5 alpha(rh) and TRIM5 alpha(hu), decreased the amount of particulate viral capsid in the cytosol of infected cells. The requirements for the TRIMCyp and TRIN15a domains in restricting different retroviruses were investigated. Potent restriction of FIV by TRIMCyp occurred in the complete absence of RING and B-box 2 domains; by contrast, efficient FIV restriction by TRIM5 alpha(rh) required these domains. Variable region 1 of the TRIM5 alpha(rh) B30.2 domain contributed to the potency of HIV-1, FIV and equine infectious anemia vir-us restriction. Thus, although differences exist in the requirements of TRIMCyp and TRIM5 alpha for RING/B-box 2 domains, both restriction factors exhibit mechanistic similarities. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pathol, Div AIDS,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Mayo Clin, Coll Med, Program Mol Med, Rochester, MN 55905 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pathol, Div AIDS,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [R21 AI076094, AI160354, R21 AI076094-01, P30 AI060354, R01 AI063987, R01 AI063987-03, AI063987] NR 42 TC 70 Z9 70 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2007 VL 369 IS 2 BP 400 EP 410 DI 10.1016/j.virol.2007.08.032 PG 11 WC Virology SC Virology GA 235VU UT WOS:000251263200016 PM 17920096 ER PT J AU van Heijnsbergen, CCRJ Meeren, HKM Grezes, J de Gelder, B AF van Heijnsbergen, C. C. R. J. Meeren, H. K. M. Grezes, J. de Gelder, B. TI Rapid detection of fear in body expressions, an ERP study SO BRAIN RESEARCH LA English DT Article DE ERP; P1; VPP; body; perception; emotion; fear ID HUMAN EXTRASTRIATE CORTEX; EVENT-RELATED POTENTIALS; FUSIFORM FACE AREA; TIME-COURSE; EMOTIONAL EXPRESSIONS; EVOKED-POTENTIALS; FACIAL EXPRESSION; VISUAL-CORTEX; BRAIN-AREAS; PERCEPTION AB Recent findings indicate that the perceptual processing of fearful expressions in the face can already be initiated around 100-120 ms after stimulus presentation, demonstrating that emotional information of a face can be encoded before the identity of the face is fully recognized. At present it is not clear whether fear signals from body expressions may be encoded equally as rapid. To answer this question we investigated the early temporal dynamics of perceiving fearful body expression by measuring EEG. Participants viewed images of whole body actions presented either in a neutral or a fearful version. We observed an early emotion effect on the P1 peak latency around 112 ms post stimulus onset hitherto only found for facial expressions. Also consistent with the majority of facial expression studies, the N170 component elicited by perceiving bodies proved not to be sensitive for the expressed fear. In line with previous work, its vertex positive counterpart, the VPP, did show a condition-specific influence for fearful body expression. Our results indicate that the information provided by fearful body expression is already encoded in the early stages of visual processing, and suggest that similar early processing mechanisms are involved in the perception of fear in faces and bodies. (c) 2007 Elsevier B.V. All rights reserved. C1 [van Heijnsbergen, C. C. R. J.; Meeren, H. K. M.; de Gelder, B.] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [de Gelder, B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Grezes, J.] Coll France, CNRS, LPPA, F-75231 Paris, France. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, POB 90153, NL-5000 LE Tilburg, Netherlands. EM degelder@uvt.nl RI Grezes, Julie/E-5060-2016 NR 66 TC 40 Z9 40 U1 3 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 19 PY 2007 VL 1186 BP 233 EP 241 DI 10.1016/j.brainres.2007.09.093 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 249BJ UT WOS:000252201500026 PM 17996856 ER PT J AU Wells, DA Ross, JS Detsky, AS AF Wells, David A. Ross, Joseph S. Detsky, Allan S. TI What is different about the market for health care? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CONTROLLED TRIAL; MEDICAL-CARE; INSURANCE; COMMONS; ADULTS; PLANS C1 Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. Mt Sinai Sch Med, Dept Adult Dev, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. James J Peters Vet Adm Med Ctr, Hlth Serv Res & Dev Serv Targeted Res Enhancement, Bronx, NY USA. James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. Univ Toronto, Dept Hlth Policy, Toronto, ON, Canada. Univ Toronto, Dept Management, Toronto, ON, Canada. Univ Toronto, Dept Evaluat & Med, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. RP Detsky, AS (reprint author), Mt Sinai Hosp, Dept Med, 600 Univ Ave,Room 427, Toronto, ON M5G 1X5, Canada. EM allan.detsky@uhn.on.ca NR 19 TC 13 Z9 13 U1 1 U2 3 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 DEC 19 PY 2007 VL 298 IS 23 BP 2785 EP 2787 DI 10.1001/jama.298.23.2785 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 242HK UT WOS:000251716000025 PM 18165673 ER PT J AU Febbo, PG Mulligan, MG Slonina, DA Stegmeir, K Di Vizio, D Martinez, PR Loda, M Taylor, SC AF Febbo, Phillip G. Mulligan, Mike G. Slonina, David A. Stegmeir, Kimberly Di Vizio, Dolores Martinez, Paul R. Loda, Massimo Taylor, Stephen C. TI Literature Lab: a method of automated literature interrogation to infer biology from microarray analysis SO BMC GENOMICS LA English DT Article ID PROSTATE INTRAEPITHELIAL NEOPLASIA; GENE-EXPRESSION; BREAST-CANCER; HUMAN GENOME; SEQUENCE; CARCINOGENESIS; METASTASIS; ANNOTATION; DISCOVERY; KNOWLEDGE AB Background: The biomedical literature is a rich source of associative information but too vast for complete manual review. We have developed an automated method of literature interrogation called "Literature Lab" that identifies and ranks associations existing in the literature between gene sets, such as those derived from microarray experiments, and curated sets of key terms (i.e. pathway names, medical subject heading (MeSH) terms, etc). Results: Literature Lab was developed using differentially expressed gene sets from three previously published cancer experiments and tested on a fourth, novel gene set. When applied to the genesets from the published data including an in vitro experiment, an in vivo mouse experiment, and an experiment with human tumor samples, Literature Lab correctly identified known biological processes occurring within each experiment. When applied to a novel set of genes differentially expressed between locally invasive and metastatic prostate cancer, Literature Lab identified a strong association between the pathway term "FOSB" and genes with increased expression in metastatic prostate cancer. Immunohistochemistry subsequently confirmed increased nuclear FOSB staining in metastatic compared to locally invasive prostate cancers. Conclusion: This work demonstrates that Literature Lab can discover key biological processes by identifying meritorious associations between experimentally derived gene sets and key terms within the biomedical literature. C1 [Febbo, Phillip G.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27710 USA. [Febbo, Phillip G.] Duke Univ, Dept Med, Sch Med, Durham, NC USA. [Febbo, Phillip G.] Duke Univ, Dept Mol Genet & Microbiol, Sch Med, Durham, NC USA. [Mulligan, Mike G.; Slonina, David A.; Martinez, Paul R.; Taylor, Stephen C.] Acumenta Corp, Boston, MA USA. [Stegmeir, Kimberly] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Di Vizio, Dolores; Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Febbo, PG (reprint author), Duke Univ, Inst Genome Sci & Policy, Durham, NC 27710 USA. EM phil.febbo@duke.edu; mmulligan@acumenta.com; dslonina@acumenta.com; kimberly_stegmaier@dfci.harvard.edua; dolores.divizio@childrens.harvard.edu; pmartinez@acumenta.com; massimo_loda@dfci.harvard.edu; staylor@acumenta.com FU NCI NIH HHS [R01 CA123175, CA123175, CA89031, K23 CA089031, K23 CA089031-05, R01 CA123175-01A2] NR 35 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 18 PY 2007 VL 8 AR 461 DI 10.1186/1471-2164-8-461 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 266VY UT WOS:000253466600001 PM 18088408 ER PT J AU Wiviott, SD Trenk, D Frelinger, AL O'Donoghue, M Neumann, FJ Michelson, AD Angiolillo, DJ Hod, H Montalescot, G Miller, DL Jakubowski, JA Cairns, R Murphy, SA McCabe, CH Antman, EM Braunwald, E AF Wiviott, Stephen D. Trenk, Dietmar Frelinger, Andrew L. O'Donoghue, Michelle Neumann, Franz-Josef Michelson, Alan D. Angiolillo, Dominick J. Hod, Hanoch Montalescot, Gilles Miller, Debra L. Jakubowski, Joseph A. Cairns, Richard Murphy, Sabina A. McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene CA PRINCIPLETIME TI Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention - The prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation-thrombolysis in myocardial infarction 44 trial SO CIRCULATION LA English DT Article DE anticoagulants; antiplatelet agents; coronary disease; platelets; thrombosis ID ASSOCIATION TASK-FORCE; RESPONSE VARIABILITY; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ACTIVE METABOLITE; AMERICAN-COLLEGE; GUIDELINE UPDATE; STENT THROMBOSIS; RESISTANCE AB Background - The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. Methods and Results - Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 mu mol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean +/- SD, 74.8 +/- 13.0%) compared with clopidogrel (31.8 +/- 21.1%; P < 0.0001). During the maintenance-dose phase, IPA with 20 mu mol/L ADP was higher in subjects receiving prasugrel (61.3 +/- 17.8%) compared with clopidogrel (46.1 +/- 21.3%; P < 0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. Conclusions - Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel. C1 [Wiviott, Stephen D.; Murphy, Sabina A.; McCabe, Carolyn H.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [O'Donoghue, Michelle] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA USA. [Trenk, Dietmar; Neumann, Franz-Josef] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. [Frelinger, Andrew L.; Michelson, Alan D.] Univ Massachusetts, Sch Med, Dept Pediat Med & Pathol, Worcester, MA USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Hod, Hanoch] Chaim Sheba Med Ctr, Sackler Fac Med, Chaim Sheba Med Ctr, Inst Heart, Tel Aviv, Israel. [Montalescot, Gilles] Petie Salpetriere Univ Hosp, INSERM, Inst Cardiol, Unit 856, Paris, France. [Miller, Debra L.; Jakubowski, Joseph A.] Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN USA. [Cairns, Richard] Nottingham Clin Res Ltd, Nottingham, England. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 38 TC 534 Z9 555 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 18 PY 2007 VL 116 IS 25 BP 2923 EP 2932 DI 10.1161/CIRCULATIONAHA.107.740324 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 242DL UT WOS:000251704600006 PM 18056526 ER PT J AU Chang, L Zhang, J Tseng, YH Xie, CQ Ilany, J Bruning, JC Sun, Z Zhu, X Cui, T Youker, KA Yang, Q Day, SM Kahn, CR Chen, YE AF Chang, Lin Zhang, Jifeng Tseng, Yu-Hua Xie, Chang-Qing Ilany, Jacob Bruning, Jens C. Sun, Zhongcui Zhu, Xiaojun Cui, Taixing Youker, Keith A. Yang, Qinglin Day, Sharlene M. Kahn, C. Ronald Chen, Y. Eugene TI Rad GTPase deficiency leads to cardiac hypertrophy SO CIRCULATION LA English DT Article DE cardiomyopathy; genes; heart diseases; hypertrophy; natriuretic peptides ID DEPENDENT PROTEIN-KINASE; TYPE-2 DIABETES-MELLITUS; VASCULAR SMOOTH-MUSCLE; IN-VIVO; MYOCYTE HYPERTROPHY; CALMODULIN KINASE; BINDING PROTEINS; HEART-FAILURE; RHO; FAMILY AB Background - Rad (Ras associated with diabetes) GTPase is the prototypic member of a subfamily of Ras-related small G proteins. The aim of the present study was to define whether Rad plays an important role in mediating cardiac hypertrophy. Methods and Results - We document for the first time that levels of Rad mRNA and protein were decreased significantly in human failing hearts (n = 10) compared with normal hearts (n = 3; P < 0.01). Similarly, Rad expression was decreased significantly in cardiac hypertrophy induced by pressure overload and in cultured cardiomyocytes with hypertrophy induced by 10 mu mol/L phenylephrine. Gain and loss of Rad function in cardiomyocytes significantly inhibited and increased phenylephrine-induced hypertrophy, respectively. In addition, activation of calcium-calmodulin-dependent kinase II (CaMKII), a strong inducer of cardiac hypertrophy, was significantly inhibited by Rad overexpression. Conversely, downregulation of CaMKII delta by RNA interference technology attenuated the phenylephrine-induced hypertrophic response in cardiomyocytes in which Rad was also knocked down. To further elucidate the potential role of Rad in vivo, we generated Rad-deficient mice and demonstrated that they were more susceptible to cardiac hypertrophy associated with increased CaMKII phosphorylation than wild-type littermate controls. Conclusions - The present data document for the first time that Rad is a novel mediator that inhibits cardiac hypertrophy through the CaMKII pathway. The present study will have significant implications for understanding the mechanisms of cardiac hypertrophy and setting the basis for the development of new strategies for treatment of cardiac hypertrophy. C1 [Chang, Lin; Zhang, Jifeng; Xie, Chang-Qing; Cui, Taixing; Day, Sharlene M.; Chen, Y. Eugene] Univ Michigan, Med Ctr, Ctr Cardiovasc, Dept Internal Med, Ann Arbor, MI 48109 USA. [Tseng, Yu-Hua; Ilany, Jacob; Bruning, Jens C.; Kahn, C. Ronald] Joslin Diabet Ctr, Harvard Med Sch, Boston, MA USA. [Sun, Zhongcui; Zhu, Xiaojun] Peking Univ, Inst Mol Med, Beijing, Peoples R China. [Youker, Keith A.] Methodist Hosp, Res Inst, Dept Cardiol, Houston, TX USA. [Yang, Qinglin] Morehouse Sch Med, Cardiol Res Inst, Atlanta, GA USA. RP Zhang, J (reprint author), Univ Michigan, Med Ctr, Ctr Cardiovasc, Dept Internal Med, Ann Arbor, MI 48109 USA. EM jifengz@umich.edu; echenum@umich.edu OI Cui, Taixing/0000-0002-9528-7299 FU NHLBI NIH HHS [R01 HL075397, HL068878, HL075397, R01 HL068878] NR 40 TC 47 Z9 53 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 DEC 18 PY 2007 VL 116 IS 25 BP 2976 EP 2983 DI 10.1161/CIRCULATIONAHA.107.707257 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 242DL UT WOS:000251704600012 PM 18056528 ER PT J AU Zaidi, FH Hull, JT Peirson, SN Wulff, K Aeschbach, D Gooley, JJ Brainard, GC Gregory-Evans, K Rizzo, JF Czeisler, CA Foster, RG Moseley, MJ Lockley, SW AF Zaidi, Farhan H. Hull, Joseph T. Peirson, Stuart N. Wulff, Katharina Aeschbach, Daniel Gooley, Joshua J. Brainard, George C. Gregory-Evans, Kevin Rizzo, Joseph F., III Czeisler, Charles A. Foster, Russell G. Moseley, Merrick J. Lockley, Steven W. TI Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina SO CURRENT BIOLOGY LA English DT Article ID GANGLION-CELLS; NON-CONE; NON-ROD; OCULAR PHOTORECEPTORS; MELATONIN REGULATION; BRAIN RESPONSES; ACTION SPECTRUM; CHROMOSOME 19Q; MELANOPSIN; BLIND AB As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight [1-11]. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength (similar to 480 nm) blue light and remain functional in the absence of rods and cones [8-10]. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus (similar to 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light. C1 [Zaidi, Farhan H.; Gregory-Evans, Kevin] Univ London Imperial Coll Sci & Technol, Fac Med, Div Neurosci & Mental Hlth, London W6 8RF, England. [Hull, Joseph T.; Aeschbach, Daniel; Gooley, Joshua J.; Czeisler, Charles A.; Lockley, Steven W.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Peirson, Stuart N.; Wulff, Katharina; Foster, Russell G.] Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Lab Ophthalmol, Oxford OX3 7BN, England. [Aeschbach, Daniel; Gooley, Joshua J.; Czeisler, Charles A.; Lockley, Steven W.] Harvard Med Sch, Div Sleep Med, Boston, MA 02115 USA. [Brainard, George C.] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. [Rizzo, Joseph F., III] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Moseley, Merrick J.] City Univ London, Dept Optometry & Visual Sci, London EC1V 0HB, England. RP Foster, RG (reprint author), Univ London Imperial Coll Sci & Technol, Fac Med, Div Neurosci & Mental Hlth, London W6 8RF, England. EM russell.foster@eye.ox.ac.uk; m.j.moseley@city.ac.uk; slockley@hms.harvard.edu RI Gregory-Evans, Kevin/G-9551-2011 FU NCCIH NIH HHS [R01 AT002129]; NCRR NIH HHS [M01 RR002635, M01 RR02635]; NINDS NIH HHS [R01 NS36590, R01 NS036590, R01 NS040982]; Wellcome Trust [069714] NR 36 TC 122 Z9 126 U1 1 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 18 PY 2007 VL 17 IS 24 BP 2122 EP 2128 DI 10.1016/j.cub.2007.11.034 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 244FQ UT WOS:000251852200024 PM 18082405 ER PT J AU Adams, DR Toner, M Langer, R AF Adams, Dana R. Toner, Mehmet Langer, Robert TI Role of trehalose in prevention of giant vesicle adsorption and encapsulated solute leakage in anhydrobiotic preservation SO LANGMUIR LA English DT Article ID PHASE-TRANSITION TEMPERATURE; MAMMALIAN-CELLS; INTRACELLULAR TREHALOSE; PHOSPHOLIPID-BILAYERS; UNILAMELLAR VESICLES; MEMBRANE; VITRIFICATION; PHOSPHATIDYLCHOLINE; LIPOSOMES; HYDRATION AB Anhydrobiotic preservation has the potential to allow the processing and storage of mammalian cells in a state of suspended animation at ambient conditions in trehalose glasses; however, stresses-particularly to the lipid bilayer-during desiccation and rehydration have thus far prevented the full realization of the promise of this technique. Giant gel-phase 1,2-distearoyi-sn-glycero-3-phosphocholine (DSPC) and liquid-crystalline-phase 1,2-dilauroyl-sn-glycero3-phosphocholine (DLPC) vesicles provide a model cell system with which to elucidate the role of trehalose in surface-lipid bilayer interactions, as well as the part played by lipid phase. In the absence of trehalose, DSPC liposoines adsorbed to polystyrene, producing irreversible structural chances and apparent leakage of all intravesicular solute upon drying and rehydration. Addition of trehalose significantly reduced vesicle adsorption with only transient intravesicular solute leakage for the rehydrated vesicles; however, at very low moisture contents, the vesicles underwent permanent structural changes. In contrast to the results with DSPC vesicles, DLPC vesicles largely avoided adsorption and exhibited high intravesicular solute retention when dried and rehydrated even in the absence of trehalose, despite significant internal structural changes. C1 [Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Adams, Dana R.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu FU NCI NIH HHS [U54-CA119349]; NIDDK NIH HHS [DK46270] NR 56 TC 12 Z9 12 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD DEC 18 PY 2007 VL 23 IS 26 BP 13013 EP 13023 DI 10.1021/la700452k PG 11 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 240JD UT WOS:000251583000035 PM 17983248 ER PT J AU Vetter, DE Katz, E Maison, SF Taranda, J Turcan, S Ballestero, J Liberman, MC Elgoyhen, B Boulter, J AF Vetter, Douglas E. Katz, Eleonora Maison, Stephane F. Taranda, Julian Turcan, Sevin Ballestero, Jimena Liberman, M. Charles Elgoyhen, Belen Boulter, Jim TI The alpha 10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cochlea; electrophysiology; inner hair cells; outer hair cells ID OUTER HAIR-CELLS; NICOTINIC ACETYLCHOLINE-RECEPTOR; CA2+-ACTIVATED K+ CHANNEL; GUINEA-PIG COCHLEA; RAT COCHLEA; PHARMACOLOGICAL-PROPERTIES; CHOLINERGIC-RECEPTORS; MAMMALIAN COCHLEA; ACTION-POTENTIALS; MESSENGER-RNA AB Although homomeric channels assembled from the alpha 9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via hetero-meric nAChRs composed of both a9 and alpha 10 subunits. To gain insight into alpha 10 subunit function in vivo, we examined olivocochlear innervation and function in alpha 10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in alpha 10(+/+) and alpha 10(+/-) mice, with no detectable responses to ACh in alpha 10(-/-) mice. In contrast, a proportion of alpha 10(-/-) outer hair cells showed small ACh-evoked currents. In alpha 10(-/-) mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual a9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, alpha 10(-/-) mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. our results demonstrate that alpha 9(-/-) and alpha 10(-/-) mice have overlapping but nonidentical phenotypes. Moreover, alpha 10 nAChR subunits are required for normal olivocochlear activity because a9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in alpha 10(-/-)mutant mice. C1 [Vetter, Douglas E.; Taranda, Julian; Elgoyhen, Belen] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Turcan, Sevin] Tufts Univ, Dept Biomed Engn, Boston, MA 02111 USA. [Katz, Eleonora; Ballestero, Jimena; Elgoyhen, Belen; Boulter, Jim] Consejo Nacl Invest Cient & Tecn, INGEBI, RA-1428 Buenos Aires, DF, Argentina. [Katz, Eleonora; Liberman, M. Charles] Univ Otol & Laryngol, Fac Ciencias Exactas & Nat, Dept Fisiol Biol Mol & Celular, RA-1428 Buenos Aires, DF, Argentina. [Maison, Stephane F.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Maison, Stephane F.] Harvard Univ, Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02115 USA. [Elgoyhen, Belen] Univ Buenos Aires, Fac Med, Dept Farmacol, RA-1121 Buenos Aires, DF, Argentina. [Boulter, Jim] Univ Calif Los Angeles, Hatos res Ctr neuropharmacol, Brain res & Mol Biol Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Vetter, DE (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02111 USA. EM douglas.vetter@tufts.edu FU NIDCD NIH HHS [P30 DC 05209, P30 DC005209, P30 DC005209-06, R01 DC000188, R01 DC000188-26, R01 DC000188-27, R01 DC006258, R01 DC0188, R01 DC6258]; NINDS NIH HHS [R21 NS050419, P30 NS047243] NR 47 TC 58 Z9 61 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2007 VL 104 IS 51 BP 20594 EP 20599 DI 10.1073/pnas.0708545105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244SG UT WOS:000251885000079 PM 18077337 ER PT J AU Yeh, RW Wiviott, SD Giugliano, RP Morrow, DA Shui, A Qin, J Scirica, B Bradner, JE Jang, IK Gibson, CM Antman, EM AF Yeh, Robert W. Wiviott, Stephen D. Giugliano, Robert P. Morrow, David A. Shui, Amy Qin, Jie Scirica, Benjamin Bradner, James E. Jang, Ik-Kyung Gibson, C. Michael Antman, Elliott M. TI Effect of thrombocytopenia on outcomes following treatment with either enoxaparin or unfractionated heparin in patients presenting with acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-SIGNIFICANCE; ISCHEMIC SYNDROMES; UNSTABLE ANGINA; ST-ELEVATION; THERAPY; ASSOCIATION; POPULATION; ANTIBODIES; TRIAL AB Thrombocytopenia is associated with an increased risk for adverse cardiac events and bleeding in patients presenting with acute coronary syndromes (ACS) treated with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes in ACS; however, its effect on the development of thrombocytopenia in this population is not well documented. This study was conducted to examine the incidence and clinical importance of thrombocytopenia in patients presenting with non-ST-elevation ACS randomized to treatment with enoxaparin or UFH. Thrombocytopenia was defined as a platelet count < 100 x 10(9)/L or a > 50% decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910 patients during the follow-up period of 14 days; the incidence was similar between study arms. The development of thrombocytopenia was associated with more frequent death, nonfatal myocardial infarction, and urgent revascularization during the study period (odds ratio 2.96, p = 0.001). This association was independent of assignment to treatment with enoxaparin or UFH (p for interaction = 0.47). Major bleeding was also more common in patients with thrombocytopenia regardless of treatment. In conclusion, thrombocytopenia is a significant correlate of adverse events in patients presenting with non-ST-elevation ACS treated with either enoxaparin or UFH. (C) 2007 Elsevier Inc. All rights reserved. C1 [Wiviott, Stephen D.; Giugliano, Robert P.; Shui, Amy; Qin, Jie; Scirica, Benjamin; Antman, Elliott M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wiviott, Stephen D.; Giugliano, Robert P.; Morrow, David A.; Shui, Amy; Qin, Jie; Scirica, Benjamin; Gibson, C. Michael; Antman, Elliott M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, TIMI Study Grp, Boston, MA 02215 USA. [Yeh, Robert W.; Shui, Amy] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 13 TC 15 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2007 VL 100 IS 12 BP 1734 EP 1738 DI 10.1016/j.amjcard.2007.07.036 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 248BQ UT WOS:000252126700005 PM 18082517 ER PT J AU Cavusoglu, E Chhabra, S Jiang, XC Hojjati, MR Chopra, V Eng, C Gupta, A Yanamadala, S Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Chhabra, Sandeep Jiang, Xian-Cheng Hojjati, Mohammad R. Chopra, Vineet Eng, Calvin Gupta, Amit Yanamadala, Sunitha Pinsky, David J. Marmur, Jonathan D. TI Relation of baseline plasma phospholipid levels to cardiovascular outcomes at two years in men with acute coronary syndrome referred for coronary angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; INDEPENDENT PREDICTOR; I-MILANO; ATHEROSCLEROSIS; CHOLESTEROL; PHOSPHATIDYLCHOLINE; MICE; SPHINGOMYELIN; INFUSION; METABOLISM AB In addition to cholesterol and triglycerides, plasma also contains phospholipids. The choline-containing phospholipids constitute > 90% of total plasma phospholipids. To date, no studies have looked specifically at the prognostic significance of total phospholipids in patients with known or suspected coronary artery disease. The present study investigated the long-term prognostic significance of total choline-containing phospholipid levels in a well-characterized cohort of 193 men with acute coronary syndromes who were referred for coronary angiography at a Department of Veterans Affairs Medical Center. All patients were followed prospectively for the development of vascular outcomes. After controlling for a variety of baseline variables (including established biomarkers such high-sensitivity C-reactive protein and fibrinogen), plasma phospholipid values (analyzed as a continuous variable) were a strong and independent predictor of each of the individual end points of all-cause mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41 to 0.90, p = 0.0126), cardiac mortality (HR 0.49, 95% CI 0.29 to 0.81, p = 0.0057), and myocardial infarction (HR 0.71, 95% CI 0.52 to 0.98, p = 0.0342) when using a Cox proportional-hazards model. In addition, baseline phospholipid values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR 0.66, 95% CI 0.49 to 0.90, p = 0.0075). In conclusion, these data demonstrate that low baseline levels of total choline-containing phospholipid are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with acute coronary syndromes. (C) 2007 Elsevier Inc. All rights reserved. C1 [Cavusoglu, Erdal; Hojjati, Mohammad R.; Gupta, Amit; Marmur, Jonathan D.] Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. [Cavusoglu, Erdal; Chhabra, Sandeep; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Jiang, Xian-Cheng] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. [Yanamadala, Sunitha; Pinsky, David J.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. EM ecavusoglu@aol.com NR 22 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2007 VL 100 IS 12 BP 1739 EP 1743 DI 10.1016/j.amjcard.2007.07.037 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 248BQ UT WOS:000252126700006 PM 18082518 ER PT J AU Varraso, R Jiang, R Barr, RG Willett, WC Camargo, CA AF Varraso, Raphaelle Jiang, Rui Barr, R. Graham Willett, Walter C. Camargo, Carlos A., Jr. TI Prospective study of cured meats consumption and risk of chronic obstructive pulmonary disease in men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; meat; men; nitrites; pulmonary disease; chronic obstructive ID LUNG-FUNCTION DECLINE; REACTIVE NITROGEN; GENERAL-POPULATION; GENDER-DIFFERENCES; NITRIC-OXIDE; NUTRITION; HEALTH; COHORT; DIET; ADULTS AB Cured meats are high in nitrites. Nitrites generate reactive nitrogen species that may cause damage to the lung. The objective is to assess the relation between frequent consumption of cured meats and the risk of newly diagnosed chronic obstructive pulmonary disease (COPD). Between 1986 and 1998, the authors identified 111 self-reported cases of newly diagnosed COPD among 42,915 men from the Health Professionals Follow-up Study. The cumulative average intake of cured meats consumption (processed meats, bacon, hot dogs) was calculated from food frequency questionnaires administrated in 1986, 1990, and 1994 and divided according to servings per week (never/almost never, < 1 serving/week, 1-3 servings/week, 4-6 servings/week, at least once/day). After adjustment for age, smoking status, pack-years, pack-years squared, energy intake, race/ethnicity, US region, body mass index, and physical activity, the consumption of cured meats was positively associated with the risk of newly diagnosed COPD (for highest vs. lowest intake: relative risk = 2.64, 95% confidence interval: 1.39, 5.00; p(trend) = 0.002). In contrast to these findings, the consumption of cured meats was not associated with the risk of adult-onset asthma. These data suggest that cured meat may worsen the adverse effects of smoking on risk of COPD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY 10027 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Varraso, R (reprint author), 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. EM varraso@vjf.inserm.fr RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU NCI NIH HHS [CA55075, P01 CA055075]; NHLBI NIH HHS [HL60712, R01 HL060712, RC1 HL100543]; NIDDK NIH HHS [P30 DK040561-12, P30 DK040561] NR 36 TC 27 Z9 28 U1 0 U2 3 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 DEC 15 PY 2007 VL 166 IS 12 BP 1438 EP 1445 DI 10.1093/aje/kwm235 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 236WP UT WOS:000251334400011 PM 17785711 ER PT J AU Gao, X Chen, H Schwarzschild, MA Glasser, DB Logroscino, G Rimm, EB Ascherio, A AF Gao, Xiang Chen, Honglei Schwarzschild, Michael A. Glasser, Dale B. Logroscino, Giancarlo Rimm, Eric B. Ascherio, Alberto TI Erectile function and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE impotence; Parkinson disease ID NONMOTOR SYMPTOMS; HEALTH-PROFESSIONALS; SEXUAL DYSFUNCTION; TESTOSTERONE; MEN; LIMITATIONS; FREQUENCY; CAFFEINE; WOMEN AB Erectile dysfunction is common among individuals with Parkinson's disease, but it is unknown whether it precedes the onset of the classic features of Parkinson's disease. To address this question, the authors examined whether erectile dysfunction was associated with Parkinson's disease risk in the Health Professionals Follow-up Study. Analyses included 32,616 men free of Parkinson's disease at baseline in 1986 who in 2000 completed a retrospective questionnaire with questions on erectile dysfunction in different time periods. Relative risks were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, history of diabetes, and other covariates. Among men who reported their erectile function before 1986, 200 were diagnosed with Parkinson's disease during 1986-2002. Men with erectile dysfunction before 1986 were 3.8 times more likely to develop Parkinson's disease during the follow-up than were those with very good erectile function (relative risk = 3.8, 95% confidence interval: 2.4, 6.0; p < 0.0001). Multivariate-adjusted relative risks of Parkinson's disease were 2.7, 3.7, and 4.0 (95% confidence interval: 1.4, 11.1; p = 0.008) for participants with first onset of erectile dysfunction (before 1986) at 60 or more, 50-59, and less than 50 years of age, respectively, relative to those without erectile dysfunction. In conclusion, in this retrospective analysis in a large cohort of men, the authors observed that erectile dysfunction was associated with a higher risk of developing Parkinson's disease. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Natl Environm Inst Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Pfizer Inc, Sexual Hlth Team, New York, NY USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Cambridge, MA 02138 USA. RP Gao, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM xgao@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2] NR 21 TC 40 Z9 46 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2007 VL 166 IS 12 BP 1446 EP 1450 DI 10.1093/aje/kwm246 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 236WP UT WOS:000251334400012 PM 17875583 ER PT J AU Greene, RE Mauskopf, J Roberts, CS Zyczynski, T Schlamm, HT AF Greene, Reginald E. Mauskopf, Josephine Roberts, Craig S. Zyczynski, Teresa Schlamm, Haran T. TI Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of invasive pulmonary aspergillosis SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE amphotericin B; antifungals; aspergillosis; drug comparisons; economics; methodology; voriconazole ID ECONOMIC-EVALUATION; NEUTROPENIC PATIENTS; MANAGEMENT; CANDIDEMIA; SURGERY AB Purpose.The comparative cost-effectiveness of voriconazole and amphotericin B in the treatment of invasive pulmonary aspergillosis (IPA) was examined. Methods. A decision-tree model was constructed comparing 12-week treatment outcomes in a subset of patients enrolled in a clinical trial comparing initial treatment of IPA with amphotericin B versus voriconazole. Patients included those with IPA who underwent a thoracic computed tomographic (CT) scan at baseline. Cost and survival were estimated for those with and without a halo sign at baseline. Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B were calculated for both patient subgroups. Results. Patients with a halo sign had similar costs and better survival rates than those without the sign. Within the subgroup of patients with the sign, total costs were lower and survival rates higher for those treated with voriconazole than for those treated with amphotericin B. For patients without a halo sign, total costs and survival rates were higher for those treated with voriconazole versus amphotericin B. Conclusion. Among patients treated for IPA, those with a baseline CT halo sign, an early indicator of the condition, appeared to have better survival rates and lower health care costs compared with patients without the sign. In patients with the halo sign, survival rates were higher and costs were lower when voriconazole rather than amphotericin B was used as first-line treatment; survival was better with voriconazole than with amphotericin B when the halo sign was not present. Voriconazole was cost-effective compared with amphotericin B when the halo sign was present, but voriconazole's cost-effectiveness when the sign was not present depended on the cost per life saved. C1 [Greene, Reginald E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Greene, Reginald E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mauskopf, Josephine] RTI Int, Res Triangle Pk, NC USA. [Roberts, Craig S.] Pfizer Inc, New York, NY USA. [Zyczynski, Teresa] Gen Elect Hlth Care, Princeton, NJ USA. [Schlamm, Haran T.] Pfizer Global Res, New York, NY USA. RP Greene, RE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM greene.reginald@mgh.harvard.edu NR 24 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD DEC 15 PY 2007 VL 64 IS 24 BP 2561 EP 2568 DI 10.2146/ajhp060584 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 246AP UT WOS:000251980200012 PM 18056944 ER PT J AU Slavotinek, AM Warmerdam, B Lin, AE Shaw, GM AF Slavotinek, Anne M. Warmerdam, Barbara Lin, Angela E. Shaw, Gary M. TI Population-based analysis of left- and right-sided diaphragmatic hernias demonstrates different frequencies of selected additional anomalies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT Festschrift Symposium 2007 held in Honor of M Michael Cohen CY MAR 31, 2007 CL Univ Utah, Salt Lake City, UT HO Univ Utah DE diaphragmatic hernia; congenital heart defects; dysmorphology; birth defects; laterality ID LIMB-REDUCTION DEFECTS; DELAYED PRESENTATION; MALFORMATIONS; EPIDEMIOLOGY; ASSOCIATION; MANAGEMENT; MORTALITY; MODEL; MICE; FOG2 AB Congenital diaphragmatic hernia (CDH) is a common birth defect that can be subdivided into several different types depending on the anatomical structures affected. Several studies have demonstrated that right-sided CDH (R-CDH) and left-sided CDH (L-CDH) in humans are associated with different clinical presentations and outcomes. We hypothesized that R-CDH and L-CDH are phenotypically and pathogenically distinct, and that the frequency of associated anomalies would differ among patients with R-CDH compared to patients with L-CDH. Using population-based data from ongoing studies in the California Birth Defects Monitoring Program (CBDMP), we compared 146 CDH cases, 38 with R-CDH (26%) and 108 with L-CDH (74%). The frequencies of atrial septal defect (1/38 R-CDH and 20/108 L-CDH cases; P = 0.015), bilateral pulmonary hypoplasia (22/ 108 L-CDH cases and 15/38 R-CDH cases; P=0.029), abnormal skull or facial shape (17/108 L-CDH patients and 1/38 R-CDH cases; P=0.043), assorted digital anomalies excluding syndactyly, polydactyly or absence of a digit (13/ 108 L-CDH patients and 0/38 R-CDH patients; P= 0.021) and assorted limb anomalies excluding limb reduction defects (18/108 L-CDH patients and 0.38 R-CDH patients; P = 0.004) all showed a statistically significant difference in frequency between R- and L-CDH patients. This descriptive epidemiological study using newborn surveillance data represents the largest comparison of right and left-sided CDH patients so far performed. Several anomalies as listed above were noted to be different in frequency between R- and L-CDH patients, although the interpretation of the significant variability in the frequency of these anomalies is not yet established and the findings require replication. Birth defects monitoring programs can provide the interface for epidemiology and clinical genetics, which in this case, may generate hypotheses to establish the pathogenesis of CDH laterality. (C) 2007 Wiley-Liss, Inc. C1 California Birth Defects Monitoring Program, Berkeley, CA USA. MassGen Hosp Children, Genet Unit, Boston, MA USA. Childrens Hosp Oakland, Res Inst, March Dimes Calif Res Div, Oakland, CA 94609 USA. Univ Calif San Francisco, Dept Pediat, Div Genet, San Francisco, CA 94143 USA. RP Slavotinek, AM (reprint author), Univ Calif San Francisco, Dept Pediat, Div Genet, 533 Parnassus St,Room U585P, San Francisco, CA 94143 USA. EM slavotia@peds.ucsf.edu NR 33 TC 8 Z9 9 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2007 VL 143A IS 24 BP 3127 EP 3136 DI 10.1002/ajmg.a.32100 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 237VS UT WOS:000251405100033 PM 18008313 ER PT J AU Seo, P Stone, JH AF Seo, Philip Stone, John H. TI Small-vessel and medium-vessel vasculitis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review ID CHURG-STRAUSS-SYNDROME; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; GRANULOMATOSIS ETANERCEPT TRIAL; PRIMARY SYSTEMIC VASCULITIDES; TNF-ALPHA BLOCKADE; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; BUERGERS-DISEASE; RANDOMIZED-TRIAL; EXTRAARTICULAR MANIFESTATIONS C1 [Seo, Philip] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Stone, John H.] UpToDate, Waltham, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumat Dis Unit, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jhstone@partners.org FU NIAMS NIH HHS [K23-AR-052820] NR 46 TC 9 Z9 9 U1 0 U2 1 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 DEC 15 PY 2007 VL 57 IS 8 BP 1552 EP 1559 DI 10.1002/art.23105 PG 8 WC Rheumatology SC Rheumatology GA 241DX UT WOS:000251638200031 PM 18050229 ER PT J AU Gusella, JF MacDonald, ME AF Gusella, James F. MacDonald, Marcy E. TI Expanding the notion of disease in huntingtons disease SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gusella, JF (reprint author), CPZN 5830,185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu NR 8 TC 0 Z9 0 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 DEC 15 PY 2007 VL 62 IS 12 BP 1340 EP 1340 DI 10.1016/j.biopsych.2007.09.009 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239CQ UT WOS:000251496400002 PM 18054536 ER PT J AU Bartzokis, G Lu, PH Geschwind, DH Tingus, K Huang, D Mendez, MF Edwards, N Mintz, J AF Bartzokis, George Lu, Po H. Geschwind, Daniel H. Tingus, Kathleen Huang, Danny Mendez, Mario F. Edwards, Nancy Mintz, Jim TI Apolipoprotein e affects both myelin breakdown and cognition: Implications for age-related trajectories of decline into dementia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE age; Alzheimer; ApoE; apolipoprotein; brain; breakdown; cognition; dementia; MRI; myelin; onset; prevention; processing; R-2; risk; speed; T-2; treatment; white matter ID INDUCED INTRAMYELINIC EDEMA; MATTER STRUCTURAL INTEGRITY; PRIMATE CEREBRAL-CORTEX; CENTRAL-NERVOUS-SYSTEM; PRIMARY VISUAL-CORTEX; ALZHEIMERS-DISEASE; RHESUS-MONKEY; APOE GENOTYPE; CORTICAL DISCONNECTION; CHOLESTEROL-METABOLISM AB Background: Age-related myelin breakdown is most evident in later-myelinating white matter (LMwm) brain regions. This process might degrade cognitive processing speed (CPS) underlying age-related cognitive decline and the predominance of age as a risk factor for Alzheimer's disease (AD). Apolipoprotein E (ApoE)4 allele is the second most important AD risk factor. We tested the hypothesis that ApoE4 accelerates age-related slowing in CPS through the process of myelin breakdown. Methods: Calculated transverse relaxation rates (R,), an indirect magnetic resonance imaging measure of myelin breakdown in LMwm, and measures of CPS were obtained in 22 ApoE4+ and 80 ApoE4-, healthy "younger-old" individuals. To assess specificity, contrasting early-myelinating white matter region and memory task were also examined. Results: The CPS versus LMwm R-2 remained significant in the ApoE4+ group even after age was statistically adjusted (r =.65, p =.001) and differed from the correlation observed in the ApoE4 - group (Fisher's z test = 3.22, p <.002). No significant associations were observed with the contrast region and memory task in either ApoE subgroup. Conclusions: A specific association between CPS and myelin breakdown in LMwm exists in asymptomatic "younger-old" individuals at increased genetic risk for AD. Although inferences of change over time and causality are limited by the cross-sectional study design, this finding lends support to the hypotheses that myelin breakdown underlies age-related slowing in CPS and that by altering the trajectory of myelin breakdown, ApoE alleles shift the age at onset of cognitive decline. Combined use of biomarkers and CPS measures might be useful in developing and targeting primary prevention treatments for AD. C1 Univ Calif Los Angeles, Alzheimers Dis Ctr, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lab Neuroimaging, David Geffen Sch Med, Div Brain Mapping, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, David Geffen Sch Med, Dept Neurol, 10911 Weyburn Ave,Room 200G, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [P50 AG 16570, R01 AG027342]; NIMH NIH HHS [MH6357-01A1, MH066029-01A2, MH51928] NR 97 TC 57 Z9 57 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2007 VL 62 IS 12 BP 1380 EP 1387 DI 10.1016/j.biopsych.2007.03.024 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239CQ UT WOS:000251496400008 PM 17659264 ER PT J AU Wright, CI Dickerson, BC Feczko, E Negeira, A Williams, D AF Wright, Christopher I. Dickerson, Bradford C. Feczko, Eric Negeira, Alyson Williams, Danielle TI A functional magnetic resonance imaging study of amygdala responses to human faces in aging and mild Alzheimer's disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE behavior; dementia; emotion; human; neuropsychiatric symptoms; novelty ID AGE-RELATED DIFFERENCES; COGNITIVE IMPAIRMENT; EMOTION PERCEPTION; BRAIN ACTIVATION; BASAL FOREBRAIN; ELDERLY ADULTS; CORTEX; NOVELTY; MEMORY; NEUROBIOLOGY AB Background: Neuropsychiatric symptoms are very common even in mild stages of Alzheimer's disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. Methods: Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. Results: Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. Conclusions: The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Aging & Emot,Psychiat Neuroimaging Res Progra, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gerontol Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Aging & Emot,Psychiat Neuroimaging Res Progra, 13th St,Bldg 149,CNY-2628, Charlestown, MA 02129 USA. EM ciwright@partners.org FU NCRR NIH HHS [P41-RR14075]; NIMH NIH HHS [K23MH64806] NR 42 TC 42 Z9 45 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2007 VL 62 IS 12 BP 1388 EP 1395 DI 10.1016/j.biopsych.2006.11.013 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239CQ UT WOS:000251496400009 PM 17336945 ER PT J AU Leleu, X Jia, XY RunnelS, J Ngo, HT Moreau, AS Farag, M Spencer, JA Pitsillides, CM Hatjiharissi, E Roccaro, A O'Sullivan, G McMillin, DW Moreno, D Kiziltepe, T Carrasco, R Treon, SP Hideshima, T Anderson, KC Lin, CP Ghobrial, IM AF Leleu, Xavier Jia, Xiaoying Runnels, Judith Ngo, Hai T. Moreau, Anne-Sophie Farag, Mena Spencer, Joel A. Pitsillides, Costas M. Hatjiharissi, Evdoxia Roccaro, Aldo O'Sullivan, Garrett McMillin, Douglas W. Moreno, Daisy Kiziltepe, Tanyel Carrasco, Ruben Treon, Steven P. Hideshima, Teru Anderson, Kenneth C. Lin, Charles P. Ghobrial, Irene M. TI The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 3-KINASE SIGNALING PATHWAYS; 2ND INTERNATIONAL WORKSHOP; MULTIPLE-MYELOMA CELLS; STEM-CELLS; IN-VITRO; CANCER; PROLIFERATION; INVOLVEMENT; PROGRESSION AB Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoplasmacytic lymphoma. We demonstrate upregulated Akt activity in WM, and that Akt down-regulation by Akt knockdown and the inhibitor perifosine leads to significant inhibition of proliferation and induction of apoptosis in WM cells in vitro, but not in normal donor peripheral blood and hematopoietic progenitors. Importantly, down-regulation of AM induced cytotoxicity of WM cells in the bone marrow micro-environment (BMM) context. Perifosine induced significant reduction in WM tumor growth in vivo in a subcutaneous xenograft model through inhibition of AM phosphorylation and downstream targets. We also demonstrated that Akt pathway down-regulation inhibited migration and adhesion in vitro and homing of WM tumor cells to the BMM in vivo. Proteomic analysis identified other signaling pathways modulated by perifosine, such as activation of ERK MAPK pathway, which induces survival of tumor cells. Interestingly, MEK inhibitor significantly enhanced perifosine-induced cytotoxicity in WM cells. Using AM knockdown experiments and specific Akt and PI3K inhibitors, we demonstrated that ERK activation is through a direct effect, rather than feedback activation, of perifosine upstream ERK pathway. These results provide understanding of biological effects of Akt: pathway in WM and provide the framework for clinical evaluation of perifosine in WM patients. C1 [Leleu, Xavier; Jia, Xiaoying; Ngo, Hai T.; Moreau, Anne-Sophie; Farag, Mena; Hatjiharissi, Evdoxia; Roccaro, Aldo; O'Sullivan, Garrett; McMillin, Douglas W.; Moreno, Daisy; Kiziltepe, Tanyel; Carrasco, Ruben; Treon, Steven P.; Hideshima, Teru; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier; Jia, Xiaoying; Ngo, Hai T.; Moreau, Anne-Sophie; Farag, Mena; Hatjiharissi, Evdoxia; Roccaro, Aldo; O'Sullivan, Garrett; McMillin, Douglas W.; Moreno, Daisy; Kiziltepe, Tanyel; Carrasco, Ruben; Treon, Steven P.; Hideshima, Teru; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Immunol Lab, Lille, France. [Runnels, Judith; Spencer, Joel A.; Pitsillides, Costas M.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 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 RI Spencer, Joel/A-4590-2013; OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [1 R21 CA126119-01A1, R21 CA126119] NR 39 TC 81 Z9 83 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4417 EP 4426 DI 10.1182/blood-2007-05-092098 PG 10 WC Hematology SC Hematology GA 246IR UT WOS:000252001200048 PM 17761832 ER PT J AU Barry, EV Clark, JJ Cools, J Roesel, J Gilliland, DG AF Barry, Elly V. Clark, Jennifer J. Cools, Jan Roesel, Johannes Gilliland, D. Gary TI Uniform sensitivity of FLT3 activation loop mutants to the tyrosine kinase inhibitor midostaurin SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC-CELLS; MUTATIONS; PKC412; RECEPTOR; PROTEIN; GENE; IDENTIFICATION AB Small molecule inhibitors that target fms-like tyrosine kinase 3 (FLT3)-activating mutations have potential in the treatment of leukemias. However, certain mutations can simultaneously activate the tyrosine kinase, and confer resistance to small molecule inhibitors. We therefore tested the sensitivity of 8 FILT3 activation loop mutants to midostaurin. Each mutant conferred IL-3 factor-independent proliferation to Ba/F3 cells, and each resulted in the constitutive activation of FLT3 and its targets, signal transducer and activator of transcription 5 (STAT5) and extracellular stimuli-responsive kinase (ERK). For each mutant tested, midostaurin inhibited cell growth and phosphorylation of FILT3, STAT5, and ERK. In contrast, midostaruin did not inhibit Ba/F3 cells stably transduced with FLT3-internal tandem duplications containing a G697R mutation that confers resistance to midostaurin, demonstrating that midostaurin inhibition of FILT3 activation loop mutants was not due to off-target effects. We conclude that midostaurin is a potent inhibitor of a spectrum of FLT3 activation loop mutations, and that acute myeloid leukemia patients with such mutations are potential candidates for clinical trials involving midostaurin. C1 [Barry, Elly V.; Clark, Jennifer J.; Gilliland, D. Gary] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barry, Elly V.; Clark, Jennifer J.] Childrens Hosp, Harvard Med Sch, Boston, MA 02115 USA. [Cools, Jan] Univ Antwerp VIB, Dept Mol & Dev Genet, Louvain, Belgium. [Roesel, Johannes] Novartis Pharmaceut, Basel, Switzerland. [Gilliland, D. Gary] Brigham & Womens Hosp, Harvard Med Sch, Howard Hughes Med Inst, Boston, MA USA. RP Barry, EV (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Cools, Jan/0000-0001-6626-5843 FU NCI NIH HHS [CA66996, P01 CA066996]; NIDDK NIH HHS [DK50654, P01 DK050654] NR 25 TC 20 Z9 21 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4476 EP 4479 DI 10.1182/blood-2007-07-101238 PG 4 WC Hematology SC Hematology GA 246IR UT WOS:000252001200054 PM 17827387 ER PT J AU Efstathiou, JA Bae, K Shipley, WU Hanks, GE Pilepich, MV Sandler, HM Smith, MR AF Efstathiou, Jason A. Bae, Kyounghwa Shipley, William U. Hanks, Gerald E. Pilepich, Miljenko V. Sandler, Howard M. Smith, Matthew R. TI Obesity and mortality in men with locally advanced prostate cancer - Analysis of RTOG 85-31 SO CANCER LA English DT Article DE obesity; BMI; mortality; prostate cancer; hormonal therapy; radiation therapy ID BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; BIOCHEMICAL FAILURE; PATHOLOGICAL STAGE; PROSPECTIVE COHORT; RADIATION-THERAPY; UNITED-STATES; RISK-FACTORS AB BACKGROUND. Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and radiation therapy (RT). Whether BMI is associated with prostate cancer-specific mortality (PCSM) was investigated in a large randomized trial of men treated with RT and androgen deprivation therapy (ADT) for locally advanced prostate cancer. METHODS. Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled in a phase 3 trial (RTOG 85-31) and randomized to RT and immediate goserelin or RT alone followed by goserelin at recurrence. Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relations between BMI and all-cause mortality, PCSM, and nonprostate cancer mortality Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI. RESULTS. The 5-year PCSM rate for men with BMI <25 kg/m(2) was 6.5%, compared with 13.1% and 12.2% in men with BMI >= 25 to <30 and BMI >= 30, respec tively (Gray's P =.005). In multivariate analyses, greater BMI was significantly associated with higher PCSM (for BMI >= 25 to <30, hazard ratio [HR] 1.52, 95% confidence interval [CI], 1.02-2.27, P =.04; for BMI >= 30, HR 1.64, 95% CI, 1.01-2.66, P =.04). BMI was not associated with nonprostate cancer or all-cause mortality. CONCLUSIONS. Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased cancer-specific mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course. C1 [Efstathiou, Jason A.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bae, Kyounghwa] Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA. [Hanks, Gerald E.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA USA. [Pilepich, Miljenko V.] Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Los Angeles, CA USA. [Sandler, Howard M.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [RTOG U10 CA21661, U10 CA037422, U10 CA032115, K24 CA121990-02, K24 CA121990, CCOP U10- CA37422, U10 CA021661, U10 CA32115] NR 60 TC 42 Z9 43 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2007 VL 110 IS 12 BP 2691 EP 2699 DI 10.1002/cncr.23093 PG 9 WC Oncology SC Oncology GA 240FW UT WOS:000251573600012 PM 17999404 ER PT J AU Xie, W Nakabayashi, M Regan, MM Oh, WK AF Xie, Wanling Nakabayashi, Mari Regan, Meredith M. Oh, William K. TI Higher prostate-specific antigen levels predict improved survival in patients with hormone-refractory prostate cancer who have skeletal metastases and normal serum alkaline phosphatase SO CANCER LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol DE prostate-specific antigen; alkaline phosphatase; hormone-refractory prostate cancer; bone metastases; survival ID MEN AB BACKGROUND. Higher prostate-specific antigen (PSA) and alkaline phosphatase (ALKP) levels predicted worse survival in men with metastatic hormone-refractory prostate cancer (HRPC). In the current study, the authors evaluated the combined effects of PSA and ALK-P on survival. METHODS. Two hundred twenty-four men who had HRPC with bone metastases and who were receiving chemotherapy were identified, and 143 of those men had data available on both ALK-P and PSA levels at chemotherapy initiation. The primary endpoint of the study was overall survival (OS) after chemotherapy. The men were dichotomized into normal and abnormal ALK-P groups according to levels based on institutional normal ranges. The effect of PSA was evaluated as both a categorical value and a continuous value using Cox regression. RESULTS. Eighty-nine of 143 patients (62%) had elevated ALK-P levels. The median PSA was 147 ng/mL (93 ng/mL in patients with normal ALK-P, 171 ng/mL in patients with elevated ALK-P). At a median follow-up of 30 months after chemotherapy initiation, 93 patients had died. The median OS after chemotherapy was 15.8 months (95% confidence interval, 12.8-18.4 months) and was significantly longer if ALK-P was in the normal range (21.3 months vs 14 months; P =.005). For the group with normal ALK-P levels, the median OS was 12.5 months, 24.5 months, and 36.9 months for patients with low, medium, and high PSA levels, respectively. In contrast, the effect of PSA on survival was not as evident in the group with elevated ALK-P levels (16.5 months vs 11.9 months vs 12.1 months, respectively; P =.14 for interaction). Age-adjusted multivariate analysis demonstrated statistically significant interactions of PSA and ALK-P with OS (P =.02). CONCLUSIONS. ALK-P significantly predicted OS in men with HRPC who had bone metastases. In patients with normal ALK-P levels, higher PSA levels were associated with improved survival. C1 [Nakabayashi, Mari; Oh, William K.] Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Xie, Wanling; Regan, Meredith M.] Harvard Med Sch, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 13 TC 6 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2007 VL 110 IS 12 BP 2709 EP 2715 DI 10.1002/cncr.23111 PG 7 WC Oncology SC Oncology GA 240FW UT WOS:000251573600014 PM 17960608 ER PT J AU Kawano, T Ito, M Raina, D Wu, Z Rosenblatt, J Avigan, D Stone, R Kufe, D AF Kawano, Takeshi Ito, Masaki Raina, Deepak Wu, Zekui Rosenblatt, Jacalyn Avigan, David Stone, Richard Kufe, Donald TI MUC1 oncoprotein regulates Bcr-Abl stability and pathogenesis in chronic myelogenous leukemia cells SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CARCINOMA-ASSOCIATED ANTIGEN; TYROSINE KINASE; C-ABL; BETA-CATENIN; APOPTOTIC RESPONSE; NEGATIVE REGULATOR; DNA-DAMAGE; SIGNALING PATHWAY; STRESS-RESPONSE AB Chronic myelogenous leukemia (CML) results from expression of the Bcr-Abl fusion protein in hematopoietic stem cells. The MUC1 heterodimeric protein is aberrantly overexpressed in diverse human carcinomas. The present studies show that MUC1 is expressed in the human K562 and KU812 CIVIL cell lines. The results show that MUC1 associates with Bcr-Abl through a direct interaction between the Bcr N-terminal region and the MUC1 cytoplasmic domain. Stable silencing of MUCI decreased cytoplasmic Bcr-Abl levels by promoting Bcr-Abl degradation. Silencing MUCI was also associated with decreases in K562 and KU812 cell self-renewal capacity and with a more differentiated erythroid phenotype. The results further show that silencing MUCI. increases sensitivity of CML cells to imatinib-induced apoptosis. Analysis of primary CML blasts confirmed that, as found with the CML cell lines, MUCI blocks differentiation and the apoptotic response to imatinib treatment. These findings indicate that MUCI stabilizes Bcr-Abl and contributes to the pathogenesis of CML cells by promoting self renewal and inhibiting differentiation and apoptosis. C1 [Ito, Masaki; Raina, Deepak; Wu, Zekui; Stone, Richard; Kufe, Donald] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rosenblatt, Jacalyn; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA100707, CA29431, R01 CA042802, CA42802, P50 CA100707, R01 CA029431] NR 50 TC 24 Z9 26 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 DEC 15 PY 2007 VL 67 IS 24 BP 11576 EP 11584 DI 10.1158/0008-5472.CAN-07-2756 PG 9 WC Oncology SC Oncology GA 244HV UT WOS:000251857900016 PM 18089786 ER PT J AU Masri, J Bernath, A Martin, J Jo, OD Vartanian, R Funk, A Gera, J AF Masri, Janine Bernath, Andrew Martin, Jheralyn Jo, Oak D. Vartanian, Raffi Funk, Alexander Gera, Joseph TI mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; SUPPRESSES TUMOR-GROWTH; BREAST-CANCER; AKT ACTIVITY; PKC-ALPHA; CYCLIN D1; RAPAMYCIN; GLIOMAGENESIS; IDENTIFICATION; TARGET AB mTORC2 is a multimeric kinase composed of the mammalian target of rapamycin kinase (mTOR), mLST8, mSin1, and rictor. The complex is insensitive to acute rapamycin exposure and has shown functions in controlling cell growth and actin cytoskeletal assembly. mTORC2 has recently been shown to phosphorylate and activate Akt. Because similar to 70% of gliomas harbor high levels of activated Akt, we investigated whether mTORC2 activity was elevated in gliomas. In this study, we found that mTORC2 activity was elevated in glioma cell lines as well as in primary tumor cells as compared with normal brain tissue (P < 0.05). Moreover, we found that rictor protein and mRNA levels were also elevated and correlated with increased mTORC2 activity. Overexpression of rictor in cell lines led to increased mTORC2 assembly and activity. These lines exhibited increased anchorage-independent growth in soft agar, increased S-phase cell cycle distribution, increased motility, and elevated integrin I and 3 expression. In contrast, small interfering RNA-mediated knockdown of rictor inhibited these oncogenic activities. Protein kinase C alpha (PKC alpha) activity was shown to be elevated in rictor-overexpressing lines but reduced in rictor-knockdown clones, consistent with the known regulation of actin organization by mTORC2 via PKC alpha. Xenograft studies using these cell lines also supported a role for increased mTORC2 activity in tumorigenesis and enhanced tumor growth. In summary, these data suggest that mTORC2 is hyperactivated in gliomas and functions in promoting tumor cell proliferation and invasive potential due to increased complex formation as a result of the overexpression of rictor. C1 [Masri, Janine; Bernath, Andrew; Martin, Jheralyn; Jo, Oak D.; Vartanian, Raffi; Funk, Alexander; Gera, Joseph] Greater Los Angeles VA Hlthcare Syst, Dept Res & Dev, Sepulveda, CA 91343 USA. [Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Gera, J (reprint author), Greater Los Angeles VA Hlthcare Syst, Dept Res & Dev, 16111 Plummer St,Bldg 1,Room C111A, Sepulveda, CA 91343 USA. EM gera@ucla.edu FU NCI NIH HHS [CA109312, CA16042]; NIAID NIH HHS [AI28697] NR 50 TC 129 Z9 136 U1 1 U2 9 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 DEC 15 PY 2007 VL 67 IS 24 BP 11712 EP 11720 DI 10.1158/0008-5472.CAN-07-2223 PG 9 WC Oncology SC Oncology GA 244HV UT WOS:000251857900031 PM 18089801 ER PT J AU Deng, J Shimamura, T Perera, S Carlson, NE Cai, D Shapiro, GI Wong, KK Letai, A AF Deng, Jing Shimamura, Takeshi Perera, Samanthi Carlson, Nicole E. Cai, Dongpo Shapiro, Geoffrey I. Wong, Kwok-Kin Letai, Anthony TI Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; GLUCOCORTICOID-INDUCED APOPTOSIS; CYTOCHROME-C; BH3 DOMAINS; ACQUIRED-RESISTANCE; KINASE DOMAIN; EGF RECEPTOR; GEFITINIB; MUTATIONS; BAX AB A subset of lung cancers expresses mutant forms of epidermal growth factor receptor (EGFR) that are constitutively activated. Cancers bearing activated EGFR can be effectively targeted with EGFR inhibitors such as erlotinib. However, the death-signaling pathways engaged after EGFR inhibition are poorly understood. Here, we show that death after inhibition of EGFR uses the mitochondrial, or intrinsic, pathway of cell death controlled by the BCL-2 family of proteins. BCL-2 inhibits cell death induced by erlotinib, but BCL-2-protected cells are thus rendered BCL-2-dependent and sensitive to the BCL-2 antagonist ABT-737. BH3 profiling reveals that mitochondrial BCL-2 is primed by death signals after EGFR inhibition in these cells. As this result implies, key death-signaling proteins of the BCL-2 family, including RIM, were found to be up-regulated after erlotinib treatment and intercepted by over-expressed BCL-2. BIM is induced by lung cancer cell lines that are sensitive to erlotinib but not by those resistant. Reduction of BIM by siRNA induces resistance to erlotinib. We show that EGFR activity is inhibited by erlotinib in H1650, a lung cancer cell line that bears a sensitizing EGFR mutation, but that 141650 is not killed. We identify the block in apoptosis in this cell line, and show that a novel form of erlotinib resistance is present, a block in BIM up-regulation downstream of EGFR inhibition. This finding has clear implications for overcoming resistance to erlotinib. Resistance to EGFR inhibition can be modulated by alterations in the intrinsic apoptotic pathway controlled by the BCL-2 family of proteins. C1 [Deng, Jing; Shimamura, Takeshi; Perera, Samanthi; Carlson, Nicole E.; Cai, Dongpo; Shapiro, Geoffrey I.; Wong, Kwok-Kin; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Letai, A (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [K08 CA10254, P20 CA90578, R01 CA90687] NR 44 TC 89 Z9 90 U1 1 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 DEC 15 PY 2007 VL 67 IS 24 BP 11867 EP 11875 DI 10.1158/0008-5472.CAN-07-1961 PG 9 WC Oncology SC Oncology GA 244HV UT WOS:000251857900047 PM 18089817 ER PT J AU Engelman, JA Zejnullahu, K Gale, CM Lifshits, E Gonzales, AJ Shimamura, T Zhao, F Vincent, PW Naumov, GN Bradner, JE Althaus, IW Gandhi, L Shapiro, GI Nelson, JM Heymach, JV Meyerson, M Wong, KK Janne, PA AF Engelman, Jeffrey A. Zejnullahu, Kreshnik Gale, Christopher-Michael Lifshits, Eugene Gonzales, Andrea J. Shimamura, Takeshi Zhao, Feng Vincent, Patrick W. Naumov, George N. Bradner, James E. Althaus, Irene W. Gandhi, Leena Shapiro, Geoffrey I. Nelson, James M. Heymach, John V. Meyerson, Matthew Wong, Kwok-Kin Janne, Pasi A. TI PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; HUMAN TUMOR XENOGRAFTS; GENE COPY NUMBER; CELL-LINES; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; ANTITUMOR-ACTIVITY; PHASE-II; ERLOTINIB AB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective treatments for a subset of non-small cell lung cancers. In particular, cancers with specific EGFR-activating mutations seem to be the most sensitive to these agents. However, despite their initial response, such cancers almost invariably develop resistance. In 50% of such cancers, a secondary EGFR mutation, T790M, has been identified that renders gefitinib and erlotinib ineffective inhibitors of EGFR kinase activity. Thus, there is a clinical need to develop novel EGFR inhibitors that can effectively inactivate T790M-containing EGFR proteins. In this study, we evaluate the effectiveness of a novel compound, PF00299804, an irreversible pan-ERBB inhibitor. The results from these studies show that PF00299804 is a potent inhibitor of EGFR-activating mutations as well as the EGFR T790M resistance mutation both in vitro and in vivo. Additionally, PF00299804 is a highly effective inhibitor of both the wild-type ERBB2 and the gefitinib-resistant oncogenic ERBB2 mutation identified in lung cancers. These preclinical evaluations support further clinical development of PF00299804 for cancers with mutations and/or amplifications of ERBB family members. C1 [Zejnullahu, Kreshnik; Shimamura, Takeshi; Zhao, Feng; Gandhi, Leena; Shapiro, Geoffrey I.; Meyerson, Matthew; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02138 USA. [Engelman, Jeffrey A.; Gale, Christopher-Michael] Beth Israel Deaconess Med Ctr, Dept Signal Transduct, Boston, MA 02215 USA. [Zejnullahu, Kreshnik; Shimamura, Takeshi; Zhao, Feng; Bradner, James E.; Gandhi, Leena; Shapiro, Geoffrey I.; Meyerson, Matthew; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shimamura, Takeshi; Gandhi, Leena; Shapiro, Geoffrey I.; Wong, Kwok-Kin; Janne, Pasi A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gonzales, Andrea J.; Althaus, Irene W.; Nelson, James M.] Canc Drug Discovery, Pfizer Global Res & Dev, Ann Arbor, MI USA. [Vincent, Patrick W.] Pfizer Global Res & Dev, Groton, CT USA. [Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Houston, TX USA. [Meyerson, Matthew] MIT, Broad Inst, Cambridge, MA 02139 USA. [Meyerson, Matthew] Harvard Univ, Cambridge, MA 02138 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820A,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org RI Meyerson, Matthew/E-7123-2012; OI Gandhi, Leena/0000-0002-2398-9179; wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [1R01CA114465-01, K08CA120060-01] NR 53 TC 359 Z9 374 U1 3 U2 24 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 DEC 15 PY 2007 VL 67 IS 24 BP 11924 EP 11932 DI 10.1158/0008-5472.CAN-07-1885 PG 9 WC Oncology SC Oncology GA 244HV UT WOS:000251857900053 PM 18089823 ER PT J AU Lord, AM North, TE Zon, LI AF Lord, Allegra M. North, Trista E. Zon, Leonard I. TI Prostaglandin E2 - Making more of your marrow SO CELL CYCLE LA English DT Article DE hematopoiesis; hematopoietic stem cell; prostaglandin; E2; zebrafish ID HEMATOPOIETIC STEM-CELLS; MACROPHAGE PRODUCTION; DUCTUS-ARTERIOSUS; ENDOTHELIAL-CELLS; E-2 BIOSYNTHESIS; EXPRESSION; CYCLOOXYGENASE-2; PROLIFERATION; GRANULOCYTE; SYNTHASE AB We have recently demonstrated through a chemical screen in the zebrafish embryo that prostaglandin E2 (PGE2) is an evolutionarily conserved regulator of hematopoietic stem cell (HSC) number. These results have further been confirmed by in vitro and in vivo studies in the murine model. Bioactive PGE2 derivatives have potential clinical application to accelerate recovery of the hematopoietic system following chemotherapy or irradiation. Ex vivo expansion of HSCs prior to stem cell transplantation may improve reconstitution of hematopoiesis and immune function. This article aims to summarize current knowledge of PGE2-mediated regulation of blood cell homeostasis as well as to discuss the proposed use of PGE2 to expand hematopoietic stem cells for transplantation in the clinical setting. C1 Childrens Hosp, Dana Farber Canc Inst, HHMI, Stem Cell Program & Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, HHMI, Stem Cell Program Hematol Oncol, Karp Family Res Bldg, 1 Lackfan Circle, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 35 TC 30 Z9 30 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2007 VL 6 IS 24 BP 3054 EP 3057 PG 4 WC Cell Biology SC Cell Biology GA 258OK UT WOS:000252877000011 PM 18075310 ER PT J AU Benz, EJ Nathan, DG AF Benz, Edward J., Jr. Nathan, David G. TI Stanley J. Korsmeyer - Dedication SO CLINICAL CANCER RESEARCH LA English DT Biographical-Item C1 [Benz, Edward J., Jr.; Nathan, David G.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 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 DEC 15 PY 2007 VL 13 IS 24 BP 7248 EP 7249 DI 10.1158/1078-0432.CCR-07-2227 PG 2 WC Oncology SC Oncology GA 245RT UT WOS:000251954200007 ER PT J AU Benz, EJ Nathan, DG Amaravadi, RK Danial, NN AF Benz, Edward J., Jr. Nathan, David G. Amaravadi, Ravi K. Danial, Nika N. TI Targeting the cell death-survival equation SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID C-MYC; BCL-2 ANTISENSE; APOPTOSIS; CANCER; TRIAL; INHIBITORS; DISCOVERY; FAMILY; CYCLE; BAX C1 [Benz, Edward J., Jr.; Nathan, David G.; Danial, Nika N.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Benz, EJ (reprint author), Harvard Univ, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM edward_benz@dfci.harvard.edu NR 24 TC 14 Z9 15 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 DEC 15 PY 2007 VL 13 IS 24 BP 7250 EP 7253 DI 10.1158/1078-0432.CCR-07-2221 PG 4 WC Oncology SC Oncology GA 245RT UT WOS:000251954200008 PM 18094404 ER PT J AU Danial, NN AF Danial, Nika N. TI BCL-2 family proteins: Critical checkpoints of apoptotic cell death SO CLINICAL CANCER RESEARCH LA English DT Review ID OUTER-MEMBRANE PERMEABILIZATION; CYTOCHROME-C RELEASE; BH3 MIMETIC ABT-737; DNA-DAMAGE RESPONSE; ENDOPLASMIC-RETICULUM; BH3-ONLY PROTEINS; MITOCHONDRIAL-MEMBRANE; CASPASE ACTIVATION; X-L; CHROMOSOMAL BREAKPOINT AB Apoptosis is a morphologically distinct form of programmed cell death essential for normal development and tissue homeostasis. Aberrant regulation of this pathway is linked to multiple human diseases, including cancer, autoimmunity, neurodegenerative disorders, and diabetes. The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members Control the release of apoptogenic factors from mitochondria. The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. Since this original discovery, remarkable efforts marshaled by many investigators around the world have advanced our knowledge of the basic biology, molecular mechanisms, and therapeutic targets in the apoptotic pathway. This review highlights findings from many laboratories that have helped uncover some of the critical control points in apoptosis. The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. C1 [Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Danial, Nika N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Danial, NN (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 756, Boston, MA 02115 USA. EM nika_danial@dfci.harvard.edu FU NCI NIH HHS [K01CA10659] NR 128 TC 230 Z9 251 U1 4 U2 22 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 DEC 15 PY 2007 VL 13 IS 24 BP 7254 EP 7263 DI 10.1158/1078-0432.CCR-07-1598 PG 10 WC Oncology SC Oncology GA 245RT UT WOS:000251954200009 PM 18094405 ER PT J AU Verdine, GL Walensky, LD AF Verdine, Gregory L. Walensky, Loren D. TI The challenge of drugging undruggable targets in cancer: Lessons learned from targeting BCL-2 family members SO CLINICAL CANCER RESEARCH LA English DT Article ID BH3 MIMETIC ABT-737; SMALL-MOLECULE INHIBITORS; PROSURVIVAL BCL-2; DRUGGABLE GENOME; APOPTOSIS; COMPLEX; PROTEINS; BCL-X(L); LIGANDS; DEATH AB The genomic and proteomic revolutions have provided us with an ever-increasing number of mechanistic insights into cancer pathogenesis. Mutated genes and pathologic protein products have emerged as the basis for modern anticancer drug development. With the increasing realization of the importance of disrupting oncogenic protein-protein interaction, new challenges have emerged for classical small molecule and protein-based drug modalities, i.e., the critical need to target flat and extended protein surfaces. Here, we highlight two distinct technologies that are being used to bridge the pharmacologic gap between small molecules and protein therapeutics. With the BCL-2 family of survival proteins as their substrate for intracellular targeting, we conclude that peptide stapling and fragment-based drug discovery show promise to traverse the critical surface features of proteins that drive human cancer. C1 [Verdine, Gregory L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Childrens Hosp, Cambridge, MA 02138 USA. [Verdine, Gregory L.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu FU NCI NIH HHS [5P01CA92625, 5R01CA50239]; NHLBI NIH HHS [5K08HL074049] NR 36 TC 183 Z9 186 U1 4 U2 64 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 DEC 15 PY 2007 VL 13 IS 24 BP 7264 EP 7270 DI 10.1158/1078-0432.CCR-07-2184 PG 7 WC Oncology SC Oncology GA 245RT UT WOS:000251954200010 PM 18094406 ER PT J AU Kuhn, JG Chang, SM Wen, PY Cloughesy, TF Greenberg, H Schiff, D Conrad, C Fink, KL Robins, HI Mehta, M DeAngelis, L Raizer, J Hess, K Lamborn, KR Dancey, J Praclos, MD AF Kuhn, John G. Chang, Susan M. Wen, Patrick Y. Cloughesy, Timothy F. Greenberg, Harry Schiff, David Conrad, Charles Fink, Karen L. Robins, H. Ian Mehta, Minesh DeAngelis, Lisa Raizer, Jeffrey Hess, Kenneth Lamborn, Kathleen R. Dancey, Janet Praclos, Michael D. TI Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID MAMMALIAN TARGET; PHASE-II; GLIOBLASTOMA-MULTIFORME; CCI-779; CANCER; MTOR; INHIBITOR; SAFETY AB Purpose: To characterize the pharmacokinetics of temsirolimus and its major metabolite, sirolimus, in patients receiving enzyme-inducing antiepileptic drugs (EIAED) compared with patients receiving non-EIAEDs. An additional objective was to determine whether concentrations of temsirolimus or sirolimus were achieved in brain tumor tissue. Experimental Design: Patients with recurrent malignant gliomas not receiving EIAEDs initially received temsirolimus weekly at a dose of 250 mg i.v. The dose was subsequently reduced to 170 mg due to intolerable side effects. For patients taking EIAEDs, the starting dose of temsirolimus was 250 mg with standard dose escalation until the maximal tolerated dose was established. Ten whole blood samples were obtained over a period of 24 h after administration of temsirolimus for pharmacokinetic assessments. Patients eligible for cytoreductive surgery received temsirolimus before tumor resection. Whole blood and tumor tissue were obtained for analysis. Results: Significant differences in the pharmacokinetic variables for temsirolimus and sirolimus were observed between the two patient groups at a comparable dose level of 250 mg. For patients receiving EIAEDs, the systemic exposure to temsirolimus was lower by 1.5-fold. Likewise, peak concentrations and exposure to sirolimus were lower by 2-fold. Measurable concentrations of ternsirolimus and sirolimus were observed in brain tumor specimens. The average tissue to whole blood ratio for ternsirolimus was 1.43 and 0.84 for sirolimus. Conclusions: Drugs that induce cytochrome P450 3A4, such as EIAEDs, significantly affect the pharmacokinetics of ternsirolimus and its active metabolite, sirolimus. Total exposure to temsirolimus and sirolimus was lower in the EIAED group at the maximum tolerated dose of 250 mg compared with the non-EIAED group at the maximum tolerated dose of 170 mg. However, brain tumor tissue concentrations of ternsirolimus and sirolimus were relatively comparable in both groups of patients at their respective dose levels. Correlative analyses of the tissue for the inhibition of the key regulators (p70(S6) kinase and 4E-binding protein 1) of mammalian target of rapamycin are necessary to define the therapeutic significance of the altered exposure to temsirolimus. C1 [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Chang, Susan M.; Lamborn, Kathleen R.; Praclos, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Greenberg, Harry] Univ Michigan Hosp, Ann Arbor, MI 48109 USA. [Schiff, David] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. [Conrad, Charles; Hess, Kenneth] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fink, Karen L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Robins, H. Ian; Mehta, Minesh] Univ Wisconsin Hosp, Madison, WI USA. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Raizer, Jeffrey] Northwestern Univ, Chicago, IL 60611 USA. [Dancey, Janet] NIH, Cancer Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kuhn, JG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM Kuhn@uthscsa.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [U01CA62422, CA16672, CA62412, CA62455, P30 CA016672, P30 CA054174, P30CA54174, U01 CA062399, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01 CA062426, U01CA62339, U01CA62399, U01CA62407, U01CA62421, U01CA62426, UM1 CA137443]; NCRR NIH HHS [M01 RR000042, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186, M01-RR00042, M01-RR00079, M01-RR00633, M01-RR03186, M01-RR0865] NR 17 TC 37 Z9 37 U1 0 U2 6 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 DEC 15 PY 2007 VL 13 IS 24 BP 7401 EP 7406 DI 10.1158/1078-0432.CCR-07-0781 PG 6 WC Oncology SC Oncology GA 245RT UT WOS:000251954200027 PM 18094423 ER PT J AU Vyas, JM Telford, SR Robbins, GK AF Vyas, Jatin M. Telford, Sam R. Robbins, Gregory K. TI Treatment of refractory Babesia microti infection with atovaquone-proguanil in an HIV-infected patient: Case report SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID GAMMA-INTERFERON; FULMINANT BABESIOSIS; EXCHANGE-TRANSFUSION; MALARIA; CELLS; IMMUNITY; MICE AB A patient with acquired immune deficiency syndrome presented with babesiosis 6 months after presumed tick exposure. Despite initial treatment with azithromycin and atovaquone, followed by quinine and clindamycin, he experienced an increasing parasite load. Finally, red blood cell exchange transfusion, anti-Babesia therapy, and the addition of atovaquone-proguanil to the treatment regimen led to symptomatic improvement and elimination of parasitemia. Low-level parasitemia recurred 20 weeks later and was eradicated by administration of atovaquone-proguanil monotherapy. Atovaquone-proguanil appears to have activity against babesiosis and should be studied as a potential therapy for patients with refractory babesiosis. C1 [Vyas, Jatin M.; Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Telford, Sam R.] Tufts Cummings Sch Vet Med, Dept Biomed Sci Infect Dis, North Grafton, MA USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 NR 17 TC 16 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 IS 12 BP 1588 EP 1590 DI 10.1086/523731 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233HI UT WOS:000251081000009 PM 18190320 ER PT J AU Goulet, JL Fultz, SL Rimland, D Butt, A Gibert, C Rodriguez-Barradas, M Bryant, K Justice, AC AF Goulet, Joseph L. Fultz, Shawn L. Rimland, David Butt, Adeel Gibert, Cynthia Rodriguez-Barradas, Maria Bryant, Kendall Justice, Amy C. TI Do patterns of comorbidity vary by HIV status, age, and HIV severity? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; VETERANS AGING COHORT; INFECTED VETERANS; PSYCHIATRIC COMORBIDITY; ADMINISTRATIVE DATA; POST-HAART; DISEASE; PERSPECTIVE; PROGNOSIS; ALCOHOL AB Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count < 200 cells/mm(3); hypertension was associated with CD4 cell count > 200 cells/mm(3). Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection. C1 [Goulet, Joseph L.; Justice, Amy C.] VA CT Hlthcare Syst, West Haven, CT 06516 USA. [Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Fultz, Shawn L.] George Washington Univ, Med Ctr, Vet Hlth Adm, Washington, DC 20037 USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Vet Affairs Med Ctr, Washington, DC 20037 USA. [Rimland, David] Vet Affairs Med Ctr, Atlanta, GA 30033 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Butt, Adeel] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Butt, Adeel] Univ Pittsburgh, Pittsburgh, PA USA. [Rodriguez-Barradas, Maria] Michael E De Bakey Vet Affairs Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Bryant, Kendall] NIH, NIAAA, Bethesda, MD 20892 USA. RP Goulet, JL (reprint author), VA CT Hlthcare Syst, 11ACSLG,Bldg 35A,Rm 2-207 950 Campbell Ave, West Haven, CT 06516 USA. EM joseph.goulet@med.va.gov OI Goulet, Joseph/0000-0002-0842-804X FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U10 AA013566, U01 AA 13566, U01 AA013566, U10 AA 13566, U24 AA020794] NR 34 TC 134 Z9 136 U1 3 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 IS 12 BP 1593 EP 1601 DI 10.1086/523577 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233HI UT WOS:000251081000011 PM 18190322 ER PT J AU Choi, AI Rodriguez, RA Bacchetti, P Volberding, PA Havlir, D Bertenthal, D Bostrom, A O'Hare, AM AF Choi, Andy I. Rodriguez, Rudolph A. Bacchetti, Peter Volberding, Paul A. Havlir, Diane Bertenthal, Daniel Bostrom, Alan O'Hare, Ann M. TI Low rates of antiretroviral therapy among HIV-infected patients with chronic kidney disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PATIENTS RECEIVING DIALYSIS; VETERAN POPULATION; MORTALITY; ADHERENCE; RECOMMENDATIONS; ASCERTAINMENT; DETERMINANTS; GUIDELINES; SURVIVAL AB Background. It is unknown whether chronic kidney disease (CKD) influences receipt of highly active antiretroviral therapy ( HAART) among patients with the human immunodeficiency virus (HIV) and whether prescription practices contribute to excess mortality. Methods. We conducted a retrospective observational study involving HIV-infected patients with established indications for HAART and an outpatient serum creatinine level measured in the Veterans Affairs health care system. Patients were followed up for the outcomes of HAART exposure (percentage of follow-up time treated with HAART), inadequate dose adjustment of renally eliminated antiretroviral medications, and time to death. Results. A total of 1041 patients (8.5%) had CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2). Compared with patients with an eGFR >= 60 mL/min/1.73 m(2), HAART exposure was 14% less (95% confidence interval [CI], 2%-24% less), 24% less (95% CI, 4% more to 45% less), 64% less (95% CI, 38%-79% less), and 49% less (95% CI, 32%-61% less) in patients who had an eGFR of 30-59 mL/min/1.73 m(2), 15-29 mL/min/1.73 m(2), and < 15 mL/min/1.73 m(2) (and were not receiving dialysis) and in patients receiving long-term dialysis, respectively. At study entry, 15.4% of patients with CKD received HAART unadjusted for the level of renal function. The adjusted hazard ratio for death was 1.36 (95% CI, 1.08-1.72) for patients with an eGFR of 30-59 mL/min/1.73 m(2), 2.17 (95% CI, 1.43-3.27) for patients with an eGFR of 15-29 mL/min/1.73 m(2), 5.97 (95% CI, 3.18-11.19) for patients with an eGFR < 15 mL/min/1.73 m(2), and 1.92 (95% CI, 1.30-2.82) for dialysis-dependent patients. Underexposure and inadequate dose adjustment of HAART were associated with 22.5%-35.5% of the excess mortality found among patients with different levels of CKD. Conclusions. Underexposure and inadequate dose adjustment of HAART may contribute to excess mortality among HIV-infected patients with CKD. C1 [Choi, Andy I.; Havlir, Diane] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Choi, Andy I.; Volberding, Paul A.; Havlir, Diane] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bacchetti, Peter; Bostrom, Alan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Choi, Andy I.; Volberding, Paul A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Bertenthal, Daniel] San Francisco VA Med Ctr, Vet Affairs Res Enhancement Award Program, San Francisco, CA USA. [Rodriguez, Rudolph A.; O'Hare, Ann M.] Vet Affairs Puget Sound Hlthcare Syst, Dept Med, Seattle, WA USA. [Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA. RP Choi, AI (reprint author), San Francisco Gen Hosp, Dept Med, Box 1341 Renal Ctr,Bldg 100 Rm 350 1001 Potrero A, San Francisco, CA 94110 USA. EM andy.choi@ucsf.edu FU NIA NIH HHS [K23-AG028980-01]; NIAID NIH HHS [K24-AI51982, P30-AI27763]; NIDDK NIH HHS [T32-DK07219] NR 39 TC 32 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 IS 12 BP 1633 EP 1639 DI 10.1086/523729 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233HI UT WOS:000251081000016 PM 18190326 ER PT J AU Safren, SA Wingood, G Altice, FL AF Safren, Steven A. Wingood, Gina Altice, Frederick L. TI Strategies for primary HIV prevention that target behavioral change SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Opportunities for Improving HIV Diagnosis, Prevention and Access to Care in the United States CY NOV 29-30, 2006 CL Washington, DC SP Amer Acad HIV Med, amfAR, Ctr Dis Control & Prevent, Forum Collaborat HIV Res, HIV Med Assoc Infect Dis Soc Amer, NIAID ID RANDOMIZED CONTROLLED-TRIAL; RISK-REDUCTION INTERVENTION; INJECTION-DRUG USERS; SEXUALLY-TRANSMITTED-DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN-AMERICAN WOMEN; OUT-OF-TREATMENT; MEN; SEX; INFECTION AB In the absence of a vaccine or cure, behavioral change remains the major method to prevent transmission of the human immunodeficiency virus (HIV). Public awareness campaigns that disseminate information about the risks and routes of transmission, although important, have an insufficient influence on the behavioral changes essential to reduce the risk of HIV infection. Because of the complex interplay of cultural and psychosocial influences that guides human behavior, specific programs to decrease high-risk behavior have been developed for target populations. In this report, tested initiatives for preventing HIV infection are summarized and their success evaluated for men who have sex with men, injection drug users, and women of minority racial groups. Objective evidence of reductions in high-risk behavior in these 3 groups, which account for the majority of HIV transmissions in the United States, has critical implications for reducing the overall rate of new HIV infections. C1 [Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Fenway Community Hlth, Boston, MA 02114 USA. [Wingood, Gina] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA USA. [Altice, Frederick L.] Yale Univ, Sch Med, Dept Med, New Haven, CT USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, 7th Fl, Boston, MA 02114 USA. EM ssafren@partners.org FU NIDA NIH HHS [K24 DA 017072, DA01860, K24 DA017072] NR 41 TC 10 Z9 10 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 SU 4 BP S300 EP S307 DI 10.1086/522554 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 240VA UT WOS:000251615100017 PM 18190303 ER PT J AU Walensky, RP Freedberg, KA Weinstein, MC Paltiel, AD AF Walensky, Rochelle P. Freedberg, Kenneth A. Weinstein, Milton C. Paltiel, A. David TI Cost-effectiveness of HIV testing and treatment in the United States SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Opportunities for Improving HIV Diagnosis, Prevention and Access to Care in the United States CY NOV 29-30, 2006 CL Washington, DC SP Amer Acad HIV Med, amfAR, Ctr Dis Control & Prevent, Forum Collaborat HIV Res, HIV Med Assoc Infect Dis Soc Amer, NIAID ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; AIDS; CARE; GUIDELINES; PROPHYLAXIS; DISEASE; ADULTS; ERA AB In September 2006, the US Centers for Disease Control and Prevention (CDC) released new guidelines calling for routine, voluntary human immunodeficiency virus (HIV) testing for all persons aged 13-64 years in health care settings. These guidelines were motivated, in part, by mounting evidence that the traditional approach of using risk factors to identify candidates for HfV testing is inadequate. Of the 1.0-1.2 million people in the United States thought to be infected with HIV, similar to 25% remain unaware of their infection, and nearly half of all infected patients develop acquired immunodeficiency syndrome <= 1 year after testing positive for HIV. Also contributing to the change in testing guidelines was recent evidence that routine HIV testing is cost-effective. Cost-effectiveness analysis, a method of assessing health care interventions in terms of the value they confer, reports results in terms of the resources that are required for the intervention to produce an additional unit of change in health effectiveness; more economically efficient programs are those with lower cost-effectiveness ratios. This article reviews the methods and results of cost-effectiveness studies in the United States and articulates why routine, voluntary HIV testing is not only of crucial public health importance but also economically justified. C1 [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Med Sch, Ctr AIDS Res, Boston, MA USA. [Freedberg, Kenneth A.; Weinstein, Milton C.] Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA USA. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, 9th Fl, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K24 AI062476-04, P30 AI060354, P30 AI060354-03, R01 AI042006, R01 AI42006, K24 AI062476, R01 AI042006-08]; NIDA NIH HHS [R01 DA015612, R01 DA015612-06]; NIMH NIH HHS [R01 MH065869, R01 MH073445-02, R01 MH65869, R01 MH065869-06, R01 MH073445] NR 35 TC 61 Z9 62 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 SU 4 BP S248 EP S254 DI 10.1086/522546 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 240VA UT WOS:000251615100009 PM 18190295 ER PT J AU Pierce, AP de Waal, E McManus, LM Shireman, PK Chaudhuri, AR AF Pierce, Anson P. de Waal, Eric McManus, Linda M. Shireman, Paula K. Chaudhuri, Asish R. TI Oxidation and structural perturbation of redox-sensitive enzymes in injured skeletal muscle SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE creatine kinase; glyceraldehyde-3-phosphate dehydrogenase; cardiotoxin; BisANS; skeletal muscle injury; free radicals ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; CREATINE-KINASE; INFLAMMATORY RESPONSE; SNAKE-VENOM; IN-VITRO; PROTEIN; MICE; PROTEASOME; REGENERATION; DEGRADATION AB Molecular events that control skeletal muscle injury and regeneration are poorly understood. However, inflammation associated with oxidative stress is considered a key player in modulating this process. To understand the consequences of oxidative stress associated with muscle injury, inflammation, and regeneration, hind-limb muscles of C57BI/6J mice were studied after injection of cardiotoxin (CT). Within 1 day post-CT injection, polymorphonuclear neutrophilic leukocyte accumulation was extensive. Compared to baseline, tissue myeloperoxidase (MPO) activity was elevated eight- and fivefold at 1 and 7 days post-CT, respectively. Ubiquitinylated protein was elevated 1 day postinjury and returned to baseline by 21 days. Cysteine residues of creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were irreversibly oxidized within 1 day post-CT injection and were associated with protein conformational changes that fully recovered after 21 days. Importantly, protein structural alterations occurred in conjunction with significant decreases in CK activity at 1, 3, and 7 days post-CT injury. Interestingly, elevations in tissue MPO activity paralleled the time course of conformational changes in CK and GAPDH. In combination, these results demonstrate that muscle proteins in vivo are structurally and functionally altered via the generation of reactive oxygen species produced during inflammatory events after muscle injury and preceding muscle regeneration. Published by Elsevier Inc. C1 [Pierce, Anson P.; McManus, Linda M.; Shireman, Paula K.; Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Pierce, Anson P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [de Waal, Eric; Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Shireman, Paula K.; Chaudhuri, Asish R.] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Chaudhuri, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. EM Chaudhurja@uthsesa.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU NHLBI NIH HHS [HL074236, HL070158]; NIA NIH HHS [AG013319] NR 36 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 15 PY 2007 VL 43 IS 12 BP 1584 EP 1593 DI 10.1016/j.freeradbiomed.2007.08.019 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 241QI UT WOS:000251670500003 PM 18037124 ER PT J AU Sharma, SV Settleman, J AF Sharma, Sreenath V. Settleman, Jeffrey TI Oncogene addiction: setting the stage for molecularly targeted cancer therapy SO GENES & DEVELOPMENT LA English DT Review DE oncogene addiction; cancer; targeted therapy; signal transduction ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; EXPRESSION INDUCES APOPTOSIS; MEDULLARY-THYROID CARCINOMA; S-PHASE ENTRY; GASTROINTESTINAL STROMAL TUMOR; FACTOR RECEPTOR GENE; HUMAN GLIOMA-CELLS; RIBOZYME-MEDIATED INACTIVATION AB In pugilistic parlance, the one-two punch is a devastating combination of blows, with the first punch setting the stage and the second delivering the knock-out. This analogy can be extended to molecularly targeted cancer therapies, with oncogene addiction serving to set the stage for tumor cell killing by a targeted therapeutic agent. While in vitro and in vivo examples abound documenting the existence of this phenomenon, the mechanistic underpinnings that govern oncogene addiction are just beginning to emerge. Our current inability to fully exploit this weakness of cancer cells stems from an incomplete understanding of oncogene addiction, which nonetheless represents one of the rare chinks in the formidable armor of cancer cells. C1 [Sharma, Sreenath V.; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. [Sharma, Sreenath V.; Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 239 TC 236 Z9 247 U1 1 U2 19 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 DEC 15 PY 2007 VL 21 IS 24 BP 3214 EP 3231 DI 10.1101/gad.1609907 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 240ZR UT WOS:000251627200002 PM 18079171 ER PT J AU Bell, DW Kim, SH Godwin, AK Schiripo, TA Harris, PL Haserlat, SM Wahrer, DCR Haiman, CA Daly, MB Niendorf, KB Smith, MR Sgroi, DC Garber, JE Olopade, OI Le Marchand, L Henderson, BE Altshuler, D Haber, DA Freedman, ML AF Bell, Daphne W. Kim, Sang H. Godwin, Andrew K. Schiripo, Taryn A. Harris, Patricia L. Haserlat, Sara M. Wahrer, Doke C. R. Haiman, Christopher A. Daly, Mary B. Niendorf, Kristin B. Smith, Matthew R. Sgroi, Dennis C. Garber, Judy E. Olopade, Olufunmilayo I. Le Marchand, Loic Henderson, Brian E. Altshuler, David Haber, Daniel A. Freedman, Matthew L. TI Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cHEK2; susceptibility; breast; cancer; mutation ID DNA-DAMAGE CHECKPOINT; HEREDITARY BREAST-CANCER; TUMOR-SUPPRESSOR; PROSTATE-CANCER; PROTEIN-KINASE; FHA DOMAIN; MUTATION ANALYSIS; BRCA1 MUTATIONS; CHEK2-ASTERISK-1100DELC; RISK AB The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population-based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Dana Farber Canc Inst, Ctr Populat Sci, Dept Oncol, Boston, MA 02115 USA. Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Broad Inst Biomed Res, Boston, MA USA. RP Bell, DW (reprint author), NHGRI, NIH, Canc Genet Branch, Room 5339,Bldg 50,50 S Dr,MSC 8000, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU Intramural NIH HHS; NCI NIH HHS [K24 CA121990, R01 CA063464, K24 CA121990-02, CA63464, CA87691, U01 CA063464] NR 52 TC 39 Z9 39 U1 0 U2 0 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 DEC 15 PY 2007 VL 121 IS 12 BP 2661 EP 2667 DI 10.1002/ijc.23026 PG 7 WC Oncology SC Oncology GA 233RW UT WOS:000251109000011 PM 17721994 ER PT J AU Wolin, KY Lee, IM Colditz, GA Glynn, RJ Fuchs, C Giovannucci, E AF Wolin, Kathleen Y. Lee, I-Min Colditz, Graham A. Glynn, Robert J. Fuchs, Charles Giovannucci, Edward TI Leisure-time physical activity patterns and risk of colon cancer in women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE physical activity; walking; colon cancer ID COLORECTAL-CANCER; RECTAL-CANCER; UNITED-STATES; LIFE-STYLE; VITAMIN-D; MEN; OBESITY; HEALTH; COHORT; PREVENTION AB Although physical activity has been consistently associated with lower risk of colon cancer, many details of the relationship remain unclear. We assessed the relation between physical activity and risk of colon cancer in 79,295 women aged 40-65 who were free of cancer, ulcerative colitis and Crohn's disease and who report their leisure-time physical activity in 1986; 547 cases were identified through 2002. Women who expended more than 21.5 metabolic equivalent hr/week of physical activity had a relative risk (RR) of colon cancer of 0.77 (95% CI 0.58-1.01), compared to women who expended < 2 metabolic equivalent hr/week. The association was stronger for distal than proximal tumors. Among women whose only reported activity was walking, there was a decreased risk of colon cancer in women walking 1-1.9 hr/week (RR = 0.69, 95% CI 0.47-1.03) compared to those who did not walk. Results were similar for increased amounts of walking, but there was no evidence of a dose response relation. Among women who participated in moderate or vigorous activity, increasing hours of activity were also associated with a decreased risk of colon cancer (p for trend = 0.01); women exercising > 4 hr/week had a 40% lower risk of colon cancer than those exercising < 1 hr/week (RR = 0.56, 95%CI 0.33-0.94). Long-term physical activity was not associated with risk of colon cancer, but the number of cases was small. A significant inverse association exists between physical activity, including that of moderate intensity, such as walking, and risk of colon cancer in women that is more pronounced for distal tumors. (c) 2007 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Siteman Canc Ctr, St Louis, MO USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Wolin, KY (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. EM wolink@wustl.edu RI Colditz, Graham/A-3963-2009; Wolin, Kathleen/I-2154-2014 OI Colditz, Graham/0000-0002-7307-0291; Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [5 T32 CA09001-28, CA 087969, P01 CA087969, R25 CA100600, R25 CA100600-01A1, T32 CA009001, T32 CA009001-28] NR 35 TC 43 Z9 44 U1 0 U2 4 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 DEC 15 PY 2007 VL 121 IS 12 BP 2776 EP 2781 DI 10.1002/ijc.23009 PG 6 WC Oncology SC Oncology GA 233RW UT WOS:000251109000028 PM 17722094 ER PT J AU Nose, H Kubota, R Seth, NP Goon, PK Tanaka, Y Izumo, S Usuku, K Ohara, Y Wucherpfennig, KW Bangham, CRM Osame, M Saito, M AF Nose, Hirohisa Kubota, Ryuji Seth, Nilufer P. Goon, Peter K. Tanaka, Yuetsu Izumo, Shuji Usuku, Koichiro Ohara, Yoshiro Wucherpfennig, Kai W. Bangham, Charles R. M. Osame, Mitsuhiro Saito, Mineki TI Ex vivo analysis of human T lymphotropic virus type 1-specific CD4(+) cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CYTOTOXIC T-LYMPHOCYTES; SPINAL-CORD LESIONS; HTLV-I; HTLV-1-INFECTED INDIVIDUALS; PROVIRAL LOAD; MYELOPATHY; TYPE-1; MEMORY AB HLA-DRB1*0101 is associated with susceptibility to human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Here, we used a synthetic tetramer of DRB1*0101 and its epitope peptide to analyze HTLV-1-specific CD4(+) T cells ex vivo. The frequency of tetramer(+) CD4(+) T cells was significantly greater in patients with HAM/TSP than in healthy HTLV-1 carriers (HCs) at a given proviral load and correlated with HTLV-1 tax messenger RNA expression in HCs but not in patients with HAM/TSP. These cells displayed an early to intermediate effector memory phenotype and were preferentially infected by HTLV-1. T cell receptor gene analyses of 2 unrelated DRB1*0101-positive patients with HAM/TSP showed similar V beta repertoires and amino acid motifs in complementarity-determining region 3. Our data suggest that efficient clonal expansion of virus-specific CD4(+) T cells in patients with HAM/TSP does not simply reflect higher viral burden but rather reflects a rapid turnover caused by preferential infection and/or in vivo stimulation by major histocompatibility complex-peptide complexes. C1 [Ohara, Yoshiro; Saito, Mineki] Kanazawa Med Univ, Dept Microbiol, Uchinada, Ishikawa 9200293, Japan. [Nose, Hirohisa] Kagoshima Univ, Dept Neurol & Geriatr, Kagoshima 890, Japan. [Kubota, Ryuji] Kagoshima Univ, Grad Sch Med & Dent Sci, Ctr Chron Viral Dis, Kagoshima, Japan. [Tanaka, Yuetsu] Univ Ryukyus, Grad Sch Med, Dept Immunol & Infect Dis, Nishihara, Okinawa 90301, Japan. [Usuku, Koichiro] Kumamoto Univ Hosp, Dept Med Informat Technol & Adm Planning, Kumamoto, Japan. [Ohara, Yoshiro; Saito, Mineki] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. [Seth, Nilufer P.; Wucherpfennig, Kai W.] Univ London Imperial Coll Sci & Technol, Wright Fleming Inst, Dept Immunol, London, England. RP Saito, M (reprint author), Kanazawa Med Univ, Dept Microbiol, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan. EM mineki@kanazawa-med.ac.jp RI Kubota, Ryuji/A-7139-2009; OI Bangham, Charles/0000-0003-2624-3599 FU NCI NIH HHS [P01 CA100265] NR 45 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2007 VL 196 IS 12 BP 1761 EP 1772 DI 10.1086/522966 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 245GH UT WOS:000251922600009 PM 18190256 ER PT J AU Counter, SA AF Counter, S. A. TI Preservation of brainstem neurophysiological function in hydranencephaly SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE hydranencephaly; MRI; brainstem auditory evoked response; visual evoked response; somatosensory evoked response; ERG; brain; cerebral hemisphere ID EVOKED-POTENTIALS; INFANT AB The preservation of central neurophysiological function was assessed in a 32-year-old woman with hydranencephaly using brainstem auditory evoked responses (BAER), auditory middle latency responses (MLR), cortical auditory evoked responses (CER), strobe electroretinograms (ERG), strobe-flash visual evoked responses (VER) and median and tibial nerve somatosensory evoked responses (SER). The BAER to the right ear stimulation revealed wave peaks I through VII with normal thresholds, morphology and latencies, while the BAER in the left ear was abnormal. The auditory MLR and CER were absent. Grossly normal strobe ERGs were acquired bilaterally with peak waves at 20 and 50 ms. Strobe VERs were poorly defined and abnormal bilaterally. Left and right median nerve SER revealed significant conduction defects in the large fiber sensory system caudal to the thalamus, above the lower pontine level. Bilateral tibial nerve stimulation revealed normal knee popliteal fossa potentials, but distinct conduction defects in the large fiber sensory system rostral to the lower spinal cord. Brainstem electrophysiological measures revealed functional auditory afferent tracts and nuclei, in the absence of cortical influence, suggesting intact unilateral auditory function, which would support clinical observations of behavioral auditory responses in hydranencephaly. (c) 2007 Elsevier B. V. All rights reserved. C1 Harvard Univ, Biol Labs, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. RP Counter, SA (reprint author), Harvard Univ, Biol Labs, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 15 PY 2007 VL 263 IS 1-2 BP 198 EP 207 DI 10.1016/j.jns.2007.06.043 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 269SY UT WOS:000253671700037 PM 17719607 ER PT J AU Chu, TF Rupnick, MA Kerkela, R Dallabrida, SM Zurakowski, D Nguyen, L Woulfe, K Pravda, E Cassiola, F Desai, J George, S Morgan, JA Harris, DM Ismail, NS Chen, JH Schoen, FJ Van den Abbeele, AD Demetri, GD Force, T Chen, MH AF Chu, Tammy F. Rupnick, Maria A. Kerkela, Risto Dallabrida, Susan M. Zurakowski, David Nguyen, Lisa Woulfe, Kathleen Pravda, Elke Cassiola, Flavia Desai, Jayesh George, Suzanne Morgan, Jeffrey A. Harris, David M. Ismail, Nesreen S. Chen, Jey-Hsin Schoen, Frederick J. Van den Abbeele, Annick D. Demetri, George D. Force, Thomas Chen, Ming Hui TI Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib SO LANCET LA English DT Article ID RENAL-CELL CARCINOMA; METASTATIC BREAST-CANCER; GASTROINTESTINAL STROMAL TUMORS; ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; FACTOR RECEPTORS; THERAPY; SU11248; HYPOTHYROIDISM AB Background Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is approved by both US and European Commission regulatory agencies for clinical use, extends survival of patients with metastatic renal-cell carcinoma and gastrointestinal stromal tumours, but concerns have arisen about its cardiac safety We therefore assessed the cardiovascular risk associated with sunitinib in patients with metastatic gastrointestinal stromal. tumours. Methods We retrospectively reviewed all cardiovascular events in 75 patients with imatinib-resistant, metastatic, gastrointestinal stromal. tumours who had been enrolled in a phase I/II trial investigating the efficacy of sunitinib. The composite cardiovascular endpoint was cardiac death, myocardial infarction, and congestive heart failure. We also examined sunitinib's effects on left ventricular ejection fraction (LVEF) and blood pressure. We investigated potential mechanisms of sunitinib-associated cardiac effects by studies in isolated rat cardiomyocytes and in mice. Findings Eight of 75 (11%) patients given repeating cycles of sunitinib in the phase I/II trial had a cardiovascular event, with congestive heart failure recorded in six of 75 (8%). Ten of 36 (28%) patients treated at the approved sunitinib dose had absolute LVEF reductions in ejection fraction (EF) of at least 10%, and seven of 36 (19%) had LVEF reductions of 15 EF% or more. Sunitinib induced increases in mean systolic and diastolic blood pressure, and 35 of 75 (47%) individuals developed hypertension (>150/100 mm Hg). Congestive heart failure and left ventricular dysfunction generally responded to sunitinib being withheld and institution of medical management. Sunitinib caused mitochondrial injury and cardiomyocyte apoptosis in mice and in cultured rat cardiomyocytes. Interpretation Left ventricular dysfunction might be due, in part, to direct cardiomyocyte toxicity, exacerbated by hypertension. Patients treated with sunitinib should be closely monitored for hypertension and LVEF reduction, especially those with a history of coronary artery disease or cardiac risk factors. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Vasc Biol Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Womens Hlth & Gender Biol Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Div Cardiol, Philadelphia, PA 19107 USA. RP Chen, MH (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM minghui.chen@cardio.chboston.org OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [R01 HL061688-10, HL61688, HL67371, R01 HL061688, R01 HL061688-09, R01 HL061688-11, R01 HL067371] NR 30 TC 489 Z9 506 U1 4 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC 15 PY 2007 VL 370 IS 9604 BP 2011 EP 2019 DI 10.1016/S0140-6736(07)61865-0 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 242BD UT WOS:000251698600028 PM 18083403 ER PT J AU Tsao, JCI Stein, JA Dobalian, A AF Tsao, Jennie C. I. Stein, Judith A. Dobalian, Aram TI Pain, problem drug use history, and aberrant analgesic use behaviors in persons living with HIV SO PAIN LA English DT Article DE pain; opioids; substance abuse; problem drug use; HIV; AIDS ID AMBULATORY AIDS PATIENTS; NATIONAL PROBABILITY SAMPLES; SUBSTANCE-ABUSE TREATMENT; LOW-PREVALENCE DISEASES; QUALITY-OF-LIFE; SERVICES UTILIZATION; UNITED-STATES; HEALTH; ADULTS; PSEUDOADDICTION AB Little is known about the relationship between pain and aberrant use of prescription analgesics in persons living with HIV. We examined the predictive and concurrent associations among pain, aberrant use of opioids, and problem drug use history in a nationally representative longitudinal sample of 2267 HIV+ persons. Covariance structure analyses tested a conceptual model wherein HIV+ patients with a history of problematic drug use (n = 870), compared to those without such history (n = 1397), were hypothesized to report more pain and aberrant opioid use, as well as use of opioids specifically for pain at baseline and 6- and 12-month follow-ups, after controlling for key sociodemographic characteristics. In support of the hypothesized model, patients with a history of problematic drug use reported more pain, and were more likely to report aberrant use of prescription analgesics, as well as use of such medications specifically for pain, compared to patients without such history. We also found a trend toward greater stability of aberrant opioid use over time in problem drug users compared with non-problem users suggesting a persistent pattern of inappropriate medication use in the former group. Our findings suggest that even though HIV+ persons with a history of problematic drug use report on-going patterns of using prescription analgesics specifically for pain, these patients continued to experience persistently higher levels of pain, relative to non-problem users. Among non-problem users, pain was not linked to aberrant use of opioids, but was linked to the use of such medications specifically for pain. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Tsao, Jennie C. I.] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Pediat Pain Program, Los Angeles, CA 90024 USA. [Stein, Judith A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Dobalian, Aram] Univ Calif Los Angeles, Sch Publ Hlth, VA Greater Los Angeles Healthcare Syst HSR&D, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA 90024 USA. [Dobalian, Aram] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Tsao, JCI (reprint author), Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Pediat Pain Program, Los Angeles, CA 90024 USA. EM jtsao@mednet.ucla.edu FU AHRQ HHS [U01 HS008578, U01HS08578]; NIDA NIH HHS [DA01070, P01 DA001070, DA017026, R03 DA017026, R03 DA017026-02] NR 44 TC 19 Z9 21 U1 5 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 15 PY 2007 VL 133 IS 1-3 BP 128 EP 137 DI 10.1016/j.pain.2007.03.016 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 247KN UT WOS:000252077800016 PM 17449182 ER PT J AU Shoji, T Sahara, H Muniappan, A Guenther, DA Wain, J Houser, SL Bravard, MA Pujara, AC Hasse, RS Sachs, DH Madsen, JC Allan, JS AF Shoji, Tsuyoshi Sahara, Hisashi Muniappan, Ashok Guenther, Dax A. Wain, JohnC. Houser, Stuart L. Bravard, Marjory A. Pujara, Akshat C. Hasse, Rebecca S. Sachs, David H. Madsen, Joren C. Allan, James S. TI Operational tolerance to class I disparate lungs can be induced despite pretransplant immunization with class I allopeptides SO TRANSPLANTATION LA English DT Article DE lung; transplantation; swine; tolerance ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; ALLOGRAFT-REJECTION; TRANSPLANTATION TOLERANCE; INDIRECT RECOGNITION; T-CELLS; LYMPHOCYTES; BLOCKADE AB Background. Using a class I-disparate swine lung transplant model, we examined whether an intensive course of 'tacrolimus could induce operational tolerance and whether preoperative allopeptide immunization would prevent the development of tolerance. Methods. Left lung grafts were performed using class I-disparate (class II-matched) donors. Recipients were treated with 12 days of postoperative tacrolimus. Three recipients were immunized prior to transplantation with class I allopeptides. Three other recipients were not immunized. Results. The nonimmunized recipients maintained their grafts long term (>497, >451, and >432 days), without developing chronic rejection. The immunized swine also maintained their grafts long term (>417, >402, >401 days), despite developing a variety of in vitro and in vivo responses to the immunizing peptides, as well as having strong mixed lymphocyte reactions to donor cells prior to transplantation. Conclusions. Using only a brief course of tacrolimus, we have been able to induce a state of operational tolerance in a class I-disparate preclinical lung transplant model. Moreover, preoperative alloimmunization did not block tolerance induction or induce chronic rejection. These data show that it is possible to create a state of operational tolerance to lung allografts even in the presence of donor-sensitized cells. C1 [Shoji, Tsuyoshi; Sahara, Hisashi; Muniappan, Ashok; Guenther, Dax A.; Wain, JohnC.; Houser, Stuart L.; Bravard, Marjory A.; Pujara, Akshat C.; Hasse, Rebecca S.; Sachs, David H.; Madsen, Joren C.; Allan, James S.] Massachusetts Gen Hosp, Harvard Med Sch, Transplantat Biol Res Ctr, Boston, MA USA. [Wain, JohnC.; Allan, James S.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Div Thorac Surg, Boston, MA USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Div Cardiac Surg, Boston, MA USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM jallan@partners.org OI Pujara, Akshat/0000-0003-1342-8981 FU NHLBI NIH HHS [R01 HL67110]; NIAID NIH HHS [P01-AI50151] NR 13 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2007 VL 84 IS 11 BP 1467 EP 1473 DI 10.1097/01.tp.0000288321.67926.13 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 241UR UT WOS:000251681800013 PM 18091523 ER PT J AU Murata, Y Tsuruzoe, K Kawashima, J Furukawa, N Kondo, T Motoshima, H Igata, M Taketa, K Sasaki, K Kishikawa, H Kahn, CR Toyonaga, T Araki, E AF Murata, Yusuke Tsuruzoe, Kaku Kawashima, Junji Furukawa, Noboru Kondo, Tatsuya Motoshima, Hiroyuki Igata, Motoyuki Taketa, Kayo Sasaki, Kazunari Kishikawa, Hideki Kahn, C. Ronald Toyonaga, Tetsushi Araki, Eiichi TI IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IRS-1; insulin resistance; TNF-alpha ID NECROSIS-FACTOR-ALPHA; PHOSPHATIDYLINOSITOL 3-KINASE; ADIPOCYTE DIFFERENTIATION; RECEPTOR SUBSTRATE-1; DIABETES-MELLITUS; PROTEIN; EXPRESSION; GENE; PATHWAY; LACKING AB Insulin receptor substrate-1 (IRS-1) is the major substrate of both the insulin receptor and the IGF-1 receptor. In this study, we created IRS-1 transgenic (IRS-1-Tg) mice which express human IRS-1 cDNA under control of the mouse IRS-1 gene promoter. In the IRS-1-Tg mice, IRS-1 mRNA expression was significantly increased in almost all tissues, but its protein expression was increased in very limited tissues (epididymal fat and skeletal muscle). IRS-1-Tg mice showed glucose intolerance and significantly enlarged epididymal fat mass, as well as elevated serum TNF-alpha concentrations. Importantly insulin signaling was significantly attenuated in the liver of IRS- 1-Tg mice, which may contribute to the glucose intolerance. Our results suggest that excess IRS- I expression may not provide a beneficial impact on glucose homeostasis in vivo. (C) 2007 Elsevier Inc. All rights reserved. C1 Kumamoto Univ, Fac Med & Pharmaceut Sci, Dept Metabol Med, Kumamoto 8608556, Japan. Kumamoto Univ, Hlth Care Ctr, Kumamoto 860, Japan. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Tsuruzoe, K (reprint author), Kumamoto Univ, Fac Med & Pharmaceut Sci, Dept Metabol Med, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM tsuruzoek@fc.kuh.kumamoto-u.ac.jp NR 19 TC 12 Z9 12 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 14 PY 2007 VL 364 IS 2 BP 301 EP 307 DI 10.1016/j.bbrc.2007.10.007 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 232LL UT WOS:000251021100018 PM 17950694 ER PT J AU Cros, D Soto, O Chiappa, KH AF Cros, Didier Soto, Oscar Chiappa, Keith H. TI Transcranial magnetic stimulation during voluntary action: Directional facilitation of outputs and relationships to force generation SO BRAIN RESEARCH LA English DT Article DE motor cortex; transcranial magnetic stimulation; facilitation; force; movement direction ID HUMAN MOTOR CORTEX; DORSAL INTEROSSEOUS MUSCLE; SIMPLE REACTION-TIME; FROGS SPINAL-CORD; BRAIN-STIMULATION; MOVEMENT DIRECTION; MACAQUE MONKEY; CORTICOSPINAL PROJECTIONS; ELECTRICAL-STIMULATION; DESCENDING VOLLEYS AB Single-pulse transcranial magnetic stimulation (TMS) of the human motor cortex evokes simple muscle jerks whose physiological significance is unclear. Indeed, in subjects performing a motor task, there is uncertainty as to whether TMS-evoked outputs reflect the ongoing behavior or, alternatively, a disrupted motor plan. Considering force direction and magnitude to reflect qualitative and quantitative features of the motor plan respectively, we studied the relationships between voluntary forces and those evoked by TMS. In five healthy adults, we recorded the isometric forces acting a hand joint and the electromyographic activity in the first dorsal interosseous (FDI) muscle. Responses obtained at rest were highly invariant. Evoked responses obtained while subjects generated static and dynamic contractions were highly codirectional with the voluntary forces. Such directional relationships were independent of stimulation intensity, stimulated cortical volume, or magnitude of voluntary force exerted. Dynamic force generation was associated with a marked increase in the magnitude of the evoked force that was linearly related to the rate of force generation. The timing of central conduction was different depending on functional role of the target muscle, as either agonist or joint fixator. These results indicate that the architecture of motor plans remain grossly undisrupted by cortical stimulation applied during voluntary motor behavior. The significant magnitude modulation of responses during dynamic force generation suggests an essential role of the corticospinal system in the specification of force changes. Finally, the corticospinal activation depends on the functional role assumed by the target muscle, either postural or agonist. (C) 2007 Elsevier B.V. All rights reserved. C1 [Cros, Didier; Soto, Oscar; Chiappa, Keith H.] Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Lab, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Lab, 3 Hawthorne Pl,Suite 112, Boston, MA 02114 USA. EM dcros@partners.org NR 62 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 14 PY 2007 VL 1185 BP 103 EP 116 DI 10.1016/j.brainres.2007.09.003 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 247FY UT WOS:000252064400011 PM 17961516 ER PT J AU Frederix, K Chauhan, AK Kisucka, J Zhao, BQ Hoff, EI Spronk, HMH ten Cate, H Wagner, DD AF Frederix, Kim Chauhan, Anil K. Kisucka, Janka Zhao, Bing-Qiao Hoff, Erik I. Spronk, Henri M. H. ten Cate, Hugo Wagner, Denisa D. TI Platelet adhesion receptors do not modulate infarct volume after a photochemically induced stroke in mice SO BRAIN RESEARCH LA English DT Article DE photochemically induced stroke; platelet adhesion receptor; aging; blood brain barrier permeability ID CEREBRAL-ARTERY OCCLUSION; VON-WILLEBRAND-FACTOR; BLOOD-BRAIN-BARRIER; P-SELECTIN; IN-VIVO; THROMBOSIS; MODEL; IDENTIFICATION; MECHANISMS; BLOCKADE AB Photochemically induced cerebral infarction has been considered a clinically relevant model for ischemic stroke. We evaluated various transgenic mice to study the role of platelet adhesion molecules in this model. Infarction to the sensorimotoric cortex was induced by erythrosin B and laser light. Infarct volumes were calculated from triphenyltetrazolium chloride stained brain slices. Thrombus formation and vessel leakage were observed in vivo by multiphoton microscopy. Mice mutant in VWF, GPIb alpha, beta 3 integrin, and P-selectin did not show any significant differences in infarct volume compared to wild type (WT). This is in contrast to the intraluminal middle cerebral artery occlusion model in which alpha IIb beta 3 integrin, GPIb alpha, and P-selectin are known to modulate infarct size. Multiphoton microscopy showed that small, non-occlusive embolizing platelet thrombi formed in the Photochemically injured brains. Massive vessel leakage was observed within 25 min of laser injury. Interestingly, we observed a significant increase in infarct size with aging, accordant with heightened fragility of the blood brain barrier (BBB) in older mice. This model of Photochemically induced stroke is closer to a BBB injury model than a thrombotic stroke model in which platelets and their adhesion molecules are crucial. This model will be useful to study mechanisms regulating BBB permeability. (C) 2007 Elsevier B.V. All rights reserved. C1 [Frederix, Kim; Spronk, Henri M. H.; ten Cate, Hugo] Maastricht Univ, Univ Hosp, Dept Internal Med, Lab Clin Thrombosis & Haemostasis, NL-6200 MD Maastricht, Netherlands. [Frederix, Kim; Spronk, Henri M. H.; ten Cate, Hugo] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Internal Med, Lab Clin Thrombosis & Haemostasis, NL-6200 MD Maastricht, Netherlands. [Chauhan, Anil K.; Kisucka, Janka; Zhao, Bing-Qiao; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chauhan, Anil K.; Kisucka, Janka; Zhao, Bing-Qiao; Wagner, Denisa D.] Harvard Univ, Sch Med, CBR INst Biomed Res, Boston, MA 02115 USA. [Hoff, Erik I.] Univ Hosp, Dept Neurol, Maastricht, Netherlands. RP ten Cate, H (reprint author), Maastricht Univ, Univ Hosp, Dept Internal Med, Lab Clin Thrombosis & Haemostasis, Univ Singel 50, NL-6200 MD Maastricht, Netherlands. EM h.tencate@bioch.unimaas.nl; wagner@cbr.med.harvard.edu OI ten Cate, Hugo/0000-0001-7796-4463 FU NHLBI NIH HHS [R37 HL041002, HL41002, R01 HL041002, R37 HL041002-21] NR 28 TC 7 Z9 7 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 14 PY 2007 VL 1185 BP 239 EP 245 DI 10.1016/j.brainres.2007.07.103 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 247FY UT WOS:000252064400025 PM 17996853 ER PT J AU Diederichs, S Haber, DA AF Diederichs, Sven Haber, Daniel A. TI Dual role for argonautes in MicroRNA processing and Posttranscriptional regulation of MicroRNA expression SO CELL LA English DT Article ID RNAI ENZYME COMPLEX; C-ELEGANS; MICROPROCESSOR COMPLEX; DROSHA-DGCR8 COMPLEX; PASSENGER-STRAND; NUCLEAR EXPORT; HUMAN-CELLS; HUMAN RISC; INTERFERENCE; DICER AB MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC) with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here, we show that all Argonautes elevate mature miRNA expression posttranscriptionally, independent of RNase activity. Also, we identify a role for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional processing intermediate, termed Ago2 cleaved precursor miRNA or ac-pre-miRNA. This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2 cleavage may facilitate removal of the nicked passenger strand from RISC after maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function. C1 [Diederichs, Sven; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Diederichs, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM sdiederichs@bics.bwh.harvard.edu; haber@helix.mgh.harvard.edu RI Diederichs, Sven/J-6237-2012 OI Diederichs, Sven/0000-0001-7901-4752 FU PHS HHS [R01 95281] NR 51 TC 332 Z9 348 U1 6 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 14 PY 2007 VL 131 IS 6 BP 1097 EP 1108 DI 10.1016/j.cell.2007.10.032 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GU UT WOS:000252217100018 PM 18083100 ER PT J AU Yu, F Yao, H Zhu, PC Zhang, XQ Pan, QH Gong, C Huang, YJ Hu, XQ Su, FX Lieberman, J Song, E AF Yu, Fengyan Yao, Herui Zhu, Pengcheng Zhang, Xiaoqin Pan, Qiuhui Gong, Chang Huang, Yijun Hu, Xiaoqu Su, Fengxi Lieberman, Judy Song, Erwei TI Iet-7 regulates self renewal and tumorigenicity of breast cancer cells SO CELL LA English DT Article ID MAMMARY STEM/PROGENITOR CELLS; IN-VITRO PROPAGATION; STEM-CELLS; LET-7; EXPRESSION; METASTASIS; SUPPRESSOR; MICRORNAS; REPRESSES; PATHWAYS AB Cancers may arise from rare self-renewing tumor- initiating cells (T-IC). However, how T-IC self renewal, multipotent differentiation, and tumorigenicity are maintained remains obscure. Because miRNAs can regulate cell-fate decisions, we compared miRNA expression in self-renewing and differentiated cells from breast cancer lines and in breast T-IC (BT-IC) and non-BT-IC from 1 degrees breast cancers. Iet-7 miRNAs were markedly reduced in BT-IC and increased with differentiation. Infecting BT-IC with Iet-7-lentivirus reduced proliferation, mammosphere formation, and the proportion of undifferentiated cells in vitro and tumor formation and metastasis in NOD/SCID mice, while antagonizing Iet-7 by antisense oligonucleotides enhanced in vitro self renewal of non-T-IC. Increased Iet-7 paralleled reduced H-RAS and HMGA2, known Iet-7 targets. Silencing H-RAS in a BT-IC-enriched cell line reduced self renewal but had no effect on differentiation, while silencing HMGA2 enhanced differentiation but did not affect self renewal. Therefore Iet-7 regulates multiple BT-IC stem cell-like properties by silencing more than one target. C1 [Yu, Fengyan; Zhu, Pengcheng; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Yu, Fengyan; Yao, Herui; Zhang, Xiaoqin; Pan, Qiuhui; Gong, Chang; Hu, Xiaoqu; Su, Fengxi; Song, Erwei] Sun Yat Sen Univ, Affiliated Hosp 2, Dept Breast Surg, Guangzhou 510120, Peoples R China. [Huang, Yijun] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, Guangzhou 510089, Peoples R China. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu; songew@mail.sysu.edu.cn RI Lieberman, Judy/A-2717-2015 NR 34 TC 1080 Z9 1216 U1 13 U2 140 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 14 PY 2007 VL 131 IS 6 BP 1109 EP 1123 DI 10.1016/j.cell.2007.10.054 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GU UT WOS:000252217100019 PM 18083101 ER PT J AU Ryo, A Hirai, A Nishi, M Liou, YC Perrem, K Lin, SC Hirano, H Lee, SW Aoki, I AF Ryo, Akihide Hirai, Akiko Nishi, Mayuko Liou, Yih-Cherng Perrem, Kilian Lin, Sheng-Cai Hirano, Hisashi Lee, Sam W. Aoki, Ichiro TI A suppressive role of the prolyl isomerase Pin1 in cellular apoptosis mediated by the death-associated protein Daxx SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANCER; ACTIVATION; INHIBITION; MACHINERY; ADAPTER; ALPHA; CELLS; LINKS; PML; JNK AB The death-associated protein Daxx is a multifunctional factor that regulates a variety of cellular processes, including transcription and apoptosis. Several previous reports have indicated that Daxx is induced upon oxidative stress and is then subjected to phosphorylation-based functional modification. However, the precise molecular events underlying these phosphorylation events remain largely unknown. We report in our current study that the peptidyl-prolyl isomerase Pin1 is highly overexpressed in malignant human gliomas and inhibits Daxx-mediated cellular apoptosis. The targeted inhibition of Pin1 by small interfering RNA in A172 glioblastoma cells significantly enhances the apoptotic response induced by hydrogen peroxide or stimulatory Fas antibodies. This is in turn accompanied by the increased induction of Daxx and the activation of the apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase pathway. Furthermore, Pin1 binds to the phosphorylated Ser(178)-Pro motif in the Daxx protein, and Pin1 overexpression results in the rapid degradation of Daxx via the ubiquitin-proteasome pathway. Moreover, a Daxx-S178A mutant, which cannot interact with Pin1, demonstrates higher proapoptotic activity and is refractory to Pin1-mediated antiapoptotic effects. We further found that the expression levels of Pin1 inversely correlate with the degree of Daxx nuclear accumulation in human glioblastoma tissues. These results together indicate that Pin1-mediated prolyl isomerization plays an important role in the negative regulation of Daxx and thereby inhibits the oxidative stress-induced cellular apoptotic response, particularly in malignant tumor cells where Pin1 is often overexpressed. C1 Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. Beaumont Hosp, Mol Oncol Lab, Dept Pathol, Royal Coll Surg Ireland, Dublin 9, Ireland. Xiamen Univ, Sch Life Sci, Key Lab Minist Educ Cell Biol, Xiamen 361005, Peoples R China. Yokohama City Univ, Int Grad Sch Arts & Sci, Yokohama, Kanagawa 2300045, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ryo, A (reprint author), Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM aryo@yokohama-cu.ac.jp RI Lin, SC/G-4666-2010 NR 31 TC 35 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36671 EP 36681 DI 10.1074/jbc.M704145200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300060 PM 17938171 ER PT J AU Dunn, RK Kingston, RE AF Dunn, Rebecca K. Kingston, Robert E. TI Gene regulation in the postgenomic era: Technology takes the wheel SO MOLECULAR CELL LA English DT Article ID EMBRYONIC STEM-CELLS; HISTONE H3; SACCHAROMYCES-CEREVISIAE; DEVELOPMENTAL REGULATORS; MICROARRAY ANALYSIS; PROTEIN COMPLEXES; LYSINE 9; CHROMATIN; TRANSCRIPTION; EXPRESSION AB Transcriptional regulation in eukaryotes is a complicated set of processes involving hundreds of proteins. The past decade has seen significant progress in the development of technologies that allow the dissection of the interplay between these regulatory factors. These methodologies have advanced the field to the point where regulation can be examined at the genome level and where intricate regulatory questions can be addressed in multicellular organisms. The application of these technologies over the coming decade promises exciting views of how complexes integrate to create defined regulatory networks. C1 [Dunn, Rebecca K.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. [Dunn, Rebecca K.; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu NR 34 TC 13 Z9 13 U1 0 U2 0 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 DEC 14 PY 2007 VL 28 IS 5 BP 708 EP 714 DI 10.1016/j.molcel.2007.11.022 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HP UT WOS:000251926000003 PM 18082595 ER PT J AU Cohn, MA Kowal, P Yang, K Haas, W Huang, TT Gygi, SP D'Andrea, AD AF Cohn, Martin A. Kowal, Przemyslaw Yang, Kailin Haas, Wilhelm Huang, Tony T. Gygi, Steven P. D'Andrea, Alan D. TI A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway SO MOLECULAR CELL LA English DT Article ID DEUBIQUITINATING ENZYME; SACCHAROMYCES-CEREVISIAE; SAGA COMPLEX; DNA-REPAIR; IDENTIFICATION; ACTIVATION; EXPRESSION; UCH37; UBP8; USP1 AB The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2, a key protein of the Fanconi anemia DNA repair pathway. Here we report the purification of a USP1 multisubunit protein complex from HeLa cells containing stoichiometric amounts of a WD40 repeat-containing protein, USP1 associated factor 1 (UAF1). In vitro reconstitution of USP1 deubiquitinating enzyme activity, using either ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) or purified monoubiquitinated FANCD2 protein as substrates, demonstrates that LIAR functions as an activator of USP1. UAF1 binding increases the catalytic turnover (k(cat)) but does not increase the affinity of the USP1 enzyme for the substrate (K(M)). Moreover, we show that DNA damage results in an immediate shutoff of transcription of the USP1 gene, leading to a rapid decline in the USP1/UAF1 protein complex. Taken together, our results describe a mechanism of regulation of the deubiquitinating enzyme, USP1, and of DNA repair. C1 [Cohn, Martin A.; Kowal, Przemyslaw; Yang, Kailin; Huang, Tony T.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Haas, Wilhelm; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013; OI Yang, Kailin/0000-0001-5968-6738; Cohn, Martin/0000-0002-2988-3009 FU NHLBI NIH HHS [HL52725, R37 HL052725]; NIDDK NIH HHS [DK43889, R01 DK043889]; PHS HHS [1U19A1067751] NR 30 TC 177 Z9 183 U1 2 U2 7 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 DEC 14 PY 2007 VL 28 IS 5 BP 786 EP 797 DI 10.1016/j.molcel.2007.09.031 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HP UT WOS:000251926000012 PM 18082604 ER PT J AU Xing, J Rochester, J Messer, CK Reiter, BP Korsten, MA AF Xing, Jinhong Rochester, Jeremy Messer, Caroline K. Reiter, Bruce P. Korsten, Mark A. TI A phantom gallbladder an endoscopic retrograde cholangiopancreatography SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE laparoscopic cholecystectomy; complication; abscess; gallbladder; endoscopic retrograde cholangiopancreatography ID LAPAROSCOPIC CHOLECYSTECTOMY AB Various complications have been related to laparoscopic cholecystectomy but most occur shortly after the procedure. In this report, we present a case with very late complications in which an abscess developed within the gallbladder fossa 6 years after laparoscopic cholecystectomy. The abscess resolved after treatment with CT-guided extrahepatic aspiration. However, 4 years later, an endoscopic retrograde cholangiopancreatography (ERCP) performed for choledocholithiasis demonstrated a "gallbladder" which communicated with the common bile duct via a patent cystic duct. This unique case indicates that a cystic duct stump may communicate with the gallbladder fossa many years following cholecystectomy. (c) 2007 WJG. All rights reserved. C1 James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Xing, Jinhong; Rochester, Jeremy; Messer, Caroline K.; Reiter, Bruce P.; Korsten, Mark A.] James J Peters VA Med Ctr, Gastroenterol & Radiol Programs, Bronx, NY 10468 USA. [Xing, Jinhong; Rochester, Jeremy; Messer, Caroline K.; Reiter, Bruce P.; Korsten, Mark A.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Xing, Jinhong; Rochester, Jeremy; Messer, Caroline K.; Reiter, Bruce P.; Korsten, Mark A.] Mt Sinai Sch Med, New York, NY USA. [Xing, Jinhong; Rochester, Jeremy; Messer, Caroline K.; Reiter, Bruce P.; Korsten, Mark A.] Albert Einstein Coll Med, Bronx, NY 10468 USA. RP Korsten, MA (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM korsten.mark@med.va.gov NR 6 TC 2 Z9 2 U1 0 U2 0 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 14 PY 2007 VL 13 IS 46 BP 6274 EP 6276 DI 10.3748/wjg.13.6274 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 244BE UT WOS:000251840200024 PM 18069773 ER PT J AU Matthews, AGW Kuo, AJ Ramon-Maiques, S Han, SM Champagne, KS Ivanov, D Gallardo, M Carney, D Cheung, P Ciccone, DN Walter, KL Utz, PJ Shi, Y Kutateladze, TG Yang, W Gozani, O Oettinger, MA AF Matthews, Adam G. W. Kuo, Alex J. Ramon-Maiques, Santiago Han, Sunmi Champagne, Karen S. Ivanov, Dmitri Gallardo, Mercedes Carney, Dylan Cheung, Peggie Ciccone, David N. Walter, Kay L. Utz, Paul J. Shi, Yang Kutateladze, Tatiana G. Yang, Wei Gozani, Or Oettinger, Marjorie A. TI RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination SO NATURE LA English DT Article ID C-TERMINUS; B-CELL; GENE REARRANGEMENT; PLANT HOMEODOMAIN; PRE-B; METHYLATION; BINDING; TRANSPOSITION; TRANSCRIPTION; ACTIVATION AB Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post- translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2 - an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen- receptor gene assembly(1) - contains a plant homeodomain ( PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 ( H3K4me3). The high- resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3- recognition by RAG2. Mutations that abrogate RAG2's recognition of H3K4me3 severely impair V( D) J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue ( W453) that constitutes a key structural component of the K4me3- binding surface and is essential for RAG2's recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read- out of histone modifications can cause an inherited human disease. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO 80045 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ogozani@stanford.edu; oettinger@frodo.mgh.harvard.edu RI Ivanov, Dmitri/B-4600-2011; Yang, Wei/D-4926-2011; OI Yang, Wei/0000-0002-3591-2195; Glass, Karen/0000-0002-2761-733X FU NIAID NIH HHS [P30 AI060354]; NIGMS NIH HHS [R01 GM048026-12, R01 GM048026] NR 40 TC 286 Z9 292 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 13 PY 2007 VL 450 IS 7172 BP 1106 EP U18 DI 10.1038/nature06431 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 240HY UT WOS:000251579900092 PM 18033247 ER PT J AU Liu, V Cutler, CS Young, AZ AF Liu, Vincent Cutler, Corey S. Young, Alison Z. TI A woman with generalized, ulcerated skin lesions - Aggressive epidermotropic CD8+cytotoxic cutaneous T-cell lymphoma, with pseudoepitheliomatous epidermal hyperplasia, possibly paraneoplastic SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TRANSPLANTATION; CARCINOMA C1 Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Dermatol, Iowa City, IA 52242 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Liu, V (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Dermatol, Iowa City, IA 52242 USA. NR 14 TC 8 Z9 8 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 DEC 13 PY 2007 VL 357 IS 24 BP 2496 EP 2505 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 240CK UT WOS:000251564400013 PM 18077814 ER PT J AU Hoschneider, DP Yang, J Guo, Y Maarek, JMI AF Hoschneider, D. P. Yang, J. Guo, Y. Maarek, J. -M. I. TI Reorganization of functional brain maps after exercise training: Importance of cerebellar-thalamic-cortical pathway SO BRAIN RESEARCH LA English DT Review DE brain mapping; cerebral blood flow; plasticity; exercise; motor training; rehabilitation ID RAT SUPERIOR COLLICULUS; RED NUCLEUS NEURONS; CEREBRAL BLOOD-FLOW; BASAL GANGLIA; MOTOR CORTEX; PARKINSONS-DISEASE; INDICATOR FRACTIONATION; SYNAPTIC REORGANIZATION; HORSERADISH-PEROXIDASE; MEDIODORSAL NUCLEUS AB Exercise training (ET) causes functional and morphologic changes in normal and injured brain. While studies have examined effects of short-term (same day) training on functional brain activation, less work has evaluated effects of long-term training, in particular treadmill running. An improved understanding is relevant as changes in neural reorganization typically require days to weeks, and treadmill training is a component of many neurorehabilitation programs. Adult, male rats (n=10) trained to run for 40 min/day, 5 days/week on a Rotarod treadmill at 11.5 cm/s, while control animals (n=10) walked for 1 min/day at 1.2 cm/s. Six weeks later, [C-14]-iodoantipyrine was injected intravenously during treadmill walking. Regional cerebral blood flow-related tissue radioactivity was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping. Exercised compared to nonexercised rats demonstrated increased influence of the cerebellar-thalamic-cortical (CbTC) circuit, with relative increases in perfusion in deep cerebellar nuclei (medial, interposed, lateral), thalamus (ventrolateral, midline, intralaminar), and paravermis, but with decreases in the vermis. In the basal ganglia-thalamic-cortical circuit, significant decreases were noted in sensorimotor cortex and striatum, with associated increases in the globus pallidus. Additional significant changes were noted in the ventral pallidum, superior colliculus, dentate gyrus (increases), and red nucleus (decreases). Following ET, the new dynamic equilibrium of the brain is characterized by increases in the efficiency of neural processing (sensorimotor cortex, striatum, vermis) and an increased influence of the CbTC circuit. Cerebral regions demonstrating changes in neural activation may point to alternate circuits, which may be mobilized during neurorehabilitation. (C) 2007 Elsevier B.V. All rights reserved. C1 [Hoschneider, D. P.] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. [Hoschneider, D. P.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Hoschneider, D. P.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. [Hoschneider, D. P.; Maarek, J. -M. I.] Univ So Calif, Viterbi Sch Engn, Dept Biomed Engn, Los Angeles, CA USA. [Hoschneider, D. P.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Hoschneider, DP (reprint author), Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, 1333 San Pablo St,BMT 403,MC 9112, Los Angeles, CA 90089 USA. EM holschne@usc.edu NR 105 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2007 VL 1184 BP 96 EP 107 DI 10.1016/j.brainres.2007.09.081 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 247RF UT WOS:000252096600012 ER PT J AU Sterjovski, J Churchill, MJ Ellett, A Gray, LR Roche, MJ Dunfee, RL Purcell, DF Saksena, N Wang, B Sonza, S Wesselingh, SL Karlsson, I Fenyo, EM Gabuzda, D Cunningham, AL Gorry, PR AF Sterjovski, Jasminka Churchill, Melissa J. Ellett, Anne Gray, Lachlan R. Roche, Michael J. Dunfee, Rebecca L. Purcell, Damian Fj Saksena, Nitin Wang, Bin Sonza, Secondo Wesselingh, Steven L. Karlsson, Ingrid Fenyo, Eva-Maria Gabuzda, Dana Cunningham, Anthony L. Gorry, Paul R. TI Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; N-LINKED GLYCOSYLATION; HUMAN MONOCLONAL-ANTIBODIES; CROSS-CLADE NEUTRALIZATION; CORECEPTOR USAGE; MACROPHAGE TROPISM; CHEMOKINE RECEPTORS; ACQUIRED-IMMUNODEFICIENCY; TYPE-1 ENVELOPE; BIOLOGICAL PHENOTYPES AB Background: CCR5-restricted (R5) human immunodeficiency virus type 1 (HIV-1) variants cause CD4+ T-cell loss in the majority of individuals who progress to AIDS, but mechanisms underlying the pathogenicity of R5 strains are poorly understood. To better understand envelope glycoprotein (Env) determinants contributing to pathogenicity of R5 viruses, we characterized 37 full-length R5 Envs from cross-sectional and longitudinal R5 viruses isolated from blood of patients with asymptomatic infection or AIDS, referred to as pre-AIDS (PA) and AIDS (A) R5 Envs, respectively. Results: Compared to PA-R5 Envs, A-R5 Envs had enhanced fusogenicity in quantitative cell-cell fusion assays, and reduced sensitivity to inhibition by the fusion inhibitor T-20. Sequence analysis identified the presence of Asn 362 (N362), a potential N-linked glycosylation site immediately N-terminal to CD4-binding site (CD4bs) residues in the C3 region of gp120, more frequently in AR5 Envs than PA-R5 Envs. N362 was associated with enhanced fusogenicity, faster entry kinetics, and increased sensitivity of Env-pseudotyped reporter viruses to neutralization by the CD4bs-directed Env mAb IgG1b12. Mutagenesis studies showed N362 contributes to enhanced fusogenicity of most A-R5 Envs. Molecular models indicate N362 is located adjacent to the CD4 binding loop of gp120, and suggest N362 may enhance fusogenicity by promoting greater exposure of the CD4bs and/or stabilizing the CD4-bound Env structure. Conclusion: Enhanced fusogenicity is a phenotype of the A-R5 Envs studied, which was associated with the presence of N362, enhanced HIV-1 entry kinetics and increased CD4bs exposure in gp120. N362 contributes to fusogenicity of R5 Envs in a strain dependent manner. Our studies suggest enhanced fusogenicity of A-R5 Envs may contribute to CD4+ T-cell loss in subjects who progress to AIDS whilst harbouring R5 HIV-1 variants. N362 may contribute to this effect in some individuals. C1 [Sterjovski, Jasminka; Churchill, Melissa J.; Ellett, Anne; Gray, Lachlan R.; Roche, Michael J.; Sonza, Secondo; Wesselingh, Steven L.; Gorry, Paul R.] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. [Sterjovski, Jasminka; Churchill, Melissa J.; Wesselingh, Steven L.; Gorry, Paul R.] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. [Sonza, Secondo] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. [Gray, Lachlan R.; Purcell, Damian Fj; Wesselingh, Steven L.; Gorry, Paul R.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. [Dunfee, Rebecca L.; Gabuzda, Dana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Saksena, Nitin; Wang, Bin; Cunningham, Anthony L.] Westmead Millennium Inst, Westmead, NSW, Australia. [Karlsson, Ingrid; Fenyo, Eva-Maria] Lund Univ, Lund, Sweden. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. EM Jasminka@burnet.edu.au; Churchill@burnet.edu.au; amellett@burnet.edu.au; lachlang@burnet.edu.au; mroche@burnet.edu.au; dunfeer@niaid.nih.gov; dfjp@unimelb.edu.au; nitin_saksena@wmi.usyd.edu.au; bin_wang@wmi.usyd.edu.au; sonza@burnet.edu.au; stevew@burnet.edu.au; ingrid.karlsson@cea.fr; eva_maria.fenyo@mmb.lu.se; dana_gabuzda@dfci.harvard.edu RI Purcell, Damian/G-5068-2011; OI Gray, Lachlan/0000-0002-9894-1049; Sterjovski, Jasminka/0000-0002-2471-3000; Roche, Michael/0000-0001-8819-0096; Cunningham, Anthony/0000-0002-6744-5667 FU NIAID NIH HHS [AI054207, R21 AI054207]; NINDS NIH HHS [NS37277, R01 NS037277] NR 96 TC 57 Z9 57 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 12 PY 2007 VL 4 AR 89 DI 10.1186/1742-4690-4-89 PG 21 WC Virology SC Virology GA 260ES UT WOS:000252994200001 PM 18076768 ER PT J AU Krasner, CN McMeekin, DS Chan, S Braly, PS Renshaw, FG Kaye, S Provencher, DM Campos, S Gore, ME AF Krasner, C. N. McMeekin, D. S. Chan, S. Braly, P. S. Renshaw, F. G. Kaye, S. Provencher, D. M. Campos, S. Gore, M. E. CA ET-743-INT-II Study Grp TI A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens SO BRITISH JOURNAL OF CANCER LA English DT Article DE trabectedin; ovarian cancer; overall response rate; platinum-sensitive; platinum-resistant; progression-free survival ID PEGYLATED LIPOSOMAL DOXORUBICIN; CONTINUOUS INTRAVENOUS-INFUSION; ANTITUMOR-ACTIVITY; SOLID TUMORS; ECTEINASCIDIN-743 ET-743; MARINE COMPOUND; MINOR-GROOVE; CARCINOMA; YONDELIS(TM); MALIGNANCIES AB The objective of this study was to determine the objective response rate in patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer to treatment with trabectedin (Yondelis (R)) administered as a 3-h infusion weekly for 3 weeks of a 4-week cycle. We carried out a multicentre Phase II trial of trabectedin in patients with advanced recurrent ovarian cancer. Trabectedin (0.58 mg m(-2)) was administered via a central line, after premedication with dexamethasone, to 147 patients as a 3-h infusion weekly for 3 weeks followed by 1-week rest. Major eligibility criteria included measurable relapsed advanced ovarian cancer and not more than two prior platinum-containing regimens. Patients were stratified according to the treatment-free interval (TFI) between having either platinum-sensitive (>= 6 months TFI) or platinum-resistant disease (< 6 months TFI)/platinum-refractory disease (progression during first line therapy). In the platinum-sensitive cohort, 62 evaluable patients with measurable disease had an overall response rate (ORR) of 29.0% (95% Cl: 18.2-41.9%) and median progression-free survival (PFS) was 5.1 months (95% Cl: 2.8-6.2). Four patients with measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) criteria had no follow-up scans at the end of treatment. In the platinum-resistant/refractory cohort, 79 patients were evaluable with an ORR of 6.3% (95% Cl: 2.1-14.2%). Median PFS was 2.0 months (95% Cl: 1.7-3.5 months). Two patients with measurable disease per RECIST criteria had no follow-up scans at the end of treatment. The most frequent (>= 2% of patients) drug-related treatment-emergent grade 3/4 adverse events were reversible liver alanine transferase elevation (10%), neutropaenia (8%), nausea, vomiting, and fatigue (5% each). Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile. C1 [Krasner, C. N.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [McMeekin, D. S.] Univ Oklahoma, Hlth Sci Ctr, Dept Gynecol Oncol, Oklahoma City, OK USA. [Chan, S.] City Hosp Nottingham, Dept Clin Oncol, Nottingham, England. [Braly, P. S.] Dept Gynecol Oncol Hematol & Oncol Specialists, New Orleans, LA USA. [Renshaw, F. G.] Johnson & Johnson Pharmaceut Res & Dev, LLC, Oncol Therapeut, Raritan, NJ USA. [Kaye, S.; Gore, M. E.] Royal Marsden Hosp, Dept Med, London SW3 6JJ, England. [Provencher, D. M.] Hop Notre Dame de Bon Secours, CHUM, Dept Gynecol, Montreal, PQ H2L 4K8, Canada. [Campos, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Krasner, CN (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, 100 Blossom St Cox 5, Boston, MA 02114 USA. EM cnkrasner@partners.org NR 39 TC 65 Z9 65 U1 0 U2 0 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 DEC 11 PY 2007 VL 97 IS 12 BP 1618 EP 1624 DI 10.1038/sj.bjc.6604088 PG 7 WC Oncology SC Oncology GA 240ZF UT WOS:000251626000004 PM 18000504 ER PT J AU Aikawa, E Nahrendorf, M Figueiredo, JL Swirski, FK Shtatland, T Kohler, RH Jaffer, FA Aikawa, M Weissleder, R AF Aikawa, Elena Nahrendorf, Matthias Figueiredo, Jose-Luiz Swirski, Filip K. Shtatland, Timur Kohler, Rainer H. Jaffer, Farouc A. Aikawa, Masanori Weissleder, Ralph TI Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo SO CIRCULATION LA English DT Article DE atherosclerosis; calcification; inflammation; imaging ID AORTIC-VALVE DISEASE; SMOOTH-MUSCLE-CELLS; VASCULAR CALCIFICATION; DEFICIENT MICE; DENSITY-LIPOPROTEIN; VULNERABLE PLAQUE; PROTEIN-KINASE; CATHEPSIN-K; MACROPHAGES; STENOSIS AB Background-Arterial calcification is associated with cardiovascular events; however, mechanisms of calcification in atherosclerosis remain obscure. Methods and Results-We tested the hypothesis that inflammation promotes osteogenesis in atherosclerotic plaques using in vivo molecular imaging in apolipoprotein E-/- mice ( 20 to 30 weeks old, n=35). A bisphosphonate-derivatized near-infrared fluorescent imaging agent ( excitation 750 nm) visualized osteogenic activity that was otherwise undetectable by x-ray computed tomography. Flow cytometry validated the target specifically in osteoblast-like cells. A spectrally distinct near-infrared fluorescent nanoparticle ( excitation 680 nm) was coinjected to simultaneously image macrophages. Fluorescence reflectance mapping demonstrated an association between osteogenic activity and macrophages in aortas of apolipoprotein E-/- mice (R-2=0.93). Intravital dual-channel fluorescence microscopy was used to further monitor osteogenic changes in inflamed carotid arteries at 20 and 30 weeks of age and revealed that macrophage burden and osteogenesis concomitantly increased during plaque progression ( P < 0.01 and P < 0.001, respectively) and decreased after statin treatment ( P < 0.0001 and P < 0.05, respectively). Fluorescence microscopy on cryosections colocalized near-infrared fluorescent osteogenic signals with alkaline phosphatase activity, bone-regulating protein expression, and hydroxyapatite nanocrystals as detected by electron microscopy, whereas von Kossa and alizarin red stains showed no evidence of calcification. Real-time reverse-transcription polymerase chain reaction revealed that macrophage-conditioned media increased alkaline phosphatase mRNA expression in vascular smooth muscle cells. Conclusions-This serial in vivo study demonstrates the real-time association of macrophage burden with osteogenic activity in early-stage atherosclerosis and offers a cellular-resolution tool to identify preclinical microcalcifications. C1 [Aikawa, Elena; Nahrendorf, Matthias; Figueiredo, Jose-Luiz; Swirski, Filip K.; Shtatland, Timur; Kohler, Rainer H.; Jaffer, Farouc A.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Aikawa, Elena; Nahrendorf, Matthias; Swirski, Filip K.; Jaffer, Farouc A.; Aikawa, Masanori; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA USA. [Aikawa, Masanori] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Aikawa, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5420, Charlestown, MA 02129 USA. EM eaikawa@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [R0I-HL078641, U0I-HL080731] NR 42 TC 246 Z9 256 U1 6 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 11 PY 2007 VL 116 IS 24 BP 2841 EP 2850 DI 10.1161/CIRCULATIONAHA.107.732867 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 239UB UT WOS:000251542200011 PM 18040026 ER PT J AU McDermott, U Sharma, SV Dowell, L Greninger, P Montagut, C Lamb, J Archibald, H Raudales, R Tam, A Lee, D Rothenberg, SM Supko, JG Sordella, R Ulkus, LE Iafrate, AJ Maheswaran, S Njauw, CN Tsao, H Drew, L Hanke, JH Ma, XJ Erlander, MG Gray, NS Haber, DA Settleman, J AF McDermott, Ultan Sharma, Sreenath V. Dowell, Lori Greninger, Patricia Montagut, Clara Lamb, Jennifer Archibald, Heidi Raudales, Raul Tam, Angela Lee, Diana Rothenberg, S. Michael Supko, Jeffrey G. Sordella, Raffaella Ulkus, Lindsey E. Iafrate, A. John Maheswaran, Shyamala Njauw, Ching Ni Tsao, Hensin Drew, Lisa Hanke, Jeff H. Ma, Xiao-Jun Erlander, Mark G. Gray, Nathanael S. Haber, Daniel A. Settleman, Jeffrey TI Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LUNG-CANCER PATIENTS; GENE COPY NUMBER; PHASE-II; GEFITINIB; GROWTH; AMPLIFICATION; MUTATIONS; EXPRESSION; MET; ADENOCARCINOMAS AB Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors. C1 [McDermott, Ultan; Sharma, Sreenath V.; Dowell, Lori; Greninger, Patricia; Montagut, Clara; Lamb, Jennifer; Archibald, Heidi; Raudales, Raul; Tam, Angela; Lee, Diana; Rothenberg, S. Michael; Supko, Jeffrey G.; Sordella, Raffaella; Ulkus, Lindsey E.; Iafrate, A. John; Maheswaran, Shyamala; Haber, Daniel A.; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. [McDermott, Ultan; Sharma, Sreenath V.; Dowell, Lori; Greninger, Patricia; Montagut, Clara; Lamb, Jennifer; Tam, Angela; Lee, Diana; Rothenberg, S. Michael; Supko, Jeffrey G.; Sordella, Raffaella; Ulkus, Lindsey E.; Iafrate, A. John; Maheswaran, Shyamala; Haber, Daniel A.; Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Drew, Lisa; Hanke, Jeff H.] AstraZeneca R&D Boston, Waltham, MA 02453 USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ma, Xiao-Jun; Erlander, Mark G.] AviaraDx Inc, Carlsbad, CA 92010 USA. [Njauw, Ching Ni; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu RI han, chao/B-6245-2011; Njauw, Ching-Ni/H-8046-2012; OI McDermott, Ultan/0000-0001-9032-4700 FU NCI NIH HHS [R01 CA115830] NR 21 TC 225 Z9 230 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 19936 EP 19941 DI 10.1073/pnas.0707498104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200053 PM 18077425 ER PT J AU Mi, SL Lu, J Sun, M Li, ZJ Zhang, H Neilly, MB Wang, Y Qian, ZJ Jin, J Zhang, YM Bohlander, SK Le Beau, MM Larson, RA Golub, TR Rowley, JD Chen, JJ AF Mi, Shuangli Lu, Jun Sun, Miao Li, Zejuan Zhang, Hao Neilly, Mary Beth Wang, Yungui Qian, Zhijian Jin, Jie Zhang, Yanming Bohlander, Stefan K. Le Beau, Michelle M. Larson, Richard A. Golub, Todd R. Rowley, Janet D. Chen, Jianjun TI MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE expression profiling; lineage classification; diagnosis; prediction; DNA copy number ID HUMAN CANCER-CELLS; GENE-EXPRESSION; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION FACTORS; MOLECULAR-GENETICS; DRUG-THERAPY; TRANSLOCATIONS; ACTIVATION; MECHANISM; DISCOVERY AB Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genomewide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias. C1 [Lu, Jun; Zhang, Hao; Golub, Todd R.] MIT, Broad Inst, Cambridge, MA 02141 USA. [Mi, Shuangli; Sun, Miao; Li, Zejuan; Neilly, Mary Beth; Qian, Zhijian; Zhang, Yanming; Le Beau, Michelle M.; Larson, Richard A.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Lu, Jun; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wang, Yungui; Jin, Jie] Zhejiang Univ, Sch Med, Inst Hematol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China. [Bohlander, Stefan K.] Univ Munich, Hosp Grossharden, Dept Med 3, D-81377 Munich, Germany. [Golub, Todd R.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Bohlander, Stefan K.] GSF Munich, Natl Res Ctr Environm Hlth, Clin Cooperat Grp Leukemia, D-81377 Munich, Germany. RP Golub, TR (reprint author), MIT, Broad Inst, Cambridge, MA 02141 USA. EM golub@broad.mit.edu; jrowley@medicine.bsd.uchicago.edu; jchen@medicine.bsd.uchicago.edu OI Bohlander, Stefan/0000-0002-2202-9088; Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA40046, P01 CA040046] NR 54 TC 262 Z9 296 U1 2 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 19971 EP 19976 DI 10.1073/pnas.0709313104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200059 PM 18056805 ER PT J AU Gounaris, E Erdman, SE Restaino, C Gurish, MF Friend, DS Gounari, F Lee, DM Zhang, G Glickman, JN Shin, K Rao, VP Poutahidis, T Weissleder, R McNagny, KM Khazaie, K AF Gounaris, Elias Erdman, Susan E. Restaino, Clifford Gurish, Michael F. Friend, Daniel S. Gounari, Fotini Lee, David M. Zhang, Guoying Glickman, Jonathan N. Shin, Kichul Rao, Varada P. Poutahidis, Theofilos Weissleder, Ralph McNagny, Kelly M. Khazaie, Khashayarsha TI Mast cells are an essential hematopoietic component for polyp development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; inflammation; polyposis; TNF alpha ID CHRONIC INFLAMMATION; STROMAL FIBROBLASTS; POOR-PROGNOSIS; KIT EXPRESSION; MICE; ANGIOGENESIS; ADENOCARCINOMA; CARCINOGENESIS; PROGRESSION; CANCER AB It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34(+) immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of beta-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention. C1 [McNagny, Kelly M.] Univ British Columbia, Biomed Res Ctr, Vancouver, BC V6T 1Z3, Canada. [Erdman, Susan E.; Rao, Varada P.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Gounaris, Elias; Restaino, Clifford; Zhang, Guoying] Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. [Gounaris, Elias; Restaino, Clifford; Gurish, Michael F.; Friend, Daniel S.; Lee, David M.; Zhang, Guoying; Glickman, Jonathan N.; Shin, Kichul] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gurish, Michael F.; Friend, Daniel S.; Lee, David M.; Glickman, Jonathan N.; Shin, Kichul] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gurish, Michael F.; Friend, Daniel S.; Lee, David M.; Glickman, Jonathan N.; Shin, Kichul] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Poutahidis, Theofilos] Aristotle Univ Thessaloniki, Fac Vet Med, Pathol Lab, Thessaloniki 54124, Greece. [Gounaris, Elias; Restaino, Clifford; Weissleder, Ralph; Khazaie, Khashayarsha] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Gounaris, Elias; Restaino, Clifford; Weissleder, Ralph; Khazaie, Khashayarsha] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Gounari, Fotini] Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Zhang, Guoying] Yantai Univ, Sch Pharm, Mol Pharmacol Lab, Lau Shan Qu 264005, Yantai, Peoples R China. RP McNagny, KM (reprint author), Univ British Columbia, Biomed Res Ctr, Vancouver, BC V6T 1Z3, Canada. EM kelly@brc.ubc.ca; khazaie@northewestern.edu RI Gounaris, Elias/B-3184-2011; McNagny, Kelly/P-5239-2014; OI McNagny, Kelly/0000-0003-4737-3499; Gounaris, Elias/0000-0001-8679-9711 FU NCI NIH HHS [R01 CA108854, R01-CA104547, R01-CA108854, R01 CA104547]; NIAID NIH HHS [R01 AI059676, R01-AI059676] NR 59 TC 130 Z9 133 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 19977 EP 19982 DI 10.1073/pnas.0704620104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200060 PM 18077429 ER PT J AU Beroukhim, R Getz, G Nghiemphu, L Barretina, J Hsueh, T Linhart, D Vivanco, I Lee, JC Huang, JH Alexander, S Du, J Kau, T Thomas, RK Shah, K Soto, H Perner, S Prensner, J Debiasi, RM Demichelis, F Hatton, C Rubin, MA Garraway, LA Nelson, SF Liau, L Mischel, PS Cloughesy, TF Meyerson, M Golub, TA Lander, ES Mellinghoff, IK Sellers, WR AF Beroukhim, Rameen Getz, Gad Nghiemphu, Leia Barretina, Jordi Hsueh, Teli Linhart, David Vivanco, Igor Lee, Jeffrey C. Huang, Julie H. Alexander, Sethu Du, Jinyan Kau, Tweeny Thomas, Roman K. Shah, Kinial Soto, Horacio Perner, Sven Prensner, John Debiasi, Ralph M. Demichelis, Francesca Hatton, Charlie Rubin, Mark A. Garraway, Levi A. Nelson, Stan F. Liau, Linda Mischel, Paul S. Cloughesy, Tim F. Meyerson, Matthew Golub, Todd A. Lander, Eric S. Mellinghoff, Ingo K. Sellers, William R. TI Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bioinformatics; comparative genomic hybridization; glioblastoma; copy-number alterations; single-nucleotide polymorphism arrays ID MET TYROSINE KINASE; HUMAN LUNG-CANCER; GLIOBLASTOMAS; IDENTIFY; RECEPTOR; TUMORS; AMPLIFICATION; MUTATIONS; SEQUENCES; DELETIONS AB Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving approximate to 35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focal EGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome. C1 [Beroukhim, Rameen; Getz, Gad; Barretina, Jordi; Linhart, David; Lee, Jeffrey C.; Alexander, Sethu; Du, Jinyan; Thomas, Roman K.; Shah, Kinial; Prensner, John; Debiasi, Ralph M.; Hatton, Charlie; Rubin, Mark A.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Lander, Eric S.; Sellers, William R.] MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Beroukhim, Rameen; Getz, Gad; Barretina, Jordi; Linhart, David; Lee, Jeffrey C.; Alexander, Sethu; Du, Jinyan; Thomas, Roman K.; Shah, Kinial; Prensner, John; Debiasi, Ralph M.; Hatton, Charlie; Rubin, Mark A.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Lander, Eric S.; Sellers, William R.] Harvard Univ, Cambridge, MA 02142 USA. [Beroukhim, Rameen; Barretina, Jordi; Linhart, David; Lee, Jeffrey C.; Alexander, Sethu; Du, Jinyan; Thomas, Roman K.; Shah, Kinial; Prensner, John; Debiasi, Ralph M.; Hatton, Charlie; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Sellers, William R.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Beroukhim, Rameen; Barretina, Jordi; Linhart, David; Lee, Jeffrey C.; Alexander, Sethu; Du, Jinyan; Thomas, Roman K.; Shah, Kinial; Prensner, John; Debiasi, Ralph M.; Hatton, Charlie; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Sellers, William R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Barretina, Jordi; Linhart, David; Lee, Jeffrey C.; Alexander, Sethu; Du, Jinyan; Thomas, Roman K.; Shah, Kinial; Prensner, John; Debiasi, Ralph M.; Hatton, Charlie; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Sellers, William R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Perner, Sven; Demichelis, Francesca; Rubin, Mark A.; Garraway, Levi A.; Sellers, William R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Perner, Sven; Demichelis, Francesca; Rubin, Mark A.; Garraway, Levi A.; Sellers, William R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen; Rubin, Mark A.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Lander, Eric S.; Sellers, William R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Rubin, Mark A.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd A.; Lander, Eric S.; Sellers, William R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Nghiemphu, Leia; Hsueh, Teli; Vivanco, Igor; Huang, Julie H.; Kau, Tweeny; Soto, Horacio; Nelson, Stan F.; Liau, Linda; Mischel, Paul S.; Cloughesy, Tim F.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Nghiemphu, Leia; Hsueh, Teli; Vivanco, Igor; Huang, Julie H.; Kau, Tweeny; Soto, Horacio; Nelson, Stan F.; Liau, Linda; Mischel, Paul S.; Cloughesy, Tim F.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Nghiemphu, Leia; Hsueh, Teli; Vivanco, Igor; Huang, Julie H.; Kau, Tweeny; Soto, Horacio; Nelson, Stan F.; Liau, Linda; Mischel, Paul S.; Cloughesy, Tim F.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Nghiemphu, Leia; Hsueh, Teli; Vivanco, Igor; Huang, Julie H.; Kau, Tweeny; Soto, Horacio; Nelson, Stan F.; Liau, Linda; Mischel, Paul S.; Cloughesy, Tim F.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Nghiemphu, Leia; Hsueh, Teli; Vivanco, Igor; Huang, Julie H.; Kau, Tweeny; Soto, Horacio; Nelson, Stan F.; Liau, Linda; Mischel, Paul S.; Cloughesy, Tim F.] Univ Calif Los Angeles, David Gaffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. [Thomas, Roman K.] Univ Cologne, Max Planck Soc, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Max Planck Inst Neurol Res, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Perner, Sven] Univ Ulm, Dept Pathol, D-89070 Ulm, Germany. [Golub, Todd A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Golub, Todd A.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM lander@broad.mit.edu; mellingi@mskcc.org; william.sellers@novartis.com RI Nelson, Stanley/D-4771-2009; leng, xianwei/F-9073-2011; Meyerson, Matthew/E-7123-2012; OI Vivanco, Igor/0000-0001-6347-9416; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [CA109038, CA126546, K08 CA122833, K08 CA122833-01A1, R01 CA109038, U24 CA126546] NR 36 TC 537 Z9 541 U1 3 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 20007 EP 20012 DI 10.1073/pnas.0710052104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200065 PM 18077431 ER PT J AU Farwell, WR Linder, JA Jha, AK AF Farwell, Wildon R. Linder, Jeffrey A. Jha, Ashish K. TI Trends in prostate-specific antigen testing from 1995 through 2004 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; CANCER; MEN; PATTERNS; CARE; US AB Background: The utility of the prostate-specific antigen (PSA) test to screen for prostate cancer has been widely debated for several years. Whether PSA testing rates have changed during this period of controversy is not well known. Methods: We examined the National Ambulatory Medical Care Survey (1995-2004) of visits to primary care providers by healthy men aged 35 years or older. We examined visits by calendar year and compared the years 2000 through 2004 with the years 1995 through 1999. We also examined visits by men in the overall population and in particular subgroups. Results: Primary care physicians ordered PSA tests in 4.7% of all visits in 1995 and in 7.0% of all visits in 2004 (P=.03). In multivariate analysis, the odds of a primary care physician ordering a PSA test during any clinic visit increased 8%( odds ratio [ OR], 1.08; 95% confidence interval [CI], 1.04-1.12; P <.001) per year from 1995 through 2004. The increase was more pronounced among men making visits for general medical examinations (11.2% in 1995 vs 32.3% in 2004; P=.003). Comparing the period 2000-2004 with the period 1995-1999, the odds of PSA testing increased in nearly all subgroups but most dramatically in black men ( OR, 2.3; 95% CI, 1.4-3.8; P=.002) and in men 35 through 49 years of age ( OR, 1.8; 95% CI, 1.3-2.6; P=.001). Conclusion: In a nationally representative sample, we found that despite the lack of clear evidence of benefit, PSA testing for prostate cancer screening has increased dramatically, especially among black men and younger men. C1 VA Boston Hlth Care Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Farwell, WR (reprint author), VA Boston Hlth Care Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston Div 151 MAV,150 S Huntington Ave, Boston, MA 02130 USA. EM Wildon.Farwell@va.gov FU AHRQ HHS [K08 HS014563] NR 23 TC 36 Z9 38 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2007 VL 167 IS 22 BP 2497 EP 2502 DI 10.1001/archinte.167.22.2497 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 239SI UT WOS:000251537600017 PM 18071173 ER PT J AU Roberts, S Calautti, E Vanderweil, S Nquyen, H Foley, A Baden, H Viel, A AF Roberts, S. Calautti, E. Vanderweil, S. Nquyen, H. O. Foley, A. Baden, H. P. Viel, A. TI Changes in localization of human discs large (hDlg) during keratinocyte differentiation are associated with expression of alternatively spliced hDlg variants (vol 313, pg 2521, 2007) SO EXPERIMENTAL CELL RESEARCH LA English DT Correction C1 Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham B15 2TT, W Midlands, England. Univ Turin, Ctr Mol Biotechnol, I-10126 Turin, Italy. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Roberts, S (reprint author), Univ Birmingham, Canc Res UK Inst Canc Studies, Vincent Dr, Edgbaston, Birmingham B15 2TT, W Midlands, England. EM s.roberts@bham.ac.uk NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 10 PY 2007 VL 313 IS 20 BP 4221 EP 4221 DI 10.1016/j.yexcr.2007.08.027 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 237EZ UT WOS:000251358200012 ER PT J AU Mack, JW Wolfe, J Cook, EF Grier, HE Cleary, PD Weeks, JC AF Mack, Jennifer W. Wolfe, Joanne Cook, E. Francis Grier, Holcombe E. Cleary, Paul D. Weeks, Jane C. TI Hope and prognostic disclosure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC PALLIATIVE CARE; ADVANCED CANCER-PATIENTS; LIFE DECISION-MAKING; FAMILY PERSPECTIVES; INFORMATION NEEDS; PATIENTS VIEWS; PATIENT; END; COMMUNICATION; PREFERENCES AB Purpose Physicians sometimes selectively convey prognostic information to support patients' hopes. However, the relationship between prognostic disclosure and hope is not known. Patients and Methods We surveyed 194 parents of children with cancer (overall response rate, 70%) in their first year of treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA), and we surveyed the children's physicians. We evaluated relationships between parental recall of prognostic disclosure by the physician and possible outcomes, including hope, trust, and emotional distress. Our main outcome was assessed by asking parents how often the way the child's oncologist communicated with them about the children's cancers made them feel hopeful. Results Nearly half of parents reported that physician communication always made them feel hopeful. Parents who reported receiving a greater number of elements of prognostic disclosure were more likely to report communication-related hope (odds ratio [OR], 1.77 per element of disclosure; P = .001), even when the likelihood of a cure was low (OR, 5.98 per element of disclosure with likelihood of a cure < 25%; P = .03). In a multivariable model, parents were more likely to report that physician communication always made them feel hopeful when they also reported receipt of more elements of prognostic disclosure (OR, 1.60; P = .03) and high-quality communication (OR, 6.58; P < .0001). Communication- related hope was inversely associated with the child's likelihood of cure (OR, 0.65; P = .005). Conclusion Although physicians sometimes limit prognostic information to preserve hope, we found no evidence that prognostic disclosure makes parents less hopeful. Instead, disclosure of prognosis by the physician can support hope, even when the prognosis is poor. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_mack@dfci.harvard.edu NR 48 TC 101 Z9 102 U1 3 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2007 VL 25 IS 35 BP 5636 EP 5642 DI 10.1200/JCO.2007.12.6110 PG 7 WC Oncology SC Oncology GA 272UN UT WOS:000253885900019 PM 18065734 ER PT J AU Wabulya, A Imitola, J Santagata, S Kesari, S AF Wabulya, Angela Imitola, Jaime Santagata, Sandro Kesari, Santosh TI Mycosis fungoides with leptomeningeal involvement SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; T-CELL LYMPHOMA; TRANSFORMATION; PATIENT; CNS; PROGNOSIS C1 [Wabulya, Angela] CURE Childrens Hosp Uganda, Mbale, Uganda. [Imitola, Jaime] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Santagata, Sandro] Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA. [Imitola, Jaime; Santagata, Sandro; Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA USA. [Kesari, Santosh] Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol,Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Wabulya, A (reprint author), CURE Childrens Hosp Uganda, Mbale, Uganda. RI Kesari, Santosh/E-8461-2013; imitola, jaime/J-8478-2015 NR 23 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2007 VL 25 IS 35 BP 5658 EP 5661 DI 10.1200/JCO.2007.14.3800 PG 5 WC Oncology SC Oncology GA 272UN UT WOS:000253885900024 PM 18065739 ER PT J AU Chen, YL de Bruin, DM Kerbage, C de Boer, JF AF Chen, Yueli de Bruin, Daniel M. Kerbage, Charles de Boer, Johannes F. TI Spectrally balanced detection for optical frequency domain imaging SO OPTICS EXPRESS LA English DT Article ID SWEPT SEMICONDUCTOR-LASER; ULTRA-HIGH-SPEED; COHERENCE TOMOGRAPHY; IN-VIVO; DOPPLER TOMOGRAPHY; HUMAN RETINA; MODE-LOCKING; TIME; EYE; INTERFEROMETRY AB In optical frequency domain imaging (OFDI) or swept-source optical coherence tomography, balanced detection is required to suppress relative intensity noise (RIN). A regular implementation of balanced detection by combining reference and sample arm signal in a 50/50 coupler and detecting the differential output with a balanced receiver is however, not perfect. Since the splitting ratio of the 50/50 coupler is wavelength dependent, RIN is not optimally canceled at the edges of the wavelength sweep. The splitting ratio has a nearly linear shift of 0.4% per nanometer. This brings as much as +/- 12% deviation at the margins of wavelength-swept range centered at 1060nm. We demonstrate a RIN suppression of 33dB by spectrally corrected balanced detection, 11dB more that regular balanced detection. (c) 2007 Optical Society of America. C1 [Chen, Yueli; de Bruin, Daniel M.; Kerbage, Charles; de Boer, Johannes F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, Yueli; de Bruin, Daniel M.; Kerbage, Charles; de Boer, Johannes F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chen, YL (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM ychen25@partners.org; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 37 TC 31 Z9 31 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 10 PY 2007 VL 15 IS 25 BP 16390 EP 16399 DI 10.1364/OE.15.016390 PG 10 WC Optics SC Optics GA 240YT UT WOS:000251624800012 PM 19550929 ER PT J AU Selb, J Dale, AM Boas, DA AF Selb, Juliette Dale, Anders M. Boas, David A. TI Linear 3D reconstruction of time-domain diffuse optical imaging differential data: improved depth localization and lateral resolution SO OPTICS EXPRESS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL HEMODYNAMICS; RESOLVED REFLECTANCE; HUMAN BRAIN; HUMAN HEAD; TOMOGRAPHY; FLIGHT; ACTIVATION; TISSUE; MODEL AB We present 3D linear reconstructions of time-domain (TD) diffuse optical imaging differential data. We first compute the sensitivity matrix at different delay gates within the diffusion approximation for a homogeneous semi-infinite medium. The matrix is then inverted using spatially varying regularization. The performances of the method and the influence of a number of parameters are evaluated with simulated data and compared to continuous-wave (CW) imaging. In addition to the expected depth resolution provided by TD, we show improved lateral resolution and localization. The method is then applied to reconstructing phantom data consisting of an absorbing inclusion located at different depths within a scattering medium. (c) 2007 Optical Society of America. C1 [Selb, Juliette; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Radiol, Dept Neurosci, La Jolla, CA 92093 USA. RP Selb, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM juliette@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41 RR014075]; NIBIB NIH HHS [R01 EB000790-05, R01 EB000790, R01 EB002482] NR 37 TC 25 Z9 25 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 10 PY 2007 VL 15 IS 25 BP 16400 EP 16412 DI 10.1364/OE.15.016400 PG 13 WC Optics SC Optics GA 240YT UT WOS:000251624800013 PM 19550930 ER PT J AU Maguluri, G Mujat, M Park, BH Kim, KH Sun, W Iftimia, NV Ferguson, RD Hammer, DX Chen, TC De Boer, JF AF Maguluri, Gopi Mujat, Mircea Park, B. H. Kim, K. H. Sun, Wei Iftimia, N. V. Ferguson, R. Daniel Hammer, Daniel X. Chen, Teresa C. De Boer, Johannes F. TI Three dimensional tracking for volumetric spectral-domain optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID HIGH-SPEED; IMAGES; NERVE; LINE AB We present a three-dimensional (3D) tracker for a clinical ophthalmic spectral domain optical coherence tomography (SD-OCT) system that combines depth-tracking with lateral tracking, providing a stabilized reference frame for 3D data recording and post acquisition analysis. The depth-tracking system is implemented through a real-time dynamic feedback mechanism to compensate for motion artifact in the axial direction. Active monitoring of the retina and adapting the reference arm of the interferometer allowed the whole thickness of the retina to be stabilized to within +/- 100 mu m. We achieve a relatively constant SNR from image to image by stabilizing the image of the retina with respect to the depth dependent sensitivity of SD-OCT. The depth tracking range of our system is 5.2 mm in air and the depth is adjusted every frame. Enhancement in the stability of the images with the depth-tracking algorithm is demonstrated on a healthy volunteer. C1 [Maguluri, Gopi; Mujat, Mircea; Park, B. H.; Kim, K. H.; Sun, Wei; De Boer, Johannes F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard Med Sch, Boston, MA 02114 USA. [Iftimia, N. V.; Ferguson, R. Daniel; Hammer, Daniel X.] Phys Sci Inc, Andover, MA 01810 USA. [Sun, Wei] Boston Univ, Dept Phys, Boston, MA 02215 USA. [Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. RP De Boer, JF (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard Med Sch, 50 Blossom St,BAR 7, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 16 TC 19 Z9 19 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 10 PY 2007 VL 15 IS 25 BP 16808 EP 16817 DI 10.1364/OE.15.016808 PG 10 WC Optics SC Optics GA 240YT UT WOS:000251624800054 PM 19550971 ER PT J AU Amin, MS Park, Y Lue, N Dasari, RR Badizadegan, K Feld, MS Popescu, G AF Amin, M. Shahrooz Park, YoungKeun Lue, Niyom Dasari, Ramachandra R. Badizadegan, Kamran Feld, Michael S. Popescu, Gabriel TI Microrheology of red blood cell membranes using dynamic scattering microscopy SO OPTICS EXPRESS LA English DT Article ID ERYTHROCYTE-MEMBRANES; FLUCTUATIONS; CYTOSKELETON; MECHANICS; SPECTRIN; COMPLEX; SHAPE AB We employ a novel optical technique, dynamic scattering microscopy (DSM), to extract the frequency dependence of the viscoelastic modulus associated with the red blood cell membrane. This approach applies the principle of dynamic light scattering to micro beads attached to the red blood cell membrane in thermal fluctuation. This allows for high-throughput characterization of a large number of cells simultaneously, which represents a significant advantage over current methods. The results in terms of the effective loss and storage moduli indicate the generic behavior of a viscoelastic material, characterized by power laws with exponents between 0 and 1. (c) 2007 Optical Society of America. C1 [Amin, M. Shahrooz; Park, YoungKeun; Lue, Niyom; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.; Popescu, Gabriel] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Harvard Med Sch, Dept Hlth Sci & Technol, Boston, MA 02114 USA. [Popescu, Gabriel] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Elect & Comp Engn, Quantitat Light Imaging Lab, Urbana, IL 61801 USA. RP Amin, MS (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM gpopescu@uiuc.edu RI Park, YongKeun/B-9017-2009 NR 38 TC 39 Z9 39 U1 3 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 10 PY 2007 VL 15 IS 25 BP 17001 EP 17009 DI 10.1364/OE.15.017001 PG 9 WC Optics SC Optics GA 240YT UT WOS:000251624800074 PM 19550991 ER PT J AU Nelson, WD Zenovich, AG Ott, HC Stolen, C Caron, GJ Panoskaltsis-Mortari, A Barnes, SA Xin, XR Taylor, DA AF Nelson, Wendy D. Zenovich, Andrey G. Ott, Harald C. Stolen, Craig Caron, Gabriel J. Panoskaltsis-Mortari, Angela Barnes, Samuel A. Xin, Xiangrong Taylor, Doris A. TI Sex-dependent attenuation of plaque growth after treatment with bone marrow mononuclear cells SO CIRCULATION RESEARCH LA English DT Article DE atherosclerosis; bone marrow; cytokines; gender; stem cells ID ENDOTHELIAL PROGENITOR CELLS; COLONY-STIMULATING FACTOR; CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; NORMAL HEMATOPOIESIS; DEFICIENT MICE; T-LYMPHOCYTES; ATHEROSCLEROSIS; MOBILIZATION; CYTOKINES AB There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells ( BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout ( apoE(-/-)) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched ( males, n = 11; females, n = 13) or -mismatched ( males, n = 12; females, n = 14) BMNCs obtained from C57BL6/J mice. The rest of the apoE(-/-) mice were vehicle treated ( males, n = 13; females, n = 20) or were age-matched untreated controls ( males, n = 9; females, n = 10). Aortic plaque burden, progenitor cell profiles in bone marrow ( BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE(-/-) recipients significantly decreased plaque formation ( P = 0.001). This reparative response univariately correlated with increased CD34(+) ( P = 0.02), CD45(+) ( P = 0.0001), and AC133(+)/CD34(+) ( P = 0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31(+)/CD45(low) cells. In a multivariate analysis, BM-AC133(+)/CD34(+) and BM-CD45(+) percentage counts correlated with a lower plaque burden (P = 0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation ( r = -0.86, P = 0.0004). In untreated apoE(-/-) mice of either sex, BM-AC133(+)/CD34(+) cells rose initially and then fell as plaque accumulated; however, BM-AC133(+)/CD34(+) percentages were higher in females at all times ( P <= 0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE(-/-) mice; this reparative response correlated with the upregulation of BM-AC133(+)/CD34(+) and CD45(+) cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE(-/-) mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted. C1 Univ Minnesota, Ctr Cardiovasc Repair, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. R&D Syst, Minneapolis, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Sci Corp, Natick, MA USA. Univ Arkansas, Sch Nursing, Fayetteville, AR 72701 USA. RP Taylor, DA (reprint author), Univ Minnesota, Ctr Cardiovasc Repair, 7-105A Nils Hasselmo Hall,312 Chruch St SE, Minneapolis, MN 55455 USA. EM dataylor@umn.edu FU NIAMS NIH HHS [T32AR007612] NR 29 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC 7 PY 2007 VL 101 IS 12 BP 1319 EP 1327 DI 10.1161/CIRCRESAHA.107.155564 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 238KC UT WOS:000251445500015 PM 17947799 ER PT J AU Ogata, N Kawaguchi, H Chung, U Roth, SI Segre, GV AF Ogata, Naoshi Kawaguchi, Hiroshi Chung, Ung-il Roth, Sanford I. Segre, Gino V. TI Continuous activation of G alpha(q) in osteoblasts results in osteopenia through impaired osteoblast differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATORY G-PROTEIN; PARATHYROID-HORMONE; BONE-FORMATION; PHOSPHOLIPASE-C; TRANSGENIC MICE; ALPHA-SUBUNITS; GROWTH-PLATE; CELLS; EXPRESSION; RECEPTOR AB We explored the role of G alpha(q)- mediated signaling on skeletal homeostasis by selectively expressing a constitutively active G alpha(q) ( mutation of Q209L) in osteoblasts. Continuous signaling via G alpha(q) in mouse osteoblastic MC3T3- E1 cells impaired differentiation. Mice that expressed the constitutively active G alpha(q) transgene in cells of the osteoblast lineage exhibited severe osteopenia in cortical and trabecular bones. Osteoblast number, bone volume, and trabecular thickness were reduced in transgenic mice, but the osteoclasts were unaffected. Osteoblasts from transgenic mice showed impaired differentiation and matrix formation. In the presence of a protein kinase C inhibitor GF109203X, this impairment was not seen, indicating mediation by the protein kinase C pathway. We propose that continuous activation of the G alpha(q) signal in osteoblasts plays a crucial, previously unrecognized role in bone formation. C1 Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1138655, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Kawaguchi, H (reprint author), Univ Tokyo, Fac Med, Bunkyo Ku, Hongo 7-3-1, Tokyo 1138655, Japan. EM kawaguchi-ort@h.u-tokyo.ac.jp FU NIDDK NIH HHS [DK11794, DK47034] NR 34 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2007 VL 282 IS 49 BP 35757 EP 35764 DI 10.1074/jbc.M611902200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OW UT WOS:000251458100037 PM 17823129 ER PT J AU Weir, BA Woo, MS Getz, G Perner, S Ding, L Beroukhim, R Lin, WM Province, MA Kraja, A Johnson, LA Shah, K Sato, M Thomas, RK Barletta, JA Borecki, IB Broderick, S Chang, AC Chiang, DY Chirieac, LR Cho, J Fujii, Y Gazdar, AF Giordano, T Greulich, H Hanna, M Johnson, BE Kris, MG Lash, A Lin, L Lindeman, N Mardis, ER McPherson, JD Minna, JD Morgan, MB Nadel, M Orringer, MB Osborne, JR Ozenberger, B Ramos, AH Robinson, J Roth, JA Rusch, V Sasaki, H Shepherd, F Sougnez, C Spitz, MR Tsao, MS Twomey, D Verhaak, RGW Weinstock, GM Wheeler, DA Winckler, W Yoshizawa, A Yu, SY Zakowski, MF Zhang, QY Beer, DG Wistuba, II Watson, MA Garraway, LA Ladanyi, M Travis, WD Pao, W Rubin, MA Gabriel, SB Gibbs, RA Varmus, HE Wilson, RK Lander, ES Meyerson, M AF Weir, Barbara A. Woo, Michele S. Getz, Gad Perner, Sven Ding, Li Beroukhim, Rameen Lin, William M. Province, Michael A. Kraja, Aldi Johnson, Laura A. Shah, Kinjal Sato, Mitsuo Thomas, Roman K. Barletta, Justine A. Borecki, Ingrid B. Broderick, Stephen Chang, Andrew C. Chiang, Derek Y. Chirieac, Lucian R. Cho, Jeonghee Fujii, Yoshitaka Gazdar, Adi F. Giordano, Thomas Greulich, Heidi Hanna, Megan Johnson, Bruce E. Kris, Mark G. Lash, Alex Lin, Ling Lindeman, Neal Mardis, Elaine R. McPherson, John D. Minna, John D. Morgan, Margaret B. Nadel, Mark Orringer, Mark B. Osborne, John R. Ozenberger, Brad Ramos, Alex H. Robinson, James Roth, Jack A. Rusch, Valerie Sasaki, Hidefumi Shepherd, Frances Sougnez, Carrie Spitz, Margaret R. Tsao, Ming-Sound Twomey, David Verhaak, Roel G. W. Weinstock, George M. Wheeler, David A. Winckler, Wendy Yoshizawa, Akihiko Yu, Soyoung Zakowski, Maureen F. Zhang, Qunyuan Beer, David G. Wistuba, Ignacio I. Watson, Mark A. Garraway, Levi A. Ladanyi, Marc Travis, William D. Pao, William Rubin, Mark A. Gabriel, Stacey B. Gibbs, Richard A. Varmus, Harold E. Wilson, Richard K. Lander, Eric S. Meyerson, Matthew TI Characterizing the cancer genome in lung adenocarcinoma SO NATURE LA English DT Article ID HIGH-RESOLUTION ANALYSIS; TRANSCRIPTION FACTOR-I; COPY-NUMBER; HOMOZYGOUS DELETIONS; LENTIVIRAL VECTOR; SOMATIC MUTATIONS; FREQUENT TARGET; GENE DELIVERY; WIDE ANALYSIS; ARRAY CGH AB Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours ( n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in similar to 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 ( NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Harvard Univ, Canc Program, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Genome Biol Program, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Ulm, Inst Pathol, D-89081 Ulm, Germany. Washington Univ, Genome Sequencing Ctr, St Louis, MO 63130 USA. Washington Univ, Div Stat Genom, St Louis, MO 63130 USA. Washington Univ, Dept Pathol & Immunol, St Louis, MO 63130 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany. Univ Cologne, Fac Med, D-50931 Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Surg, Nagoya, Aichi 4678602, Japan. Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Hlth Network, Toronto, ON M5G 2C4, Canada. Princess Margaret Hosp, Toronto, ON M5G 2C4, Canada. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Sato, MITSUO/I-7280-2014; OI Kris, Mark/0000-0002-7317-5341; Chang, Andrew/0000-0001-9506-0425; Lash, Alex/0000-0003-3787-1590; Rubin, Mark/0000-0002-8321-9950; Giordano, Thomas/0000-0003-0641-8873 FU NCI NIH HHS [F32 CA113126-01A1, F32 CA113126-02, K08 CA122833-01A1, P50 CA070907] NR 40 TC 661 Z9 679 U1 4 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 6 PY 2007 VL 450 IS 7171 BP 893 EP U22 DI 10.1038/nature06358 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 237RU UT WOS:000251394900059 PM 17982442 ER PT J AU Andrews-Hanna, JR Snyder, AZ Vincent, JL Lustig, C Head, D Raichle, ME Buckner, RL AF Andrews-Hanna, Jessica R. Snyder, Abraham Z. Vincent, Justin L. Lustig, Cindy Head, Denise Raichle, Marcus E. Buckner, Randy L. TI Disruption of large-scale brain systems in advanced aging SO NEURON LA English DT Article ID FUNCTIONAL MAGNETIC-RESONANCE; RESTING-STATE; DEFAULT-MODE; ALZHEIMERS-DISEASE; WHITE-MATTER; WORKING-MEMORY; OLDER ADULTS; CONNECTIVITY; AGE; DIFFUSION AB Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition. C1 [Andrews-Hanna, Jessica R.; Vincent, Justin L.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. [Andrews-Hanna, Jessica R.; Vincent, Justin L.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Snyder, Abraham Z.; Head, Denise; Raichle, Marcus E.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Snyder, Abraham Z.; Raichle, Marcus E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Lustig, Cindy] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Head, Denise] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02155 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Buckner, RL (reprint author), Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. EM rbuckner@wjh.harvard.edu RI Vincent, Justin/B-5033-2012 FU NIA NIH HHS [AG05886, AG21910, F32 AG005886, F32 AG005886-02, AG00030, F32 AG005886-03, P01 AG003991, P01 AG003991-219005, P01 AG003991-229005, AG03991, P01 AG003991-239005, P01 AG003991-249005, P01 AG003991-259005, P50 AG005681, P50 AG005681-25, P50 AG05681, T32 AG000030] NR 54 TC 596 Z9 614 U1 5 U2 65 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 6 PY 2007 VL 56 IS 5 BP 924 EP 935 DI 10.1016/j.neuron.2007.10.038 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 241MA UT WOS:000251659300016 PM 18054866 ER PT J AU Falutz, J Allas, S Blot, K Potvin, D Kotler, D Somero, M Berger, D Brown, S Richmond, G Fessel, J Turner, R Grinspoon, S AF Falutz, Julian Allas, Soraya Blot, Koenraad Potvin, Diane Kotler, Donald Somero, Michael Berger, Daniel Brown, Stephen Richmond, Gary Fessel, Jeffrey Turner, Ralph Grinspoon, Steven TI Metabolic effects of a growth hormone-releasing factor in patients with HIV SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; VISCERAL ADIPOSE-TISSUE; INFECTED PATIENTS; BODY-COMPOSITION; FAT DISTRIBUTION; MYOCARDIAL-INFARCTION; WEIGHT-LOSS AB Background: Visceral adipose tissue accumulates during antiretroviral therapy in many patients who are infected with the human immunodeficiency virus (HIV); this process is associated with an increased cardiovascular risk. We assessed the use of a growth hormone-releasing factor analogue, tesamorelin, to decrease visceral adiposity. Methods: We randomly assigned 412 patients with HIV (86% of whom were men) who had an accumulation of abdominal fat to receive a daily subcutaneous injection of either 2 mg of tesamorelin or placebo for 26 weeks. The primary end point was the percent change from baseline in visceral adipose tissue as shown on computed tomography. Secondary end points included triglyceride levels, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, the level of insulin-like growth factor I (IGF-I), and self-assessed body image. Glycemic measures included glucose and insulin levels. Results: The measure of visceral adipose tissue decreased by 15.2% in the tesamorelin group and increased by 5.0% in the placebo group; the levels of triglycerides decreased by 50 mg per deciliter and increased by 9 mg per deciliter, respectively, and the ratio of total cholesterol to HDL cholesterol decreased by 0.31 and increased by 0.21, respectively (P<0.001 for all comparisons). Levels of total cholesterol and HDL cholesterol also improved significantly in the tesamorelin group. Levels of IGF-I increased by 81.0% in the tesamorelin group and decreased by 5.0% in the placebo group (P<0.001). Adverse events did not differ significantly between the two study groups, but more patients in the tesamorelin group withdrew from the study because of an adverse event. No significant differences were observed in glycemic measures. Conclusions: Daily tesamorelin for 26 weeks decreased visceral fat and improved lipid profiles, effects that might be useful in HIV-infected patients who have treatment-associated central fat accumulation. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. McGill Univ, Montreal Gen Hosp, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. Theratechnol, Montreal, PQ, Canada. Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Northstar Hlth Care, Chicago, IL USA. AIDS Res Alliance, W Hollywood, CA USA. Kaiser Fdn Res Inst, San Francisco, CA USA. Phase V Technol, Wellesley Hills, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 37 TC 106 Z9 107 U1 1 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 DEC 6 PY 2007 VL 357 IS 23 BP 2359 EP 2370 DI 10.1056/NEJMoa072375 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 237QA UT WOS:000251389200006 PM 18057338 ER PT J AU Thase, ME AF Thase, Michael E. TI Molecules that mediate mood SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 3 TC 7 Z9 7 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 DEC 6 PY 2007 VL 357 IS 23 BP 2400 EP 2402 DI 10.1056/NEJMcibr0706377 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 237QA UT WOS:000251389200014 PM 18057345 ER PT J AU McQueen, MB Bertram, L Lange, C Becker, KD Albert, MS Tanzi, RE Blacker, D AF McQueen, Matthew B. Bertram, Lars Lange, Christoph Becker, K. D. Albert, Marilyn S. Tanzi, Rudolph E. Blacker, Deborah TI Exploring candidate gene associations with neuropsychological performance SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE neuropsychological; genetic; longitudinal ID ALZHEIMERS-DISEASE; DEMENTIA; DEFICITS AB We hypothesize that quantitative phenotypes related to Alzheimer's disease (AD), rather than the dichotomous disease phenotype, will increase the statistical power for identifying genetic risk factors. Neuropsychological test scores, which allow for the measurement of loss of cognitive function over time, are a particularly promising option for this approach. Using data from a cohort study of prodromal AD in 365 community-recruited subjects with and without memory problems with a baseline and often one or more follow-up administrations of a detailed neuropsychological test battery, we performed both. cross-sectional and longitudinal analyses using the known AD gene APOE and four other putative AD genes as predictors. APOE and a promoter polymorphism in insulin degrading enzyme (IDE_4U) showed evidence for association with cross-sectional and longitudinal changes in memory (P=0.016-0.025) and other cognitive functions. APOE and a polymorphism in the alpha-2-macroglobulin gene (A2M18i) also showed evidence for association with cross-sectional and longitudinal changes in executive functioning (P=0.010-0.042). In some cases, longitudinal analysis offered stronger evidence for association than could be seen cross-sectionally. These preliminary results suggest that this approach has promised the development of a quantitative phenotype related to AD, but more elaborate methods will be required to address multiple comparisons issues in the setting of correlated data. (c) 2007 Wiley-Liss, Inc. C1 Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Torrey Pines Therapeut, La Jolla, CA USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gerontol Res Unit, Boston, MA USA. RP McQueen, MB (reprint author), Univ Colorado, Inst Behav Genet, 1480 30th St,447 UCB, Boulder, CO 80309 USA. EM matthew.mcqueen@colorado.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NICHD NIH HHS [R01 HD060726] NR 25 TC 13 Z9 13 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2007 VL 144B IS 8 BP 987 EP 991 DI 10.1002/ajmg.b.30500 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 233ND UT WOS:000251096700004 PM 17579348 ER PT J AU Stewart, SE Fagerness, JA Platko, J Smoller, JW Scharf, JM Illmann, C Jenike, E Chabane, N Leboyer, M Delorme, R Jenike, MA Pauls, DL AF Stewart, S. Evelyn Fagerness, Jesen A. Platko, Jill Smoller, Jordan W. Scharf, Jeremiah M. Illmann, Cornelia Jenike, Eric Chabane, Nadia Leboyer, Marion Delorme, Richard Jenike, Michael A. Pauls, David L. TI Association ofthe SLC1A1 glutantate transporter gene and obsessive-compulsive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive-compulsive disorder; candidate gene; gender; anxiety disorders; glutamic acid; glutamate plasma membrane transport proteins; physiopathology ID GENDER-RELATED DIFFERENCES; MAJOR DEPRESSION; SCHIZOPHRENIA; GLUTAMATE; LINKAGE; OCD; SUSCEPTIBILITY; AUGMENTATION; RELIABILITY; DYSFUNCTION AB Context: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required. Objectives: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females. Design: Family-based association candidate gene study. Setting: Participants were recruited from tertiary care OCD specialty clinics. Participants: OCD probands and their first degree relatives. Main outcomes measures: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes. Results: Association between OCD and the three-marker haplotype, rs12682807/rs2072657/rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P=0.0015) and in males (global P=0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P=0.045). Conclusions: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neurodev & Genet Unit, Boston, MA 02114 USA. Hop Robert Debre, Dept Psychiat, F-75019 Paris, France. Univ Paris, Mondor Chenevier Hosp, Dept Psychiat, F-75252 Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Obsess Compuls Disorder Clin, Boston, MA 02114 USA. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neurodev & Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU NINDS NIH HHS [R01 NS16648] NR 50 TC 91 Z9 93 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2007 VL 144B IS 8 BP 1027 EP 1033 DI 10.1002/ajmg.b.30533 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 233ND UT WOS:000251096700011 PM 17894418 ER PT J AU Kurozumi, K Hardcastle, J Thakur, R Yang, M Christoforidis, G Fulci, G Hochberg, FH Weissleder, R Carson, W Chiocca, EA Kaur, B AF Kurozumi, Kazuhiko Hardcastle, Jayson Thakur, Roopa Yang, Ming Christoforidis, Gregory Fulci, Giulia Hochberg, Fred H. Weissleder, Ralph Carson, William Chiocca, E. Antonio Kaur, Balveen TI Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BRAIN-TUMOR; PHASE-I; HYPERSENSITIVITY REACTIONS; MALIGNANT GLIOMAS; IMMUNE-RESPONSES; GROWTH-FACTOR; ANGIOGENESIS; CYCLOPHOSPHAMIDE; INFLAMMATION; EXPRESSION AB Background The tumor microenvironment is being increasingly recognized as an important determinant of tumor progression as well as of therapeutic response. We investigated oncolytic virus (OV) therapy-induced changes in tumor blood vessels and the impact of modulating tumor vasculature on the efficacy of oncolytic virus therapy. Methods Rat glioma cells (D74/HveC) were implanted intracranially in immune-competent rats. Seven days later, the rats (groups of 3-7 rats) were treated with oncolytic virus (hrR3), and, 3 days later, brains were harvested for evaluation. Some rats were treated with angiostatic cRGD peptide 4 days before oncolytic virus treatment. Some rats were treated with cyclophosphamide (CPA), an immunosuppressant, 2 days before oncolytic virus treatment. Changes in tumor vascular perfusion were evaluated by magnetic resonance imaging of live rats and by fluorescence microscopy of tumor sections from rats perfused with Texas red-conjugated lectin immediately before euthanasia. Leukocyte infiltration in tumors was evaluated by anti-CD45 immunohistochemistry, and the presence of oncolytic virus in tumors was evaluated by viral titration. Changes in cytokine gene expression in tumors were measured by quantitative real-time polymerase chain reaction-based microarrays. Survival was analyzed by the Kaplan-Meier method. All statistical tests were two-sided. Results Oncolytic virus treatment of experimental rat gliomas increased tumor vascular permeability, host leukocyte infiltration into tumors, and intratumoral expression of inflammatory cytokine genes, including interferon gamma (IFN-gamma). The increase in vascular permeability was suppressed in rats pretreated with cyclophosphamide. Compared with rats treated with hrR3 alone, rats pretreated with a single dose of cRGD peptide before hrR3 treatment had reduced tumor vascular permeability, leukocyte infiltration, and IFN-gamma protein levels (mean IFN-gamma level for hrR3 versus hrR3 + cRGD = 203 versus 65.6 mu g/mg, difference = 137 mu g/mg, 95% confidence interval = 72.7 to 202.9 mu g/mg, P=.006); increased viral titers in tumor tissue; and longer median survival (21 days versus 17 days, P<.001). Conclusions A single dose of angiostatic eRGD peptide treatment before oncolytic virus treatment enhanced the antitumor efficacy of oncolytic virus. C1 Ohio State Univ, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Med Ctr, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Integrated Biol Grad Program Studies, James Comprehens Canc Ctr, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Dept Radiol, James Comprehens Canc Ctr, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Dept Surg, James Comprehens Canc Ctr, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. RP Kaur, B (reprint author), Ohio State Univ, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Med Ctr, 385-D OSUCCC,410 W 12th Ave, Columbus, OH 43210 USA. EM ea.chiocca@osumc.edu; balveen.kaur@osumc.edu RI kaur, Balveen/E-3355-2011; Carson, William/E-2846-2011 FU NCI NIH HHS [P01 CA069246]; NINDS NIH HHS [R01 NS064607] NR 54 TC 96 Z9 98 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1768 EP 1781 DI 10.1093/jnci/djm229 PG 14 WC Oncology SC Oncology GA 239VE UT WOS:000251545600009 PM 18042934 ER PT J AU Applebaum, KM Furniss, CS Zeka, A Posner, MR Smith, JF Bryan, J Eisen, EA Peters, ES McClean, MD Kelsey, KT AF Applebaum, Katie M. Furniss, C. Sloane Zeka, Ariana Posner, Marshall R. Smith, Judith F. Bryan, Janine Eisen, Ellen A. Peters, Edward S. McClean, Michael D. Kelsey, Karl T. TI Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; ORAL EXFOLIATED CELLS; PHARYNGEAL CANCER; LARYNGEAL-CANCER; SEXUAL-BEHAVIOR; RISK-FACTORS; CIGARETTE-SMOKING; POOLED ANALYSIS; BREAST-CANCER AB Background Human papillomavirus type 16 (HPV16) seropositivity and alcohol and tobacco use have been associated with risk of head and neck squamous cell carcinoma (HNSCC). However, it is less clear whether HPV16 influences HNSCC risk associated with alcohol and tobacco use. Methods Incident cases of HNSCC diagnosed between December 1999 and December 2003 were identified from nine medical facilities in Greater Boston, MA. Control subjects were frequency matched to case subjects on age, sex, and town of residence. A total of 485 case subjects and 549 control subjects reported information on lifetime smoking and alcohol consumption and provided sera, which was used to determine presence of HPV16 antibodies. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of HNSCC risk by alcohol consumption (drinks per week: <3, 3 to <8, 8 to <25, >= 25) and smoking (pack-years: none, >0 to <20, 20 to <45, >= 45), adjusting for age, sex, race, education, and HPV16 serology. Polytomous logistic regression was used to estimate odds ratios and 95% confidence intervals for the association of HPV16 serology, alcohol consumption, and tobacco use in site-specific analyses. All statistical tests were two-sided. Results The strongest risk factors by tumor site were smoking for laryngeal cancer, alcohol for cancer of the oral cavity, and HPV16 for pharyngeal cancer. For pharyngeal cancer, risk increased with increasing alcohol consumption (OR >= 25versus<3drinks per week = 5.1, 95% CI = 2.4 to 11.0) and smoking (OR >= 45pack-years (versus never smoker) = 6.9, 95% CI = 3.1 to 15.1) among HPV16-seronegative subjects but not among HPV16-seropositive subjects (P-interaction, (HPV16 serology and alcohol) = .002; P-interaction, (HPV16 serology and smoking) =.007). Among light drinkers or never smokers, HPV16 seropositivity was associated with a 30-fold increased risk of pharyngeal cancer. Conclusions Alcohol or tobacco use does not further increase risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking, alcohol, and HPV16 differs by tumor site. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Brunel Univ, Inst Environm, London, England. Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Merck & Co Inc, Dept Vaccine Biol Res, West Point, PA USA. Louisiana State Univ Hlth Sci, Sch Publ Hlth, Program Epidemiol, New Orleans, LA USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Brown Univ, Dept Pathol & Lab Med, Ctr Environm Hlth & Technol, Providence, RI 02912 USA. RP Kelsey, KT (reprint author), Brown Univ, Dept Community Hlth, Ctr Environm Hlth & Technol, Providence, RI 02912 USA. EM karl_kelsey@brown.edu RI Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823; Zeka, Ariana/0000-0002-9570-8831; /0000-0003-4928-6532 FU NCI NIH HHS [CA100679, CA78609, R01 CA078609, R01 CA100679]; NIEHS NIH HHS [T32 ES007155, T32 ES07155] NR 63 TC 138 Z9 142 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1801 EP 1810 DI 10.1093/jnci/djm233 PG 10 WC Oncology SC Oncology GA 239VE UT WOS:000251545600012 PM 18042931 ER PT J AU Yoshiuchi, K Cook, DB Ohashi, K Kumano, H Kuboki, T Yamamoto, Y Natelson, BH AF Yoshiuchi, Kazuhiro Cook, Dane B. Ohashi, Kyoko Kumano, Hiroaki Kuboki, Tomifusa Yamamoto, Yoshiharu Natelson, Beniamin H. TI A real-time assessment of the effect of exercise in chronic fatigue syndrome SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE chronic fatigue syndrome; ecological momentary assessment; multilevel modeling ID CONTINUOUS PERFORMANCE-TEST; WORKING-MEMORY DEFICITS; DEPRESSION; MOMENTARY; PAIN; PERSPECTIVE; DEFINITION; MOOD AB Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days. Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1 week before and 2weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling. Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise. (C) 2007 Elsevier Inc. All rights reserved. C1 [Cook, Dane B.; Kumano, Hiroaki; Kuboki, Tomifusa] Univ Tokyo, Fac Med, Dept Psychosomat Med, Bunkyo Ku, Tokyo 1138655, Japan. [Yoshiuchi, Kazuhiro; Natelson, Beniamin H.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. [Cook, Dane B.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Res Serv, Madison, WI 53706 USA. [Cook, Dane B.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Ohashi, Kyoko; Yamamoto, Yoshiharu] Univ Tokyo, Grad Sch Educ, Educ Physiol Lab, Tokyo, Japan. RP Yoshiuchi, K (reprint author), Univ Tokyo, Fac Med, Dept Psychosomat Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kyoshiuc-tky@umin.ac.jp FU NIAID NIH HHS [AI-32247, U01 AI032247, U01 AI032247-11] NR 26 TC 21 Z9 21 U1 5 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 5 PY 2007 VL 92 IS 5 BP 963 EP 968 DI 10.1016/j.physbeh.2007.07.001 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 242BB UT WOS:000251698400024 PM 17655887 ER PT J AU Gwinn, K Corriveau, RA Mitsumoto, H Bednarz, K Brown, RH Cudkowicz, M Gordon, PH Hardy, J Kasarskis, EJ Kaufmann, P Miller, R Sorenson, E Tandan, R Traynor, BJ Nash, J Sherman, A Mailman, MD Ostell, J Bruijn, L Cwik, V Rich, SS Singleton, A Refolo, L Andrews, J Zhang, R Conwit, R Keller, MA AF Gwinn, Katrina Corriveau, Roderick A. Mitsumoto, Hiroshi Bednarz, Kate Brown, Robert H., Jr. Cudkowicz, Merit Gordon, Paul H. Hardy, John Kasarskis, Edward J. Kaufmann, Petra Miller, Robert Sorenson, Eric Tandan, Rup Traynor, Bryan J. Nash, Josefina Sherman, Alex Mailman, Matthew D. Ostell, James Bruijn, Lucie Cwik, Valerie Rich, Stephen S. Singleton, Andrew Refolo, Larry Andrews, Jaime Zhang, Ran Conwit, Robin Keller, Margaret A. CA ALS Res Grp TI Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery SO PLOS ONE LA English DT Article AB Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms ( SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples ( such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS. C1 [Gwinn, Katrina; Refolo, Larry; Zhang, Ran; Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. [Corriveau, Roderick A.; Nash, Josefina; Andrews, Jaime; Keller, Margaret A.] Coriell Inst Med Res, Camden, NJ USA. [Mitsumoto, Hiroshi; Bednarz, Kate; Gordon, Paul H.; Kaufmann, Petra] Columbia Univ, Eleanor & Lou Gehrig MDA ALS Res Ctr, New York, NY USA. [Brown, Robert H., Jr.; Cudkowicz, Merit; Sherman, Alex] Massachusetts Gen Hosp, Charlestown, MA USA. [Hardy, John; Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. [Kasarskis, Edward J.] Univ Kentucky, Lexington, KY USA. [Miller, Robert] Calif Pacific Med Ctr, San Francisco, CA USA. [Sorenson, Eric] Mayo Med Ctr, Rochester, MN USA. [Tandan, Rup] Univ Vermont, Burlington, VT USA. [Traynor, Bryan J.] NIMH, NIH, Bethesda, MD 20892 USA. [Mailman, Matthew D.; Ostell, James] NIH, Natl Ctr Bioinformat, Bethesda, MD 20892 USA. [Bruijn, Lucie] ALS Assoc, Calabasas Hills, CA USA. [Cwik, Valerie] Muscular Dystrophy Assoc, Tucson, AZ USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Gwinn, K (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM GwinnK@ninds.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; OI Thakore, Nimish/0000-0003-3418-3362; Carter, Gregory/0000-0001-7617-4750; Gwinn, Katrina/0000-0002-8277-651X FU NINDS [N01-NS-2-2349, NOT-03-016, R01 NS049640-01, R01 NS045294-01, R01 NS045087-01, R01 NS048125-01, R01 NS044887-01, R01 NS042759-01]; ALS Association; NIA Intramural Laboratory of Neurogenetics; NIMH Intramural; NIH [RR-00109]; NCBI dbGaP FX The work described herein was created with funding by NINDS (RAC, JN, JA, MK, Repository, Contract NINDS N01-NS-2-2349, NINDS Supplement Notice NOT-03-016), The ALS Association, NINDS R01 grants (RHB, R01 NS049640-01; MC, R01 NS049640-01; PHG R01 NS045294-01; EK R01 NS045087-01; PK R01 NS048125-01; RM R01 NS044887-01; ES R01 NS042759-01), NIA Intramural Laboratory of Neurogenetics, (JH, AS), NIMH Intramural (BT), NIH RR-00109 ( RT), and NCBI dbGaP ( http://www.ncbi.nlm.nih.gov/sites/entrez?db = gap). NR 47 TC 10 Z9 10 U1 0 U2 1 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 DEC 5 PY 2007 VL 2 IS 12 AR e1254 DI 10.1371/journal.pone.0001254 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JD UT WOS:000207459400003 PM 18060051 ER PT J AU Campbell, EG Regan, S Gruen, RL Ferris, TG Rao, SR Cleary, PD Blumenthal, D AF Campbell, Eric G. Regan, Susan Gruen, Russell L. Ferris, Timothy G. Rao, Sowmya R. Cleary, Paul D. Blumenthal, David TI Professionalism in medicine: Results of a national survey of physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MILLENNIUM; EXPERIENCE; QUALITY; CHARTER; CARE AB Background: The prospect of improving care through increasing professionalism has been gaining momentum among physician organizations. Although there have been efforts to define and promote professionalism, few data are available on physician attitudes toward and conformance with professional norms. Objective: To ascertain the extent to which practicing physicians agree with and act consistently with norms of professionalism. Design: National survey using a stratified random sample. Setting: Medical care in the United States. Participants: 3504 practicing physicians in internal medicine, family practice, pediatrics, surgery, anesthesiology, and cardiology. Measurements: Attitudes and behaviors were assessed by using indicators for each domain of professionalism developed by the American College of Physicians and the American Board of Internal Medicine. Of the eligible sampled physicians, 1662 responded, yielding a 58% weighted response rate ( adjusting for noneligible physicians). Results: Ninety percent or more of the respondents agreed with specific statements about principles of fair distribution of finite resources, improving access to and quality of care, managing conflicts of interest, and professional self-regulation. Twenty-four percent disagreed that periodic recertification was desirable. Physician behavior did not always reflect the standards they endorsed. For example, although 96% of respondents agreed that physicians should report impaired or incompetent colleagues to relevant authorities, 45% of respondents who encountered such colleagues had not reported them. Limitations: Our measures of behavior did not capture all activities that may reflect on the norms in question. Furthermore, behaviors were self-reported, and the results may not be generalizable to physicians in specialties not included in the study. Conclusion: Physicians agreed with standards of professional behavior promulgated by professional societies. Reported behavior, however, did not always conform to those norms. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. Univ Melbourne, Royal Melbourne Hosp, Med Res Ctr, Parkville, Vic, Australia. RP Campbell, EG (reprint author), Inst Hlth Policy, 50 Staniford St, 9th Fl, Boston, MA 02114 USA. EM ecampbell@partners.org NR 23 TC 113 Z9 113 U1 4 U2 14 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 4 PY 2007 VL 147 IS 11 BP 795 EP U60 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 239SX UT WOS:000251539100008 PM 18056665 ER PT J AU Breton, CV Kile, ML Catalano, PJ Hoffman, E Quamruzzaman, Q Rahman, M Mahiuddin, G Christiani, DC AF Breton, Carrie V. Kile, Molly L. Catalano, Paul J. Hoffman, Elaine Quamruzzaman, Quazi Rahman, Mahmuder Mahiuddin, Golam Christiani, David C. TI GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study SO ENVIRONMENTAL HEALTH LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; S-TRANSFERASE GENOTYPES; DNA-DAMAGE; URINARY 8-HYDROXY-2'-DEOXYGUANOSINE; DRINKING-WATER; POLYMORPHISMS; EXPOSURE; CARCINOGENESIS; SUSCEPTIBILITY; RESIDENTS AB Background: Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods: To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1), human 8-oxoguanine glycosylase (hOGG1) and apurinic/apyrimidinic endonuclease (APE1) genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results: A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95% CI -0.73, -0.07) compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase ( 95% CI 0.27, 1.42), a 0.98 increase ( 95% CI 033, 1.66) and a 0.85 increase ( 95% CI 0.27, 1.44) in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion: These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme. C1 [Breton, Carrie V.; Kile, Molly L.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Breton, Carrie V.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Catalano, Paul J.; Hoffman, Elaine] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam] Dhaka Community Hosp, Dhaka 1217, Bangladesh. RP Breton, CV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM breton@usc.edu; mkile@hsph.harvard.edu; pcata@jimmy.harvard.edu; ehoffman@hsph.harvard.edu; dch@bangla.net; dch@bangla.net; dch@bangla.net; dchris@hsph.harvard.edu RI Kile, Molly/A-8582-2012 FU NIEHS NIH HHS [P42 ES005947, P30 ES000002, ES05947, ES011622, ES00002, T32 ES007069, T32 ES07069, R01 ES011622] NR 40 TC 16 Z9 16 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD DEC 4 PY 2007 VL 6 AR 39 DI 10.1186/1476-069X-6-39 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 260LU UT WOS:000253012600001 PM 18053222 ER PT J AU Albert, CM Rosenthal, L Calkins, H Steinberg, JS Ruskin, JN Wang, P Muller, JE Mittleman, MA AF Albert, Christine M. Rosenthal, Lawrence Calkins, Hugh Steinberg, Jonathan S. Ruskin, Jeremy N. Wang, Paul Muller, James E. Mittleman, Murray A. CA TOVA Investigators TI Driving and implantable cardioverter-defibrillator shocks for ventricular arrhythmias SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID AMERICAN-HEART-ASSOCIATION; PARTICULATE AIR-POLLUTION; RATE-VARIABILITY; CASE-CROSSOVER; PUBLIC SAFETY; SUDDEN-DEATH; EXPOSURE; DISEASE; RECOMMENDATIONS; LIFE AB Objectives This study examined the risk of implantable cardioverter-defibrillator (ICD) shocks for ventricular tachycardla (VT) or ventricular fibrillation (VF) associated with driving. Background Concerns regarding VT/VF occurring during driving are the basis for driving restrictions in ICD patients; however, limited data are available to inform recommendations. Methods This study used a prospective nested case-crossover design to compare the risk of ICD shock for VT/VF both during and up to 60 min after an episode of driving as compared with that during other activities among 1,188 ICD patients enrolled in the TOVA (Triggers of Ventricular Arrhythmia) study. Results Over a median follow-up of 562 days, there were 193 ICD shocks for Vr/VF with data on exposure to driving before ICD shock. The absolute risk of ICD shock for VT/VF within 1 h of driving was estimated to be 1 episode per 25,116 person-hours spent driving. The ICD shocks for VT/VF were twice as likely to occur within 1 h of driving a car as compared with other times (relative risk [RR] 2.24, 95% confidence interval [Cl] 1.57 to 3.18). This risk was specific for shocks for VT/VF and occurred primarily during the 30-min period after driving (RR 4.46, 95% Cl 2.92 to 6.82) rather than during the driving episode itself (RR 1.05, 95% Cl 0.48 to 2.30). Conclusions Although the risk of ICD shock for VT/VF was transiently increased in the 30-min period after driving, the risk was not elevated during driving and the absolute risk was low. These data provide reassurance that driving by lCD patients should not translate into an important rate of personal or public injury. C1 Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02215 USA. Univ Massachusetts, Mem Ctr Hosp, Div Cardiovasc, Worcester, MA 01605 USA. Johns Hopkins Univ Hosp, Div Cardiovasc, Baltimore, MD 21287 USA. St Lukes Roosevelt Hosp, Div Cardiovasc, New York, NY USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Stanford Univ, Ctr Med, Div Cardiovasc, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM calbert@partners.org FU NHLBI NIH HHS [R01 HL041016] NR 30 TC 29 Z9 31 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 DEC 4 PY 2007 VL 50 IS 23 BP 2233 EP 2240 DI 10.1016/j.jacc.2007.06.059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 236VF UT WOS:000251330800007 PM 18061071 ER PT J AU Wendell, LC Freeman, SH Plotkin, SR Sims, JR AF Wendell, Linda C. Freeman, Stefanie H. Plotkin, Scott R. Sims, John R. TI Clinical Reasoning: A case of multiple intracerebral hemorrhages SO NEUROLOGY LA English DT Article ID CEREBRAL METASTASIS; HEART; SARCOMA; ANGIOSARCOMA; TUMORS C1 Brown Univ, Rhode Isl Hosp, Dept Neurol, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Sims, JR (reprint author), CNY 149 Rm 6403, Charlestown, MA 02129 USA. EM jsims@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 4 PY 2007 VL 69 IS 23 BP E30 EP E34 DI 10.1212/01.wnl.0000295676.85960.7c PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 237GF UT WOS:000251361500014 PM 18056573 ER PT J AU Christine, LT Hofbauer, M Towle, CA AF Christine, L. Tam Hofbauer, Maria Towle, Christine A. TI Requirement for protein kinase R in interleukin-1 alpha-stimulated effects in cartilage SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cartilage; interleukin-1; protein kinase R; degradation; cyclooxygenase-2; eukaryotic initiation factor 2 ID TUMOR-HOST INTERACTIONS; NF-KAPPA-B; NITRIC-OXIDE; ARTICULAR CHONDROCYTES; ER STRESS; PKR; INTERLEUKIN-1; EXPRESSION; PACT; PHOSPHORYLATION AB Interleukin-1 (IL-1) has pleiotropic effects in cartilage. The interferon-induced, double stranded RNA-activated protein kinase PKR that phosphorylates eukaryotic initiation factor 2 (eIF2) alpha has been implicated in cytokine effects in chondrocytes. A compound was recently identified that potently suppresses PKR autophosphorylation (IC50 approximately 200 eta M) and partially restores PKR-inhibited translation in a cell-free system with significant effect in the nanomolar range. The objectives of this study were to exploit this potent PKR inhibitor to assess whether PKR kinase activity is required for catabolic and proinflammatory effects of IL-1 alpha in cartilage and to determine whether IL-1 alpha causes an increase in eIF2 alpha phosphorylation that is antagonized by the PKR inhibitor. Cartilage explants were incubated with the PKR inhibitor and IL-1 alpha. Culture media were assessed for sulfated glycosaminoglycan as an indicator of proteoglycan degradation and for prostaglandin E-2. Cartilage extracts were analyzed by Western blot for cyclooxygenase-2 and phosphorylated signaling molecules. Nanomolar concentrations of the PKR inhibitor suppressed proteoglycan degradation and cyclooxygenase-2 accumulation in IL-1 alpha-activated cartilage. The PKR inhibitor stimulated or inhibited PGE(2) production with a biphasic dose response relationship. IL-1 alpha increased the phosphorylation of both PKR and eIF2 alpha, and nanomolar concentrations of PKR inhibitor suppressed the IL-1 alpha-induced changes in phosphorylation. The results strongly support PKR involvement in pathways activated by IL-1 alpha in chondrocytes. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, GRJ 1108,55 Fruit St, Boston, MA 02114 USA. EM catowle@post.harvard.edu NR 36 TC 0 Z9 0 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 3 PY 2007 VL 74 IS 11 BP 1636 EP 1641 DI 10.1016/j.bcp.2007.08.002 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 233VO UT WOS:000251118600009 ER PT J AU Biederman, J Petty, CR Hirshfeld-Becker, DR Henin, A Faraone, SV Fraire, M Henry, B McQuade, J Rosenbaum, JF AF Biederman, Joseph Petty, Carter R. Hirshfeld-Becker, Dina R. Henin, Aude Faraone, Stephen V. Fraire, Maria Henry, Brianne McQuade, Julia Rosenbaum, Jerrold F. TI Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression SO PSYCHIATRY RESEARCH LA English DT Article DE panic disorder; separation anxiety disorder; depression; children; Comorbidity; family; high risk ID DIAGNOSTIC INTERVIEW SCHEDULE; SEPARATION ANXIETY; PROSPECTIVE COMMUNITY; CHILDHOOD HISTORY; YOUNG-CHILDREN; ADULTS; ADOLESCENTS; RELIABILITY; PARENTS; PSYCHOPATHOLOGY AB The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Patient Care YAW 6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI McQuade, Julia/0000-0001-9278-3345; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-47077-05, R01 MH047077, R01 MH047077-07] NR 40 TC 24 Z9 27 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 3 PY 2007 VL 153 IS 3 BP 245 EP 252 DI 10.1016/j.psychres.2007.02.016 PG 8 WC Psychiatry SC Psychiatry GA 234ZT UT WOS:000251204000005 PM 17764753 ER PT J AU Sullivan, AF Camargo, CA Cleary, PD Gordon, JA Guadagnoli, E Kaushal, R Magid, DJ Rao, SR Blumenthal, D AF Sullivan, Ashley F. Camargo, Carlos A., Jr. Cleary, Paul D. Gordon, James A. Guadagnoli, Edward Kaushal, Rainu Magid, David J. Rao, Sowmya R. Blumenthal, David TI The National Emergency Department Safety Study: Study rationale and design SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 16-19, 2007 CL Chicago, IL SP Soc Acad Emergency Med DE emergency department; patient safety; methodology ID ACUTE MYOCARDIAL-INFARCTION; ADVERSE DRUG EVENTS; HOSPITALIZED-PATIENTS; PRACTICE GUIDELINES; MISSED DIAGNOSES; TASK-FORCE; MANAGEMENT; ANALGESIA; SEDATION; ERRORS AB The significance of medical errors is widely appreciated. Given the frequency and significance of errors in medicine, it is important to learn how to reduce their frequency; however, the identification of factors that increase the likelihood of errors poses a considerable challenge. The National Emergency Department Safety Study (NEDSS) sought to characterize organizational- and clinician-associated factors related to the likelihood of errors occurring in emergency departments (EDs). NEDSS was a large multicenter study coordinated by the Emergency Medicine Network (EMNet; www.emnet-usa.org). It was designed to determine if reports by ED personnel about safety processes are significantly correlated with the actual occurrence of errors in EDs. If so, staff reports can be used to accurately identify processes for safety improvements. Staff perceptions were assessed with a survey, while errors were assessed through chart review of three conditions: acute myocardial infarction, acute asthma, and reductions of dislocations under procedural sedation. NEDSS also examined the characteristics of EDs associated with the occurrence of errors. NEDSS is the first comprehensive national study of the frequency and types of medical errors in EDs. This article describes the methods used to develop and implement the study. C1 [Sullivan, Ashley F.; Camargo, Carlos A., Jr.; Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Rao, Sowmya R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Unit, Boston, MA USA. [Blumenthal, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.; Gordon, James A.; Rao, Sowmya R.; Blumenthal, David] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Cleary, Paul D.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Guadagnoli, Edward] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Kaushal, Rainu] Cornell Univ, Weill Med Coll, New York, NY USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY USA. [Magid, David J.] Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. RP Sullivan, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. EM afsuilivan@partners.org FU AHRQ HHS [5 R01 HS013099] NR 31 TC 20 Z9 20 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2007 VL 14 IS 12 BP 1182 EP 1189 DI 10.1197/j.aem.2007.07.014 PG 8 WC Emergency Medicine SC Emergency Medicine GA 240GP UT WOS:000251575700011 PM 18045895 ER PT J AU Tondo, L Lepri, B Baldessarini, RJ AF Tondo, L. Lepri, B. Baldessarini, R. J. TI Suicidal risks among 2826 sardinian major affective disorder patients SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE attempts; bipolar disorders; ideation; major depression; risk factors; sex; suicide; temperament ID RANDOMIZED CONTROLLED-TRIALS; SEROTONIN REUPTAKE INHIBITORS; TERM LITHIUM TREATMENT; BIPOLAR-II DISORDERS; CLINICAL-TRIALS; UNIPOLAR DEPRESSION; UNITED-STATES; IDEATION; BEHAVIOR; ANTIDEPRESSANTS AB Objective: We estimated risks of suicidal behaviors in 2826 mood-disorder patients evaluated and followed in a Sardinian mood disorders research center over the past 30 years. Method: We determined rates of suicidal ideation, attempts, and suicides, with associated risk factors, in men and women with DSM-IV bipolar I (BP-I; n = 529), BP-II; (n = 314), or major depressive disorders (MDD; n = 1983), at risk for an average of 11 years of illness. Results: Observed rates (% of patients/year) of suicide ranked: BP-II (0.16) >= BP-I (0.14) > MDD (0.05); attempts: BP-I (1.52) > BP-II (0.82) > MDD (0.48); ideation: BP-II (42.7) > MDD (33.8) > BP-I (22.7). The ratio of attempts/suicides (lethality index) ranked: BP-II (5.12) < MDD (9.60) <= BP-I (10.8). Male/female risk-ratios were greater for suicide than attempts or ideation. One-third of all reported acts occurred within the first year of illness, and earliest among MDD patients. Factors associated independently with suicidal acts included BP diagnosis, hospitalizations/person, and early illness-onset; factors associated with suicidal ideation were having an affective temperament, BP-II diagnosis, and higher suicidality-corrected depression score at intake. Conclusion: Suicidal behaviors were more prevalent among BPD than MDD out-patients. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Boston, MA 02114 USA. Lucio Bini Mood Disorders Res Ctr, Cagliari, Italy. Univ Cagliari, Dept Psychol, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Elmont, MA 02478 USA. EM rjb@mclean.org FU NIMH NIH HHS [MH-073779] NR 55 TC 92 Z9 94 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 2007 VL 116 IS 6 BP 419 EP 428 DI 10.1111/j.1600-0447.2007.01066.x PG 10 WC Psychiatry SC Psychiatry GA 229OS UT WOS:000250814500003 PM 17997721 ER PT J AU Katic, M Kennedy, AR Leykin, I Norris, A McGettrick, A Gesta, S Russell, SJ Bluher, M Maratos-Flier, E Kahn, CR AF Katic, Masa Kennedy, Adam R. Leykin, Igor Norris, Andrew McGettrick, Aileen Gesta, Stephane Russell, Steven J. Bluher, Matthias Maratos-Flier, Eleftheria Kahn, C. Ronald TI Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice SO AGING CELL LA English DT Article DE calorie restriction; diabetes; insulin resistance; mitochondria; obesity; PGC-1 alpha ID AGE-RELATED-CHANGES; CALORIE RESTRICTION; CAENORHABDITIS-ELEGANS; SACCHAROMYCES-CEREVISIAE; ADIPOSE-TISSUE; ENERGY-EXPENDITURE; POTENTIAL ROLE; CYTOCHROME-C; VISCERAL FAT; RESISTANCE AB Caloric restriction, leanness and decreased activity of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling are associated with increased longevity in a wide range of organisms from Caenorhabditis elegans to humans. Fat-specific insulin receptor knock-out (FIRKO) mice represent an interesting dichotomy, with leanness and increased lifespan, despite normal or increased food intake. To determine the mechanisms by which a lack of insulin signaling in adipose tissue might exert this effect, we performed physiological and gene expression studies in FIRKO and control mice as they aged. At the whole body level, FIRKO mice demonstrated an increase in basal metabolic rate and respiratory exchange ratio. Analysis of gene expression in white adipose tissue (WAT) of FIRKO mice from 6 to 36 months of age revealed persistently high expression of the nuclear-encoded mitochondrial genes involved in glycolysis, tricarboxylic acid cycle, beta-oxidation and oxidative phosphorylation as compared to expression of the same genes in WAT from controls that showed a tendency to decline in expression with age. These changes in gene expression were correlated with increased cytochrome c and cytochrome c oxidase subunit IV at the protein level, increased citrate synthase activity, increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) and PGC-1 beta, and an increase in mitochondrial DNA in WAT of FIRKO mice. Together, these data suggest that maintenance of mitochondrial activity and metabolic rates in adipose tissue may be important contributors to the increased lifespan of the FIRKO mouse. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Norris, Andrew/0000-0001-8396-9543 FU NIDDK NIH HHS [DK31036, DK60837, P01 DK056116, R01 DK056113, R01 DK069983] NR 73 TC 81 Z9 85 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2007 VL 6 IS 6 BP 827 EP 839 DI 10.1111/j.1474-9726.2007.00346.x PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 231HV UT WOS:000250938400012 PM 18001293 ER PT J AU Parnell, SE Chen, SY Charness, ME Hodge, CW Dehart, DB Sulik, KK AF Parnell, Scott E. Chen, Shao-Yu Charness, Michael E. Hodge, Clyde W. Dehart, Deborah B. Sulik, Kathleen K. TI Concurrent dietary administration of D-SAL and ethanol diminishes ethanol's teratogenesis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fetal alcohol spectrum disorders; SAL; eye; activity-dependent neurotrophic factor ID FETAL ALCOHOL SYNDROME; DEPENDENT NEUROTROPHIC FACTOR; MOUSE MODEL; CELL-ADHESION; NEUROPROTECTIVE PEPTIDE; SPECTRUM DISORDERS; NEURITE OUTGROWTH; OXIDATIVE STRESS; EMBRYONIC GROWTH; BINDING-SITE AB Background: SAL (SALLRSIPA) is a peptide fragment of activity-dependent neurotrophic factor. Both L- and D-SAL diminish ethanol's pathogenesis, however, the D-peptide is protease resistant, and can therefore be effectively administered in a diet. The present study tested the hypothesis that D-SAL provided in a liquid diet containing ethanol will prevent ethanol-induced teratogenicity in mice. Methods: Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination with 5.6 mu g/ml D-SAL. At these doses, the mice received approximately 75 mu g of D-SAL on each day and achieved peak blood-alcohol concentrations on GD 8 that ranged from 148-162 mg/dl. On GD 14, the fetuses were examined for the presence of ocular abnormalities including microphthalmia and irregularly shaped pupils, teratogenic effects known to result from this ethanol exposure paradigm. Results: Dietary D-SAL reduced the incidence of ocular defects in ethanol-exposed fetuses from 29 to 10% in the right eyes and from 21 to 7.5% in the left eyes; levels similar to those observed in pair-fed controls. In addition to decreasing their incidence, D-SAL also reduced the severity of the ocular defects. Conclusion: These results demonstrate that oral D-SAL can prevent ethanol-induced ocular defects. Because ocular defects are commonly associated with CNS damage, oral D-SAL may also prove valuable in preventing ethanol-induced brain defects. C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Harvard Univ, Dept Neurol, Sch Med, VA Boston Hlth Care Syst, W Roxbury, MA USA. RP Parnell, SE (reprint author), Univ N Carolina, Bowles Ctr Alcohol Studies, CB 7178, Chapel Hill, NC 27599 USA. EM sparnell@med.unc.edu OI Charness, Michael/0000-0002-3301-8966 FU NIAAA NIH HHS [K01 AA013908, AA014983, AA11605, AA12974, AA013908] NR 42 TC 16 Z9 18 U1 0 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 DEC PY 2007 VL 31 IS 12 BP 2059 EP 2064 DI 10.1111/j.1530-0277.2007.00524.x PG 6 WC Substance Abuse SC Substance Abuse GA 234SR UT WOS:000251184800013 PM 17949468 ER PT J AU Kaplan, GG Hur, C Korzenik, J Sands, BE AF Kaplan, G. G. Hur, C. Korzenik, J. Sands, B. E. TI Infliximab dose escalation vs. initiation of adalimumab for loss of response in Crohn's disease: a cost-effectiveness analysis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MAINTENANCE TREATMENT; ECONOMIC EVALUATIONS; ACTIVITY INDEX; REMISSION; TRIAL; HOSPITALIZATIONS; SURGERIES; BENEFITS; EFFICACY; DECREASE AB Background Crohn's disease patients who have lost response to 5 mg/kg of infliximab may regain response by increasing the dose of infliximab to 10 mg/kg. Alternatively, adalimumab can be used as a rescue therapy. Aim To determine whether dose escalation of infliximab was a cost-effective strategy compared with adalimumab initiation after loss of response to 5 mg/kg of infliximab. Methods A decision-analysis model simulated two cohorts of Crohn's patients: (i) infliximab dose was escalated to 10 mg/kg and (ii) infliximab was discontinued and patients were started on adalimumab. The time horizon was 1 year. One-and two-way sensitivity analyses were performed. Results The infliximab dose escalation strategy yielded more quality-adjusted life years (0.79) compared with the adalimumab strategy (0.76). The incremental cost-effectiveness ratio was $332 032/quality-adjusted life year. Sensitivity analysis demonstrated that the model findings were robust. The most significant variables were the cost of infliximab and that of adalimumab, such that a reduction in the cost of infliximab by 1/3 resulted in an incremental cost-effectiveness ratio below $80 000/quality-adjusted life year. Conclusion After a Crohn's patient has lost response to 5 mg/kg of infliximab, dose escalation will yield more quality-adjusted life-year compared with switching to adaliumamb; however, the cost was considerable. C1 [Kaplan, G. G.; Korzenik, J.; Sands, B. E.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Kaplan, G. G.; Hur, C.; Korzenik, J.; Sands, B. E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hur, C.] Inst Technol Assessment, Boston, MA USA. [Kaplan, G. G.; Hur, C.; Korzenik, J.; Sands, B. E.] Harvard Univ, Sch Med, Boston, MA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org OI Kaplan, Gilaad/0000-0003-2719-0556; Hur, Chin/0000-0002-2819-7576 NR 31 TC 56 Z9 58 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD DEC PY 2007 VL 26 IS 11-12 BP 1509 EP 1520 DI 10.1111/j.1365-2036.2007.03548.x PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 249GR UT WOS:000252216800006 PM 17931345 ER PT J AU Glickman, SW Boulding, W Staelin, R Mulgund, J Roe, MT Lytle, BL Rumsfeld, JS Gibler, WB Ohman, EM Schulman, KA Peterson, ED AF Glickman, Seth W. Boulding, William Staelin, Richard Mulgund, Jyotsna Roe, Matthew T. Lytle, Barbara L. Rumsfeld, John S. Gibler, W. Brian Ohman, E. Magnus Schulman, Kevin A. Peterson, Eric D. TI A framework for quality improvement: An analysis of factors responsible for improvement at hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; HEALTH-CARE; OPINION LEADERS; PERFORMANCE; MANAGEMENT; MORTALITY; MEDICARE; CULTURE; TRIAL AB Background Hospitals are under increasing pressure to improve their quality of care. However, a key question remains: how can hospitals best design and implement successful quality improvement (Ql) programs? Hospitals currently employ a variety of Ql initiatives but have little empirical evidence on which to base their quality efforts. Methods We designed and applied a hospital cross-sectional survey to 212 hospitals participating in CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), a voluntary Ql initiative of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). We factor analysis and an ordinary least squares regression model to determine the key hospital factors most associated with unexpected improvements in institutional Ql in the treatment of NSTE ACS. Results From 2002 to 2004, the following factors had a significant association with unexpected increases in the 2004 Ql in NSTE ACS treatment: the use of CRUSADE Q tools, clinical commitment to quality by a cardiology coadvocate, institutional financial commitment to quality, and barriers to Ql related to resource availability and cultural resistance to change (all P <.10). Of these factors, optimal use of CRUSADE Ql tools was associated with the highest absolute improvement in process adherence score relative to other factors. Conclusions We identified several institutional factors associated with improved quality of care in the treatment of high-risk NSTE ACS. We hope that this evidence-based framework will help guide the development and implementation of future Ql programs in order to improve the institutional quality of care for NSTE ACS. C1 Duke Univ, Duke Clin Res Inst, Durham, NC 27715 USA. Duke Univ, Med Ctr, Ctr Clin & Genet Econ, Durham, NC USA. Duke Univ, Fuqua Sch Business, Durham, NC 27706 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 Univ, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM peter016@mc.duke.edu NR 26 TC 21 Z9 21 U1 3 U2 5 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 DEC PY 2007 VL 154 IS 6 BP 1206 EP 1212 DI 10.1016/j.ahj.2007.08.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 237SH UT WOS:000251396200030 PM 18035096 ER PT J AU Morrow, DA Antman, EM Murphy, SA Qin, J Ruda, M Guneri, S Jacob, AJ Budaj, A Braunwald, E AF Morrow, David A. Antman, Elliott M. Murphy, Sabina A. Qin, Jie Ruda, Mikhail Guneri, Sema Jacob, Ashok Joseph Budaj, Andrej Braunwald, Eugene CA TIMI Study Grp TI Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST-elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) trial SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; ANTITHROMBIN THERAPY; BLOOD-GLUCOSE; MELLITUS; RISK; MORTALITY; HEART; COMPLICATIONS; FIBRINOLYSIS AB Background Patients with diabetes mellitus (DM) are at higher risk for complications after ST-elevation myocardial infarction (STEMI) than patients without DM. Potent antithrombotic therapies may offer particular benefit for these high-risk patients and must be balanced against the potential for increased bleeding. Methods We performed a prospectively planned analysis of efficacy and safety in patients with DM among 20479 patients with STEMI treated with fibrinolysis and randomized to a strategy of enoxaparin (up to 8 days) or unfractionoted heparin (UFH) (48 hours) in ExTRACT-TIMI 25. Results Patients with DM (n = 3060) were older and more likely to be women and to present with heart failure (P <.0001 for each) than those without DM. After adjustment for the TIMI Risk Score, sex, and renal function, patients with DM were at 30% higher risk for death or myocardial infarction (MI) by 30 days (OR(adj) 1.29, 95% CI 1.14-1.46). Among patients with DM, the enoxaparin strategy reduced mortality (9.5% vs; 11.8%, relative risk [RR] 0.81, 95% CI 0.66-0.99), death/Ml (13.6% vs 17.1%, RR 0.80; 95% CI 0.67-0.94), and death/Ml/urgent revascularization (116.0% vs 19.7%, RR 0.81, 95% CI 0.70-0.94). The enoxaparin strategy was associated with a trend toward higher major bleeding (2.6% vs 1.6%, RR 1.63, 95% CI 0.99-2.69). Taking efficacy and safety into account, the enoxaparin strategy offered superior net clinical benefit (death/MI/major bleed, 14.8% vs; 18.0%, RR 0.83, 95% CI 0.70-0.97) compared with, UFH in patients with DM. Conclusions In a subgroup analysis, a reperfusion strategy including enoxaparin significantly improved outcomes compared with UFH among high-risk STEMI patients with DM undergoing fibrinolysis. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Cardiol Res Ctr, Dept Emergency Cardiol, Moscow 121552, Russia. Dokuz Eyful Univ, Izmir, Turkey. CMKP Hosp, Warsaw, Poland. St Johns Hosp, Livingston, W Lothian, Scotland. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 34 TC 14 Z9 14 U1 1 U2 1 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 DEC PY 2007 VL 154 IS 6 AR 1078-84 DI 10.1016/j.ahj.2007.07.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 237SH UT WOS:000251396200012 PM 18035078 ER PT J AU Song, YQ Manson, JE Meigs, JB Ridker, PM Buring, JE Liu, SM AF Song, Yiqing Manson, JoAnn E. Meigs, James B. Ridker, Paul M. Buring, Julie E. Liu, Simin TI Comparison of usefulness of body mass index versus metabolic risk factors in predicting 10-year risk of cardiovascular events in women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; MORTALITY; OBESITY; MEN; ATHEROSCLEROSIS; PREVENTION AB The objective of this study was to prospectively examine the comparative importance of body mass index (BMI) and metabolic syndrome (MS) related risk factors in predicting future risk of cardiovascular disease (CVD) in women. Of 25,626 women aged >= 45 years and free of CVD, cancer, and diabetes at baseline in the Women's Health Study, all women were classified into 6 groups according to 3 BMI categories (<25, 25 to 29.9, and >= 30 kg/m(2)) and the presence or absence of MS, defined using modified criteria of the National Cholesterol Education Program Adult Treatment Program III. During a median 10-year follow-up, 724 incident eVD events were documented. Compared with lean women without MS, multivariate relative risks of CVD, adjusting for age, physical activity, and other covariates, were 2.40 (95% confidence interval [CI] 1.71 to 3.37) for lean women who had MS, 1.08 (95% CI 0.87 to 1.33) for overweight women who had no MS, 3.01 (95% CI 2.30 to 3.94) for overweight women with MS, 1.58 (95% CI 1.21 to 2.08) for obese women without MS, and 2.89 (95% CI 2.19 to 3.80) for obese women with MS. Similar associations were evident for total coronary heart disease, but were not significant for total stroke. Overall, although C-reactive protein added additional prognostic information beyond BMI and MS, it did not fully account for the observed high risk of CVD associated with MS. In conclusion, MS may largely account for the increased risk of CVD associated with BMI in apparently healthy women. (c) 2007 Elsevier Inc. All rights reserved. C1 [Song, Yiqing; Manson, JoAnn E.; Ridker, Paul M.; Buring, Julie E.; Liu, Simin] Brigham & Womens Hosp, Harvard Univ, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. [Manson, JoAnn E.; Buring, Julie E.; Liu, Simin] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. [Ridker, Paul M.] Harvard Univ, Sch Med,Brigham & Womens Hosp, Donald Reynolds Ctr Cardiovasc Res, Div Cardiovasc Dis,Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Med Sch, Dept Ambulatory Care & Prevent, Boston, MA USA. [Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Liu, Simin] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Song, YQ (reprint author), Brigham & Womens Hosp, Harvard Univ, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. EM ysong3@rics.bwh.harvard.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [R01 CA047988-14, CA-47988, R01 CA047988]; NHLBI NIH HHS [HL-65727, R01 HL043851, R01 HL043851-09]; NIDDK NIH HHS [DK66401, R01 DK066401, R01 DK066401-04] NR 20 TC 61 Z9 62 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2007 VL 100 IS 11 BP 1654 EP 1658 DI 10.1016/j.amjcard.2007.06.073 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 240DM UT WOS:000251567400010 PM 18036364 ER PT J AU Delling, FN Sanborn, DY Levine, RA Picard, MH Fifer, MA Palacios, IF Lowry, PA Vlahakes, GJ Vaturi, M Hung, J AF Delling, Francesea N. Sanborn, Danita Y. Levine, Robert A. Picard, Michael H. Fifer, Michael A. Palacios, Igor F. Lowry, Patricia A. Vlahakes, Gus J. Vaturi, Mordehay Hung, Judy TI Frequency and mechanism of persistent systolic anterior motion and mitral regurgitation after septal ablation in obstructive hypertrophic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OUTFLOW TRACT OBSTRUCTION; MYOCARDIAL ABLATION; VALVE REPLACEMENT; MYOTOMY-MYECTOMY; FOLLOW-UP; REDUCTION; SEVERITY; DISEASE; SERIES AB Relief of obstruction using ventricular septal ablation (VSA) may not eliminate systolic anterior motion (SAM) of the mitral valve and mitral regurgitation (MR), in patients with obstructive hypertrophic cardiomyopathy. The hypothesis was that persistent SAM after VSA was secondary to anterior papillary muscle displacement and malcoaptation of mitral valve leaflets and that these findings could predict persistence of SAM. Echocardiograms were examined from 37 patients with obstructive hypertrophic cardiomyopathy before and 12 +/- 3 months after VSA. Anterior leaflet malposition (anterior-to-posterior leaflet coaptation position ratio), papillary muscle malposition (septal-to-lateral/left ventricular internal diameter ratio), and anterior position of coaptation relative to the septum (coaptation-to-septal distance) were assessed. MR proximal jet width was also measured. Of 37 patients, 30 underwent successful VSA (left ventricular outflow tract gradient reduction >50%); 22 of 30 and 7 of 7 with <50% reduction (total 29 of 37; 78%) showed persistent SAM at 12 +/- 3 months. These patients had more anterior malposition of the mitral valve and less MR reduction than those without SAM: anterior-to-posterior leaflet coaptation position ratio 0.42 +/- 0.06 versus 0.56 +/- 0.09, septal-tolateral/left ventricular internal diameter ratio 0.39 +/- 0.12 versus 0.55 +/- 0.12, coaptation-to-septal distance 1.8 +/- 0.42 versus 2.8 +/- 0.30 cm, and MR reduction by 29 +/- 22% versus 71 12% (p <0.0001). Gradients, both at rest and provokable, were higher (27 +/- 33 vs 4 +/- 5 turn Hg, p = 0.0004; >45 mm Hg in 9 vs 0, p = 0.03, respectively) in patients with persistent SAM. Anterior malposition was present before VSA, with anterior-to-posterior leaflet coaptation position ratio <0.5 predicting SAM after VSA (p <0.0001). In conclusion, SAM and MR were often not eliminated using VSA. Mitral valve malposition was a strong predictor of SAM and MR reduction after VSA and may need to be considered in optimizing results of this procedure. (c) 2007 Elsevier Inc. All rights reserved. C1 [Delling, Francesea N.; Sanborn, Danita Y.; Levine, Robert A.; Picard, Michael H.; Vaturi, Mordehay; Hung, Judy] Harvard Univ, Sch Med, Cradiac Ultrasound Lab, Boston, MA 02115 USA. [Fifer, Michael A.; Palacios, Igor F.; Lowry, Patricia A.] Harvard Univ, Sch Med, Cardiac Catheterizat Lab, Boston, MA 02115 USA. [Vlahakes, Gus J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02115 USA. RP Hung, J (reprint author), Harvard Univ, Sch Med, Cradiac Ultrasound Lab, Boston, MA 02115 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [K24 HL67434, K23 HL04504, R01 HL72265] NR 28 TC 23 Z9 25 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2007 VL 100 IS 11 BP 1691 EP 1695 DI 10.1016/j.amjcard.2007.07.020 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 240DM UT WOS:000251567400016 PM 18036370 ER PT J AU Tay, FR Pashley, DH Loushine, RJ Kuttler, S Garcia-Godoy, F King, NM Ferrari, M AF Tay, Franklin R. Pashley, David H. Loushine, Robert J. Kuttler, Sergio Garcia-Godoy, Franklin King, Nigel M. Ferrari, Marco TI Susceptibility of a polycaprolactone-based root canal filling material to degradation. Evidence of biodegradation from a simulated field test SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID ENDODONTIC INFECTIONS; APICAL PERIODONTITIS; GUTTA-PERCHA; PART 2; POLYMERS; POLYESTERS; PLASTICS; RESILON; MICROORGANISMS; HYDROLYSIS AB Purpose: To examine if Resilon, a polycaprolactone-based root filling material, was susceptible to microbial biodegradation by using a simulated field test that consisted of incubating the material in wet dental sludge under mesophilic and aerobic conditions. Methods: Pressed disks prepared from Resilon, polycaprolactone (positive control) and gutta-percha (negative control) were incubated in wet dental sludge for up to 4 months and examined for topographical changes using scanning electron microscopy. Results: Gutta-percha exhibited minimal changes in surface integrity, while polycaprolactone and Resilon exhibited severe surface pitting and erosion. In the latter, disappearance of the polymer matrix was accompanied by exposure of mineral and bioactive glass fillers. Bacteria and hyphae-like structures were present on the disk surfaces. C1 [Tay, Franklin R.; Pashley, David H.] Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Pathol, Augusta, GA 30912 USA. [Tay, Franklin R.] Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Pathol, Dept Endodont, Augusta, GA 30912 USA. [Loushine, Robert J.] Med Coll Georgia, Sch Dent, Dept Endodont, Augusta, GA 30912 USA. [Kuttler, Sergio] Nova SE Univ, Coll Dent Med, Dept Endodont, Ft Lauderdale, FL USA. [Garcia-Godoy, Franklin] Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. [King, Nigel M.] Univ Hong Kong, Dept Pediat Dent & Orthodont, Hong Hom, Hong Kong, Peoples R China. [Ferrari, Marco] Univ Siena, Sch Dent, Dept Restorat Dent & Dent Mat, Siena, Italy. RP Tay, FR (reprint author), Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Pathol, Augusta, GA 30912 USA. EM tayfranklin7@gmail.com FU NIDCR NIH HHS [DE 015306, DE 014911] NR 34 TC 4 Z9 4 U1 0 U2 2 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD DEC PY 2007 VL 20 IS 6 BP 365 EP 369 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 243VQ UT WOS:000251825800004 PM 18269126 ER PT J AU Walters, RF Groben, PA Busam, K Millikan, RC Rabinovitz, H Cognetta, A Mihm, MC Prieto, VG Googe, PB King, R Moore, DT Woosley, J Thomas, NE AF Walters, Ruth Fulghum Groben, Pamela A. Busam, Klaus Millikan, Robert C. Rabinovitz, Harold Cognetta, Armand Mihm, Martin C., Jr. Prieto, Victor G. Googe, Paul B. King, Roy Moore, Dominic T. Woosley, John Thomas, Nancy E. TI Consumption of the epidermis: A criterion in the differential diagnosis of melanoma and dysplastic nevi that is associated with increasing Breslow depth and ulceration SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE dysplastic nevus; pathology; dermatology; mitosis; ulceration ID MELANOCYTIC NEVI; MALIGNANT-MELANOMA; HALO NEVI; EPIDEMIOLOGY; LESIONS; SKIN AB Consumption of the epidermis (COE), defined as thinning of the epidermis with attenuation of basal and suprabasal layers and loss of rete ridges adjacent to collections of melanocytes, is a recently coined term encompassing changes of the epidermal architecture associated with melanoma. To evaluate this feature as an additional diagnostic criterion for melanoma, we examined COE in 453 melanocytic lesions, including 213 invasive melanomas from a population-based series and 240 suspicious pigmented lesions from a clinic-based series, excluding halo and Spitz nevi. In the population-based series, COE was identified in 92/213 (43%) invasive melanomas and became progressively more frequent with increasing Breslow depth (P < 0.0001) and Clark level (P = 0.0002). COE was more frequent when mitotic figures (P < 0.0001), ulceration (P = 0.005), or vertical growth phase (P = 0.009) were present, but it was not significantly associated with age, gender, site, regression, or tumor-infiltrating lymphocytes. In the clinic-based series of pigmented lesions, COE was present in 2/25 (8%) in situ melanomas, 1/29 (3%) lesions classified as melanoma in situ/high-grade dysplastic nevi, and 1/40 (2.5%) high-grade dysplastic nevi. COE was not identified in 146 low-grade dysplastic, congenital, or common nevi. In the combined datasets, 94/96 (98%) lesions exhibiting COE were classified as melanoma. This study demonstrates that COE is frequently present in invasive melanomas, is associated with more aggressive histopathologic features (including increased Breslow depth and ulceration) and may be a useful supplementary diagnostic criterion for melanoma. Furthermore, the process leading to COE may be the first step in a progression to ulceration. C1 Univ N Carolina Hosp, Dept Pathol, Chapel Hill, NC USA. Univ N Carolina Hosp, Dept Dermatol, Chapel Hill, NC USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ N Carolina Hosp, Dept Epidemiol, Chapel Hill, NC USA. Univ Miami, Miller Sch Med, Dept Dermatol, Miami, FL 33152 USA. Dermatol Associates Tallahassee, Tallahassee, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX USA. Univ Tennessee, Grad Sch Med, Dept Pathol, Knoxville, TN USA. Univ Tennessee, Grad Sch Med, Knoxville Dermatopathol Lab, Knoxville, TN USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. Univ N Carolina Hosp, Dept Biostat, Chapel Hill, NC USA. RP Thomas, NE (reprint author), Univ N Carolina, Dept Dermatol, 3100 Thurston Bowles CB 7287, Chapel Hill, NC 27599 USA. EM nthomas@med.unc.edu FU NCI NIH HHS [R01 CA112243-04, K07 CA102096, K07 CA102096-02, R03 CA103089, CA112243, CA102096, R01 CA112243] NR 36 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD DEC PY 2007 VL 29 IS 6 BP 527 EP 533 PG 7 WC Dermatology SC Dermatology GA 233OG UT WOS:000251099600001 PM 18032946 ER PT J AU Metz, DC Sostek, MB Ruszniewski, P Forsmark, CE Monyak, J Pisegna, JR AF Metz, David C. Sostek, Mark B. Ruszniewski, Philippe Forsmark, Christopher E. Monyak, John Pisegna, Joseph R. TI Effects of esomeprazole on acid output in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PROTON PUMP INHIBITORS; ORAL PANTOPRAZOLE; INTRAGASTRIC PH; OMEPRAZOLE; LANSOPRAZOLE; THERAPY; EFFICACY; SAFETY AB OBJECTIVES: To evaluate the efficacy and safety of oral esomeprazole in the control of gastric acid hypersecretion in patients with hypersecretory states. METHODS: In this 12-month, open-label, multicenter study, acid output (AO) was evaluated at baseline, day 10, and months 3, 6, and 12. The starting dose of esomeprazole was 40 mg or 80 mg twice daily. On day 10, patients with controlled AO were maintained on the same dose, while those with uncontrolled AO had their doses increased (maximum dose 240 mg/day) until control was attained. Esophagogastroduodenoscopy (EGD) was performed at baseline and at 6 and 12 months. Safety and tolerability were assessed throughout the study by EGD, gastric analysis, and adverse events. RESULTS: Twenty-one patients (19 with Zollinger-Ellison syndrome [ZES], 2 with idiopathic gastric acid hypersecretion [IGH]) completed the study. Of the 20 patients with controlled AO at day 10, 18 (90%) had sustained AO control for the rest of the study. At 12 months, AO was controlled in 14 of 16 patients receiving esomeprazole 40 mg twice daily, in all 4 patients receiving esomeprazole 80 mg twice daily, and in the 1 patient receiving esomeprazole 80 mg 3 times daily. At 6 and 12 months, no patient had endoscopic evidence of mucosal disease. Esomeprazole was well tolerated; 1 patient had a serious adverse event (hypomagnesemia) attributed to treatment that resolved with magnesium supplementation during continued treatment. CONCLUSION: Esomeprazole in appropriately titrated doses controls AO over 12 months in patients with hypersecretory states and is well tolerated. C1 Univ Penn, Philadelphia, PA 19104 USA. AstraZeneca LP, Wilmington, DE USA. Beaujon Hosp, Clichy, France. Univ Florida, Gainesville, FL USA. Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Metz, DC (reprint author), Univ Penn Hlth Syst, Div Gastroenterol, 3rd Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [M01-RR00865] NR 22 TC 26 Z9 27 U1 0 U2 3 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 DEC PY 2007 VL 102 IS 12 BP 2648 EP 2654 DI 10.1111/j.1572-0241.2007.01509.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 235QL UT WOS:000251249300007 PM 17764495 ER PT J AU Naliboff, BD AF Naliboff, Bruce D. TI Towards a nondualistic approach to multisystem illness SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID IRRITABLE-BOWEL-SYNDROME; DISORDERS; SYMPTOMS; ANXIETY; PAIN AB There is an increasing interest in understanding the etiology and treatment of patients who present with multiple chronic symptoms. The thesis of this comment is that the understanding of these problems and progress on effective treatment will be greatly enhanced by emerging new models that go beyond dualistic distinctions like those between organic versus functional disorders and psychological versus physiological causation. The outline of this new model includes a focus on common neurobiological and behavioral mechanisms that operate across disorders including altered pain modulation, affect regulation, and illness coping. Exciting new areas of research include functional and structural brain imaging studies and more recent studies linking imaging with genetic markers, behavior, and autonomic responses. These new studies, carried out across illness populations, hold great promise to tie together the data on psychosocial, genetic, and biological mechanisms of these complicated clinical problems. C1 Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Naliboff, BD (reprint author), VA WLA Healthcare Ctr, Bldg 115-Rm 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK64539]; NINR NIH HHS [NR007768] NR 18 TC 16 Z9 16 U1 6 U2 7 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 DEC PY 2007 VL 102 IS 12 BP 2777 EP 2780 DI 10.1111/j.1572-0241.2007.01535.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 235QL UT WOS:000251249300026 PM 18042107 ER PT J AU Quinn, MM Sembajwe, G Stoddard, AM Kriebel, D Krieger, N Sorensen, G Hartman, C Naishadham, D Barbeau, EM AF Quinn, Margaret M. Sembajwe, Grace Stoddard, Anne M. Kriebel, David Krieger, Nancy Sorensen, Glorian Hartman, Cathy Naishadham, Deepa Barbeau, Elizabeth M. TI Social disparities in the burden of occupational exposures: Results of a cross-sectional study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE exposure assessment; social inequalities in occupational health and safety; occupational exposures and social disparities; occupational health questionnaires ID HEALTH DISPARITIES; WORK CONDITIONS; ASSOCIATION; EPIDEMIOLOGY; HAZARDS; COHORT; WOMEN; BLACK AB Background Most occupational studies evaluate a single exposure in relation to a particular disease. However, workers typically experience multiple exposures simultaneously. There is also increasing evidence of disparities in health by sociodemographic characteristics, mostly related to social position such as gender, race/ethnicity, immigration status, income, and education. Little information exists on the worker experience of multiple occupational exposures as they vary among social groups. The objectives of this article were to: assess the burden of exposures reported within 1 year by a socially diverse population working in a range of industries; and evaluate whether sociodemographic characteristics affected the patterns of these exposures. Methods Study participants were from 14 unionized worksites in meat processing, electrical lighting manufacturing, retail grocery stores, and school bus driving. A cross-sectional study design used a self-administered, computer-assisted questionnaire (English and Spanish) to assess sociodemographic characteristics and nine workplace exposures, within the past year An interviewer-administered job history also was collected. Results Twelve hundred eighty-two workers (72%) completed the survey: 36% women, 23% Latino, 39% black, 24% white, and 48% born outside the US. The prevalence of high exposures ranged from 21% (chemicals) to 39% (neck strain). Forty-six percent reported three or more high exposures. Exposure reporting varied among sociodemographic groups. Some of the disparities were explained by the jobs held by different groups, but after statistically controlling for job, many disparities remained. Conclusions Sociodemographic characteristics should be considered when conducting exposure assessments using questionnaires. More research is needed to understand how social characteristics may influence exposures. Am. J. Ind. Med. 50:861-875, 2007. (c) 2007 Wiley-Liss, Inc. C1 Univ Massachusetts, Dept Work Environm, Lowell, MA 01854 USA. New England Res Inst, Dept Stat Anal & Res, Watertown, MA 02172 USA. Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Quinn, MM (reprint author), Univ Massachusetts, Dept Work Environm, Lowell, MA 01854 USA. EM margaretquinn@uml.edu FU NIOSH CDC HHS [R01 OH07366-01S, R01 OH07366-01] NR 47 TC 39 Z9 39 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2007 VL 50 IS 12 BP 861 EP 875 DI 10.1002/ajim.20529 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 234GW UT WOS:000251149700001 PM 17979135 ER PT J AU Rajab, A Manzini, MC Mochida, GH Walsh, CA Ross, ME AF Rajab, Anna Manzini, M. Chiara Mochida, Ganeshwaran H. Walsh, Christopher A. Ross, M. Elizabeth TI A novel form of lethal microcephaly with simplified gyral pattern and brain stem hypoplasia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE lethal microcephaly; simplified gyral pattern; fetal distress; apnea; autosomal recessive inheritance ID BOWEN-CONRADI-SYNDROME; SIZE; MALFORMATIONS; DISORDER; CHILDREN; GROWTH AB We report on four patients from the same family affected by a lethal form of autosomal recessive microcephaly of prenatal onset. Symptoms include low birth-weight and length with disproportionately small head, fetal distress, apnea, seizures and facial features reminiscent of Amish microcephaly and Bowen-Conradi syndrome. Brain imaging revealed a simplified gyral pattern with normal to slightly thinned cortical gray matter, thin corpus callosum, mild brainstem and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton, and no striking dysmorphic facial features were found to be associated with this syndrome. All patients died within hours to weeks after birth following severe apnea attacks and central hypoventilation. Recessive primary microcephaly with lethality in early infancy is rarely reported. The patients described here do not resemble any other published cases of such clinical severity and the locus for the only reported early lethal microcephaly gene found in Amish families was excluded. Therefore, this appears to be a distinct genetic cause of lethal microcephaly. (C) 2007 Wiley-Liss, Inc. C1 DGHA, Minist Hlth, Genet Unit, Muscat 113, Oman. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Dept Neurol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Lab Neurogenet & Dev, New York, NY USA. RP Rajab, A (reprint author), DGHA, Minist Hlth, Genet Unit, PO Box 880, Muscat 113, Oman. EM drarajab@omantel.net.om OI Manzini, M. Chiara/0000-0001-7175-1096 FU NINDS NIH HHS [P01NS048120, R37-NS35129] NR 20 TC 11 Z9 11 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2007 VL 143A IS 23 BP 2761 EP 2767 DI 10.1002/ajmg.a.31955 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 237DR UT WOS:000251353800002 PM 17975804 ER PT J AU Dhingra, R Gona, P Nam, BH D'Agostino, RB Wilson, PWF Benjamin, EJ O'Donnell, CJ AF Dhingra, Ravi Gona, Philimon Nam, Byung-Ho D'Agostino, Ralph B. Wilson, Peter W. F. Benjamin, Emelia J. O'Donnell, Christopher J. TI C-reactive protein, inflammatory conditions, and cardiovascular disease risk SO AMERICAN JOURNAL OF MEDICINE 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 arthritis; C-reactive protein; cardiovascular disease; cohort study; inflammation ID CORONARY-HEART-DISEASE; PUBLIC-HEALTH PRACTICE; RHEUMATOID-ARTHRITIS; PLASMA-CONCENTRATION; TISSUE FACTOR; MARKERS; MEN; PREDICTION; WOMEN; SERUM AB BACKGROUND: It is uncertain to what extent high C-reactive protein (CRP) concentrations reflect the presence of inflammatory conditions in the community. METHODS: We evaluated 3782 Framingham Offspring Study participants (mean age 55 years; 52% women) free of baseline cardiovascular disease. Logistic regression models examined the prevalence of common inflammatory conditions by CRP categories, while a separate matched case-referent analysis evaluated the prevalence of uncommon inflammatory conditions. Cox models were used to assess the influence of common inflammatory conditions on relations between CRP and incident cardiovascular disease. RESULTS: Common inflammatory conditions were reported by nearly half of the participants; these individuals were more likely to have markedly high CRP concentrations (> 10 mg/L, P for trend =.001). In multivariable models, there were increased odds of having at least one common inflammatory condition with CRP concentrations of 1-3.0, 3.01-10, and > 10 mg/ L, compared with the referent category (< 1 mg/ L); the respective odds ratios with 95% confidence intervals were 1.41 (1.07-1.86), 1.45 (1.07-1.98), and 1.64 (1.09-2.47) in men, and 1.08 (0.82-1.43), 1.07 (0.80-1.44), and 1.38 (0.97-1.96) in women. In case-referent analyses, uncommon inflammatory conditions were more common in individuals with CRP > 10 mg/L compared with those with CRP < 1 mg/ L (12.1% vs 6.6%; P=.0001). In multivariable models, higher CRP categories were not associated with incident cardiovascular disease, and with additional adjustment for inflammatory conditions, results remained unchanged. CONCLUSION: There is high prevalence of common and uncommon inflammatory conditions in individuals with high CRP concentrations. Higher CRP concentrations should be interpreted with caution in cardiovascular disease risk assessment. (c) 2007 Elsevier Inc. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Alice Peck Day Mem Hosp, Lebanon, NH USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [N01 HC 25195, N01 HC025195, R01 HL 073272 01, R01 HL 076784, R01 HL 64753, R01 HL073272, R01 HL076784] NR 40 TC 36 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2007 VL 120 IS 12 BP 1054 EP 1062 DI 10.1016/j.amjmed.2007.08.037 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 238ZI UT WOS:000251486700010 PM 18060926 ER PT J AU Jneid, H Moukarbel, GV Dawson, B Hajjar, RJ Francis, GS AF Jneid, Hani Moukarbel, George V. Dawson, Bart Hajjar, Roger J. Francis, Gary S. TI Combining neuroendocrine inhibitors in heart failure: Reflections on safety and efficacy SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE aldosterone; angiotensin; beta-blocker; heart failure; neuroendocrine; systolic dysfunction ID CONVERTING-ENZYME-INHIBITORS; LEFT-VENTRICULAR DYSFUNCTION; CARDIAC-INSUFFICIENCY BISOPROLOL; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; SYSTOLIC FUNCTION; ANGIOTENSIN; MORTALITY; MORBIDITY; CANDESARTAN AB Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Univ Kentucky, Div Cardiol, Lexington, KY USA. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. RP Jneid, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. EM Jneid.Hani@mgh.harvard.edu NR 40 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2007 VL 120 IS 12 DI 10.1016/j.amjmed.2007.02.029 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 238ZI UT WOS:000251486700015 ER PT J AU Brubaker, S Riley, L AF Brubaker, Sara Riley, Laura TI GBS colonization in the first trimester and risk of preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Brubaker, Sara; Riley, Laura] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 211 BP S70 EP S70 DI 10.1016/j.ajog.2007.10.224 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500212 ER PT J AU Carr, D Newton, K Hitti, J Easterling, T Utzschneider, K Faulenbach, M Kahn, S Heckbert, S AF Carr, Darcy Newton, Katherine Hitti, Jane Easterling, Thomas Utzschneider, Kristina Faulenbach, Mirjam Kahn, Steven Heckbert, Susan TI Preterm delivery is associated with future diabetes independent of preeclampsia or gestational diabetes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Carr, Darcy; Hitti, Jane; Easterling, Thomas; Heckbert, Susan] Univ Washington, Seattle, WA 98195 USA. [Newton, Katherine] Grp Hlth Ctr Hlth Studies, Washington, DC USA. [Utzschneider, Kristina; Faulenbach, Mirjam; Kahn, Steven] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 678 BP S194 EP S194 DI 10.1016/j.ajog.2007.10.706 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500670 ER PT J AU Carr, D Newton, K Hitti, J Easterling, T Utzschneider, K Faulenbach, M Kahn, S Heckbert, S AF Carr, Darcy Newton, Katherine Hitti, Jane Easterling, Thomas Utzschneider, Kristina Faulenbach, Mirjam Kahn, Steven Heckbert, Susan TI Vitamin D deficiency is common in pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Carr, Darcy; Hitti, Jane; Easterling, Thomas; Heckbert, Susan] Univ Washington, Seattle, WA 98195 USA. [Newton, Katherine] Grp Hlth Ctr Hlth Studies, Washington, DC USA. [Utzschneider, Kristina; Faulenbach, Mirjam; Kahn, Steven] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 679 BP S194 EP S194 DI 10.1016/j.ajog.2007.10.707 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500671 ER PT J AU Nadel, A Likhite, M AF Nadel, Allan Likhite, Marisa TI First trimester aneuploidy screening in a high risk population SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Nadel, Allan; Likhite, Marisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 144 BP S52 EP S52 DI 10.1016/j.ajog.2007.10.156 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500145 ER PT J AU Rana, S Rauh-Hain, A Karumanchi, A Thadhani, R AF Rana, Sarosh Rauh-Hain, Alejandro Karumanchi, Ananth Thadhani, Ravi TI First-trimester serum angiogenic factors and the risk of intrauterine fetal demise SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Rana, Sarosh] Brown Univ, Women & Infants Hosp Rhode Isl, Providence, RI 02912 USA. [Rauh-Hain, Alejandro] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Med Obstetr & Gynecol, Boston, MA 02215 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 25 BP S12 EP S12 DI 10.1016/j.ajog.2007.10.028 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500028 ER PT J AU Bradley, CS Nygaard, IE Brown, MB Gutman, RE Kenton, KS Whitehead, WE Goode, PS Wren, PA Ghetti, C Weber, AM AF Bradley, Catherine S. Nygaard, Ingrid E. Brown, Morton B. Gutman, Robert E. Kenton, Kimberly S. Whitehead, William E. Goode, Patricia S. Wren, Patricia A. Ghetti, Chiara Weber, Anne M. CA Pelvic Floor Disorders Network TI Bowel symptoms in women 1 year after sacrocolpopexy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE abdominal sacrocolpopexy; bowel symptoms; constipation; pelvic organ prolapse; questionnaires ID PELVIC ORGAN PROLAPSE; RECTOVAGINAL FASCIA REATTACHMENT; RECTOCELE REPAIR; ABDOMINAL SACROCOLPOPEXY; POSTERIOR COMPARTMENT; FLOOR DISORDERS; DYSFUNCTION; CONSTIPATION; POPULATION; COLPOPEXY AB OBJECTIVE: The objective of the study was to evaluate changes in bowel symptoms after sacrocolpopexy. STUDY DESIGN: This was a prospectively planned, ancillary analysis of the Colpopexy and Urinary Reduction Efforts study, a randomized trial of sacrocolpopexy with or without Burch colposuspension in stress continent women with stages II - IV prolapse. In addition to sacrocolpopexy (+/- Burch), subjects underwent posterior vaginal or perineal procedures ( PR) at each surgeon's discretion. The preoperative and 1 year postoperative Colorectal-anal Distress Inventory (CRADI) scores were compared within and between groups using Wilcoxon signed-rank and rank-sum tests, respectively. RESULTS: The sacrocolpopexy + PR group (n = 87) had more baseline obstructive colorectal symptoms (higher CRADI and CRADI-obstructive scores: P = .04 and < .01, respectively) than the sacrocolpopexy alone group ( n = 211). CRADI total, obstructive, and pain/irritation scores significantly improved in both groups ( all P < .01). Most bothersome symptoms resolved after surgery in both groups. CONCLUSION: Most bowel symptoms improve in women with moderate to severe pelvic organ prolapse after sacrocolpopexy. C1 [Bradley, Catherine S.] Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. [Nygaard, Ingrid E.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Brown, Morton B.] Univ Michigan, Dept Biostat, Ann Arbor, MI USA. [Gutman, Robert E.] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD USA. [Kenton, Kimberly S.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Whitehead, William E.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Goode, Patricia S.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham Atlanta Geriat Res Educ & Clin Ctr, Dept Med, Birmingham, AL USA. [Wren, Patricia A.] Oakland Univ, Sch Hlth Sci, Dept Wellness Hlth Promot & Injury Prevent, Rochester, MI USA. [Ghetti, Chiara] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Weber, Anne M.] NIH, NICHHD, Bethesda, MD USA. RP Bradley, CS (reprint author), Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 AR 642.e1 DI 10.1016/j.ajog.2007.08.023 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700033 ER PT J AU Burgio, KL Nygaard, IE Richter, HE Brubaker, L Gutman, RE Leng, W Wei, J Weber, AM AF Burgio, Kathryn L. Nygaard, Ingrid E. Richter, Holly E. Brubaker, Linda Gutman, Robert E. Leng, Wendy Wei, John Weber, Anne M. CA Pelvic Fl Disorders Network TI Bladder symptoms 1 year after abdominal sacrocolpopexy with and without Burch colposuspension in women without preoperative stress incontinence symptoms SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE irritative urinary symptoms; obstructive urinary symptoms; pelvic organ prolapse; sacrocolpopexy; urinary incontinence ID QUALITY-OF-LIFE; URINARY-INCONTINENCE; GENITAL PROLAPSE AB OBJECTIVE: The objective of the study was to examine changes in bladder symptoms 1 year after abdominal sacrocolpopexy (ASC) with vs without Burch colposuspension. STUDY DESIGN: Women without stress urinary incontinence (SUI) symptoms undergoing ASC were randomized to receive or not receive Burch. One year later, irritative, obstructive, and SUI symptoms were assessed in 305 women using Urogenital Distress Inventory subscales. A composite "stress endpoint" combined SUI symptoms, positive stress test, and retreatment. RESULTS: In all women, the mean irritative score decreased from 19.6 +/- 16.3 ( mean +/- SD) to 9.1 +/- 10.6; for obstructive symptoms, from 34.8 +/- 21.0 to 6.3 +/- 10.4 ( both P < .001). Preoperative bothersome irritative symptoms resolved in 74.6% ( 126 of 169) and obstructive symptoms in 85.1% ( 212 of 249), independent of Burch. Fewer women with Burch had urge incontinence (14.5% vs 26.8%, P = .048) and fulfilled the stress endpoint (25.0% vs 40.1%, P = .012). CONCLUSION: ASC reduced bothersome irritative and obstructive symptoms. Prophylactic Burch reduced stress and urge incontinence. C1 [Burgio, Kathryn L.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35233 USA. [Richter, Holly E.] Univ Alabama, Sch Med, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Burgio, Kathryn L.] Geriat Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Nygaard, Ingrid E.] Univ Utah, Ctr Hlth Sci, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. [Brubaker, Linda] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Chicago, IL USA. [Gutman, Robert E.] Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD USA. [Leng, Wendy] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15260 USA. [Wei, John] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI USA. [Weber, Anne M.] NIH, NICHHD, Bethesda, MD USA. RP Burgio, KL (reprint author), Univ Alabama, Birmingham VA Med Ctr, 11G, 700 S 19th St, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu NR 15 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 AR 647. e1 DI 10.1016/j.ajog.2007.08.048 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700035 ER PT J AU Handa, VL Zyczynski, HM Burgio, KL Fitzgerald, MP Borello-France, D Janz, NK Fine, PM Whitehead, W Brown, MB Weber, AM AF Handa, Victoria L. Zyczynski, Halina M. Burgio, Kathryn L. Fitzgerald, Mary Pat Borello-France, Diane Janz, Nancy K. Fine, Paul M. Whitehead, William Brown, Morton B. Weber, Anne M. CA Pelvic Floor Disorders Network TI The impact of fecal and urinary incontinence on quality of life 6 months after childbirth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE childbirth; fecal incontinence; quality of life; urinary incontinence ID ANAL-SPHINCTER DISRUPTION; VAGINAL DELIVERY; PRIMIPAROUS WOMEN; OBSTETRICS UNIT; SEVERITY INDEX; SHORT-FORM; PREVALENCE; SYMPTOMS; STRESS; RISK AB OBJECTIVE: The objective of the study was to investigate the impact of postpartum fecal incontinence (FI) and urinary incontinence (UI) on quality of life (QOL). STUDY DESIGN: Seven hundred fifty-nine primiparous women in the Childbirth and Pelvic Symptoms study were interviewed 6 months postpartum. FI and UI were assessed with validated questionnaires. We measured QOL with SF-12 summary scores, health utility index score ( a measure of self-rated overall health), and the modified Manchester Health Questionnaire. RESULTS: Women with FI had worse self-rated health utility index scores (85.1 +/- 9.8 vs 88.0 +/- 11.6, P = .02) and Medical Outcomes Study Short Form Health Survey (SF-12) mental summary scores ( 46.8 +/- 9.2 vs 51.1 +/- 8.7, P <.0001) than women without FI or flatal incontinence. Women with UI had worse SF-12 mental summary scores (48.3 +/- 9.8 vs 51.6 +/- 7.8, P <.01) and self-rated health utility index scores (84.1 +/- 12.5 vs 88.7 +/- 10.1, P <.01) than women without UI. Women with both FI and UI had the lowest SF-12 mental summary scores (44.5 +/- 9.0). CONCLUSION: Six months after delivery, women experiencing FI or UI reported negative effects on health-related QOL. FI and UI together have a greater impact than either condition alone. C1 [Handa, Victoria L.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Burgio, Kathryn L.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Burgio, Kathryn L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Fitzgerald, Mary Pat] Loyola Univ, Chicago, IL USA. [Borello-France, Diane] Duquesne Univ, Pittsburgh, PA USA. [Janz, Nancy K.; Brown, Morton B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Fine, Paul M.] Baylor Coll Med, Houston, TX USA. [Whitehead, William] Univ N Carolina, Chapel Hill, NC USA. [Weber, Anne M.] NIH, NICHHD, Chapel Hill, NC USA. RP Handa, VL (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. FU NCRR NIH HHS [M01 RR002719-225499, M01 RR002719]; NICHD NIH HHS [U10 HD041268, U10 HD041263, U10 HD41268, U10 HD041248, U10 HD41250, U10 HD041268-05, U10 HD041267, U01 HD41249, U10 HD41248, U10 HD041269, U01 HD041249, U10 HD41269, U10 HD041261, U10 HD041250, U10 HD41267, U10 HD41263, U10 HD41261] NR 28 TC 4 Z9 4 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 AR 636.e1 DI 10.1016/j.ajog.2007.08.020 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700030 PM 18060960 ER PT J AU Sataranatarajan, K Mariappan, MM Lee, MJ Feliers, D Choudhury, GG Barnes, JL Kasinath, BS AF Sataranatarajan, Kavithalakshmi Mariappan, Meenalakshmi M. Lee, Myung Ja Feliers, Denis Choudhury, Goutarn Ghosh Barnes, Jeffrey L. Kasinath, Balakuntalam S. TI Regulation of elongation phase of mRNA translation in diabetic nephropathy - Amelioration by rapamycin SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RENAL EPITHELIAL-CELLS; MAMMALIAN TARGET; KIDNEY-DISEASE; PROTEIN-KINASE; DB/DB MICE; RAT MODEL; FACTOR-II; MTOR; HYPERTROPHY; GROWTH AB High glucose and high insulin, pathogenic factors in type 2 diabetes, induce rapid synthesis of the matrix protein laminin-beta 1 in renal proximal tubular epithelial cells by stimulation of initiation phase of mRNA translation. We investigated if elongation phase of translation also contributes to high glucose and high insulin induction of laminin-beta 1 synthesis in proximal tubular epithelial cells. High glucose or high insulin rapidly increased activating Thr56 dephosphorylation of eEF2 and inactivating Ser366 phosphorylation of eEF2 kinase, events that facilitate elongation. Studies with inhibitors showed that PI3 kinase-Akt-mTOR-p70S6 kinase pathway controlled changes in phosphorylation of eEF2 and eEF2 kinase induced by high glucose or high insulin. Renal cortical homogenates from db/db mice in early stage of type 2 diabetes showed decrease in eEF2 phosphorylation and increment in eEF2 kinase phosphorylation in association with renal hypertrophy and glomerular and tubular increase in laminin-beta 1 content. Rapamycin, an inhibitor of mTOR, abolished diabetes-induced changes in phosphorylation of eEF2, eEF2 kinase, and p70S6 kinase and ameliorated renal hypertrophy and laminin-beta 1 protein content, without affecting hyperglycemia. These data show that mTOR is an attractive target for amelioration of diabetes-induced renal injury. C1 [Sataranatarajan, Kavithalakshmi; Mariappan, Meenalakshmi M.; Lee, Myung Ja; Feliers, Denis; Choudhury, Goutarn Ghosh; Barnes, Jeffrey L.; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Choudhury, Goutarn Ghosh; Barnes, Jeffrey L.; Kasinath, Balakuntalam S.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, OBrien Kidney Res Ctr, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU NIDDK NIH HHS [R01 DK077295, DK050190, P50 DK061597, R29 DK050190, R01 DK050190, DK077295, DK061597] NR 37 TC 66 Z9 70 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2007 VL 171 IS 6 BP 1733 EP 1742 DI 10.2353/ajpath.2007.070412 PG 10 WC Pathology SC Pathology GA 241EE UT WOS:000251638900002 PM 17991718 ER PT J AU Quinn, LS Anderson, BG Plymate, SR AF Quinn, LeBris S. Anderson, Barbara G. Plymate, Stephen R. TI Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin-like growth factor; insulin-like growth factor receptor; protein synthesis; protein degradation; sarcopenia ID GROWTH-FACTOR-I; STIMULATES PROTEIN-SYNTHESIS; MAMMALIAN SKELETAL-MUSCLE; DIGITORUM LONGUS MUSCLE; SATELLITE CELL-ACTIVITY; TRANSGENIC MICE; MYOTUBE HYPERTROPHY; MYONUCLEAR NUMBER; GAMMA-IRRADIATION; UBIQUITIN LIGASES AB Quinn LS, Anderson BG, Plymate SR. Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling. Am J Physiol Endocrinol Metab 293: E1538-E1551, 2007. First published October 16, 2007; doi: 10.1152/ajpendo.00160.2007. - The insulinlike growth factors (IGF-I and IGF-II), working through the type 1 IGF receptor (IGF-1R), are key mediators of skeletal muscle fiber growth and hypertrophy. These processes are largely dependent on stimulation of proliferation and differentiation of muscle precursor cells, termed myoblasts. It has not been rigorously determined whether the IGFs can also mediate skeletal muscle hypertrophy in a myoblast-independent fashion. Similarly, although the phosphatidylinositol 3-kinase (PI3K) and calcineurin signaling pathways have been implicated in skeletal muscle hypertrophy, these pathways are also involved in skeletal myoblast differentiation. To determine whether the IGFs can stimulate skeletal muscle hypertrophy in a myoblast-independent fashion, we developed and validated a retroviral expression vector that mediated overexpression of the human IGF-1R in rat L6 skeletal myotubes (immature muscle fibers), but not in myoblasts. L6 myotubes transduced with this vector accumulated significantly higher amounts of myofibrillar proteins, in a ligand-and receptor-dependent manner, than controls and demonstrated significantly increased rates of protein synthesis. Stimulation of myotube hypertrophy was independent of myoblast contributions, inasmuch as these cultures did not exhibit increased levels of myoblast proliferation or differentiation. Experiments with PI3K and calcineurin inhibitors indicated that myoblast-independent myotube hypertrophy was mediated by PI3K, but not calcineurin, signaling. This study demonstrates that IGF can mediate skeletal muscle hypertrophy in a myoblast-independent fashion and suggests that muscle-specific overexpression of the IGF-1R or stimulation of its signaling pathways could be used to develop strategies to ameliorate muscle wasting without stimulating proliferative pathways leading to carcinogenesis or other pathological sequelae. C1 Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Washington, DC USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, 151 Amer Lake Div, Tacoma, WA 98493 USA. EM quinnL@u.washington.edu FU NIA NIH HHS [R01 AG-024136] NR 81 TC 19 Z9 21 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2007 VL 293 IS 6 BP E1538 EP E1551 DI 10.1152/ajpendo.00160.2007 PG 14 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 239HU UT WOS:000251510200009 PM 17940216 ER PT J AU Akiba, Y Mizumori, M Guth, PH Engel, E Kaunitz, JD AF Akiba, Yasutada Mizumori, Misa Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. TI Duodenal brush border intestinal alkaline phosphatase activity affects bicarbonate secretion in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE duodenum; brush-border membrane; ELF-97 phosphate ID STIMULATED ATPASE ACTIVITY; HCO3-SECRETION; EPITHELIAL-CELLS; PANCREATIC-DUCT; ADENOSINE-TRIPHOSPHATASE; CARBONIC-ANHYDRASES; HYDROGEN-SULFIDE; LUMINAL CO2; GUINEA-PIG; RECEPTORS AB We hypothesized that duodenal HCO3- secretion alkalinizes the microclimate surrounding intestinal alkaline phosphatase (IAP), increasing its activity. We measured AP activity in rat duodenum in situ in frozen sections with the fluorogenic substrate ELF-97 phosphate and measured duodenal HCO3-secretion with a pH-stat in perfused duodenal loops. We examined the effects of the IAP inhibitors L-cysteine or L-phenylalanine ( 0.1 - 10 mM) or the tissue nonspecific AP inhibitor levamisole ( 0.1 - 10 mM) on AP activity in vitro and on acid-induced duodenal HCO3- secretion in vivo. AP activity was the highest in the duodenal brush border, decreasing longitudinally to the large intestine with no activity in stomach. Villous surface AP activity measured in vivo was enhanced by PGE(2) intravenously and inhibited by luminal L-cysteine. Furthermore, incubation with a pH 2.2 solution reduced AP activity in vivo, whereas pretreatment with the cystic fibrosis transmembrane regulator (CFTR) inhibitor CFTRinh-172 abolished AP activity at pH 2.2. L-Cysteine and L-phenylalanine enhanced acid-augmented duodenal HCO3- secretion. The nonselective P2 receptor antagonist suramin (1 mM) reduced acid-induced HCO3- secretion. Moreover, L-cysteine or the competitive AP inhibitor glycerol phosphate (10 mM) increased HCO3- secretion, inhibited by suramin. In conclusion, enhancement of the duodenal HCO3- secretory rate increased AP activity, whereas inhibition of AP activity increased the HCO3- secretory rate. These data support our hypothesis that HCO3- secretion increases AP activity by increasing local pH at its catalytic site and that AP hydrolyzes endogenous luminal phosphates, presumably ATP, which increases HCO3- secretion via activation of P2 receptors. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [P30 DK0413, R01 DK54221] NR 69 TC 44 Z9 48 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 2007 VL 293 IS 6 BP G1223 EP G1233 DI 10.1152/ajpgi.00313.2007 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 239HX UT WOS:000251510500014 PM 17916646 ER PT J AU Durst, R Danenberg, H Gallily, R Mechoulam, R Meir, K Grad, E Beeri, R Pugatsch, T Tarsish, E Lotan, C AF Durst, Ronen Danenberg, Haim Gallily, Ruth Mechoulam, Raphael Meir, Keren Grad, Etty Beeri, Ronen Pugatsch, Thea Tarsish, Elizabet Lotan, Chaim TI Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE ischemia-reperfusion; myocardial infarction; cannabinoids; pharmacotherapy ID C-REACTIVE PROTEIN; RECEPTOR ACTIVATION; MULTIPLE-SCLEROSIS; CONTROLLED-TRIAL; INFARCT SIZE; CB1; ANANDAMIDE; HEART; ENDOCANNABINOIDS; LYMPHOCYTES AB Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia. C1 Hadassah Hebrew Univ, Med Ctr, Dept Cardiol, Jerusalem, Israel. Hadassah Hebrew Univ, Med Ctr, Dept Pathol, Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Med, Lautenberg Ctr Gen & Tumor Immunol, IL-91010 Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Med, Sch Pharm, Dept Med Chem & Nat Prod, IL-91010 Jerusalem, Israel. RP Durst, R (reprint author), Massachusetts Gen Hosp, Cardiac Echo Lab, Blake 2,Rm 255,55 Fruit St, Boston, MA 02114 USA. EM rdurst@partners.org NR 38 TC 40 Z9 40 U1 3 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2007 VL 293 IS 6 BP H3602 EP H3607 DI 10.1152/ajpheart.00098.2007 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TW UT WOS:000251400300045 PM 17890433 ER PT J AU Paunescu, TG Russo, LM Da Silva, N Kovacikova, J Mohebbi, N Van Hoek, AN Mckee, M Wagner, CA Breton, S Brown, D AF Paunescu, Teodor G. Russo, Leileata M. Da Silva, Nicolas Kovacikova, Jana Mohebbi, Nilufar Van Hoek, Alfred N. Mckee, Mary Wagner, Carsten A. Breton, Sylvie Brown, Dennis TI Compensatory membrane expression of the V-ATPase B2 subunit isoform in renal medullary intercalated cells of B1-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proton pump; immunofluorescence; pH homeostasis; urinary acidification; Atp6v1b1-/; mice ID VACUOLAR H+-ATPASE; SECRETING EPITHELIAL-CELLS; MALE REPRODUCTIVE-TRACT; KIDNEY COLLECTING DUCT; TUBULAR-ACIDOSIS; B1 SUBUNIT; MOLECULAR-CLONING; C-SUBUNIT; LUMINAL ACIDIFICATION; PLASMA-MEMBRANES AB Mice deficient in the ATP6V1B1 ("B1") subunit of the vacuolar proton-pumping ATPase (V-ATPase) maintain body acid-base homeostasis under normal conditions, but not when exposed to an acid load. Here, compensatory mechanisms involving the alternate ATP6V1B2 ("B2") isoform were examined to explain the persistence of baseline pH regulation in these animals. By immunocytochemistry, the mean pixel intensity of apical B2 immunostaining in medullary A intercalated cells (A-ICs) was twofold greater in B1-/- mice than in B1+/+ animals, and B2 was colocalized with other V-ATPase subunits. No significant upregulation of B2 mRNA or protein expression was detected in B1-/- mice compared with wild-type controls. We conclude that increased apical B2 staining is due to relocalization of B2-containing V-ATPase complexes from the cytosol to the plasma membrane. Recycling of B2-containing holoenzymes between these domains was confirmed by the intracellular accumulation of B1-deficient V-ATPases in response to the microtubule-disrupting drug colchicine. V-ATPase membrane expression is further supported by the presence of "rod-shaped" intramembranous particles seen by freeze fracture microscopy in apical membranes of normal and B1-deficient A-ICs. Intracellular pH recovery assays show that significant (28-40% of normal) V-ATPase function is preserved in medullary ICs from B1-/- mice. We conclude that the activity of apical B2-containing V-ATPase holoenzymes in A-ICs is sufficient to maintain baseline acid-base homeostasis in B1-deficient mice. However, our results show no increase in cell surface V-ATPase activity in response to metabolic acidosis in ICs from these animals, consistent with their inability to appropriately acidify their urine under these conditions. C1 Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Div Nephrol,Program Membrane Biol, Boston, MA 02114 USA. Univ Zurich, Zurich Ctr Integrat Human Physiol, Inst Physiol, Zurich, Switzerland. RP Paunescu, TG (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, 185 Cambridge St, CPZN 8150, Boston, MA 02114 USA. EM paunescu@receptor.mgh.harvard.edu FU NICHD NIH HHS [HD-40793]; NIDDK NIH HHS [DK-42956, DK-38452, DK-43266] NR 68 TC 43 Z9 45 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2007 VL 293 IS 6 BP F1915 EP F1926 DI 10.1152/ajprenal.00160.2007 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 235OK UT WOS:000251244000019 PM 17898041 ER PT J AU Viguera, AC Whitfield, T Baldessarini, RJ Newport, DJ Stowe, Z Reminick, A Zurick, A Cohen, LS AF Viguera, Adele C. Whitfield, Theodore Baldessarini, Ross J. Newport, D. Jeffrey Stowe, Zachary Reminick, Alison Zurick, Amanda Cohen, Lee S. TI Risk of recurrence in women with bipolar disorder during pregnancy: Prospective study of mood stabilizer discontinuation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT TREATMENT; GRADUAL DISCONTINUATION; LITHIUM MAINTENANCE; II DISORDERS; DEPRESSION; IMPACT; CHILDBEARING; REPLICATION; MANAGEMENT; MORBIDITY AB Objective: This study estimated the risk of recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued treatment with mood stabilizers during pregnancy. Method: In a prospective observational clinical cohort study, the authors determined recurrence risk and survival-analysis-based time to recurrence of a new episode in 89 pregnant women with DSM-IV bipolar disorder. Eligible subjects were euthymic at conception and continued mood stabilizer treatment or discontinued treatment proximate to conception. Results: The overall risk of at least one recurrence in pregnancy was 71%. Among women who discontinued versus continued mood stabilizer treatment, recurrence risk was twofold greater, median time to first recurrence was more than fourfold shorter, and the proportion of weeks ill during pregnancy was five times greater. Median recurrence latency was 11 times shorter after abrupt/rapid versus gradual discontinuation of mood stabilizer. Most recurrences were depressive or mixed (74%), and 47% occurred during the first trimester. Predictors of recurrence included bipolar 11 disorder diagnosis, earlier onset, more recurrences/year, recent illness, use of antidepressants, and use of anticonvulsants versus lithium. Conclusions: Discontinuation of mood stabilizer, particularly abruptly, during pregnancy carries a high risk for new morbidity in women with bipolar disorder, especially for early depressive and dysphoric states. However, this risk is reduced markedly by continued mood stabilizer treatment. Treatment planning for pregnant women with bipolar disorder should consider not only the relative risks of fetal exposure to mood stabilizers but also the high risk of recurrence and morbidity associated with stopping maintenance mood stabilizer treatment. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Perinatal Psychiat Unit, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland Clin, Neurol Inst, Dept Psychiat & Psychol, Cleveland, OH 44195 USA. Biostat Solut, Cambridge, MA USA. McLean Hosp, Belmont, MA 02178 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30322 USA. RP Viguera, AC (reprint author), Cleveland Clin Fdn, Cleveland Clin, Neurol Inst, Dept Psychiat & Psychol, 9500 Euclid Ave,P57, Cleveland, OH 44195 USA. EM viguerav@ccf.org RI Newport, Donald/H-9846-2013; Kothari, Khyati/B-5008-2014; OI Newport, D. Jeffrey/0000-0003-1695-9710 FU NIMH NIH HHS [K23 MH 011609, R01 MH 071531, R01 MH 071762] NR 46 TC 150 Z9 153 U1 0 U2 13 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 DEC PY 2007 VL 164 IS 12 BP 1817 EP 1824 DI 10.1176/appi.ajp.2007.06101639 PG 8 WC Psychiatry SC Psychiatry GA 238VN UT WOS:000251476200012 PM 18056236 ER PT J AU Martin, LF Hall, MH Ross, RG Zerbe, G Freedman, R Olincy, A AF Martin, Laura F. Hall, Mei-Hua Ross, Randal G. Zerbe, Gary Freedman, Robert Olincy, Ann TI Physiology of schizophrenia, bipolar disorder, and Schizoaffective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 11th International Congress on Schizophrenia Research/8th Biennial Mt Sinai Conference on Cognition in Schizophrenia CY MAR 27-APR 01, 2007 CL Colorado Springs, CO ID PURSUIT EYE-MOVEMENTS; SMOOTH-PURSUIT; SACCADIC ABNORMALITIES; ANTICIPATORY SACCADES; PSYCHOTIC-PATIENTS; VOLUNTARY CONTROL; GRAY-MATTER; TASK; PERFORMANCE; MANIA AB Objective: Endophenotypes have been proposed to identify the genetic and biological substrates of complex disorders. Three physiological inhibitory endophenotypes of large effect size in schizophrenia include suppression of P50 auditory evoked responses, inhibition of leading (small anticipatory) saccades during smooth pursuit eye movements, and cancellation of reflexive saccades in the anti-saccade eye movement task. The aim of this study was to determine if the pattern of endophenotype abnormalities within individuals with schizophrenia differed from that within individuals with bipolar disorder. A second aim was to determine whether subjects with schizoaffective disorder, bipolar type, were neurophysiologically more similar to subjects with schizophrenia or subjects with bipolar disorder. Method: Endophenotypes were recorded for subjects diagnosed with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and schizoaffective disorder, bipolar type (N=18). Data from normal comparison subjects were used to establish normal performance. Results: Logistic regression determined that P50 ratio and frequency of leading saccades identified subjects with schizophrenia and bipolar disorder with a sensitivity of 95% and a specificity of 83%. The schizoaffective disorder group was split, with six subjects physiologically classified as schizophrenia-like and 12 subjects as bipolar-like. Those classified as schizophrenia-like were significantly younger at illness onset and had higher symptom ratings. Conclusion: A composite endophenotype of P50 ratio and frequency of leading saccades is consistent with the current clinical nosology of schizophrenia and bipolar disorder and parses patients with schizoaffective disorder, bipolar type, into two subgroups. C1 Hlth Sci Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Dept Psychiat, Denver, CO USA. Univ Colorado, Dept Prevent Med & Biometr, Denver, CO USA. Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. RP Martin, LF (reprint author), Univ Colorado, Dept Psychiat, 4200 E 9th Ave,C268-71, Denver, CO 80262 USA. EM laura.martin@uchsc.edu FU NIMH NIH HHS [MH 38321] NR 39 TC 38 Z9 39 U1 1 U2 6 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 DEC PY 2007 VL 164 IS 12 BP 1900 EP 1906 DI 10.1176/appi.ajp.2007.06010017 PG 7 WC Psychiatry SC Psychiatry GA 238VN UT WOS:000251476200022 PM 18056246 ER PT J AU Ibrahim, SA AF Ibrahim, S. A. TI The Veterans Health Administration: A domestic model for a national health care system? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID QUALITY-OF-CARE C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U, Pittsburgh, PA 15240 USA. EM said.ibrahim2@va.gov FU NIAMS NIH HHS [K24AR055259, K24 AR055259] NR 16 TC 5 Z9 5 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2007 VL 97 IS 12 BP 2124 EP 2126 DI 10.2105/AJPH.2007125575 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 237SE UT WOS:000251395900012 PM 17971535 ER PT J AU Volpp, KG AF Volpp, Kevin G. TI Designing a model health care system SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID QUALITY-OF-CARE; REGIONALIZATION; PERFORMANCE; OUTCOMES; PAY C1 Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Dept Med, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), Philadelphia Vet Affairs Med Ctr, Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2007 VL 97 IS 12 BP 2126 EP 2128 DI 10.2105/AJPH.2007.124461 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 237SE UT WOS:000251395900013 PM 17971536 ER PT J AU Good, CB Valentino, M AF Good, Chester B. Valentino, Michael TI Access to affordable medications: The department of veterans affairs pharmacy plan as a national model SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Ctr Healthcare Equ Res & Promot, Pittsburgh, PA 15206 USA. Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Washington, DC USA. RP Good, CB (reprint author), VA Pittsburgh Healthcare Syst, Ctr Healthcare Equ Res & Promot, 7180 High-Land Dr 151C-H, Pittsburgh, PA 15206 USA. EM chester.good@va.gov NR 5 TC 10 Z9 10 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2007 VL 97 IS 12 BP 2129 EP 2131 DI 10.2105/AJPH.2007.124008 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 237SE UT WOS:000251395900014 PM 17971537 ER PT J AU Yano, EM Simon, BF Lanto, AB Rubenstein, LV AF Yano, Elizabeth M. Simon, Barbara F. Lanto, Andrew B. Rubenstein, Lisa V. TI The evolution of changes in primary care delivery underlying the Veterans Health Administration's quality transformation SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ORGANIZATIONAL CHARACTERISTICS; MATRIX MANAGEMENT; AMBULATORY CARE; OF-CARE; SYSTEM; AFFAIRS; VA; NETWORKS; LESSONS AB Objectives. Suffering from waning demand, poor quality, and reform efforts enabling veterans to "vote with their feet" and leave, the Veterans Health Administration (VA) health care system transformed itself through a series of substantive changes. We examined the evolution of primary care changes underlying VA's transformation. Methods. We used 3 national organizational surveys from 1993, 1996, and 1999 that measured primary care organization, staffing, management, and resource sufficiency to evaluate changes in VA primary care delivery. Results. Only rudimentary primary care was in place in 1993. Primary care enrollment grew from 38% in 1993 to 45% in 1996, and to 95% in 1999 as VA adopted team structures and increased the assignment of patients to individual providers. Specialists initially staffed primary care until generalist physicians and nonphysican providers increased. Primary care-based quality improvement and authority expanded, and resource sufficiency (e.g., computers, space) grew. Provider notification of admissions and emergency department, urgent-care visit, and subspecialty-consult results increased nearly 5 times. Conclusions. Although VA's quality transformation had many underlying causes, investment in primary care development may have served as an essential substrate for many VA quality gains. C1 Vet Hlth Adm Greater Los Angeles HSR&D Ctr Excell, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 56 TC 26 Z9 26 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2007 VL 97 IS 12 BP 2151 EP 2159 DI 10.2105/AJPH.2007.115709 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 237SE UT WOS:000251395900019 PM 17971540 ER PT J AU Evgenov, OV Kohane, DS Bloch, KD Stasch, JP Volpato, GP Bellas, E Evgenov, NV Buys, ES Gnoth, MJ Graveline, AR Liu, R Hess, DR Langer, R Zapol, WM AF Evgenov, Oleg V. Kohane, Daniel S. Bloch, Kenneth D. Stasch, Johannes-Peter Volpato, Gian P. Bellas, Evangelia Evgenov, Natalia V. Buys, Emmanuel S. Gnoth, Mark J. Graveline, Amanda R. Liu, Rong Hess, Dean R. Langer, Robert Zapol, Warren M. TI Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pulmonary hypertension; soluble guanylate cyclase; BAY 41-2272; BAY 41-8543; BAY 58-2667 ID LARGE POROUS PARTICLES; NITRIC-OXIDE; AWAKE LAMBS; HYPERTENSION; INHIBITION; ACTIVATOR; BAY-41-2272; INHALATION; AUGMENTS; DELIVERY AB Rationale: Nitric oxide-independent agonists of soluble guanylate cyclase (sGC) have been developed. Objectives: We tested whether inhalation of novel dry-powder microparticle formulations containing sGC stimulators (BAY 41-2272, BAY 41-8543) or an sGC activator (BAY 58-2667) would produce selective pulmonary vasodilation in lambs with acute pulmonary hypertension. We also evaluated the combined administration of BAY 41-8543 microparticles and inhaled nitric oxide (NO). Finally, we examined whether inhaling BAY 58-2667 microparticles would produce pulmonary vasodilation when the response to NO is impaired. Methods: In awake, spontaneously breathing lambs instrumented with vascular catheters and a tracheostomy tube, U-46619 was infused intravenously to increase mean pulmonary arterial pressure to 35 mm Hg. Measurements and Main Results: Inhalation of microparticles composed of either BAY 41-2272, BAY 41-8543, or BAY 58-2667 and excipients (dipalmitoylphosphatidylcholine, albumin, lactose) produced dose-dependent pulmonary vasodilation and increased transpulmonary cGMP release without significant effect on mean arterial pressure. Inhalation of microparticles containing BAY 41-8543 or BAY 58-2667 increased systemic arterial oxygenation. The magnitude and duration of pulmonary vasodilation induced by NO were augmented after inhaling BAY 41-8543 microparticles. Intravenous administration of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which oxidizes the prosthetic heme group of sGC, markedly reduced the pulmonary vasodilator effect of NO. In contrast, pulmonary vasodilation and transpulmonary cGMP release induced by inhaling BAY 58-2667 microparticles were greatly enhanced after treatment with ODQ. Conclusions: Inhalation of microparticles containing agonists of sGC may provide an effective novel treatment for patients with pulmonary hypertension, particularly when responsiveness to NO is impaired by oxidation of sGC. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Childrens Hosp, Lab Biomat & Drug Delivery, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Bayer HealthCare, Pharma Res Ctr, Wuppertal, Germany. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM evgenov@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [HL42397, HL70896]; NIBIB NIH HHS [EB-00351] NR 29 TC 41 Z9 47 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2007 VL 176 IS 11 BP 1138 EP 1145 DI 10.1164/rccm.200707-1121OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 237OG UT WOS:000251384100012 PM 17872487 ER PT J AU Holdsworth, CH Badawi, RD Manola, JB Kijewski, MF Israel, DA Demetri, GD Van den Abbeele, AD AF Holdsworth, Clay H. Badawi, Ramsey D. Manola, Judith B. Kijewski, Marie F. Israel, David A. Demetri, George D. Van den Abbeele, Annick D. TI CT and PET: Early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; gastrointestinal stromal tumor; imatinib mesylate; oncologic imaging; PET ID POSITRON-EMISSION-TOMOGRAPHY; LUNG-CANCER; FDG-PET; THERAPY; ERLOTINIB; ONCOLOGY; SURVIVAL; CRITERIA; STI571; GIST AB OBJECTIVE. We report results from a pilot study aimed at optimizing the use of CT bidimensional measurements and F-18-FDG PET maximum standardized uptake values (SUVs(max)) for determining response to prolonged imatinib mesylate treatment in patients with advanced gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS. Sixty-three patients enrolled in a multicenter trial evaluating imatinib mesylate therapy for advanced GIST underwent FDG PET at baseline and 1 month after initiation of treatment. Of these 63 patients, 58 underwent concomitant CT. Time-to-treatment failure (TTF) was used as the outcome measure. Patients were followed up over a range of 23.7 to 37 months (median, 31.7 months). The predictive power of change in CT bidimensional measurements, change in PET SUVmax, and PET SUVmax at 1 month after initiation of treatment were determined, optimized, and compared. The effectiveness of combining metrics was also evaluated. RESULTS. Both a threshold PET SUVmax value of 2.5 at 1 month (p = 0.04) and the European Organization for Research and Treatment of Cancer (EORTC) criteria for partial response on FDG PET (25% reduction in PET SUVmax) at 1 month (p = 0.004) were predictive of prolonged treatment success. The Southwest Oncology Group (SWOG) criteria for partial response (>= 50% reduction in CT bidimensional measurements) at 1 month were not predictive (p = 0.55) of TTF. Optimizing metrics improved results performance. An optimized PET SUVmax threshold of 3.4 (p = 0.00002), a reduction in the SUVmax of 40% (p = 0.002), and an optimized CT bidimensional measurement threshold-that is, no growth from baseline to 1 month (p = 0.00005)-outperformed the existing standards (i. e., EORTC and SWOG criteria). Combinations of metrics did not improve performance. CONCLUSION. The two best metrics were the optimized PET SUVmax threshold of 3.4 at 1 month (p = 0.00002) and the optimized CT bidimensional measurement threshold (no growth from baseline to 1 month, p = 0.00005) in this patient group. C1 Massachusetts Coll Pharm & Hlth Sci, Salem, NH 03079 USA. Dana Farber Canc Inst, Boston, MA USA. Univ Calif Davis, Sch Med, Sacramento, CA USA. Brigham & Womens Hosp, Boston, MA USA. RP Holdsworth, CH (reprint author), Massachusetts Coll Pharm & Hlth Sci, 4 Brook Rd, Unit 11, Salem, NH 03079 USA. EM clayholdsworth@yahoo.com FU NIBIB NIH HHS [R01 EB000802] NR 30 TC 88 Z9 90 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2007 VL 189 IS 6 BP W324 EP W330 DI 10.2214/AJR.07.2496 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234NY UT WOS:000251172000051 PM 18029844 ER PT J AU Khunamornpong, S Siriaunkgul, S Suprasert, P Pojehamarnwiputh, S Chiangmai, WN Young, RH AF Khunamornpong, Surapan Siriaunkgul, Sumalee Suprasert, Prapaporn Pojehamarnwiputh, Suivalee Chiangmai, Wittanee Na Young, Robert H. TI Intrahepatic cholangiocarcinoma metastatic to the ovary: A report of 16 cases of an underemphasized form of secondary tumor in the ovary that may mimic primary neoplasia SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; metastasis; cholangiocarcinoma; liver neoplasia ID MUCINOUS TUMORS; INTESTINAL-TYPE; CLINICOPATHOLOGICAL ANALYSIS; BORDERLINE TUMORS; KRUKENBERG TUMOR; DIFFERENTIAL-DIAGNOSIS; INTRABILIARY GROWTH; BILIARY-TRACT; CYTOKERATIN 7; CARCINOMAS AB The potential for adenocarcinoma metastatic to the ovary to mimic primary mucinous neoplasms is a well-known issue to surgical pathologists, most of the recent literature emphasizing pancreatic and various other origins for the ovarian metastases. Although an origin in the gallbladder or extrahepatic bile ducts is acknowledged for some cases little information exists on tumors originating within the intrahepatic bile ducts. Sixteen cases of this type were retrieved from the surgical pathology files of the Chiang Mai University Hospital between January 1992 and December 2006. The patients ranged from 38 to 74 years (mean 52). Thirteen presented with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The hepatic tumors were radiologically detected before the ovarian lesion in 2 cases. Hepatic and ovarian masses were simultaneously detected by preoperative radiologic studies or at exploratory laparotomy in 10 cases. In the remaining 4 cases, the hepatic lesions were detected postoperatively. There were a total of 26 metastatic ovarian lesions which included 22 clinically recognized ovarian masses (range 3 to 20cm, mean 11.8cm). Bilateral involvement was present in 10 cases (62%) and unilateral involvement in 6 (38%). The cut surfaces of the 22 grossly enlarged ovaries were predominantly solid in 5, solidcystic in 10, and multicystic in 7. Microscopically, surface implants were observed in 80% of tumors, multinodular growth in 48%, and infiltrative stromal invasion (including microinvasionlike foci as it would be applied if the tumors were primary) in 86%. The neoplastic epithelium typically formed glands that ranged from small to large and cystically dilated, but small clusters of cells and individual cells were also seen. The epithelium ranged from tall, columnar, and mucinous in appearance to cuboidal or flattened and nonspecific. The tumors most closely mimicked primary mucinous neoplasms although a resemblance to other mullerian neoplasms was also seen. Foci often mimicked mucinous borderline tumors of typical type or with intraepithelial carcinoma and benign-appearing mucinous epithelium was seen in 62% of tumors. Immunohistochemical studies in 15 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 5 cases. Intrahepatic cholangiocarcinoma should be included in the list of origins of possible ovarian metastatic tumors that mimic primary ovarian mucinous neoplasia, particularly in parts of the world where cholangiocarcinoma of the liver is relatively common. C1 [Khunamornpong, Surapan; Siriaunkgul, Sumalee] Chiang Mai Univ, Fac Med, Dept Pathol, Chiang Mai 50200, Thailand. [Suprasert, Prapaporn] Chiang Mai Univ, Dept Obstet & Gynecol, Chiang Mai 50200, Thailand. [Pojehamarnwiputh, Suivalee; Chiangmai, Wittanee Na] Chiang Mai Univ, Dept Radiol, Chiang Mai 50200, Thailand. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Lab, Boston, MA USA. RP Khunamornpong, S (reprint author), Chiang Mai Univ, Fac Med, Dept Pathol, Chiang Mai 50200, Thailand. EM skhunamo@mail.med.cmu.ac.th NR 37 TC 12 Z9 12 U1 0 U2 6 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 DEC PY 2007 VL 31 IS 12 BP 1788 EP 1799 DI 10.1097/PAS.0b013e3180674ded PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 241EA UT WOS:000251638500002 PM 18043033 ER PT J AU Colvin, RB AF Colvin, R. B. TI Getting out of flatland: Into the third dimension of microarrays SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID RENAL-ALLOGRAFTS; ACUTE REJECTION; REPRODUCIBILITY; BIOPSIES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu NR 10 TC 5 Z9 5 U1 0 U2 0 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 DEC PY 2007 VL 7 IS 12 BP 2650 EP 2651 DI 10.1111/j.1600-6143.2007.02024.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 226JK UT WOS:000250585100002 PM 17983388 ER PT J AU Fishman, JA Greenwald, MA Kuehnert, MJ AF Fishman, J. A. Greenwald, M. A. Kuehnert, M. J. TI Enhancing transplant safety: A new era in the microbiologic evaluation of organ donors ? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID WEST-NILE-VIRUS; RECIPIENTS; INFECTION; TRANSMISSION C1 Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. US FDA, CDR,Off Cellular Tissue & Gene Therapies, US Publ Hlth Serv,Div Human Tissues, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. CDC, Coordinating Ctr Infect Dis,US Publ Hlth Serv,CDR, Natl Ctr Preparedness Detect & Control Infect Dis, Div Healthcare Promot,Off Blood Organ & Other Tis, Atlanta, GA 30333 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. EM jfishman@partners.org NR 11 TC 20 Z9 21 U1 0 U2 0 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 DEC PY 2007 VL 7 IS 12 BP 2652 EP 2654 DI 10.1111/j.1600-6143.2007.02023.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 226JK UT WOS:000250585100003 PM 17983389 ER PT J AU Kitchens, WH Chase, CM Uehara, S Cornell, LD Colvin, RB Russell, PS Madsen, JC AF Kitchens, W. H. Chase, C. M. Uehara, S. Cornell, L. D. Colvin, R. B. Russell, P. S. Madsen, J. C. TI Macrophage depletion suppresses cardiac allograft vasculopathy in mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE cardiac allograft vasculopathy; heart; macrophage; mouse; transplant arteriopathy ID TRANSPLANTED MOUSE HEARTS; CHRONIC REJECTION; CORONARY ATHEROSCLEROSIS; NEOINTIMAL FORMATION; IMMUNOLOGICAL BASIS; INTERFERON-GAMMA; GROWTH-FACTOR; UP-REGULATION; RAT; ACTIVATION AB Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 x BALB/c)F-1 recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30-80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02115 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL071932] NR 49 TC 45 Z9 47 U1 1 U2 4 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 DEC PY 2007 VL 7 IS 12 BP 2675 EP 2682 DI 10.1111/j.1600-6143.2007.01997.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 226JK UT WOS:000250585100007 PM 17924996 ER PT J AU Saidi, RF Elias, N Kawai, T Hertl, M Farrell, ML Goes, N Wong, W Hartono, C Fishman, JA Kotton, CN Tolkoff-Rubin, N Delmonico, FL Cosimi, AB Ko, DSC AF Saidi, R. F. Elias, N. Kawai, T. Hertl, M. Farrell, M.-L. Goes, N. Wong, W. Hartono, C. Fishman, J. A. Kotton, C. N. Tolkoff-Rubin, N. Delmonico, F. L. Cosimi, A. B. Ko, D. S. C. TI Outcome of kidney transplantation using expanded criteria donors and donation after cardiac death kidneys: Realities and costs SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article; Proceedings Paper CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA DE financial analysis; kidney transplantation; outcomes; resource utilization ID HEART-BEATING DONORS; RENAL-TRANSPLANTATION; ORGAN PROCUREMENT; SHORT-TERM; EXPERIENCE; RECIPIENTS; SURVIVAL AB Expanded criteria donors (ECDs) and donation after cardiac death (DCD) provide more kidneys in the donor pool. However, the financial impact and the long-term benefits of these kidneys have been questioned. From 1998 to 2005, we performed 271 deceased donor kidney transplants into adult recipients. There were 163 (60.1%) SCDs, 44 (16.2%) ECDs, 53 (19.6%) DCDs and 11 (4.1%) ECD/DCDs. The mean follow-up was 50 months. ECD and DCD kidneys had a significantly higher incidence of delayed graft function, longer time to reach serum creatinine below 3 (mg/dL), longer length of stay and more readmissions compared to SCDs. The hospital charge was also higher for ECD, ECD/DCD and DCD kidneys compared to SCDs, primarily due to the longer length of stay and increased requirement for dialysis ($70 030, $72 438, $72 789 and $47 462, respectively, p < 0.001). Early graft survival rates were comparable among all groups. However, after a mean follow-up of 50 months, graft survival was significantly less in the ECD group compared to other groups. Although our observations support the utilization of ECD and DCD kidneys, these transplants are associated with increased costs and resource utilization. Revised reimbursement guidelines will be required for centers that utilize these organs. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. RP Ko, DSC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. EM ko.dicken@mgh.harvard.edu NR 27 TC 92 Z9 93 U1 0 U2 2 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 DEC PY 2007 VL 7 IS 12 BP 2769 EP 2774 DI 10.1111/j.1600-6143.2007.01993.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 226JK UT WOS:000250585100018 PM 17927805 ER PT J AU Taktak, S Sosnovik, D Cima, MJ Weissfeder, R Josephson, L AF Taktak, Sonia Sosnovik, David Cima, Michael J. Weissfeder, Ralph Josephson, Lee TI Multiparameter magnetic relaxation switch assays SO ANALYTICAL CHEMISTRY LA English DT Article ID IRON-OXIDE NANOPARTICLES; MRI CONTRAST AGENTS; TRANSVERSE RELAXATION; MOLECULAR-INTERACTIONS; SUSCEPTIBILITY; PROBES; NANOSENSORS; RELAXIVITY; PARTICLES; MEDIA AB Magnetic nanoparticles (NPs) can serve as magnetic relaxation switches (MRSVs), switching from a dispersed to a clustered state, or the reverse, due to the presence of molecular targets, with changes in the spin-spin relaxation time of water (T-2). Biotinylated NP probes reacted with an avidin molecular target to form stable NP clusters, which permitted several NMR parameters to be measured as a function of cluster size. Associated with avidin-induced NP cluster formation was an increase in the spin-spin relation rate (1/T-2), while the spin-lattice relaxation rate (1/T-1)was unaffected. On the basis of the selective effects of NP cluster formation on T-2, we developed a T-1/T-2 interrogation method where NP probe concentration and avidin analyte were unknown and both were determined. A third NMR parameter examined was the replication of T-2 measurements, which were used to rapidly determine whether the ratio of avidin to biotinylated NP was optimal or whether additional biotinylated NP was needed. The T-1/T-2 and T-2 replication interrogation methods illustrate how MRSw assays can employ multiple parameters, instead of relying only on T-2, to obtain information about the reaction of NPs with molecular targets. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA 02129 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. T2 Biosyst Inc, Cambridge, MA 02141 USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. EM josephso@helix.mgll.harvard.edu FU NIBIB NIH HHS [R01-EB004626] NR 30 TC 47 Z9 48 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 1 PY 2007 VL 79 IS 23 BP 8863 EP 8869 DI 10.1021/ac701976p PG 7 WC Chemistry, Analytical SC Chemistry GA 236OH UT WOS:000251311900012 PM 17983206 ER PT J AU Liu, SS Brown, EN AF Liu, Spencer S. Brown, Emory N. TI Will seeing become believing? SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID MECHANISMS; SOLDIERS; INJURY; PAIN C1 Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA. Cornell Univ, Coll Med, New York, NY USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, MIT, Dept Brain & Cognit Sci, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Liu, SS (reprint author), Hosp Special Surg, Dept Anesthesiol, 535 E 70th St, New York, NY 10021 USA. EM liusp@hss.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2007 VL 105 IS 6 BP 1526 EP 1527 DI 10.1213/01.ane.0000295853.53423.44 PG 2 WC Anesthesiology SC Anesthesiology GA 236AC UT WOS:000251274400002 PM 18042841 ER PT J AU Singla, A Stojanovic, MP Chen, L Mao, J AF Singla, Aneesh Stojanovic, Milan P. Chen, Lucy Mao, Jianren TI A differential diagnosis of hyperalgesia, toxicity, and withdrawal from intrathecal morphine infusion SO ANESTHESIA AND ANALGESIA LA English DT Review ID ABNORMAL PAIN SENSITIVITY; TOLERANCE; THERAPY; RATS; SYMPTOMS AB Opioid-induced hyperalgesia, toxicity, and withdrawal are phenomena that may occur with intrathecal opioid infusion. We present a case in which a patient received intrathecal morphine infusion, and then experienced a clinical course that may have involved hyperalgesia, toxicity, and/or withdrawal. The possible differential diagnosis of opioid-induced hyperalgesia, toxicity, and withdrawal, and its implications in clinical pain management, are discussed. This report demonstrates the complexity of treating patients with long-term continuous intrathecal opioids when modest adjustment of the intrathecal cocktail results in a paradoxical clinical course. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02138 USA. Harvard Univ, Sch Med, MGH Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02138 USA. Harvard Univ, Sch Med, MGH Ctr Translat Pain Res, Dept Anesthesia & Crit Care, Boston, MA 02138 USA. RP Singla, A (reprint author), Dept Anesthesia & Crit Care, 35 Fay St, e-504, Boston, MA 02118 USA. EM asingla@partners.org NR 20 TC 15 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2007 VL 105 IS 6 BP 1816 EP 1819 DI 10.1213/01.ane.0000290338.39037.38 PG 4 WC Anesthesiology SC Anesthesiology GA 236AC UT WOS:000251274400048 PM 18042887 ER PT J AU Siegel, SM Lee, JW Oaklander, AL AF Siegel, Sandra M. Lee, Jeung W. Oaklander, Anne Louise TI Needlestick distal nerve injury in rats models symptoms of complex regional pain syndrome SO ANESTHESIA AND ANALGESIA LA English DT Article ID REFLEX SYMPATHETIC DYSTROPHY; SYNDROME-TYPE-I; NEUROPATHIC PAIN; PERIPHERAL MONONEUROPATHY; POSTHERPETIC NEURALGIA; ANIMAL-MODEL; SKIN BIOPSY; DISORDERS; DEGENERATION; HYPERALGESIA AB BACKGROUND: Complex Regional Pain Syndrome (CRPS)-I consists of chronic limb pain and dysautonomia triggered by traumas that sometime seem too trivial to be causative. Several pathological studies have identified minor distal nerve injuries (DNIs) in CRPS-1 patients, but retrospective studies cannot establish causality. Therefore, we, prospectively investigated whether DNIs are sufficient to cause CRPS-like abnormalities in animals. We used needlestick, a cause of human CRPS, to evaluate lesion-size effects. METHODS: Left tibial nerves of male Sprague-Dawley rats were transfixed once by 30G, 22G, or 18G needles. Unoperated and sham-operated rats provided controls. Hindpaw sensory function, edema, and posture were measured. RESULTS: At Day-7 postoperatively, thresholds for ipsilateral-hindpaw withdrawal from Semmes-Weinstein monofilaments were reduced by >= 51% in 0% of sham-operated controls; 67% of rats that received 18G-DNI, 88% that received 22G-DNI, and 89% that received 30G-DNI Fifty-seven percent of all DNI rats had contralateral hindpaw "mirror" changes. The prevalence and severity of allodynia appeared independent of lesion size. Hyperalgesic responses to cold and pinprick applied to the plantar hindpaw were less common and were ipsilesional only, as was neurogenic hindpaw edema. Ipsilesional-only, tonic, dystonic-like hindpaw postures were evident in 42% of 18G-DNI, 6% of 22G-DNI, and no 30G-DNI or sham-operated control rats. The prevalence of postural abnormalities correlated with needle diameter (P = 0.001). Counting protein gene product 9.5-immunolabeled axons in skin biopsies from rats' ipsilesional hindpaws demonstrated mean reductions of 0% after 30G-needlestick, 15% after 22G-needlestick, and 26% after 18G-needlestick, which closely reproduces the 29% mean epidermal neurite losses of CRPS-l patients. CONCLUSIONS: Needlestick DNI models several clinical and pathological features of human CRPS and provides direct prospective evidence that even minor DNI can cause CRPS-like abnormalities in rats. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Anesthesiol & Pathol, Boston, MA USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 275 Charles St Warren 310, Boston, MA 02114 USA. EM aoaklander@partners.org FU NINDS NIH HHS [R01NS42866] NR 42 TC 29 Z9 29 U1 1 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 DEC PY 2007 VL 105 IS 6 BP 1820 EP 1829 DI 10.1213/01.ane.0000295234.21892.bc PG 10 WC Anesthesiology SC Anesthesiology GA 236AC UT WOS:000251274400049 PM 18042888 ER PT J AU Harris, KC Rathmell, JP AF Harris, Kenneth C. Rathmell, James P. TI Forward-deployed anesthesiologists and pain treatment in combat support hospitals - Making decisions about deployment of anesthesiologists in support of the Global War on Terrorism SO ANESTHESIOLOGY LA English DT Editorial Material ID RISK-FACTORS C1 USA, Med Corps, Ft Sam Houston, TX 78234 USA. Massachusetts Gen Hosp, Massachusetts Gen Hosp Pain Ctr, Dept Anesthesia & Crit Care, Harvard Med Sch, Boston, MA USA. RP Harris, KC (reprint author), USA, Med Corps, Ft Sam Houston, TX 78234 USA. EM jrathmell@partners.org NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2007 VL 107 IS 6 BP 872 EP 874 PG 3 WC Anesthesiology SC Anesthesiology GA 236AM UT WOS:000251275400004 PM 18043054 ER PT J AU Macdonald, GJ Wise, TH Sluss, PM Ford, JJ AF Macdonald, G. J. Wise, T. H. Sluss, P. M. Ford, J. J. TI Breed differences in clearance of porcine FSH in hypophysectomized rats SO ANIMAL REPRODUCTION SCIENCE LA English DT Article DE swine; porcine follicle-stimulating hormone; assays; testosterone ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; CHINESE MEISHAN; IN-VITRO; PITUITARY; PROLACTIN; HETEROGENEITY; CASTRATION; SECRETION; ISOFORMS AB Extracts of anterior pituitary (AP) glands were infused i.v. into hypophysectomized male rats followed by sequential sampling of blood for 120 min. Determination of follicle-stimulating hormone (FSH) concentrations established that FSH from Chinese Meishan males decreased in the circulation of rats more slowly than FSH in extracts of AP from crossbred occidental pigs (P < 0.003). Additionally, FSH from AP extracts of castrated males disappeared somewhat more slowly (P < (1.06) than FSH from extracts of boars. Evaluation of FSH by bioassay and radioimmunoassay yielded similar concentrations in AP from Meishan and crossbred boars. Serum testosterone concentrations increased with time through 90 min after infusion of AP, but the rate of increase of testosterone was not related to amount of luteinizing hormone (LH) that was administered indicating LH receptor saturation. Unexpectedly, the rate of increase in testosterone was more rapid with AP extracts from boars than with extracts from castrated males. Observations from the current study imply structural alterations of FSH in the AP of Meishan males relative to crossbred males allowing sustained concentrations in the circulation, and this FSH possesses similar activation of the FSH receptor. The amount of LH in the AP extracts saturated the LH receptors of the hypophysectomized male rats, but some factor in extracts of boars differed from those of castrated males. Published by Elsevier B.V. C1 USDA ARS, Meat Anim Res Ctr, Clay Ctr, NE 68933 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet & Gynecol, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Ford, JJ (reprint author), USDA ARS, Meat Anim Res Ctr, Clay Ctr, NE 68933 USA. EM joe.ford@ars.usda.gov NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4320 J9 ANIM REPROD SCI JI Anim. Reprod. Sci. PD DEC PY 2007 VL 102 IS 3-4 BP 328 EP 334 DI 10.1016/j.anireprosci.2007.03.008 PG 7 WC Agriculture, Dairy & Animal Science; Reproductive Biology SC Agriculture; Reproductive Biology GA 229KP UT WOS:000250802100016 PM 17418509 ER PT J AU Hamilos, DL D'Urzo, A Levy, RJ Marcus, M Tripp, K Parsey, M Baumgartner, RA McVicar, WK AF Hamilos, Daniel L. D'Urzo, Anthony Levy, Robin J. Marcus, Michael Tripp, Kenneth Parsey, Merdad Baumgartner, Rudolf A. McVicar, William K. TI Long-term safety study of levalbuterol administered via metered-dose inhaler in patients with asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID AIRWAY SMOOTH-MUSCLE; (S)-ALBUTEROL INCREASES; PEDIATRIC-PATIENTS; RACEMIC ALBUTEROL; BETA-AGONISTS; S-SALBUTAMOL; PHARMACOKINETICS; ENANTIOMERS; CHILDREN; CELLS AB Background: Previous studies have raised concerns regarding the safety of regular use of beta(2)-agonists for treating asthma. Few studies have explored the safety of at least 1 year of use of racemic albuterol, and none have examined long-term dosing of levalbuterol. Objective: To examine the long-term safety of levalbuterol hydrofluoroalkane (HFA) vs racemic albuterol HFA administered via metered-dose inhaler (MDI) in patients with stable asthma. Methods: Patients with mild to moderate asthma (mean forced expiratory volume in 1 second [FEV1], 68.3% of predicted) 12 years or older participated in a multicenter, parallel-group, open-label study. Patients were randomized to levalbuterol HFA MDI (90 mu g: 2 actuations of 45 mu g; n = 496) or racemic albuterol HFA MDI (180 mu g; 2 actuations of 90 mu g; n = 250) for 52 weeks of 4 times daily dosing. The primary end point was the incidence of postrandomization adverse events. Asthma exacerbations and pulmonary parameters were also assessed. Results: The overall incidence of adverse events was similar for levalbuterol (72.0%) and racemic albuterol (76.8%). Rates of P-mediated adverse events, serious adverse events, and discontinuations because of adverse events were low (< 15%) and were comparable between groups. Rates of asthma adverse events for levalbuterol and racemic albuterol were 18.3% and 19.6%, respectively. Mean percentage of predicted FEV1 improved after dosing and was stable for both groups. Conclusion: In this trial, up to 52 weeks of regular use of levalbuterol HFA MDI or racemic albuterol HFA MDI was well tolerated. and no deterioration of lung function was detected during the study period. C1 [Tripp, Kenneth; Parsey, Merdad; Baumgartner, Rudolf A.; McVicar, William K.] Sepracor Inc, Marlborough, MA 01752 USA. [Hamilos, Daniel L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [D'Urzo, Anthony] Primary Care Lung Clin, Toronto, ON, Canada. [Levy, Robin J.] Family Allergy & Asthma Ctr, Atlanta, GA USA. RP McVicar, WK (reprint author), Sepracor Inc, 84 Waterford dr, Marlborough, MA 01752 USA. EM william.mcvicar@sepracor.com NR 44 TC 5 Z9 5 U1 0 U2 0 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 DEC PY 2007 VL 99 IS 6 BP 540 EP 548 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 243UO UT WOS:000251823000012 PM 18219836 ER PT J AU Albers, AB Siegel, MB Cheng, DM Lois, B Rigotti, NA AF Albers, Alison B. Siegel, Michael B. Cheng, Debbie M. Lois, Biener Rigotti, Nancy A. TI THE EFFECT OF HOUSEHOLD SMOKING BANS ON ANTI-SMOKING ATTITUDES: A COHORT STUDY OF ADOLESCENTS WHO DO AND DO NOT LIVE WITH SMOKERS IN THE HOME SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Lois, Biener] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. EM aalbers@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S15 EP S15 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300055 ER PT J AU Bennett, GG Marquez, DX McNeill, LH Arredondo, EM AF Bennett, Gary G. Marquez, David X. McNeill, Lorna H. Arredondo, Elva M. TI MULTILEVEL APPROACHES TO UNDERSTANDING PHYSICAL ACTIVITY AMONG RACIAL/ETHNIC MINORITY POPULATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Marquez, David X.] Univ Massachusetts, Amherst, MA 01003 USA. [Bennett, Gary G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arredondo, Elva M.] San Diego State Univ, San Diego, CA 92182 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S216 EP S216 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300845 ER PT J AU Berg, CJ Snyder, CR Hamilton, N AF Berg, Carla J. Snyder, C. R. Hamilton, Nancy TI THE EFFECTIVENESS OF A HOPE INTERVENTION IN COPING WITH COLD PRESSOR PAIN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Berg, Carla J.; Snyder, C. R.; Hamilton, Nancy] Univ Kansas, Lawrence, KS 66045 USA. [Berg, Carla J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cjberg@partners.org NR 0 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S102 EP S102 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300400 ER PT J AU Bober, SL Recklitis, C Diller, L AF Bober, Sharon L. Recklitis, Christopher Diller, Lisa TI RE-ENGAGING THE DISCONNECTED: INTERVENTION WITH LONG-TERM FEMALE HODGKINS' SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bober, Sharon L.; Recklitis, Christopher; Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. EM sharon_bober@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S90 EP S90 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300351 ER PT J AU Boudreaux, ED Baumann, B Perry, J Marks, D Francies, S Velazques, M Reinglass, A Camargo, C Ziedonis, D AF Boudreaux, Edwin D. Baumann, B. Perry, J. Marks, D. Francies, S. Velazques, M. Reinglass, A. Camargo, C. Ziedonis, D. TI EMERGENCY DEPARTMENT INITIATED TREATMENTS FOR TOBACCO SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Boudreaux, Edwin D.; Baumann, B.; Perry, J.; Marks, D.; Francies, S.; Velazques, M.; Reinglass, A.; Ziedonis, D.] UMDNJ, RWJMS, Camden, NJ USA. [Camargo, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM boudreaux-edwin@cooperhealth.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S98 EP S98 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300383 ER PT J AU Knight, SJ Latini, DM Sands, LP Chang, CH AF Knight, Sara J. Latini, David M. Sands, Laura P. Chang, Chih-Hung TI PATIENT VALUES AND PREFERENCES FOR CARE: METHODS FOR IMPROVING MEASURES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Knight, Sara J.] San Francisco VA Med Ctr, Hlth Serv Res & Dev, San Francisco, CA 94121 USA. [Latini, David M.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. [Chang, Chih-Hung] Northwestern Univ, Feinberg Sch Med, Buehler Ctr Aging Hlth & Soc, Chicago, IL 60611 USA. [Knight, Sara J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Latini, David M.] Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. [Latini, David M.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. EM sara.knight@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S1 EP S1 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300003 ER PT J AU Lyle, J Tomcho, TJ Juryea, B Sayers, SL AF Lyle, Jennifer Tomcho, Thomas J. Juryea, Bambi Sayers, Steven L. TI RCTS OF TELEPHONE INTERVENTIONS FOR CANCER: META-ANALYSIS OF PSYCHOLOGICAL OUTCOMES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Lyle, Jennifer; Tomcho, Thomas J.; Juryea, Bambi; Sayers, Steven L.] Philadelphia VA Med Ctr, Philadelphia, PA USA. EM jenniferlyle@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S172 EP S172 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300669 ER PT J AU Manne, S Chung, D Vig, H Cabral, M Driesbaugh, J Shannon, K Meropol, N AF Manne, Sharon Chung, Daniel Vig, Hetal Cabral, Melissa Driesbaugh, Jason Shannon, Kristen Meropol, Neal TI KNOWLEDGE AND ATTITUDES ABOUT MICROSATELLITE INSTABILITY TESTING AMONG INDIVIDUALS AT RISK FOR HNPCC SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Manne, Sharon; Vig, Hetal; Cabral, Melissa; Driesbaugh, Jason; Meropol, Neal] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chung, Daniel; Shannon, Kristen] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Sharon.manne@fccc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S99 EP S99 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300386 ER PT J AU Park, ER Bober, S AF Park, Elyse R. Bober, Sharon TI QUALITATIVE RESEARCH FOR BEHAVIORAL MEDICINE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Park, Elyse R.] MGH, Boston, MA 02114 USA. [Bober, Sharon] DFCI, Boston, MA USA. EM epark@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S2 EP S2 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300007 ER PT J AU Purnell, J Andersen, B AF Purnell, Jason Andersen, Barbara TI TESTING A SOCIOCULTURAL MODEL OF COLORECTAL CANCER SCREENING AMONG AFRICAN AMERICANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Purnell, Jason; Andersen, Barbara] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Purnell, Jason] Ohio State Univ, Columbus, OH 43210 USA. EM Jason.Purnell@va.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S84 EP S84 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300328 ER PT J AU Ramanadhan, S Bond, K Earle, C Schneider, E Viswanath, K AF Ramanadhan, Shoba Bond, Kathleen Earle, Craig Schneider, Eric Viswanath, K. TI REDEFINING INFORMATION SEEKING AMONG CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ramanadhan, Shoba; Schneider, Eric; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ramanadhan, Shoba; Bond, Kathleen; Earle, Craig; Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM sramanad@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S11 EP S11 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300040 ER PT J AU Ritholz, M Smaldone, A Lee, J Atakov-Castillo, A Wolpert, H Weinger, K AF Ritholz, Marilyn Smaldone, Arlene Lee, Jarim Atakov-Castillo, Astrid Wolpert, Howard Weinger, Katie TI PERCEPTIONS OF PSYCHOSOCIAL FACTORS AND THE INSULIN PUMP SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ritholz, Marilyn; Lee, Jarim; Atakov-Castillo, Astrid; Wolpert, Howard; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, Marilyn; Wolpert, Howard; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Smaldone, Arlene] Columbia Univ, New York, NY USA. EM katie.weinger@joslin.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S177 EP S177 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300690 ER PT J AU Tercyak, KP Patenaude, AF Peshkin, B DeMarco, T Schneider, K Schwartz, M Garber, J Valdimarsdottir, H AF Tercyak, Kenneth P. Patenaude, Andrea F. Peshkin, Beth DeMarco, Tiffani Schneider, Katherine Schwartz, Marc Garber, Judy Valdimarsdottir, Heiddis TI CANCER GENETIC COMMUNICATION IN FAMILIES: A HEURISTIC MODEL OF PARENT-CHILD TRANSACTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tercyak, Kenneth P.; Peshkin, Beth; DeMarco, Tiffani; Schwartz, Marc] Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Patenaude, Andrea F.; Schneider, Katherine; Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Valdimarsdottir, Heiddis] Ruttenberg Canc Ctr, New York, NY USA. EM tercyakk@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S110 EP S110 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300431 ER PT J AU Tercyak, KP DeMarco, T Patenaude, AF Peshkin, B Schneider, K Schwartz, M Garber, J Valdimarsdottir, H AF Tercyak, Kenneth P. DeMarco, Tiffani Patenaude, Andrea F. Peshkin, Beth Schneider, Katherine Schwartz, Marc Garber, Judy Valdimarsdottir, Heiddis TI INFORMATION NEEDS OF MOTHERS ABOUT COMMUNICATING BRCA1/2 TEST RESULTS TO CHILDREN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tercyak, Kenneth P.; DeMarco, Tiffani; Peshkin, Beth; Schwartz, Marc] Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Patenaude, Andrea F.; Schneider, Katherine; Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Valdimarsdottir, Heiddis] Ruttenberg Canc Ctr, New York, NY USA. EM tercyakk@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300248 ER PT J AU Winzer, J Hoogenboom, W Sitnikov, L Lo, S Weinstein, C Ganda, O Caballero, E Weinger, K AF Winzer, Jocelyn Hoogenboom, Wouter Sitnikov, Lilya Lo, Soda Weinstein, Cheryl Ganda, Om Caballero, Enrique Weinger, Katie TI ORGANIZATIONAL ABILITY AND DIABETES SELF-CARE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Winzer, Jocelyn; Hoogenboom, Wouter; Sitnikov, Lilya; Lo, Soda; Ganda, Om; Caballero, Enrique; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weinstein, Cheryl; Ganda, Om; Caballero, Enrique; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Hoogenboom, Wouter] Maastricht Univ, Maastricht, Netherlands. [Winzer, Jocelyn] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S86 EP S86 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300336 ER PT J AU Sun, C Jain, RK Munn, LL AF Sun, Chenghai Jain, Rakesh K. Munn, Lance L. TI Non-uniform plasma leakage affects local hematocrit and blood flow: Implications for inflammation and tumor perfusion SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE blood rheology; vessel leak; apparent viscosity; Lattice Boltzmann ID ENDOTHELIAL GROWTH-FACTOR; LATTICE BOLTZMANN ANALYSIS; INTERSTITIAL FLUID PRESSURE; VASCULAR-PERMEABILITY; ANTIANGIOGENIC THERAPY; MICROVASCULAR PERMEABILITY; POSTCAPILLARY EXPANSIONS; ERYTHROCYTE AGGREGATION; VISCOUS RESISTANCE; RECTAL-CANCER AB Vessel leakiness is a hallmark of inflammation and cancer. In inflammation, plasma extravasation and leukocyte adhesion occur in a coordinated manner to enable the immune response, but also to maintain tissue perfusion. In tumors, similar mechanisms operate, but they are not well regulated. Therefore, blood perfusion in tumors is non-uniform, and delivery of blood-borne therapeutics is difficult. In order to analyze the interplay among plasma leakage, blood viscosity, and vessel geometry, we developed a mathematical model that explicitly includes blood cells, vessel branching, and focal leakage. The results show that local hemoconcentration due to plasma leakage can greatly increase the flow resistance in individual vascular segments, diverting flow to other regions. Similarly, leukocyte rolling can increase flow resistance by partially blocking flow. Vessel dilation can counter these effects, and likely occurs in inflammation to maintain blood flow. These results suggest that potential strategies for improving perfusion through tumor networks include (i) eliminating non-uniform plasma leakage, (ii) inhibiting leukocyte interactions, and (iii) preventing RBC aggregation in sluggish vessels. Normalization of tumor vessels by anti-angiogenic therapy may improve tumor perfusion via the first two mechanisms. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Exa Corp, Burlington, MA USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124, P01 CA080124-080006]; NHLBI NIH HHS [R01 HL064240, R01 HL064240-03, R01 HL064240-04, R01 HL064240-05, R01 HL064240-06, R01 HL064240-07, R01 HL064240-08, R01 HL64240] NR 50 TC 18 Z9 19 U1 0 U2 4 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 DEC PY 2007 VL 35 IS 12 BP 2121 EP 2129 DI 10.1007/s10439-007-9377-8 PG 9 WC Engineering, Biomedical SC Engineering GA 231UZ UT WOS:000250976000009 PM 17846892 ER PT J AU Wu, D Yu, WH Kishikawa, H Folkerth, RD Iafrate, AJ Shen, YP Xin, WM Sims, K Hu, GF AF Wu, David Yu, Wenhao Kishikawa, Hiroko Folkerth, Rebecca D. Iafrate, A. John Shen, Yiping Xin, Winme Sims, Katherine Hu, Guo-Fu TI Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE MUTATIONS; ENDOTHELIAL-CELLS; RIBONUCLEOLYTIC ACTIVITY; MOTONEURON DEGENERATION; NUCLEAR TRANSLOCATION; ALS; VEGF; GENE; PROLIFERATION; DELIVERY AB Objective: Heterozygous missense mutations in the coding region of angiogenin (ANG), an angiogenic ribonuclease, have been reported in amyotrophic lateral sclerosis (ALS) patients. However, the role of ANG in motor neuron physiology and the functional consequences of these mutations are unknown. We searched for new mutations and sought to define the functional consequences of these mutations. Methods: We sequenced the coding region of ANG in an independent cohort of North American ALS patients. Identified ANG mutations were then characterized using functional assays of angiogenesis, ribonucleolysis, and nuclear translocation. We also examined expression of ANG in normal human fetal and adult spinal cords. Results: We identified four mutations in the coding region of ANG from 298 ALS patients. Three of these mutations are present in the mature protein. Among the four mutations, P(-4)S, S28N, and P112L are novel, and K17I has been reported previously. Functional assays show that these ANG mutations result in complete loss of function. The mutant ANG proteins are unable to induce angiogenesis because of a deficiency in ribonuclease activity, nuclear translocation, or both. As a correlate, we demonstrate strong ANG expression in both endothelial cells and motor neurons of normal human spinal cords from the developing fetus and adult. Interpretation: We provide the first evidence that ANG mutations, identified in ALS patients, are associated with functional loss of ANG activity. Moreover, strong ANG expression, in normal human fetal and adult spinal cord neurons and endothelial cells, confirms the plausibility of ANG dysfunction being relevant to the pathogenesis of ALS. C1 [Shen, Yiping; Xin, Winme; Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Shen, Yiping; Xin, Winme; Sims, Katherine] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yu, Wenhao; Kishikawa, Hiroko; Hu, Guo-Fu] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wu, David; Folkerth, Rebecca D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sims, K (reprint author), Massachusetts Gen Hosp, Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA. EM ksims@partners.org; guofu_hu@hms.harvard.edu FU NCI NIH HHS [R01 CA105241, R01 CA105241-03] NR 39 TC 97 Z9 108 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2007 VL 62 IS 6 BP 609 EP 617 DI 10.1002/ana.21221 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 248AM UT WOS:000252123700010 PM 17886298 ER PT J AU Broadhurst, MS Kobler, JB Burns, JA Anderson, RR Zeitels, SM AF Broadhurst, Matthew S. Kobler, James B. Burns, James A. Anderson, R. Rox Zeitels, Steven M. TI Chick chorioallantoic membrane as a model for simulating human true vocal folds SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE chorioallantoic membrane; KTP laser; larynx; laser; phonosurgery; pulsed dye laser; vocal cord; vocal fold ID LASER TREATMENT; PAPILLOMATOSIS; DYSPLASIA AB Objectives: Evolving photoangiolytic laser techniques for treating vocal fold lesions motivated the development of a model for research and surgical training. The chick chorioallantoic membrane (CAM), which is composed of a microvasculature suspended within the egg albumen, simulates the vocal fold microcirculation within the superficial lamina propria (SLP). To characterize this model, we compared measurements of vessel diameters to superficial vessels in human vocal folds. Methods: The diameters of first-, second-, and third-order CAM vessels were measured in fertilized chicken eggs. The superficial blood vessels of the human vocal fold were measured from intraoperative images. Results: According to the branching pattern, vessel segments were identified as first-, second-, or third-order, with average diameters of 0.035 mm (0.02 to 0.1 mm), 0.18 mm (0.12 to 0.41 mm), and 0.8 mm (0.6 to 0.98 mm), respectively. The total vessels measured included 362 first-order, 119 second-order, and 82 third-order vessels. In 10 adult human vocal folds, an average vessel diameter of 0.04 mm (0.015 to 0.1 mm) was observed in 50 vessels. Conclusions: The CAM microvasculature suspended in albumen provides a useful surgical model simulating the microcirculation within the SLP of the human vocal fold. Although first-order CAM vessels best approximate the size of normal vocal fold subepithelial vessels seen at surgery, second- and third-order vessels resemble the vascular abnormalities frequently encountered during microsurgery for phonotraumatic lesions. C1 [Broadhurst, Matthew S.; Kobler, James B.; Burns, James A.; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, Boston, MA 02114 USA. [Broadhurst, Matthew S.; Kobler, James B.; Burns, James A.; Zeitels, Steven M.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Boston, MA 02114 USA. [Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, Boston, MA 02114 USA. NR 15 TC 6 Z9 6 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2007 VL 116 IS 12 BP 917 EP 921 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 243VI UT WOS:000251825000010 PM 18217511 ER PT J AU Bilimoria, KY Stewart, AK Tomlinson, JS Gay, EG Ko, CY Talamonti, MS Bentrem, DJ AF Bilimoria, Karl Y. Stewart, Andrew K. Tomlinson, James S. Gay, E. Greer Ko, Clifford Y. Talamonti, Mark S. Bentrem, David J. TI Impact of adjuvant radiation on survival: A note of caution when using cancer registry data to evaluate adjuvant treatments SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE survival; radiation; chemotherapy; National Cancer Data Base; SEER; adjuvant therapy; chemoradiation ID COLORECTAL-CANCER; THERAPY; CHEMOTHERAPY; INFORMATION; CARCINOMA AB Background: With increasing frequency, studies using cancer registries have evaluated the treatment effect of adjuvant radiation; however, these analyses generally do not include chemotherapy treatment data. Our objective is to evaluate the potential impact the absence of adjuvant chemotherapy data has on the estimated survival benefit attributed to adjuvant radiation therapy. Methods: Using the National Cancer Data Base, patients were identified who underwent surgery for cancers that often require radiation therapy: breast, esophageal, gastric, pancreatic, and rectal cancer. Cox proportional hazards modeling with and without chemotherapy as a predictor variable was used to assess the impact of radiation therapy on 5-year survival. Results: From 1998 to 1999, 295,206 patients underwent surgical resection for one of five cancers. Chemotherapy administration ranged from 27.5% for gastric to 56.1% for rectal cancer. For cancers where chemotherapy affected survival, the impact of radiation therapy was overestimated in the multivariate model when chemotherapy was not included. For example, radiation treatment for rectal cancer was associated with a 31% decrease in the risk of death in the model that did not control for chemotherapy; however, the addition of chemotherapy to the model resulted in only a 14% decrease in the risk of death associated with receiving radiation therapy. Conclusions: For selected tumor sites, the administration of chemotherapy is not evenly distributed among patients receiving and not receiving radiation. Survival analyses that do not include chemotherapy administration overestimate the beneficial impact of radiation on survival. Evaluating the effect of radiation on survival retrospectively without adjusting for chemotherapy administration should be done cautiously. C1 Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. Amer Coll Surg, Canc Program, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. EM dbentrem@nmff.org NR 27 TC 7 Z9 7 U1 0 U2 4 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 DEC PY 2007 VL 14 IS 12 BP 3321 EP 3327 DI 10.1245/s10434-007-9576-4 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 231VE UT WOS:000250976500011 PM 17899285 ER PT J AU Javid, SH Carlson, JW Garber, JE Birdwell, RL Lester, S Lipsitz, S Golshan, M AF Javid, Sara H. Carlson, Joseph W. Garber, Judy E. Birdwell, Robyn L. Lester, Susan Lipsitz, Stuart Golshan, Mehra TI Breast MRI wire-guided excisional biopsy: Specimen size as compared to mammogram wire-guided excisional biopsy and implications for use SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast MRI; invasive breast cancer; wire localized biopsy ID PREOPERATIVE EVALUATION; CANCER; RESONANCE; LOCALIZATION; LESIONS; WOMEN; EXPERIENCE; DIAGNOSIS; RISK AB Background: Breast magnetic resonance imaging (MRI) has been implemented as a screening tool for early detection and as a diagnostic test in the management of breast cancer. Lesions identified by MRI but not amenable to conventional biopsy techniques require MRI wire-guided excisional biopsy (MRIbx). We hypothesized that more tissue would be resected with MRIbx compared to Mammobx. We also sought to evaluate factors that might predict the presence of breast cancer in patients undergoing MRIbx. Methods: We reviewed consecutive cases of breast MRIbx from 2004 to 2006 performed by seven surgeons. MRI was performed in patients with either a synchronous breast cancer or significant risk factors. Lesions visualized only by MRI underwent diagnostic MRIbx. The control group was comprised of consecutive cases that underwent diagnostic Mammobx during the same time period. The volumes of tissue resected, overall and by pathologic outcome, were compared. Results: Seventy-one patients, with a mean age of 48, underwent MRIbx. Eleven (15.5%) invasive breast cancers and eight cases (11.3%) of ductal carcinoma in situ (DCIS) were identified. The median volume of tissue resected was significantly greater than that in the Mammobx group (28.8 cm(3) vs 21.1 cm(3), respectively). DCIS-containing MRIbx specimens were significantly larger than benign or invasive cancer-containing specimens. There was no significant overall association between either the indication for MRIbx or the size of the MRI lesion and the frequency of cancer. Conclusions: In patients undergoing breast MRIbx, 27% were found to have DCIS or invasive breast cancer. MRIbx was associated with significantly larger specimen volumes than Mammobx. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org OI Carlson, Joseph/0000-0002-3006-4107 NR 20 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2007 VL 14 IS 12 BP 3352 EP 3358 DI 10.1245/s10434-007-9543-0 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 231VE UT WOS:000250976500015 PM 17849165 ER PT J AU Ito, H Hornick, JL Bertagnolli, MM George, S Morgan, JA Baldini, EH Wagner, AJ Demetri, GD Raut, CP AF Ito, Hiromichi Hornick, Jason L. Bertagnolli, Monica M. George, Suzanne Morgan, Jeffrey A. Baldini, Elizabeth H. Wagner, Andrew J. Demetri, George D. Raut, Chandrajit P. TI Leiomyosarcoma of the inferior vena cava: Survival after aggressive management SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol DE leiomyosarcoma; inferior vena cava; surgery; chemotherapy; radiation therapy ID SOFT-TISSUE SARCOMA; RETROPERITONEAL SARCOMA; PROGNOSIS AB Background: Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is exceedingly rare. The role of adjuvant therapy remains undefined. This study evaluated outcomes after aggressive management. Methods: Records on 20 patients undergoing surgery for IVC LMS between January 1990 and April 2006 were retrieved. Histology was confirmed upon re-review. Most patients received perioperative chemotherapy (CT), radiation therapy (RT), or both (CRT). Disease-free and overall survival (DFS, OS) rates were calculated using the Kaplan-Meier method. Results: Twenty patients (60% women, median age 57 years) with primary IVC LMS were treated with curative intent. Median follow-up was 41 months. All patients underwent resection of the primary tumor; one was found to have unresectable liver metastases. The IVC was managed with ligation (3), primary repair (12), or prosthetic graft (5). Additional organs were resected in 14 (70%) patients. Chemotherapy and/or RT were administered to 9 (45%) patients preoperatively (CT 2, RT 6, CRT 1) and 8 (40%) postoperatively (CT 4, RT 1, CRT 3). Median DFS was 21 months. Of 13 (68%) patients who developed recurrence, 4 underwent surgery, and 11 received CT. Median OS for 19 patients who underwent complete resection was 71 months. Tumor size was associated with disease recurrence (P = .004). No variables were prognostic for OS. Conclusions: Patients with IVC LMS treated with curative intent develop early recurrent disease. Nevertheless, long-term OS can be achieved even in the setting of metastatic disease. The independent impact of perioperative CT, RT, or CRT treatments cannot be adequately determined. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 13 TC 36 Z9 38 U1 0 U2 1 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 DEC PY 2007 VL 14 IS 12 BP 3534 EP 3541 DI 10.1245/s10434-007-9552-z PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 231VE UT WOS:000250976500037 PM 17896156 ER PT J AU Hill, CL Hunter, DJ Niu, J Clancy, M Guermazi, A Genant, H Gale, D Grainger, A Conaghan, P Felson, DT AF Hill, C. L. Hunter, D. J. Niu, J. Clancy, M. Guermazi, A. Genant, H. Gale, D. Grainger, A. Conaghan, P. Felson, D. T. TI Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; BONE-MARROW; DOUBLE-BLIND; INFLAMMATION; ASSOCIATION; PROGRESSION; MECHANISMS; ARTHRITIS; MEMBRANE; LESIONS AB Objective: To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis. Methods: Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging ( MRI), BMI and pain assessment ( VAS) over the last week. Synovitis was scored at 3 locations ( infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale ( 0-3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score ( 0-9). Results: We assessed 270 subjects whose mean ( SD) age was 66.7 ( 9.2) years, BMI 31.5 ( 5.7) kg/m(2); 42% were female. There was no correlation of baseline synovitis with baseline pain score ( r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain ( r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score ( 0-100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment. Conclusions: Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis ( OA) needs to consider treatment of synovitis. C1 Queen Elizabeth Hosp, Rheumatol Unit, Woodville, SA 5011, Australia. Synarc Inc, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Boston Healthcare Syst, Boston, MA USA. Leeds Teaching Hosp Trust & Leeds Primary Care Tr, Dept Radiol, Leeds, W Yorkshire, England. Leeds Teaching Hosp Trust & Leeds Primary Care Tr, Dept Rheumatol, Leeds, W Yorkshire, England. RP Felson, DT (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, A203,80 E Concord St, Boston, MA 02118 USA. EM dfelson@bu.edu RI Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Felson, David/0000-0002-2668-2447; Niu, Jingbo/0000-0002-6170-1965 FU NIAMS NIH HHS [AR47785, P60 AR047785] NR 23 TC 216 Z9 221 U1 1 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 2007 VL 66 IS 12 BP 1599 EP 1603 DI 10.1136/ard.2006.067470 PG 5 WC Rheumatology SC Rheumatology GA 230UW UT WOS:000250902600009 PM 17491096 ER PT J AU Dickerson, BC Sperling, RA Hyman, BT Albert, MS Blacker, D AF Dickerson, Bradford C. Sperling, Reisa A. Hyman, Bradley T. Albert, Marilyn S. Blacker, Deborah TI Clinical prediction of Alzheimer disease dementia across the spectrum of mild cognitive impairment SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC-CRITERIA; RATING-SCALE; DECLINE; INDIVIDUALS; POPULATION; INTERVIEW; DEFICITS; LOBE; MCI; AD AB Objective: To determine whether clinical assessment methods that grade the severity of impairments within the spectrum of mild cognitive impairment (MCI) can predict clinical course, particularly among very mildly impaired individuals who do not meet formal MCI criteria as implemented in clinical trials. Design: Cohort. Setting: Community volunteers. Participants: From a longitudinal study of normal (Clinical Dementia Rating [CDR]= 0; n=77) and mildly impaired (CDR=0.5; n=167) participants with 5 or more annual clinical assessments, baseline level of cognitive impairment in daily life was graded using CDR sum of boxes (CDR-SB) and level of cognitive performance impairment was graded using neuropsychological test scores. Main Outcome Measures: Five-year outcome measures included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical '' decline '' (CDR-SB increase >= 1.0). Logistic regression models were used to assess the ability of baseline measures to predict outcomes in the full sample and separately in the subjects who did not meet formal MCI criteria as implemented in a multicenter clinical trial (n= 125; '' very mild cognitive impairment '' [vMCI]). Results: The presence of both higher CDR-SB and lower verbal memory and executive function at baseline predicted greater likelihood of probable AD and decline. Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were intermediate between normal participants (0%, AD; 28%, decline) and participants with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was predicted by higher CDR-SB and lower executive function. Conclusions: Even in very mildly impaired individuals who do not meet strict MCI criteria as implemented in clinical trials, the degree of cognitive impairment in daily life and performance on neuropsychological testing predict likelihood of an AD diagnosis within 5 years. The clinical determination of relative severity of impairment along the spectrum of MCI may be valuable for trials of putative disease-modifying compounds, particularly as target populations are broadened to include less impaired individuals. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NIA NIH HHS [P01 AG004953, K23 AG022509, K23 AG022509-03, K23 AG022509-04, K23 AG022509-05, K23-AG22509, L30 AG022814, L30 AG022814-01, P01-AG04953, P50 AG005134, P50-AG05134, R01 AG029411, R01 AG029411-01A1, R01-AG029411]; NINDS NIH HHS [K23 NS002189] NR 51 TC 82 Z9 86 U1 1 U2 4 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 DEC PY 2007 VL 64 IS 12 BP 1443 EP 1450 DI 10.1001/archpsyc.64.12.1443 PG 8 WC Psychiatry SC Psychiatry GA 237LF UT WOS:000251374500014 PM 18056553 ER PT J AU Kumar, A Cannon, CR AF Kumar, Amit Cannon, Christopher R. TI The current role of statins in acute coronary syndrome SO ARCHIVES OF MEDICAL SCIENCE LA English DT Review DE ACS; intensive statin therapy; CRP; pleiotropic effects ID LOW-DENSITY-LIPOPROTEIN; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE ATORVASTATIN; RISK-ASSESSMENT STRATEGIES; RECURRENT ISCHEMIC EVENTS; REACTIVE PROTEIN-LEVELS; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; PROVE IT-TIMI-22; HEART-DISEASE AB Statins have long been known to be effective for primary and secondary prevention of coronary heart disease (CHD), and reduction of low density lipoprotein-cholesterol (LDC-C) levels over time was thought to be the mechanism by which statins exerted their clinical effectiveness. Data from recent large randomized trials have established the efficacy and safety of intensive statin therapy started early after ACS and have provided new insights into the mechanism of action of statins. While the early benefits appear to be related more to dose dependent LDL-C independent "pleiotropic" effects and reduction in C-reactive protein (CRP), which is an inflammatory biomarker, the long-term benefits are related to reductions in both LDL-C and CRP. The current state of evidence, based upon key trials of statins in ACS, supports a central role for statin therapy, in particular intensive statin therapy, in the management of patients with ACS. C1 [Kumar, Amit] UMass Marlborough Hlth Syst, Marlborough, MA USA. [Cannon, Christopher R.] Harvard Univ, Boston, MA 02115 USA. [Cannon, Christopher R.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Cannon, CR (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 33 TC 6 Z9 6 U1 0 U2 0 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1734-1922 J9 ARCH MED SCI JI Arch. Med. Sci. PD DEC PY 2007 VL 3 IS 4A SI SI BP S115 EP S125 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 280WE UT WOS:000254456500009 ER PT J AU Scarmeas, N Brandt, J Blacker, D Albert, M Hadjigeorgiou, G Dubois, B Devanand, D Honig, L Stern, Y AF Scarmeas, Nikolaos Brandt, Jason Blacker, Deborah Albert, Marilyn Hadjigeorgiou, Georgios Dubois, Bruno Devanand, Davangere Honig, Lawrence Stern, Yaakov TI Disruptive Behavior as a predictor in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; PSYCHIATRIC-SYMPTOMS; COGNITIVE DECLINE; PSYCHOPATHOLOGICAL FEATURES; PSYCHOLOGICAL SYMPTOMS; EXTRAPYRAMIDAL SIGNS; AGGRESSIVE-BEHAVIOR; MOTOR SIGNS; DEMENTIA; PROGRESSION AB Background: Disruptive behavior is common in Alzheimer disease (AD). There are conflicting reports regarding its ability to predict cognitive decline, functional decline, institutionalization, and mortality. Objective: To examine whether the presence of disruptive behavior has predictive value for important outcomes in AD. Design: Using the Columbia University Scale for Psychopathology in Alzheimer Disease (administered every 6 months, for a total of 3438 visit-assessments and an average of 6.9 per patient), the presence of disruptive behavior (wandering, verbal outbursts, physical threats/violence, agitation/restlessness, and sundowning) was extracted and examined as a time-dependent predictor in Cox models. The models controlled for the recruitment cohort, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and functional performance, and neuroleptic use. Setting: Five university-based AD centers in the United States and Europe (Predictors Study). Participants: Four hundred ninety-seven patients with early-stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry) who were recruited and who underwent semiannual follow-up for as long as 14 (mean, 4.4) years. Main Outcome Measures: Cognitive (Columbia Mini-Mental State Examination score, <= 20 of 57 [approximate Folstein Mini-Mental State Examination score, <= 10 of 30]) and functional ( Blessed Dementia Rating Scale score, parts I and II, >= 10) ratings, institutionalization equivalent index, and death. Results: At least 1 disruptive behavioral symptom was noted in 48% of patients at baseline and in 83% at any evaluation. Their presence was associated with increased risks of cognitive decline (hazard ratio 1.45 [95% confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17-2.36]), and institutionalization (1.47 [95% CI, 1.101.97]). Sundowning was associated with faster cognitive decline, wandering with faster functional decline and institutionalization, and agitation/restlessness with faster cognitive and functional decline. There was no association between disruptive behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). Conclusion: Disruptive behavior is very common in AD and predicts cognitive decline, functional decline, and institutionalization but not mortality. C1 [Scarmeas, Nikolaos; Devanand, Davangere; Honig, Lawrence; Stern, Yaakov] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain,Cognit, New York, NY 10032 USA. [Scarmeas, Nikolaos; Honig, Lawrence; Stern, Yaakov] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Devanand, Davangere; Stern, Yaakov] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Dept Behav Sci, Baltimore, MD USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Hadjigeorgiou, Georgios] Univ Thessaly, Dept Neurol, Larisa, Greece. [Dubois, Bruno] Hosp Salpetriere, Paris, France. RP Scarmeas, N (reprint author), Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain,Cognit, 622 W 168th St,PH 19th Floor, New York, NY 10032 USA. EM ns257@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [M01 RR000645, RR00645]; NIA NIH HHS [P50 AG08702, P50 AG008702, R01 AG007370, R01 AG007370-18, Z01 AG007370] NR 44 TC 64 Z9 66 U1 2 U2 4 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 DEC PY 2007 VL 64 IS 12 BP 1755 EP 1761 DI 10.1001/archneur.64.12.1755 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 239SP UT WOS:000251538300010 PM 18071039 ER PT J AU Van Cleave, J Heisler, M Devries, JM Joiner, TA Davries, MM AF Van Cleave, Jeanne Heisler, Michelle Devries, Jeffrey M. Joiner, Terence A. Davries, Matthew M. TI Discussion of illness during well-child care visits with parents of children with and without special health care needs SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PATIENTS EXPECTATIONS; PREVENTIVE SERVICES; DELIVERY; PATIENT AB Objectives: To compare parents of children with special health care needs (CSHCN) with other parents to determine parents' expectations and priorities for discussing concerns related to a child's acute or chronic illness at well-child care visits, the association of unmet expectations and priorities with satisfaction, and whether discussing illness displaces prevention topics. Design: Written, self-administered survey of parents at well-child care visits. Setting: Two community-based pediatric practices in suburban southeast Michigan. Participants: Five hundred parents with children aged 6 months to 12 years. Main Exposure: Having a special health care need. Main Outcome Measures: Expectations and priorities for discussing illness-related topics (chronic and acute illnesses, medications, specialist referrals, and effects of health on life overall), actual discussion regarding illness and preventive topics, and satisfaction. Results: Compared with parents of children without chronic conditions, parents of CSHCN were more likely to expect to discuss their child's illness (81% vs 92%, respectively; P < .001); 79% of parents of CSHCN ranked illness among their top 3 priorities (vs 53% of other parents [P < .001]). Parents of CSHCN reported discussing a mean of 3.2 illness topics, as compared with a mean of 2.2 illness topics for other parents (P < .001). Having more than 1 unmet expectation for discussing illness was associated with higher odds of lower satisfaction (for parents of CSHCN: odds ratio, 7.2; 95% confidence interval, 2.918.3; for other parents: odds ratio, 3.0; 95% confidence interval, 1.7-5.5). Discussing more illness topics was associated with discussing more preventive topics (P < .001). Conclusions: Discussing illness is frequently expected and highly prioritized at well-child care visits, particularly for parents of CSHCN. Unmet expectations are associated with lower satisfaction. Incorporating illness concerns at well-child care visits may improve chronic disease management. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Univ Michigan, Vet Affairs Ctr Practice Management & Outcomes Re, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Michigan Diabet Res & Training Ctr, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Michigan Diabet Res & Training Ctr, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Div Gen Pediat, Ann Arbor, MI USA. Univ Michigan, Child Hlth Evaluat & Res Unit, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI USA. Univ Michigan, Gerald R Fold Sch Publ Policy, Ann Arbor, MI USA. Childrens Hosp Michigan, Detroit, MI USA. RP Van Cleave, J (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Stanford St,Ste 901, Boston, MA 02114 USA. EM jvancleave@partners.org RI Heisler, Michele/B-5774-2015 OI Heisler, Michele/0000-0002-6889-2063 NR 22 TC 11 Z9 11 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 2007 VL 161 IS 12 BP 1170 EP 1175 DI 10.1001/archpedi.161.12.1170 PG 6 WC Pediatrics SC Pediatrics GA 237LE UT WOS:000251374400008 PM 18056562 ER PT J AU Gotsman, I Gupta, R Lichtman, AH AF Gotsman, Israel Gupta, Rajat Lichtman, Andrew H. TI The influence of the regulatory T lymphocytes on atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID CELLS; INFLAMMATION; TOLERANCE; SELF; MICE C1 Hadassah Univ Hosp, Inst Heart, IL-91120 Jerusalem, Israel. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lichtman, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, 77 Ave Louis Pasteur,NRB 752N, Boston, MA 02115 USA. EM alichtman@rics.bwh.harvard.edu OI Gotsman, Israel/0000-0001-9608-2298 NR 17 TC 29 Z9 33 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 DEC PY 2007 VL 27 IS 12 BP 2493 EP 2495 DI 10.1161/ATVBAHA.107.153064 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 234EK UT WOS:000251143300004 PM 17901372 ER PT J AU Kannian, P McHugh, G Johnson, BJB Bacon, RM Glickstein, LJ Steere, AC AF Kannian, Priya McHugh, Gail Johnson, Barbara J. B. Bacon, Rendi M. Glickstein, Lisa J. Steere, Allen C. TI Antibody responses to Borrelia burgdorfeti in patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic-treated lyme arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; SURFACE PROTEIN-A; ANTIGENIC VARIATION; PEPTIDE ANTIGENS; DISEASE; RECOMBINANT; VLSE; INFECTION; OSPA; SERODIAGNOSIS AB Objective. To compare the pattern of antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or nonantibiotic-treated Lyme arthritis as an indirect measure of spirochetal persistence or eradication. Methods. At least 3 serial serum samples from 41 patients with antibiotic- refractory arthritis and 23 patients with antibiotic-responsive arthritis, and samples from 10 non-antibiotic-treated, historical control patients were tested for IgG reactivity with B burgdorferi sonicate and 4 differentially expressed outer surface lipoproteins of the spirochete, by enzyme-linked immunosorbent assay. Results. Among non-antibiotic-treated patients, antibody titers to B burgdorferi antigens remained high throughout a 2-5-year period of arthritis. In contrast, in patients with antibiotic-responsive arthritis, in whom joint swelling usually resolved during a 1-month course of oral antibiotic therapy, the median antibody titers to most of the spirochetal antigens remained steady or decreased during the first 1-3 months after starting antibiotic therapy. In patients with. antibiotic-refractory arthritis, who had persistent joint swelling for a median duration of 10 months despite 2-3 months of oral or intravenous antibiotics, the median titers to most antigens increased slightly during the first 1-3 months. However, by 4-6 months after starting antibiotic therapy, reactivity with all antigens declined similarly in both antibiotic-treated groups. Conclusion. Whereas the antibody titers to B burgdorferi remained high in non-antibiotic-treated patients, the titers declined similarly 4-6 months after starting therapy in patients with antibiotic-responsive or a ntibiotic- refractory arthritis, suggesting that synovial inflammation persisted in patients with antibioticrefractory arthritis after the period of infection. C1 [Kannian, Priya; McHugh, Gail; Glickstein, Lisa J.; Steere, Allen C.] Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, Boston, MA 02114 USA. [Johnson, Barbara J. B.; Bacon, Rendi M.] Nat Ctr Infect Dis, CDC, Ft Collins, CO USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM asteere@partners.org FU NIAMS NIH HHS [AR 20358]; PHS HHS [CCU 110291] NR 37 TC 27 Z9 27 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 4216 EP 4225 DI 10.1002/art.23135 PG 10 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200039 PM 18050219 ER PT J AU Friday, RP Means, TK Luster, AD AF Friday, Robert P. Means, Terry K. Luster, Andrew D. TI Human neutrophil responsiveness to SLE immune complexes via Toll-like receptors SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 71st Annual Meeting of the American-College-of-Rheumatology CY NOV 06-11, 2007 CL Boston, MA SP Amer Coll Rheumatol C1 [Friday, Robert P.; Means, Terry K.; Luster, Andrew D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 4254 EP 4255 PG 2 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200087 ER PT J AU Nasir, K Santos, RD Tufail, K Rivera, J Carvalho, JAM Meneghello, R Brady, TD Blumenthal, RS AF Nasir, Khurram Santos, Raul D. Tufail, Kashif Rivera, Juan Carvalho, Jose A. M. Meneghello, Romeu Brady, Thomas D. Blumenthal, Roger S. TI High-normal fasting blood glucose in non-diabetic range is associated with increased coronary artery calcium burden in asymptomatic men SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery calcification; Fasting blood glucose; Subclinical atherosclerosis; Electron-beam tomography ID BEAM COMPUTED-TOMOGRAPHY; SUBCLINICAL CARDIOVASCULAR-DISEASE; FACTOR ASSESSMENT EQUATIONS; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; COLLEGE-OF-CARDIOLOGY; RISK-FACTOR; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; DIABETES-MELLITUS AB Objective: : The objective of the study is to evaluate whether high fasting blood glucose (FBG) in the non-diabetic range (<126 mg/dl) is associated with subclinical coronary atherosclerosis as determined by coronary artery calcium (CAC) independent of clustering of metabolic syndrome (MS) risk factors. Methods & results: : Previously non-diabetic, 458 asymptomatic non-diabetic Brazilian men (mean age: 46 +/- 7 years, range: 29-65) underwent clinical consultation including FBG measurements and electron-beam tomography (EBT). The mean FBG of the study population was 88 +/- 10 mg/dl. Overall, 190 (42%) of men had CAC>0. The prevalence of CAC was significantly higher among men with high-normal FBG (4th quartile: 94-125 mg/dl) versus normal FBG group (lower three quartiles: 66-93 mg/dl) (62% versus 35%, p < 0.0001). In age adjusted analyses the odds ratio (OR) for any CAC among men with high-normal FBG versus normal FBG was 2.19 (95% CI: 1.33-3.58). On further adjustment for risk factors the relationship was slightly attenuated, however remained statistically significant (OR = 1.78, 95% CI 1.05-3.00, p = 0.03). In sub-stratified analyses high-normal FBG was associated with CAC among men without MS (OR: 1.99, 95% CI: 1.04-3.78) and with MS (OR: 2.12, 95% CI: 0.95-4.80). Similar relations with high-normal FBG were observed among individuals classified low risk (OR: 2.34, 95% CI: 1.14-4.83) as well intermediate high-risk men (OR: 1.95, 95% CI: 0.99-3.86) by Framingham risk score (FRS), respectively. Conclusions: : Fasting blood glucose in the upper normal range appears to be associated with the presence of CAC in apparently non-diabetic Brazilian men. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Nasir, Khurram; Brady, Thomas D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, Boston, MA 02114 USA. [Nasir, Khurram; Rivera, Juan; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Santos, Raul D.; Carvalho, Jose A. M.; Meneghello, Romeu] Albert Einstein Hosp, Prevent Med Ctr, Sao Paulo, Brazil. [Santos, Raul D.] Univ Sao Paulo, Med Sch Hosp, Heart Inst Incor, Sao Paulo, Brazil. RP Nasir, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, Boston, MA 02114 USA. EM knasir@partners.org RI Santos, Raul/A-1170-2010 OI Santos, Raul/0000-0002-9860-6582 FU National Institute of Health, Bethesda, Maryland [1T32 HL0761 36-02] FX Khurram Nasir is supported by Grant No. 1T32 HL0761 36-02 from the National Institute of Health, Bethesda, Maryland. NR 38 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2007 VL 195 IS 2 BP E155 EP E160 DI 10.1016/j.atherosclerosis.2007.05.025 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V13FR UT WOS:000207653200019 PM 17606259 ER PT J AU Kelly, MM Forsyth, JP AF Kelly, Megan M. Forsyth, John P. TI Sex differences in response to an observational fear conditioning procedure SO BEHAVIOR THERAPY LA English DT Article; Proceedings Paper CT 38th Annual Convention of the Association-for-Behavioral-and-Cognitive-Therapies CY NOV, 2004 CL New Orleans, LA SP Assoc Behav & Cognit Therapies ID LEARNING-THEORY PERSPECTIVE; PANIC DISORDER; ANXIETY DISORDERS; ACQUISITION; WOMEN; MEN; CLASSIFICATION; 20-PERCENT; CHALLENGE; ETIOLOGY AB The present study evaluated sex differences in observational fear conditioning using modeled "mock" panic attacks as an unconditioned stimulus (UCS). Fifty-nine carefully prescreened healthy undergraduate participants (30 women) underwent 3 consecutive differential conditioning phases: habituation, acquisition, and extinction. It was expected that participants watching a confederate display mock panic attacks (UCS) paired with a previously neutral stimulus (CS+) would learn to respond fearfully to the CS+, but not to the CS- (i.e., a stimulus never associated with displays of panic). Women also were expected to report more distress and ratings of panic to the CS+ than the CS- compared to men, but no sex differences were anticipated on autonomic indices of conditioning (i.e., electrodermal responses). Consistent with expectation, aversive conditioning was demonstrated by greater magnitude electrodermal and verbal-evaluative (e.g., subjective units of distress scale, panic ratings) responses to the CS+ over the CS-, with women reporting more distress to the CS+ over the CS-, but not greater autonomic conditioning, compared to men. Overall, the results support the notion that modeled panic attacks can serve as a potent UCS for both men and women. Discussion focuses on sex differences in observational fear conditioning and its relation to the clinical presentation of anxiety disorders. C1 [Kelly, Megan M.; Forsyth, John P.] SUNY Albany, Albany, NY 12222 USA. RP Kelly, MM (reprint author), VA Boston Healthcare System, Natl Ctr PTSD 116B 5, 150 S Huntington Ave, Boston, MA 02130 USA. EM Megan.Kelly@va.gov FU NIMH NIH HHS [MH6010701] NR 46 TC 14 Z9 14 U1 0 U2 9 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 DEC PY 2007 VL 38 IS 4 BP 340 EP 349 DI 10.1016/j.beth.2006.10.007 PG 10 WC Psychology, Clinical SC Psychology GA 323BL UT WOS:000257418900003 PM 18021949 ER PT J AU Podar, K Richardson, PG Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Richardson, Paul G. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI The malignant clone and the bone-marrow environment SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE multiple myeloma; translocations; mutations; epigenesist; telomeres; extracellular matrix; bone-marrow microenvironment; bone-marrow niches; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; MULTIPLE-MYELOMA CELLS; FACTOR-KAPPA-B; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; DONOR LYMPHOCYTE INFUSION; TYROSINE KINASE INHIBITOR; NECROSIS-FACTOR-ALPHA; RESISTANCE CAM-DR; RECEPTOR ACTIVATOR; FACTOR-I AB Multiple myeloma (MM) is characterized by the clonal expansion of monoclonal immunoglobulin-secreting plasma cells within the bone marrow (BM). It has become clear that the intimate reciprocal relationship between the tumor cell clone and the niches of the BM microenvironment plays a pivotal pathophysiologic role in MM. We and others have identified several new molecular targets and derived novel therapies which induce cytotoxicity against MM cells in the BM milieu, including thalidomide, bortezomib, and lenalidomide. Importantly, these agents induce tumor-cell death, as well as inhibit MM-cell-BM-stromal-cell (BMSC) adhesion and related tumor-cell growth, survival, and migration. Moreover, they block both constitutive and MM-cell binding-induced growth factor and cytokine secretion in BMSCs. Further, they also block tumor angiogenesis and can augment anti-MM immunity. Although all three of these agents are now FDA-approved to treat MM, patients inevitably relapse, and further improvements remain urgently needed. Here we review our current knowledge of the MM cell clone, as well as the impact of the BM microenvironment on tumor-cell growth, survival, migration and drug resistance. Delineating the mechanisms and sequelae of the reciprocal relationship between the MM cell clone, distinct BM extracellular matrix proteins, and accessory cell compartments may provide the basis for new effective therapeutic strategies to reestablish BM homeostasis and thereby improve MM patient outcome. C1 [Podar, Klaus; Richardson, Paul G.; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Mulitple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Mulitple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu NR 151 TC 53 Z9 58 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2007 VL 20 IS 4 BP 597 EP 612 DI 10.1016/j.beha.2007.08.002 PG 16 WC Hematology SC Hematology GA 248HF UT WOS:000252142800003 PM 18070708 ER PT J AU Mitsiades, CS Hayden, PJ Anderson, KC Richardson, PG AF Mitsiades, Constantine S. Hayden, Patrick J. Anderson, Kenneth C. Richardson, Paul G. TI From the bench to the bedside: emerging new treatments in multiple myeloma SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE myeloma; targeted therapy; immunomodulatory; thalidomide; lenalidomide; bortezomib; hsp90 inhibitor ID NF-KAPPA-B; BONE-MARROW MICROENVIRONMENT; OVERCOMES DRUG-RESISTANCE; HISTONE DEACETYLASE INHIBITION; UBIQUITIN-PROTEASOME PATHWAY; ACID COMBINATION THERAPY; PHASE-II; ANTITUMOR-ACTIVITY; ARSENIC TRIOXIDE; TYROSINE KINASE AB Within the last decade, several novel classes of anti-myeloma therapeutics have become available. The clinical successes achieved by thalidomide, lenalidomide, and the proteasome inhibitor bortezomib, and in particular the ability of these agents to lead to major clinical responses in patients resistant to conventional or high-dose chemotherapy, have highlighted the importance of expanding further the spectrum of classes of agents utilized for the treatment of myeloma. Herein, we review the current status for the development of novel anti-myeloma agents, with emphasis on classes of therapeutics which have already translated into clinical trials or those in advanced stages of preclinical development. These include second-generation proteasome inhibitors (NPI-0052 and PR-171), heat shock protein 90 (hsp90) inhibitors, 2-methoxyestradiol, histone deacetylase (HDAC) inhibitors (e.g. SAHA and LBH589), fibroblast growth factor receptor 3 (FGF-R3) inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, mTOR inhibitors, monoclonal antibodies, and agents specifically targeting the tumor microenvironment, such as defibrotide. C1 [Mitsiades, Constantine S.; Hayden, Patrick J.; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myelopma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myelopma Ctr, Dept Med Oncol,Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul-richardson@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378] NR 120 TC 48 Z9 49 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2007 VL 20 IS 4 BP 797 EP 816 DI 10.1016/j.beha.2007.09.008 PG 20 WC Hematology SC Hematology GA 248HF UT WOS:000252142800015 PM 18070720 ER PT J AU Blackledge, NP Carter, EJ Evans, JR Lawson, V Rowntree, RK Harris, A AF Blackledge, Neil P. Carter, Emma J. Evans, Joanne R. Lawson, Victoria Rowntree, Rebecca K. Harris, Ann TI CTCF mediates insulator function at the CFTR locus SO BIOCHEMICAL JOURNAL LA English DT Article DE CCCTC-binding factor (CTCF); chromatin structure; cystic fibrosis transmembrane conductance regulator (CFTR); DNase I-hypersensitive site; histone modification; insulator ID RETINOID-X-RECEPTOR; I-HYPERSENSITIVE SITES; POTENTIAL REGULATORY ELEMENTS; TRANSCRIPTION FACTOR-BINDING; ENHANCER-BLOCKING ACTIVITY; THYROID-HORMONE RECEPTOR; BETA-GLOBIN INSULATOR; CYSTIC-FIBROSIS; GENE-EXPRESSION; PROTEIN CTCF AB Regulatory elements that lie outside the basal promoter of a gene may be revealed by local changes in chromatin structure and histone modifications. The promoter of the CFTR (cystic fibrosis transmembrane conductance regulator) gene is not responsible for its complex pattern of expression. To identify important regulatory elements for CFTR we have previously mapped DHS (DNase I-hypersensitive sites) across 400 kb spanning the locus. Of particular interest were two DHS that flank the CFTR gene, upstream at -20.9 kb with respect to the translational start site, and downstream at + 15.6 kb. In the present study we show that these two DHS possess enhancer-blocking activity and bind proteins that are characteristic of known insulator elements. The DHS core at - 20.9 kb binds CTCF (CCCTC-binding factor) both in vitro and in vivo; however, the + 15.6 kb core appears to bind other factors. Histone-modification analysis across the CFTR locus highlights structural differences between the - 20.9 kb and + 15.6 kb DHS, further suggesting that these two insulator elements may operate by distinct mechanisms. We propose that these two DHS mark the boundaries of the CFTR gene functional unit and establish a chromatin domain within which the complex profile of CFTR expression is maintained. C1 Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Chicago, IL 60614 USA. Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England. Inst Canc Res, London SW3 6JB, England. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. RP Harris, A (reprint author), Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, 2300 Childrens Plaza 211, Chicago, IL 60614 USA. EM ann-harris@northwestern.edu NR 53 TC 27 Z9 30 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2007 VL 408 BP 267 EP 275 DI 10.1042/BJ20070429 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 239CU UT WOS:000251496900013 PM 17696881 ER PT J AU Papakostas, GI Thase, ME Fava, M Nelson, JC Shelton, RC AF Papakostas, George I. Thase, Michael E. Fava, Maurizio Nelson, J. Craig Shelton, Richard C. TI Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents SO BIOLOGICAL PSYCHIATRY LA English DT Review DE antidepressant; combined; mechanism; norepinephrine; selective; serotonin ID VENLAFAXINE EXTENDED-RELEASE; DOUBLE-BLIND TRIAL; TREATMENT-RESISTANT DEPRESSION; PAROXETINE-CONTROLLED TRIAL; CLINICAL-TRIAL; RANDOMIZED-TRIAL; PRIMARY-CARE; CONVENTIONAL ANTIDEPRESSANTS; TRICYCLIC ANTIDEPRESSANTS; GERIATRIC OUTPATIENTS AB Background: Recent studies suggest that the treatment of major depressive disorder (MDD) with newer antidepressant drugs that simultaneously enhance norepinephrine and serotonin neurotransmission might result in higher response and remission rates than the selective serotonin reuptake inhibitors (SSRIs). The goal of our work was to compare response rates among patients with MDD treated with either of these two broad categories of antidepressant drugs. Methods: Medline/Pubmed, EMBase, clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies were searched for double-blind, randomized trials comparing a newer serotonergic-noradrenergic antidepressant drug (venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, or moclobemide) with an SSRI for MDD. Results: Ninety-three trials (n = 17,036) were combined using a random-effects model. Treatment with serotonergic + noradrenergic antidepressant drugs was more likely to result in clinical response than the SSRIs (risk ratio [RR] = 1.059; response rates 63.6% versus 59.3%; p = .003). There was no evidence for heterogeneity among studies combined (p = 1.0). Excluding each individual agent did not significantly alter the pooled RR. With the exception of duloxetine (.985), RRs for response for each individual serotonergic + noradrenergic antidepressant drug were within the 95% confidence interval of the pooled RR (1.019-1.101). Conclusions: Serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared with SSRIs in MDD. With the Number Needed to Treat (NNT) statistic as one indicator of clinical significance, nearly 24 patients would need to be treated with dual-action antidepressant drugs instead of SSRIs in order to obtain one additional responder. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom's National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of depressed patients treated with SSRI/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant drugs. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH 069629] NR 140 TC 168 Z9 173 U1 9 U2 46 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2007 VL 62 IS 11 BP 1217 EP 1227 DI 10.1016/j.biopsych.2007.03.027 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 233VY UT WOS:000251119600004 PM 17588546 ER PT J AU Townsend, SA Evrony, GD Gu, FX Schulz, MP Brown, RH Langer, R AF Townsend, Seth A. Evrony, Gilad D. Gu, Frank X. Schulz, Martin P. Brown, Robert H., Jr. Langer, Robert TI Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons SO BIOMATERIALS LA English DT Article DE nanoparticle; drug delivery; brain; cell culture; nerve; protein ID IN-VIVO; BINDING; LIGAND; AGGREGATION; TRANSPORT; CARRIER; DOMAIN; CELLS; MODEL; GENE AB The use of nanoparticles for targeted drug delivery is often facilitated by specific conjugation of functional targeting molecules to the nanoparticle surface. We compared different biotin-binding proteins (avidin, streptavidin, or neutravidin) as crosslinkers to conjugate proteins to biodegradable nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-biotin polymers. Avidin gave the highest levels of overall protein conjugation, whereas neutravidin minimized protein non-specific binding to the polymer. The tetanus toxin C fragment (TTC), which is efficiently retrogradely transported in neurons and binds to neurons with high specificity and affinity, retained the ability to bind to neuroblastoma cells following amine group modifications. TTC was conjugated to nanoparticles using neutravidin, and the resulting nanoparticles were shown to selectively target neuroblastoma cells in vitro. TTC-conjugated nanoparticles have the potential to serve as drug delivery vehicles targeted to the central nervous system. (C) 2007 Elsevier Ltd. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Biol Engn, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp East, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu RI Gu, Frank/C-5187-2008; Gu, Frank/G-8381-2011 OI Gu, Frank/0000-0001-8749-9075 FU NCRR NIH HHS [1S10RR13886-01]; NHLBI NIH HHS [HL60435, R01 HL060435, R01 HL060435-02]; NIDCR NIH HHS [R01 DE016516-01, DE16516, R01 DE016516] NR 33 TC 53 Z9 57 U1 3 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD DEC PY 2007 VL 28 IS 34 BP 5176 EP 5184 DI 10.1016/j.biomaterials.2007.08.011 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 227NJ UT WOS:000250663100024 PM 17854886 ER PT J AU Oral, E Wannomae, KK Rowell, SL Muratoglu, OK AF Oral, Ebru Wannomae, Keith K. Rowell, Shannon L. Muratoglu, Orhun K. TI Diffusion of vitamin E in ultra-high molecular weight polyethylene SO BIOMATERIALS LA English DT Article DE vitamin E; highly crosslinked polyethylene; joint arthroplasty ID ALPHA-TOCOPHEROL; MECHANICAL-PROPERTIES; WEAR; UHMWPE; HIP; RESISTANCE; ALLOARTHROPLASTY; OSTEOLYSIS; RADIATION AB Vitamin E-doped, radiation crosslinked ultra-high molecular weight polyethylene (UHMWPE) is developed as an alternate oxidation and wear resistant bearing surface in joint arthroplasty. We analyzed the diffusion behavior of vitamin E through UHMWPE and predicted penetration depth following doping with vitamin E and subsequent homogenization in inert gas used to penetrate implant components with vitamin E. Crosslinked UHMWPE (65- and 100-kGy irradiation) had higher activation energy and lower diffusion coefficients than uncrosslinked UHMWPE, but there were only slight differences in vitamin E profiles and penetration depth between the two doses. By using homogenization in inert gas below the melting point of the polymer following doping in pure vitamin E, the surface concentration of vitamin E was decreased and vitamin E stabilization was achieved throughout a desired thickness. We developed an analytical model based on Fickian theory that closely predicted vitamin E concentration as a function of depth following doping and homogenization. (C) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St,GRJ-1206, Boston, MA 02114 USA. EM omuratoglu@partners.org FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-02, R01 AR051142-01, R01 AR051142-03] NR 24 TC 62 Z9 65 U1 1 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD DEC PY 2007 VL 28 IS 35 BP 5225 EP 5237 DI 10.1016/j.biomaterials.2007.08.025 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 230EW UT WOS:000250860000003 PM 17881049 ER PT J AU Lovett, M Cannizzaro, C Daheron, L Messmer, B Vunjak-Novakovic, G Kaplan, DL AF Lovett, Michael Cannizzaro, Christopher Daheron, Laurence Messmer, Brady Vunjak-Novakovic, Gordana Kaplan, David L. TI Silk fibroin microtubes for blood vessel engineering SO BIOMATERIALS LA English DT Article DE silk fibroin; vascular grafts; arterial tissue engineering; porosity; endothelial cells; bioreactor ID IN-VITRO; STEM-CELLS; GRAFTS; BIOMATERIALS; SCAFFOLDS; BYPASS AB Currently available synthetic grafts demonstrate moderate success at the macrovascular level, but fail at the microvascular scale ( <6 mm inner diameter). We report on the development of silk fibroin microtubes for blood vessel repair with several advantages over existing scaffold materials/designs. These microtubes were prepared by dipping straight lengths of stainless steel wire into aqueous silk fibroin, where the addition of poly(ethylene oxide) (PEO) enabled control of microtube porosity. The microtube properties were characterized in terms of pore size, burst strength, protein permeability, enzymatic degradation, and cell migration. Low porosity microtubes demonstrated superior mechanical properties in terms of higher burst pressures, but displayed poor protein permeability; whereas higher porosity tubes had lower burst strengths but increased permeability and enhanced protein transport. The microtubes also exhibited cellular barrier functions as low porosity tubes prevented outward migration of GFP-transduced HUVECs, while the high porosity microtubes allowed a few cells per tube to migrate outward during perfusion. When combined with the biocompatible and suturability features of silk fibroin, these results suggest that silk microtubes, either implanted directly or preseeded with cells, are an attractive biomaterial for microvascular grafts. (C) 2007 Elsevier Ltd. All rights reserved. C1 Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. RP Kaplan, DL (reprint author), Tufts Univ, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA. EM David.Kaplan@tufts.edu RI vunjak-novakovic, gordana/J-9279-2012; OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574 FU NIBIB NIH HHS [P41 EB002520, EB002520, P41 EB002520-06A1, R01 EB003210, R01 EB003210-06] NR 27 TC 140 Z9 156 U1 5 U2 58 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD DEC PY 2007 VL 28 IS 35 BP 5271 EP 5279 DI 10.1016/j.biomterials.2007.08.008 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 230EW UT WOS:000250860000007 PM 17727944 ER PT J AU Ma, J Tian, WM Hou, SP Xu, QY Spector, M Cui, FZ AF Ma, Jun Tian, Wei-Ming Hou, Shao-Ping Xu, Qun-Yuan Spector, Myron Cui, Fu-Zhai TI An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model SO BIOMEDICAL MATERIALS LA English DT Article ID NEURITE GROWTH-INHIBITORS; CEREBRAL-ARTERY OCCLUSION; SPINAL-CORD-INJURY; AXONAL REGENERATION; FUNCTIONAL RECOVERY; ADULT RATS; IN-VITRO; PLASTICITY; BRAIN; SCAFFOLDS AB The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III beta-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain. C1 [Ma, Jun; Tian, Wei-Ming; Cui, Fu-Zhai] Tsing Hua Univ, Dept Mat Sci & Engn, Biomat Lab, Beijing 100084, Peoples R China. [Hou, Shao-Ping; Xu, Qun-Yuan] Capital Univ Med Sci, Beijing Inst Neurosci, Beijing 100054, Peoples R China. [Spector, Myron] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Cui, FZ (reprint author), Tsing Hua Univ, Dept Mat Sci & Engn, Biomat Lab, Beijing 100084, Peoples R China. EM cuifz@mail.tsinghua.edu.cn RI Ma, Jun/K-2084-2012; OI Ma, Jun/0000-0001-5167-1750; Tian, Weiming/0000-0003-4958-4118 NR 32 TC 27 Z9 30 U1 0 U2 12 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD DEC PY 2007 VL 2 IS 4 BP 233 EP 240 DI 10.1088/1748-6041/2/4/005 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 259VO UT WOS:000252969200008 PM 18458480 ER PT J AU Bajaj, P Akin, D Gupta, A Sherman, D Shi, B Auciello, O Bashir, R AF Bajaj, Piyush Akin, Demir Gupta, Amit Sherman, Debby Shi, Bing Auciello, Orlando Bashir, Rashid TI Ultrananocrystalline diamond film as an optimal cell interface for biomedical applications SO BIOMEDICAL MICRODEVICES LA English DT Article DE ultrananocrystalline diamond; MEMS; BioMEMS; biocompatibility; nanomaterial; UNCD ID MICROWAVE PLASMAS; IN-VITRO; GROWTH AB Surfaces of materials that promote cell adhesion, proliferation, and growth are critical for new generation of implantable biomedical devices. These films should be able to coat complex geometrical shapes very conformally, with smooth surfaces to produce hermetic bioinert protective coatings, or to provide surfaces for cell grafting through appropriate functionalization. Upon performing a survey of desirable properties such as chemical inertness, low friction coefficient, high wear resistance, and a high Young's modulus, diamond films emerge as very attractive candidates for coatings for biomedical devices. A promising novel material is ultrananocrystalline diamond (UNCD (R)) in thin film form, since UNCD possesses the desirable properties of diamond and can be deposited as a very smooth, conformal coating using chemical vapor deposition. In this paper, we compared cell adhesion, proliferation, and growth on UNCD films, silicon, and platinum films substrates using different cell lines. Our results showed that UNCD films exhibited superior characteristics including cell number, total cell area, and cell spreading. The results could be attributed to the nanostructured nature or a combination of nanostructure/surface chemistry of UNCD, which provides a high surface energy, hence promoting adhesion between the receptors on the cell surface and the UNCD films. C1 Purdue Univ, Bindley Biosci Ctr, Brick Nanotechnol Ctr, W Lafayette, IN 47907 USA. Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. Purdue Univ, Dept Biol, Electron Microscopy Facil, W Lafayette, IN 47907 USA. Argonne Natl Lab, Div Mat Sci, Argonne, IL 60439 USA. Argonne Natl Lab, Ctr Nanoscale Mat, Argonne, IL 60439 USA. Massachusetts Gen Hosp, BioMEMS Resource Ctr, Cambridge, MA USA. RP Bashir, R (reprint author), Purdue Univ, Bindley Biosci Ctr, Brick Nanotechnol Ctr, W Lafayette, IN 47907 USA. EM auciello@anl.gov; bashir@purdue.edu RI Akin, Demir/D-3581-2012; Bajaj, Piyush/H-6058-2013 OI Akin, Demir/0000-0002-2296-4674; Bajaj, Piyush/0000-0002-9540-5988 NR 18 TC 70 Z9 70 U1 2 U2 20 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD DEC PY 2007 VL 9 IS 6 BP 787 EP 794 DI 10.1007/s10544-007-9090-2 PG 8 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 224QT UT WOS:000250462200002 PM 17530409 ER PT J AU Wang, L Zhou, XH AF Wang, Lan Zhou, Xiao-Hua TI Assessing the adequacy of variance function in heteroscedastic regression models SO BIOMETRICS LA English DT Article DE goodness-of-fit test; heteroscedastic errors; kernel smoothing; pseudolikelihood; variance function ID LINEAR-MODELS; COVARIANCE; CHECKING AB Heteroscedastic data arise in many applications. In heteroscedastic regression analysis, the variance is often modeled as a parametric function of the covariates or the regression mean. We propose a kernel-smoothing type nonparametric test for checking the adequacy of a given parametric variance structure. The test does not need to specify a parametric distribution for the random errors. It is shown that the test statistic has an asymptotical normal distribution under the null hypothesis and is powerful against a large class of alternatives. We suggest a simple bootstrap algorithm to approximate the distribution of the test statistic in finite sample size. Numerical simulations demonstrate the satisfactory performance of the proposed test. We also illustrate the application by the analysis of a radioimmunoassay data set. C1 Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98101 USA. Univ Washington, Dept Biostat, Seattle, WA 98198 USA. RP Wang, L (reprint author), Univ Minnesota, Sch Stat, 224 Church St SE, Minneapolis, MN 55455 USA. EM lan@stat.umn.edu; azhou@u.washington.edu FU AHRQ HHS [R01HS013105] NR 19 TC 5 Z9 5 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2007 VL 63 IS 4 BP 1218 EP 1225 DI 10.1111/j.1541-0420.2007.00805.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 239HB UT WOS:000251508300027 PM 17484775 ER PT J AU Dahlberg, SE Wang, M AF Dahlberg, Suzanne E. Wang, Molin TI A proportional hazards cure model for the analysis of time to event with frequently unidentifiable causes SO BIOMETRICS LA English DT Article DE competing risks; cure rate; masked cause; proportional hazards model ID COMPETING RISKS MODEL; BREAST-CANCER; SURVIVAL-DATA; MASKED CAUSES; EM ALGORITHM; MIXTURE MODEL; FAILURE; REGRESSION; INFERENCE AB We propose a semiparametric method for the analysis of masked-cause failure data that are also subject to a cure. We present estimators for the failure time distribution, the cure rate, and the covariate effect on each of these, assuming a proportional hazards cure model for the time to event of interest and we use the expectation-maximization algorithm to conduct the likelihood maximization. The method is applied to data from a breast cancer clinical trial. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Dahlberg, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. EM dahlberg@jimmy.harvard.edu FU NCI NIH HHS [CA-75362] NR 23 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2007 VL 63 IS 4 BP 1237 EP 1244 DI 10.1111/j.1541-0420.2007.00811.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 239HB UT WOS:000251508300029 PM 18078485 ER PT J AU Papas, KK Pisania, A Wu, H Weir, GC Colton, CK AF Papas, Klearchos K. Pisania, Anna Wu, Haiyan Weir, Gordon C. Colton, Clark K. TI A stirred microchamber for oxygen consumption rate measurements with pancreatic islets SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE islets of Langerhans; islet viability; oxygen consumption rate; stirred microchamber; islet quality ID 3-(4,5-DIMETHYLTHIAZOL-2-YL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE MTT; BETA-TC3 CELL-CULTURES; INSULIN-SECRETION; BIOARTIFICIAL PANCREAS; COLORIMETRIC ASSAY; DIABETES-MELLITUS; ENERGY-METABOLISM; RAPID ASSESSMENT; O-2 CONSUMPTION; QUALITY-CONTROL AB Improvements in pancreatic islet transplantation for treatment of diabetes are hindered by the absence of meaningful islet quality assessment methods. Oxygen consumption rate (OCR) has previously been used to assess the quality of organs and primary tissue for transplantation. In this study, we describe and characterize a stirred micro-chamber for measuring OCR with small quantities of islets. The device has a titanium body with a chamber volume of about 200 mu L and is magnetically stirred and water jacketed for temperature control. Oxygen partial pressure (PO2) is measured by fluorescence quenching with a fiber optic probe, and OCR is determined from the linear decrease of pO(2) with time. We demonstrate that measurements can be made. rapidly and with high precision. Measurements with beta TC3 cells and islets show that OCR is directly proportional to the number of viable cells in mixtures of live and dead cells and correlate linearly with membrane integrity measurements made with cells that have been cultured for 24 h under various stressful conditions. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Minnesota, Diabet Inst Immunol & Transplantat, Dept Surg, Minneapolis, MN USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, 25 Ames St, Cambridge, MA 02139 USA. EM ckcolton@milt.edu FU NCRR NIH HHS [U42 RR016606, U42 RR016606-01, U42 RR016606-02, U42 RR016606-03, U42 RR016606-04]; NIDDK NIH HHS [R01 DK063108-03, R01 DK063108, R01 DK063108-01A1, R01 DK063108-02]; PHS HHS [R01-KD063108-01A1, U4Z 16606] NR 81 TC 59 Z9 59 U1 0 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD DEC 1 PY 2007 VL 98 IS 5 BP 1071 EP 1082 DI 10.1002/bit.21486 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 228PG UT WOS:000250741300013 PM 17497731 ER PT J AU Frazier, JA Breeze, JL Papadimitriou, G Kennedy, DN Hodge, SM Moore, CM Howard, JD Rohan, MP Caviness, VS Makris, N AF Frazier, Jean A. Breeze, Janis L. Papadimitriou, George Kennedy, David N. Hodge, Steven M. Moore, Constance M. Howard, James D. Rohan, Michael P. Caviness, Verne S. Makris, Nikos TI White matter abnormalities in children with and at risk for bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; child psychiatry; diffusion tensor imaging; magnetic resonance imaging; mood disorders ID DIFFUSION TENSOR; TOPOGRAPHIC PARCELLATION; EMOTION PERCEPTION; LIMBIC CORTEX; BRAIN IMAGES; RATING-SCALE; IN-VIVO; MANIA; CONNECTIONS; ACCURATE AB Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the integrity of white matter (WM) tracts in the brain. Children with bipolar disorder (BPD) may have WM abnormalities that precede illness onset. To more fully examine this possibility, we scanned children with DSM-IV BPD and compared them to healthy peers and children at risk for BPD (AR-BPD), defined as having a first-degree relative with the disorder. Ten children with BPD, eight healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5 Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial slices. Fractional anisotropy (FA) values were compared between groups to determine regions of significant difference (p < 0.05). Compared to HC, children with BPD had decreased FA in right and left superior frontal tracts, including the superior longitudinal fasciculus I (SLF I) and the cingulate-paracingulate WM (CG-PAC(WM)). In addition, the BPD group had reduced FA in left orbital frontal WM and the right corpus callosum body. Compared to AR-BPD, children with BPD showed reduced FA in the right and left CG-PAC(WM). Both the BPD and AR-BPD groups showed reduced FA relative to HC in bilateral SLF I. The bilateral SLF I finding in both the BPD and AR-BPD groups may represent a trait-based marker or endophenotype of the disorder. The finding of decreased FA in the right and left CG-PAC(WM) in children with BPD compared to the other two groups may represent a disease-state related finding. C1 Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. RP Frazier, JA (reprint author), Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, 1493 Cambridge St, Cambridge, MA 02139 USA. EM jfrazier@challiance.org RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [K01 MH001978, K01 MH01798]; NINDS NIH HHS [R01 NS34189] NR 55 TC 96 Z9 98 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2007 VL 9 IS 8 BP 799 EP 809 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 237YZ UT WOS:000251414300002 PM 18076529 ER PT J AU Biederman, J Mick, E Spencer, T Dougherty, M Aleardi, M Wozniak, J AF Biederman, Joseph Mick, Eric Spencer, Thomas Dougherty, Meghan Aleardi, Megan Wozniak, Janet TI A prospective open-label treatment trial of ziprasidone monotherapy in children and adolescents with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; children; ziprasidone ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; DIVALPROEX SODIUM; RATING-SCALE; ACUTE MANIA; OLANZAPINE; RISPERIDONE; RELIABILITY; DEPRESSION; SYMPTOMS AB To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania. This was an eight-week, open-label, prospective study of ziprasidone monotherapy (57.3 +/- 33.9 mg/day) in 21 bipolar youth [manic, mixed, or bipolar not otherwise specified (NOS); 6-17 years old]. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. Fourteen of the 21 youth (67%) completed the study. Ziprasidone treatment was associated with clinically and statistically significant improvement in mean YMRS scores (-10.8 +/- 8.4, p < 0.0001) and 57% had a CGI-I <= 2 at endpoint. Ziprasidone was well tolerated with no statistically significant increase in body weight (0.6 +/- 0.4 kg, p = 0.2) or QTc interval (-3.7 +/- 4.7, p = 0.5). Open-label ziprasidone treatment was associated with a significant short-term improvement of symptoms of pediatric bipolar disorder. Future placebo-controlled, double-blind studies are warranted. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res, Yawkey Ctr Outpatient Care Yaw 6A, 32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 30 TC 34 Z9 35 U1 1 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 DEC PY 2007 VL 9 IS 8 BP 888 EP 894 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 237YZ UT WOS:000251414300012 PM 18076539 ER PT J AU Maytal, G Zalta, AK Thompson, E Chow, CW Perlman, C Ostacher, MJ Pollack, MH Shear, K Simon, NM AF Maytal, Guy Zalta, Alyson K. Thompson, Elizabeth Chow, Candice W. Perlman, Carol Ostacher, Michael J. Pollack, Mark H. Shear, Katherine Simon, Naomi M. TI Complicated grief and impaired sleep in patients with bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bereavement; bipolar disorder; complicated grief; ICG; insomnia; PSQI; sleep; sleep disturbance ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC GRIEF; DIAGNOSTIC-CRITERIA; PRODROMAL SYMPTOMS; QUALITY INDEX; SCALE; LIFE; BEREAVEMENT; PREVALENCE; ONSET AB To examine the relationship of sleep disturbance with complicated grief (CG) in patients with bipolar disorder (BD). Adults with DSM-IV BD were asked if they ever experienced significant loss and, if so, completed the Inventory of Complicated Grief. Subjective sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). The association of CG with sleep disturbance was assessed in univariate t-tests, and in multivariate analyses controlling for the presence of anxiety disorder comorbidity and current bipolar recovery status. Individuals with CG had significantly higher mean PSQI scores (10.9 versus 7.9, p = 0.003) than those without CG. Further, within the group of BD participants who had experienced a significant loss, those with CG had significantly poorer sleep (p = 0.01). CG remained significantly associated with greater sleep impairment after adjustment for comorbid anxiety disorder and bipolar mood state. This additive impairment in sleep with CG comorbidity was evident for four of the PSQI component scales: sleep quality, sleep duration, sleep efficiency and sleep disturbance. Our data indicate a significant association of CG with poor sleep in individuals with BD. Disturbed sleep may be a mechanism by which CG increases the burden of illness in BD. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Columbia Univ, Sch Social Work, New York, NY USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org OI Ostacher, Michael/0000-0003-0353-7535; Zalta, Alyson/0000-0002-5159-8431 NR 35 TC 11 Z9 11 U1 4 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2007 VL 9 IS 8 BP 913 EP 917 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 237YZ UT WOS:000251414300016 PM 18076543 ER PT J AU Cho, PS Lo, DP Wikiel, KJ Rowland, HC Coburn, RC McMorrow, IM Goodrich, JG Arn, JS Billiter, RA Houser, SL Shimizu, A Yang, YG Sachs, DH Huang, CA AF Cho, Patricia S. Lo, Diana P. Wikiel, Krzysztof J. Rowland, Haley C. Coburn, Rebecca C. McMorrow, Isabel M. Goodrich, Jennifer G. Arn, J. Scott Billiter, Robert A. Houser, Stuart L. Shimizu, Akira Yang, Yong-Guang Sachs, David H. Huang, Christene A. TI Establishment of transplantable porcine tumor cell lines derived from MHC-inbred miniature swine SO BLOOD LA English DT Article ID LARGE-ANIMAL-MODEL; CD WORKSHOP; LYMPHOPROLIFERATIVE DISEASE; ORTHOTOPIC MODELS; MOUSE MODELS; ANTIBODIES; CANCER; THERAPY; HOST; NEURAMINIDASE AB The lack of transplantable tumors has limited assessment of graft-versus-tumor effects following hematopoietic cell transplantation in clinically relevant large-animal models. We describe the derivation and characterization of porcine tumor cell lines with initial efforts of tumor transplantation using immunocompromised mice and highly inbred sublines of Massachusetts General Hospital major histocompatibility complex (MHC)-inbred miniature swine. Autopsies were performed routinely on swine that died unexpectedly or had suspicion of malignancy based on clinical symptoms or peripheral blood analysis. Tissue samples were obtained for pathology, phenotyped by flow cytometry, and placed in culture. Based on growth, lines were selected for passage into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and miniature swine. Porcine tumor recipients were preconditioned with total body irradiation from 0 to 500 cGy or with a 30-day course of oral cyclosporine. We identified 19 cases of hematologic tumors. Nine distinct tumor cell lines were established from 8 of these cases, including 3 derived from highly inbred sublines. In vivo tumor growth and serial transfer were observed in immunocompromised mice for one tumor cell line and in miniature swine for 1 of 2 tumor cell lines expanded for this purpose. These results suggest the possibility of developing a transplantable tumor model in this large-animal system. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Med Sch, Boston, MA USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149-9019 13th St, Boston, MA 02129 USA. EM huangc@helix.iiigh.harvard.edu FU NCI NIH HHS [P01 CA111519, P01 CA111519-01A2] NR 57 TC 14 Z9 14 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 DEC 1 PY 2007 VL 110 IS 12 BP 3996 EP 4004 DI 10.1182/blood-2007-02-074450 PG 9 WC Hematology SC Hematology GA 235ZG UT WOS:000251272200030 PM 17702898 ER PT J AU Lee, SA Haiman, CA Burtt, NP Pooler, LC Cheng, I Kolonel, LN Pike, MC Altshuler, D Hirschhorn, JN Henderson, BE Stram, DO AF Lee, Sulggi A. Haiman, Christopher A. Burtt, Noel P. Pooler, Loreall C. Cheng, Iona Kolonel, Laurence N. Pike, Malcolm C. Altshuler, David Hirschhorn, Joel N. Henderson, Brian E. Stram, Daniel O. TI A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the Multiethnic Cohort SO BMC MEDICAL GENETICS LA English DT Article ID GROWTH-HORMONE; PROMOTER UTILIZATION; PREMENOPAUSAL WOMEN; ENDOGENOUS HORMONES; MAMMARY-CARCINOMA; HUMAN GENOME; ASSOCIATION; EXPRESSION; CELLS; MICE AB Background: Studies in animals and humans clearly indicate a role for prolactin (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis. Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk. Methods: We evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as predictors of plasma PRL levels and breast cancer risk among African-American, Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both the public (dbSNP) and private (Celera) databases to construct high density SNP maps that included up to 20 kilobases (kb) upstream of the transcription initiation site and 10 kb downstream of the last exon of each gene, for a total coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173 SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each racial/ethnic group) to uncover putative functional variation. A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (R(h)(2) >= 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC. We also assessed the association of common genetic variation with circulating PRL levels in 362 postmenopausal controls without a history of hormone therapy use at blood draw. Because of the large number of comparisons being performed we used a relatively stringent type I error criteria (p < 0.0005) for evaluating the significance of any single association to correct for performing approximately 100 independent tests, close to the number of tagSNPs genotyped for both genes. Results: We observed no significant associations between PRL and PRLR haplotypes or individual SNPs in relation to breast cancer risk. A nominally significant association was noted between prolactin levels and a tagSNP (tagSNP 44, rs2244502) in intron 1 of PRL. This SNP showed approximately a 50% increase in levels between minor allele homozygotes vs. major allele homozygotes. However, this association was not significant (p = 0.002) using our type I error criteria to correct for multiple testing, nor was this SNP associated with breast cancer risk (p = 0.58). Conclusion: In this comprehensive analysis covering 59 kb of the PRL locus and 210 kb of the PRLR locus, we found no significant association between common variation in these candidate genes and breast cancer risk or plasma PRL levels. The LD characterization of PRL and PRLR in this multiethnic population provide a framework for studying these genes in relation to other disease outcomes that have been associated with PRL, as well as for larger studies of plasma PRL levels. C1 [Lee, Sulggi A.; Haiman, Christopher A.; Pooler, Loreall C.; Pike, Malcolm C.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Etiol Program, Honolulu, HI 96813 USA. [Burtt, Noel P.; Altshuler, David; Hirschhorn, Joel N.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Altshuler, David; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Dept Pediat, Boston, MA USA. [Cheng, Iona] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cheng, Iona] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Lee, SA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM sulggi@stanford.edu; haiman@usc.edu; burtt@broad.mit.edu; pooler_l@ccnt.hsc.usc.edu; chengi@humgen.ucsf.edu; lkolonel@crch.hawaii.edu; mcpike@usc.edu; altshuler@molbio.mgh.harvard.edu; joelh@broad.mit.edu; behender@usc.edu; stram@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA63464, U01 CA063464, CA54281, R01 CA054281, R01 CA063464, R37 CA054281]; NIAID NIH HHS [T32 AI060530] NR 56 TC 28 Z9 29 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD DEC 1 PY 2007 VL 8 AR 72 DI 10.1186/1471-2350-8-72 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 256NW UT WOS:000252736900001 PM 18053149 ER PT J AU Buhlmann, U Cook, LM Fama, JM Wilhelm, S AF Buhlmann, Ulrike Cook, Laura M. Fama, Jeanne M. Wilhelm, Sabine TI Perceived teasing experiences in body dysmorphic disorder SO BODY IMAGE LA English DT Article DE body dysmorphic disorder; appearance concerns; body image; perceived teasing experience ID OBSESSIVE-COMPULSIVE SCALE; RELIABILITY AB Individuals with body dysmorphic disorder (BDD) are excessively concerned about imagined or slight defects in their appearance (e.g., asymmetrical facial features). Cognitive-behavioral models of BDD propose that several factors, including dysfunctional appearance-related beliefs and life experiences, such as teasing, contribute to the avoidance behaviors or rituals (e.g., mirror checking, grooming) characteristic of BDD. Previous research has demonstrated an association between perceived teasing and body dissatisfaction. In the current study, we examined whether individuals with BDD (n = 16) report to have been teased more often than do mentally healthy controls (n = 17). The group comprising individuals with BDD reported more appearance- and competency-related teasing than did control participants. This study provides preliminary evidence for the association between perceived teasing and BDD. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Buhlmann, Ulrike; Fama, Jeanne M.; Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Body Dysmorph Disorder Clin,Dept Psychiat, Boston, MA 02114 USA. [Cook, Laura M.] SUNY Binghamton, Binghamton, NY 13902 USA. RP Wilhelm, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Body Dysmorph Disorder Clin,Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 21 TC 32 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD DEC PY 2007 VL 4 IS 4 BP 381 EP 385 DI 10.1016/j.bodyim.2007.06.004 PG 5 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 320NK UT WOS:000257241600006 PM 18089284 ER PT J AU Sirohi, B Powles, R Harousseau, JL Anderson, KC AF Sirohi, B. Powles, R. Harousseau, J. L. Anderson, K. C. TI The evolving background for high-dose treatment for myeloma SO BONE MARROW TRANSPLANTATION LA English DT Review DE myeloma; transplantation; treatment paradigms ID BONE-MARROW-TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; INTENSIVE TREATMENT; STAGING SYSTEM; INTRAVENOUS MELPHALAN; COMPLETE REMISSION; SINGLE-CENTER; CHEMOTHERAPY; THERAPY AB In the constantly evolving field of myeloma, this special issue is slanted towards how the newer targeted treatments fit in with various transplantation strategies. High-dose treatment for myeloma with autologous stem cell transplantation started 25 years ago, with the consequence of producing complete remissions and a doubling of survival. Since then, its role has been refined and it has been accepted as standard treatment. The current challenge is to optimize its use into a background of the development, availability and regulatory approval of newer targeted therapies such as Thalidomide, Revlimid (Lenalidomide) and Velcade (Bortezomib). This special issue addresses these problems, and gives particular emphasis on the attainment of very long-term survival, with normal quality of life for patients with myeloma who do not necessarily need to be cured of their molecular disease, that is, they are 'operationally cured.' It is hoped that the reader will find the information in this issue useful in the day-to-day management of patients and we hope that this will also inspire new research directions designed to improve the outcome of patients with myeloma. C1 Parkside Canc Ctr, Leukaemia & Myeloma Unit, London SW19 5NB, England. Royal Marsden NHS Fdn Trust, Dept Med Oncol, London, England. CHU Nantes, Hotel Dieu, Dept Haematol, F-44035 Nantes 01, France. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Powles, R (reprint author), Parkside Canc Ctr, Leukaemia & Myeloma Unit, 49 Parkside, London SW19 5NB, England. EM myeloma@clara.co.uk NR 25 TC 3 Z9 3 U1 3 U2 4 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 DEC PY 2007 VL 40 IS 12 BP 1097 EP 1100 DI 10.1038/sj.bmt.1705867 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 235WI UT WOS:000251264600001 PM 17906702 ER PT J AU Raab, MS Breitkreutz, I Anderson, KC AF Raab, M. S. Breitkreutz, I. Anderson, K. C. TI Targeted treatments to improve stem cell outcome: old and new drugs SO BONE MARROW TRANSPLANTATION LA English DT Review DE high-dose therapy; autologous transplantation; bortezomib; lenalidomide; thalidomide; multiple myeloma ID RELAPSED MULTIPLE-MYELOMA; THALIDOMIDE PLUS DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; LOW-DOSE THALIDOMIDE; VERSUS-HOST-DISEASE; SALVAGE THERAPY; COMBINATION THERAPY; PHASE-II; AUTOLOGOUS TRANSPLANTATION; MAINTENANCE THERAPY AB Thalidomide, lenalidomide and bortezomib have been approved for the treatment of relapsed or refractory multiple myeloma in the recent years. These agents are now being increasingly integrated into therapeutic regimens for newly diagnosed patients. First data are available on the promising activity of these novel agents in induction therapy, as well as maintenance treatment to improve outcome after stem cell transplantation. Whether these early results will lead to prolonged overall survival and thereby ultimately redefine the role of stem cell transplantation in first-line treatment of multiple myeloma will be one of the most important questions to be answered in the coming years. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu NR 75 TC 3 Z9 3 U1 0 U2 0 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 DEC PY 2007 VL 40 IS 12 BP 1129 EP 1137 DI 10.1038/sj.bmt.1705829 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 235WI UT WOS:000251264600005 PM 17768392 ER PT J AU Roodman, GD AF Roodman, G. D. TI Treatment strategies for bone disease SO BONE MARROW TRANSPLANTATION LA English DT Review DE osteoclast; osteoblast; myeloma; MIP; 1 alpha;; RANKL; DKK1; IL-6; IL-3; IL-7 ID KAPPA-B LIGAND; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MARROW STROMAL CELLS; TUMOR-NECROSIS-FACTOR; FORMATION IN-VITRO; MULTIPLE-MYELOMA; RECEPTOR ACTIVATOR; OSTEOCLAST FORMATION; ZOLEDRONIC ACID; OSTEOPROTEGERIN LIGAND AB Multiple myeloma is characterized by extensive bone destruction with little or no new bone formation. A multiplicity of factors including receptor activator NF-kappa B (RANKL), macrophage inflammatory protein-1 alpha, interleukin-3 and interleukin-6 can induce osteoclast formation in myeloma and drive the bone destructive process. Furthermore, factors are also produced either in the microenvironment or by myeloma cells themselves, which inhibit osteoblast differentiation and new bone formation. The combination of increased osteoclast formation with little or no bone repair in response to the previous bone destruction explains the severity of the bone disease in myeloma. Studies of the pathophysiology of myeloma bone disease have identified several novel therapeutic targets. These include antibodies to RANKL, chemokine receptor antagonists, which block the effects of chemokines on osteoclast differentiation and proteasome antagonists, which can affect both RANKL production and osteoprotegerin levels as well as inhibit osteoclast and enhance osteoblast differentiation. In addition, many of the new biologic agents being used for the treatment of patients with myeloma also further inhibit the bone destructive process. New therapies that can target both the tumor as well as the severe bone disease should be on the horizon to treat this devastating complication of myeloma. C1 Univ Pittsburgh, Dept Med Hematol Oncol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Dept Med Hematol Oncol, VA Pittsburgh Healthcare Syst Res & Dev 151 U, Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 70 TC 21 Z9 25 U1 0 U2 2 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 DEC PY 2007 VL 40 IS 12 BP 1139 EP 1146 DI 10.1038/sj.bmt.1705802 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 235WI UT WOS:000251264600006 PM 17680018 ER PT J AU Golshan, M Rusby, J Dominguez, F Smith, BL AF Golshan, Mehra Rusby, Jennifer Dominguez, Francisco Smith, Barbara L. TI Breast conservation for male breast carcinoma SO BREAST LA English DT Article DE male breast cancer; lumpectomy; local therapy ID LYMPH-NODE BIOPSY; CANCER PATIENTS; STAGE-I; FOLLOW-UP; MASTECTOMY AB Male breast cancer in genera[ is treated by modified radical mastectomy. Data have emerged supporting the replacement of the axittary lymph node dissection by a sentinel lymph node biopsy in the mate patient with breast carcinoma. Local therapy in the breast continues to be primarily mastectomy. The reasons suggested for this include the central location of many of the mate breast tumors and the paucity of breast tissue. Our experience with breast conservation over the last decade in mate breast carcinoma and a review of the literature is outlined here. Between 1996 and 2006, seven men underwent breast conservation for breast carcinoma and to date with a median 'follow-up of 67 months, there have been no local recurrences. Breast carcinoma in mates can be treated with breast conservation with acceptable local recurrence. Breast-conserving surgery in mate breast cancer patients should be considered an option in patients without overt nipple/areolar involvement. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Rusby, Jennifer; Dominguez, Francisco; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 18 TC 26 Z9 28 U1 0 U2 1 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 DEC PY 2007 VL 16 IS 6 BP 653 EP 656 DI 10.1016/j.breast.2007.05.012 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZQ UT WOS:000257274200011 PM 17606375 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Cognitive side-effects of adjuvant treatments SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Primary Therapy of Early Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE cognitive dysfunction; "chemo brain"; adjuvant chemotherapy; breast cancer ID BREAST-CANCER; CHEMOTHERAPY; WOMEN; IMPAIRMENT; CARCINOMA; SURVIVORS AB Symptoms associated with cognitive dysfunction-difficulties with memory, concentration, and language-are frequent among breast cancer survivors after chemotherapy. The true incidence, functional significance, and causes of these symptoms remain unclear. Models of cognitive dysfunction suggest multiple possible contributors including changes in hormonal milieu, direct effects of chemotherapy, medications given as supportive care, psychiatric changes including depression and anxiety, and mediators of inflammation. Novel neuro-cognitive testing and imaging methods are being evaluated in breast cancer survivors to better understand cognitive side-effects of therapy. (C) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 13 TC 13 Z9 13 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 DEC PY 2007 VL 16 SU 2 BP S166 EP S168 DI 10.1016/j.breast.2007.07.027 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200029 PM 17719225 ER PT J AU Chung, CS Harris, JR AF Chung, Christine S. Harris, Jay R. TI Post-mastectomy radiation therapy: Translating local benefits into improved survival SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Primary Therapy of Early Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE breast cancer; post-mastectomy radiation therapy ID BREAST-CANCER PATIENTS; RECEIVING ADJUVANT CHEMOTHERAPY; DOXORUBICIN-BASED CHEMOTHERAPY; CLINICAL-PRACTICE GUIDELINES; POSITIVE AXILLARY NODES; TERM-FOLLOW-UP; LOCOREGIONAL RECURRENCE; POSTOPERATIVE RADIOTHERAPY; CONSERVING THERAPY; TUMOR RECURRENCE AB Several randomized trials and the most recent meta-analysis from the Oxford Overview have confirmed the efficacy of post-mastectomy radiation therapy (PMRT) in improving local control and long-term survival. The survival advantage of PMRT has been established in patients with a >= 10% risk of local regional recurrence. Patients with four or more positive lymph nodes fall in this category, even with effective systemic therapy. However, it remains difficult to identify the subset of patients with 1-3 positive lymph nodes at highest risk of local recurrence, who would most likely demonstrate a survival benefit with PMRT. When PMRT is used, careful treatment planning, particularly with regard to cardiac dose, is critical to minimizing serious late effects of treatment. Further developments in pathologic stratification of these patients, guided by expression profiles or novel biologic markers, are required to enable individualized assessment of long-term therapeutic risks and benefits. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Chung, Christine S.; Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chung, Christine S.; Harris, Jay R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Harris, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Room 1622,44 Binney St, Boston, MA 02115 USA. EM jharris@lroc.harvard.edu NR 64 TC 12 Z9 12 U1 0 U2 1 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 DEC PY 2007 VL 16 SU 2 BP S78 EP S83 DI 10.1016/j.breast.2007.07.018 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200016 PM 17714945 ER PT J AU Goss, P Wu, M AF Goss, Paul Wu, Melinda TI Application of aromatase inhibitors in endocrine responsive breast cancers SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Primary Therapy of Early Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE aromatase inhibitors; adjuvant therapy; endocrine therapy resistance; extended treatment ID QUALITY-OF-LIFE; PLASMA ESTROGEN-LEVELS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN RESISTANCE; OVARIECTOMIZED RATS; ADJUVANT TREATMENT; THERAPY; EXEMESTANE AB Aromatase (estrogen synthetase) inhibitors (AIs) have been incorporated into adjuvant treatment of early-stage breast cancer in postmenopausal women and their role in pre-menopausal is being investigated. Several questions regarding AIs remain unanswered: optimal sequence with tamoxifen; optimal duration and the best agent in the class. The benefits of extending therapy beyond 5 years has been established by the MA17 trial and many follow-on trials are exploring prolonged therapy. Several strategies to overcome de novo and acquired resistance are being explored. Improving on the "total estrogen blockade" by adding fulvestrant is one example; blocking collaborating cell signaling pathways is another. Candidate targets for this include the erbB2, IGFIR and the mTOR cell survival pathway. Identification of both host (pharmacogenomic) and tumor (genomic) signatures as prognostic and predictive factors will help to select patients for appropriate therapies in the future and reduce the number needed to treat to benefit a few. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Goss, Paul; Wu, Melinda] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goss, P (reprint author), Massachusetts Gen Hosp, 55 Fruit St,,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 31 TC 3 Z9 3 U1 0 U2 2 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 DEC PY 2007 VL 16 SU 2 BP S114 EP S119 DI 10.1016/j.breast.2007.07.011 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200021 PM 17719783 ER PT J AU Partridge, AH Ruddy, KJ AF Partridge, Ann H. Ruddy, Kathryn J. TI Fertility and adjuvant treatment in young women with breast cancer SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Primary Therapy of Early Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE breast cancer; young women; fertility; amenorrhea; pregnancy ID CRYOPRESERVED OVARIAN TISSUE; PRESERVE FERTILITY; PROGNOSTIC IMPACT; HODGKINS-DISEASE; TRIAL-VI; PREGNANCY; CARCINOMA; CHEMOTHERAPY; AGE; TRANSPLANTATION AB Women of childbearing age with breast cancer are often concerned about whether they will become infertile after treatment, and for those who wish to bear children, whether a subsequent pregnancy will alter their risk of disease recurrence. The risk of chemotherapy-related amenorrhea (CRA), menopause, and infertility appear to be related to patient age and type of treatment received, though data regarding actual fertility following treatment are limited. There are options available for fertility preservation for young women who wish to have a biologic child after breast cancer and are at risk for infertility. Options include cryopreservation of embryos, oocytes, ovarian tissue prior to treatment, and ovarian suppression through chemotherapy. However, most of these are considered experimental, and there are limited data regarding the safety of Such strategies. There has been concern that pregnancy after breast cancer may worsen prognosis in light of the endocrine manipulations used to treat breast cancer, particularly for women with hormone sensitive disease. Several studies addressing the potential risk of pregnancy after breast cancer have not revealed any negative effect on prognosis. However, these studies have significant limitations, and concerns about a negative impact for some remain. Ongoing and future prospective studies evaluating fertility and pregnancy issues for young breast cancer survivors are warranted for this Vulnerable population facing this difficult issue. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Partridge, Ann H.; Ruddy, Kathryn J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 56 TC 39 Z9 42 U1 4 U2 6 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 DEC PY 2007 VL 16 SU 2 BP S175 EP S181 DI 10.1016/j.breast.2007.07.029 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200031 PM 17804236 ER PT J AU Regan, MM Gelber, RD AF Regan, Meredith M. Gelber, Richard D. CA Int Breast Canc Study Grp Breast Int Grp TI Using clinical trial data to tailor adjuvant treatments for individual patients SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Primary Therapy of Early Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE breast cancer; subgroup analysis; estrogen receptors; progesterone receptors; HER2; adjuvant therapy; chemotherapy; endocrine therapy; trastuzumab; STEPP ID HER2-POSITIVE BREAST-CANCER; PRIMARY THERAPY; CHEMOTHERAPY; TRASTUZUMAB; PATTERNS; SUBSETS AB The 2005 St. Gallen Consensus Panel provided recommendations for the treatment of early breast cancer which rely on target identification first. The foremost advance since 2005-demonstration of trastuzumab efficacy for patients with HER2-positive disease-was realized because an effective treatment was being evaluated and because the trial patients had the targeted disease as determined by quality-controlled assessment prior to study entry. The BIG 1-98 trial provides a striking reminder of patients' benefit from reliable pathological tumor assessment so that targeted therapies are effectively utilized. Several statistical methods facilitate use of clinical trial data for individualizing treatment. Subgroup analyses summarized using forest plots are essential for better understanding the disease and its treatment. The HERA trial illustrates the interpretation of relative and absolute treatment effects and estimating hazard rates over time as means to distinguish relevant differences across subgroups. Overview analyses, joint analyses, the STEPP (subpopulation treatment effect pattern plot) method and recursive partitioning are valuable tools. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Regan, Meredith M.; Gelber, Richard D.; Int Breast Canc Study Grp; Breast Int Grp] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, 44 Binney St, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu FU NCI NIH HHS [U24 CA075362-11, CA-75362, U24 CA075362] NR 26 TC 4 Z9 4 U1 0 U2 4 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 DEC PY 2007 VL 16 SU 2 BP S98 EP S104 DI 10.1016/j.breast.2007.07.016 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200019 PM 17719227 ER PT J AU Tolaney, SM Winer, EP AF Tolaney, Sara M. Winer, Eric P. TI Follow-up care of patients with breast cancer SO BREAST LA English DT Article; Proceedings Paper CT 10th International Conference on Breast Cancer CY MAR 14-17, 2007 CL St Gallen, SWITZERLAND DE staging; locoregional recurrence; metastasis; guidelines; surveillance ID RANDOMIZED CONTROLLED-TRIAL; ADJUVANT CHEMOTHERAPY; CONTRALATERAL BREAST; SPECIALIST CARE; AMERICAN-SOCIETY; 15-YEAR SURVIVAL; WEIGHT-GAIN; RECURRENCE; WOMEN; RISK AB In the US, over 200,000 new cases of invasive breast cancer are diagnosed each year, with an additional 60,000 cases of ductal carcinoma in situ. The majority of these women will never experience a recurrence of their disease, and Most Will Survive more than 5 years. Follow-up care for these women is focused on addressing long-term complications of therapy, and early detection of new primary cancers and locoregional recurrences. There is no evidence that early detection of distant metastases will lead to an increase in survival, and currently routine imaging studies are not recommended. With the growing number of breast cancer survivors, further studies should be undertaken to study the cost-effectiveness of surveillance strategies. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Tolaney, Sara M.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 2, Boston, MA 02115 USA. EM stolaney@partners.org NR 56 TC 9 Z9 9 U1 1 U2 2 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 DEC PY 2007 VL 16 SU 2 BP S45 EP S50 DI 10.1016/j.breast.2007.07.005 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 324AF UT WOS:000257489200008 PM 17697780 ER PT J AU Rusby, JE Brachtel, EF Michaelson, JS Koerner, FC Smith, BL AF Rusby, Jennifer E. Brachtel, Elena F. Michaelson, James S. Koerner, Frederick C. Smith, Barbara L. TI Breast duct anatomy in the human nipple: Three-dimensional patterns and clinical implications SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE anatomy; breast; cancer; ductal lavage; ductoscopy; ducts; mastectomy; nipple-sparing; reconstruction ID SKIN-SPARING MASTECTOMY; CANCER; CARCINOMA; RECONSTRUCTION; DISEASE; LAVAGE AB Background The anatomy of the nipple has become clinically relevant. Diagnostic techniques access the breast through nipple ducts and surgeons offer nipple-sparing mastectomy. There is variation in the number of ducts reported and little is known about the spatial location of ducts, their size, and their relationship to orifices on the surface. Methods Nipple specimens were taken from 129 consecutive mastectomies. Each was sectioned coronally into 3 mm blocks and one section was prepared from each block. The number of ducts and cross-sectional areas of nipple and duct 'bundle' were recorded. Three nipples were sectioned at 50 mu m intervals and digitally reconstructed in three dimensions. Results The median number of ducts was 23 (interquartile range 19-28). Reconstructions and summary data from 25 nipples show a central duct bundle narrowing to form a 'waist' as the ducts enter breast parenchyma. A three-dimensional reconstruction focusing on one nipple tip demonstrated 29 ducts arising from 15 orifices. Beneath the skin, most ducts are very narrow, gradually becoming larger deeper within the nipple. Conclusions This work demonstrates that many ducts share a few common openings onto the surface of the nipple, explaining the observed discrepancy between number of ducts and of orifices. Neither duct diameter nor position predicts whether a duct system will terminate close to the nipple or pass deeper into the breast. These new insights into nipple anatomy will be of use in considering the reliability of a ductal approach to diagnosis and in planning nipple-sparing mastectomy. C1 Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM BLSmith1@partners.org NR 21 TC 35 Z9 39 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 IS 2 BP 171 EP 179 DI 10.1007/s10549-006-9487-2 PG 9 WC Oncology SC Oncology GA 226HI UT WOS:000250579600003 PM 17221150 ER PT J AU Barkley, CR Bafford, AC Burstein, HJ Winer, EP Lipsitz, SR Smith, BL Iglehart, JD Golshan, M AF Barkley, C. R. Bafford, A. C. Burstein, H. J. Winer, E. P. Lipsitz, S. R. Smith, B. L. Iglehart, J. D. Golshan, M. TI Breast surgery for women presenting with stage IV breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S235 EP S236 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500657 ER PT J AU Burstein, H Awada, A Badwe, R Dirix, L Tan, A Jacod, S Lustgarten, S Vermette, J Zacharchuk, C AF Burstein, H. Awada, A. Badwe, R. Dirix, L. Tan, A. Jacod, S. Lustgarten, S. Vermette, J. Zacharchuk, C. TI HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase 2 results in patients with advanced breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Med Oncol Clin, Brussels, Belgium. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Inst Canc New Jersey, New Brunswick, NJ USA. Wyeth Ayerst Res, Paris, France. Wyeth Ayerst Res, Cambridge, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S268 EP S268 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500751 ER PT J AU Cigler, T Yaffe, MJ Johnston, D Verma, S Findlay, B Wadden, N Pater, JL Richardson, H Tu, D Shangle, Q Goss, PE AF Cigler, T. Yaffe, M. J. Johnston, D. Verma, S. Findlay, B. Wadden, N. Pater, J. L. Richardson, H. Tu, D. Shangle, Q. Goss, P. E. TI A placebo-controlled trial examining the effects of letrozole on mammographic breast density and bone and lipid metabolism SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ottawa Hosp, Ottawa, ON, Canada. Niagara Hlth Syst, St Catharines, ON, Canada. Mem Univ Newfoundland, St John, NF, Canada. Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S112 EP S112 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500307 ER PT J AU Cigler, T Fabian, CF Yaffe, MJ Johnston, D Ingle, JN Nassif, E Brunner, R Wadden, N Pater, JL Richardson, H Tu, D Shangle, Q Goss, PE AF Cigler, T. Fabian, C. F. Yaffe, M. J. Johnston, D. Ingle, J. N. Nassif, E. Brunner, R. Wadden, N. Pater, J. L. Richardson, H. Tu, D. Shangle, Q. Goss, P. E. TI Effects of the steroidal aromatase inhibitor exemestane on mammographic breast density and other end-organ functions. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Mayo Clin, Rochester, MN USA. Notre Dame Hosp, Montreal, PQ, Canada. Univ Nevada, Sch Med, Reno, NV 89557 USA. Mem Univ Newfoundland, St John, NF, Canada. Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S50 EP S50 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500135 ER PT J AU Gonzalez, LG Park, J Geistlinger, TR Pearlberg, J Endege, W Degot, S Sawyer, J Hu, Y Harlow, E Labaer, J AF Gonzalez, L. G. Park, J. Geistlinger, T. R. Pearlberg, J. Endege, W. Degot, S. Sawyer, J. Hu, Y. Harlow, E. Labaer, J. TI Kinome survey of molecular pathways lead to tamoxifen-resistant breast cancer cell growth SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Harvard Inst Proteom, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S205 EP S205 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500571 ER PT J AU Harris, LN Eklund, AC Carter, S Li, X Winer, EP Hilsenbeck, S Esteva, FJ Symmans, WF Pusztai, L Szallasi, Z Chang, J AF Harris, L. N. Eklund, A. C. Carter, S. Li, X. Winer, E. P. Hilsenbeck, S. Esteva, F. J. Symmans, W. F. Pusztai, L. Szallasi, Z. Chang, J. TI HER2 tumors are heterogeneous, clinically, molecularly, and in response to preoperative trastuzumab: pathway analysis of gene expression profiles from three breast cancer datasets SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Yale Univ, New Haven, CT USA. Childrens Informat Program, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Univ, Houston, TX 77030 USA. MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S87 EP S87 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500236 ER PT J AU Kirstein, LJ MacDonald, S Abi Raad, R Taghian, AG Smith, BL Specht, MC AF Kirstein, L. J. MacDonald, S. Abi Raad, R. Taghian, A. G. Smith, B. L. Specht, M. C. TI Radiation after axillary lymph node dissection: impact of neoadjuvant chemotherapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [Kirstein, L. J.; MacDonald, S.; Abi Raad, R.; Taghian, A. G.; Smith, B. L.; Specht, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S240 EP S240 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500670 ER PT J AU Krop, IE Beeram, M Modi, S Rabbee, N Girish, S Tibbitts, J Holden, SN Lutzker, SG Burris, HA AF Krop, I. E. Beeram, M. Modi, S. Rabbee, N. Girish, S. Tibbitts, J. Holden, S. N. Lutzker, S. G. Burris, H. A. TI A phase I study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate, in patients with advanced HER2+ breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Drug Dev, San Antonio, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genentech Inc, San Francisco, CA USA. Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S33 EP S33 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500090 ER PT J AU Kuler, I Hegg, R Singer, CF Badwe, R Lowe, E AF Kuler, I Hegg, R. Singer, C. F. Badwe, R. Lowe, E. CA NEWEST Investigators TI Fulvestrant 500 mg vs 250 mg: first results from NEWEST, a randomized, phase II neoadjuvant trial in postmenopausal women with locally advanced, estrogen receptor-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Sao Paulo, Perola Bygton Hosp, Sao Paulo, Brazil. Med Univ Vienna, Vienna, Austria. Tata Mem Hosp, Bombay 400012, Maharashtra, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S7 EP S7 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500019 ER PT J AU Lin, NU Paul, D Dieras, V Liu, M Greil, R Roche, H Rubin, SD Zembryki, D Oliva, C Jayawardene, D Winer, EP AF Lin, N. U. Paul, D. Dieras, V Liu, M. Greil, R. Roche, H. Rubin, S. D. Zembryki, D. Oliva, C. Jayawardene, D. Winer, E. P. TI Lapatinib and capecitabine for the treatment of brain metastases in patients with HER2+breast cancer - an updated analysis from EGF105084. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Inst Curie, Paris, France. Georgetown Univ Hosp, Washington, DC 20007 USA. LKH, Salzburg, Austria. Ctr Claudius Regaud, Toulouse, France. GlaxoSmithKline Inc, Collegeville, PA USA. GlaxoSmithKline Inc, Greenford, Middx, England. RI Roche, Henri/O-9211-2014; Greil, Richard/C-7673-2017 OI Roche, Henri/0000-0001-7463-205X; Greil, Richard/0000-0002-4462-3694 NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S272 EP S273 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500765 ER PT J AU Lipton, A Cook, R Major, P Smith, M Coleman, R AF Lipton A Cook R Major P Smith M Coleman R TI Survival in breast cancer patients with bone metastases and reductions in markers of bone resorption during zoledronic acid treatment. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Milton S Hershey Med Ctr, Hershey, PA USA. Univ Waterloo, Waterloo, ON, Canada. Juravinski Can Ctr, Hamilton, ON, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Sheffield, Sheffield, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S39 EP S39 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500106 ER PT J AU Mayer, EL Hamel, S Savoie, J Parker, LM Lin, NU Anderson, K Heymach, JV Gelman, R Ivy, SP Winer, EP Burstein, HJ AF Mayer, E. L. Hamel, S. Savoie, J. Parker, L. M. Lin, N. U. Anderson, K. Heymach, J., V Gelman, R. Ivy, S. P. Winer, E. P. Burstein, H. J. TI AZD2171 for refractory breast cancer: a phase 2 trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. NCI, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S274 EP S274 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500769 ER PT J AU McCaskill-Stevens, W Procter, M Goodbrand, J Azambuja, E Leyland-Jones, B Ruschoff, J Dowselt, M Wermuth, P Dolci, S Gelber, RD Piccart-Gebhart, M AF McCaskill-Stevens, W. Procter, M. Goodbrand, J. Azambuja, E. Leyland-Jones, B. Ruschoff, J. Dowselt, M. Wermuth, P. Dolci, S. Gelber, R. D. Piccart-Gebhart, M. TI Disease-free survival according to local immunohistochemistry for HER2 and central fluorescence in situ hydridization for patients treated with adjuvant chemotherapy with and without trastuzumab in the HERA (BIG01-01) trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Natl Canc Inst, Bethesda, MD USA. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Inst Jules Bordet, B-1000 Brussels, Belgium. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Emory Univ, Atlanta, GA 30322 USA. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] TARGOS Mol Pathol GmbH, Klinikum Kasseland, Kassel, Germany. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Hoffmann La Roche AG, Basel, Switzerland. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Royal Marsden Hosp Hlth Serv Trust, London, England. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S18 EP S18 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500049 ER PT J AU Michaelson, JS Chen, L Martei, Y Smith, B Younger, J AF Michaelson, J. S. Chen, L. Martei, Y. Smith, B. Younger, J. TI Web calculators for estimating the risk of breast cancer death and the impact of adjuvant treatment on that risk SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [Michaelson, J. S.; Chen, L.; Martei, Y.; Smith, B.; Younger, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S215 EP S215 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500599 ER PT J AU Miller, KD ONeill, A Perez, EA Seidman, AD Sledge, GW AF Miller, K. D. ONeill, A. Perez, E. A. Seidman, A. D. Sledge, G. W. TI Phase II feasibility trial incorporating bevacizumab into dose dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial of the Eastern Cooperative Oncology Group (E2104) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN 55905 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S147 EP S147 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500409 ER PT J AU Moy, B Richardson, H Johnston, D Paler, JL Chlebowski, R Ales-Martinez, JE Ingle, J Goss, PE AF Moy, B. Richardson, H. Johnston, D. Paler, J. L. Chlebowski, R. Ales-Martinez, J. E. Ingle, J. Goss, P. E. TI NCICCTG MAP.3: enrollment and study drug adherence of ethnic minority women in a breast cancer prevention trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Univ Calif Los Angeles, Torrance, CA USA. Hosp Ruber Int, Madrid, Spain. Mayo Clin, Rochester, MN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S141 EP S142 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500394 ER PT J AU Sepucha, K Ozanne, E Partridge, A Moy, B AF Sepucha, K. Ozanne, E. Partridge, A. Moy, B. TI Challenges in metastatic breast cancer: optimistic vs realistic goals for treatment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S277 EP S278 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500780 ER PT J AU Dai, Q Xu, M Yao, M Sun, B AF Dai, Q. Xu, M. Yao, M. Sun, B. TI Angiotensin AT1 receptor antagonists exert antiinflammatory effects in spontaneously hypertensive rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE AT1 receptor antagonist; spontaneous hypersensitive rats (SHRs); MCP-1/CCR2; PI3K/Akt ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NITRIC-OXIDE SYNTHESIS; HYPERCHOLESTEROLEMIC MICE; VASCULAR INFLAMMATION; ANEURYSM FORMATION; CHRONIC BLOCKADE; TYPE-1 RECEPTOR; KAPPA-B; ATHEROSCLEROSIS; CCR2 AB Background and purpose: Although the main therapeutic effect of angiotensin AT1 receptor antagonists is to decrease blood pressure, they also exert anti-inflammatory effects in the cardiovascular system. However, the underlying mechanisms remain unclear. We investigated the inhibitory effect of AT1 antagonists on the chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) in rat monocytes and aortas. Experimental approach: Spontaneous hypertensive rats (SHRs) were treated with the AT1 antagonists losartan or telmisartan for 4 weeks, and Wistar-Kyoto rats (WKYs) were used as normotensive controls. Systolic arterial pressure was measured, and the number of macrophages in the aortic vessel wall was assessed by anti-ED-1 antibody immunolabelling. Key results: Compared with WKYs, SHRs showed significantly increased ED-1 positive macrophages in the aortic wall, which were decreased after high doses of losartan or telmisartan. Low doses of losartan did not improve blood pressure significantly as did the high doses, but markedly decreased macrophage infiltration in the vessel wall. AT1 antagonists, particularly at high doses, improved aortic remodeling in SHR. At the molecular level, AT1 antagonists attenuated the expression of MCP-1 and CCR2 in the aorta and peripheral blood monocytes and lowered the serum level of MCP-1. In addition, Western blotting showed that AT1 antagonists inhibited the phosphorylation of Akt in mouse monocytes. Conclusions and implications: AT1 antagonism inhibited vessel wall inflammation and inhibition of PI3K/Akt may be involved in the modulation of the MCP-1/CCR2 system by AT1 antagonists in SHRs. C1 Jiao Tong Univ, Shanghai First Peoples Hosp, Dept Cardiol, Shanghai 200080, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02115 USA. RP Sun, B (reprint author), Jiao Tong Univ, Shanghai First Peoples Hosp, Dept Cardiol, Wujin Rd 85, Shanghai 200080, Peoples R China. EM bg_sun@yahoo.com NR 18 TC 50 Z9 51 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 2007 VL 152 IS 7 BP 1042 EP 1048 DI 10.1038/sj.bjp.0707454 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 234CZ UT WOS:000251139600008 PM 17922026 ER PT J AU Sands, BE Adams, PC AF Sands, Bruce E. Adams, Paul C. TI Crohn's disease: Advise and consent SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID INFLIXIMAB; EFFICACY; RISKS C1 [Sands, Bruce E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crohns & Colitis Ctr, Boston, MA USA. [Adams, Paul C.] Univ Western Ontario, Univ Hosp, London, ON N6A 5A5, Canada. RP Sands, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD DEC PY 2007 VL 21 IS 12 BP 791 EP 793 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 246HN UT WOS:000251998200001 ER PT J AU Burke, ME Albritton, K Marina, N AF Burke, Megan E. Albritton, Karen Marina, Neyssa TI Challenges in the recruitment of adolescents and young adults to cancer clinical trials SO CANCER LA English DT Review DE adolescent and young adult; cancer; clinical trials; survival ID GERM-CELL TUMORS; PEDIATRIC-ONCOLOGY-GROUP; SOFT-TISSUE SARCOMAS; COMBINATION CHEMOTHERAPY; EUROPEAN ORGANIZATION; PROGNOSTIC-FACTORS; OLDER ADOLESCENTS; CHILDREN; SURVIVAL; RHABDOMYOSARCOMA AB The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA-specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA-specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA-specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival. C1 Cleveland Clin Childrens Hosp, Dept Pediat Hematol & Oncol, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Stanford Univ, Ctr Med, Dept Pediat, Stanford, CA 94305 USA. RP Burke, ME (reprint author), Cleveland Clin Childrens Hosp, Dept Pediat Hematol & Oncol, 9500 Euclid Ave,Mailcode S20, Cleveland, OH 44195 USA. EM burkem2@ccf.org NR 50 TC 68 Z9 70 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2007 VL 110 IS 11 BP 2385 EP 2393 DI 10.1002/cncr.23060 PG 9 WC Oncology SC Oncology GA 235BS UT WOS:000251209100004 PM 17918260 ER PT J AU Sankaran, S Crone, DE Palazzo, RE Parvin, JD AF Sankaran, Satish Crone, Donna E. Palazzo, Robert E. Parvin, Jeffrey D. TI BRCA1 regulates gamma-tubulin binding to centrosomes SO CANCER BIOLOGY & THERAPY LA English DT Article DE BRCA1; breast cancer; centrosome; ubiquitin; microtubules; gamma-tubulin; microtubule nucleation ID MICROTUBULE NUCLEATION; BRCA1-DEPENDENT UBIQUITINATION; RING COMPLEX; IDENTIFICATION; INSTABILITY; RECRUITMENT; PROTEIN AB Centrosomes are the cellular organelles that nucleate microtubules (MTs) via the activity of gamma-tubulin ring complex(s) (gamma TuRC) bound to the pericentriolar material of the centrosomes. BRCA1, the breast and ovarian cancer specific tumor suppressor, inhibits centrosomal MT nucleation via its ubiquitin ligase activity, and one of the known BRCA1 substrates is the key gamma TuRC component, gamma-tubulin. We analyzed the mechanism by which BRCA1 regulates centrosome function using an in vitro reconstitution assay, which includes separately staged steps. Our results are most consistent with a model by which the BRCA1 ubiquitin ligase modifies both gamma-tubulin plus a second centrosomal protein that controls localization of gamma TuRC to the centrosome. We suggest that this second protein is an adapter protein or protein complex that docks gamma TuRC to the centrosome. By controlling gamma-TuRC localization, BRCA1 appropriately inhibits centrosome function, and loss of BRCA1 would result in centrosome hyperactivity, supernumerary centrosomes and, possibly, aneuploidy. C1 [Parvin, Jeffrey D.] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Sankaran, Satish; Parvin, Jeffrey D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sankaran, Satish] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Crone, Donna E.; Palazzo, Robert E.] Rensselaer Polytech Inst, Dept Biol, Troy, NY 12180 USA. [Crone, Donna E.; Palazzo, Robert E.] Biol Marine Lab, Woods Hole, MA USA. RP Parvin, JD (reprint author), Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. EM Jeffrey.Parvin@osumc.edu RI Parvin, Jeffrey/C-8955-2009 FU NCI NIH HHS [CA111480, R01 CA111480, R01 CA111480-04]; NIGMS NIH HHS [GM43264, R01 GM043264] NR 22 TC 26 Z9 27 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2007 VL 6 IS 12 BP 1853 EP 1857 PG 5 WC Oncology SC Oncology GA 273PT UT WOS:000253944900013 PM 18087219 ER PT J AU Frohling, S Scholl, C Levine, RL Loriaux, M Boggon, TJ Bernard, OA Berger, R Dohner, H Dohner, K Ebert, BL Teckie, S Golub, TR Jiang, JR Schittenhelm, MM Lee, BH Griffin, JD Stone, RM Heinrich, MC Deininger, MW Druker, BJ Gilliland, DG AF Froehling, Stefan Scholl, Claudia Levine, Ross L. Loriaux, Marc Boggon, Titus J. Bernard, Olivier A. Berger, Roland Doehner, Hartmut Doehner, Konstanze Ebert, Benjamin L. Teckie, Sewit Golub, Todd R. Jiang, Jingrui Schittenhelm, Marcus M. Lee, Benjamin H. Griffin, James D. Stone, Richard M. Heinrich, Michael C. Deininger, Michael W. Druker, Brian J. Gilliland, D. Gary TI Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE DOMAIN; ACUTE MYELOGENOUS LEUKEMIA; FACTOR RECEPTOR MUTANTS; HUMAN CANCER; ACTIVATING MUTATIONS; POINT MUTATIONS; JUXTAMEMBRANE DOMAIN; COLORECTAL CANCERS AB Mutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in AML patients without known FLT3 mutations and experimentally tested the consequences of each candidate leukemogenic allele. This approach identified gain-of-function mutations that activated downstream signaling and conferred sensitivity to FLT3 inhibition and alleles that were not associated with kinase activation, including mutations in the catalytic domain. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation and underscore the importance of functional studies to distinguish "driver" mutations underlying tumorigenesis from biologically neutral "passenger" alterations. C1 [Froehling, Stefan; Scholl, Claudia; Levine, Ross L.; Ebert, Benjamin L.; Lee, Benjamin H.; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Levine, Ross L.; Ebert, Benjamin L.; Golub, Todd R.; Jiang, Jingrui; Griffin, James D.; Stone, Richard M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Golub, Todd R.; Druker, Brian J.; Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Boggon, Titus J.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Bernard, Olivier A.; Berger, Roland] Inst Fed & Rech Necker Enfants Malades, Inst Natl Sante & Rech Med E0210, F-75743 Paris, France. [Doehner, Hartmut; Doehner, Konstanze] Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany. [Ebert, Benjamin L.; Teckie, Sewit; Golub, Todd R.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Ebert, Benjamin L.; Teckie, Sewit; Golub, Todd R.] MIT, Cambridge, MA 02142 USA. [Schittenhelm, Marcus M.] Univ Tubingen Hosp, Dept Hematol Oncol Immunol Rheumatol & Pneumol, D-72076 Tubingen, Germany. [Loriaux, Marc] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Heinrich, Michael C.; Deininger, Michael W.; Druker, Brian J.] Oregon Hlth & Sci Univ, Dept Hematol & Med Oncol, Portland, OR 97239 USA. [Deininger, Michael W.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Bernard, Olivier/E-5721-2016 FU NCI NIH HHS [CA105423, CA113434, CA66996, T32 CA009172]; NHLBI NIH HHS [HL082677] NR 56 TC 95 Z9 96 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2007 VL 12 IS 6 BP 501 EP 513 DI 10.1016/j.ccr.2007.11.005 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 242VG UT WOS:000251753700004 PM 18068628 ER PT J AU Li, Z Tognon, CE Godinho, FJ Yasaitis, L Hock, H Herschkowitz, JI Lannon, CL Cho, E Kim, SJ Bronson, RT Perou, CM Sorensen, PH Orkin, SH AF Li, Zhe Tognon, Cristina E. Godinho, Frank J. Yasaitis, Laura Hock, Hanno Herschkowitz, Jason I. Lannon, Chris L. Cho, Eunah Kim, Seong-Jin Bronson, Roderick T. Perou, Charles M. Sorensen, Poul H. Orkin, Stuart H. TI ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex SO CANCER CELL LA English DT Article ID PROTEIN-TYROSINE KINASE; GENE FUSION; STEM-CELLS; GLAND DEVELOPMENT; EPITHELIAL-CELLS; PROSTATE-CANCER; CONGENITAL FIBROSARCOMA; TGF-BETA-1 EXPRESSION; MESOBLASTIC NEPHROMA; TRANSGENIC MICE AB To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;1 5)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61* luminal progenitors are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models. C1 [Li, Zhe; Godinho, Frank J.; Yasaitis, Laura; Hock, Hanno; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godinho, Frank J.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Li, Zhe; Hock, Hanno; Bronson, Roderick T.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Li, Zhe; Hock, Hanno; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Tognon, Cristina E.; Lannon, Chris L.; Sorensen, Poul H.] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada. [Herschkowitz, Jason I.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Herschkowitz, Jason I.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. [Cho, Eunah; Kim, Seong-Jin] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [U01 CA105423-03, N01-CN43308, N01CN43308, R01 CA101227, R01-CA-101227, U01 CA105423, U01 CA105423-04] NR 56 TC 66 Z9 67 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2007 VL 12 IS 6 BP 542 EP 558 DI 10.1016/j.ccr.2007.11.012 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 242VG UT WOS:000251753700007 PM 18068631 ER PT J AU Kaelin, WG Sawyers, CL Mihich, E AF Kaelin, William G. Sawyers, Charles L. Mihich, Enrico TI Nineteenth annual pezcoller symposium: Hypothesis-driven clinical investigation in cancer SO CANCER RESEARCH LA English DT Article AB This symposium was held in Trento, Italy, from June 14 to 16, 2007, and was cochaired by William G. Kaelin, Enrico Mihich, and Charles L. Sawyers. A session was deveted to the proof of concept derived from successes in target-oriented therapeutics. Molecular targets must be identified in each patients because they are equally present in all patients with the same tumor type. A session was devoted to the identification of markers of drug effectiveness. Two sessions were focused on opportunities for developing new specific molecular target-oriented therapies. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mihich, E (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM enrico.mihich@roswellpark.org RI Sawyers, Charles/G-5327-2016 NR 0 TC 1 Z9 2 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2007 VL 67 IS 23 BP 11102 EP 11105 DI 10.1158/0008-5472.CAN-07-3230 PG 4 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100003 PM 18045966 ER PT J AU Kim, TK Lee, JS Oh, SY Jin, X Choi, YJ Lee, TH Lee, EH Choi, YK You, S Chung, YG Lee, JB DePinho, RA Chin, L Kim, H AF Kim, Tae-Kyung Lee, Joong-Seob Oh, Se-Yeong Jin, Xun Choi, Yun-Jaie Lee, Tae-Hoon Lee, Eun ho Choi, Young-Ki You, Seungkwon Chung, Yong Gu Lee, Jang-Bo DePinho, Ronald A. Chin, Lynda Kim, Hyunggee TI Direct transcriptional activation of promyelocytic leukemia protein by IFN regulatory factor 3 induces the p53-dependent growth inhibition of cancer cells SO CANCER RESEARCH LA English DT Article ID CREB-BINDING-PROTEIN; PROLYL ISOMERASE PIN1; NF-KAPPA-B; NUCLEAR-BODIES; P53 ACETYLATION; DNA-DAMAGE; IN-VIVO; PML; INTERFERON; PATHWAYS AB IFN regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection, and is also involved in p53-dependent inhibition of cell growth. Although functional activation of IRF33 by viral infection is relatively well documented, the biological role and regulatory mechanism underlying cell growth inhibition by IRF3 are poorly understood. Here, we show a novel regulatory pathway connecting IRF3-promyelocytic leukemia protein (PML)-p53 in primary and cancer cell lines. Overexpression of IRF3 induces p53-dependent cell growth inhibition in cancer cell lines with normal p53 activity. In addition, doxycycline-induced expression of IRF3 in U87MG cells inhibits tumor growth in nude mice in vivo. IRF3 is found to increase expression of PML by a direct transcriptional activation as determined by PML-promoter-luciferase and chromatin immunoprecipitation assays. When PML is depleted by RNA interference-mediated knockdown, IRF3 fails to increase p53 acetylation and its transcriptional activity. Taken together, the results of the present study indicate that direct transcriptional activation of PML by IRF3 results in the p53-dependent growth inhibition of normal and cancer cells in vitro and in vivo, which is suggestive of a novel regulatory network between the innate immune response and tumor suppression. C1 Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Cell Growth Regulat Lab, Seoul 136713, South Korea. Korea Univ, Sch Med, Dept Neurosurg, Seoul, South Korea. Seoul Natl Univ, Div Anim Biotechnol, Seoul, South Korea. Chonnam Natl Univ, The 2nd Stage Brain Korea 21 Dent Sch, Dent Sci Res Inst, Dept Oral Biochem, Kwangju, South Korea. Chungbuk Natl Univ, Coll Med, Inst Med Res, Dept Microbiol, Cheongju, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02138 USA. Harvard Univ, Sch Med, Dept Med & Genet, Dept Dermatol, Boston, MA 02138 USA. RP Kim, H (reprint author), Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Cell Growth Regulat Lab, Seoul 136713, South Korea. EM hg-kim@korea.ac.kr RI Kim, Hyunggee/F-2673-2013; Kang, Phil Jun/F-4716-2013; You, Seungkwon/H-3067-2015; OI Kim, Hyunggee/0000-0002-4738-0990; jin, xun/0000-0002-1550-2199 NR 40 TC 22 Z9 24 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 DEC 1 PY 2007 VL 67 IS 23 BP 11133 EP 11140 DI 10.1158/0008-5472.CAN-07-1342 PG 8 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100009 PM 18056437 ER PT J AU Ravitz, MJ Chen, L Lynch, M Schmidt, EV AF Ravitz, Michael J. Chen, Li Lynch, Mary Schmidt, Emmett V. TI c-myc repression of TSC2 contributes to control of translation initiation and myc-induced transformation SO CANCER RESEARCH LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; CELL-GROWTH; FACTOR 4E; SIGNALING PATHWAYS; MAMMALIAN TARGET; MTOR INHIBITORS; E-BOX; BINDING; RAPAMYCIN; PROMOTER AB The c-myc oncogene plays a key role in cellular growth control, and translation initiation factors are among the transcriptional targets of Myc. Here, we describe a defect in translation initiation control in myc-null cells due to alterations in the mammalian target of rapamycin (mTOR) pathway. Myc loss increased sensitivity to dominant inhibition of eukaryotic translation initiation factor 4E function. Polysomal profiles of myc(-/-) cells revealed decreased translation initiation rates, which were accompanied by decreased 40S/ 60S ribosomal subunit ratios. Because the 40S small ribosomal subunit contains the key regulatory ribosomal protein S6 (rpS6), we considered that myc loss might affect expression of components of the mTOR signaling pathway that regulate rpS6 function. Among mTOR signaling components, Myc directly affected transcription of tuberous sclerosis 2 (TSC2), as shown by quantitative mRNA analysis and by Myc binding to its promoter in chromatin immunoprecipitation assays. Importantly, Myc acted as a strong and direct repressor for TSC2 expression because its loss increased TSC2 mRNA in myc-null and in HL60 shRNA experiments, activation of a mycER construct in myc-/- cells suppressed TSC2 induction in a myc box II-dependent manner, and mycER activation recruited Myc to the TSC2 promoter. The biological significance of the effect of Myc on TSC2 expression was shown by markedly reduced TSC2 mRNA levels in mye-transformed cells, stimulation of S6 kinase activity in myc-null cells by TSC2 siRNA, and decreased Myc-induced soft agar colony formation following retroviral transduction of TSC2. Together, these findings show that regulation of TSC2 can contribute to the effects of Myc on cell proliferation and neoplastic growth. C1 Harvard Univ, MGH Canc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Res Ctr, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Pediat, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Harvard Univ, MGH Canc Res Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM Schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [5T32 CA009216-24, R01 CA063117, R01 CA063117-10, R01 CA069069, R01 CA069069-10, R01-CA63117, R01-CA69069, T32 CA009216] NR 43 TC 31 Z9 31 U1 0 U2 0 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 DEC 1 PY 2007 VL 67 IS 23 BP 11209 EP 11217 DI 10.1158/0008-5472.CAN-06-4351 PG 9 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100018 PM 18056446 ER PT J AU Hansford, LM Mckee, AE Zhang, LB George, RE Gerstle, JT Thorner, PS Smith, KM Look, AT Yeger, H Miller, FD Irwin, MS Thiele, CJ Kaplan, DR AF Hansford, Loen M. Mckee, Amy E. Zhang, Libo George, Rani E. Gerstle, J. Ted Thorner, Paul S. Smith, Kristen M. Look, A. Thomas Yeger, Herman Miller, Freda D. Irwin, Meredith S. Thiele, Carol J. Kaplan, David R. TI Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell SO CANCER RESEARCH LA English DT Article ID MINIMAL RESIDUAL DISEASE; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER CELLS; STEM-CELL; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; MONOCLONAL-ANTIBODIES; EXPRESSION; DIFFERENTIATION; IDENTIFICATION AB Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor. C1 Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1L7, Canada. Hosp Sick Children, Dept Surg, Toronto, ON, Canada. Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada. Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA USA. RP Kaplan, DR (reprint author), Hosp Sick Children, Cell Biol Program, Rm 12-314,Flr 12,Toronto Med Discovery Tower,101, Toronto, ON M5G 1L7, Canada. EM dkaplan@sickkids.ca FU Intramural NIH HHS NR 47 TC 99 Z9 103 U1 1 U2 5 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 DEC 1 PY 2007 VL 67 IS 23 BP 11234 EP 11243 DI 10.1158/0008-5472.CANT-07-0718 PG 10 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100021 PM 18056449 ER PT J AU Ribiczey, P Tordai, A Andrikovics, H Filoteo, AG Penniston, JT Enouf, J Enyedi, A Papp, B Kovacs, T AF Ribiczey, Polett Tordai, Attila Andrikovics, Hajnalka Filoteo, Adelaida G. Penniston, John T. Enouf, Jocelyne Enyedi, Agnes Papp, Bela Kovacs, Tuende TI Isoform-specific up-regulation of plasma membrane Ca(2+)ATPase expression during colon and gastric cancer cell differentiation SO CELL CALCIUM LA English DT Article DE gastric/colon carcinoma; Ca2+ homeostasis; differentiation induction; plasma membrane Ca(2+)ATPase; gene expression ID HISTONE-DEACETYLASE INHIBITORS; SARCOLEMMAL CALCIUM-PUMP; MESSENGER-RNA LEVELS; CA2+ PUMP; ENDOPLASMIC-RETICULUM; PROSTATE-CANCER; MONOCLONAL-ANTIBODIES; EXTRACELLULAR CALCIUM; SENSING RECEPTOR; EPITHELIAL-CELLS AB In this work we demonstrate a differentiation-induced up-regulation of the expression of plasma membrane Ca(2+)ATPase (PMCA) isoforms being present in various gastric/colon cancer cell types. We found PMCA1b as the major isoform in non-differentiated cancer cell lines, whereas the expression level of PMCA4b was significantly lower. Cell differentiation initiated with short chain fatty acids (SCFAs) and trichostatin A, or spontaneous differentiation of post-confluent cell cultures resulted in a marked induction of PMCA4b expression, while only moderately increased PMCA1b levels. Up-regulation of PMCA4b expression was demonstrated both at the protein and mRNA levels, and closely correlated with the induction of established differentiation markers. In contrast, the expression level of the Na+/K+-ATPase or that of the sarco/endoplasmic reticulum Ca(2+)ATPase 2 protein did not change significantly under these conditions. In membrane vesicles obtained from SCFA-treated gastric/colon cancer cells a marked increase in the PMCA-dependent Ca2+ transport activity was observed, indicating a general increase of PMCA function during the differentiation of these cancer cells. Because various PMCA isoforms display distinct functional characteristics, we suggest that up-regulated PMCA expression, together with a major switch in PMCA isoform pattern may significantly contribute to the differentiation of gastric/colon cancer cells. The analysis of PMCA expression may provide a new diagnostic tool for monitoring the tumor phenotype. (c) 2007 Elsevier Ltd. All rights reserved. C1 Natl Med Ctr, Inst Haematol & Immunol, H-1113 Budapest, Hungary. Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Inst Natl Sante & Rech Med, U689 E4, Paris, France. Univ Paris 07, Paris, France. INSERM, U718, Lab Biol Cellular Hematopoiet, Paris, France. Univ Paris 07, Fac Med, St Louis Inst Univ Hematol, Paris, France. RP Kovacs, T (reprint author), Natl Med Ctr, Inst Haematol & Immunol, Dioszegi u 64, H-1113 Budapest, Hungary. EM kovax@kkk.org.hu RI Enyedi, Agnes/N-9742-2013 OI Enyedi, Agnes/0000-0002-7366-9376 FU NIGMS NIH HHS [GM28835, R01 GM028835, R01 GM028835-22A1] NR 99 TC 25 Z9 25 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD DEC PY 2007 VL 42 IS 6 BP 590 EP 605 DI 10.1016/j.ceca.2007.02.003 PG 16 WC Cell Biology SC Cell Biology GA 235BT UT WOS:000251209200007 PM 17433436 ER PT J AU Ptaszek, LM Cowan, CA AF Ptaszek, Leon M. Cowan, Chad A. TI New tools for genome modification in human embryonic stem cells SO CELL STEM CELL LA English DT Editorial Material AB Two recent papers outline improvements in gene editing technology that may facilitate the analysis of signaling networks important for development. The systems developed by both Thyagarajan and coworkers (Thyagarajan et al., 2007) in Nature Biotechnology, and Lombardo and colleagues (Lombardo et al., 2007) in Stem Cells, have the potential to advance our understanding of human embryonic stem cells. C1 [Ptaszek, Leon M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ptaszek, Leon M.; Cowan, Chad A.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Regenerat Med, Stowers Med Inst, Boston, MA 02114 USA. RP Ptaszek, LM (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM lptaszek@partners.org NR 5 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD DEC PY 2007 VL 1 IS 6 BP 600 EP 602 DI 10.1016/j.stem.2007.11.004 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 243GU UT WOS:000251784300005 PM 18371400 ER PT J AU Breunig, JJ Arellano, JI Macklis, JD Rakic, P AF Breunig, Joshua J. Arellano, Jon I. Macklis, Jeffrey D. Rakic, Pasko TI Everything that glitters isn't gold: A critical review of postnatal neural precursor analyses SO CELL STEM CELL LA English DT Review ID MAMMALIAN SUBSTANTIA-NIGRA; NEWLY GENERATED NEURONS; CENTRAL-NERVOUS-SYSTEM; MARROW-DERIVED CELLS; RAT SPINAL-CORD; STEM-CELLS; ADULT-RAT; IN-VIVO; CRE RECOMBINASE; DNA-SYNTHESIS AB Adult neurogenesis research has made enormous strides in the last decade but has been complicated by several failures to replicate promising findings. Prevalent use of highly sensitive methods with inherent sources of error has led to extraordinary conclusions without adequate crossvalidation. Perhaps the biggest culprit is the reliance on molecules involved in DNA synthesis and genetic markers to indicate neuronal neogenesis. In this Protocol Review, we present an overview of common methodological issues in the field and suggest alternative approaches, including viral vectors, siRNA, and inducible transgenic/knockout mice. A multipronged approach will enhance the overall rigor of research on stem cell biology and related fields by allowing increased replication of findings between groups and across systems. C1 [Breunig, Joshua J.; Arellano, Jon I.; Rakic, Pasko] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Breunig, Joshua J.; Arellano, Jon I.; Rakic, Pasko] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurol, Boston, MA 02114 USA. [Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Nayef Al Rodhan Labs Cellular Neurosurg, Boston, MA 02114 USA. [Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Program Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Macklis, Jeffrey D.] Harvard Univ, Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. RP Rakic, P (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06510 USA. EM pasko.rakic@yale.edu RI Breunig, Joshua/F-8490-2012 NR 133 TC 66 Z9 67 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD DEC PY 2007 VL 1 IS 6 BP 612 EP 627 DI 10.1016/j.stem.2007.11.008 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 243GU UT WOS:000251784300009 PM 18371403 ER PT J AU Culhane, AC Howlin, J AF Culhane, A. C. Howlin, J. TI Molecular profiling of breast cancer: transcriptomic studies and beyond SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE breast cancer; genomics; transcriptomics; data integration; data analysis; molecular classification ID GENE-EXPRESSION PROFILES; DNA MICROARRAY TECHNOLOGY; NIPPLE ASPIRATE FLUID; CELL-LINES; DIFFERENTIAL EXPRESSION; METHYLATION PROFILES; PROGNOSTIC SIGNATURE; PROTEOMIC ANALYSIS; CLINICAL MARKERS; PROBE SETS AB Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, highthroughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. C1 [Culhane, A. C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Culhane, A. C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Howlin, J.] Lund Univ, Malmo Univ Hosp, Clin Res Ctr, S-20502 Malmo, Sweden. RP Culhane, AC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St,Smith 822C, Boston, MA 02115 USA. EM aedin@jimmy.harvard.edu; jillian.howlin@med.lu.se RI Howlin, Jill /G-9665-2011 OI Howlin, Jill /0000-0002-2766-3002 NR 118 TC 10 Z9 10 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 2007 VL 64 IS 24 BP 3185 EP 3200 DI 10.1007/s00018-007-7387-1 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249HN UT WOS:000252219000005 PM 17957338 ER PT J AU Vincent, MB Hadjikhani, N AF Vincent, M. B. Hadjikhani, N. TI Migraine aura and related phenomena: beyond scotomata and scintillations SO CEPHALALGIA LA English DT Article DE migraine; aura; spreading depression; cortical dysfunction ID TRANSIENT VISUAL DISTURBANCES; SPREADING DEPRESSION; CLASSIC MIGRAINE; ALIEN HAND; CORTEX; ACHROMATOPSIA; SYMPTOM; LIMB; HALLUCINATIONS; PROSOPAGNOSIA AB Migraine affects the cortical physiology and may induce dysfunction both ictally and interictally. Although visual symptoms predominate during aura, other contiguous cortical areas related to less impressive symptoms are also impaired in migraine. Answers from 72.2% migraine with aura and 48.6% of migraine without aura patients on human faces and objects recognition, colour perception, proper names recalling and memory in general showed dysfunctions suggestive of prosopagnosia, dyschromatopsia, ideational apraxia, alien hand syndrome, proper name anomia or aphasia, varying in duration and severity. Symptoms frequently occurred in a successively building-up pattern fitting with the geographical distribution of the various cortical functions. When specifically inquired, migraineurs reveal less evident symptoms that are not usually considered during routine examination. Spreading depression most likely underlies the aura symptoms progression. Interictal involvement indicates that MWA and MWoA are not completely silent outside attacks, and that both subforms of migraine may share common mechanisms. C1 Univ Fed Rio de Janeiro, Fac Med, Hosp Univ Clementino Fraga Filho, BR-21941 Rio De Janeiro, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. RP Vincent, MB (reprint author), Avenida Amer,1155-504, BR-22631000 Rio De Janeiro, Brazil. EM vincent@ufrj.br 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 55 TC 52 Z9 52 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD DEC PY 2007 VL 27 IS 12 BP 1368 EP 1377 DI 10.1111/j.1468-2982.2007.01388.x PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234TF UT WOS:000251186200004 PM 17944958 ER PT J AU Sharon, D Jancke, D Chavane, F Na'aman, S Grinvald, A AF Sharon, Dahlia Jancke, Dirk Chavane, Frederic Na'aman, Shmuel Grinvald, Amiram TI Cortical response field dynamics in cat visual cortex SO CEREBRAL CORTEX LA English DT Article DE area 18; local oriented grating; optical imaging; orientation map; voltage-sensitive dye imaging ID NEURONS IN-VIVO; ELECTRICAL-ACTIVITY; SENSORY RESPONSES; BARREL CORTEX; LAYER 2/3; ORIENTATION; ATTENTION; AREA-18; ORGANIZATION; SELECTIVITY AB Little is known about the "inverse" of the receptive field-the region of cortical space whose spatiotemporal pattern of electrical activity is influenced by a given sensory stimulus. We refer to this activated area as the cortical response field, the properties of which remain unexplored. Here, the dynamics of cortical response fields evoked in visual cortex by small, local drifting-oriented gratings were explored using voltage-sensitive dyes. We found that the cortical response field was often characterized by a plateau of activity, beyond the rim of which activity diminished quickly. Plateau rim location was largely independent of stimulus orientation. However, approximately 20 ms following plateau onset, 1-3 peaks emerged on it and were amplified for 25 ms. Spiking was limited to the peak zones, whose location strongly depended on stimulus orientation. Thus, alongside selective amplification of a spatially restricted suprathreshold response, wider activation to just below threshold encompasses all orientation domains within a well-defined retinotopic vicinity of the current stimulus, priming the cortex for processing of subsequent stimuli. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Sharon, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM dahlia@nmr.mgh.harvard.edu RI Jancke, Dirk/A-2961-2015; Jancke, Dirk/A-6721-2015; OI Naaman, Shmuel/0000-0002-5406-6967 NR 40 TC 27 Z9 27 U1 0 U2 3 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 DEC PY 2007 VL 17 IS 12 BP 2866 EP 2877 DI 10.1093/cercor/bhm019 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 232QW UT WOS:000251035300013 PM 17395608 ER PT J AU Stemp, EDA Estonactoc, A Madison, A Scala, J Ochoa, CE Schaefer, K Kurbanyan, K AF Stemp, Eric D. A. Estonactoc, Alina Madison, Amanda Scala, Julianna Ochoa, Carmen E. Schaefer, Kathryn Kurbanyan, Kristina TI Influence of guanine oxidation potential on DNA-protein cross-linking reactions SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 234th ACS National Meeting CY AUG 19-23, 2007 CL Boston, MA SP Amer Chem Soc, Div Chem Toxicol C1 [Stemp, Eric D. A.; Estonactoc, Alina; Madison, Amanda; Ochoa, Carmen E.; Schaefer, Kathryn] Mt St Marys Coll, Dept Phys Sci & Math, Los Angeles, CA 90049 USA. [Scala, Julianna] Mt St Marys Coll, Los Angeles, CA 90049 USA. [Kurbanyan, Kristina] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Bell, Tiffany/F-4403-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 MA 82 BP 2005 EP 2006 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400113 ER PT J AU Zwillich, C Welsh, CH AF Zwillich, Clifford Welsh, Carolyn. H. TI Hypercapnic obstructive sleep apnea: An underappreciated marker of severity SO CHEST LA English DT Editorial Material ID OBESITY-HYPOVENTILATION-SYNDROME C1 [Zwillich, Clifford] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Welsh, Carolyn. H.] Univ Colorado, Denver Hlth Sci Ctr, Div Plum Sci & Crit Care Med, Denver, CO 80202 USA. RP Zwillich, C (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80202 USA. EM Clifford.zwillich@va.gov NR 8 TC 1 Z9 1 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 DEC PY 2007 VL 132 IS 6 BP 1729 EP 1730 DI 10.1378/chest.07-1792 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 246HA UT WOS:000251996900006 PM 18079215 ER PT J AU McGhan, R Radcliff, T Fish, R Sutherland, ER Welsh, C Make, B AF McGhan, Ryan Radcliff, Tiffany Fish, Ron Sutherland, E. Rand Welsh, Carolyn Make, Barry TI Predictors of rehospitalization and death after a severe exacerbation of COPD SO CHEST LA English DT Article DE age; chronic obstructive; comorbidity; exacerbation; gender; hospitalization; mortality; population groups; pulmonary disease; race; risk factors; US Department of Veterans Affairs ID OBSTRUCTIVE PULMONARY-DISEASE; INHALED CORTICOSTEROIDS; GENDER-DIFFERENCES; LUNG-FUNCTION; RISK-FACTORS; MORTALITY; HOSPITALIZATION; CARE; MORBIDITY; AMERICANS AB Background: Patients who survive a severe exacerbation of COPD are at high risk of rehospitalization for COPD and death. The objective of this study was to determine predictors of these events in a large cohort of Veterans Affairs (VA) patients. Methods: We identified 51,353 patients who were discharged after an exacerbation of COPD in the VA health-care system from 1999 to 2003, and determined the rates of rehospitalization for COPD and death from all causes. Potential risk factors were assessed with univariate and multivariate survival analysis. Results: On average, the cohort was elderly (mean age, 69 years), predominately white (78% white, 13% black, 3% other, and 6% unknown), and male (97%), consistent with the underlying VA population. The risk of death was 21% at 1 year, and 55% at 5 years. Independent risk factors for death were age, male gender, prior hospitalizations, and comorbidities including weight loss and pulmonary hypertension; nonwhite race and other comorbidities (asthma, hypertension, and obesity) were associated with decreased mortality. The risk of rehospitalization for COPD was 25% at I year, and 44% at 5 years, and was increased by age, male gender, prior hospitalizations, and comorbidities including asthma and pulmonary hypertension. Hispanic ethnicity and other comorbidities (diabetes and hypertension) were associated with a decreased risk of rehospitalization. Conclusions: Age, male gender, prior hospitalizations, and certain comorbid conditions were risk factors for death and rehospitalization in patients discharged after a severe COPD exacerbation. Nonwhite race and other comorbidities were associated with decreased risk. C1 [Sutherland, E. Rand] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Boulder, CO 80309 USA. [McGhan, Ryan] Denver Hlth & Hosp Author, Denver, CO USA. [Radcliff, Tiffany; Welsh, Carolyn] Denver Vet Affairs Med Ctr, Denver, CO USA. [Fish, Ron] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Hlth Care Policy & Res, Boulder, CO 80309 USA. [Make, Barry] Natl Jewish Med & Res Ctr, Denver, CO USA. RP McGhan, R (reprint author), 2841 DeBarr Rd,St 771, Anchorage, AK 99508 USA. EM ryanmcghan11@hotmail.com RI Sutherland, Everett/B-7666-2008 FU NHLBI NIH HHS [2 T32 HL 007085] NR 41 TC 111 Z9 112 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2007 VL 132 IS 6 BP 1748 EP 1755 DI 10.1378/chest.06-3018 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 246HA UT WOS:000251996900010 PM 17890477 ER PT J AU Alexeeff, SE Litonjua, AA Suh, H Sparrow, D Vokonas, PS Schwartz, J AF Alexeeff, Stacey E. Litonjua, Augusto A. Suh, Helen Sparrow, David Vokonas, Pantel S. Schwartz, Joel TI Ozone exposure and lung function - Effect modified by obesity and airways hyperresponsiveness in the VA normative aging study SO CHEST LA English DT Article DE air pollution; airway hyperresponsiveness; FEV1; FVC; lung function obesity; ozone ID BODY-MASS INDEX; PULMONARY-FUNCTION; AIR-POLLUTION; BRONCHIAL RESPONSIVENESS; ETHNIC-DIFFERENCES; TIME-SERIES; ASTHMA; RESPONSES; MORTALITY; CHILDREN AB Background: Ozone has heterogeneous effects on lung function. We investigated whether obesity and airways hyperresponsiveness (AHR) modify the acute effects of ozone on lung function in the elderly. Methods: We studied 904 elderly men from the Normative Aging Study whose lung function (FVC, FEV1) was measured approximately every 3 years from 1995 to 2005. We defined obesity as a body mass index of at least 30 kg/m(2). Using a standardized methacholine challenge test, we defined AHR as a FEV, decline of 20% after inhalation of a cumulative dosage of 0 to 8.58 mu mol of methacholine. Ambient ozone in the Greater Boston area was measured continuously. We estimated effects using mixed linear models, adjusting for known confounders. Results: An increase in ozone of 15 parts per billion during the previous 48 h was associated with a greater decline in FEV1 in the obese (-2.07%; 95% confidence interval [CI], -3.25 to -0.89%) than in the nonobese (-0.96%; 95% CI, -1.70 to - 0.20%). The same exposure was also associated with a greater decline in FEV1 for those with AHR (-3.07%; 95% CI, -4.75 to -1.36%) compared to those without AHR (-1.32%; 95% CI, -2.06 to -0.57%). A three-way interaction trend test demonstrated a multiplicative effect of those two risk factors (p < 0.001). We found similar associations for FVC. Conclusions: Our results indicate that both obesity and AHR modify the acute effect of ozone on lung function in the elderly, with evidence of interaction between AHR and obesity that causes a greater than additive effect. C1 [Alexeeff, Stacey E.; Suh, Helen; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02215 USA. [Litonjua, Augusto A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, VA Normat Aging Study, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Alexeeff, SE (reprint author), Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Landmark Ctr W 415,401 Pk Dr, Boston, MA 02215 USA. EM sackerma@hsph.harvard.edu FU NIEHS NIH HHS [ES015172-01, ES0002] NR 53 TC 36 Z9 37 U1 2 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2007 VL 132 IS 6 BP 1890 EP 1897 DI 10.1378/chest.07-1126 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 246HA UT WOS:000251996900030 PM 17925423 ER PT J AU Al-Ansari, E Du, HK Yu, LY Ochoa, CD Garg, HG Quinn, DA Hales, CA AF Al-Ansari, Essam Du, Hong-Kai Yu, Lunyin Ochoa, Cristhiaan D. Garg, Hari G. Quinn, Deborah A. Hales, Charles A. TI Low-molecular-weight heparin inhibits hypoxic pulmonary hypertension and vascular remodeling in guinea pigs SO CHEST LA English DT Article DE dalteparin; enoxapain; hypoxia; low-molecular-weight heparin ID MUSCLE-CELL-PROLIFERATION; GROWTH; DISEASE; ANTICOAGULANT; CIRCULATION; INJURY; CHARGE; HEART; MODEL; LUNG AB Rationale: We have shown previously that antiproliferative unfractionated heparins block hypoxia-induced pulmonary arterial hypertension (PAH) and vascular remodeling, and hypothesized that low-molecular-weight heparins (LMWHs) would too. Objectives: To determine the potential role and mechanisms of dalteparin and enoxaparin (two LMWHs) in inhibiting hypoxic PAH and vascular remodeling. Methods: Male Hartley guinea pigs were exposed for 10 days to normobaric 10% oxygen with dalteparin (5 mg/kg), enoxaparin (5 mg/kg), or with an equivalent volume of normal saline solution. Normoxic control animals (n = 5) received room air for 10 days. Bovine pulmonary artery smooth-muscle cells (PASMCs) were grown in 10% fetal bovine serum without heparin, with dalteparin (1 mu g/mL) or with enoxaparin (1 mu g/mL). Measurements: Pulmonary arterial pressure (PAP), cardiac index, right ventricular heart weight divided by left ventricular plus septum weight (RV/LV+S), hematocrit, percentage of wall thickness of intraacinar vessels (%WT-IA), percentage of wall thickness of terminal bronchiole vessels (%WT-TA), and the percentage of thick-walled vessels (%Thick) were determined. In PASMCs, expression of p27 and cell growth were compared because in mice whole heparin depends on p27 for its antiproliferative action. Main results: In hypoxic animals, hematocrit, PAT, total pulmonary vascular resistance index, RV/LV+S, %WT-IA, %WT-TA, and %Thick all rose significantly vs normoxic control animals (p < 0.05); cardiac index was unchanged. Dalteparin but not enoxaparin significantly reduced PAP, total pulmonary vascular resistance index, and RV/LV + S (p < 0.05 vs hypoxia alone); inhibited PASMC growth; and upregulated p27 expression. Enoxaparin moderately reduced vascular remodeling, which did not translate into less pulmonary hypertension. Conclusions: Not all LMWHs are the same. Dalteparin was more effective than enoxaparin in inhibiting pulmonary hypertension and vascular remodeling in hypoxic guinea pigs. C1 [Al-Ansari, Essam; Du, Hong-Kai; Yu, Lunyin; Ochoa, Cristhiaan D.; Garg, Hari G.; Quinn, Deborah A.; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, 55 Fruit St,Bullfinch 148, Boston, MA 02114 USA. EM chales@partners.org FU NHLBI NIH HHS [HL03920, HL39150] NR 43 TC 11 Z9 12 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2007 VL 132 IS 6 BP 1898 EP 1905 DI 10.1378/chest.06-0941 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 246HA UT WOS:000251996900031 PM 18079223 ER PT J AU Yamamoto, R Akazawa, H Ito, K Toko, H Sano, M Yasuda, N Qin, Y Kudo, Y Sugaya, T Chien, KR Komuro, I AF Yamamoto, Rie Akazawa, Hiroshi Ito, Kaoru Toko, Haruhiro Sano, Masanori Yasuda, Noritaka Qin, Yingjie Kudo, Yoko Sugaya, Takeshi Chien, Kenneth R. Komuro, Issei TI Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-Deficient mice SO CIRCULATION JOURNAL LA English DT Article DE angiotensin II; cardiomyopathy; heart failure; remodeling; sarcoplasmic reticulum ID MECHANICAL STRETCH SENSOR; MUSCLE LIM PROTEIN; DILATED CARDIOMYOPATHY; DIASTOLIC DYSFUNCTION; KNOCKOUT MICE; VENTRICULAR HYPERTROPHY; MYOCARDIAL-INFARCTION; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; ENZYME-INHIBITION AB Background Angiotensin It (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT(1)) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT(1) receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes. Method and Results Hearts from MLP knockout (MLPKO) mice and MLP-AT(1a), receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts. Conclusions The AT(1a) receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy. C1 Chiba Univ, Grad Sch Med, Dept Cardiovasc Sci & Med, Chuo Ku, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Div Cardiovasc Physiopathol, Chiba 2608670, Japan. Tanabe Seiyaku Co Ltd, Discovery Lab, Osaka, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Komuro, I (reprint author), Chiba Univ, Grad Sch Med, Dept Cardiovasc Sci & Med, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM komuro-tky@umin.ac.jp NR 47 TC 13 Z9 15 U1 0 U2 0 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD DEC PY 2007 VL 71 IS 12 BP 1958 EP 1964 DI 10.1253/circj.71.1958 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 237BL UT WOS:000251347500023 PM 18037754 ER PT J AU Sakata, S Liang, L Sakata, N Sakata, Y Chemaly, ER Lebeche, D Takewa, Y Chen, J Park, WJ Kawase, Y Hajjar, RJ AF Sakata, Susumu Liang, Lifan Sakata, Naoya Sakata, Yuri Chemaly, Elie R. Lebeche, Djamel Takewa, Yoshiaki Chen, Jiqiu Park, Woo Jin Kawase, Yoshiaki Hajjar, Roger J. TI Preservation of mechanical and energetic function after adenoviral gene transfer in normal rat hearts SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE adenovirus; gene transfer; mechanoenergetics; oxygen consumption ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; VENTRICULAR-FUNCTION; DIASTOLIC FUNCTION; IN-VIVO; MYOCARDIUM; FAILURE; CALCIUM; CALSEQUESTRIN; MYOCYTES; THERAPY AB 1. The aim of the present study was to examine the acute and chronic effects of adenoviral gene transfer on cardiac function in terms of left ventricular (LV) mechanoenergetic function. Recombinant adenoviral vector carrying beta-galactosidase and green fluorescent protein genes (Ad.beta gal-GFP) was used. Cardiac function was examined in cross-circulated rat heart preparations, where end-systolic/diastolic pressure-volume relationships (ESPVR/EDPVR), systolic pressure-volume area (PVA), LV relaxation rate, equivalent maximal elastance at mid-range LV volume (eE(max) at mLVV), coronary blood flow, coronary vascular resistance and myocardial oxygen consumption (VO2) were also measured. 2. To examine the ex vivo acute effects of the adenoviral vector, data were obtained before and 30-90 min after intracoronary infusion of Ad.beta gal-GFP in the excised, cross-circulated hearts that underwent serotonin pretreatment. To examine the in vivo chronic effects of adenoviral gene transfer, normal rat hearts received Ad.beta gal-GFP or saline by a catheter-based technique and data were obtained 3 days after the injection of Ad.beta gal-GFP or saline. 3. The ESPVR, EDPVR, LV relaxation rate, eE(max) at mLVV, coronary blood flow and coronary vascular resistance remained unchanged in Ad.beta gal-GFP-transfected hearts in both ex vivo acute and in vivo chronic experiments. Moreover, the ex vivo and in vivo transfection caused no change in the slope and VO2 intercept of the VO2-PVA relationship, VO2 for basal metabolism and for Ca2+ handling in excitation-contraction coupling and O-2 costs of LV contractility. 4. These results indicate that adenoviral gene transfer has neither acute nor chronic toxic effects on LV mechanical and energetic function. A special combination of in vivo adenoviral gene transfer and a cross-circulation experimental system may provide a useful novel strategy to explore the functional and mechanoenergetic role of specifically targeted genes in the diseased heart. C1 Nara Med Univ, Sch Med, Dept Physiol 2, Nara 6348521, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. RP Sakata, S (reprint author), Nara Med Univ, Sch Med, Dept Physiol 2, 840 Shijo Cho, Nara 6348521, Japan. EM ssakata@naramed-u.ac.jp FU NHLBI NIH HHS [K01 HL076659, HL083156, HL057263, R01 HL078691, HL080498, HL071763] NR 26 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD DEC PY 2007 VL 34 IS 12 BP 1300 EP 1306 DI 10.1111/j.1440-1681.2007.04742.x PG 7 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 224GI UT WOS:000250435100015 PM 17973872 ER PT J AU Shalaby, AA El-Saed, A Nemec, J Moossy, JJ Balzer, JR AF Shalaby, Alaa A. El-Saed, Aiman Nemec, Jan Moossy, John J. Balzer, Jeffrey R. TI Exacerbation of electrical storm subsequent to implantation of a right vagal stimulator SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE implantable defibrillator; vagal stimulation; ventricular tachycardia; cardiac arrhythmia; treatment; autonomic nervous system ID NERVE-STIMULATION; HEART-FAILURE; VENTRICULAR-ARRHYTHMIAS; CARDIAC TISSUE; PROPAGATION; CONDUCTION; SURVIVAL; PROTEIN; SUDDEN; DEATH AB A patient with advanced ischemic cardiomyopathy underwent implantation of a vagal stimulator in an attempt to control recurrent drug refractory ventricular arrhythmia. Electrical storm was exacerbated after the implant and continued after neurostimulation was discontinued. The report aims to provide a cautionary note to application of vagal stimulation for control of cardiac arrhythmia. C1 [Shalaby, Alaa A.; Nemec, Jan] Univ Pittsburgh, Div Cardiol, Pittsburgh, PA 15240 USA. [Shalaby, Alaa A.; Moossy, John J.; Balzer, Jeffrey R.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [El-Saed, Aiman] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Moossy, John J.] Univ Pittsburgh, Div Neurosurg, Pittsburgh, PA USA. [Balzer, Jeffrey R.] Univ Pittsburgh, Div Neurosci, Pittsburgh, PA USA. RP Shalaby, AA (reprint author), Univ Pittsburgh, Div Cardiol, 111C Univ Dr, Pittsburgh, PA 15240 USA. EM alaa.shalaby@med.va.gov OI El-Saed, Aiman/0000-0002-1781-2203 NR 18 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD DEC PY 2007 VL 17 IS 6 BP 385 EP 390 DI 10.1007/s10286-007-0440-1 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 241FC UT WOS:000251641300011 PM 17898926 ER PT J AU Friebel, TM Domchek, SM Neuhausen, SL Wagner, T Evans, DG Isaacs, C Garber, JE Daly, MB Eeles, R Matloff, E Tomlinson, G Lynch, HT Tung, N Blum, JL Weitzel, J Rubinstein, WS Ganz, PA Couch, F Rebbeck, TR AF Friebel, Tara M. Domchek, Susan M. Neuhausen, Susan L. Wagner, Theresa Evans, D. Gareth Isaacs, Claudine Garber, Judy E. Daly, Mary B. Eeles, Rosalind Matloff, Ellen Tomlinson, Gail Lynch, Henry T. Tung, Nadine Blum, Joanne L. Weitzel, Jeffrey Rubinstein, Wendy S. Ganz, Patricia A. Couch, Fergus Rebbeck, Timothy R. TI Bilateral prophylactic oophorectomy and bilateral prophylactic mastectomy in a prospective cohort of unaffected BRCA1 and BRCA2 mutation carriers SO CLINICAL BREAST CANCER LA English DT Article DE genetic testing; hereditary breast cancer; surgery ID BREAST-CANCER RISK; SALPINGO-OOPHORECTOMY; OVARIAN-CANCER; PREVENTIVE MEASURES; GENE MUTATION; WOMEN; SURGERY; POPULATION AB Background: Women with BRCA1 or BRCA2 (BRCA1/2) mutations can reduce cancer incidence and mortality by using bilateral prophylactic oophorectomy (BPO) or bilateral prophylactic mastectomy (BPM). The availability of these risk-reduction strategies is an important consideration in the decision to undergo genetic testing. Patients and Methods: We evaluated the use of BPO and BPM in a prospective sample of 537 female BRCA1/2 mutation carriers from 17 centers in North America and Europe. These women were aged > 30 years, had no BPM, BPO, breast cancer, or ovarian cancer before the disclosure of their genetic test results and were followed for > 6 months. Results: Bilateral prophylactic oophorectomy is used significantly more frequently than BPM (55% vs. 21%; P < .001). Bilateral prophylactic oophorectomy was more common among women age >= 40 years compared with women aged < 40 years (68% vs. 43%; P < .001) and among porous women compared with nulliparous women (60% vs. 39%; P < .001). There was no difference in BPM (P = .83) or BPO (P = .09) in BRCA1 versus BRCA2 carriers. Multivariate models identified age and parity as a predictor of BPO in BRCA1 carriers; age and ovarian cancer family history in BRCA2 carriers; parity and ovarian cancer family history as a predictor of BPM in BRCA1 carriers; and smoking and ovarian cancer family history in BRCA2 carriers. Conclusion: Bilateral prophylactic oophorectomy is more commonly used than BPM in unaffected BRCA1/2 mutation carriers. Parity, age, and family history can also influence BPO and BPM uptake. Consistent with current recommendations, BPO is used by the majority of porous women aged > 40 years. C1 [Friebel, Tara M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Domchek, Susan M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Neuhausen, Susan L.] Univ Calif Irvine, Irvine, CA 92717 USA. [Wagner, Theresa] Univ Vienna, A-1010 Vienna, Austria. [Evans, D. Gareth] St Marys Hosp, Manchester M13 0JH, Lancs, England. [Isaacs, Claudine] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Eeles, Rosalind] Royal Marsden Hosp, NHS Trust, Sutton, Surrey, England. [Matloff, Ellen] Yale Univ, New Haven, CT 06520 USA. [Lynch, Henry T.] Creighton Univ, Omaha, NE 68178 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Blum, Joanne L.] Baylor Univ, Med Ctr, Dallas, TX USA. [Weitzel, Jeffrey] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Rubinstein, Wendy S.] Evanston NW Hlthcare Ctr Med Genet, Evanston, IL USA. [Couch, Fergus] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Couch, Fergus] Mayo Clin, Coll Med, Rochester, MN USA. RP Friebel, TM (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, 909 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM tfriebel@mail.med.upenn.edu FU NCI NIH HHS [5U01 CA86389, R01-CA74415] NR 26 TC 40 Z9 42 U1 0 U2 4 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 DEC PY 2007 VL 7 IS 11 BP 875 EP 882 DI 10.3816/CBC.2007.n.053 PG 8 WC Oncology SC Oncology GA 247RX UT WOS:000252098700008 PM 18269778 ER PT J AU Goss, PE Richardson, H Chlebowski, R Johnston, D Sarto, GE Maunsell, E Ingle, JN Ales-Martinez, JE AF Goss, Paul E. Richardson, Harriet Chlebowski, Rowan Johnston, Dianne Sarto, Gloria E. Maunsell, Elizabeth Ingle, James N. Ales-Martinez, Jose E. TI National cancer institute of Canada clinical trials group MAP.3 trial: Evaluation of exemestane to prevent breast cancer in postmenopausal women SO CLINICAL BREAST CANCER LA English DT Article DE aromatase inhibitors; estrogen receptor; selective estrogen receptor modulators ID QUALITY-OF-LIFE; ONCOLOGY-TECHNOLOGY-ASSESSMENT; STAR P-2 TRIAL; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; TAMOXIFEN THERAPY; ADJUVANT THERAPY; RISK REDUCTION; DRUG-THERAPY; RALOXIFENE C1 [Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Richardson, Harriet; Johnston, Dianne] Queens Univ, Natl Canc Inst, Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Chlebowski, Rowan] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Sarto, Gloria E.] Univ Wisconsin, Sch Med, Madison, WI 53706 USA. [Maunsell, Elizabeth] Univ Laval, Fac Med, Unite Rech Sante Populat, Quebec City, PQ G1K 7P4, Canada. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Ales-Martinez, Jose E.] Hosp Ruber Internacl, Madrid, Spain. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 35 TC 13 Z9 13 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 DEC PY 2007 VL 7 IS 11 BP 895 EP 900 DI 10.3816/CBC.2007.n.057 PG 6 WC Oncology SC Oncology GA 247RX UT WOS:000252098700012 PM 18269782 ER PT J AU Loghin, ME Prados, MD Wen, P Junck, L Lieberman, F Fine, H Fink, KL Metha, M Kuhn, J Lamborn, K Chang, SM Cloughesy, T DeAngelis, LM Robins, IH Aldape, KD Yung, WKA AF Loghin, Monica E. Prados, Michael D. Wen, Patrick Junck, Larry Lieberman, Frank Fine, Howard Fink, Karen L. Metha, Minesh Kuhn, John Lamborn, Kathleen Chang, Susan M. Cloughesy, Timothy DeAngelis, Lisa M. Robins, Ian H. Aldape, Kenneth D. Yung, W. K. Alfred TI Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in patients receiving enzyme-inducing antiepileptic drugs: A North American brain tumor consortium study SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-GRADE GLIOMA; ANTITUMOR IMIDAZOTETRAZINES; TOPOISOMERASE-I; SOLID TUMORS; CPT-11; TRIAL; PHARMACOKINETICS; CANCER; CAMPTOTHECIN; XENOGRAFTS AB Purpose:To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. Design: Patients with recurrent malignant glioma received a fixed dose of temozolomide (150 mg/m(2)) daily for 5 days from days 1 to 5 every 28 days, and an i.v. infusion of irinotecan on 2 days 1 and 15 of each cycle. The starting dose of irinotecan was 350 mg/m(2), which was escalated to 550 mg/m(2) in 50-mg/m(2) increments. The plasma pharmacokinetics of irinotecan and its active metabolite, SN-38, were determined during the infusion of irinotecan on cycle 1, day 1. Results: Thirty-three patients were enrolled into the study and treated. Thirty-one patients were evaluable for both tumor response and toxicity and two patients were evaluable for toxicity only. Common toxicities included neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose for irinotecan was determined to be 500 mg/m(2). Conclusions: The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan. C1 Univ Texas Houston, MD Anderson Canc Ctr, Unit 431, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan Hosp, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Med Ctr Canc Pavilion, Pittsburgh, PA USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. Univ Wisconsin Hosp, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Yung, WKA (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Unit 431, Dept Neurooncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM wyung@mdanderson.org FU NCI NIH HHS [U01CA62399, U01 CA062399, U01CA62426, UM1 CA137443, U01CA62412, U01 CA062426, U01 CA062412] NR 35 TC 14 Z9 14 U1 0 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 DEC 1 PY 2007 VL 13 IS 23 BP 7133 EP 7138 DI 10.1158/1078-0432.CCR-07-0874 PG 6 WC Oncology SC Oncology GA 239PA UT WOS:000251529000030 PM 18056194 ER PT J AU Zhang, XP Li, WH Olumi, AF AF Zhang, Xiaoping Li, Wenhua Olumi, Aria F. TI Low-dose 12-O-tetradecanoylphorbol-13-acetate enhances tumor necrosis factor - Related apoptosis-inducing ligand - Induced apoptosis in prostate cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID TRAIL-INDUCED APOPTOSIS; PHORBOL ESTER; DEATH RECEPTORS; DECOY RECEPTORS; CARCINOMA-CELLS; TARGETING DEATH; LEUKEMIA-CELLS; LNCAP CELLS; IN-VITRO; RESISTANCE AB Purpose: Previously, we have shown that c-Fos/activator protein-1 (AP-1) promotes tumor necrosis factor (TNF) - related apoptosis-inducing ligand (TRAIL) - induced apoptosis by repressing the antiapoptotic molecule c-FLIP(L). In this study, we investigated whether synthetic induction of c-Fos/AP-1 by 12-O-tetradecanoylphorbol-13-acetate (TPA) converts the phenotype of TRAIL-resistant prostate cancer cells to a TRAIL- sensitive phenotype in vitro and in vivo. Experimental Design: Low-dose TPA was used to determine whether LNCaP prostate cancer cells could be converted to a TRAIL-sensitive phenotype in in vitro and in vivo studies. We also assessed whether TPA enhancement of TRAIL-induced apoptosis varies between androgen-sensitive and androgen-insensitive prostate cancer cells and evaluated the role of TRAIL receptors, DR4 and DR5, in TPA-enhanced TRAIL-induced apoptosis. Results: We show that the combination of TRAIL with low-dose TPA has no effect on nonmalignant prostate epithelial cells; however, TPA up-regulates most AP-1 proteins and AP-1 activity, reduces c-FLIP(L), and potentiates TRAIL- induced apoptosis. We show that the combination of TPA + TRAIL is effective in promoting apoptosis in both hormone-sensitive LNCaP and hormone-insensitive LNCaP-C4-2 prostate cancer cells. Although TPA enhances the TRAIL-receptor 1 (DR4) level, sensitization of prostate cancer cells seems to be more dependent on TRAIL-receptor 2 (DR5) than TRAIL- receptor 1 levels. In vivo xenograft experiments suggest that TPA elevates the expression of c-Fos and reduces c-FLIP(L). Combination of TPA with TRAIL-receptor 2 agonist antibody, lexatumumab, effectively increases apoptosis and reduces LNCaP xenograft tumor burden. Conclusions: TPA, when combined with the proapoptotic agent TRAIL, is effective in changing the phenotype of some TRAIL- resistant prostate cancer cells to a TRAIL-sensitive phenotype. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Yawkey Bldg,Suite 7E, Boston, MA 02114 USA. EM aolumi@partners.org FU NIDDK NIH HHS [DK64062] NR 48 TC 12 Z9 14 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 DEC 1 PY 2007 VL 13 IS 23 BP 7181 EP 7190 DI 10.1158/1078-0432.CCFI-07-1133 PG 10 WC Oncology SC Oncology GA 239PA UT WOS:000251529000036 PM 18056199 ER PT J AU Shen, YP Irons, M Miller, DT Cheung, SW Lip, V Sheng, X Tomaszewicz, K Shao, H Fang, H Tang, HS Walsh, CA Platt, O Gusella, JF Wu, BL AF Shen, Yiping Irons, Mira Miller, David T. Cheung, Sau Wai Lip, Va Sheng, Xiaoming Tomaszewicz, Keith Shao, Hong Fang, Hong Tang, Hung Siv Walsh, Christopher A. Platt, Orah Gusella, James F. Wu, Bai-Lin TI Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance SO CLINICAL CHEMISTRY LA English DT Article ID COPY-NUMBER VARIATIONS; MENTAL-RETARDATION; CGH; MICROARRAY; DELETIONS; CHILDREN; BAC AB Background. Submicroscopic genomic imbalance underlies well-defined microdeletion and microduplication syndromes and contributes to general developmental disorders such as mental retardation and autism. Array comparative genomic hybridization (CGH) complements routine cytogenetic methods such as karyotyping and fluorescence in situ hybridization (FISH) for the detection of genomic imbalance. Oligonucleotide arrays in particular offer advantages in ease of manufacturing, but standard arrays for single-nucleotide polymorphism genotyping or linkage analysis offer variable coverage in clinically relevant regions. We report the design and validation of a focused oligonucleotide-array CGH assay for clinical laboratory diagnosis of genomic imbalance. Methods: We selected >10 000 60-mer oligonucleotide features from Agilent's eArray probe library to interrogate all subtelomeric and pericentromeric regions and 95 additional clinically relevant regions for a total of 179 loci. Sensitivity and specificity were measured for 105 patient samples, including 51 with known genomic-imbalance events, as detected by bacterial artificial chromosome-based array CGH, FISH, or multiplex ligation-dependent probe amplification. Results: Focused array CGH detected all known regions of genomic imbalance in 51 validation samples with 100% concordance and an excellent signal-to-noise ratio. The mean SD among 1092 ratios of all noncontrol features without copy number alteration was 0.062 (median, 0.055). Clinical testing of another 211 samples from individuals with developmental delay, unexplained mental retardation, dysmorphic features, or multiple congenital anomalies revealed genomic imbalance in 25 samples (11.9%). Conclusions: This focused oligonucleotide-array CGH assay, a flexible, robust method for clinically diagnosing genetic disorders associated with genomic imbalance, offers appreciable advantages over currently available platforms. (C) 2007 American Association for Clinical Chemistry. C1 Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Wu, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bai-lin.wu@childrens.harvard.edu FU NINDS NIH HHS [NS24279, R37 NS35129] NR 26 TC 39 Z9 43 U1 1 U2 3 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 DEC PY 2007 VL 53 IS 12 BP 2051 EP 2059 DI 10.1373/clinchem.2007.090290 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 236CR UT WOS:000251281100004 PM 17901113 ER PT J AU Bonanno, C Shehi, E Adlerstein, D Makrigiorgos, GM AF Bonanno, Cinzia Shehi, Erlet Adlerstein, Daniel Makrigiorgos, G. Mike TI MS-FLAG, a novel real-time signal generation method for methylation-specific PCR SO CLINICAL CHEMISTRY LA English DT Article ID POLYMERASE-CHAIN-REACTION; DNA METHYLATION; CPG ISLAND; HUMAN CANCER; LUNG-CANCER; GENE; HYPERMETHYLATION; ASSAY; AMPLIFICATION; FLUORESCENCE AB Background: Aberrant promoter methylation is a major mechanism for silencing tumor suppressor genes in cancer. Detection of hypermethylation is used as a molecular marker for early cancer diagnosis, as a prognostic index, or to define therapeutic targets for reversion of aberrant methylation. We report on a novel signal generation technology for real-time PCR to detect gene promoter methylation. Methods: FLAG (fluorescent amplicon generation) is a homogeneous signal generation technology based on the exceptionally thermostable endonuclease PspGI. FLAG provides real-time signal generation during PCR by PspGI-mediated cleavage of quenched fluorophories at the 5' end of double-stranded PCR products. Methylation-specific PCR (MSP) applied on bisulfite-treated DNA was adapted to a real-time format (methylation-specific FLAG; MS-FLAG) for quantifying methylation in the promoter of CDKN2A (p16), GATA5, and RASSF1. We validated MS-FLAG on plasmids and genomic DNA with known methylation status and applied it to detection of methylation in a limited number of clinical samples. We also conducted bisulfite sequencing on these samples. Results: Real-time PCR results obtained via MS-FLAG agreed with results obtained via conventional, gel-based MSP. The new technology showed high specificity, sensitivity (2-3 plasmid copies), and selectivity (0.01% of methylated DNA) on control samples. It enabled correct prediction of the methylation status of all 3 gene promoters in 21 lung adenocarcinoma samples, as confirmed by bisulfite sequencing. We also developed a multiplex MS-FLAG assay for GATA5 and RASSF1 promoters. Conclusion: MS-FLAG provides a new, quantitative, high-throughput method for detecting gene promoter methylation and is a convenient alternative to agarose gel-based MSP for screening methylation. In addition to methylation, FLAG-based real-time signal generation may have broad applications in DNA diagnostics. (C) 2007 American Association for Clinical Chemistry. C1 Univ Milano Biocca, Milan, Italy. DiaSorin SpA, Saluggia, VC, Italy. Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Adlerstein, D (reprint author), Diasorin SpA, Viale Pasteur 10, I-20014 Nerviano, MI, Italy. FU NCI NIH HHS [CA111994-01, CA115439-01] NR 40 TC 21 Z9 23 U1 1 U2 6 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 DEC PY 2007 VL 53 IS 12 BP 2119 EP 2127 DI 10.1373/clinchem.2007.094011 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 236CR UT WOS:000251281100012 PM 17962364 ER PT J AU Linglart, A Bastepe, M Juppner, H AF Linglart, Agnes Bastepe, Murat Juppner, Harald TI Similar clinical and laboratory findings in patients with symptomatic autosomal dominant and sporadic pseudohypoparathyroidism type Ib despite different epigenetic changes at the GNAS locus SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; IMPRINTING CONTROL ELEMENT; GENE; MUTATIONS; METHYLATION; RESISTANCE; DELETION; REGION; DEFECT AB Objective Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry an identical maternally inherited 3-kb microdeletion up-stream of GNAS (STX16del4-6(mat)), which is associated with a methylation loss restricted to exon A/B. STX16del4-6(mat) is not found in sporadic PHP-Ib (sporPHP-Ib) patients, who show broad GNAS methylation changes. Because of the epigenetic differences between both groups, we searched for clinical and/or laboratory differences. Patients and methods Age at diagnosis, calcium, phosphorus and PTH were analysed in 43 patients with AD-PHP-Ib due to STX16del4-6(mat) and in 22 patients with sporPHP-Ib. Results All AD-PHP-Ib patients with STX16del4-6(mat) showed only loss of exon A/B methylation. Of the 43 individuals, 26 were symptomatic when diagnosis was established at age 12 center dot 1 +/- 1 center dot 34 years (mean +/- SEM); laboratory findings at presentation were calcium 1 center dot 69 +/- 0 center dot 06 mmol/l, phosphorus 2 center dot 25 +/- 0 center dot 12 mmol/l and PTH 442 +/- 54 center dot 1 pg/ml. The remaining 17 individuals with STX16del46(mat) were asymptomatic when diagnosed at age 23 center dot 5 +/- 3 center dot 93 years (calcium 2 center dot 18 +/- 0 center dot 05 mmol/l, phosphorus 1 center dot 63 +/- 0 center dot 10 mmol/l, PTH 222 +/- 40 center dot 3 pg/ml). Patients with sporPHP-Ib showed methylation changes at two or more GNAS exons, presented at age 10 center dot 0 +/- 1 center dot 01 years and had, as a group, similar laboratory findings as patients with symptomatic AD-PHP-Ib (calcium 1 center dot 51 +/- 0 center dot 06 mmol/l, phosphorus 2 center dot 65 +/- 0 center dot 10 mmol/l, PTH 634 +/- 162 center dot 1 pg/ml). However, sporPHP-Ib females appeared to be more severely affected. Conclusions Patients with symptomatic AD-PHP-Ib due to STX16del4-6(mat) and sporPHP-Ib have similar changes in calcium, phosphate and PTH. STX16del4-6(mat) often leads to asymptomatic disease and screening of all siblings of affected individuals is therefore advised. The cause of the apparent sexual dimorphism in patients with sporPHP-Ib remains uncertain. C1 Harvard Univ, Sch Med, Endocrine Unit, Cambridge, MA 02138 USA. Hop St Vincent de Paul, INSERM, U561, Paris, France. Massachusetts Gen Hosp, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM hjueppner@partners.org FU NIDDK NIH HHS [KO1-DK-062973]; PHS HHS [R0146718-10] NR 31 TC 53 Z9 56 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2007 VL 67 IS 6 BP 822 EP 831 DI 10.1111/j.1365-2265.2007.02969.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232NC UT WOS:000251025400004 PM 17651445 ER PT J AU Brambilla, DJ O'Donnell, AB Matsumoto, AM McKinlay, JB AF Brambilla, Donald J. O'Donnell, Amy B. Matsumoto, Alvin M. McKinlay, John B. TI Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men SO CLINICAL ENDOCRINOLOGY LA English DT Article ID MIDDLE-AGED MEN; HEALTHY-MEN; LUTEINIZING-HORMONE; CIRCADIAN VARIATION; BOUND TESTOSTERONE; BINDING GLOBULIN; HYPOGONADAL MEN; ELDERLY-MEN; YOUNG MEN; FOLLITROPIN AB Background Estimates of intraindividual variation in hormone levels provide the basis for interpreting hormone measurements clinically and for developing eligibility criteria for trials of hormone replacement therapy. However, reliable systematic estimates of such variation are lacking. Objective To estimate intraindividual variation of serum total, free and bioavailable testosterone (T), dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and the contributions of biological and assay variation to the total. Design Paired blood samples were obtained 1-3 days apart at entry and again 3 months and 6 months later (maximum six samples per subject). Each sample consisted of a pool of equal aliquots of two blood draws 20 min apart. Study participants Men aged 30-79 years were randomly selected from the respondents to the Boston Area Community Health Survey, a study of the health of the general population of Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all six visits, 8 who completed the first two visits and 3 who completed the first four visits. Measurements Day-to-day and 3-month (long-term) intraindividual standard deviations, after transforming measurements to logarithms to eliminate the contribution of hormone level to intraindividual variation. Results Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time. Conclusions Given the level of intraindividual variability in hormone levels found in this study, one sample is generally not sufficient to characterize an individual's hormone levels but collecting more than three is probably not warranted. This is true for clinical measurements and for hormone measurements used to determine eligibility for a clinical trial of hormone replacement therapy. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Brambilla, DJ (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM dbrambilla@neriscience.com RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIA NIH HHS [AG23027] NR 36 TC 77 Z9 79 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2007 VL 67 IS 6 BP 853 EP 862 DI 10.1111/j.1365-2265.2007.02976.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232NC UT WOS:000251025400008 PM 18052942 ER PT J AU Rutherford, AE Hynan, LS Borges, CBS Forcione, DG Blackard, JT Lin, W Gorman, AR Shaikh, OS Reuben, A Harrison, E Reddy, KR Le, WM Chung, RT AF Rutherford, Anna E. Hynan, Linda S. Borges, Carolina B. S. Forcione, David G. Blackard, Jason T. Lin, Wenyu Gorman, April R. Shaikh, Obaid Shakil Reuben, Adrian Harrison, Edwyn Reddy, K. Rajender Le, William M. Chung, Raymond T. CA ALF Study Grp TI Serum apoptosis markers in acute liver failure: A pilot study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FULMINANT HEPATIC-FAILURE; MEDIATED APOPTOSIS; SOLUBLE FAS; INJURY; INVOLVEMENT; RECEPTOR; LIGAND; DAMAGE; MICE AB Background & Aims: We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition. Methods: Serum levels of soluble Fas (sFas), tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF), and interleukin-6 (IL-6) were measured in 67 acute liver failure patients, as well as controls. In a subset of the groups, we measured serum M-30 antigen, an exposed neoepitope from caspase cleavage. We also assessed M-30 immunoreactivity in liver tissue of ALF patients and controls. Results: Median levels for TNF-alpha, HGF, IL-6, and M-30 antigen were at least 10-fold greater in ALF than in hepatitis C virus or normal controls (P < .0001). Median day 1 sFas, day 3 sFas, and day 1 HGF levels varied according to etiology of acute liver failure (P = .004, P = .011, and P = .019, respectively), with values for drug-induced liver injury and acetaminophen-related ALF higher than other etiologies. Median M-30 antigen levels were significantly higher in patients who were transplanted and/or died (2183 U/L) than spontaneous survivors (1004 U/L) (P = .026). M-30 immunoreactivity in liver tissue was significantly greater in ALF patients than HCV controls (P = .004). Conclusions: TNF-alpha, HGF, IL-6, and M-30 antigen were significantly elevated in ALF. High levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF. Higher levels of M-30 antigen are associated with poor clinical outcomes in ALF. C1 [Rutherford, Anna E.; Borges, Carolina B. S.; Forcione, David G.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hynan, Linda S.; Gorman, April R.] Univ Texas SW Med Ctr Dallas, Div Biostat, Dept Clin Sci, Dallas, TX 75390 USA. [Blackard, Jason T.] Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH USA. [Shaikh, Obaid Shakil] Univ Pittsburgh, Med Ctr, Ctr Liver Dis, Pittsburgh, PA USA. [Reuben, Adrian] Med Univ S Carolina, Charleston, SC 29425 USA. [Harrison, Edwyn] Mayo Clin Scottsdale, Phoenix, AZ USA. [Reddy, K. Rajender] Hosp Univ Penn, GI Div, Philadelphia, PA USA. [Le, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 10,1007C,55 Fruit St, Boston, MA 02114 USA. EM RTChung@partners.org OI Hynan, Linda/0000-0002-4642-7769 FU NIDDK NIH HHS [2 U01 DK058369, R01 DK058369] NR 15 TC 35 Z9 40 U1 0 U2 6 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 DEC PY 2007 VL 5 IS 12 BP 1477 EP 1483 DI 10.1016/j.cgh.2007.08.007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 240GJ UT WOS:000251575000020 PM 17967565 ER PT J AU Bhanji, RA Eystathioy, T Chan, EKL Bloch, DB Fritzler, MJ AF Bhanji, Rahima A. Eystathioy, Theophany Chan, Edward K. L. Bloch, Donald B. Fritzler, Marvin J. TI Clinical and serological features of patients with autoantibodies to GW/P bodies SO CLINICAL IMMUNOLOGY LA English DT Article DE autoantibodies; P bodies GW182; Ago2; Ge-1 ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RNA INTERFERENCE PATHWAY; PROCESSING BODY; SJOGRENS-SYNDROME; NUCLEAR RIBONUCLEOPROTEIN; CYTOPLASMIC AUTOANTIGEN; MONOCLONAL-ANTIBODIES; AUTOIMMUNE-DISEASE; DECAPPING ENZYME; PROTEIN AB GW bodies (GWBs) are unique cytoplasmic structures involved in messenger RNA (mRNA) processing and RNA interference (RNAi). GWBs contain mRNA, components of the RNA-induced silencing complex (RISC), microRNA (miRNA), Argonaute proteins, the Ge-l/Hedls protein and other enzymes involving mRNA degradation. The objective of this study was to identify the target GWB autoantigens reactive with 55 sera from patients with anti-GWB autoantibodies and to identify clinical features associated with these antibodies. Analysis by addressable laser bead immunoassay (ALBIA) and immunoprecipitation of recombinant proteins indicated that autoantibodies in this cohort of anti-GWB sera were directed against Ge-1 /Hedls (58%), GW182 (40%) and Ago2 (16%). GWB autoantibodies targeted epitopes that included the N-terminus of Ago2 and the nuclear localization signal (NLS) containing region of Ge-1/Hedls. Clinical data were available on 42 patients of which 39 were female and the mean age was 61 years. The most common clinical presentations were neurological symptoms (i.e. ataxia, motor and sensory neuropathy) (33%), Sjogren's syndrome (SjS) (31%) and the remainder had a variety of other diagnoses that included systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary biliary cirrhosis (PBC). Moreover, 44% of patients with anti-GWB antibodies had reactivity to Ro52. These studies indicate that Ge-1 is a common target of anti-GWB sera and the majority of patients in a GWB cohort had SjS and neurological disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA. Massachusetts Gen Hosp, Gen Med Serv, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fritzler, MJ (reprint author), Univ Calgary, Fac Med, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM fritzler@ucalgary.ca RI Chan, Edward/B-5671-2009 OI Chan, Edward/0000-0003-3938-9503 FU NIAID NIH HHS [R21 AI047859, AI47859, R01 AI047859, R01 AI047859-07A1] NR 50 TC 53 Z9 57 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2007 VL 125 IS 3 BP 247 EP 256 DI 10.1016/j.clim.2007.07.016 PG 10 WC Immunology SC Immunology GA 238ZC UT WOS:000251486100005 PM 17870671 ER PT J AU Neragi-Miandoab, S Kim, J Vlahakes, GJ AF Neragi-Miandoab, S. Kim, J. Vlahakes, G. J. TI Malignant tumours of the heart: A review of tumour type, diagnosis and therapy SO CLINICAL ONCOLOGY LA English DT Editorial Material DE cardiac neoplasms; diagnosis; sarcomas; therapy ID PRIMARY CARDIAC TUMORS; RENAL-CELL CARCINOMA; CARNEY COMPLEX; SURGICAL-TREATMENT; NONCARDIAC TUMORS; ATRIAL-MYXOMA; EXPERIENCE; SARCOMA; P53; TRANSPLANTATION AB Primary cardiac neoplasms are rare and occur less commonly than metastatic disease of the heart. In this overview, current published studies concerning malignant neoplasms of the heart are reviewed, together with some insights into their aetiology, diagnosis and management-We searched medline using the subject 'cardiac neoplasms'. We selected about 110 articles from between 1973 and 2006, of which 76 sources were used to complete the review. Sarcomas are the most common cardiac tumours and include myxosarcoma, liposarcoma, angiosarcoma, fibrosarcoma, leiomyosarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, neurofibrosarcoma, malignant fibrous histiocytoma and undifferentiated sarcoma. The classic symptoms of cardiac tumours are intracardiac obstruction, signs of systemic embolisation, and systemic or constitutional symptoms. However, serious complications including stroke, myocardial infarction and even sudden death from arrhythmia may be the first signs of a tumour. Echocardiography and angiography are essential diagnostic tools for evaluating cardiac neoplasms. Computed tomography and magnetic resonance imaging studies have improved the diagnostic approach in recent decades. Successful treatment for benign cardiac tumours is usually achieved by surgical resection. Unfortunately, resection of the tumour is not always feasible. The prognosis after surgery is usually excellent in the case of benign tumours, but the prognosis of malignant tumours remains dismal. In conclusion, there are limited published data concerning cardiac neoplasms. Therefore, a high level of suspicion is required for early diagnosis. Surgery is the cornerstone of therapy. However, a multi-treatment approach, including chemotherapy, radiation as well as evolving approaches such as gene therapy, might provide a better palliative and curative result. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Surg, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Boston, MA 02114 USA. RP Neragi-Miandoab, S (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Surg, Cleveland, OH 44106 USA. EM sneragi@yahoo.com NR 77 TC 79 Z9 84 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD DEC PY 2007 VL 19 IS 10 BP 748 EP 756 DI 10.1016/j.clon.2007.06.009 PG 9 WC Oncology SC Oncology GA 239PV UT WOS:000251531100003 PM 17693068 ER PT J AU Crawford, MJ Dy, CJ Alexander, JW Thompson, M Schroder, SJ Vega, CE Patel, RV Miller, AR McCarthy, JC Lowe, WR Noble, PC AF Crawford, Matthew J. Dy, Christopher J. Alexander, Jerry W. Thompson, Matthew Schroder, Steven J. Vega, Charles E. Patel, Rikin V. Miller, Andrew R. McCarthy, Joseph C. Lowe, Walter R. Noble, Philip C. TI The 2007 Frank Stinchfield Award - The biomechanies of the hip labrum and the stability of the hip SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Meeting of the Hip-Society CY 2007 CL San Diego, CA ID TORN ACETABULAR LABRUM; FINITE-ELEMENT MODEL; FEMOROACETABULAR IMPINGEMENT; OSTEOARTHRITIS; ARTHROSCOPY; CARTILAGE; SEAL AB We explored the mechanical factors leading to the formation of labral tears and the effect of these lesions on hip kinematics at the extremes of joint motion. Using a 3D motion analysis system. the stability of six cadaveric hips was measured during loading maneuvers known to impose anterior loads on the joint margin. These measurements were repeated following venting of the capsule, and after creation of a 15-mm tear in the intact labrum. Compared to the intact hip, 43% and 60% less force was required to distract the femur by 3 nun after venting and creation of a tear. An ER torque of 177 in-lbf in 30 degrees of flexion caused the vented and torn specimens to rotate 1.5 degrees +/- 2.7 degrees and 7.1 degrees +/- 4.7 degrees more than the intact specimen, and the femoral head to displace 1.21 +/- 0.53 mm and 0.67 +/- 0.35 mm, respectively. A breach of the integrity of labral function is shown to lead to decreased femoral stability relative to the acetabulum during extreme ranges of motion. C1 Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA. Inst Orthoped Res & Educ, Houston, TX USA. Methodist Hosp, Dept Orthoped Surg, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Noble, PC (reprint author), 6550 Fannin,Suite 2512, Houston, TX 77030 USA. EM pnoble@bcm.edu NR 23 TC 118 Z9 119 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2007 IS 465 BP 16 EP 22 DI 10.1097/BLO.0b013e31815b181f PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 238JV UT WOS:000251444600005 PM 17906586 ER PT J AU Bragdon, CR Kwon, YM Geller, JA Greene, ME Freiberg, AA Harris, WH Malchau, H AF Bragdon, Charles R. Kwon, Young Min Geller, Jeffrey A. Greene, Meridith E. Freiberg, Andrew A. Harris, William H. Malchau, Henrik TI Minimum 6-year followup of highly cross-linked polyethylene in THA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Meeting of the Hip-Society CY 2007 CL San Diego, CA ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; DIAMETER FEMORAL HEADS; IN-VIVO WEAR; CLINICAL-PERFORMANCE; OSTEOLYSIS; REPLACEMENT; ARTHRITIS; RATES; CUPS AB To reduce wear rates and particulate debris, highly crosslinked polyethylene has been in use in total hip arthroplasty for 8 years. We designed this followup study to primarily determine the total penetration rate of the femoral head and the steady-state Wear rate of cross-linked polyethylene in patients undergoing primary total hip arthroplasty. We retrospectively reviewed data from 182 patients (200 hips) with a minimum 6-year followup (mean, 6.9 years; range, 6-8 years) and an average age of 60.2 years at surgery. The average Harris hip score, University of California-Los Angeles activity score, and WOMAC score were 91.1, 6.3, and 11.3. respectively. Radiographic evaluation showed no evidence of loosening or osteolytic lesions around the cup or stem. No revisions were performed for polyethylene wear or liner fracture. The average steady-state wear rate was -0.002 +/- 0.01 mm per year and -0.026 +/- 0.13 mm per year for 28-mm and 32-mm head sizes, respectively. We observed no correlation between the total wear rate and femoral head size.. brand of polyethylene, age, gender, primary diagnosis, mode of fixation, surgical approach, University of California-Los Angeles activity score, Harris hip score, or WOMAC. Highly cross-linked polyethylene liners are associated with excellent midterm clinical, radiographic, and wear results in this group of patients. C1 Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Columbia Presbyterian Med Ctr, Dept Orthoped Surg, New York, NY USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM cbragdon@partners.org NR 26 TC 61 Z9 62 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2007 IS 465 BP 122 EP 127 DI 10.1097/BLO.0b013e31815760b1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 238JV UT WOS:000251444600020 PM 18090469 ER PT J AU Sloan, DM Kring, AM AF Sloan, Denise M. Kring, Ann M. TI Measuring changes in emotion during psychotherapy: Conceptual and methodological issues SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE emotion; emotional awareness; emotional expression; emotion regulation ID GENERALIZED ANXIETY DISORDER; TORONTO-ALEXITHYMIA-SCALE; BORDERLINE PERSONALITY-DISORDER; CHILDHOOD SEXUAL-ABUSE; INDIVIDUAL-DIFFERENCES; SELF-REPORT; FACIAL EXPRESSIVITY; FACTORIAL VALIDITY; EATING-DISORDERS; NEGATIVE AFFECT AB A selective review of measures that can be used to assess various aspects of emotional responding during the course of psychotherapy is provided. We pay special attention to measures that index emotion regulation, emotional experience, emotional expression, and emotional awareness across self-report, observer-based, and psychophysiological methods. The review concludes with considerations that should be taken into account when selecting emotion measure(s) for use in psychotherapy research and practice. These considerations include having a clear working definition of emotion, reliability issues that arise when measures reflect a state-dependent construct (e.g., emotional experience), and the potential need to assess more than one component of emotional responding. C1 VA Boston Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Sloan, DM (reprint author), VA Boston Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov NR 98 TC 44 Z9 44 U1 5 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD DEC PY 2007 VL 14 IS 4 BP 307 EP 322 DI 10.1111/j.1468-2850.2007.00092.x PG 16 WC Psychology, Clinical SC Psychology GA 231II UT WOS:000250939700001 ER PT J AU Henderson, DC AF Henderson, David C. TI Considerations for inpatient versus outpatient treatment with antipsychotics SO CNS SPECTRUMS LA English DT Editorial Material ID SCHIZOAFFECTIVE DISORDER; ATYPICAL ANTIPSYCHOTICS; 1ST EPISODE; SCHIZOPHRENIA; MEDICATION; ADHERENCE C1 [Henderson, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Diabet & Weight Reduct Res Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2007 VL 12 IS 12 SU 21 BP 3 EP 5 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250WL UT WOS:000252331900001 PM 18389922 ER PT J AU Thase, ME AF Thase, Michael E. TI Augmentation strategies for depression: History and concepts SO CNS SPECTRUMS LA English DT Editorial Material ID RESISTANT RECURRENT DEPRESSION; OPEN CLINICAL-TRIAL; THYROID-HORMONE; REFRACTORY DEPRESSION; LITHIUM AUGMENTATION; UNIPOLAR DEPRESSION; IMIPRAMINE; CHLORDIAZEPOXIDE; TRANYLCYPROMINE; AMITRIPTYLINE C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 24 TC 9 Z9 10 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2007 VL 12 IS 12 SU 22 BP 3 EP 5 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250WN UT WOS:000252332100001 PM 18396507 ER PT J AU Papakostas, GI AF Papakostas, George I. TI Examining the evidence on augmentation with atypical antipsychotics SO CNS SPECTRUMS LA English DT Editorial Material ID MAJOR DEPRESSIVE DISORDER; TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; OLANZAPINE/FLUOXETINE COMBINATION; RISPERIDONE AUGMENTATION; OLANZAPINE; FLUOXETINE; PLACEBO; SSRI C1 [Papakostas, George I.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Papakostas, George I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 19 TC 4 Z9 4 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2007 VL 12 IS 12 SU 22 BP 10 EP 12 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250WN UT WOS:000252332100003 PM 18396509 ER PT J AU Harissi-Dagher, M Dana, MR Jurkunas, UV AF Harissi-Dagher, Mona Dana, M. Reza Jurkunas, Ula V. TI Keratoglobus in association with posterior polymorphous dystrophy SO CORNEA LA English DT Article DE posterior polymorphous dystrophy; keratoglobus; keratoconus; topography ID CORNEAL-DYSTROPHY; KERATOCONUS; DEGENERATION; MUTATIONS; GENE; VSX1 AB Purpose: To report a case of a 34-year-old woman presenting with keratoglobus and posterior polymorphous corneal dystrophy (PPMD). Methods: Observational case report including ophthalmologic examination, topographic findings, and specular microscopy findings. Results: This patient presented with corneal steepening on topography consistent with keratoglobus, as well as large areas of irregular polymorphous changes of the corneal endothelium on specular microscopy consistent with PPMD. Conclusions: We report the first case with clinical features of both keratoglobus and PPMD. This report brings forth the description of keratoglobus findings on Orbscan topography. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & External Dis Serv, Boston, MA 02114 USA. RP Jurkunas, UV (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Ula_Jurkunas@meei.harvard.edu NR 18 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD DEC PY 2007 VL 26 IS 10 BP 1288 EP 1291 PG 4 WC Ophthalmology SC Ophthalmology GA 238JX UT WOS:000251444800030 PM 18043197 ER PT J AU Conrad, C Niess, H Jauch, KW Bruns, CJ Hartl, WH Welker, L AF Conrad, Claudius Niess, Hanno Jauch, Karl-Walter Bruns, Christiane J. Hartl, Wolfgang H. Welker, Lorenz TI Overture for growth hormone: Requiem for interleukin-6? SO CRITICAL CARE MEDICINE LA English DT Article DE mozart; mozart effect; relaxation; interieukin-6; growth hormone; intensive care unit ID IMMUNE-SYSTEM; MUSIC-THERAPY; NEUROENDOCRINE; AXIS; INTERVENTION; LYMPHOCYTES; PERFORMANCE; ANESTHESIA; EXPRESSION; CYTOKINES AB Background: Music has been used for therapeutic purposes since the beginning of cultural history. However, despite numerous descriptions of beneficial effects, the precise mechanisms by which music may improve human well-being remain unclear. Methods: We conducted a randomized study in ten critically ill patients to identify mechanisms of music-induced relaxation using a special selection of slow movements of Mozart's piano sonatas. These sonatas were analyzed for compositional elements of relaxation. We measured circulatory variables, brain electrical activity, serum levels of stress hormones and cytokines, requirements for sedative drugs, and level of sedation before and at the end of a 1-hr therapeutic session. Results: Compared with controls, we found that music application significantly reduced the amount of sedative drugs needed to achieve a comparable degree of sedation. Simultaneously, among those receiving the music intervention, plasma concentrations of growth hormone increased, whereas those of interleukin-6 and epinephrine decreased. The reduction in systemic stress hormone levels was associated with a significantly lower blood pressure and heart rate. Conclusion. Based on the effects of slow movements of Mozart's piano sonatas, we propose a neurohumoral pathway by which music might exert its sedative action. This model includes an interaction of the hypothalamic-pituitary axis with the adrenal medulla via mediators of the unspecific immune system. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Munich, Dept Surg, Munich, Germany. Univ Munich, Dept Fine Arts, Inst Mus Sci, Munich, Germany. RP Conrad, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 48 TC 44 Z9 45 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 BP 2709 EP 2713 DI 10.1097/01.CCM.0000291648.99043.B9 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 237BD UT WOS:000251346700005 PM 18074473 ER PT J AU Liu, KD Glidden, DV Eisner, MD Parsons, PE Ware, LB Wheeler, A Korpak, A Thompson, T Chertow, GM Matthay, MA AF Liu, Kathleen D. Glidden, David V. Eisner, Mark D. Parsons, Polly E. Ware, Lorraine B. Wheeler, Arthur Korpak, Anna Thompson, Taylor Chertow, Glenn M. Matthay, Michael A. CA Natl Heart Lung TI Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; acute lung injury; acute respiratory; distress syndrome; biological marker; predictive value; interieukin-6; soluble tumor necrosis factor receptor; plasminogen; activator inhibitor-1 ID ACUTE-RENAL-FAILURE; RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; REPLACEMENT THERAPY; CONTROLLED-TRIAL; MORTALITY; MULTICENTER; RECEPTORS AB Objective: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. Design: Secondary data analysis from a multicenter, randomized clinical trial. Setting: Intensive care units in ten university medical centers. Patients: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. Interventions: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. Measurements and Main Results: We tested the association of baseline levels of interieukin-6, interleukin-8, interieukin-10, von Willebrand factor, tumor necrosis factor-alpha, type I and -II soluble tumor necrosis factor receptors (sTNFR-1 and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of > 50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003). Conclusions: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury. C1 Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Occupat Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Liu, KD (reprint author), Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. FU NCRR NIH HHS [8 K12 RR023262, K12 RR023262]; NHLBI NIH HHS [N01-HR46054-46064, N01HR46054, R37 HL051856, R37 HL051856-14] NR 32 TC 82 Z9 84 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 BP 2755 EP 2761 DI 10.1097/01.CCM.0000291649.72238.6D PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 237BD UT WOS:000251346700012 PM 18074478 ER PT J AU Lovich, MA Peterfreund, GL Sims, NM Peterfreund, RA AF Lovich, Mark A. Peterfreund, Gregory L. Sims, Nathaniel M. Peterfreund, Robert A. TI Central venous catheter infusions: A laboratory model shows large differences in drug delivery dynamics related to catheter dead volume SO CRITICAL CARE MEDICINE 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 DE central venous catheter; drug infusion; dead volume; medication safety ID SYRINGE-PUMP INFUSION; RATES; SET AB Objective: Central venous catheters (CVCs) are conduits for drug infusions. Dead volumes of different CVC lumens vary considerably. This study quantitatively evaluated drug delivery dynamics of CVCs in a laboratory model of continuous drug infusion. Design: CVCs studied included a triple-lumen catheter (16-gauge and 18-gauge lumens), the proximal infusion port of a pulmonary artery catheter, and a 9-Fr introducer sheath, with and without a pulmonary artery catheter in the lumen. One syringe pump infused a carrier. A second pump infused the model drug methylene blue (3 mL/hr), joining the carrier immediately upstream of the CVC. Samples were collected every minute for quantitative analysis. Setting: Laboratory model. Subjects: None. Interventions: At low fixed flow rates, experiments characterized drug delivery kinetics of different CVCs. Data collection then assessed effects of increased carrier flow. Measurement and Main Results: The time to steady-state delivery after initiation of methylene blue infusion differed between CVCs. At a carrier flow of 10 mL/hr, the fastest achievement of steady-state delivery was with the 18-gauge lumen of a triple-lumen catheter. The 9-Fr introducer had the slowest time to achieve steady-state delivery. Other CVCs had intermediate kinetics. Reducing drug delivery from steady state to zero after cessation of methylene blue infusion was fastest with the 18-gauge lumen and slowest with the 9-Fr introducer. Increasing carrier flow rates from 10 to 60 mL/hr hastened the time to target for initiation and cessation of methylene blue delivery. Conclusions: Experiments demonstrate large differences between CVCs in the dynamics for delivery of model drug methylene blue. Achieving targeted steady-state delivery, and termination of a planned continuous drug infusion, may be far slower than typically appreciated. Delivery kinetics depend on the dead volume and the rate of carrier flow. Safe and effective management of continuous drug infusions depends on understanding the dynamics of the delivery system. C1 Cartias St Elizabeths Med Ctr, Dept Anesthesia & Pain Med, Brighton, MA 02135 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Lovich, MA (reprint author), Cartias St Elizabeths Med Ctr, Dept Anesthesia & Pain Med, Brighton, MA 02135 USA. NR 12 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 BP 2792 EP 2798 DI 10.1097/01.CCM.0000295587.04882.4F PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 237BD UT WOS:000251346700017 PM 18074479 ER PT J AU Lang, JD Chaiwat, O AF Lang, John D. Chaiwat, Onuma TI Clinical use of hydroxyethylstarch: Colloidal confusion or clarity? SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; VOLUME REPLACEMENT; FLUID RESUSCITATION; STARCH; ADHESION; INFUSION; SURGERY; GELATIN; ALBUMIN C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA 98195 USA. RP Lang, JD (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA 98195 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 BP 2864 EP 2866 DI 10.1097/01.CCM.0000288095.96147.47 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 237BD UT WOS:000251346700032 PM 18043209 ER PT J AU Durall, A Wolfe, J AF Durall, Amy Wolfe, Joanne TI Clinician perspectives on advanced care discussions and the DNR order at a children's hospital SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Durall, Amy] Childrens Hosp, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 690 BP A189 EP A189 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901163 ER PT J AU Restrepo, MI Mortensen, EM Echevarria, K Frei, C Castellanos-Matteus, P Malave, A Sanchez, JF Swiggum, J Velez, JA Anzueto, A AF Restrepo, Marcos I. Mortensen, Eric M. Echevarria, Kelly Frei, Christopher Castellanos-Matteus, Patricia Malave, Adriel Sanchez, Juan F. Swiggum, Joseph Velez, Jose A. Anzueto, Antonio TI Impact of MRSA on outcomes in patients with HAP/VAP patients SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Restrepo, Marcos I.; Mortensen, Eric M.; Echevarria, Kelly; Frei, Christopher] S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX USA. [Castellanos-Matteus, Patricia; Malave, Adriel; Sanchez, Juan F.; Swiggum, Joseph; Velez, Jose A.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 635 BP A176 EP A176 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901115 ER PT J AU Restrepo, MJ Mortensen, EM Echevarria, K Frei, CR Castellanos-Matteus, P Malave, A Sanchez, JF Swiggun, J Velez, JA Anzueto, A AF Restrepo, Marcos J. Mortensen, Eric M. Echevarria, Kelly Frei, Christopher R. Castellanos-Matteus, Patricia Malave, Adriel Sanchez, Juan F. Swiggun, Joseph Velez, Jose A. Anzueto, Antonio TI Outcomes in HCAP/HAP/VAP patients with multidrug resistant risk factors SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Restrepo, Marcos J.; Mortensen, Eric M.; Echevarria, Kelly] S Texas Vet Hlth Care Syst, Audie L Murphys Div, San Antonio, TX USA. [Frei, Christopher R.; Castellanos-Matteus, Patricia; Malave, Adriel; Sanchez, Juan F.; Swiggun, Joseph; Velez, Jose A.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 654 BP A181 EP A181 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901136 ER PT J AU Rice, TW Bernard, GR Wheeler, AP Thomson, T Wiedemann, HP AF Rice, Todd W. Bernard, Gordon R. Wheeler, Arthur P. Thomson, Taylor Wiedemann, Herbert P. TI Safety and efficacy of a conservative fluid management strategy in acute lung injury patients with shock SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Rice, Todd W.; Bernard, Gordon R.; Wheeler, Arthur P.] Vanderbilt Univ, Nashville, TN USA. [Thomson, Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wiedemann, Herbert P.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 835 BP A231 EP A231 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901307 ER PT J AU Rice, TW Bernard, GR Wheeler, AP Thompson, T Wiedemann, HP AF Rice, Todd W. Bernard, Gordon R. Wheeler, Arthur P. Thompson, Taylor Wiedemann, Herbert P. TI Comparison of liberal vs. conservative fluid management in acute lung injury patients withoutshock SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Rice, Todd W.; Bernard, Gordon R.; Wheeler, Arthur P.] Vanderbilt Univ, Nashville, TN USA. [Thompson, Taylor] Massachusetts Gen Hosp, ARDS Network Coordinating Ctr, Boston, MA 02114 USA. [Wiedemann, Herbert P.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 833 BP A231 EP A231 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901306 ER PT J AU Schmidt, UH Kumwilaisak, K Bittner, E George, E Hess, D AF Schmidt, Ulrich H. Kumwilaisak, Kanya Bittner, Edward George, Edward Hess, Dean TI Effects of supervision by an attending anesthesiologist on complications of emergency airway management. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Schmidt, Ulrich H.; Kumwilaisak, Kanya; Bittner, Edward; George, Edward; Hess, Dean] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 614 BP A171 EP A171 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901096 ER PT J AU Risco, R Elmoazzen, H Doughty, M He, XM Toner, M AF Risco, Ramon Elmoazzen, Heidi Doughty, Marshal He, Xiaoming Toner, Mehmet TI Thermal performance of quartz capillaries for vitrification SO CRYOBIOLOGY LA English DT Article DE vitrification; 1,2-propanediol; sucrose; quartz microcapillary; open pulled straw; slush nitrogen; oocyte; ultrafast cooling rates ID OPEN-PULLED STRAWS; HIGH SUCROSE CONCENTRATION; BOVINE OOCYTES; ETHYLENE-GLYCOL; CRYOPROTECTIVE SOLUTIONS; CONVENTIONAL STRAWS; MEIOTIC SPINDLES; NUCLEAR TRANSFER; CATTLE EMBRYOS; CRYOPRESERVATION AB In this paper we report the thermal behavior of a new approach for vitrification. Thermal performance of traditional open pulled straws is compared with a new technique based on the combined use of quartz capillaries with slush nitrogen. This new method of vitrification achieved ultrafast cooling rates of 250,000 degrees C/min. As a result, a much lower concentration of cryoprotectant was needed to reach vitrification. In fact, a cryoprotectant solution typically used in oocyte slow freezing protocols was shown to remain transparent after cooling to liquid nitrogen temperatures indicating apparent "vitrification". This approach offers a new and very promising technique for vitrification of cells using low levels of cryoprotectants. (C) 2007 Elsevier Inc. All rights reserved. C1 [Risco, Ramon] Univ Seville, Escuela Super Ingn, Seville 41092, Spain. [Risco, Ramon; Elmoazzen, Heidi; Doughty, Marshal; He, Xiaoming; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Risco, R (reprint author), Univ Seville, Escuela Super Ingn, Seville 41092, Spain. EM ramon@us.es RI He, Xiaoming/C-5499-2008; OI He, Xiaoming/0000-0003-0125-6086; Risco Delgado, Ramon/0000-0001-5995-6590 FU NIBIB NIH HHS [EB002340] NR 45 TC 29 Z9 30 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 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD DEC PY 2007 VL 55 IS 3 BP 222 EP 229 DI 10.1016/j.cryobiol.2007.08.006 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 244GZ UT WOS:000251855700007 PM 17919532 ER PT J AU Tesco, G AF Tesco, Giuseppina TI New advances in Alzheimer's disease: From biology to therapy SO CURRENT GENOMICS LA English DT Editorial Material ID AMYLOID PRECURSOR PROTEIN; ALPHA-SECRETASE CLEAVAGE; GAMMA-SECRETASE; BETA-SECRETASE; EPIDEMIOLOGY C1 Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Boston, MA 02129 USA. RP Tesco, G (reprint author), Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Genet & Aging Res Unit, 114,16th St,Room 3900, Boston, MA 02129 USA. EM tescog@helix.mgh.harvard.edu NR 9 TC 1 Z9 1 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 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD DEC PY 2007 VL 8 IS 8 BP 484 EP 485 DI 10.2174/138920207783769558 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 283RK UT WOS:000254654000001 PM 19415124 ER PT J AU Farmer, SR Spiegelman, BM AF Farmer, Stephen R. Spiegelman, Bruce M. TI Cell differentiation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 [Farmer, Stephen R.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Farmer, SR (reprint author), Boston Univ, Sch Med, Dept Biochem, 715 Albany St, Boston, MA 02118 USA. EM farmer@biochem.bumc.bu.edu; bruce-spiegelman@dfci.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2007 VL 19 IS 6 BP 603 EP 604 DI 10.1016/j.ceb.2007.11.002 PG 2 WC Cell Biology SC Cell Biology GA 248HH UT WOS:000252143000001 ER PT J AU Schwartz, GG AF Schwartz, Gregory G. TI Lipid management after acute coronary syndrome SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE acute coronary syndrome; HDL-cholesterol; HMG-CoA reductase inhibitor; statin ID MYOCARDIAL-ISCHEMIA REDUCTION; CHOLESTEROL-LOWERING MIRACL; INTENSIVE STATIN THERAPY; LOW-DENSITY-LIPOPROTEIN; RANDOMIZED CONTROLLED-TRIALS; HIGH-DOSE ATORVASTATIN; SHORT-TERM PROGNOSIS; CLINICAL-OUTCOMES; METABOLIC SYNDROME; PROVE IT-TIMI-22 AB Early, intensive statin therapy is safe and effective after acute coronary syndrome. Future research will determine whether drugs that raise or mimic HDL-cholesterol are effective adjuncts to statin therapy. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. [Schwartz, Gregory G.] Univ Colorado, Hlth Sci Ctr, VA Med Ctr, Denver, CO USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect, 1055 Clermont St, Denver, CO 80220 USA. EM gregory.schwartz@va.gov NR 39 TC 1 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 18 IS 6 BP 626 EP 632 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 242YU UT WOS:000251762900003 PM 17993807 ER PT J AU Kawai, T Cosimi, AB Sachs, DH AF Kawai, Tatsuc Cosimi, A. Benedict Sachs, David H. TI Donor bone marrow transplantation as an approach to tolerance induction for clinical kidney transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE kidney transplantation; mixed chimerism; tolerance ID TOTAL-LYMPHOID IRRADIATION; RENAL-ALLOGRAFT REJECTION; MONOCLONAL-ANTIBODY; CYNOMOLGUS MONKEYS; NONHUMAN-PRIMATES; MIXED CHIMERISM; IN-VIVO; LYMPHOHEMATOPOIETIC CHIMERISM; MULTIPLE-MYELOMA; GRAFT-SURVIVAL AB Purpose of review Despite recent improvements of short-term results in clinical organ transplantation, long-term results are still not satisfactory. To further improve long-term results, clinical trials for the induction of tolerance are underway. This review summarizes the background and results of clinical tolerance induction trials, especially those using donor bone marrow infusion/transplantation. Recent findings The strategies for tolerance induction that have been successful in nonhuman primates can be categorized as follows: use of total lymphoid irradiation; costimulatory blockade; profound depletion of recipient T cells; infusion of regulatory cells; and donor bone marrow infusion/transplantation. Among these approaches, however, induction of mixed chimerism through donor bone marrow transplantation is the only approach that has been successfully translated to clinical kidney transplantation to date. Summary Induction of tolerance in clinical kidney transplantation has been achieved via a mixed chimerism approach. Better understanding of the mechanisms of tolerance and improvements in the morbidity of conditioning regimens for tolerance induction will undoubtedly be important in bringing this modality to wider clinical applications. C1 [Kawai, Tatsuc; Cosimi, A. Benedict] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Charlestown, MA 02129 USA. [Kawai, Tatsuc; Cosimi, A. Benedict; Sachs, David H.] Harvard Univ, Sch Med, Charlestown, MA USA. [Kawai, Tatsuc; Cosimi, A. Benedict] Massachusetts Gen Hosp, Dept Surg, Transplant Ctr, Charlestown, MA USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, 149 13th St,149-9019, Charlestown, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu NR 55 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2007 VL 12 IS 6 BP 618 EP 623 PG 6 WC Transplantation SC Transplantation GA 242DP UT WOS:000251705000006 ER PT J AU Bradesi, S Mayer, EA AF Bradesi, Sylvie Mayer, Emeran A. TI Novel therapeutic approaches in IBS SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL GASTROINTESTINAL DISORDERS; CORTICOTROPIN-RELEASING HORMONE; CHLORIDE CHANNEL ACTIVATOR; BRAIN-GUT AXIS; SYNDROME C-IBS; DOUBLE-BLIND; RECEPTOR ANTAGONISTS; VISCERAL HYPERALGESIA; SENSORY FUNCTION AB Irritable bowel syndrome (IBS) remains an incompletely understood, common syndrome with significant unmet medical needs. Significant progress has been made in the development of novel therapies aimed at normalizing bowel habit alterations and abdominal discomfort, even though some of the most effective treatments are currently only available for patients under a restricted access program from the FDA. Preclinical evidence supports the potential usefulness of several compounds in development for the treatment of chronic abdominal pain. Recent new evidence for a possible role of altered microflora and altered host microbial interactions may provide new treatment targets in the future. C1 [Bradesi, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, UCLA Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, UCLA Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, UCLA Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Bradesi, Sylvie] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, UCLA Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. EM emayer@ucla.edu FU NCCIH NIH HHS [R24 AT002681, R24 AT 002681]; NIDDK NIH HHS [R01 DK048351, R01 DK 48351, P50 DK 64539, P50 DK064539] NR 59 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2007 VL 7 IS 6 BP 598 EP 604 DI 10.1016/j.coph.2007.09.012 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 244HK UT WOS:000251856800008 PM 18006379 ER PT J AU Pitman, MB Deshpande, V AF Pitman, M. B. Deshpande, V. TI Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions SO CYTOPATHOLOGY LA English DT Review DE pancreas; endoscopic ultrasound; fine needle aspiration cytology; EUS-FNAC; pancreatic carcinoma; pancreatic cysts ID PAPILLARY-MUCINOUS TUMORS; ACINAR-CELL-CARCINOMA; SEROUS-CYSTADENOMA; FLUID ANALYSIS; AUTOIMMUNE PANCREATITIS; DIFFERENTIAL-DIAGNOSIS; RETROSPECTIVE ANALYSIS; PSEUDOPAPILLARY TUMOR; MOLECULAR ANALYSIS; CENTER EXPERIENCE AB Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions Cytological evaluation of pancreatic masses and cysts is the preferred pre-operative diagnostic modality and is increasingly being performed by endoscopic ultrasound. This review focuses on the multimodal approach at the Massachusetts General Hospital that utilizes clinical, cytological, radiological and ancillary studies in rendering a final cytological diagnosis. C1 Massachusetts Gen Hosp, Dept Pathol, Fine Needle Aspirat Biopsy Serv, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 92 TC 40 Z9 40 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD DEC PY 2007 VL 18 IS 6 BP 331 EP 347 DI 10.1111/j.1365-2303.2007.00457.x PG 17 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 234TP UT WOS:000251187200002 PM 17559566 ER PT J AU Schalock, PC Zug, KA AF Schalock, Peter C. Zug, Kathryn A. TI Acneiform reaction to erlotinib SO DERMATITIS LA English DT Article ID MANAGEMENT AB Erlotinib is a reversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) newly approved for the treatment of refractory, locally advanced, or metastatic nonsmall cell lung cancer. Acneiform skin reactions with EGFR inhibitors are common, with a dose-dependent skin reaction being seen in 50 to 100% of patients. This case illustrates the typical skin reaction seen with EGFR-TK inhibitors and illustrates the lack of reaction in skin with sebaceous glands that have been destroyed by radiation. Discussion of this skin reaction in the literature of dermatology is limited; this case illustrates a pattern of reaction that may suggest a mechanism for this skin reaction pattern to erlotinib. C1 [Schalock, Peter C.; Zug, Kathryn A.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Schalock, Peter C.; Zug, Kathryn A.] Dartmouth Med Sch, Dept Med Dermatol, Hanover, NH USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol BAR622, 55 Fruit St, Boston, MA 02114 USA. EM schalock@gmail.com OI Schalock, Peter/0000-0001-8953-4639 NR 4 TC 2 Z9 2 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1710-3568 J9 DERMATITIS JI Dermatitis PD DEC PY 2007 VL 18 IS 4 BP 230 EP 231 DI 10.2310/6620.2007.06037 PG 2 WC Dermatology SC Dermatology GA 241EQ UT WOS:000251640100009 PM 18021605 ER PT J AU Kramer, HF Taylor, EB Witczak, CA Fujii, N Hirshman, MF Goodyear, LJ AF Kramer, Henning F. Taylor, Eric B. Witczak, Carol A. Fujii, Nobuharu Hirshman, Michael F. Goodyear, Laurie J. TI Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle SO DIABETES LA English DT Article ID GTPASE-ACTIVATING-PROTEIN; GLUT4 TRANSLOCATION; KINASE-C; AKT SUBSTRATE; PHOSPHATIDYLINOSITOL 3-KINASE; PLASMA-MEMBRANE; RAB-GAP; TRANSPORT; PHOSPHORYLATION; EXERCISE AB OBJECTIVE-Insulin and contraction increase skeletal muscle glucose uptake through distinct and additive mechanisms. However, recent reports have demonstrated that both signals converge on the Akt substrate of 160 kDa (AS160), a protein that regulates GLUT4 translocation. Although AS160 phosphorylation is believed to be the primary factor affecting its activity, AS160 also possesses a calmodulin-binding domain (CBD). This raise the possibility that contraction-stimulated increases in Ca2+/calmodulin could also modulate AS160 function. RESEARCH DESIGN AND METHODS-To evaluate the AS160 CBD in skeletal muscle, empty-vector, wild-type, or CBD-mutant AS160 cDNAs were injected into mouse muscles followed by in vivo electroporation. One week later, AS160 was overexpressed by similar to 14-fold over endogenous protein. RESULTS-Immunoprecipitates of wild-type and CBD-mutant AS160 were incubated with biotinylated calmodulin in the presence of Ca2+. Wild-type AS160, but not the CBD-mutant AS160, associated with calmodulin. Next, we measured insulin- and contraction-stimulated glucose uptake in vivo. Compared with empty-vector and wild-type AS160, insulin-stimulated glucose uptake was not altered in muscles expressing CBD-mutant AS160. In contrast, contraction-stimulated glucose uptake was significantly decreased in CBD-mutant-expressing muscles. This inhibitory effect on glucose uptake was not associated with aberrant contraction-stimulated AS160 phosphorylation. Interestingly, AS160 expressing both calmodulin-binding and Rab-GAP (GTPase-activating protein) domain point mutations (CBD + R/K) fully restored contraction-stimulated glucose uptake. CONCLUSIONS-Our results suggest that the AS160 CBD directly regulates contraction-induced glucose uptake in mouse muscle and that calmodulin provides an additional means of modulating AS160 Rab-GAP function independent of phosphorylation. These findings define a novel AS160 signaling component, unique to contraction and not insulin, leading to glucose uptake in skeletal muscle. C1 Joslin Diabet Ctr, Div Res, Dept Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, Dept Metab, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR45670, F32AR051663, AR42238]; NIDDK NIH HHS [F32 DK075851] NR 49 TC 32 Z9 36 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 2854 EP 2862 DI 10.2337/db07-0681 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400005 PM 17717281 ER PT J AU Yano, T Liu, ZY Donovan, J Thomas, MK Habener, JF AF Yano, Tatsuya Liu, Zhengyu Donovan, Jennifer Thomas, Melissa K. Habener, Joel F. TI Stromal cell-derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt SO DIABETES LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; CENTRAL-NERVOUS-SYSTEM; ENDOTHELIAL-CELLS; INSULIN-SECRETION; BRANCHING MORPHOGENESIS; PROGENITOR CELLS; CHEMOKINE SDF-1; DOWN-REGULATION; BAX EXPRESSION; STEM-CELLS AB OBJECTIVE-Diabetes is caused by a deficiency of pancreatic beta-cells that produce insulin. Approaches to enhance beta-cell mass by increasing proliferation and survival are desirable. We determined whether stromal cell-derived factor (SDF)-l/CXCL12 and its receptor, CX chemokine receptor (CXCR)4, are important for the survival of beta-cells. RESEARCH DESIGN AND METHODS-Mouse pancreata and clonal P-cells were examined for expression of SDF-1 and CXCR4, activation of AKT and downstream signaling pathways by SDF-1, and protection against apoptosis and diabetes induced by streptozotocin (STZ). RESULTS-CXCR4 is expressed in beta-cells, and SDF-1 is expressed in microvascular endothelial cells within the islets and in surrounding interstitial stromal tissue. Transgenic mice overexpressing SDF-1 within their beta-cells (RIP-SDF-1 mice) are resistant to STZ-induced beta-cell apoptosis and diabetes. In MIN6 beta-cells, a CXCR4 antagonist (AMD3100) induces apoptosis, increases reactive oxygen species, decreases expression levels of the anti-apoptotic protein Bcl-2, and reduces phosphorylation the proapoptotic protein Bad. Active phosphorylated prosurvival kinase Akt is increased both in the P-cells of RIP-SDF-1 mice in INS-1 cells treated with SDF-1 and sensitive to AMD3100. Inhibition of AKT expression by small interfering RNA attenuates the ameliorative effects of SDF-1 on caspase-dependent apoptosis induced by thapsigargin or glucose deprivation in INS-1 P-cells. Specific inhibition of Akt activation by a soluble inhibitor (SH-5) reverses the anti-apoptotic effects of SDF-1 in INS-1 cells and mouse islets. CONCLUSIONS-SDF-1 promotes pancreatic beta-cell survival via activation of Akt, suggesting that SDF-1 agonists may prove beneficial for treatment of diabetes. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,Thier 306, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK55365, DK61251, P30 DK040561, P30 DK040561-12, P30DK057521] NR 48 TC 69 Z9 71 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 2946 EP 2957 DI 10.2337/db07-0291 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400016 PM 17878289 ER PT J AU Florez, JC Manning, AK Dupuis, J McAteer, J Irenze, K Gianniny, L Mirel, DB Fox, CS Cupples, LA Meigs, JB AF Florez, Jose C. Manning, Alisa K. Dupuis, Josee McAteer, Jarred Irenze, Kathryn Gianniny, Lauren Mirel, Daniel B. Fox, Caroline S. Cupples, L. Adrienne Meigs, James B. TI A 100K genome-wide association scan for diabetes and related traits in the Framingham Heart Study SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; TCF7L2 POLYMORPHISMS; GENETIC ASSOCIATION; COMPLEX TRAITS; TYPE-2; GLUCOSE; POPULATION; DISEASE; RISK AB OBJECTIVE-To use genome-wide fixed marker arrays and improved analytical tools to detect genetic associations with type 2 diabetes in a carefully phenotyped human sample. RESEARCH DESIGN AND METHODS-A total of 1,087 Framingham Heart Study (FHS) family members were genotyped on the Affymetrix 100K single nucleotide polymorphism (SNP) array and examined for association with incident diabetes and six diabetes-related quantitative traits. Quality control filters yielded 66,543 SNPs for association testing. We used two complementary SNP selection strategies (a "lowest P value" strategy and a,'multiple related trait" strategy) to prioritize 763 SNPs for replication. We genotyped a subset of 150 SNPs in a nonoverlapping sample of 1,465 FHS unrelated subjects and examined all 763 SNPs for in silico replication in three other 100K and one 500K genome-wide association (GWA) datasets. RESULTS- We replicated associations of 13 SNPs with one or more traits in the FHS unrelated sample (16 expected under the null); none of them showed convincing in silico replication in 100K scans. Seventy-eight SNPs were nominally associated with diabetes in one other 100K GWA scan, and two (rs2863389 and rs7935082) in more than one. Twenty-five SNPs showed promising associations with diabetes-related traits in 500K GWA reported associations were confirmed in our initial dataset. CONCLUSIONS- The FHS 100K GWA resource is useful for follow-up of genetic associations with diabetes-related quantitative traits. Discovery of new diabetes genes will require larger samples and a denser array combined with well-powered replication strategies. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU NCRR NIH HHS [1S10RR163736-01A1, U54 RR020278-01]; NHLBI NIH HHS [N01-HC-25195]; NIDDK NIH HHS [K23 DK-65978-04] NR 44 TC 51 Z9 54 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 3063 EP 3074 DI 10.2337/db07-0451 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400030 PM 17848626 ER PT J AU Halanych, JH Safford, MM Keys, WC Person, SD Shikany, JM Kim, YI Centor, RM Allison, JJ AF Halanych, Jewell H. Safford, Monika M. Keys, Wendy C. Person, Sharina D. Shikany, James M. Kim, Young-Il Centor, Robert M. Allison, Jeroan J. TI Burden of comorbid medical conditions and quality of diabetes care SO DIABETES CARE LA English DT Article ID OF-CARE; GLUCOSE CONTROL; MORTALITY; DISEASE; HEALTH; MULTIMORBIDITY; PERFORMANCE; GUIDELINES; TRIALS; INDEX AB OBJECTIVE - With performance-based reimbursement pressures, it is concerning that most performance measurements treat each condition in isolation, ignoring the complexities of patients with multiple comorbidities. We sought to examine the relationship between comorbidity and commonly assessed services for diabetic patients in a managed care organization. RESEARCH DESIGN AND METHODS - In 6,032 diabetic patients, we determined the association between the independent variable medical comorbidity, measured by the Charlson Comorbidity Index (CCI), and the dependent variables AlC testing, lipid testing, dilated eye exam, and urinary microalbumin testing. We calculated predicted probabilities of receiving tests for patients with increasing comorbid illnesses, adjusting for patient demographics. RESULTS - AlC and lipid testing decreased slightly at higher CCI: predicted probabilities for CCI quartiles 1, 2, 3, and 4 were 0.83 (95% CI 0.70-0.91), 0.83 (0.69-0.92), 0.82 (0.68-0.91), and 0.78 (0.61-0.88) for AlC, respectively, and 0.82 (0.69-0.91), 0.81(0.67-0.90), 0.79 (0.64-0.89), and 0.77 (0.61-0.88) for lipids. Dilated eye exam and urinary microalbumin testing did not differ across CCI quartiles: for quartiles 1, 2, 3, and 4, predicted probabilities were 0.48 (0.33-0.63), 0.54 (0.38-0.69), 0.50 (0.34-0.65), and 0.50 (0.34-0.65) for eye exam, respectively, and 0.23 (0.12-0.40), 0.24 (0.12-0.42), 0.24 (0.12-0.41), and 23 (0.11-0.40) for urinary microalbumin. CONCLUSIONS - Services received did not differ based on comorbid illness burden. Because it is not clear whether equally aggressive care confers equal benefits to patients with varying comorbid illness burden, more evidence confirming such benefits may be warranted before widespread implementation of pay-for-performance programs using currently available "one size fits all" performance measures. C1 Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Univ Alabama, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA. RP Halanych, JH (reprint author), MT 639,1530 3rd Ave S, Birmingham, AL 35294 USA. EM jhalanych@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 FU NHLBI NIH HHS [N01-HC-48047]; NIMHD NIH HHS [P60MD00502-01] NR 31 TC 25 Z9 25 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 DEC PY 2007 VL 30 IS 12 BP 2999 EP 3004 DI 10.2337/dc06-1836 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HQ UT WOS:000251365200003 PM 17717287 ER PT J AU Franks, PW Jablonski, KA Delahanty, L Hanson, RL Kahn, SE Altshuler, D Knowler, WC Florez, JC AF Franks, P. W. Jablonski, K. A. Delahanty, L. Hanson, R. L. Kahn, S. E. Altshuler, D. Knowler, W. C. Florez, J. C. CA Diabetes Prevention Program Res G TI The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE computed tomography; gene-environment interaction; obesity; peroxisome proliferator-activated receptor gamma; PPARG; PUFA intake; randomised clinical trial; subcutaneous fat; visceral fat ID DIETARY-FAT INTAKE; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; PPAR-GAMMA; INSULIN SENSITIVITY; P12A POLYMORPHISM; PHYSICAL-ACTIVITY; WEIGHT CHANGE; BASE-LINE; RISK AB Aims/hypothesis Peroxisome proliferator-activated receptor. (PPAR.), encoded by the PPARG gene, regulates insulin sensitivity and adipogenesis, and may bind polyunsaturated fatty acids (PUFA) and thiazolidinediones in a ligand-dependent manner. The PPARG proline for alanine substitution at position 12 (Pro12Ala polymorphism) has been related with obesity directly and via interaction with PUFA. Methods We tested the effect-modifying role of Pro12Ala on the 1 year change in obesity-related traits in a randomised clinical trial of treatment with metformin (n= 989), troglitazone (n= 363) or lifestyle modification (n= 1,004) vs placebo (n= 1,000) for diabetes prevention in high- risk individuals. Results At baseline, Ala12 carriers had larger waists (p< 0.001) and, in a subset, more subcutaneous adipose tissue (SAT; lumbar 2/ 3; p= 0.04) than Pro12 homozygotes. There was a genotype- by- intervention interaction on 1- year weight change (p= 0.01); in the placebo arm, Pro12 homozygotes gained weight and Ala12 carriers lost weight (p= 0.001). In the metformin and lifestyle arms, weight loss occurred across genotypes, but was greatest in Ala12 carriers (p< 0.05). Troglitazone treatment induced weight gain, which tended to be greater in Ala12 carriers (p= 0.08). In the placebo group, SAT (lumbar 2/3, lumbar 4/5) decreased in Ala12 allele carriers, but was unchanged in Pro12 homozygotes (p <= 0.005). With metformin treatment, SAT decreased independently of genotype. In the lifestyle arm, SAT (lumbar 2/ 3) reductions occurred across genotypes, but were greater in Ala12 carriers (p= 0.03). A genotype-by-PUFA intake interaction on reduction in visceral fat (lumbar 4/ 5; p= 0.04) was also observed, which was most evident with metformin treatment (p< 0.001). Conclusions/ interpretation Within the Diabetes Prevention Program, the Ala12 allele influences central obesity, an effect which may differ by treatment group and dietary PUFA intake (ClinicalTrials.gov ID no: NCT00004992). C1 George Washington Univ, Ctr Biostat, Diabetes Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Umea Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. NIH, NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. RP Franks, PW (reprint author), George Washington Univ, Ctr Biostat, Diabetes Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; Hanson, Robert/O-3238-2015; OI Altshuler, David/0000-0002-7250-4107; Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489-06, U01 DK048489] NR 39 TC 43 Z9 45 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 DEC PY 2007 VL 50 IS 12 BP 2451 EP 2460 DI 10.1007/s00125-007-0826-6 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228HQ UT WOS:000250721400007 PM 17898990 ER EF