FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Stone, RA Mor, MK Lave, JR Hough, LJ Fine, MJ AF Stone, RA Mor, MK Lave, JR Hough, LJ Fine, MJ TI Implementation of an inpatient management and discharge strategy for patients with community-acquired pneumonia SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INITIAL ANTIMICROBIAL THERAPY; ANTIBIOTIC-THERAPY; HOSPITAL STAY; EARLY SWITCH; PRACTICE GUIDELINES; MEDICAL OUTCOMES; CONTROLLED-TRIAL; LENGTH; ADULTS; DURATION AB Objective: To assess the effectiveness and safety of implementing an inpatient management and discharge strategy based on empiric antibiotic therapy with ceftriaxone sodium and a guideline to promote timely discharge for clinically stable patients hospitalized with community-acquired pneumonia. Study Design: A cluster randomized controlled clinical trial with 30 days of patient follow-up at 8 teaching hospitals and 17 nonteaching hospitals nationwide. Methods: Participants included 240 intervention patients and 209 control patients admitted by 85 physician groups between December 1998 and December 1999. Within each hospital, defined physician practice groups were randomized to the intervention arm (physician notification coupled with ceftriaxone sodium as empiric therapy) or control arm (neither component). Physicians in the intervention arm were notified when their patients met guideline criteria for clinical stability; physicians in the control arm were not contacted. Results: The median length of stay was 4 days in both study arms. The observed reduction in costs associated with the intervention was riot statistically significant when cost outliers were excluded. Mortality, serious adverse event, and rehospitalization rates did not differ significantly across study arms. Conclusions: Implementation of an inpatient management strategy based on physician reminders coupled with empiric use of ceftriaxone sodium did not reduce length of stay or associated medical care costs for patients hospitalized with community-acquired pneumonia. These negative findings are most likely due to insufficient potency of the intervention, inadequate guideline implementation, or imbalances in baseline Patient characteristics. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Med, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15261 USA. VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Stone, RA (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, 304 Parran Hall, Pittsburgh, PA 15261 USA. EM roslyn@pitt.edu NR 41 TC 8 Z9 8 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2005 VL 11 IS 8 BP 491 EP 499 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 955QX UT WOS:000231243000004 PM 16095435 ER PT J AU Jaff, MR AF Jaff, MR TI Venous thromboembolic disease - Introduction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Dept Vasc Med, 55 Fruit St,Yawkey 5938, Boston, MA 02114 USA. EM mjaff@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2005 VL 118 SU 8A BP 1S EP 2S DI 10.1016/j.amjmed.2005.06.004 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 954KU UT WOS:000231154800001 ER PT J AU Kim, AI Saab, S AF Kim, AI Saab, S TI Treatment of hepatitis C SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE hepatitis C ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER-TRANSPLANT RECIPIENTS; PEGINTERFERON ALPHA-2A; UNITED-STATES; LONG-TERM; PEGYLATED INTERFERON-ALPHA-2B; INITIAL TREATMENT; INFECTED PATIENTS; CONTROLLED-TRIAL AB Hepatitis C virus is a leading cause of chronic liver disease, with over 170 million people infected worldwide. It is also the leading indication for liver transplantation. Complications from chronic hepatitis C infection include cirrhosis, hepatic decompensation, and hepatocellular carcinoma. As a result, treatment strategies to prevent such complications have been widely researched, although many questions remain unanswered. To date, the standard therapy for chronic hepatitis C infection is the combination of peginterferon and ribavirin. Treatment strategies differ based on factors such as genotype and liver biopsy results. Other strategies must be considered for special groups, such as patients with acute hepatitis C infection, hepatitis C/human immunodeficiency virus (HIV) coinfection, and prior nonresponse to interferon or relapse after its use. The goal of therapy is to achieve a sustained virologic response (ie, no detectable hepatitis C ribonucleic acid 6 months after completion of therapy). The substantial adverse effects associated with both interferon alfa and ribavirin often make it difficult for patients to continue with their therapies. (C) 2005 Elsevier Inc. All rights reserved. C1 W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. RP Saab, S (reprint author), Pfleger Liver Inst, 200 Med Plaza,Suite 214,Box 957302, Los Angeles, CA 90095 USA. EM SSaab@mednet.ucla.edu NR 85 TC 53 Z9 60 U1 5 U2 8 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2005 VL 118 IS 8 BP 808 EP 815 DI 10.1016/j.amjmed.2005.01.073 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 952WR UT WOS:000231037100002 PM 16084169 ER PT J AU Schwamm, LH Rosenthal, ES Swap, CJ Rosand, J Rordorf, G Buonanno, FS Vangel, MG Koroshetz, WJ Lev, MH AF Schwamm, LH Rosenthal, ES Swap, CJ Rosand, J Rordorf, G Buonanno, FS Vangel, MG Koroshetz, WJ Lev, MH TI Hypoattenuation on CT angiographic source images predicts risk of intracerebral hemorrhage and outcome after intra-arterial reperfusion therapy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; CEREBRAL-ARTERY STROKE; APPARENT DIFFUSION-COEFFICIENT; COOPERATIVE ACUTE STROKE; ACUTE HEMISPHERIC STROKE; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; HYPERACUTE STROKE; PROACT-II AB BACKGROUND AND PURPOSE: Symptomatic hemorrhagic transformation (HT) is a significant complication of intravenous and catheter-based reperfusion. We hypothesized that the degree of vascular insufficiency, reflected as hypoattenuation on initial CT angiography (CTA) axial source images, is predictive of HT risk in stroke patients receiving intra-arterial reperfusion therapy. METHODS: We examined initial CTA source images and follow-up CT scans in 32 consecutive patients. Regions of interest were semiautomatically segmented and reviewed. Mean intensity was determined in the region of maximal hypoattenuation and in normal contralateral tissue, and the arithmetic difference (Delta HU) calculated. Receiver operator characteristic (ROC) curves and cross-validation were used to identify threshold Delta HU values. RESULTS: Thirteen patients had HT on follow-up CT (seven with parenchymal hematoma, six with hemorrhagic infarction). Patients with and those without HT did not differ in age, blood glucose level, lesion volume, or time to treatment or recanalization, though the former had a greater mean Delta HU (9.0 vs 6.3, P = .006). The ROC threshold at Delta HU >= 8.1 was 69% sensitive and 90% specific for patients who developed HT (odds ratio = 19.1; 95% confidence interval: 2.9, 125; P = .002) and was predictive of poor clinical outcome (modified Rankin scale score > 2, P = .03). Neither HT in general nor parenchymal hematoma subtype was associated with poor outcome. CONCLUSION: The degree of hypoattenuation on initial CTA source images is a risk factor for HT and poor clinical outcome after intra-arterial reperfusion therapy. Prospective validation of this relationship in large populations may permit feasible real-time risk stratification. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 42 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2005 VL 26 IS 7 BP 1798 EP 1803 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 954VI UT WOS:000231182800032 PM 16091532 ER PT J AU Inada, A Nagai, K Arai, H Miyazaki, J Nomura, K Kanamori, H Toyokuni, S Yamada, Y Bonner-Weir, S Weir, GC Fukatsu, A Seino, Y AF Inada, A Nagai, K Arai, H Miyazaki, J Nomura, K Kanamori, H Toyokuni, S Yamada, Y Bonner-Weir, S Weir, GC Fukatsu, A Seino, Y TI Establishment of a diabetic mouse model with progressive diabetic nephropathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-PROLIFERATION; KIDNEY-DISEASE; RENAL-DISEASE; BETA-CELLS; MICE; MELLITUS; GENE; RATS; GLOMERULOSCLEROSIS; HYPERGLYCEMIA AB Although diabetic animal models exist, no single animal model develops renal changes identical to those seen in humans. Here we show that transgenic mice that overexpress inducible cAMP early repressor (ICER I gamma) in pancreatic beta cells are a good model to study the pathogenesis of diabetic nephropathy. Although ICER I gamma transgenic mice exhibit extremely high blood glucose levels throughout their lives, they survive long enough to develop diabetic nephropathy. Using this model we followed the progress of diabetic renal changes compared to those seen in humans. By 8 weeks of age, the glomerular filtration rate (GFR) was already increased, and glomerular hypertrophy was prominent. At 20 weeks, GFR reached its peak, and urine albumin excretion rate was elevated. Finally, at 40 weeks, diffuse glomerular sclerotic lesions were prominently accompanied by increased expression of collagen type IV and laminin and reduced expression of matrix metalloproteinase-2. Nodular lesions were absent, but glomerular basement membrane thickening was prominent. At this point, GFR declined and urinary albumin excretion rate increased, causing a nephrotic state with lower serum albumin and higher serum total cholesterol. Thus, similar to human diabetic nephropathy, ICER I gamma transgenic mice exhibit a stable and progressive phenotype of diabetic kidney disease due solely to chronic hyperglycemia without other modulating factors. C1 Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Kyoto, Japan. Kyoto Univ, Grad Sch Med, Dept Nephrol, Kyoto, Japan. Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Kyoto, Japan. Osaka Univ, Sch Med, Div Stem Cell Regulat Res G6, Osaka, Japan. Osaka Univ, Sch Med, Suita, Osaka 565, Japan. Kansai Denroyku Hosp, Osaka, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Arai, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. EM harai@kuhp.kyoto-u.ac.jp; afukatsu@kuhp.kyoto-u.ac.jp RI Toyokuni, Shinya/C-1358-2010; Miyazaki, Jun-ichi/N-1976-2015 OI Toyokuni, Shinya/0000-0002-5757-1109; Miyazaki, Jun-ichi/0000-0003-2475-589X NR 32 TC 34 Z9 40 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2005 VL 167 IS 2 BP 327 EP 336 DI 10.1016/S0002-9440(10)62978-1 PG 10 WC Pathology SC Pathology GA 951GN UT WOS:000230917600005 PM 16049320 ER PT J AU McLean, DC Spruill, I Argyropoulos, G Page, GP Shriver, MD Garvey, WT AF McLean, DC Spruill, I Argyropoulos, G Page, GP Shriver, MD Garvey, WT TI Mitochondrial DNA (mtDNA) haplotypes reveal maternal population genetic affinities of sea island Gullah-speaking African Americans SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE admixture; population genetic substructure; phi-statistics ID ADMIXTURE; INHERITANCE; HAPLOGROUPS; PROPORTIONS; MECHANISMS; DISTANCES; EVOLUTION; ANCIENT; NEGROES; MODELS AB To better understand the population substructure of African Americans living in coastal South Carolina, we used restriction site polymorphisms and an insertion/deletion in mitochondrial DNA (mtDNA) to construct seven-position haplotypes across 1,395 individuals from Sierra Leone, Africa, from U.S. European Americans, and from the New World African-derived populations of Jamaica, Gullah-speaking African Americans of the South Carolina Sea Islands (Gullahs), African Americans living in Charleston, South Carolina, and West Coast African Americans. Analyses showed a high degree of similarity within the New World African-derived populations, where haplotype frequencies and diversities were similar. Phi-statistics indicated that very little genetic differentiation has occurred within New World African-derived populations, but that there has been significant differentiation of these populations from Sierra Leoneans. Genetic distance estimates indicated a close relationship of Gullahs and Jamaicans with Sierra Leoneans, while African Americans living in Charleston and the West Coast were progressively more distantly related to the Sierra Leoneans. We observed low maternal European American admixture in the Jamaican and Gullah samples (m = 0.020 and 0.064, respectively) that increased sharply in a clinal pattern from Charleston African Americans to West Coast African Americans (m = 0.099 and 0.205, respectively). The appreciably reduced maternal European American admixture noted in the Gullah indicates that the Gullah may be uniquely situated to allow genetic epidemiology studies of complex diseases in African Americans with low European American admixture. (c) 2004 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Sea Isl Families Project, Charleston, SC USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Project Sugar, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. RP McLean, DC (reprint author), Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, 135 Cannon St,Suite 305R,POB 250835, Charleston, SC 29425 USA. EM mcleandc@musc.edu FU NIDDK NIH HHS [DK-47461] NR 35 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD AUG PY 2005 VL 127 IS 4 BP 427 EP 438 DI 10.1002/ajpa.20047 PG 12 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 947RO UT WOS:000230664100006 PM 15624208 ER PT J AU Burns, SP Rad, MY Bryant, S Kapur, V AF Burns, SP Rad, MY Bryant, S Kapur, V TI Long-term treatment of sleep apnea in persons with spinal cord injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article; Proceedings Paper CT 47th Annual Conference of the American-Paraplegia-Society CY SEP 05, 2001 CL Las Vegas, NV SP Amer Paraplegia Soc DE spinal cord injuries; sleep apnea syndromes; continuous positive airway pressure; patient compliance ID POSITIVE AIRWAY PRESSURE; CPAP THERAPY; APNEA/HYPOPNEA SYNDROME; NASAL CPAP; DAYTIME SLEEPINESS; HEART HEALTH; DISEASE; MEN AB Objective: Although numerous studies have documented a high prevalence of sleep apnea in persons with spinal cord injury, relatively little has been published regarding treatment of sleep apnea in this population. The purpose of this study was to describe long-term treatment outcomes and side effects of sleep apnea treatment in persons with spinal cord injury. Design: Descriptive, postal mail survey to spinal cord injury individuals with sleep apnea followed by a Veterans Affairs Spinal Cord Injury Service. Results: The response rate to the mailed survey was 54%, with complete surveys obtained from 40 individuals with spinal cord injury and sleep apnea. The majority of participants (93%) had been diagnosed with sleep apnea through routine clinical care, and patients had been diagnosed a mean of 4 yrs earlier. Continuous positive airway pressure was the most commonly used treatment. Continuous positive airway pressure was tried by 80% of patients, and of these, 63% continued to use continuous positive airway pressure, with mean usage 6.5 nights per week and 6.9 hrs per night. Continuous positive airway pressure was rated as beneficial in comparison with its side effects. The most common side effects were nasal congestion and mask discomfort. Conclusion: Many spinal cord injury individuals with sleep apnea become long-term users of continuous positive airway pressure and perceive a subjective benefit from the treatment. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv 128, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Kapur, Vishesh/K-1054-2014 OI Kapur, Vishesh/0000-0002-5417-1097 NR 30 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2005 VL 84 IS 8 BP 620 EP 626 DI 10.1097/01.phm.0000171008.69453.b9 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 950LO UT WOS:000230858900008 PM 16034232 ER PT J AU Jarrahy, R Huang, WB Rudkin, GH Lee, JM Ishida, K Berry, MD Sukkarieh, M Wu, BM Yamaguchi, DT Miller, TA AF Jarrahy, R Huang, WB Rudkin, GH Lee, JM Ishida, K Berry, MD Sukkarieh, M Wu, BM Yamaguchi, DT Miller, TA TI Osteogenic differentiation is inhibited and angiogenic expression is enhanced in MC3T3-E1 cells cultured on three-dimensional scaffolds SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE gene expression; osteogenesis; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; VIVO GENE-THERAPY; MARROW STROMAL CELLS; MESENCHYMAL STEM-CELLS; BONE REGENERATION; IN-VITRO; POLY(LACTIDE-CO-GLYCOLIDE) SCAFFOLDS; BIODEGRADABLE POLYMERS; MECHANICAL-PROPERTIES; OSTEOBLAST FUNCTION AB Osteogenic differentiation of osteoprogenitor cells in three-dimensional (3D) in vitro culture remains poorly understood. Using quantitative real-time RT-PCR techniques, we examined mRNA expression of alkaline phosphatase, osteocalcin, and vascular endothelial growth factor (VEGF) in murine preosteoblastic MC3T3-E1 cells cultured for 48 h and 14 days on conventional two-dimensional (2D) poly(L-lactide-coglycolide) (PLGA) films and 3D PLGA scaffolds. Differences in VEGF secretion and function between 2D and 3D culture systems were examined using Western blots and an in vitro Matrigel-based angiogenesis assay. Expression of both alkaline phosphatase and osteocalcin in cells cultured on 3D scaffolds was significantly down-regulated relative to 2D controls in 48 h and 14 day cultures. In contrast, elevated levels of VEGF expression in 3D culture were noted at every time point in short- and long-term culture. VEGF protein secretion in 3D cultures was triple the amount of secretion observed in 2D controls. Conditioned medium from 3D cultures induced an enhanced level of angiogenic activity, as evidenced by increases in branch points observed in in vitro angiogenesis assays. These results collectively indicate that MC3T3-E1 cells commit to osteogenic differentiation at a slower rate when cultured on 3D PLGA scaffolds and that VEGF is preferentially expressed by these cells when they are cultured in three dimensions. C1 Vet Adm Greater Los Angeles Healthcare Syst, Plast Surg Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Div Plast Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA. RP Miller, TA (reprint author), GLAHS, Plast Surg Lab, 11301 Wilshire Blvd,Rm 221,Bldg 114, Los Angeles, CA 90073 USA. EM millerlab@hotmail.com NR 59 TC 26 Z9 27 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 2005 VL 289 IS 2 BP C408 EP C414 DI 10.1152/ajpcell.00196.2004 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 943CB UT WOS:000230328300020 PM 16002625 ER PT J AU Hennige, AM Ozcan, U Okada, T Jhala, US Schubert, M White, MF Kulkarni, RN AF Hennige, AM Ozcan, U Okada, T Jhala, US Schubert, M White, MF Kulkarni, RN TI Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin receptor substrate proteins; islets; transplantation; insulin resistance; beta-cell growth ID TYPE-2 DIABETES-MELLITUS; PANCREATIC-ISLETS; FACTOR-I; PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; SECRETORY DEFECT; IRS-1 GENE; IGF-I; MICE AB Insulin and IGF-I activate antiapoptotic pathways via insulin receptor substrate (IRS) proteins in most mammalian cells, including beta-cells. IRS-1 knockout (IRS-1KO) mice show growth retardation, hyperinsulinemia, and hyperplastic but dysfunctional islets without developing overt diabetes, whereas IRS-2KOs develop insulin resistance and islet hypoplasia leading to diabetes. Because both models display insulin resistance, it is difficult to differentiate islet response to insulin resistance from islet defects due to loss of proteins in the islets themselves. We used a transplantation approach, as a means of separating host insulin resistance from islet function, to examine alterations in proteins in insulin/IGF-I signaling pathways that may contribute to beta-cell proliferation and/or apoptosis in IRS-1KO islets. Islets isolated from wild-type ( WT) or IRS-1KO mice were transplanted into WT or insulin-resistant IRS-1KO males under the kidney capsule. The beta-cell mitotic rate in transplanted islets in IRS-1KO recipients was increased 1.5-fold compared with WT recipients and was similar to that in endogenous pancreases of IRS-1KOs, whereas beta-cell apoptosis was reduced by similar to 80% in IRS-1KO grafts in IRS-1KO recipients compared with WT recipients. Immunohistochemistry showed a substantial increase in IRS-2 expression in IRS-1KO islets transplanted into IRS-1KO mice as well as in endogenous islets from IRS-1KOs. Furthermore, enhanced cytosolic forkhead transcription factor (FoxO1) staining in IRS-1KO grafts suggests intact Akt/PKB activity. Together, these data indicate that, even in the absence of insulin resistance, beta-cells deficient in IRS-1 exhibit a compensatory increase in IRS-2, which is associated with islet growth and is characterized by both proliferative and antiapoptotic effects that likely occur via an insulin/IGF-I/IRS-2 pathway. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. Univ Calif San Diego, Whittier Inst, Islet Res Labs, La Jolla, CA 92093 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Schubert, Markus/F-5150-2010 FU NIDDK NIH HHS [P30-DK-36836, R03-DK66207, DK-02885, R01-DK-68721, R01-DK-67536] NR 52 TC 25 Z9 27 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2005 VL 289 IS 2 BP E337 EP E346 DI 10.1152/ajpendo.00032.2004 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 945CA UT WOS:000230477700022 PM 15827066 ER PT J AU Misra, M Miller, KK Kuo, K Griffin, K Stewart, V Hunter, E Herzog, DB Klibanski, A AF Misra, M Miller, KK Kuo, K Griffin, K Stewart, V Hunter, E Herzog, DB Klibanski, A TI Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE growth hormone; cortisol; total triiodothyronine; estradiol; luteinizing hormone; insulin resistance ID GROWTH-HORMONE-SECRETION; POLYCYSTIC-OVARY-SYNDROME; GH-RELEASING HORMONE; SOLUBLE LEPTIN RECEPTOR; INSULIN SENSITIVITY; PLASMA-LEVELS; HUMAN OBESITY; SERUM LEPTIN; SECRETAGOGUE RECEPTOR; LUTEINIZING-HORMONE AB Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org RI Griffin, Kathryn/K-1677-2016 OI Griffin, Kathryn/0000-0002-3154-3273 FU NCRR NIH HHS [M01-RR-01066, K23-RR-018851]; NIDDK NIH HHS [DK062249] NR 67 TC 82 Z9 83 U1 0 U2 0 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 AUG PY 2005 VL 289 IS 2 BP E347 EP E356 DI 10.1152/ajpendo.00615.2004 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 945CA UT WOS:000230477700023 PM 15755766 ER PT J AU Alkhoury, F Malo, MS Mozumder, M Mostafa, G Hodin, RA AF Alkhoury, F Malo, MS Mozumder, M Mostafa, G Hodin, RA TI Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cell cycle; enterocyte differentiation; gene regulation; gut development; homeostasis; intestinal alkaline phosphatase; tumorigenesis ID HOMEOBOX GENE; HOMEODOMAIN PROTEINS; EPITHELIAL-CELLS; THYROID-HORMONE; DOWN-REGULATION; TRANSCRIPTION; MARKER; PROLIFERATION; ACTIVATION; PROMOTER AB Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2. Am J Physiol Gastrointest Liver Physiol 289:G285-G290, 2005. First published March 17, 2005; doi:10.1152/ajpgi.00037.2005.-We have examined the role that the caudal-related homeobox transcription factors Cdx1 and Cdx2 play in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase (IAP). Human colon cancer Caco-2 cells were transiently transfected with Cdx1 and/or Cdx2, and semiquantitative RT-PCR was used to study the effects on IAP mRNA expression. Transfections with a variety of IAP-luciferase reporter constructs were used to identify a Cdx response element located within the human IAP gene promoter. Protein-DNA interactions were examined by EMSA. Results showed that Cdx1 markedly induced IAP mRNA expression, whereas Cdx2 did not, and, in fact, inhibited the Cdx1 effects. Functional analysis revealed that Cdx1 transactivates ( fourfold, P < 0.05) the IAP promoter through a novel Cdx response element (GTTTAGA) located between -2369 and -2375 upstream of the translational start site. EMSA showed that both Cdx1 and Cdx2 could bind to the cis element, but in cotransfection experiments, Cdx2 inhibited the Cdx1 effects by similar to 50%. Thus we have identified a previously unrecognized interaction between two important gut transcription factors, Cdx1 and Cdx2, in the context of IAP gene regulation. Cdx1 activates the IAP gene via a novel cis element, whereas Cdx2 inhibits the Cdx1 effects. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Gray 504,55 Fruit St, Boston, MA 02114 USA. EM rhodin@partners.org NR 40 TC 24 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 2005 VL 289 IS 2 BP G285 EP G290 DI 10.1152/ajpgi.00037.2005 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 945CB UT WOS:000230477800016 PM 15774940 ER PT J AU Lu, L Khan, S Lencer, W Walker, WA AF Lu, L Khan, S Lencer, W Walker, WA TI Endocytosis of cholera toxin by human enterocytes is developmentally regulated SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE clathrin; caveolae; endocytosis; intestinal development ID BRUSH-BORDER MEMBRANES; EPITHELIAL-CELL LINE; NECROTIZING ENTEROCOLITIS; INCREASED SENSITIVITY; POLARIZED EPITHELIA; SIGNAL-TRANSDUCTION; GOLGI-APPARATUS; HUMAN INTESTINE; FINE STRUCTURE; RAT AB Endocytosis of cholera toxin by human enterocytes is developmentally regulated. Am J Physiol Gastrointest Liver Physiol 289: G332-G341, 2005. First published March 24, 2005;doi:10.1152/ajpgi.00521.2004. Many secretory diarrheas including cholera are more prevalent and fulminant in young infants than in older children and adults. Cholera toxin (CT) elicits a cAMP-dependent chloride secretory response in intestinal epithelia, which accounts for the fundamental pathogenesis of this toxigenic diarrhea. We have previously reported that the action of this bacterial enterotoxin is excessive in immature enterocytes and under developmental regulation. In this study, we tested the hypothesis that enhanced endocytosis by immature human enterocytes may, in part, account for the excessive secretory response to CT noted in the immature intestine and that enterocyte endocytosis of CT is developmentally regulated. To test this hypothesis, we used specific inhibitors to define endocytic pathways in mature and immature cell lines. We showed that internalization of CT in adult enterocytes is less and occurs via the caveolae/raft-mediated pathway in contrast to an enhanced immature human enterocyte CT uptake that occurs via a clathrin pathway. We also present evidence that this clathrin pathway is developmentally regulated as demonstrated by its response to corticosteroids, a known maturation factor that causes a decreased CT endocytosis by this pathway. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Charlestown, MA 02129 USA. Aga Kan Univ Hosp, Karachi, Pakistan. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NIDDK NIH HHS [P01 DK 33506, R01 DK 70260, P30 DK 40561] NR 46 TC 14 Z9 16 U1 2 U2 8 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 AUG PY 2005 VL 289 IS 2 BP G332 EP G341 DI 10.1152/ajpgi.00521.2004 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 945CB UT WOS:000230477800021 PM 15790757 ER PT J AU Chacko, BK Chandler, RT Mundhekar, A Khoo, N Pruitt, HM Kucik, DF Parks, DA Kevil, CG Barnes, S Patel, RP AF Chacko, BK Chandler, RT Mundhekar, A Khoo, N Pruitt, HM Kucik, DF Parks, DA Kevil, CG Barnes, S Patel, RP TI Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE inflammation; genistein; peroxisomal proliferator-activated receptor-gamma; atherosclerosis; monocytes ID ACTIVATED-RECEPTOR-GAMMA; AKT-DEPENDENT ACTIVATION; LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; PHYTOESTROGEN GENISTEIN; ANTIOXIDANT PROPERTIES; PLATELET-AGGREGATION; POSTMENOPAUSAL WOMEN; ATHEROSCLEROSIS AB The antiatherogenic effects of soy isoflavone consumption have been demonstrated in a variety of studies. However, the mechanisms involved remain poorly defined. Adhesion of monocytes to vascular endothelial cells is a key step within the inflammatory cascade that leads to atherogenesis. Many factors, including the physical forces associated with blood flow, regulate this process. Using an in vitro flow assay, we report that genistein, a principal component of most isoflavone preparations, inhibits monocyte adhesion to cytokine (TNF-alpha)-stimulated human vascular endothelial cells at physiologically relevant concentrations (0-1 mu M). This effect is absolutely dependent on flow and is not observed under static conditions. Furthermore, this inhibition was dependent on activation of endothelial peroxisomal proliferator-activated receptor-gamma. No significant role for other reported properties of genistein, including antioxidant effects, inhibition of tyrosine kinases, or activation of estrogen receptors, was observed. Furthermore, the antiadhesive effects of genistein did not occur via modulation of the adhesion molecules E-selectin, ICAM-1, VCAM-1, or platelet-endothelial cell adhesion molecule-1. These data reveal a novel anti-inflammatory mechanism for isoflavones and identify the physical forces associated with blood flow and a critical mediator of this function. C1 Purdue Univ, Birmingham Bot Ctr Age Related Dis, Dept Pathol, Birmingham, AL USA. Purdue Univ, Birmingham Bot Ctr Age Related Dis, Dept Pharmacol, Birmingham, AL USA. Purdue Univ, Birmingham Bot Ctr Age Related Dis, Dept Anesthesiol, Birmingham, AL USA. Univ Alabama, Ctr Free Radical Biol, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. Louisiana State Univ, Dept Pathol, Shreveport, LA 71105 USA. RP Patel, RP (reprint author), Univ Alabama, Dept Pathol, 901 19th St S,BMR-2,Rm 307, Birmingham, AL 35294 USA. EM patel@path.uab.edu RI Kevil, Christopher/G-9318-2011; OI Patel, Rakesh/0000-0002-1526-4303 FU NCCIH NIH HHS [P50 AT-00477]; NIAID NIH HHS [R21 AI-054552]; NIEHS NIH HHS [R03 ES/DK-11504] NR 50 TC 53 Z9 56 U1 0 U2 3 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 AUG PY 2005 VL 289 IS 2 BP H908 EP H915 DI 10.1152/ajpheart.00781.2004 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 944VO UT WOS:000230458800052 PM 15805228 ER PT J AU Liu, FF Stone, JR Schuldt, AJT Okoshi, K Okoshi, MP Nakayama, M Ho, KKL Manning, WJ Marchionni, MA Lorell, BH Morgan, JP Yan, XH AF Liu, FF Stone, JR Schuldt, AJT Okoshi, K Okoshi, MP Nakayama, M Ho, KKL Manning, WJ Marchionni, MA Lorell, BH Morgan, JP Yan, XH TI Heterozygous knockout of neuregulin-1 gene in mice exacerbates doxorubicin-induced heart failure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE erbB2; receptors; transgenic mice ID METASTATIC BREAST-CANCER; ERBB SIGNALING NETWORK; INDUCED APOPTOSIS; VENTRICULAR MYOCYTES; DILATED CARDIOMYOPATHY; CARDIAC DEVELOPMENT; AORTIC-STENOSIS; CARDIOTOXICITY; RECEPTOR; TRASTUZUMAB AB Neuregulins and their erbB receptors are essential for cardiac development and postulated to be cardioprotective in the presence of injury in the postnatal heart. We tested the hypothesis that the development of doxorubicin-induced cardiotoxicity in vivo is more severe in mice with heterozygous knockout of the neuregulin-1 gene (NRG-1(+/-)) compared with wild-type mice (WT). Three-month old NRG-1(+/-) and WT mice were injected with a single dose of doxorubicin ( 20 mg/kg ip). Survival was analyzed by the Kaplan-Meier approach. Left ventricular (LV) function and signaling pathways were analyzed 4 days after treatment. Fifteen days after treatment, survival was significantly lower in doxorubicin-treated NRG-1(+/-) mice (NRG-1(+/-) Dox) compared with doxorubicin-treated WT mice (WT- Dox) (15% vs. 33%, P < 0.01). LV mass was significantly lower in NRG-1(+/-)-Dox but not in WT- Dox compared with nontreated animals. LV systolic pressure and LV midwall fractional shortening were significantly lower in NRG-1(+/-)- Dox compared with WT- Dox mice. LV protein levels of NRG-1, erbB2, and erbB4 receptors were similar in WT- Dox and NRG-1(+/-)-Dox mice. However, levels of phosphorylated erbB2, Akt, and ERK-1/2 were significantly decreased in NRG1(+/-)- Dox compared with WT- Dox mice. A significant decrease in phosphorylated P70S6K levels was also observed in NRG-1 (+/-)-Dox compared with nontreated NRG-1(+/-) mice. These results demonstrate that heterozygous knockout of the neuregulin-1 gene worsens survival and LV function in the presence of doxorubicin-induced cardiac injury in vivo. This is associated with the depression of activation of the erbB2 receptor as well as Akt, p70S6K, and ERK-1/2 pathways. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NRG Biotech, Arlington, MA USA. RP Yan, XH (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, 330 Brookline Ave,Rm SL-221, Boston, MA 02215 USA. EM xyan@bidmc.harvard.edu RI Okoshi, Marina/F-4809-2010; Okoshi, Katashi/A-3955-2011 FU NHLBI NIH HHS [HL-52864-07] NR 41 TC 55 Z9 60 U1 1 U2 2 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 AUG PY 2005 VL 289 IS 2 BP H660 EP H666 DI 10.1152/ajpheart.00268.2005 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 944VO UT WOS:000230458800022 PM 15833803 ER PT J AU Quinn, VP Stevens, VJ Hollis, JF Rigotti, NA Solberg, LI Gordon, N Ritzwoller, D Smith, KS Hu, WM Zapka, J AF Quinn, VP Stevens, VJ Hollis, JF Rigotti, NA Solberg, LI Gordon, N Ritzwoller, D Smith, KS Hu, WM Zapka, J TI Tobacco-cessation services and patient satisfaction in nine nonprofit HMOs SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 9th Annual HMO Research Network Conference CY APR 01-02, 2003 CL Denver, CO ID CLINICAL-PRACTICE GUIDELINE; SMOKING-CESSATION; COMPETING DEMANDS; HEART-DISEASE; PRIMARY-CARE; HALF EMPTY; PHYSICIANS; SMOKERS; INTERVENTIONS; CANCER AB Background: The U.S. Public Health Service clinical practice guideline calls for clinicians and healthcare organizations to identify and treat every tobacco user seen in a healthcare setting. There is little information on the extent of compliance with the guideline's treatment model described by the "5A's" (Ask, Advise, Assess, Assist, Arrange). Methods: In 1999-2000 a survey was mailed to 64,764 members aged 25 to 75 years, of nine nonprofit HMOs participating in the National Cancer Institute-funded Cancer Research Network. These plans provide medical care to more than 8 million Americans including a minority enrollment of 30%. Smokers were asked about tobacco-cessation treatments received during primary care visits in the past year. Results: A 70% response rate identified a smoking prevalence of 10% (n =4207). Results indicated that 90% of smokers were asked about smoking, 71% were advised to quit, 56% were assessed for their willingness to quit, 49% received assistance interventions, and 9% had follow-up arranged. Treatment was provided more often to smokers who asked for help and/or intended to quit. Few and only modest associations were found between other patient characteristics and receipt of 5A's cessation services. In contrast to widely reported concerns about smokers' resistance to tobacco interventions, smokers who received treatment were more satisfied with health plan services. Conclusions: Results demonstrate substantial clinician compliance with the first two steps-Ask and Advise. Greater efforts are needed in providing the more effective tobacco treatments-Assist and Arrange. Compliance with the guideline is associated with greater patient satisfaction. C1 Kaiser Permanente, Res & Evaluat Dept, Pasadena, CA 91188 USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Cambridge, MA 02138 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. HealthPartners Res Fdn, Minneapolis, MN USA. Kaiser Permanente, Div Res, Oakland, CA USA. Kaiser Permanente, Aurora, CO USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Meyers Primary Care Inst, Fallon Healthcare Syst, Worcester, MA 01605 USA. RP Quinn, VP (reprint author), Kaiser Permanente, Res & Evaluat Dept, 100 So Los Robles Ave,2nd Fl,Overnight Zip Code 9, Pasadena, CA 91188 USA. EM virginia.p.quinn@kp.org NR 44 TC 70 Z9 70 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD AUG PY 2005 VL 29 IS 2 BP 77 EP 84 DI 10.1016/j.amepre.2005.04.006 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 947HR UT WOS:000230634500001 PM 16005802 ER PT J AU O'Brien, CP AF O'Brien, CP TI Anticraving medications for relapse prevention: A possible new class of psychoactive medications SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc ID PLACEBO-CONTROLLED TRIAL; OPIOID RECEPTOR GENE; RANDOMIZED CONTROLLED-TRIAL; GAMMA-VINYL-GABA; ALCOHOL DEPENDENCE; COCAINE DEPENDENCE; DOUBLE-BLIND; BETA-ENDORPHIN; CLINICAL-TRIAL; DRUG-ABUSE AB Psychiatrists have gradually developed a list of medications that are effective in the treatment of addictive disorders. Although alcoholism has received the most attention, nicotine, heroin, and cocaine have all been shown to be influenced by heredity. Of course, the immediate goal is the reduction of drug craving and the prevention of relapse to compulsive drug taking. A medication that can aid in the maintenance of the opiate-free state is naltrexone, a specific opiate antagonist. Naltrexone is also a good example of an anticraving medication used in the treatment of alcoholism. Clinicians currently have two types of medication to aid in the treatment of tobacco use disorder, arguably the most important addiction. Bupropion propion and nicotine replacement can be given in a coordinated fashion to provide the best available results. At present, no medication is approved by the Food and Drug Administration for the indication of cocaine addiction. Recently, however, five different medications, already approved for other purposes, have been found to be effective among cocaine addicts. Despite clinical trials that show benefit, anti-craving medications are not well known and are underused by clinicians. Addiction is a heterogeneous condition, with variability in reactivity to the drug of abuse and to the medications available to treat it. Recent developments in pharmacogenetics may result in improved selection of medications based on genotype. C1 Univ Penn, Treatment Res Ctr, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP O'Brien, CP (reprint author), Univ Penn, Treatment Res Ctr, Philadelphia VA Med Ctr, 3900 Chestnut St,Rm 6178, Philadelphia, PA 19104 USA. EM obrien@mail.trc.upenn.edu FU NIDA NIH HHS [DA-P50-12756, DA-P60-05186] NR 71 TC 218 Z9 223 U1 6 U2 20 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 AUG PY 2005 VL 162 IS 8 BP 1423 EP 1431 DI 10.1176/appi.ajp.162.8.1423 PG 9 WC Psychiatry SC Psychiatry GA 950LA UT WOS:000230857400004 PM 16055763 ER PT J AU Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, B Mintz, J AF Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, B Mintz, J TI Modulation of attention during visual masking in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CONSCIOUSNESS; MECHANISM AB Objective: Schizophrenia patients consistently demonstrate performance deficits on visual masking procedures. The present study examined whether attentional manipulation would improve subjects' performance on visual masking. Method: A metacontrast task was administered to 105 schizophrenia patients and 52 healthy comparison subjects. Attention was manipulated by associating selected trials of the task with monetary reward. Results: Schizophrenia patients exhibited poorer performance than the comparison subjects across conditions. Patients demonstrated modest, but statistically significant, improvement in performance with the attentional manipulation. This improvement was not significant for the comparison subjects. Conclusions: These findings suggest that early visual processes in schizophrenia are responsive to attentional manipulation but that the degree of improvement is relatively small, suggesting that these processes are not easily altered. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Rassovsky, Y (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Geffen Sch Med, 760 Westwood Plaza C8-747-NPI, Los Angeles, CA 90024 USA. EM yurir@ucla.edu FU NIMH NIH HHS [MH-37705, MH-43292] NR 12 TC 27 Z9 28 U1 0 U2 1 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 AUG PY 2005 VL 162 IS 8 BP 1533 EP U8 DI 10.1176/appi.ajp.162.8.1533 PG 3 WC Psychiatry SC Psychiatry GA 950LA UT WOS:000230857400020 PM 16055778 ER PT J AU Sorensen, G Barbeau, E Stoddard, AM Hunt, MK Kaphingst, K Wallace, L AF Sorensen, G Barbeau, E Stoddard, AM Hunt, MK Kaphingst, K Wallace, L TI Promoting behavior change among working-class, multiethnic workers: Results of the healthy directions-small business study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID COLON-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; LIFE-STYLE; COLORECTAL-CANCER; MULTIVITAMIN USE; SOCIAL-CLASS; RISK; PREVENTION; INTERVENTION AB Objectives. We examined the efficacy of a cancer prevention intervention designed to improve health behaviors among working-class, multiethnic populations employed in small manufacturing businesses. Methods. Worksites were randomly assigned to an intervention or minimal-intervention control condition. The intervention targeted fruit and vegetable consumption, red meat consumption, multivitamin use, and physical activity. Results. Employees in the intervention group showed greater improvements for every outcome compared with employees in the control group. Differences in improvement were statistically significant for multivitamin use and physical activity. Intervention effects were larger among workers than among managers for fruit and vegetable consumption and for physical activity. Conclusions. The social-context model holds promise for reducing disparities in health behaviors. Further research is needed to improve the effectiveness of the intervention. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM glorian_sorensen@dfci.harvard.edu FU NCI NIH HHS [P01 CA 75308, P01 CA075308] NR 57 TC 74 Z9 75 U1 2 U2 14 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 AUG PY 2005 VL 95 IS 8 BP 1389 EP 1395 DI 10.2105/AJPH.2004.038745 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 950LE UT WOS:000230857800021 PM 16006422 ER PT J AU Jacobs, EA Karavolos, K Rathouz, PJ Ferris, TG Powell, LH AF Jacobs, EA Karavolos, K Rathouz, PJ Ferris, TG Powell, LH TI Limited English proficiency and breast and cervical cancer screening in a multiethnic population SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; WOMEN; LANGUAGE; KNOWLEDGE; AMERICAN; CHINESE; CARE AB Objectives. We examined the relationship between ability to speak English and receipt of Papanicolaou tests, clinical breast examinations, and mammography in a multiethnic group of women in the United States. Methods. We used longitudinal data from the Study of Women Across the Nation to examine receipt of breast and cervical cancer screening among Chinese, Japanese, Hispanic, and White women who reported reading and speaking (1) only a language other than English, (2) another language more fluently than English, or (3) only English or another language and English with equal fluency. Logistic regression was used to analyze the data. Results. Reading and speaking only a language other than English and reading and speaking another language more fluently than English, were significantly and negatively associated with receipt of breast and cervical cancer screening in unadjusted models. Although these findings were attenuated in adjusted models, not speaking English well or at all remained negatively associated with receipt of cancer screening. Conclusions. These findings suggest that language barriers contribute to health disparities by impeding adequate health communication. C1 John H Stroger Jr Hosp Cook Cty, Chicago, IL USA. Rush Univ, Ctr Med, Dept Prevent Med, Biostat Sect, Chicago, IL 60612 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Med & Pediat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Jacobs, EA (reprint author), 1900 W Polk St,16th Floor, Chicago, IL 60612 USA. EM ejacobs@rush.edu FU NIA NIH HHS [U01 AG012553, U01 AG 012554, U01 AG012456, U01 AG012495, U01 AG012505, U01 AG012531, U01 AG012535, U01 AG012546, U01 AG012554, U01AG012531]; NINR NIH HHS [U01 NR004061, U01 NR04061]; PHS HHS [U01 A012539] NR 31 TC 117 Z9 117 U1 2 U2 7 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 AUG PY 2005 VL 95 IS 8 BP 1410 EP 1416 DI 10.2105/AJPH.2004.041418 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 950LE UT WOS:000230857800024 PM 16043670 ER PT J AU Caironi, P Ichinose, F Liu, R Ones, RC Bloch, KD Zapol, WM AF Caironi, P Ichinose, F Liu, R Ones, RC Bloch, KD Zapol, WM TI 5-lipoxygenase deficiency prevents respiratory failure during ventilator-induced lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hypoxic pulmonary vasoconstriction; leukotrienes; ventilator-induced lung injury ID HYPOXIC PULMONARY VASOCONSTRICTION; CYTOSOLIC PHOSPHOLIPASE A(2); VIVO RAT MODEL; DISTRESS-SYNDROME; INFLAMMATORY RESPONSES; MECHANICAL VENTILATION; CYSTEINYL LEUKOTRIENES; ENDOTHELIAL-CELLS; STRESS FAILURE; EDEMA FLUID AB Rationale: Mechanical ventilation with high VT (HVT) progressively leads to lung injury and decreased efficiency of gas exchange. Hypoxic pulmonary vasoconstriction (HPV) directs blood flow to well-ventilated lung regions, preserving systemic oxygenation during pulmonary injury. Recent experimental studies have revealed an important role for leukotriene (LT) biosynthesis by 5-lipoxygenase (5LO) in the impairment of HPV by endotoxin. Objectives:To investigate whether or not impairment of HPV contributes to the hypoxemia associated with HVT and to evaluate the role of LTs in ventilator-induced lung injury. Methods: We studied wild-type and 5LO-deficient mice ventilated for up to 10 hours with low VT (LVT) or HVT. Results: In wild-type mice, HVT, but not LVT, increased pulmonary vascular permeability and edema formation, impaired systemic oxygenation, and reduced survival. HPV, as reflected by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion, was markedly impaired in animals ventilated with HVT. HVT ventilation increased bronchoalveolar lavage levels of LTs and neutrophils. In 5LO-deficient mice, the HVT-induced increase of pulmonary vascular permeability and worsening of respiratory mechanics were markedly attenuated, systemic oxygenation was preserved, and survival increased. Moreover, in 5LO-deficient mice, HVT ventilation did not impair the ability of left mainstem bronchus occlusion to increase left pulmonary vascular resistance. Administration of MK886, a 5LO-activity inhibitor, or MK571, a selective cysteinyl-LT1 receptor antagonist, largely prevented ventilator-induced lung injury. Conclusions: These results indicate that LTs play a central role in the lung injury and impaired oxygenation induced by HVT ventilation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org FU NHLBI NIH HHS [HL-42397, HL-71987, HL-74352] NR 47 TC 37 Z9 38 U1 0 U2 2 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 AUG 1 PY 2005 VL 172 IS 3 BP 334 EP 343 DI 10.1164/rccm.200501-034OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 949IM UT WOS:000230778600011 PM 15894604 ER PT J AU Xie, AL Skatrud, JB Khayat, R Dempsey, JA Morgan, B Russell, D AF Xie, AL Skatrud, JB Khayat, R Dempsey, JA Morgan, B Russell, D TI Cerebrovascular response to carbon dioxide in patients with congestive heart failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE central sleep apnea; cerebral blood flow; hypercapnia; hypocapnia ID CEREBRAL-BLOOD-FLOW; CHEYNE-STOKES RESPIRATION; CENTRAL SLEEP-APNEA; OXYGEN-SENSING NEURONS; END-TIDAL PCO2; DILATED CARDIOMYOPATHY; GRADED REDUCTION; CARDIAC-FAILURE; NERVOUS-SYSTEM; HUMANS AB Rationale: Cerebrovascular reactivity to CO2 provides an important counterregulatory mechanism that serves to minimize the change in H+ at the central chemoreceptor, thereby stabilizing the breathing pattern in the face of perturbations in Pa-CO2. However, there are no studies relating cerebral circulation abnormality to the presence or absence of central sleep apnea in patients with heart failure. Objectives: To determine whether patients with congestive heart failure and central sleep apnea have an attenuated cerebrovascular responsibility to CO2. Methods: Cerebral blood flow velocity in the middle cerebral artery was measured in patients with stable congestive heart failure with (n = 9) and without (n = 8) central sleep apnea using transcranial ultrasound during eucapnia (room air), hypercapnia (inspired CO2, 3 and 5%), and hypocapnia (voluntary hyperventilation). In addition, eight subjects with apnea and nine without apnea performed a 20-second breath-hold to investigate the dynamic cerebrovascular response to apnea. Measurements and Main Results: The overall cerebrovascular reactivity to CO2 (hyper- and hypocapnia) was lower in patients with apnea than in the control group (1.8 +/- 0.2 vs. 2.5 +/- 0.2%/mm Hg, p < 0.05), mainly due to the prominent reduction of cerebrovascular reactivity to hypocapnia (1.2 +/- 0.3 vs. 2.2 +/- 0.1%/mm Hg, p < 0.05). Similarly, brain blood flow demonstrated a smaller surge after a 20-second breath-hold (peak velocity, 119 +/- 4 vs. 141 +/- 8% of baseline, p < 0.05). Conclusion: Patients with central sleep apnea have a diminished cerebrovascular response to PETCO2, especially to hypocapnia. The compromised cerebrovascular reacticity to CO2 might affect stability of the breathing pattern by causing ventilatory overshooting during hypercapnia and undershooting during hypocapnia. C1 William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Orthopaed & Rehabil, Madison, WI 53706 USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@facstaff.wisc.edu RI Khayat, Rami/E-3380-2011 NR 58 TC 80 Z9 82 U1 0 U2 3 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 AUG 1 PY 2005 VL 172 IS 3 BP 371 EP 378 DI 10.1164/rccm.200406-807OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 949IM UT WOS:000230778600016 PM 15901613 ER PT J AU Parimon, T Madtes, DK Au, DH Clark, JG Chien, JW AF Parimon, T Madtes, DK Au, DH Clark, JG Chien, JW TI Pretransplant lung function, respiratory failure, and mortality after stem cell transplantation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE bone marrow transplantation; mortality; pretransplant pulmonary function tests; respiratory failure ID BONE-MARROW TRANSPLANTATION; PULMONARY-FUNCTION TESTS; VERSUS-HOST-DISEASE; CHRONIC GRAFT; VENTILATION; CAPACITY AB Rationale: The role of pulmonary function before stem cell transplant as a potential risk factor for the development of early post-transplant respiratory failure and mortality is controversial. Methods: We conducted a retrospective analysis of the pretransplant pulmonary function of 2,852 patients who received their transplant between 1990 and 2001. Measurements: Pretransplant FEV1, FVC, total lung capacity (TLC), diffusing capacity of carbon monoxide (DLCO), and the alveolar-arterial oxygen tension difference P(A-a)O-2 were measured and assessed for association with development of early respiratory failure and mortality in Cox proportional hazard logistic models. Main Results: In multivariate analyses, progressive decrease of all lung function parameters was associated with a stepwise increase in risk of developing early respiratory failure and mortality when assessed in independent models. On the basis of a significant correlation between FEV1 and FVC (r = 0.81), FEV, and TLC (r = 0.61), and FVC and TLC (r = 0.80), and a lack of correlation between FEV, and DLCO, we developed a pretransplant lung function score based on pretransplant FEV, and DLCO to determine the extent of pulmonary compromise before transplant. Multivariate analysis indicated that higher pretransplant lung function scores are associated with a significant increased risk for developing early respiratory failure (category II hazard ratio [HR], 1.4; category III HR, 2.2; category IV HR, 3.1; p < 0.001) and death (category II HR, 1.2; category III HR, 2.2; category IV HR, 2.7; p < 0.005). Conclusions: These results suggest that not only does compromised pretransplant lung function contribute to the risk for development of early respiratory failure and mortality but this risk may be estimated before transplant by grading the extent of FEV, and DLCO compromise. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. US Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Chien, JW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,Suite D5-280, Seattle, WA 98109 USA. EM jchien@fhcrc.org FU NCI NIH HHS [CA78902, CA18029, P01 CA078902, CA15704]; NHLBI NIH HHS [1K23HL69860-01, 1R01 HL71914-01, HL36444] NR 22 TC 50 Z9 51 U1 0 U2 2 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 AUG 1 PY 2005 VL 172 IS 3 BP 384 EP 390 DI 10.1164/rccm.200502-212OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 949IM UT WOS:000230778600018 PM 15894602 ER PT J AU Chapman, VM Kalra, M Halpern, E Grottkau, B Albright, M Jaramillo, D AF Chapman, VM Kalra, M Halpern, E Grottkau, B Albright, M Jaramillo, D TI 16-MDCT of the posttraumatic pediatric elbow: Optimum parameters and associated radiation dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; CT; OPTIMIZATION AB OBJECTIVE. Our objective was to investigate a low-radiation-dose protocol for 16-MDCT of the posttraumatic pediatric elbow using z-axis automatic tube-current modulation, based on optimum scanning parameters determined in a porcine fracture model, and to report the radiation dose from this technique in nine children with acute elbow trauma. CONCLUSION. For the posttraumatic pediatric elbow, 16-MDCT using z-axis automatic tube-current modulation was optimal at 100 kVp with a noise index of 20 and a minimum amperage of 25 mA. C1 Massachusetts Gen Hosp, Methuen, MA 01844 USA. RP Chapman, VM (reprint author), Massachusetts Gen Hosp, 7 Norwich Lane, Methuen, MA 01844 USA. EM vchapman@partners.org NR 11 TC 4 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2005 VL 185 IS 2 BP 516 EP 521 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 948TL UT WOS:000230738500037 PM 16037530 ER PT J AU Irving, JA Young, RH AF Irving, JA Young, RH TI Lung carcinoma metastatic to the ovary - A clinicopothologic study of 32 cases emphasizing their morphologic spectrum and problems in differential diagnosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; lung; metastasis; small cell carcinoma; adenocarcinoma; squamous cell carcinoma; large cell carcinoma; thyroid transcription factor-1 ID TRANSCRIPTION FACTOR-I; SQUAMOUS-CELL CARCINOMA; IMMUNOHISTOCHEMICAL MARKER; PULMONARY TYPE; TUMORS; ADENOCARCINOMA; CANCER; ORIGIN; CERVIX; TRACT AB Thirty-two cases of lung carcinoma metastatic to the ovary in women 26 to 76 years of age (mean, 47 years) are reported. A history of prior lung carcinoma was documented in 53% of cases (17 of 32), with the ovarian tumor detected at a mean interval of I year. In 10 cases (31%), the lung and ovarian tumors occurred synchronously, and in 5 (16%) the ovarian tumor was detected up to 26 months before the lung cancer. Small cell carcinoma was more likely to present with ovarian manifestations than other subtypes. A history of smoking was obtained in 9 cases (28%), but detailed histories were not always available and the figure may be spuriously low. Forty-four percent of the tumors were small cell carcinomas (14 of 32), 34% adenocarcinomas (11 of 32), and 16% large cell carcinomas (5 of 32); there was a single squamous cell carcinoma and one atypical carcinoid. Thirteen percent of cases (4 of 32) had a coexisting primary ovarian tumor. The mean ovarian tumor size was 9.7 cm, and one third of the ovarian metastases were bilateral. Tumor was limited to the lung and one or both ovaries in 13 cases (40%). Morphologic features common to many of the ovarian turners were multinodular growth, widespread necrosis, and extensive lymphovascular invasion; involvement of the ovarian surface was rare. Attention to these features, to the usual absence of associated typical surface epithelial neoplasia, and to the clinical history enabled the correct diagnosis to be made in the majority of cases without need of special studies. In a minority of cases, immunohistochemical staining for thyroid transcription factor-1 was a useful ancillary marker in the distinction from primary ovarian carcinoma. The differential diagnosis with the primary ovarian tumors most often meriting consideration, including unusual variants of surface epithelial tumors, is discussed. C1 Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Irving, JA (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. EM jirving@vanhosp.bc.ca NR 45 TC 35 Z9 37 U1 0 U2 0 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 AUG PY 2005 VL 29 IS 8 BP 997 EP 1006 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 949EU UT WOS:000230768500002 PM 16006793 ER PT J AU Sandberg, WS Daily, B Egan, M Stahl, JE Goldman, JM Wiklund, RA Rattner, D AF Sandberg, WS Daily, B Egan, M Stahl, JE Goldman, JM Wiklund, RA Rattner, D TI Deliberate perioperative systems design improves operating room throughput SO ANESTHESIOLOGY LA English DT Article ID ANESTHESIA-CONTROLLED TIME; SURGICAL-PROCEDURE TIMES; SURGERY; COST; SIMULATION; EFFICIENCY; RESIDENTS AB Background: New operating room (OR) design focuses more on the surgical environment than on the process of care. The authors sought to improve OR throughput and reduce time per case by goal-directed design of a demonstration OR and the perioperative processes occurring within and around it. Methods: The authors constructed a three-room suite including an OR, an induction room, and an early recovery area. Traditionally sequential activities were run in parallel, and nonsurgical activities were moved from the OR to the supporting spaces. The new workflow was supported by additional anesthesia and nursing personnel. The authors used a retrospective, case- and surgeon-matched design to compare the throughput, cost, and revenue performance of the new OR to traditional ORs. Results: For surgeons performing the same case mix in both environments, the new OR processed more cases per day than traditional ORs and used less time per case. Throughput improvement came from superior nonoperative performance. Nonoperative Time was reduced from 67 min (95% confidence interval, 64-70 min) to 38 min (95% confidence interval, 35-40 min) in the new OR. All components of Nonoperative Time were meaningfully reduced. Operative Time decreased by approximately 5%. Hospital and anesthesia costs per case increased, but the increased throughput offset costs and the global net margin was unchanged. Conclusions: Deliberate OR and perioperative process redesign improved throughput. Performance improvement derived from relocating and reorganizing nonoperative activities. Better OR throughput entailed additional costs but allowed additional patients to be accommodated in the OR while generating revenue that balanced these additional costs. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, OR Informat Syst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM wsandberg@partners.org OI Sandberg, Warren/0000-0002-9246-777X NR 18 TC 104 Z9 104 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2005 VL 103 IS 2 BP 406 EP 418 DI 10.1097/00000542-200508000-00025 PG 13 WC Anesthesiology SC Anesthesiology GA 952EA UT WOS:000230983800024 PM 16052124 ER PT J AU Oaklander, AL Buchbinder, BR AF Oaklander, AL Buchbinder, BR TI Pregabalin-withdrawal encephalopathy and splenial edema: A link to high-altitude illness? SO ANNALS OF NEUROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CORPUS-CALLOSUM; POSTHERPETIC NEURALGIA; EPILEPTIC PATIENTS; TRANSIENT LESION; CEREBRAL EDEMA; ABNORMALITIES; GABAPENTIN; PATIENT; SEIZURES AB A postherpetic-neuralgia patient abruptly discontinued pregabalin. Thirty hours later, unexplained nausea, headache, and ataxia developed, progressing to delirium 8 days later. Magnetic resonance imaging indicated T2-hyperintense lesions of her splenium. Similar magnetic resonance imaging abnormalities, interpreted as focal vasogenic edema, develop in some epileptic patients after rapid anticonvulsant withdrawal. Patients with high-altitude cerebral edema have similar splenial-predominant magnetic resonance imaging abnormalities that accompany these same neurological symptoms. This case is the first to associate anticonvulsant-withdrawal splenial abnormalities with neurological symptoms, with gabapentin-type anticonvulsants, and is among the first in nonepileptic patients, suggesting that sudden anticonvulsant withdrawal alone, unaccompanied by seizures, can initiate symptomatic focal brain edema. The similarity of this syndrome to high-altitude cerebral edema suggests a possible common pathophysiology and offers potential therapies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nerve Injury Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Neuropathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nerve Injury Unit, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM aoaklander@partners.org FU NINDS NIH HHS [R01NS42866] NR 20 TC 19 Z9 22 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2005 VL 58 IS 2 BP 309 EP 312 DI 10.1002/ana.20583 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 950KM UT WOS:000230856000015 PM 15991228 ER PT J AU Colleoni, M Gelber, S Goldhirsch, A AF Colleoni, M Gelber, S Goldhirsch, A TI Treatment of advanced breast cancer: the good, the bad and the ugly SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID COST; CHEMOTHERAPY; THERAPY; CARE C1 European Inst Oncol, Dept Med, Div Med Oncol, Milan, Italy. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Int Breast Canc Study Grp, Ctr Stat, Boston, MA USA. RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Div Med Oncol, Milan, Italy. EM marco.colleoni@ieo.it NR 15 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2005 VL 16 IS 8 BP 1219 EP 1221 DI 10.1093/annonc/mdi255 PG 3 WC Oncology SC Oncology GA 955LX UT WOS:000231228500002 PM 15894547 ER PT J AU Terada, S Fuchs, JR Yoshimoto, H Fauza, DO Vacanti, JP AF Terada, S Fuchs, JR Yoshimoto, H Fauza, DO Vacanti, JP TI In vitro cartilage regeneration from proliferated adult elastic chondrocytes SO ANNALS OF PLASTIC SURGERY LA English DT Article DE tissue engineering; cartilage; regenerative medicine; aging ID GROWTH-FACTOR-BETA; TISSUE-ENGINEERED CARTILAGE; ARTICULAR CHONDROCYTES; PROTEOGLYCAN SYNTHESIS; CHONDROGENIC DIFFERENTIATION; PHENOTYPIC TRAITS; GENE-EXPRESSION; II COLLAGEN; IGF-I; CULTURE AB The purpose of this study was to investigate cellular feasibility in the proliferation and differentiation status of adult chondrocytes for cartilage regeneration in comparison to fetal chondrocytes. Primary cells were isolated from adult (n = 6) and fetal (n = 6) sheep ear cartilages and expanded in 10% fetal bovine serum (FBS) containing Ham's F12 medium, in which adult and fetal cell proliferation rates were compared using a WST-1 assay kit. Approximately 4 million cells were seeded onto each 1 x 1 x 0.2-cm (200 mu L) nonwoven fabric scaffold made from polyglycolic acid. Cell/polymer constructs were cultured in serum-free DMEM/F12 medium supplemented with 5 ng/mL TGF-beta(2) and 5 ng/mL des(1-3)IGF-I (adult chondrocytes, group A) or in 10% FBS containing Ham's F12 medium (adult chondrocytes, group 13, and fetal chondrocytes, group C) as controls in a rotating bioreactor for 6 weeks. The proliferation assay showed that fetal cells had a significantly better growth potential than did adult cells. Histology and extracellular matrix analyses revealed that groups A and C qualitatively displayed better matrix deposition than did group B. In conclusion, although adult sheep elastic chondrocytes had less growth potential than did fetal cells, the serum-free medium supplemented with growth factors significantly enhanced the production of cartilage matrix secreted from proliferated adult sheep elastic chondrocytes. C1 Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Ctr Minimally Invas Surg, Boston, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org NR 40 TC 11 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD AUG PY 2005 VL 55 IS 2 BP 196 EP 201 DI 10.1097/01.sap.0000164388.33965.4e PG 6 WC Surgery SC Surgery GA 950MA UT WOS:000230860100017 PM 16034253 ER PT J AU Darouiche, RO Berger, DH Khardori, N Robertson, CS Wall, MJ Metzler, MH Shah, S Mansouri, MD Cerra-Stewart, C Versalovic, J Reardon, MJ Raad, II AF Darouiche, RO Berger, DH Khardori, N Robertson, CS Wall, MJ Metzler, MH Shah, S Mansouri, MD Cerra-Stewart, C Versalovic, J Reardon, MJ Raad, II TI Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters - A randomized controlled trial SO ANNALS OF SURGERY LA English DT Article ID BLOOD-STREAM INFECTION; BACTERIAL-RESISTANCE; IN-VITRO; PREVENTION; MINOCYCLINE; EFFICACY; RIFAMPIN; COLONIZATION; TECHNOLOGY; DEVICES AB Objective: We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection. Summary Background Data: Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established. Methods: A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for >= 2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined. Results: Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from anti microbial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days). Conclusions: Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters. C1 Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. So Illinois Univ, Sch Med, Dept Med, Springfield, IL 62708 USA. Univ Missouri, Dept Surg, Columbia, MO USA. Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 32 TC 63 Z9 65 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2005 VL 242 IS 2 BP 193 EP 200 DI 10.1097/01.sla.0000171874.29934.61 PG 8 WC Surgery SC Surgery GA 950LG UT WOS:000230858000007 PM 16041209 ER PT J AU Wong, DR Agnihotri, AK Hung, JW Vlahakes, GJ Akins, CW Hilgenberg, AD Madsen, JC MacGillivray, TE Picard, MH Torchiana, DF AF Wong, DR Agnihotri, AK Hung, JW Vlahakes, GJ Akins, CW Hilgenberg, AD Madsen, JC MacGillivray, TE Picard, MH Torchiana, DF TI Long-term survival after surgical revascularization for moderate ischemic mitral regurgitation SO ANNALS OF THORACIC SURGERY LA English DT Article ID MILD-TO-MODERATE; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; VALVE REPAIR; BYPASS; ANNULOPLASTY; INTERVENTION; CARDIOMYOPATHY AB Background. We sought to characterize patient survival and degree of late mitral regurgitation (MR) in patients undergoing surgical revascularization with moderate ischemic MR. Methods. We retrospectively reviewed 251 patients undergoing coronary artery bypass graft (CABG) surgery between 1991 and 2001 with 3+ ischemic MR, including 31 patients who had concomitant mitral annuloplasty. Univariate and multivariable testing was employed. Results. Actuarial 1-, 5-, and 10-year survival was 84.0%, 67.5%, and 37.1% in the overall group of 251 patients. Independent predictors of long-term mortality were age 70 years or more (hazard ratio 2.50 [95% confidence interval 1.82 to 3.44]), prior myocardial infarction (3.99 [2.15 to 7.39]), unstable angina (2.27 [1.69 to 3.04]), chronic renal failure (4.87 [3.13 to 7.58]), atrial fibrillation (2.21 [1.65 to 2.96]), left internal mammary artery to left anterior descending artery graft (0.28 [0.18 to 0.43]), preoperative beta-blocker (0.43 [0.28 to 0.67]), ejection fraction (0.71/10% [0.64 to 0.80]), left atrium size (0.88/mm [0.84 to 0.92]), diffuse wall motion abnormalities (2.83 [1.77 to 4.55]), and mitral leaflet restriction (3.85 [2.46 to 5.99]). The model controlled for the performance of annuloplasty, which did not emerge as an independent predictor. Patients undergoing annuloplasty did have less mean late MR than those having CABG alone (p = 0.005). Overall, 57.8% of patients (63 of 109) with follow-up echocardiograms had improvement in grade of MR compared with baseline. In 54 of 95 patients (56.8%), intraoperative transesophageal echocardiography downgraded the degree of MR compared with the preoperative study. Conclusions. Patients with moderate ischemic MR undergoing CABG had relatively poor long-term survival, with significant differences when stratified according to preoperative characteristics. Performance of mitral annuloplasty reduced the degree of regurgitation but was not a predictor of long-term survival. Intraoperative transesophageal echocardiography frequently downgraded the degree of MR. (c) 2005 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Maritime Heart Ctr, Halifax, NS, Canada. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,BUL 209, Boston, MA 02114 USA. EM torchiana.david@mgh.harvard.edu OI Picard, Michael/0000-0002-9264-3243 NR 33 TC 67 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2005 VL 80 IS 2 BP 570 EP 578 DI 10.1016/j.athoracsur.2005.03.034 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 951IU UT WOS:000230923800031 PM 16039207 ER PT J AU White, JK Agnihotri, AK Titus, JS Torchiana, DF AF White, JK Agnihotri, AK Titus, JS Torchiana, DF TI A stentless trileaflet valve from a sheet of decellularized porcine small intestinal submucosa SO ANNALS OF THORACIC SURGERY LA English DT Article ID HEART-VALVES AB Purpose. The purpose of this study was to investigate the function of a trileaflet pulmonary valve constructed from a sheet of porcine small intestinal submucosa. Description. In four sheep, the native pulmonary valve and a segment of the pulmonary trunk was excised and replaced with a trileaflet valve constructed from decellularized porcine small intestinal submucosa. The valve construct was created from a sheet of the xenograft material by a method of involuting flaps of tissue inside a cylinder of itself. The function of the valve was assessed by echocardiography, catheter pullback across the valve, and observation of an excised valve in a flow simulator. Evaluation. The valve constructs exhibited low gradients and symmetrical leaflet movement with good mobility when tested under physiologic conditions in an acute sheep model. Conclusions. This method offers a means to create a functional trileaflet valve replacement from a sheet of tissue. (c) 2005 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP White, JK (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Bullfinch 119-50 Fruit St, Boston, MA 02114 USA. EM jkwhite@partners.org NR 10 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2005 VL 80 IS 2 BP 704 EP 707 DI 10.1016/j.athoracsur.2004.08.063 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 951IU UT WOS:000230923800051 PM 16039233 ER PT J AU Cannon, CP Mehta, SR Aranki, SF AF Cannon, CP Mehta, SR Aranki, SF TI Balancing the benefit and risk of oral antiplatelet agents in coronary artery bypass surgery SO ANNALS OF THORACIC SURGERY LA English DT Review ID CARDIAC SURGICAL-PATIENTS; VEIN-GRAFT PATENCY; POSTOPERATIVE BLOOD-LOSS; PREOPERATIVE ASPIRIN THERAPY; ST-SEGMENT ELEVATION; CARDIOPULMONARY BYPASS; PLATELET-FUNCTION; SAPHENOUS-VEIN; DOUBLE-BLIND; TRANSFUSION REQUIREMENTS AB Concern about possible hemorrhagic complications arising from use of oral antiplatelet agents in immediate proximity to coronary artery bypass graft (CABG) surgery leads many clinicians to avoid or discontinue these agents preoperatively. Recent evidence suggests that aspirin and clopidogrel can be used with relative safety in the preoperative period; dual antiplatelet therapy in the 5 days immediately preceding CABG surgery results in a moderate and variable increase in the risk of procedural bleeding. This modest hemorrhagic risk may be acceptable, given the clinical benefits of sustained antiplatelet therapy in preventing graft occlusion and ischemic complications pre- and post-CABG. Because the bleeding risk with aspirin is dose dependent, use of a low dose is preferred post-CABG. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. McMaster Univ, Dept Med, Div Cardiol, Hamilton, ON, Canada. Hamilton Hlth Sci, Hamilton, ON, Canada. RP Cannon, CP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 85 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2005 VL 80 IS 2 BP 768 EP 779 DI 10.1016/j.athoracsur.2004.09.058 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 951IU UT WOS:000230923800077 PM 16039260 ER PT J AU Tremblay, CL Giguel, F Guan, YB Chou, TC Takashima, K Hirsch, MS AF Tremblay, CL Giguel, F Guan, YB Chou, TC Takashima, K Hirsch, MS TI TAK-220, a novel small-molecule CCR5 antagonist, has favorable anti-human immunodeficiency virus interactions with other antiretrovirals in vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ENTRY; ZIDOVUDINE; INHIBITORS; COMBINATIONS; STAVUDINE AB TAK-220 is a CCR5 antagonist, part of the new class of anti-human immunodeficiency virus type I (anti-HIV-1) entry inhibitors. We evaluated the anti-HIV-1 interactions between TAK-220 and various antiretrovirals in vitro. Synergy was observed with all drugs at the 90 and 95% inhibitory concentrations. The favorable drug interactions observed suggest that further clinical evaluation is warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Cambridge, MA 02139 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Takeda Pharmaceut Co Ltd, Osaka, Japan. CHU Montreal, Montreal, PQ, Canada. RP Hirsch, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, 65 Landsdowne St,Room 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 NR 17 TC 27 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2005 VL 49 IS 8 BP 3483 EP 3485 DI 10.1128/AAC.49.8.3483-3485.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 951SI UT WOS:000230950700055 PM 16048964 ER PT J AU Tolleson, WH Doss, JC Latendresse, J Warbritton, AR Melchior, WB Chin, L Dubielzig, RR Albert, DM AF Tolleson, WH Doss, JC Latendresse, J Warbritton, AR Melchior, WB Chin, L Dubielzig, RR Albert, DM TI Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS+ Ink4a/Arf-/- mice SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR MELANOMA; MALIGNANT-MELANOMA; GERMLINE MUTATIONS; CHOROIDAL MELANOMA; RISK-FACTORS; IN-VIVO; TUMORS; MODEL; P16(INK4A); P14(ARF) AB Objective: To characterize a murine model of spontaneous amelanotic melanoma arising in the uvea of transgenic mice bearing a targeted deletion of the Ink4a/Arf tumor suppressor locus (exons 2 and 3) and expressing human H-ras controlled by the human tyrosinase promoter. Methods: Ocular lesions developed in 20 (15.7%) of 127 male albino Tyr-RAS+ Ink4a/Arf-/- transgenic FVB/N mice within 6 months, and were evaluated histologically and ultrastructurally. Results: Uveal melanomas were locally invasive but confined to the eye, with no evidence of metastasis. Tumor cells exhibited epithelioid and spindle-shaped morphological features and closely resembled the human counterpart. Melan-A, SIN and neuron-specific enolase expression were detected immuno his to chemically. Melanosomal structures were detected using electron microscopy. The retinal pigment epithelium was intact above small melanomas, and electron microscopy of the tumors failed to show the presence of basement membrane formation or desmosomes. Conclusion: Spontaneous uveal malignant melanomas occurring in male Tyr-RAS+ Ink4a/Arf-/- transgenic mice arise within the choroid or ciliary body and share histopathological features characteristic of human uveal melanoma. Clinical Relevance: Uveal melanoma research has benefited from xenograft models, but engineered mouse models of spontaneous uveal amelanotic melanoma will undoubtedly further our understanding of the genetic underpinning for this disease. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. RP Tolleson, WH (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wtolleson@nctr.fda.gov FU NCI NIH HHS [R01 CA 93947]; NEI NIH HHS [EY 01917] NR 38 TC 15 Z9 15 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2005 VL 123 IS 8 BP 1088 EP 1094 DI 10.1001/archopht.123.8.1088 PG 7 WC Ophthalmology SC Ophthalmology GA 955OY UT WOS:000231236900009 PM 16087843 ER PT J AU Srivastava, A Nielsen, PG Dal Cin, P Rosenberg, AE AF Srivastava, A Nielsen, PG Dal Cin, P Rosenberg, AE TI Monophasic synovial sarcoma of the liver SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MALIGNANT FIBROUS HISTIOCYTOMA; PARAFFIN-EMBEDDED TISSUE; LEIOMYOSARCOMA; DIAGNOSIS; SYT-SSX2 AB We report a hepatic monophasic synovial sarcoma in a 60-year-old woman who presented with right upper quadrant pain subsequent to an intrahepatic bleed from a highly vascular tumor mass. Imaging studies showed A dominant tumor mass in the right hepatic lobe with multiple satellite nodules. A detailed physical examination and radiologic workup failed to reveal a primary tumor elsewhere. A right partial hepatectomy was performed with a preoperative differential diagnosis of angiosarcoma versus hepatocellular carcinoma. The morphologic, immunophenotypic, and cytogenetic findings (t(X;18)(p1 1.2;q11.2)) were consistent with a monophasic synovial sarcoma. Postoperative clinical evaluation of the extremities and a positron emission tomographic scan performed 4 weeks after surgery showed no evidence of recurrent or metastatic disease. The patient was started on an aggressive 4-drug chemotherapy regimen, but died 3 months thereafter from widespread metastatic disease. No autopsy was performed. The presence of multiple lesions in the liver certainly suggests the possibility of metastatic disease. It would, however, be very unusual for a synovial sarcoma to present as an occult primary, and the negative radiologic workup I month after the partial hepatectomy also argues against this possibility. The clinical presentation, radiographic findings, and subsequent course in this patient was therefore most consistent with a primary monophasic synovial sarcoma of the liver. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Brigham & Womens Hosp, Div Cytogenet, Dept Pathol, Boston, MA 02115 USA. RP Rosenberg, AE (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 55 Fruit St,Warren Bldg,Room 225, Boston, MA 02114 USA. EM arosenberg@partners.org RI Srivastava, Amitabh/A-9386-2009 NR 14 TC 8 Z9 9 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2005 VL 129 IS 8 BP 1047 EP 1049 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 950NE UT WOS:000230863200016 PM 16048399 ER PT J AU Chamlin, SL Mattson, CL Frieden, IJ Williams, ML Mancini, AJ Cella, D Chren, MM AF Chamlin, SL Mattson, CL Frieden, IJ Williams, ML Mancini, AJ Cella, D Chren, MM TI The price of pruritus - Sleep disturbance and cosleeping in atopic dermatitis SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID EUROPEAN TASK-FORCE; CONSENSUS REPORT; SCORAD INDEX; CHILDREN; ECZEMA; INFANT AB Background: Atopic dermatitis is a common skin disorder that most often begins in infancy. Sleep disturbances in children with atopic dermatitis are likely due to itching and scratching and not only impact the afflicted child but may also affect the entire family. Sleep characteristics in young children with atopic dermatitis and their families have not been thoroughly investigated. Objective: To evaluate sleep disturbance and cosleeping in young children with atopic dermatitis and evaluate the association between sleep characteristics and features of the disease. Design and Methods: Parents of 300 children ranging in age from birth to 6 years with atopic dermatitis responded to 4 questions about sleep characteristics of their child and family. Analyses determined the prevalence of reported sleep disturbance and cosleeping, and their association with features of the patients and disease severity. Results: Sleep disturbance attributed to atopic dermatitis was common; most parents (> 60%) reported that the dermatitis affected how well they or their child slept. Cosleeping because of the skin condition was reported by 30% of families, and most of these parents (66%) were bothered by the cosleeping. Sleep disturbance and cosleeping were directly associated with severity of atopic dermatitis and with the degree to which parents reported that the atopic dermatitis affected the child and family's happiness. Conclusions: Sleep disturbances were more common in children with atopic dermatitis than have been reported in children overall. These results demonstrate important sequelae of a very common childhood condition that warrant further investigation and the development of intervention strategies. C1 Childrens Mem Hosp, Div Pediat Dermatol, Chicago, IL 60614 USA. Univ Calif San Francisco, Dept Dermatol & Pediat, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Serv Dermatol, San Francisco, CA USA. Northwestern Univ, Feinberg Sch Med, Evanston Northwestern Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. RP Chamlin, SL (reprint author), Childrens Mem Hosp, Div Pediat Dermatol, Chicago, IL 60614 USA. EM schamlin@childrensmemorial.org OI Frieden, Ilona/0000-0001-7305-5940 NR 15 TC 62 Z9 63 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2005 VL 159 IS 8 BP 745 EP 750 DI 10.1001/archpedi.159.8.745 PG 6 WC Pediatrics SC Pediatrics GA 951RR UT WOS:000230948900008 PM 16061782 ER PT J AU Grandas, NF Jain, NB Denckla, JB Brown, R Tun, CG Gallagher, ME Garshick, E AF Grandas, NF Jain, NB Denckla, JB Brown, R Tun, CG Gallagher, ME Garshick, E TI Dyspnea during daily activities in chronic spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE dyspnea; rehabilitation; smoking; speech; spinal cord injuries ID ADVANCED LUNG-CANCER; DAILY-LIFE ACTIVITIES; AMBULATORY PATIENTS; COORDINATION; RESPIRATION; PREVALENCE; SYMPTOMS AB Grandas NF, Jain NB, Denckla JB, Brown R, Tun CG, Gallagher ME, Garshick E. Dyspnea during daily activities in chronic spinal cord injury. Arch Phys Med Rehabil 2005;86:1631-5. Objective: To assess factors associated with breathlessness in chronic spinal cord injury (SCI) during daily activities. Design: Cross-sectional survey. Settings: Veterans Affairs SCI service and the community. Participants: Four hundred forty-one participants 1 or more years post-SCI, and without acute illness, were recruited between 1994 and 2003 and were categorized according to their ability to walk unassisted, walk with an aid, or to move about by either hand-propelled wheelchair or motorized wheelchair (MWC). Interventions: Assessment of injury extent, respiratory symptoms, cigarette smoking, comorbid medical conditions, and spirometry. Main Outcome Measures: Breathlessness during talking, eating, or dressing. Results: Breathlessness was more common in MWC users (20/85 users, 24%) than in nonusers (20/356, 6%). The main activity associated with breathlessness in 15 MWC users was talking (18%). In MWC users, the risk of breathlessness was related to lifetime cigarette smoking (odds ratio [OR]= 1.02; 95% confidence interval [CI], 1.00-1.03 per pack year), and reports of chronic cough (OR=7.8; 95% Cl, 2.0-32.7), and wheeze (OR=3.5; 95% CI, 1.04-13.6). SCI level, percentage of predicted forced vital capacity and forced expiratory volume in I second, and maximal inspiratory pressures were not related to breathlessness. Conclusions: Breathlessness during selected daily activities (most commonly talking) was greatest in SCI participants who were most impaired with regard to mobility and was associated with reports of coughing, wheezing, and cigarette smoking. (c) 2005 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. Phys Med & Rehabil Serv, W Roxbury, MA 02132 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Med Res Serv, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM eric.garshick@med.va.gov FU NCI NIH HHS [R33 CA094304]; NICHD NIH HHS [R01 HD042141, R01 HD42141] NR 30 TC 21 Z9 21 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2005 VL 86 IS 8 BP 1631 EP 1635 DI 10.1016/j.apmr.2005.02.006 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 953LN UT WOS:000231077900019 PM 16084818 ER PT J AU Brown, CVR Velmahos, GC Neville, AL Rhee, P Salim, A Sangthong, B Demetriades, D AF Brown, CVR Velmahos, GC Neville, AL Rhee, P Salim, A Sangthong, B Demetriades, D TI Hemodynamically "Stable" patients with peritonitis after penetrating abdominal trauma - Identifying those who are bleeding SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 76th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 19, 2005 CL Dana Point, CA SP Pacific Coast Surg Assoc ID SELECTIVE NONOPERATIVE MANAGEMENT; GUNSHOT WOUNDS; RELATIVE BRADYCARDIA; HYPOTENSION; HEMATOCRIT; INJURY AB Hypothesis: Despite initial presentation, hemodynamically stable patients with penetrating abdominal trauma may have significant ongoing hemorrhage and major intra-abdominal injuries requiring emergent surgical intervention. Design: Cohort analytic study. Setting: Academic, level 1 trauma center. Patients: One hundred thirty-nine consecutive hemodynamically stable patients with penetrating abdominal trauma in whom peritonitis was the sole indication for laparotomy. Main Outome Measures: The primary outcome was the amount of blood initially found at laparotomy. Secondary outcomes included additional intraoperative blood loss, intraoperative hypotension, transfusion, fluid, and vasopressor requirement; need for admission to the intensive care unit and mechanical ventilation; complications; survivor length of stay in the hospital and intensive care unit; and mortality. Results: The admission systolic blood pressure (mean +/- SD, 131 +/- 22 mm Hg) and heart rate (mean +/- SD, 91 +/- 22 beats/min) were normal. Median time from peritonitis to incision was 40 minutes. Ninety-seven percent of patients had intra-abdominal injury, including 81%, hollow visceral; 36%, solid organ; and 11%, vascular injury. Though most patients had less than 750 mL(3) of blood found initially at laparotomy, there were 11% with 750 to 1500 mL(3) and 7% with 1500 mL(3) or more. Intraoperative hypotension (25%) and blood transfusion (39%) were common. Postoperatively, 40% of patients required intensive care (78% of them requiring mechanical ventilation) and 19% required additional transfusion within 24 hours. Complications occurred in 25% of patients, with intra-abdominal abscess (12%) and wound infection (7%) being the most common. Three patients died, 2 of exsanguination and 1 of multisystem organ failure. Conclusions: Following penetrating abdominal trauma, peritonitis should be a trigger for emergent operation regardless of vital signs, because hemodynamic "stability" does not reliably exclude significant hemorrhage. Vascular injury, subsequent hypotension, blood transfusion, and complicated postoperative course are common in this population. C1 Univ So Calif, Keck Sch Med, Div Trauma & Crit Care, Dept Surg, Los Angeles, CA 90033 USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Crit Care, Boston, MA 02115 USA. RP Brown, CVR (reprint author), Univ So Calif, Keck Sch Med, Div Trauma & Crit Care, Dept Surg, 1200 N State St,6341, Los Angeles, CA 90033 USA. EM carlosbr@usc.edu NR 15 TC 20 Z9 20 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2005 VL 140 IS 8 BP 767 EP 771 DI 10.1001/archsurg.140.8.767 PG 5 WC Surgery SC Surgery GA 951RM UT WOS:000230948300015 PM 16103287 ER PT J AU Khanna, D Ranganath, VK FitzGerald, J Park, GS Altman, RD Elashoff, D Gold, RH Sharp, JT Furst, DE Paulus, HE AF Khanna, D Ranganath, VK FitzGerald, J Park, GS Altman, RD Elashoff, D Gold, RH Sharp, JT Furst, DE Paulus, HE CA Western Consortium Practicing Rheu TI Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLEGE-OF-RHEUMATOLOGY; DISEASE-ACTIVITY; UNITED-STATES; AGE; PREVALENCE; YOUNGER; ABNORMALITIES; DEFINITION; VALIDITY; SEX AB Objective. To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA). Methods. We studied 186 patients with RA of < 15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (> 55 years) and younger patients (<= 55 years) were compared by t-test, Mann-Whitney U test, chi-square, or Fisher's exact test. Multiple linear regression models were also constructed. Results. The older group (n = 74) had a higher baseline total Sharp score (median 6.21) compared with the younger group (n = 112) (median 2.33) (P = 0.0002). This was mainly due to a higher baseline JSN score in the older group (median 3.96 versus 1.08) and not to differences in erosion score (median 0.91 versus 0.70). Disease activity and duration of RA symptoms were similar in the 2 groups, as were progression rates of the TSS, JSN score, and erosion score. At baseline, 26% of patients had osteophytes, with a prevalence of 13% in the younger age group and 50% in the older group. The presence of OA-JSN was highly correlated with the presence of osteophytes (r = 0.72). Also, increased age and RA-JSN were associated with increased severity of osteophytes and OA-JSN at baseline. Multiple linear regression analysis showed that both age and hand osteophytes contributed to the increase in baseline RA-JSN score and TSS, but not to erosion score. Conclusion. In a cohort of patients with early RA, an increase in the baseline RA-JSN score and TSS can be accounted for in part by the presence of hand OA. C1 Univ Cincinnati, Dept Med, Div Immunol, Cincinnati, OH 45267 USA. VAMC, Cincinnati, OH 45267 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Washington, Seattle, WA 98195 USA. RP Khanna, D (reprint author), Univ Cincinnati, Dept Med, Div Immunol, 231 Albert Sabin Way,ML0563,POB 670563, Cincinnati, OH 45267 USA. EM dinesh.khanna@uc.edu NR 34 TC 18 Z9 18 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 AUG PY 2005 VL 52 IS 8 BP 2284 EP 2292 DI 10.1002/art.21221 PG 9 WC Rheumatology SC Rheumatology GA 953LW UT WOS:000231078800010 PM 16052588 ER PT J AU Vickers, K McNally, RJ AF Vickers, K McNally, RJ TI Respiratory symptoms and panic in the National Comorbidity Survey: a test of Klein's suffocation false alarm theory SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE panic; respiration ID DISORDER; ATTACKS; PREVALENCE AB According to suffocation false alarm theory (Arch. Gen. Psychiatry 50 (1993) 31), respiratory symptoms are the symptoms that best distinguish the panic attacks of individuals with panic disorder (PD) from those of individuals without PD. Using National Comorbidity Survey data from those 609 respondents who had lifetime histories of panic attacks or PD, we tested this prediction. Neither respiratory symptom (smothering; dyspnea) strongly differentiated between respondents with PD and those with only panic attacks. Respiratory symptom endorsement was unrelated to PD when the number of other symptoms endorsed was controlled; furthermore, respiratory symptoms had slight effect sizes and were not included in a multivariate context. In contrast, fear of dying had the largest effect size, an association with PD that persisted after control for other symptom endorsement, and a continuing importance in multivariate analyses. Strikingly, panic attack respondents who reported having had only one panic attack were as likely as PD respondents to report respiratory symptoms during panic. These findings, although based on retrospective self-report and thus subject to recall bias, are inconsistent with the hypothesis that respiratory symptoms during panic have diagnostic significance. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Vickers, K (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorders, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM kristin@wjh.harvard.edu FU NIMH NIH HHS [R01 MH49098, R01 MH/DA 46376, R01 MH/DA46376] NR 18 TC 21 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 2005 VL 43 IS 8 BP 1011 EP 1018 DI 10.1016/j.brat.2004.06.019 PG 8 WC Psychology, Clinical SC Psychology GA 954DI UT WOS:000231133900004 PM 15967172 ER PT J AU Djebbari, A Karamycheva, S Howe, E Quackenbush, J AF Djebbari, A Karamycheva, S Howe, E Quackenbush, J TI MeSHer: Identifying biological concepts in microarray assays based on PubMed references and MeSH terms SO BIOINFORMATICS LA English DT Article ID TIGR GENE INDEXES; ALZHEIMERS-DISEASE; CHOLESTEROL; INFORMATION; SEQUENCES; RESOURCE; LINK; TOOL AB MeSHer uses a simple statistical approach to identify biological concepts in the form of Medical Subject Headings (MeSH terms) obtained from the PubMed database that are significantly overrepresented within the identified gene set relative to those associated with the overall collection of genes on the underlying DNA microarray platform. As a demonstration, we apply this approach to gene lists acquired from a published study of the effects of angiotensin II (Ang II) treatment on cardiac gene expression and demonstrate that this approach can aid in the interpretation of the resulting 'significant' gene set. Availability: The software is available at http://www.tm4.org Contact: johnq@jimmy.harvard.edu Supplementary information: Results from the analysis of significant genes from the published Ang II study. C1 Inst Genom Res, Rockville, MD 20850 USA. George Washington Univ, Dept Comp Sci, Washington, DC USA. George Washington Univ, Dept Biochem, Washington, DC USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Stat, Baltimore, MD USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. EM johnq@jimmy.harvard.edu NR 18 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2005 VL 21 IS 15 BP 3324 EP 3326 DI 10.1093/bioinformatics/bti503 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 945OY UT WOS:000230513200022 PM 15919728 ER PT J AU Ho, VT Cutler, C Carter, S Martin, P Adams, R Horowitz, M Ferrara, J Soiffer, R Giralt, S AF Ho, VT Cutler, C Carter, S Martin, P Adams, R Horowitz, M Ferrara, J Soiffer, R Giralt, S TI Blood and marrow transplant clinical trials network toxicity committee consensus summary: Thrombotic microangiopathy after hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE hemolytic uremic syndrome; thrombotic thrombocytopenic purpura; microangiopathy anemia; thrombocytopenia; stem cell transport ID THROMBOCYTOPENIC PURPURA; PLASMA-EXCHANGE; CASE SERIES; INFECTION; MANAGEMENT; CHILDREN; ANEMIA AB The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Boston, MA 02114 USA. Blood & Marrow Transplant Clin Trials Network Tox, Boston, MA USA. EMMES Corp, Rockville, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mayo Clin, Minneapolis, MN USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. MD Anderson Canc Ctr, Houston, TX USA. RP Ho, VT (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02114 USA. EM vincent_ho@dfci.harvard.edu FU NCI NIH HHS [U24 CA076518]; NHLBI NIH HHS [U10 HL069249, U10 HL069254, U10 HL069294, U10 HL069330] NR 23 TC 143 Z9 153 U1 0 U2 5 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2005 VL 11 IS 8 BP 571 EP 575 DI 10.1016/j.bbmt.2005.06.001 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 954ZE UT WOS:000231193400001 PM 16041306 ER PT J AU Narmoneva, DA Oni, O Sieminski, AL Zhang, SG Gertler, JP Kamm, RD Lee, RT AF Narmoneva, DA Oni, O Sieminski, AL Zhang, SG Gertler, JP Kamm, RD Lee, RT TI Self-assembling short oligopeptides and the promotion of angiogenesis SO BIOMATERIALS LA English DT Article DE angiogenesis; endothelial cell; peptide; scaffold ID 3-DIMENSIONAL COLLAGEN LATTICE; ENDOTHELIAL-CELL MORPHOGENESIS; IN-VITRO MODEL; MECHANICAL-PROPERTIES; LUMEN FORMATION; TUBE FORMATION; FIBRIN MATRIX; GROWTH-FACTOR; VASCULOGENESIS; INTEGRINS AB Because an adequate blood supply to and within tissues is an essential factor for successful tissue regeneration, promoting a functional microvasculature is a crucial factor for biomaterials. In this study, we demonstrate that short self-assembling peptides form scaffolds that provide an angiogenic environment promoting long-term cell survival and capillary-like network formation in three-dimensional cultures of human microvascular endothelial cells. Our data show that, in contrast to collagen type I, the peptide scaffold inhibits endothelial cell apoptosis in the absence of added angiogenic factors, accompanied by enhanced gene expression of the angiogenic factor VEGF. In addition, our results suggest that the process of capillary-like network formation and the size and spatial organization of cell networks may be controlled through manipulation of the scaffold properties, with a more rigid scaffold promoting extended structures with a larger inter-structure distance, as compared with more dense structures of smaller size observed in a more compliant scaffold. These findings indicate that self-assembling peptide scaffolds have potential for engineering vascularized tissues with control over angiogenic processes. Since these peptides can be modified in many ways, they may be uniquely valuable in regeneration of vascularized tissues. (C) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02139 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02139 USA. MIT, Div Biol Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Vasc Surg, Vasc Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, RT (reprint author), Brigham & Womens Hosp, Room 279,65 Landsdowne St, Cambridge, MA 02139 USA. EM rlee@rics.bwh.harvard.edu OI /0000-0002-7232-304X NR 44 TC 122 Z9 126 U1 4 U2 30 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 AUG PY 2005 VL 26 IS 23 BP 4837 EP 4846 DI 10.1016/j.biomaterials.2005.01.005 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 915PI UT WOS:000228315900015 PM 15763263 ER PT J AU Berghmans, S Jette, C Langenau, D Hsu, K Stewart, R Look, T Kanki, JP AF Berghmans, S Jette, C Langenau, D Hsu, K Stewart, R Look, T Kanki, JP TI Making waves in cancer research: new models in the zebrafish SO BIOTECHNIQUES LA English DT Review ID DIFFERENT DEVELOPMENTAL-STAGES; TRANSGENIC MICE; DANIO-RERIO; INSERTIONAL MUTAGENESIS; CAENORHABDITIS-ELEGANS; TYROSINE KINASE; EXPOSURE ROUTES; GENE-EXPRESSION; C-MYC; VERTEBRATE AB The zebrafish (Danio rerio) has proven to be a powerful vertebrate model system. for the genetic analysis of developrnental pathways and is only beginning to be exploited as a model for human disease and clinical research. The attributes that have led to the emergence of the zebrafish as a preeminent embryological model, including its capacity for forward and reverse genetic analyses, provides a unique opportunity to uncover novel insights into the molecular genetics of cancer. Some of the advantages of the zebrafish animal model system include fecundity, with each female capable of laying 200-300 eggs per week, external fertilization that permits manipulation of embryos ex utero, and rapid development of optically clear embryos, which allows the direct observation of developing internal organs and tissues in vivo. The zebrafish is amenable to transgenic and both forward and reverse genetic strategies that can be used to identify or generate zebrafish models of different types of cancer and may also present significant advantages for the discovery of termor suppressor genes that promote tumorigenesis when mutationally inactivated. Importantly, the transparency and accessibility of the zebrafish embryo allows the unprecedented direct analysis of pathologic processes in vivo, including neoplastic cell transformation and tumorigenic progression. Ultimately, high-throughput modifier screens based on zebrafish cancer models can lead to the identification of chemicals or genes involved in the suppression or prevention of the malignant phenotype. The identification of small molecules or gene products through such screens will serve as ideal entry points for novel drug development for the treatment of cancer. This review focuses on the current technology that takes advantage of the zebrafish model system to further our understanding of the genetic basis of cancer and its treatment. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kanki, JP (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM john_kanki@dfci.harvard.edu OI Berghmans, Stephane/0000-0001-5414-8674; Stewart, Rodney/0000-0003-1220-1830 NR 88 TC 88 Z9 93 U1 2 U2 30 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 2005 VL 39 IS 2 BP 227 EP 237 DI 10.2144/05392RV02 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 954AR UT WOS:000231127000013 PM 16116796 ER PT J AU Munshi, NC AF Munshi, NC TI Determining the undetermined SO BLOOD LA English DT Editorial Material ID MONOCLONAL GAMMOPATHY; MYELOMA AB Although a limited proportion of patients with monoclonal gammopathy of undetermined significance (MGUS) progress to multiple myeloma and related disorders, inability to distinguish those who progress has required life-long follow-up of all patients. In this issue of Blood, Rajkumar and colleagues have determined that a subgroup of patients with MGUS (non-immunoglobulin G [IgG] isotype, abnormal serum free light chain [FLC] ratio, and serum M protein level less than 15 g/L) have a 58% chance of progression, while patients without these features have only a 5% chance of progression at 20 years. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2005 VL 106 IS 3 BP 767 EP 768 DI 10.1182/blood-2005-05-2001 PG 2 WC Hematology SC Hematology GA 951RT UT WOS:000230949100003 ER PT J AU Lee, SK Dykxhoorn, DM Kumar, P Ranjbar, S Song, E Maliszewski, LE Francois-Bongarcon, V Goldfeld, A Swamy, NM Lieberman, J Shankar, P AF Lee, SK Dykxhoorn, DM Kumar, P Ranjbar, S Song, E Maliszewski, LE Francois-Bongarcon, V Goldfeld, A Swamy, NM Lieberman, J Shankar, P TI Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV SO BLOOD LA English DT Article ID SMALL INTERFERING RNA; VIRUS TYPE-1 REPLICATION; PRIMARY MACROPHAGES; ENZYME COMPLEX; INHIBITION; INFECTION; SIRNAS; SUPPRESSION; EXPRESSION; DISEASE AB Viral heterogeneity is a major hurdle for potential therapeutic use of RNA interference (RNA!) against HIV-1. To determine the extent of RNAi tolerance to mutations, we tested 3 viral target sites with differing propensity for mutations: a highly variable rev sequence, a gag sequence conserved only among clade B isolates, and a vif sequence highly conserved across clades. Lentiviral expression of all 3 shRNAs inhibited replication of the homologous HIVIIIB strain. However, they differed in their ability to protect primary CD4 T cells against multiple isolates within and across HIV clades. The least conserved rev sequence inhibited only 2 of 5 clade B isolates. The gag sequence (conserved within clade B) protected 5 of 5 clade B isolates but not other clade viruses with 2 or 3 mutations in the central region. In contrast, the vif sequence, which was conserved across clades except for single mutations at positions 14 and 17, inhibited viruses from 5 different clades. Moreover, siRNAs with introduced mutations at sites of gag sequence polymorphisms showed reduced antiviral activity, whereas mutations in vif siRNA only modestly decreased silencing. Thus, although 1 or 2 mutations at peripheral sites are tolerated, mutations in the central target cleavage region abolish RNAi activity. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Shankar, P (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM shankar@cbr.med.harvard.edu RI Kumar, Priti/C-5699-2009; Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015; Francois, Bruno/O-8404-2016 OI Francois, Bruno/0000-0002-2531-1652 FU NIAID NIH HHS [AI49792] NR 50 TC 71 Z9 85 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2005 VL 106 IS 3 BP 818 EP 826 DI 10.1182/blood-2004-10-3959 PG 9 WC Hematology SC Hematology GA 951RT UT WOS:000230949100019 PM 15831707 ER PT J AU Boggon, TJ Li, YQ Manley, PW Eck, MJ AF Boggon, TJ Li, YQ Manley, PW Eck, MJ TI Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; RECEPTOR TYROSINE KINASE; CONSTITUTIVE ACTIVATION; MOLECULAR-CLONING; ABL ONCOGENE; PROTEIN; FAMILY; CRYSTALLOGRAPHY; PHOSPHORYLATION; INHIBITORS AB Jak (Janus kinase) family nonreceptor tyrosine kinases are central mediators of cytokine signaling. The Jak kinases exhibit distinct cytokine receptor association profiles and so transduce different signals. Jak3 expression is limited to the immune system, where it plays a key role in signal transduction from cytolkine receptors containing the common gammachain, gamma c. Patients unable to signal via gamma c present with severe combined immunodeficiency (SCID). The finding that Jak3 mutations result in SCID has made it a target for development of lymphocytespecific immunosuppressants. Here, we present the crystal structure of the Jak3 kinase domain in complex with staurosporine analog AFN941. The kinase domain is in the active conformation, with both activation loop tyrosine residues phosphorylated. The phosphate group on pTyr981 in the activation loop is in part coordinated by an arginine residue in the regulatory C-helix, suggesting a direct mechanism by which the active position of the C-helix is induced by phosphorylation of the activation loop. Such a direct coupling has not been previously observed in tyrosine kinases and may be unique to Jak kinases. The crystal structure provides a detailed view of the Jak3 active site and will facilitate computational and structure-directed approaches to development of Jak3-specific inhibitors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Rm SM 10-36,44 Binney St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NCI NIH HHS [CA080942] NR 39 TC 112 Z9 118 U1 4 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2005 VL 106 IS 3 BP 996 EP 1002 DI 10.1182/blood-2005-02-0707 PG 7 WC Hematology SC Hematology GA 951RT UT WOS:000230949100044 PM 15831699 ER PT J AU Raje, N Kumar, S Hideshima, T Roccaro, A Ishitsuka, K Yasui, H Shiraishi, N Chauhan, D Munshi, NC Green, SR Anderson, KC AF Raje, N Kumar, S Hideshima, T Roccaro, A Ishitsuka, K Yasui, H Shiraishi, N Chauhan, D Munshi, NC Green, SR Anderson, KC TI Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma SO BLOOD LA English DT Article ID NF-KAPPA-B; OVERCOMES DRUG-RESISTANCE; CELL-ADHESION; UP-REGULATION; APOPTOSIS; ACTIVATION; SURVIVAL; PROTEIN; FLAVOPIRIDOL; THALIDOMIDE AB Cyclin-dependent kinase (CDK) inhibitors have the potential to induce cell-cycle arrest and apoptosis in cancer cells. Seliciclib (CYC202 or R-roscovitine) is a potent CDK inhibitor currently undergoing phase-2 clinical testing in lung and B-cell malignancies. Here we studied the in vitro cytotoxic activity of seliciclib against multiple myeloma (MM) cells. Our data demonstrate that seliciclib has potent cytotoxicity against MM cells that are both sensitive and resistant to conventional therapy as well as primary MM cells from patients. Cell-cycle and Western blot analysis confirmed apoptosis. Importantly, seliciclib triggered a rapid down-regulation of Mcl-1 transcription and protein expression independent of caspase cleavage. Adherence of MM cells to bone marrow stromal cells (BMSCs) induced increased Mcl-1 expression associated with signal transducer and activator of transcription 3 (STAT3) phosphorylation, which was inhibited in a time- and dose-dependent manner by seliciclib. Furthermore, seliciclib inhibited interleukin 6 (IL-6) transcription and secretion triggered by tumor cell binding to BMSCs. Up-regulation of Mcl-1 expression in cocultures; was only partially blocked by neutralizing antibody to IL-6, suggesting alternative mechanisms of Mcl-1 modulation by seliciclib. Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM. C1 VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Cyclacel Ltd, Dundee, Scotland. RP Anderson, KC (reprint author), VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947]; PHS HHS [P0-1 78378] NR 40 TC 125 Z9 127 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2005 VL 106 IS 3 BP 1042 EP 1047 DI 10.1182/blood-2005-01-0320 PG 6 WC Hematology SC Hematology GA 951RT UT WOS:000230949100051 PM 15827128 ER PT J AU Sun, L Jin, Z Zang, YF Zeng, YW Liu, G Li, Y Seidman, LJ Faraone, SV Wang, YF AF Sun, L Jin, Z Zang, YF Zeng, YW Liu, G Li, Y Seidman, LJ Faraone, SV Wang, YF TI Differences between attention-deficit disorder with and without hyperactivity: a H-1-magnetic resonance spectroscopy study SO BRAIN & DEVELOPMENT LA English DT Article DE attention deficit hyperactivity disorder; subtype; H-1-magnetic resonance spectroscopy; lenticular nucleus; N-aceytylaspartate ID DEFICIT/HYPERACTIVITY DISORDER; BASAL GANGLIA; H-1 MRS; CHILDREN; BRAIN; SCHIZOPHRENIA; MEDICATION; METABOLISM; THALAMUS; SUBTYPE AB Using proton magnetic resonance spectroscopy (H-1-MRS) to investigate possible neurometabolic differences between the predominantly inattentive subtype (ADHD-1), the combined subtype (ADHD-C) and normal controls. Proton spectra were acquired bilaterally on the lenticular nucleus in 20 schoolboys having ADHD and 10 matched controls. The boys with ADHD were divided into ADHD-C subtype (n = 10) and ADHD-1 subtype (n = 10) according to DSM-IV criteria. The peaks of N-acetylaspartate (NAA), Choline moieties (Cho), myoinositol (mI), creatine (Cr) and alpha-Glx were measured and their ratios to Cr were calculated. One-way ANOVA and post-hoc Bonferroni tests were used to detect the difference of the peak-area ratios of NAA, Cho, ml, and a-Glx to Cr among the three groups. There was a significant overall group difference in the NAA/Cr ratio both in the right and left lenticular nucleus (right: P = 0.002; left: P = 0.003). Only the ADHD-C subtype group showed a significant difference with controls (right: P = 0.001; left: P = 0.003) the right lenticular nucleus, the NAA/Cr ratio in the ADHD-C group was significantly lower than that in the ADHD-1 group (P = 0.012). In the left lenticular nucleus, the NAA/Cr ratio in the ADHD-C group showed a significant trend compared to the ADHD-1 group (P = 0.06). This study demonstrated the existence of measurable difference between children with ADHD-C and ADHD-1 using H-1-MRS. (c) 2004 Elsevier B.V. All rights reserved. C1 Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. Hosp 306, Ctr fMRI, Beijing 100101, Peoples R China. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Wang, YF (reprint author), Peking Univ, Inst Mental Hlth, Huayuanbeilu 51, Beijing 100083, Peoples R China. EM wangyf@bjmu.edu.cn RI ZANG, Yu-Feng/J-1558-2012; OI ZANG, Yu-Feng/0000-0003-1833-8010; Faraone, Stephen/0000-0002-9217-3982 NR 36 TC 26 Z9 28 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD AUG PY 2005 VL 27 IS 5 BP 340 EP 344 DI 10.1016/j.braindev.2004.09.004 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 952JU UT WOS:000231000600004 PM 16023548 ER PT J AU Castellon, SA Silverman, DHS Ganz, PA AF Castellon, SA Silverman, DHS Ganz, PA TI Breast cancer treatment and cognitive functioning: current status and future challenges in assessment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material DE adjuvant therapy; breast cancer; chemotherapy; cognitive functioning; late effects; neuroimaging; neuropsychological ID QUALITY-OF-LIFE; RECEIVING ADJUVANT CHEMOTHERAPY; POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL VOLUME; ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; HORMONE-THERAPY; LONG-TERM; WOMEN; TAMOXIFEN C1 Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Castellon, SA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst & Hosp, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. EM scastell@ucla.edu NR 47 TC 24 Z9 24 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 AUG PY 2005 VL 92 IS 3 BP 199 EP 206 DI 10.1007/s10549-005-5342-0 PG 8 WC Oncology SC Oncology GA 963LQ UT WOS:000231806200001 PM 16155790 ER PT J AU Balmana, J Diez, O Campos, B Majewski, M Sanz, J Alonso, C Baiget, M Garber, JE AF Balmana, J Diez, O Campos, B Majewski, M Sanz, J Alonso, C Baiget, M Garber, JE TI Sex ratio distortion in offspring of families with BRCA1 or BRCA2 mutant alleles: an ascertainment bias phenomenon? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; hereditary breast and ovarian cancer syndrome; sex ratio ID CANCER; STATEMENT; CARRIERS AB Background. There has been controversy regarding whether BRCA1 germline mutations favor female births or whether the sex imbalances observed are attributable to ascertainment bias. Our aims were to compare the sex ratios among offspring of BRCA1-positive, BRCA2-positive, and BRCA-negative families undergoing genetic testing in clinical programs, and to determine whether ascertainment bias is responsible for the observed preponderance of female offspring. Patients and methods. A total of 145 breast and/or ovarian cancer families with mutations in BRCA1 (n = 83) or BRCA2 (n = 62), and 90 families without identifiable mutation were collected for the study from familial cancer clinics in Barcelona, Spain, and Boston, US. Sex ratio was analyzed among all births in the families and offspring of all (tested and obligate) carriers. In order to minimize the effect of family history of cancer, the analysis was also performed among offspring of the most recent generation of mutation-positive carriers who did not have affected children and compared with a control group comprised of the offspring of the most recent adult generation of non-carriers from families with a known mutation. Results. There was a statistically higher proportion of female births in all groups (BRCA1 59% (95% CI = 57-61%), BRCA2 58% (56-61%), and BRCA-negative 59% (56-61%), respectively). The female preponderance persisted in analyses limited to offspring of BRCA1 and BRCA2 carriers (61% (57-65%), and 62% (58-66%), respectively), with no differences between the two mutation groups. In contrast, the excess of female offspring disappeared when ascertainment or recall biases were minimized, 44% (37-52%), and 39% (26-53%) for BRCA1; 51% (44-58%), and 46% (33-60%) for BRCA2. Conclusions. Our findings suggest that there is no asymmetry in birth outcomes among BRCA1 or BRCA2 mutations carriers. Rather ascertainment bias in families participating in genetic testing, or in the family history information they provide is likely to account for excess of female offspring previously reported. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Dept Med Oncol, E-08193 Barcelona, Spain. Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Dept Genet, E-08193 Barcelona, Spain. RP Garber, JE (reprint author), Dana Farber Canc Inst, Div Populat Sci, Smith 209,44 Binney St, Boston, MA 02115 USA. EM judyegarber@partners.org NR 10 TC 4 Z9 4 U1 0 U2 1 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 AUG PY 2005 VL 92 IS 3 BP 273 EP 277 DI 10.1007/s10549-005-3377-x PG 5 WC Oncology SC Oncology GA 963LQ UT WOS:000231806200009 PM 16155798 ER PT J AU Baehring, JM Androudi, S Longtine, JJ Betensky, RA Sklar, J Foster, CS Hochberg, FH AF Baehring, JM Androudi, S Longtine, JJ Betensky, RA Sklar, J Foster, CS Hochberg, FH TI Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma SO CANCER LA English DT Article DE intraocular lymphoma; primary central nervous system lymphoma; immunoglobulin G heavy chain gene rearrangement; chronic vitritis ID PRIMARY INTRAOCULAR LYMPHOMA; NERVOUS-SYSTEM LYMPHOMAS; RECEPTOR GENE REARRANGEMENTS; CENTER B-CELLS; CLINICAL-FEATURES; PCR ANALYSIS; DIAGNOSIS; MICRODISSECTION; NEOPLASMS; UVEITIS AB BACKGROUND. The morphologic diagnosis of primary and metastatic intraocular lymphoma (IOL) was made difficult by the paucicellular specimens with fragile populations of lymphocytes retrieved through pars plana vitrectomy (PPV). The analysis of immunoglobulin heavy chain (IgH) gene rearrangements (AIGHR) was used as an adjunct to cytopathology and flow cytometry in systemic lymphoma. In 10L, the sensitivity and specificity of AIGHR are unknown. METHODS. The authors reviewed the clinical records of patients who underwent PPV for suspicion of IOL at the Immunology and Uveitis Service of the Massachusetts Eye and Ear infirmary (Boston, MA) between 2000 and 2002. AIGHR was performed as a routine diagnostic test on cell lysates isolated from < 0.5 mL of vitreous fluid. The authors used seminested polymerase chain reaction (PCR) with consensus primers for the VDJ-region of the IgH gene. PCR products were analyzed by polyacrylamide gel electrophoresis. RESULTS. Thirty patients (37 specimens) with chronic vitritis and 17 patients (23 specimens) with IOL were included. The specificity of vitreous fluid cytopathology, flow cytometry, and AIGHR was 1.0, and the sensitivity values were 0.24, 0.36, and respectively. AIGHR was negative in two patients for whom cytopathology or 0.64, flow cytometry revealed the diagnosis of lymphoma. Clonal IGHR was found in four specimens classified as negative for lymphoma based on cytopathology and flow cytometry. CONCLUSIONS. AIGHR supplemented cytopathology and flow cytometry to increase the diagnostic yield in IOL. Cancer 2005;104:591-7. (c) 2005 American Cancer Society. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. EM fhochberg@partners.org NR 28 TC 22 Z9 25 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 AUG 1 PY 2005 VL 104 IS 3 BP 591 EP 597 DI 10.1002/cncr.21191 PG 7 WC Oncology SC Oncology GA 947GP UT WOS:000230631700018 PM 15973665 ER PT J AU Hussein, MR Ahmed, RA AF Hussein, MR Ahmed, RA TI Analysis of the mononuclear inflammatory cell infiltrate in the non-tumorigenic, pre-tumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin SO CANCER BIOLOGY & THERAPY LA English DT Article DE inflammatory cells; actinic keratosis; squamous cell carcinoma ID PSORIASIS; EXPRESSION; ANTIGENS AB Background: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions. Methods: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1). Results: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase(p = < 0.05) in: (1) CD20(+) B lymphocytes (0.0 +/- 0.0 vs. 3.1 +/- 0.5 vs. 7.5 +/- 0.3 vs. 14.5 +/- 5.5); (2) CD68 histiocytes (4.0 +/- 1.0 vs. 26.5 +/- 3.9 vs. 23 +/- 1.9 vs. 41.3 +/- 6.8); (3) CD3(+) T lymphocytes (3.0 +/- 1.1 vs. 58.3 +/- 10.3 vs. 54.5 +/- 0.2 vs. 41.0 +/- 16.0); and (4) TIA-1(+) cytotoxic T cells (1.8 +/- 0.4 vs. 2.9 +/- 0.7 vs. 9.6 +/- 1.1 vs. 13.7 +/- 5.2). Conclusions: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions. C1 Assiut Univ, Assiut Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt. Univ Wisconsin, Sch Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ, Assiut Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt. EM mrh17@swissinfo.org NR 15 TC 26 Z9 26 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD AUG PY 2005 VL 4 IS 8 BP 819 EP 821 PG 3 WC Oncology SC Oncology GA 022GK UT WOS:000236043200012 PM 16210913 ER PT J AU Kirley, SD D'Apuzzo, M Lauwers, GY Graeme-Cook, F Chung, DC Zukerberg, LR AF Kirley, SD D'Apuzzo, M Lauwers, GY Graeme-Cook, F Chung, DC Zukerberg, LR TI The cables gene on chromosome 18Q regulates colon cancer progression in vivo SO CANCER BIOLOGY & THERAPY LA English DT Article DE Cables1; colorectal cancer; chromosome 18q; candidate tumor suppressor gene ID HUMAN COLORECTAL CANCERS; DCC GENE; SOMATIC ALTERATIONS; MICE; PROTEIN; 1,2-DIMETHYLHYDRAZINE; PHOSPHORYLATION; INDUCTION; ENCODES; DPC4 AB Early events involved in the pathogenesis of colorectal cancer include mutations in the Adenomatous Polyposis Coli tumor-suppressor gene and oncogenic KRAS mutations. Later events include deletions on chromosome 18q, which are observed in a high proportion of colorectal cancers. However, the important tumor suppressor genes targeted by these deletions have not been fully defined. A previous study found Cables is located on human chromosome 18q11-12. Loss of Cables expression as determined by immunohistochemical staining (IHC) occurred in 60-70% of sporadic colorectal cancers that were usually correlated to loss of heterozygosity at 18q. To determine if Cables is an important target for the chromosome 18q deletions, the susceptibility of Cables(-/-) mice to develop colon tumors was studied. A well characterized colonic carcinogen, 1,2-dimethylhydrazine (DMH) was used as a tumor initiator. Cables(-/-) mice (n = 25) and the Cables(+/+) littermates (n = 25) were treated with subcutaneous DMH injections over 20 weeks to initiate tumorigenesis. The median survival after DMH injections was significantly shorter for the Cables(-/-) mice compared to Cables(+/+) littermates. The total number of colorectal tumors that developed in the Cables(-/-) mice was 46 tumors versus 21 tumors. The increased numbers of colorectal tumors, as well as shorter survival of the Cables(-/-) mice provides compelling evidence that Cables could play an important role in the pathogenesis and progression of colon cancer in mice. These data coupled with previous observations support the hypothesis that Cables is a relevant target of the chromosome 18q deletions frequently seen in human colorectal cancer. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP Kirley, SD (reprint author), Massachusetts Gen Hosp, Dept Urol Pathol, Bigelow 11, Boston, MA 02114 USA. EM skirley@partners.org NR 21 TC 13 Z9 13 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD AUG PY 2005 VL 4 IS 8 BP 861 EP 863 PG 3 WC Oncology SC Oncology GA 022GK UT WOS:000236043200020 PM 16210915 ER PT J AU Kotsopoulos, J Lubinski, J Lynch, HT Neuhausen, SL Ghadirian, P Isaacs, C Weber, B Kim-Sing, C Foulkes, WD Gershoni-Baruch, R Ainsworth, P Friedman, E Daly, M Garber, JE Karlan, B Olopade, OI Tung, N Saal, HM Eisen, A Osborne, M Olsson, H Gilchrist, D Sun, P Narod, SA AF Kotsopoulos, J Lubinski, J Lynch, HT Neuhausen, SL Ghadirian, P Isaacs, C Weber, B Kim-Sing, C Foulkes, WD Gershoni-Baruch, R Ainsworth, P Friedman, E Daly, M Garber, JE Karlan, B Olopade, OI Tung, N Saal, HM Eisen, A Osborne, M Olsson, H Gilchrist, D Sun, P Narod, SA TI Age at menarche and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers SO CANCER CAUSES & CONTROL LA English DT Article DE BRCA1; BRCA2; age at menarche; breast cancer; case-control study; reproductive modifiers ID BILATERAL PROPHYLACTIC OOPHORECTOMY; BODY-MASS INDEX; REPRODUCTIVE FACTORS; FAMILY-HISTORY; EARLY-LIFE; EXPRESSION; PREVENTION; CELLS; DIFFERENTIATION; SUSCEPTIBILITY AB Age at menarche is a strong and consistent predictor of breast cancer risk in the general population, but has not been well studied in women with a family history of breast cancer. We conducted this study to examine whether the presence of a deleterious BRCA1 or BRCA2 mutation influences age at menarche and to investigate whether or not there is an association between age at menarche and the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. The presence of a deleterious BRCA1 or BRCA2 mutation did not appear to influence a woman's age at menarche. A matched case-control study was conducted on 1311 pairs of women who have been identified to be carriers of a deleterious mutation in either the BRCA1 (n = 945 pairs) or the BRCA2 gene (n = 366 pairs). Information about age at menarche was derived from a questionnaire routinely administered to carriers of a mutation in either gene. Among women who carried a deleterious BRCA1 mutation, age at menarche was inversely associated with the risk of breast cancer (p trend = 0.0002). This association was not observed among BRCA2 mutation carriers (p trend = 0.49). Compared with BRCA1 carriers whose age at menarche was <= 11 years, women with a menarcheal age between 14 and 15 years old had a 54% reduction in risk (OR = 0.46; 95% CI 0.30-0.69). This study implicates early age at menarche as a determinant of breast cancer among women with a BRCA1 mutation. C1 Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. Pomeranian Med Univ, Hereditary Canc Ctr, Szczecin, Poland. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. CHU Montreal, CHUM Hotel Dieu, Res Ctr, Epidemiol Res Unit,Dept Nutr,Fac Med, Montreal, PQ, Canada. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. Rambam Med Ctr, Inst Genet, Haifa, Israel. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Chaim Sheba Med Ctr, Suzanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA. Beth Israel Med Ctr, Boston, MA USA. Childrens Hosp Med Ctr, Div Human Genet, Hereditary Canc Program, Cincinnati, OH USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Strang Canc Prevent Ctr, New York, NY USA. Univ Lund Hosp, Dept Oncol, Jubileum Inst, S-22185 Lund, Sweden. WCM Univ Alberta, Edmonton, AB, Canada. RP Narod, SA (reprint author), Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, 790 Bay St,Room 750,7th Floor, Toronto, ON M5G 1N8, Canada. EM steven.narod@swchsc.on.ca OI foulkes, william/0000-0001-7427-4651 FU NCI NIH HHS [CA 74415] NR 51 TC 47 Z9 48 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2005 VL 16 IS 6 BP 667 EP 674 DI 10.1007/s10552-005-1724-1 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 950GC UT WOS:000230844600006 PM 16049805 ER PT J AU Acker, T Diez-Juan, A Aragones, J Tjwa, M Brusselmans, K Moons, L Fukumura, D Moreno-Murciano, MP Herbert, JM Burger, A Riedel, J Elverl, G Flamme, I Maxwell, PH Collen, D Dewerchin, M Jain, RK Plate, KH Carmeliet, P AF Acker, T Diez-Juan, A Aragones, J Tjwa, M Brusselmans, K Moons, L Fukumura, D Moreno-Murciano, MP Herbert, JM Burger, A Riedel, J Elverl, G Flamme, I Maxwell, PH Collen, D Dewerchin, M Jain, RK Plate, KH Carmeliet, P TI Genetic evidence for a tumor suppressor role of HIF-2 alpha SO CANCER CELL LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; RESPONSIVE TRANSCRIPTION FACTOR; PAS DOMAIN PROTEIN-1; FACTORS HIF-1-ALPHA; FACTOR 1-ALPHA; FACTOR-2-ALPHA HIF-2-ALPHA; FACTOR (HIF)-1-ALPHA; EMBRYOS LACKING AB The hypoxia-inducible transcription factors HIF-1 alpha and HIF-2 alpha are activated in hypoxic tumor regions. However, their role in tumorigenesis remains controversial, as tumor growth promoter and suppressor activities have been ascribed to HIF-1 alpha, while the role of HIF-2 alpha remains largely unknown. Here, we show that overexpression of HIF-2 alpha in rat glioma tumors enhances angiogenesis but reduces growth of these tumors, in part by increasing tumor cell apoptosis. Moreover, siRNA knockdown of HIF-2 alpha reduced apoptosis in hypoxic human malignant glioblastoma cells. Furthermore, inhibition of HIF by overexpression of a dominant-negative HIF transgene in glioma cells or HIF-2 alpha deficiency in teratomas reduced vascularization but accelerated growth of these tumor types. These findings urge careful consideration of using HIF inhibitors as cancer therapeutic strategies. C1 Univ Frankfurt, Edinger Inst, D-60528 Frankfurt, Germany. Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Sanofi Aventis, Cardiovasc Thrombosis Res Dept, F-31036 Toulouse, France. Tumor Biol Ctr, D-79108 Freiburg, Germany. Ctr Mol Med, D-50931 Cologne, Germany. Univ London Imperial Coll Sci & Technol, Renal Sect, London W12 0NN, England. RP Acker, T (reprint author), Univ Frankfurt, Edinger Inst, D-60528 Frankfurt, Germany. EM till.acker@med.uni-frankfurt.de; peter.carmeliet@med.kuleuven.be RI Maxwell, Patrick/C-5557-2008; Moreno, Paz/K-6870-2012; Diez-Juan, Antonio/H-5464-2015 OI Maxwell, Patrick/0000-0002-0338-2679; Aragones Lopez, Julian/0000-0002-0193-4679; Diez-Juan, Antonio/0000-0002-0166-1869 FU NCI NIH HHS [P01 CA80124] NR 72 TC 121 Z9 126 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2005 VL 8 IS 2 BP 131 EP 141 DI 10.1016/j.ccr.2005.07.003 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 956WG UT WOS:000231330100008 PM 16098466 ER PT J AU Lee, S Nakamura, E Yang, HF Wei, WY Linggi, MS Sajan, MP Farese, RV Freeman, RS Carter, BD Kaelin, WG Schlisio, S AF Lee, S Nakamura, E Yang, HF Wei, WY Linggi, MS Sajan, MP Farese, RV Freeman, RS Carter, BD Kaelin, WG Schlisio, S TI Neuronal apoptosis linked to EgIN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer SO CANCER CELL LA English DT Article ID NERVE GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU PROTEIN; PROGRAMMED CELL-DEATH; SYMPATHETIC NEURONS; C-JUN; KINASE-C; FACTOR EXPRESSION; OXIDATIVE STRESS AB Germline NF1, c-RET, SDH, and VHL mutations cause familial pheochromocytoma. Pheochromocytomas derive from sympathetic neuronal precursor cells. Many of these cells undergo c-Jun-dependent apoptosis during normal development as NGF becomes limiting. NF1 encodes a GAP for the NGF receptor TrkA, and NF1 mutations promote survival after NGF withdrawal. We found that pheochromocytoma-associated c-RET and VHL mutations lead to increased JunB, which blunts neuronal apoptosis after NGF withdrawal. We also found that the prolyl hydroxylase EgIN3 acts downstream of c-Jun and is specifically required among the three EgIN family members for apoptosis in this setting. Moreover, EgIN3 proapoptotic activity requires SDH activity because EgIN3 is feedback inhibited by succinate. These studies suggest that failure of developmental apoptosis plays a role in pheochromocytoma pathogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. James A Haley Vet Hosp, Dept Internal Med, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Tampa, FL 33612 USA. Univ Rochester, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Nashville, TN 37232 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [R01 DK065969]; NINDS NIH HHS [R01 NS034400] NR 78 TC 330 Z9 339 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2005 VL 8 IS 2 BP 155 EP 167 DI 10.1016/j.ccr.2005.06.015 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 956WG UT WOS:000231330100010 PM 16098468 ER PT J AU Bertone-Johnson, ER Chen, WY Holick, MF Hollis, BW Colditz, GA Willett, WC Hankinson, SE AF Bertone-Johnson, ER Chen, WY Holick, MF Hollis, BW Colditz, GA Willett, WC Hankinson, SE TI Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D DEFICIENCY; POSTMENOPAUSAL WOMEN; EXPOSURE; CALCIUM; SUNLIGHT; D-1-ALPHA-HYDROXYLASE; HYPOTHESIS; PREVENTION; FRACTURES; MORTALITY AB Several lines of evidence suggest that vitamin D may reduce incidence of breast cancer, but few epidemiologic studies have addressed the relation of plasma vitamin D metabolites to the risk of this disease. We prospectively examined the relationship between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and risk of breast cancer in a case-control study nested within the Nurses' Health Study cohort. Blood samples were collected from study participants in 1989-1990. Breast cancer cases developing between blood collection and June 1, 1996, were matched to cancer-free controls on the basis of age, menopausal status, and other factors. Stored plasma samples from 701 cases and 724 controls were available for metabolite analysis. Cases had a lower mean 25(OH)D level than controls (P = 0.01), but mean 1,25(OH)(2)D levels were similar (P = 0.49). High levels of both metabolites were associated with a nonsignificant lower risk of breast cancer. Women in the highest quintile of 25(OH)D had a relative risk of 0.73 (95% confidence interval = 0.49-1.07; P-trend = 0.06) compared with those in the lowest quintile. For 1,25(OH)2D, the comparable relative risk was 0.76 (95% confidence interval = 0.52-1.11; P-trend = 0.39). For both metabolites, the association was stronger in women ages 60 years and older, but results were not statistically significant. Our findings suggest that high levels of 25(OH)D, and perhaps 1,25(OH)(2)D, may be modestly associated with reduced risk of breast cancer. C1 Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Bertone-Johnson, ER (reprint author), Univ Massachusetts, Dept Publ Hlth, 715 N Pleasant St, Amherst, MA 01003 USA. EM ebertone@schoolph.umass.edu RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Holick, Michael/0000-0001-6023-9062 FU NCI NIH HHS [CA49449, CA87969] NR 32 TC 221 Z9 226 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2005 VL 14 IS 8 BP 1991 EP 1997 DI 10.1158/1055-9965.EPI-04-0722 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 954ZZ UT WOS:000231195600028 PM 16103450 ER PT J AU Tyminski, E LeRoy, S Terada, K Finkelstein, DM Hyatt, JL Danks, MK Potter, PM Saeki, Y Chiocca, EA AF Tyminski, E LeRoy, S Terada, K Finkelstein, DM Hyatt, JL Danks, MK Potter, PM Saeki, Y Chiocca, EA TI Brain tumor oncolysis with replication-conditional herpes simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and secreted Human intestinal carboxylesterase, in combination with cyclophosphamide and irinotecan SO CANCER RESEARCH LA English DT Article ID RABBIT LIVER CARBOXYLESTERASE; SCHEDULE-DEPENDENT ACTIVITY; THYMIDINE KINASE GENE; MALIGNANT GLIOMA; CPT-11; CELLS; THERAPY; MUTANT; VECTOR; DNA AB The treatment of malignant glioma is currently ineffective. Oncolytic viruses are being explored as a means to selectively lyse tumor cells in the brain. We have engineered a mutant herpes simplex virus type I with deletions in the viral UL39 and gamma(1)34.5 genes and an insertion of the two prodrug activating genes, CYP2BI and secreted human intestinal carboxylesterase. Each of these can convert the inactive prodrugs, cyclophosphamide and irinotecan (CPT-11), into their active metabolites, respectively. This new oncolytic virus (MGH2) displays increased antitumor efficacy against human glioma cells both in vitro and in vivo when combined with cyclophosphamide and CPT-11. Importantly, cyclophosphamide, CPT-11, or the combination of cyclophosphamide and CPT-11 does not significantly affect oncolytic virus replication. Therefore, MGH2 provides effective multimodal therapy for gliomas in preclinical models when combined with these chemotherapy agents. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Charlestown, MA USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. RP Chiocca, EA (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Ctr Neurooncol, N1017 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM chiocca-1@medetr.osu.edu RI Potter, Philip/J-4515-2013 FU NCI NIH HHS [R01 CA85139, P01 CA69246, P30 CA21765]; NINDS NIH HHS [NS41571] NR 33 TC 67 Z9 69 U1 0 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 AUG 1 PY 2005 VL 65 IS 15 BP 6850 EP 6857 DI 10.1158/0008-5472.CAN-05-0154 PG 8 WC Oncology SC Oncology GA 950DN UT WOS:000230837900047 PM 16061668 ER PT J AU Chan, MM Lu, X Merchant, FM Iglehart, JD Miron, PL AF Chan, MM Lu, X Merchant, FM Iglehart, JD Miron, PL TI Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer SO CARCINOGENESIS LA English DT Article ID NITROSO-N-METHYLUREA; DENSITY OLIGONUCLEOTIDE ARRAYS; TRANSGENIC RATS; AROMATASE INHIBITOR; CDNA MICROARRAY; CARCINOGENESIS; CARCINOMAS; CLASSIFICATION; LESIONS; GLAND AB Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The NMU breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease. To assess the validity of this model from a more global molecular perspective, and also to devise a general technique to compare animal profiles with human microarray studies, we have characterized 25 NMU-induced mammary tumors and 11 normal glands using a combination of immunohistochemical and microarray analyses. The rat mammary carcinomas were classified as non-invasive, ER-positive ductal carcinomas with a composition of differentiated epithelial and myoepithelial cell lineages. Gene expression profiles generated using rat Affymetrix arrays containing 15 866 genes demonstrated that the rat mammary tumors are homogeneous and that H-ras mutations did not confer a unique molecular signature. We compared the resulting rat profiles with those obtained from a human dataset by merging the raw microarray data, using an approach that involves a combination of cross-species and cross-platform analysis. Using this novel strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the classification of human tumors derived from human Affymetrix arrays. The gene expression profiles of the NMU-induced primary tumors were most similar to ER-positive, low to intermediate grade breast cancer. Our technique provides a means to correlate gene expression data from animal models of cancer to human cancer and disease states. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Miron, PL (reprint author), 44 Binney St,Room 822,Smith Bldg, Boston, MA 02115 USA. EM penelope_miron@dfci.harvard.edu FU NCI NIH HHS [T32 CA09535-18]; NHGRI NIH HHS [1R01HG02341] NR 71 TC 67 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2005 VL 26 IS 8 BP 1343 EP 1353 DI 10.1093/carcin/bgi100 PG 11 WC Oncology SC Oncology GA 948OD UT WOS:000230724700004 PM 15845649 ER PT J AU Diaz-Sandoval, LJ Bourna, BE Tearney, GJ Jang, IK AF Diaz-Sandoval, LJ Bourna, BE Tearney, GJ Jang, IK TI Optical coherence tomography as a tool for percutaneous coronary interventions SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE tomography; catheters; imaging; plaque; coronary intervention ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; STENT; RESTENOSIS AB This study was performed to demonstrate the ability of intravascular optical coherence tomography (OCT) to identify characteristic vascular responses to percutaneous coronary interventions (PCI). OCT provides cross-sectional images of tissue in situ at approximately 10 mu m, rendering detailed structural information. Intravascular ultrasound and OCT images were obtained from 10 patients before and after PCI. Images were evaluated to identify balloon-induced dissections/disruptions, thrombus, cutting balloon-induced vascular changes, tissue protrusion, stent apposition and symmetry, and intimal hyperplasia. The disrupted intima, intraluminal thrombus, depth of balloon-induced dissections, cutting balloon cuts, tissue prolapse, underdeployed struts, and intimal hyperplasia were all noticed with OCT. This is the first report of the use of OCT to identify in vivo human intracoronary pathology after PCI. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,Mailstop 843,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 22 TC 35 Z9 40 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD AUG PY 2005 VL 65 IS 4 BP 492 EP 496 DI 10.1002/ccd.20340 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 950LH UT WOS:000230858100006 PM 15920721 ER PT J AU Xing, DY Orsulic, S AF Xing, DY Orsulic, S TI Modeling resistance to pathway-targeted therapy in ovarian cancer SO CELL CYCLE LA English DT Article DE MEK/ERK; mouse model; pathway-targeted therapy; PD98059; PI3K/Akt/mTOR; rapamycin; tumor resistance ID CELL-CYCLE ARREST; MTOR INHIBITOR RAPAMYCIN; GLIOBLASTOMA FORMATION; MULTIPLE-MYELOMA; RAS; AKT; P21(WAF1/CIP1); PHOSPHORYLATION; PROLIFERATION; TRANSLATION AB A detailed understanding of the biochemical pathways that are responsible for cancer initiation and maintenance is critical to designing targeted cancer therapy. Although we have accumulated knowledge about individual molecular changes that underlie cancer development, we are still learning how multiple biochemical pathways cooperate in cancer. This cooperation and cross-talk between redundant biochemical pathways appear to be the main reasons for the failure of therapeutic agents that are designed to interfere with a specific molecular target. In order to simulate the cooperation of several biochemical pathways in cancer development, we have engineered mouse ovarian cancer cell lines and tumors with different combinations of defined genetic alterations. We have used this system to determine the functional contributions of individual pathways that are necessary for cell proliferation and tumor maintenance, as well as to test the molecular mechanisms of tumor resistance to pathway-targeted therapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Xing, DY (reprint author), 13th St,Bldg 149,CNY7, Charlestown, MA 02129 USA. EM dxing@partners.org FU NCI NIH HHS [R01 CA103924-03, R01 CA103924-02, UO1CA105492, U01 CA105492, R01 CA103924-04, P50 CA105009, R01 CA103924, R01 CA103924-01, R01CA103924, P50CA105009] NR 32 TC 10 Z9 10 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD AUG PY 2005 VL 4 IS 8 BP 1004 EP 1006 DI 10.4161/cc.4.8.1869 PG 3 WC Cell Biology SC Cell Biology GA 952EY UT WOS:000230986700005 PM 15970711 ER PT J AU Haber, DA Settleman, J AF Haber, DA Settleman, J TI Overcoming acquired resistance to Iressa/Tarceva with inhibitors of a different class SO CELL CYCLE LA English DT Article DE epidermal growth factor receptor; lung cancer; Iressa; Tarceva; drug resistance ID CELL LUNG-CANCER; IRREVERSIBLE INHIBITORS; IMATINIB MESYLATE; EGF RECEPTOR; GEFITINIB; MUTATIONS; MECHANISMS; TUMORS AB Small molecule kinase inhibitors of the epidermal growth factor receptor ( EGFR) have recently been found to exhibit clinical efficacy in the setting of nonsmall cell lung cancers that harbor activating EGFR mutations. However, the remissions induced by these drugs ( Iressa and Tarceva) are typically short-lived, presumably due to acquired drug resistance. We recently reported findings demonstrating that a distinct class of EGFR inhibitors may overcome some mechanisms of secondary drug resistance in these tumors and may therefore be useful in treating lung cancer patients that initially responded to Iressa or Tarceva and eventually relapsed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Mol Therapeut, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 14 TC 12 Z9 15 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD AUG PY 2005 VL 4 IS 8 BP 1057 EP 1059 PG 3 WC Cell Biology SC Cell Biology GA 952EY UT WOS:000230986700020 PM 15970680 ER PT J AU Furukawa, N Ongusaha, P Jahng, WJ Araki, K Choi, CS Kim, HJ Lee, YH Kaibuchi, K Kahn, BB Masuzaki, H Kim, JK Lee, SW Kim, YB AF Furukawa, N Ongusaha, P Jahng, WJ Araki, K Choi, CS Kim, HJ Lee, YH Kaibuchi, K Kahn, BB Masuzaki, H Kim, JK Lee, SW Kim, YB TI Role of Rho-kinase in regulation of insulin action and glucose homeostasis SO CELL METABOLISM LA English DT Article ID SUBSTRATE-1 TYROSINE PHOSPHORYLATION; SMALL GTPASE RHO; PROTEIN-KINASE; RECEPTOR SUBSTRATE-1; MUSCLE-CELLS; IN-VIVO; SKELETAL-MUSCLE; ROK-ALPHA; ACTIVATION; RESISTANCE AB Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Dept Internal Med, Sect Endocrinol & Metab, New Haven, CT 06520 USA. Chungbuk Natl Univ, Inst Tumor Res, Chungbuk 361763, South Korea. Chungbuk Natl Univ, Coll Med, Chungbuk 361763, South Korea. Nagoya Univ, Dept Cell Pharmacol, Grad Sch Med, Aichi 4668550, Japan. Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Kyoto 6068507, Japan. RP Kim, YB (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM ykim2@bidmc.harvard.edu FU NCI NIH HHS [CA107574, R01 CA85681]; NIDDK NIH HHS [R01 DK080756, R01 DK43051]; PHS HHS [R01-2005-000-10386] NR 38 TC 90 Z9 93 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD AUG PY 2005 VL 2 IS 2 BP 119 EP 129 DI 10.1016/j.cmet.2005.06.011 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 957AT UT WOS:000231342300008 PM 16098829 ER PT J AU Law, B Weissleder, R Tung, CH AF Law, B Weissleder, R Tung, CH TI Mechanism-based fluorescent reporter for protein kinase A detection SO CHEMBIOCHEM LA English DT Article DE fluorescein; fluorescence; kinases; probes; rhodamine ID CATALYTIC SUBUNIT; LIVING CELLS; MEDIATED PHOSPHORYLATION; EXCITON MODEL; SUBSTRATE; ASSAY; DESIGN; MUSCLE AB A novel mechanism-based fluorescent reporter was designed for the detection of protein kinase A (PKA), which is known to mediate a variety of cellular responses in most eukaryotic cells. The probe consists of a specific binding peptide sequence, LRRRRFAFC, conjugated with 2 '-thioethyl-5-(or -6)-carboxyfluoresceinamide (FAMS; 2) and 5-(or 6-)carboxytetromethylrhodamine (TAMRA) at the cysteine and leucine residues, respectively. In the absence of PKA, the two fluorophores associate by hydrophobic interactions, forming an intromolecular ground-state dimer; this results in fluorescein quenching (> 93%). Upon PKA addition, the reporter reacts with the sulfhydryl functionality at Cys199 through a disulfide-exchange mechanism. FAMS is subsequently released, resulting in significant fluorescence amplification. The remaining peptide sequence, which acts as an inhibitor, is attached covalently to the enzyme. Our results suggest that this type of sensors could hove far-reaching applications in the molecular sensing of enzymes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385] NR 29 TC 8 Z9 9 U1 1 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD AUG PY 2005 VL 6 IS 8 BP 1361 EP 1367 DI 10.1002/cbic.200500027 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 955MM UT WOS:000231230000013 PM 16010698 ER PT J AU Robertson, MJ Schacterle, RS Mackin, GA Wilson, SN Bloomingdale, KL Ritz, J Komaroff, AL AF Robertson, MJ Schacterle, RS Mackin, GA Wilson, SN Bloomingdale, KL Ritz, J Komaroff, AL TI Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE B cell; chronic fatigue syndrome; depression; NK cell; multiple sclerosis; T cell ID PITUITARY-ADRENAL AXIS; URINARY FREE CORTISOL; NATURAL-KILLER-CELLS; IMMUNE ACTIVATION; PERIPHERAL-BLOOD; IMMUNOLOGICAL ABNORMALITIES; CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; PHENOTYPE; SUBPOPULATIONS AB Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects. No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies. Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Multiple Sclerosis Clin & Res Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Robertson, MJ (reprint author), Indiana Univ, Med Ctr, Bone Marrow & Stem Cell Transplantat Program, 1044 W Walnut St,Room R4-202, Indianapolis, IN 46202 USA. EM mjrobert@iupui.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCRR NIH HHS [M01 RR0075-27S3]; NIAID NIH HHS [U01-AI32246, R01-AI27314] NR 68 TC 41 Z9 45 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 2005 VL 141 IS 2 BP 326 EP 332 DI 10.1111/j.1365-2249.2005.02833.x PG 7 WC Immunology SC Immunology GA 942OE UT WOS:000230290900016 PM 15996197 ER PT J AU Axelrod, FB Goldberg, JD Rolnitzky, L Mull, J Mann, SR von Simson, GG Berlin, D Slaugenhaupt, SA AF Axelrod, FB Goldberg, JD Rolnitzky, L Mull, J Mann, SR von Simson, GG Berlin, D Slaugenhaupt, SA TI Fludrocortisone in patients with familial dysautonomia - Assessing effect on clinical parameters and gene expression SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE familial dysautonomia; fludrocortisone; mRNA splicing; midodrine; orthostatic hypotension ID MESSENGER-RNA; DEFECTS AB The common familial dysautonomia (FD) mutation causes a splicing defect that leads to production of both wild-type (WT) and mutant (MU) IKBKAP mRNA. Because drugs may alter splicing, seven drugs, fludrocortisone, midodrine, diazepam, albuterol, clonidine, caffeine, and dopamine were screened. Since only fludrocortisone negatively altered gene expression, we assessed fludrocortisone's efficacy in treating postural hypotension, and its effect on survival and secondary long-term FD problems. For 341 FD patients we obtained demographic data and clinical information from the last Center evaluation (most current or prior to death) including mean blood pressures (supine, 1 min erect and 5 min erect) and history regarding syncope and presyncope symptoms. For 175 fludrocortisone-treated patients, data from the evaluation prior to start of fludrocortisone and from the last Center evaluation were compared. The fludrocortisone-treated patient cohort was compared to the nontreated patient cohort with respect to overall survival and event-free survival for crisis frequency, worsening gait, frequent fractures, spine curvature, renal insufficiency, and pacemaker insertion. Overall survivals of patients on fludrocortisone alone, on fludrocortisone and midodrine, and on neither drug were compared. Cumulative survival was significantly higher in fludrocortisone-treated patients than in non-treated patients during the first decade. In subsequent decades, the addition of midodrine improved cumulative survival. Fludrocortisone significantly increased mean blood pressures and decreased dizziness and leg cramping, but not headaches or syncope. Fludrocortisone was associated with more long-term problems, which may reflect more symptomatic status associated with longer survival. Our data suggest that fludrocortisone has clinical efficacy despite negative in vitro observations on gene expression. C1 NYU, Med Ctr, Dysautonomia Treatment & Evaluat Ctr, New York, NY 10016 USA. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NYU, Sch Med, Div Biostat, New York, NY 10016 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Axelrod, FB (reprint author), NYU, Med Ctr, Dysautonomia Treatment & Evaluat Ctr, 530 1St Ave, New York, NY 10016 USA. EM felicia.axelrod@med.nyu.edu NR 23 TC 10 Z9 10 U1 0 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD AUG PY 2005 VL 15 IS 4 BP 284 EP 291 DI 10.1007/s10286-005-0288-1 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 954RX UT WOS:000231173600009 PM 16032383 ER PT J AU Li, G Park, SE DeFrate, LE Schutzer, ME Ji, LN Gill, TJ Rubash, HE AF Li, G Park, SE DeFrate, LE Schutzer, ME Ji, LN Gill, TJ Rubash, HE TI The cartilage thickness distribution in the tibiofemoral joint and its correlation with cartilage-to-cartilage contact SO CLINICAL BIOMECHANICS LA English DT Article DE cartilage; cartilage thickness; cartilage contact; MRI; 3D Modeling ID CRUCIATE LIGAMENT RECONSTRUCTION; MAGNETIC-RESONANCE IMAGES; SIMULATED MUSCLE LOADS; STATE FREE PRECESSION; KNEE-JOINT; ARTICULAR-CARTILAGE; DEFICIENT KNEE; OSTEOARTHRITIS; KINEMATICS; MRI AB Objective. The objective of this study was to investigate whether regions of cartilage in the tibiofemoral joint where cartilage-to-cartilage contact occurred was thicker than other regions. Design. In vivo human subjects. Background. The thickness of the cartilage in the knee has been investigated in various studies. However, the factors that influence the thickness distribution within the joint remain unclear. Methods. Six healthy living knees (5 male, I female, average age = 27) were scanned using magnetic resonance imaging. Three-dimensional models of the tibial and femoral cartilage layers were created. The cartilage thickness distribution was compared between regions where cartilage-to-cartilage contact was observed during in vivo weightbearing flexion and regions with no contact. Results. The regions with cartilage-to-cartilage contact were significantly thicker than the regions without cartilage-to-cartilage contact (P < 0.05). On the medial condyle, the cartilage-to-cartilage contact regions were up to 40% thicker than regions with no contact. On the lateral femoral condyle, the maximum difference between these regions was 20%. On the tibial plateau, the maximal differences between regions with and without cartilage-to-cartilage contact were found to be 40% on the medial side and 50% on the lateral side. Conclusions. The data suggested that in normal knees, the cartilage was thicker in regions where cartilage-to-cartilage contact was present. Future studies should investigate the effects of in vivo loading on cartilage maintenance and growth. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R01AR 052408] NR 34 TC 86 Z9 90 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD AUG PY 2005 VL 20 IS 7 BP 736 EP 744 DI 10.1016/j.clinbiomech.2005.04.001 PG 9 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 945SW UT WOS:000230523500011 PM 15963613 ER PT J AU Clark, JW Eder, JP Ryan, D Lathia, C Lenz, HJ AF Clark, JW Eder, JP Ryan, D Lathia, C Lenz, HJ TI Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; TYROSINE KINASES; HUMAN CANCER; PATHWAY; PROGRESSION; MUTATIONS; MELANOMA; BRAF AB Purpose: BAY 43-9006, a novel multikinase inhibitor, prevents tumor growth by combining two antitumor activities: inhibition of both tumor cell proliferation and tumor angiogenesis. This phase 1, open-label, nonrandomized, noncontrolled, single-arm, dose escalation study was done to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, effect on biomarkers, and tumor response with BAY 43-9006 in 19 patients with advanced, refractory solid tumors. Experimental Design: BAY 43-9006 was given orally in repeated cycles of 1-week on/1-week off. The study comprised five dose levels, ranging from 100 mg twice daily (bid) to 800 mg bid. Treatment of each patient continued until unacceptable toxicity, tumor progression, or death. Results: Rash and hypertension were the dose-limiting toxicities at the 800 mg bid dose requiring study drug discontinuation; therefore, the MTD of BAY 43-9006 in this study was determined to be 600 mg bid. BAY 43-9006 was generally well tolerated, with mild to moderate toxicities. Pharmacokinetic analysis showed early absorption followed by delayed secondary peaks and slow terminal elimination. Stable disease was achieved in five patients: one patient showed reduced tumor activity (positron emission tomography scan) and reduced mitogen-activated protein kinase signaling (lower phospho-ERK); one patient remained on treatment until study end point. Conclusions: The results confirm the favorable safety profile of BAY 43-9006 and support the development of this compound for the treatment of solid tumors. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Bayer Pharmaceut Corp, West Haven, CT USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Clark, JW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Cox Bldg,Site 640,55 Fruit St, Boston, MA 02114 USA. EM jclark@partners.org NR 18 TC 240 Z9 263 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 AUG 1 PY 2005 VL 11 IS 15 BP 5472 EP 5480 DI 10.1158/1078-0432.CCR-04-2658 PG 9 WC Oncology SC Oncology GA 950SX UT WOS:000230878900021 PM 16061863 ER PT J AU Lieberman, DA Holub, J Eisen, G Kraemer, D Morris, CD AF Lieberman, DA Holub, J Eisen, G Kraemer, D Morris, CD TI Prevalence of polyps greater than 9 mm in a consortium of diverse clinical practice settings in the United States SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; ASYMPTOMATIC ADULTS; TASK-FORCE; COLONOSCOPY; RISK; AGE; GUIDELINES; CARCINOMA; ADENOMAS AB Background & Aims: Colonoscopy is often performed with the goal of identification of patients with serious colon neoplasia. We determined the prevalence of colon masses or polyps greater than 9 mm on the basis of age, gender, race, and procedure indication in diverse clinical practice settings and compared occurrence in patients receiving colonoscopy for screening, surveillance, or evaluation of symptoms. Methods: We obtained patient demographics, procedure indication, and endoscopic findings from colonoscopy reports in the Clinical Outcomes Research Initiative data repository, which receives endoscopy reports from 73 diverse practice sites in the United States. A multivariate model was developed to measure risk variables for a mass or polyps >9 mm. Absolute risk was calculated in the model on the basis of the number needed to endoscope (NNE) to identify 1 patient with a mass or polyp >9 mm. Results: From 2000-2002, colonoscopies in 141,413 unique patients were analyzed. Sixty-nine percent of the reports came from private practice (nonacademic) settings. Increasing age, male gender, and black race were associated with increased risk of mass or polyps >9 mm. In the 50- to 59-year-old average-risk group, 28 women and 18 men would need to have screening colonoscopy to identify 1 patient with a mass/polyp >9 mm. Patients with positive fecal occult blood test results, hematochezia, and anemia had lower NNE, whereas men older than 60 years receiving adenoma surveillance and patients with irritable bowel symptoms had similar NNE compared with average-risk subjects. Conclusions: The prevalence of a colon lesion >9 mm varies on the basis of age, gender, race, and procedure indication. Understanding utilization and outcomes can lead to more optimal use of colonoscopy. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Lieberman, DA (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, P3-GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA. EM lieberma@ohsu.edu FU NCI NIH HHS [U01 CA 89389-01]; NIDDK NIH HHS [R33-DK61778-01] NR 30 TC 56 Z9 56 U1 0 U2 1 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 AUG PY 2005 VL 3 IS 8 BP 798 EP 805 DI 10.1053/S1542-3565(05)00405-2 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995MZ UT WOS:000234105700014 PM 16234009 ER PT J AU Sigg, D Rich, R Ashby, S Jabour, B Glass, E AF Sigg, D Rich, R Ashby, S Jabour, B Glass, E TI Radionuclide shuntogram demonstrating migration of distal ventriculoperitoneal shunt tubing out of the peritoneal cavity SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE hydrocephalus; cisternogram; ventriculoperitoneal shunt; In-111 DTPA; scintigraphy ID COILING AB An 81-year-old man with a history of ventriculoperitoneal (V-P) shunt placement for symptomatic normal pressure hydrocephalus presented with recurrence of confusion and gait disturbance. Radionuclide cisternography demonstrated loculation of In-111 DTPA in the abdominal wall. A soft tissue mass palpated at the location of tracer accumulation was confirmed to be extraperitoneal pooling of fluid at the site of coiling of the distal shunt tip. After surgical revision, with repositioning of the distal tube in the peritoneal cavity, the patient's symptoms promptly improved. When symptoms of hydrocephalus recur after successful V-P shunt placement, shunt malfunction should be suspected and evaluation for mechanical failure pursued. Catheter migration should be recognized as a correctable cause of shunt malfunction. C1 Med Imaging Ctr So Calif, Santa Monica, CA USA. RP Glass, E (reprint author), W Los Angeles VAMC, Nucl Med Serv 115, 11301 Wilshire Blvd, Los Angeles, CA USA. EM edwin.glass@med.va.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD AUG PY 2005 VL 30 IS 8 BP 552 EP 554 DI 10.1097/01.rlu.0000170041.00657.fe PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947GL UT WOS:000230631300007 PM 16024953 ER PT J AU Randall, RL Dailey, A Albritton, KH Olson, PR Coffin, CM AF Randall, RL Dailey, A Albritton, KH Olson, PR Coffin, CM TI Fibrosarcoma metastatic to the sciatic nerve SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SEGMENTAL NEUROFIBROMATOSIS; MALIGNANT-LYMPHOMA; SCHWANNOMA; SCALP AB Fibrosarcoma that metastasizes to the central nervous system has been documented in the literature. However, we know of no recorded case of spread to a major peripheral nerve. We report a unique occurrence of fibrosarcoma with metastatic involvement of the sciatic nerve, and a review of the literature. C1 Univ Utah, Huntsman Canc Inst, Sarcoma Serv, Salt Lake City, UT 84132 USA. Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT 84132 USA. Univ Utah, Dept Orthopaed, Salt Lake City, UT 84132 USA. Univ Utah, Dept Pathol, Salt Lake City, UT 84132 USA. Rocky Mt Neurosurg Alliance, Englewood, CO USA. Dana Farber Canc Inst, Div Adolescent Oncol, Boston, MA 02115 USA. RP Randall, RL (reprint author), Univ Utah, Huntsman Canc Inst, Sarcoma Serv, 2000 Circle Hope,Suite 4260, Salt Lake City, UT 84132 USA. EM R.Lor.Randall@lisc.utah.edu NR 30 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 2005 IS 437 BP 242 EP 246 DI 10.1097/01.blo.0000169082.69022.57 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 953JM UT WOS:000231072500039 PM 16056055 ER PT J AU Ranganath, VK Furst, DE AF Ranganath, VK Furst, DE TI Disease-modifying antirheumatic drug use in the elderly rheumatoid arthritis patient SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID LOW-DOSE METHOTREXATE; DOUBLE-BLIND; CONTROLLED TRIAL; CLINICAL-TRIAL; ETANERCEPT ENBREL(R); PULSE METHOTREXATE; 2ND-LINE DRUGS; OLDER PATIENTS; EFFICACY; THERAPY AB During the 10-year period since the last review was done by Gardner and Furst, studies have furthered our knowledge of use of disease-modifying antirheumatic drugs (DMARDs) in the elderly rheumatoid arthritis (RA) patient. This article will briefly review the clinical pharmacology of human as they age, and detail the effects of aging on the specific pharmacokinetics and responses to commonly used DMARDs. There has been some progress in understanding the elderly RA patient, however, there is insufficient data for much confidence in DMARDs effects in the elderly. C1 Univ Calif Los Angeles, Dept Med, Div Rheumatol, David Geffen Sch Med, Los Angeles, CA 90025 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Furst, DE (reprint author), Univ Calif Los Angeles, Dept Med, Div Rheumatol, David Geffen Sch Med, 1000 Vet Ave,Room 32-59, Los Angeles, CA 90025 USA. EM defurst@mednet.ucla.edu NR 89 TC 3 Z9 3 U1 1 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 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2005 VL 21 IS 3 BP 649 EP + DI 10.1016/j.cger.2005.02.010 PG 22 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 940FE UT WOS:000230128300012 PM 15911212 ER PT J AU Budimlija, ZM Lechpammer, M Popiolek, D Fogt, F Prinz, M Bieber, FR AF Budimlija, ZM Lechpammer, M Popiolek, D Fogt, F Prinz, M Bieber, FR TI Forensic applications of Laser Capture Microdissection: Use in DNA-based parentage testing and platform validation SO CROATIAN MEDICAL JOURNAL LA English DT Article ID PREGNANCY TERMINATION; FETAL MATERIAL; PCR AB Aim To report on the successful use of Laser Capture Microdissection (LCM) as a tool for isolation of human chorionic villi from admixed maternal tissue. Subsequent DNA isolation for forensic short tandem repeat (STR) analysis for parentage testing was performed in two cases of alleged sexual assault of female victims. We also performed validation of the LCM instrument platform, using archival formalin-fixed human fetal products of conception (POC), for which microdissection was utilized to separate maternal (decidua) and fetal (chorionic villus) components. Methods To isolate DNA from placental chorionic villi admixed with maternal decidua recovered after spontaneous ortherapeutic abortion, LCM was used to separate fetal from maternal cells. In contrast to the relatively crude conventional microdissection performed using a narrow pipette, needle, or scalpel blade, LCM allows cell- or tissue-specific isolation of placental chorionic villi from archival paraffin-embedded tissue sections, leaving the maternal tissue intact. Results After polymerase chain reaction (PCR) amplification of villi after LCM of 9-15 STR loci, the quantity and quality of DNA yielded from fetal cells isolated by LCM was sufficient for PCR analysis and successful forensic parentage testing. The validation data obtained on two sets of formalin-fixed archival POC tissues from anonymous donors demonstrated the encouraging reproducibility of these protocols and procedures. Conclusion We demonstrated the reliability and utility of LCM for forensic applications when high specificity of a particular analyzed cell population or tissue is required. Care must be taken during routine pathology procedures to avoid contamination of tissues with admixture of extraneous DNA. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. New York City Off Chief Med Examiner, Dept Forens Biol, New York, NY USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bieber, FR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM FBIEBER@partners.org NR 17 TC 24 Z9 29 U1 0 U2 1 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD AUG PY 2005 VL 46 IS 4 BP 549 EP 555 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 959FO UT WOS:000231503100008 PM 16100757 ER PT J AU Ng, DPK Krolewski, AS AF Ng, DPK Krolewski, AS TI Molecular genetic approaches for studying the etiology of diabetic nephropathy SO CURRENT MOLECULAR MEDICINE LA English DT Review ID GROWTH-FACTOR-BETA; ALDOSE REDUCTASE GENE; OXIDE SYNTHASE GENE; RAT MESANGIAL CELLS; SPONTANEOUSLY HYPERTENSIVE-RATS; TRANSGENIC (MREN-2)27 RAT; URINARY ALBUMIN EXCRETION; STAGE RENAL-DISEASE; RENIN-ANGIOTENSIN SYSTEM; LONG-TERM COMPLICATIONS AB A critical challenge faced by clinical nephrologists today is the escalating number of patients developing end stage renal disease, a major proportion of which is attributed to diabetic nephropathy (DN). The need for new measures to prevent and treat this disease cannot be overemphasized. To this end, modern genetic approaches provide powerful tools to investigate the etiology of DN. Human studies have already established the importance of genetic susceptibility for DN. Several major susceptibility loci have been identified using linkage studies. In addition, linkage studies in rodents have pinpointed promising chromosomal segments that influence renal traits. Besides augmenting our understanding of disease pathogenesis, these animal studies may facilitate the cloning of disease susceptibility genes in man through the identification of homologous regions that contribute to renal disease. In human diabetes, various genes have been evaluated for their risk contribution to DN. This widespread strategy has been propelled by our knowledge of the glucose-activated pathways underlying DN. Evidence has emerged that a true association does indeed exist for some candidate genes. Furthermore, the in vivo manipulation of gene expression has shown that these genes can modify features of DN in transgenic and knockout rodent models, thus corroborating the findings from human association studies. Still, the exact molecular mechanisms involving these genes remain to be fully eluciated. This formidable task may be accomplished by continuing to harness the synergy between human and experimental genetic approaches. In this respect, our review provides a first synthesis of the current literature to facilitate this challenging effort. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Room 368,1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewsk@joslin.harvard.edu FU NIDDK NIH HHS [DK58549, DK-53534] NR 190 TC 27 Z9 27 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 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD AUG PY 2005 VL 5 IS 5 BP 509 EP 525 DI 10.2174/1566524054553504 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 948WU UT WOS:000230747200007 PM 16101480 ER PT J AU Yoshida, S Guillet, M Pellman, D AF Yoshida, S Guillet, M Pellman, D TI MEN signaling: Daughter bound pole must escape her mother to be fully active SO DEVELOPMENTAL CELL LA English DT Editorial Material ID SPINDLE POSITION; MITOTIC-EXIT; MITOSIS; COMPLEX; CDC5 AB Budding yeast divide asymmetrically and must therefore align the position of the mitotic spindle with the plane of division. The success of this process is monitored by a checkpoint-signaling mechanism. Two recent papers in Molecular Cell reveal an important new facet of this signal transduction pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Yoshida, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI Yoshida, Satoshi/C-5016-2011 NR 10 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG PY 2005 VL 9 IS 2 BP 168 EP 170 DI 10.1016/j.devcel.2005.07.006 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 956DT UT WOS:000231280100002 PM 16054023 ER PT J AU Albertson, RC Payne-Ferreira, TL Postlethwait, J Yelick, PC AF Albertson, RC Payne-Ferreira, TL Postlethwait, J Yelick, PC TI Zebrafish acvr2a and acvr2b exhibit distinct roles in craniofacial development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE activin signaling; TGF beta; craniofacial development; zebrafish ID II ACTIVIN RECEPTORS; BRANCHIAL ARCH MUTANTS; TGF-BETA; BONE-FORMATION; DEFICIENT MICE; A RECEPTOR; KINASE RECEPTOR; CHICK-EMBRYO; EXPRESSION; PROTEIN AB To examine the roles of activin type 11 receptor signaling in craniofacial development, full-length zebrafish acvr2a and aevr2b clones were isolated. Although ubiquitously expressed as maternal mRNAs and in early embryogenesis, by 24 hr postfertilization (hpf), acvr2a and acvr2b exhibit restricted expression in neural, hindbrain, and neural crest cells (NCCs). A morpholino-based targeted protein depletion approach was used to reveal discrete functions for each acvr2 gene product. The acvr2a morphants exhibited defects in the development of most cranial NCC-derived cartilage, bone, and pharyngeal tooth structures, whereas acvr2b morphant defects were largely restricted to posterior arch structures and included the absence and/or aberrant migration of posterior NCC streams, defects in NCC-derived posterior arch cartilages, and dysmorphic pharyngeal tooth development. These studies revealed previously uncharacterized roles for acvr2a and acvr2b in hindbrain and NCC patterning, in NCC derived pharyngeal arch cartilage and joint formation, and in tooth development. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst,Dept Oral & Dev Biol, Boston, MA 02115 USA. Univ Oregon 1254, Inst Neurosci, Eugene, OR USA. RP Yelick, PC (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst,Dept Oral & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org NR 71 TC 20 Z9 21 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2005 VL 233 IS 4 BP 1405 EP 1418 DI 10.1002/dvdy.20480 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 945QU UT WOS:000230518000020 PM 15977175 ER PT J AU Winckler, W Burtt, NP Holmkvist, J Cervin, C de Bakker, PIW Sun, M Almgren, P Tuomi, T Gaudet, D Hudson, TJ Ardlie, KG Daly, MJ Hirschhorn, JN Altshuler, D Groop, L AF Winckler, W Burtt, NP Holmkvist, J Cervin, C de Bakker, PIW Sun, M Almgren, P Tuomi, T Gaudet, D Hudson, TJ Ardlie, KG Daly, MJ Hirschhorn, JN Altshuler, D Groop, L TI Association of common variation in the HNF1 alpha gene region with risk of type 2 diabetes SO DIABETES LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HEPATIC NUCLEAR FACTOR-1-ALPHA; LATE-ONSET NIDDM; I ALPHA-GENE; LINKAGE DISEQUILIBRIUM; POPULATION; MUTATIONS; MELLITUS; SUSCEPTIBILITY; VARIANTS AB It is currently unclear how often genes that are mutated to cause rare, early-onset monogenic forms of disease also harbor common variants that contribute to the more typical polygenic form of each disease. The gene for MODY3 diabetes, HNF1 alpha, lies in a region that has shown linkage to late-onset type 2 diabetes (12q24, NIDDM2), and previous association studies have suggested a weak trend toward association for common missense variants in HNF1a with glucose-related traits. Based on genotyping of 79 common SNPs in the 118 kb spanning HNF1 alpha, we selected 21 haplotype tag single nucleotide polymorphisms (SNPs) and genotyped them in > 4,000 diabetic patients and control subjects from Sweden, Finland, and Canada. Several SNPs from the coding region and 5' of the gene demonstrated nominal association with type 2 diabetes, with the most significant marker (rs1920792) having an odds ratio of 1.17 and a P value of 0.002. We then genotyped three SNPs with the strongest evidence for association to type 2 diabetes (rs1920792, I27L, and A98V) in an additional 4,400 type 2 diabetic and control subjects from North America and Poland and compared our results with those of the original sample and of Weedon et al. None of the results were consistently observed across all samples, with the possible exception of a modest association of the rare (3-5%) A98V variant. These results indicate that common variants in HNF1 alpha either play no role in type 2 diabetes, a very small role, or a role that cannot be consistently observed without consideration of as yet unmeasured genetic or environmental modifiers. C1 Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Folkhalsan Inst Genet,Folkhalsan Res Ctr, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Univ Montreal, Chicoutimi Hosp, Community Genom Ctr, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. Genom Collaborat Inc, Cambridge, MA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. EM leif.groop@endo.mas.lu.se RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 NR 40 TC 50 Z9 57 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2005 VL 54 IS 8 BP 2336 EP 2342 DI 10.2337/diabetes.54.8.2336 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950PN UT WOS:000230869500009 PM 16046299 ER PT J AU Hood, KK Johnson, SB Carmichael, SK Laffel, LMB She, JX Schatz, DA AF Hood, KK Johnson, SB Carmichael, SK Laffel, LMB She, JX Schatz, DA TI Depressive symptoms in mothers of infants identified as genetically at risk for type 1 diabetes SO DIABETES CARE LA English DT Article ID STRUCTURED CLINICAL INTERVIEW; PSYCHIATRIC-DISORDERS; POSTNATAL DEPRESSION; POPULATION; PREVALENCE; CHILDREN AB OBJECTIVE - This study describes maternal depression associated with newborn genetic screening for type 1 diabetes after risk notification. RESEARCH DESIGN AND METHODS - Mothers of at-risk infants (n = 192), identified through newborn genetic screening as part of the Prospective Assessment of Newborns for Diabetes Autoimmunity study, were administered a Structured telephone interview assessing maternal depressive symptoms I and 3.5 months after risk notification. Statistical analyses were conducted to examine predictors and correlates of maternal depressive symptoms. RESULTS - For the total sample, maternal depressive symptoms in response to infant risk status were not elevated at I and 3.5 months after risk notification. However, at the first interview, mothers from ethnic minority backgrounds (P < 0.002), with limited education (P < 0.001), and with postpartum depression symptomatology (P < 0.001) reported significantly more depressive symptoms in response to risk notification (r(2) = 0.354). At the second inter-view, postpartum depression symptomatology remained a powerful predictor of depressive Symptoms in response to risk notification (P < 0.001). In addition, certain coping styles (wishful thinking, self-blame, and seeking social support) were associated with increased depressive symptoms. A history of major depression was a correlate of both postpartum depressive symptomatology (r = 0.26) and maternal depressive response to risk notification (r = 0.21). CONCLUSIONS - For the most part, mothers of infants genetically at risk for type I diabetes do not appear to evidence elevated depressive symptoms. This suggests that most mothers are resilient when notified of infant risk. However, certain maternal characteristics such as ethnic minority status, less than a high school education, postpartum depression symptomatology, a history of major depression, and certain coping strategies (wishful thinking, self, blame, and seeking social support) appear to be associated with a more difficult maternal response to the news of an infants increased genetic risk for type I diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit,Genet & Epidemiol Sect,B, Boston, MA 02115 USA. Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA. Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. RP Hood, KK (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit,Genet & Epidemiol Sect,B, 1 Joslin Pl, Boston, MA 02115 USA. EM korey.hood@joslin.harvard.edu FU CCR NIH HHS [CRCGRR00082]; NICHD NIH HHS [K04-HD-00686, R01HD37800-01]; NIDDK NIH HHS [P01-DK-39079] NR 27 TC 14 Z9 14 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2005 VL 28 IS 8 BP 1898 EP 1903 DI 10.2337/diacare.28.8.1898 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950PP UT WOS:000230869700008 PM 16043729 ER PT J AU Ahmed, SB Hovind, P Parving, HH Rossing, P Price, DA Laffel, LM Lansang, MC Stevanovic, R Fisher, NDL Hollenberg, NK AF Ahmed, SB Hovind, P Parving, HH Rossing, P Price, DA Laffel, LM Lansang, MC Stevanovic, R Fisher, NDL Hollenberg, NK TI Oral contraceptives, angiotensin-dependent renal vasoconstriction, and risk of diabetic nephropathy SO DIABETES CARE LA English DT Article; Proceedings Paper CT 19th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 18-22, 2004 CL New York, NY SP Amer Soc Hypertens ID INTENSIVE TREATMENT; TYPE-2 DIABETES/; ACE-INHIBITION; YOUNG-WOMEN; PROGRESSION; MELLITUS; SYSTEM; COMPLICATIONS; DISEASE; GENDER AB OBJECTIVE - Diabetes, the leading cause of end-stage renal disease in the U:S., is believed to involve activation of the renin angiotensin system (PAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear. RESEARCH DESIGN AND METHODS - Renal plasma flow (RPF) response to captopril, as an index of PAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1-24). RESULTS - Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril (9 +/- 10 ml (.) min(-1) (.) 1.73 m(-2), p = 0.6). In comparison, nondiabetic OC users showed a significant increase (69 - 35 ml - min(-1) - 1.73 m(-2), p = 0.02) (P = 0.04 vs. riondiabetic OC nonusers). Diabetic OC nonusers demonstrated the anticipated vasodilator response (58 +/- 12 ml (.) min(-1) (.) 1.73 m(-2), p < 0.0001). Diabetic OC users showed the largest responses (84 +/- 12 ml (.) min(-1) (.) 1.73 m(-2), p = 0.602) (P = 0.04 vs. diabetic OC nonusers). Plasma renin activity did not vary with OC use (P = 0.3). The RPF responses to captopril and angiotensin receptor blocker were highly correlated (r = 0.72, P < 0.001), Suggesting clear involvement Of the RAS. In the observational study, 18% (6/33 [95% CI 4.3-32.1]) of OC users developed macroalbuminuria compared with 2% (2/81 [0-5.9]) of OC nonusers (P = 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression model, OC use remained a predictor for the development of macroalbuminuria (relative risk 8.00 [95%CI 1.79-44.36], P = 0.008). CONCLUSIONS - The strong association of OC use with angiotensin-dependent control of the renal circulation and the development of macroalbuminuria suggest that OC use may be a risk factor for diabetic nephropathy. Large prospective studies are required to further investigate this relationship. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Ahmed, SB (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St,PBB-3, Boston, MA 02115 USA. EM sahmed7@partners.org RI Ahmed, Sofia/J-7876-2015 FU NHLBI NIH HHS [T32 HL-07609]; PHS HHS [1P50ML530000-01, P01AC00059916] NR 43 TC 33 Z9 33 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2005 VL 28 IS 8 BP 1988 EP 1994 DI 10.2337/diacare.28.8.1988 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950PP UT WOS:000230869700022 PM 16043743 ER PT J AU Whitsel, EA Boyko, EJ Rautaharju, PM Raghunathan, TE Lin, DY Pearce, RM Weinmann, SA Siscovick, DS AF Whitsel, EA Boyko, EJ Rautaharju, PM Raghunathan, TE Lin, DY Pearce, RM Weinmann, SA Siscovick, DS TI Electrocardiographic QT interval prolongation and risk of primary cardiac arrest in diabetic patients SO DIABETES CARE LA English DT Article ID RECOGNIZED HEART-DISEASE; SUDDEN CORONARY DEATH; AUTONOMIC NEUROPATHY; MYOCARDIAL-INFARCTION; UNITED-STATES; CRITERIA; WOMEN; TIME C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Kaiser Permanente, Portland, OR USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Whitsel, EA (reprint author), Bank Amer Ctr, Dept Epidemiol, Cardiovasc Dis Program, Suite 306,137 E Franklin St, Chapel Hill, NC 27514 USA. EM ewhitsel@email.unc.edu FU NHLBI NIH HHS [HL-42456-03, 5-T32-HL07055] NR 29 TC 26 Z9 29 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2005 VL 28 IS 8 BP 2045 EP 2047 DI 10.2337/diacare.28.8.2045 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950PP UT WOS:000230869700036 PM 16043757 ER PT J AU Herbert, A Liu, C Karamohamed, S Schiller, J Liu, J Yang, Q Wilson, PWF Cupples, LA Meigs, JB AF Herbert, A Liu, C Karamohamed, S Schiller, J Liu, J Yang, Q Wilson, PWF Cupples, LA Meigs, JB TI The -174 IL-6 GG genotype is associated with a reduced risk of type 2 diabetes mellitus in a family sample from the National Heart, Lung and Blood Institute's Framingham Heart Study SO DIABETOLOGIA LA English DT Article DE association; family; IL-6; -174 polymorphism; type 2 diabetes ID PROMOTER POLYMORPHISM; INSULIN SENSITIVITY AB Aims/hypothesis: We evaluated the -174 IL-6 gene polymorphism as a risk factor for type 2 diabetes mellitus in a family-based analysis.Methods: We tested for associations between the -174 IL-6 G/C promoter polymorphism and fasting plasma glucose (FPG) and type 2 diabetes in a sample of 1,428 individuals from the largest 182 families in the National Heart, Lung and Blood Institute's Framingham Heart Study population. Results: A significant association was found with FPG (p=0.01) and log (FPG) (p=0.005) using a modified family-based transmission disequilibrium test, the family-based association test (FBAT). The association between IL-6 genotype and FPG (p=0.035) and log (FPG) (p=0.03) was also found in the subset of families that were informative in FBAT using a mixed-effects regression model and strengthened after adjustment for potential confounders (p=0.008 for log [FPG]). The mean glucose level estimated from models with log (FPG) as the dependent variable for the GG genotype in the informative families was significantly lower (5.20 +/- 0.06 mmol/l) than for the GC (5.41 +/- 0.06 mmol/l) and CC (5.38 +/- 0.06 mmol/l) genotypes (p=0.03 for contrast between GG and GC genotypes). In the subset of informative families, the risk of type 2 diabetes associated with the GG genotype was lower relative to the GC and CC genotypes combined (potential confounder-adjusted, mixed-effects odds ratio 0.35, 95% CI 0.14-0.88, p=0.026, unaffected n=391, affected n=32). Conclusion/Interpretaion: These results are consistent with a protective role for the -174 IL-6 G allele against type 2 diabetes and warrant further analysis of this polymorphism. C1 Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study Genet Lab, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. RP Herbert, A (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study Genet Lab, 715 Albany St, Boston, MA 02118 USA. EM aherbert@bu.edu RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [HL64753, N01-HC-25195] NR 10 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2005 VL 48 IS 8 BP 1492 EP 1495 DI 10.1007/s00125-005-1830-3 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955II UT WOS:000231219200011 PM 15965659 ER PT J AU Simpson, TL Kivlahan, DR Bush, KR McFall, ME AF Simpson, TL Kivlahan, DR Bush, KR McFall, ME TI Telephone self-monitoring among alcohol use disorder patients in early recovery: a randomized study of feasibility and measurement reactivity SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE daily monitoring; feasibility; alcohol use disorders; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; ECOLOGICAL MOMENTARY ASSESSMENT; SUBSTANCE USE DISORDERS; TIMELINE FOLLOW-BACK; MAJOR MENTAL-ILLNESS; TREATED ALCOHOLICS; DRINKING PATTERNS; CONSUMPTION; ABUSE; PTSD AB Frequent symptom self-monitoring protocols have become popular tools in the addiction field. Interactive Voice Response (IVR) is a telephone monitoring system that has been shown to be feasible for collecting frequent self-reports from a variety of research populations. Little is known, however, about the feasibility of using IVR monitoring in clinical samples, and few controlled trials exist assessing the impact of any type of frequent self-report monitoring on the behaviors monitored. This pilot study with patients in early recovery from an alcohol use disorder (n =98) evaluated compliance with two IVR monitoring protocols, subjective experiences with monitoring, and change in symptoms associated with monitoring (i.e., measurement reactivity). Participants were randomly assigned to call an IVR system daily for 28 days, once per week for 4 weeks, or only to complete 28-day follow-up assessment including retrospective drinking reports. Monitoring calls assessed alcohol craving, substance use, emotional well-being, and PTSD symptoms. Most monitoring participants completed calls on at least 75% of scheduled days (72.2% and 59.2% for daily and weekly, respectively). Including reconstructed data from follow-up of missed calls yielded 77.8% and 74.1% of maximum data points, respectively. Most monitoring participants indicated the protocol was manageable and reported positive or no effects of monitoring on urges to use alcohol, actual drinking, and PTSD symptoms. Analyses of measurement reactivity based on assessment one month after randomization found no significant group differences on drinking, craving for alcohol, or PTSD-related symptoms. Results suggest that IVR technology is feasible and appropriate for telephone symptom monitoring in similar clinical samples. Published by Elsevier Ireland Ltd. C1 Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Simpson, TL (reprint author), Mental Illness Res Educ & Clin Ctr, VISN 20, Seattle, WA 98108 USA. EM tracy.simpson@med.va.gov NR 50 TC 50 Z9 50 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2005 VL 79 IS 2 BP 241 EP 250 DI 10.1016/j.drugalcdep.2005.02.001 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 949OB UT WOS:000230796900013 PM 16002033 ER PT J AU Krupitsky, EM Horton, NJ Williams, EC Lioznov, D Kuznetsova, M Zvartau, E Samet, JH AF Krupitsky, EM Horton, NJ Williams, EC Lioznov, D Kuznetsova, M Zvartau, E Samet, JH TI Alcohol use and HIV risk behaviors among HIV infected hospitalized patients in St. Petersburg, Russia SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE HIV risk; alcohol abuse; Russia ID INCONSISTENT CONDOM USE; INJECTION-DRUG USERS; SEXUAL-BEHAVIOR; CONSUMPTION; PREVALENCE; DEPENDENCE; EXPECTANCIES; TRANSMISSION; STUDENTS; MEN AB Purpose: Russia has high per capita alcohol consumption and an injection-drug-use-driven HIV epidemic. However, the role of alcohol in the spread of HIV infection in Russia is largely unexplored. Thus, we assessed recent alcohol use and associated HIV risk behaviors among HIV-infected persons in St. Petersburg, Russia. Methods: we recruited HIV-infected hospitalized patients from the Botkin Irfectious Disease Hospital between June 2001 and March 2002. Interviewers assessed alcohol and drug use with the addiction severity index (ASI) and sex- and drug-risk behaviors with the risk assessment battery (RAB). Lifetime abuse or dependence diagnoses for alcohol and drugs were established by a physician with addiction medicine training. Results: Among 201 subjects, diagnoses of abuse or dependence (AB/DEP) were common: 9% (19/201) had only alcohol AB/DEP; 39% (78/201) had alcohol and drug AB/DEP; 47% (95/201) had only drug AWDEP; and 4% (9/201) had no diagnosis of alcohol or drug AB/DEP. Sex- and drug-risk behaviors varied significantly by substance use diagnosis. Subjects with any alcohol AB/DEP had higher sex-risk RAB scores than those with drug only AB/DEP (6.1 versus 3.9, p <.0001). Among subjects with any diagnosis of drug AB/DEP, having in addition an alcohol diagnosis was associated with unclean needle use in the last six months (33% (26/78) versus 21% (20/95), p=0.08). Conclusions: Lifetime alcohol diagnoses of abuse or dependence were present in nearly one-half of hospitalized HIV-infected patients in St. Petersburg. Russia and were associated with significantly higher sex-risk behaviors and borderline significantly higher drug-risk behaviors. As HIV infection spreads rapidly in Russia and Eastern Europe, these data support the need for HIV risk-reduction interventions in alcohol abusing populations and raise the potential of benefit by addressing alcohol use in HIV-infected populations. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Boston Univ, Med Ctr, Dept Med, Sect Gen Internal Med,CARE, Boston, MA 02118 USA. St Petersburg State Pavlov Med Univ, St Petersburg Sci Res Ctr Addict & Psychopharmaco, St Petersburg 197089, Russia. Boston Univ, Sch Med, Boston, MA 02118 USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Treatment & Educ, Seattle, WA 98108 USA. RP Samet, JH (reprint author), Boston Univ, Med Ctr, Dept Med, Sect Gen Internal Med,CARE, Boston, MA 02118 USA. EM jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; Lioznov, Dmitry/J-2539-2013; OI Lioznov, Dmitry/0000-0003-3643-7354; Samet, Jeffrey/0000-0002-0897-3400; Horton, Nicholas/0000-0003-3332-4311 FU NIAAA NIH HHS [R01 AA011785, R01-AA11785] NR 41 TC 26 Z9 26 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2005 VL 79 IS 2 BP 251 EP 256 DI 10.1016/j.drugalcdep.2005.01.015 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 949OB UT WOS:000230796900014 PM 16002034 ER PT J AU Laham, RJ Post, M Rezaee, M Donnell-Fink, L Wykrzykowska, JJ Lee, SU Baim, DS Sellke, FW AF Laham, RJ Post, M Rezaee, M Donnell-Fink, L Wykrzykowska, JJ Lee, SU Baim, DS Sellke, FW TI Transendocardial and transepicardial intramyocardial fibroblast growth factor-2 administration: Myocardial and tissue distribution SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CORONARY-ARTERY-DISEASE; PORCINE HEARTS; GENE-THERAPY; DOUBLE-BLIND; ANGIOGENESIS; ISCHEMIA; INTRACORONARY; DELIVERY; REVASCULARIZATION; INJECTION AB Effective local delivery to the heart remains an obstacle to successful therapeutic application of a number of drugs and biological agents. This study was designed to study and optimize the delivery characteristics of transendocardial intramyocardial (IM) administration, determine myocardial deposition and retention over time, and compare it to transepicardial IM injection. Thirty-nine pigs were used for the study (15 for catheter optimization, 15 for transendocardial IM delivery, and 9 for transepicardial IM delivery). I-125-Fibroblast growth factor-2 (FGF2) (25 mu Ci) was used as the prototype molecule. Tissue and myocardial distribution was determined at 1 and 24 h and 7 days. Using 1-h I-125-FGF2 myocardial deposition as a parameter for delivery efficiency, the optimal needle length and delivery volume for transendocardial based delivery were determined to be 6 mm and 0.1 ml, respectively. Using these parameters for endocardial delivery, I-125-FGF2 cardiac activity was 18.01 +/- 3.84% of delivered activity at 1 h, 11.65 +/- 5.17% at 24 h, and 2.32 +/- 0.87% at 7 days in ischemic animals. Studies in non-ischemic animals produced similar results. For transepicardial delivery, I-125-FGF2 cardiac-specific activity was 23.14 +/- 12.67% for the 6-mm needle, declining to 12.32 +/- 8.50% at 24 h, and did not significantly differ from values obtained following transendocardial delivery. Thus, optimized transendocardial intramyocardial delivery using Biosense guidance results in efficient delivery of FGF2 to the target myocardium that is comparable with transepicardial delivery, both providing markedly higher myocardial deposition and retention and lower systemic recirculation of FGF2 than intracoronary, intrapericardial, or intravenous delivery. However, myocardial distribution is limited to injection sites. C1 Beth Israel Deaconess Med Ctr, Cardiovasc Angiogenesis Ctr, Cardiol & Cardiovasc Div, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. EM rlaham@bidmc.harvard.edu FU NCRR NIH HHS [M01-RR01032]; NHLBI NIH HHS [HL42279, HL60901] NR 30 TC 21 Z9 24 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD AUG PY 2005 VL 33 IS 8 BP 1101 EP 1107 DI 10.1124/dmd.104.002774 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 949VS UT WOS:000230816800003 PM 15879496 ER PT J AU Catley, L Tai, YT Chauhan, D Anderson, KC AF Catley, L Tai, YT Chauhan, D Anderson, KC TI Perspectives for combination therapy to overcome drug-resistant multiple myeloma SO DRUG RESISTANCE UPDATES LA English DT Review DE multiple myeloma; bortezomib; thalidomide; rapamycin; HDAC inhibitors; proteasome inhibitors; drug resistance ID HISTONE DEACETYLASE INHIBITOR; STEM-CELL TRANSPLANTATION; MARROW STROMAL CELLS; TYROSINE KINASE INHIBITOR; NF-KAPPA-B; PREVIOUSLY UNTREATED PATIENTS; GROWTH-FACTOR SECRETION; TELOMERASE ACTIVITY; IN-VIVO; ARSENIC TRIOXIDE AB The introduction of melphalan and prednisone 40 years ago was a significant advance in the treatment of multiple myeloma (MM). In the following decades, significant advances were few, but included landmarks, such as the introduction of VAD and autologous transplantation during the 1980s and bisphosphonates in the 1990s. Although response rates to therapy were increased, overall survival was not significantly improved. In 1999, the treatment of myeloma was revolutionized by the introduction of thalidomide. Subsequently, the development of the immunomodulatory thalidomide analogues and the proteasome inhibitor bortezomib have impacted on response rates to therapy in relapsed and refractory myeloma and are currently being evaluated as primary therapy for myeloma. Early results suggest activity in combination with standard therapy to overcome drug resistance in patients with early stage disease and are changing treatment strategies in multiple myeloma. As an increasing number of other novel therapeutics is identified and mechanisms of resistance are elucidated, combinations of these drugs will be developed to optimize new therapeutic regimens. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Catley, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Mayer 551,44 Binney St, Boston, MA 02115 USA. EM Laurence_Catley@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 NR 136 TC 34 Z9 35 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD AUG PY 2005 VL 8 IS 4 BP 205 EP 218 DI 10.1016/j.drup.2005.06.001 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 983KN UT WOS:000233230400003 PM 16019253 ER PT J AU Xia, Y Sidis, Y Mukherjee, A Samad, TA Brenner, G Woolf, CJ Lin, HY Schneyer, A AF Xia, Y Sidis, Y Mukherjee, A Samad, TA Brenner, G Woolf, CJ Lin, HY Schneyer, A TI Localization and action of dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LIPID RAFTS; DEVELOPMENTAL EXPRESSION; CELL-LINE; RECEPTOR; MOUSE; SPERMATOGENESIS; MEMBRANE; SYSTEM; FAMILY AB Bone morphogenetic proteins (BMPs) play important roles in reproduction including primordial germ cell formation, follicular development, spermatogenesis, and FSH secretion. Dragon, a recently identified glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, is also a BMP coreceptor. In the present study, we determined the tissue and cellular localization of Dragon in reproductive organs using immunohistochemistry and in situ hybridization. Among reproductive organs, Dragon was expressed in testis, epididymis, ovary, uterus, and pituitary. In the testis of early postnatal mice, Dragon was found in gonocytes and spermatogonia, whereas in immature testes, Dragon was only weakly expressed in spermatogonia. Interestingly, pregnant mare serum gonadotropin treatment of immature mice robustly induced Dragon production in spermatocytes. In adult testis, Dragon was found in spermatocytes and round spermatids. In the ovary, Dragon was detected exclusively within oocytes and primarily those within secondary follicles. In the pituitary, Dragon-expressing cells overlapped FSH-expressing cells. Dragon was also expressed in a number of cell lines originating from reproductive tissues including Ishikawa, Hela, L beta T2, MCF-7, and JEG3 cells. Immunocytochemistry and gradient sucrose ultracentrifugation studies showed Dragon was localized in lipid rafts within the plasma membrane. In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4. The present studies demonstrate that Dragon expression is dynamically regulated throughout the reproductive tract and that Dragon protein modulates BMP signaling in cells from reproductive tissues. The overlap between Dragon expression and the functional BMP signaling system suggests that Dragon may play a role in mammalian reproduction. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA. EM Schneyer.alan@mgh.harvard.edu FU NICHD NIH HHS [HD038533, R01 HD039777, HD039777, R01 HD038533]; NIDDK NIH HHS [DK055838, R01 DK055838, R01 DK069533, DK069533, R01 DK071837, DK071837]; NIGMS NIH HHS [GM075267]; NINDS NIH HHS [R01 NS038253, NS038253] NR 36 TC 25 Z9 28 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2005 VL 146 IS 8 BP 3614 EP 3621 DI 10.1210/en.2004-1676 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 944KR UT WOS:000230427400046 PM 15890774 ER PT J AU Morales, KH Ryan, LM AF Morales, KH Ryan, LM TI Benchmark dose estimation based on epidemiologic cohort data SO ENVIRONMETRICS LA English DT Article; Proceedings Paper CT International Conference on Environmental Statistics and Health CY JUL 16-18, 2003 CL Santiago de Compostela, SPAIN SP US Natl Sci Fdn, US EPA, US Natl Ctr Hlth Statist & Ctr Dis Control & Prevent, Spanish Minist Ciecia Tecnol, Spanish Dept Sci Technol DE age-specific incidence; environmental epidemiology; Poisson regression; SMR ID CANCERS; WATER; RISK AB Risk assessments based on epidemiologic studies are becoming increasingly common in evaluating environmental health risks and setting health standards. This article will discuss and compare some of the available methods for exposure-response modeling and risk estimation based on environmental epidemiologic studies with age-specific incidence and mortality data. Recommendations will be made regarding approaches that can be used in practice. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Ryan, LM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM lryan@hsph.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 22 TC 5 Z9 5 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD AUG PY 2005 VL 16 IS 5 SI SI BP 435 EP 447 DI 10.1002/env.713 PG 13 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 945OA UT WOS:000230510600003 ER PT J AU Shiraishi, H Ahlfors, SP Stufflebeam, SM Takano, K Okajima, M Knake, S Hatanaka, K Kohsaka, S Saitoh, S Dale, AM Halgren, E AF Shiraishi, H Ahlfors, SP Stufflebeam, SM Takano, K Okajima, M Knake, S Hatanaka, K Kohsaka, S Saitoh, S Dale, AM Halgren, E TI Application of magnetoencephalography in epilepsy patients with widespread spike or slow-wave activity SO EPILEPSIA LA English DT Article DE MEG; dynamic statistical parametric mapping; generalized spike; slow wave; epilepsy ID SURFACE-BASED ANALYSIS; SPATIOTEMPORAL MAPS; CORTICAL ACTIVITY; BRAIN ACTIVITY; MEG; LOCALIZATION; EEG; RECONSTRUCTION AB Purpose: To examine whether magnetoencephalography (MEG) can be used to determine patterns of brain activity underlying widespread paroxysms of epilepsy patients, thereby extending the applicability of MEG to a larger population of epilepsy patients. Methods: We studied two children with symptomatic localization-related epilepsy. Case 1 had widespread spikes in EEG with an operation scar from a resection of a brain tumor; Case 2 had hemispheric slow-wave activity in EEG with sensory auras. MEG was collected with a 204-channel helmet-shaped sensor array. Dynamic statistical parametric maps ( dSPMs) were constructed to estimate the cortical distribution of interictal discharges for these patients. Equivalent current dipoles (ECDs) also were calculated for comparison with the results of dSPM. Results: In case 1 with widespread spikes, dSPM presented the major activity at the vicinity of the operation scar in the left frontal lobe at the peak of the spikes, and some activities were detected in the left temporal lobe just before the peak in some spikes. In case 2 with hemispheric slow waves, the most active area was located in the left parietal lobe, and additional activity was seen at the ipsilateral temporal and frontal lobes in dSPM. The source estimates correlated well with the ictal manifestation and interictal single-photon emission computed tomography (SPECT) findings for this patient. In comparison with the results of ECDs, ECDs could not express a prior activity at the left temporal lobe in case 1 and did not model well the MEG data in case 2. Conclusions: We suggest that by means of dSPM, MEG is useful for presurgical evaluation of patients, not only with localized epileptiform activity, but also with widespread spikes or slow waves, because it requires no selections of channels and no time-point selection. C1 Hokkaido Univ, Grad Sch Med, Dept Pediat, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA USA. Okayama Univ Sci, Dept Appl Phys, Okayama 700, Japan. RP Shiraishi, H (reprint author), Hokkaido Univ, Grad Sch Med, Dept Pediat, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM siraisi@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Shiraishi, Hideaki/A-8427-2012; Ahlfors, Seppo/P-3644-2016; OI Saitoh, Shinji/0000-0001-6911-3351 FU NINDS NIH HHS [NS18741, R01 NS018741] NR 25 TC 37 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2005 VL 46 IS 8 BP 1264 EP 1272 DI 10.1111/j.1528-1167.2005.65504.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 949DI UT WOS:000230764700015 PM 16060938 ER PT J AU Schwammenthal, E Levine, RA AF Schwammenthal, E Levine, RA TI The non-ischaemic dynamics of ischaemic mitral regurgitation: solving the paradox SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION; EXERCISE-INDUCED CHANGES; SYSTOLIC DYSFUNCTION; ORIFICE AREA; MECHANISM; ANNULOPLASTY; FLOW C1 Tel Aviv Univ, Chaim Sheba Med Ctr, Cardiac Rehabil Inst, IL-52621 Tel Hashomer, Israel. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA USA. RP Schwammenthal, E (reprint author), Tel Aviv Univ, Chaim Sheba Med Ctr, Cardiac Rehabil Inst, IL-52621 Tel Hashomer, Israel. EM sehud@post.tau.ac.il NR 13 TC 8 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2005 VL 26 IS 15 BP 1454 EP 1455 DI 10.1093/eurheartj/ehi189 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 952ZX UT WOS:000231046200002 PM 15917274 ER PT J AU Calon, F Lim, GP Morihara, T Yang, FS Ubeda, O Salem, N Frautschy, SA Cole, GM AF Calon, F Lim, GP Morihara, T Yang, FS Ubeda, O Salem, N Frautschy, SA Cole, GM TI Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; DOCOSAHEXAENOIC ACID; LIPID-PEROXIDATION; NEURODEGENERATIVE DISORDERS; NEUROFIBRILLARY TANGLES; PRECURSOR PROTEIN; OXIDATIVE STRESS; BETA-PEPTIDE; APOPTOSIS; DEMENTIA AB Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca(2+)/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85 alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res,NIH, Rockville, MD 20852 USA. RP Cole, GM (reprint author), Vet Adm Med Ctr, Greater Los Angeles Healthcare Syst, 16111 Plummer St,Bldg 7,Room A102, North Hills, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [R01 AT003008]; NIA NIH HHS [AG10685, AG13471, AG16793, P50 AG016570, R01 AG010685, R01 AG013741]; NINDS NIH HHS [NS43946] NR 84 TC 143 Z9 154 U1 1 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2005 VL 22 IS 3 BP 617 EP 626 DI 10.1111/j.1460-9568.2005.04253.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 954IE UT WOS:000231147700008 PM 16101743 ER PT J AU von Campenhausen, S Bornschein, B Wick, R Botzel, K Sampaio, C Poewe, W Oertel, W Siebert, U Berger, K Dodel, R AF von Campenhausen, S Bornschein, B Wick, R Botzel, K Sampaio, C Poewe, W Oertel, W Siebert, U Berger, K Dodel, R TI Prevalence and incidence of Parkinson's disease in Europe SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Parkinson disease; epidemiology; prevalence; incidence; cost, Europe ID DOOR-TO-DOOR; 3 ELDERLY POPULATIONS; CENTRAL SPAIN; NEUROLOGICAL DISORDERS; ANTIPARKINSONIAN DRUGS; DIAGNOSTIC-CRITERIA; UNITED-KINGDOM; EPIDEMIOLOGY; ASCERTAINMENT; CONSUMPTION AB Objective: To provide an overview on the prevalence and incidence of Parkinson's disease (PD) in selected European countries. Background: PD is a common disease of unknown etiology. Accurate information on the epidemiology of PD is critical to inform health policy. An aging population will lead to more patients with PD; thus, the high financial burden PD places on society will increase. Material and methods: A systematic literature search was performed to identify studies on the prevalence and incidence of PD in the following European countries: Austria, the Czech Republic, France, Germany, Italy, The Netherlands, Portugal, Spain, Sweden and United Kingdom. Only published studies were included. Abstracts, reviews, meta-analyses and letters to the editor were excluded. There were no language restrictions. Data were extracted using a standardized assessment form, and evidence tables were used to systematically report and compare the data. Results: Of 39 identified studies, most (87%) reported estimates of PD prevalence rates, while only a few (13%) reported estimates of PD annual incidence rates. Crude prevalence rate estimates ranged from 65.6 per 100,000 to 12,500 per 100,000 and annual incidence estimates ranged from 5 per 100,000 to 346 per 100,000. No publications could be identified for Austria or the Czech Republic. Discussion and conclusion: The observed variations in prevalence and incidence rates may result from environmental or genetic factors, but might also be a consequence of differences in methodologies for case ascertainment, diagnostic criteria, or age distributions of the study populations. The comparability of existing studies is limited. (c) 2005 Elsevier B.V and ECNP. All rights reserved. C1 Univ Bonn, Dept Neurol, D-53127 Bonn, Germany. Univ Marburg, Dept Neurol, Marburg, Germany. Univ Lisbon, Dept Neurol, P-1699 Lisbon, Portugal. Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. Univ Munich, Dept Neurol, D-8000 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Dodel, R (reprint author), Univ Bonn, Dept Neurol, Sigmund Freud Str 25, D-53127 Bonn, Germany. EM richard.dodel@ukb.uni-bonn.de NR 64 TC 185 Z9 189 U1 4 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2005 VL 15 IS 4 BP 473 EP 490 DI 10.1016/j.euroneuro.2005.04.007 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 951QM UT WOS:000230945600012 PM 15963700 ER PT J AU Bono, P Cordero, E Johnson, K Borowsky, M Ramesh, V Jacks, T Hynes, RO AF Bono, P Cordero, E Johnson, K Borowsky, M Ramesh, V Jacks, T Hynes, RO TI Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE layilin; talin; merlin; radixin; ERM proteins; hyaluronan receptor; ruffles ID NF2 TUMOR-SUPPRESSOR; CORTICAL ACTIN ORGANIZATION; C-TERMINAL DOMAIN; ERM PROTEINS; GENE-PRODUCT; DROSOPHILA HOMOLOGS; APICAL MICROVILLI; MEMBRANE RUFFLES; T-LYMPHOCYTES; MARGINAL BAND AB Layilin is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. We have identified merlin, the neurofibromatosis type 2 tumor suppressor protein and radixin, as other interactors with the carboxy-terminal domain of layilin. We show that the carboxy-terminal domain of layilin is capable of binding to the amino-terminal domain of radixin. An interdomain interaction between the amino- and the carboxy-terminal domains of radixin inhibits its ability to bind to layilin. In the presence of acidic phospholipids, the interdomain interaction of radixin is inhibited and layilin can bind to full-length radixin. In contrast, layilin binds both full-length and amino-terminal merlin-GST fusion proteins without a requirement for phospholipids. Furthennore, layilin antibody can immunoprecipitate merlin, confirming association in vivo between these two proteins, which also display similar subcellular localizations in ruffling membranes. No interaction was observed between layilin and ezrin or layilin and moesin. These findings expand the known binding partners of layilin to include other members of the talin/band 4.1/EPM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. This in turn suggests that layilin may mediate signals from extracellular matrix to the cell cytoskeleton via interaction with different intracellular binding partners and thereby be involved in the modulation of cortical structures in the cell. (c) 2005 Published by Elsevier Inc. C1 MIT, Howard Hughes Med Inst, Canc Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Hynes, RO (reprint author), MIT, Howard Hughes Med Inst, Canc Res Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rohynes@mit.edu FU NCI NIH HHS [R01CA17007] NR 60 TC 22 Z9 28 U1 2 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 2005 VL 308 IS 1 BP 177 EP 187 DI 10.1016/j.yexcr.2005.04.017 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 948FV UT WOS:000230702300016 PM 15913605 ER PT J AU Koh, S Santos, TC Cole, AJ AF Koh, S Santos, TC Cole, AJ TI Susceptibility to seizure-induced injury and acquired microencephaly following intraventricular injection of saporin-conjugated 192 IgG in developing rat brain SO EXPERIMENTAL NEUROLOGY LA English DT Article DE p75(NTR); neurotrophins; microcephaly; epilepsy; neonatal; kainate ID NERVE GROWTH-FACTOR; FOREBRAIN CHOLINERGIC NEURONS; TEMPORAL-LOBE EPILEPSY; INDUCED MEMORY IMPAIRMENT; KAINIC ACID SEIZURES; FACTOR MESSENGER-RNA; BASAL FOREBRAIN; NEUROTROPHIC FACTOR; DEVELOPMENTAL NEUROTOXICITY; SIGNAL-TRANSDUCTION AB To study the role of neurotrophin-responsive neurons in brain growth and developmental resistance to seizure-induced injury, we infused saporin-conjugated 192-IgG (192 IgG-saporin), a monoclonal antibody directed at the P75 neurotrophin receptors (p75(NTR)), into the ventricles of postnatal day 8 (P8) rat pups. 7-10 days after immunotoxin treatment, loss of p75(NTR) immunoreactivity was associated with depletion of basal forebrain cholinergic projection to the neocortex and hippocampus. Kainic acid (KA)-induced seizures on P15 resulted in hippocampal neuronal injury in the majority of toxin-treated animals (13/16), but only rarely in saline-injected controls (2/25) (P < 0.001). In addition, widespread cerebral atrophy and a significant decrease in brain weight with preserved body weight were observed. Volumetric analysis of the hippocampal hilar region revealed a 2-fold reduction in perikaryal size and a 1.7-fold increase in cell packing density after 192 IgG-sapotin injection. These observations indicate that neurotrophin-responsive neurons including basal forebrain magnocellular cholinergic neurons may be critical for normal brain growth and play a protective role in preventing excitotoxic neuronal injury during development. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MGH Epiepsy Serv, Epiepsy Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epiepsy Serv, Epiepsy Res Lab, VBK 830,55 Fruit St, Boston, MA 02114 USA. EM Cole.Andrew@MGH.Harvard.edu FU NINDS NIH HHS [K08 NS002068, K08 NS02068, NS036224] NR 79 TC 9 Z9 9 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 2005 VL 194 IS 2 BP 457 EP 466 DI 10.1016/j.expneurol.2005.03.002 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 950RW UT WOS:000230876100014 PM 16022871 ER PT J AU Reid, DC Kimball, AB AF Reid, DC Kimball, AB TI Clobetasol propionate foam in the treatment of psoriasis SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE clinical trials; clobetasol foam; compliance; psoriasis; quality of life; steroid vehicle ID QUALITY-OF-LIFE; ADRENAL SUPPRESSION; VEHICLE PREFERENCE; ENHANCED DELIVERY; 0.05-PERCENT FOAM; EFFICACY; BIOAVAILABILITY; CORTICOSTEROIDS; EPIDEMIOLOGY; MEDICATION AB Psoriasis is a common, chronic, distressing skin disorder that frequently affects the scalp, skin, nails and joints. Despite treatment, many patients suffer from unremitting disease and decreased quality of life. Scalp-type psoriasis is particularly difficult to treat. Although topical corticosteroids are the mainstay of therapy for moderate-to-severe disease, patients frequently object to the messiness and unfavourable cosmetic appearance of topical treatments. In this context, foam vehicles, which have the advantage of minimal residue and increased ease of application, have emerged as novel alternatives to traditional creams, ointments and solutions. Clobetasol propionate foam 0.05% (OLUX (TM), Connetics Corporation), a high potency topical steroid, has been shown to alleviate symptoms of several dermatological conditions, including scalp and body psoriasis, improve disease severity and increase quality of life. Dose should be limited to 50 g/week, given the risk of adrenal suppression. Because patient preference is an important determinant of medication efficacy in clinical practice, clobetasol foam is a useful new formulation in the treatment of psoriasis and other skin conditions. C1 Harvard Univ, Massachusetts Gen Hosp, Med Sch, Clin Unit Res Trials Skin, Cambridge, MA 02138 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Med Sch, Clin Unit Res Trials Skin, Prof Off Bldg,405, Cambridge, MA 02138 USA. EM akimball@partners.org NR 30 TC 11 Z9 12 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD AUG PY 2005 VL 6 IS 10 BP 1735 EP 1740 DI 10.1517/14656566.6.10.1735 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957AB UT WOS:000231340400010 PM 16086659 ER PT J AU Hopfer, U Fukai, N Hopfer, H Wolf, G Joyce, N Li, E Olsen, BR AF Hopfer, U Fukai, N Hopfer, H Wolf, G Joyce, N Li, E Olsen, BR TI Targeted disruption of Col8a1 and Col8a2 genes in mice leads to anterior segment abnormalities in the eye SO FASEB JOURNAL LA English DT Article DE type VIII collagen; corneal endothelial cells; proliferation ID POSTERIOR POLYMORPHOUS DYSTROPHY; SHORT-CHAIN COLLAGEN; ENDOTHELIAL-CELL-PROLIFERATION; EPIDERMAL GROWTH-FACTOR; TRIPLE-HELICAL DOMAINS; SMOOTH-MUSCLE-CELLS; VIII COLLAGEN; CORNEAL ENDOTHELIUM; DESCEMETS-MEMBRANE; DIFFERENTIAL EXPRESSION AB Collagen VIII is localized in subendothelial and subepithelial extracellular matrices. It is a major component of Descemet's membrane, a thick basement membrane under the corneal endothelium, where it forms a hexagonal lattice structure; a similar structure, albeit less extensive, may be formed in other basement membranes. We have examined the function of collagen VIII in mice by targeted inactivation of the genes encoding the two polypeptide subunits, Co18a1 and Co18a2. Analysis of these mice reveals no major structural defects in most organs, but demonstrates that type VIII collagen is required for normal anterior eye development, particularly the formation of a corneal stroma with the appropriate number of fibroblastic cell layers and Descemet's membrane of appropriate thickness. Complete lack of type VIII collagen leads to dysgenesis of the anterior segment of the eye: a globoid, keratoglobus- like protrusion of the anterior chamber with a thin corneal stroma. Descemet's membrane is markedly thinned. The corneal endothelial cells are enlarged and reduced in number, and show a decreased ability to proliferate in response to different growth factors in vitro. An important function of collagen VIII may therefore be to generate a peri- or subcellular matrix environment that permits or stimulates cell proliferation. C1 Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Univ Hamburg, Dept Pathol, Hamburg, Germany. Univ Hamburg, Dept Med, Hamburg, Germany. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Div, Boston, MA 02114 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM bjorn_olsen@hms.harvard.edu FU NIAMS NIH HHS [AR36819, AR36820] NR 62 TC 54 Z9 54 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2005 VL 19 IS 10 BP 1232 EP 1244 DI 10.1096/fj.04-3019com PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 963YW UT WOS:000231843700030 PM 16051690 ER PT J AU Sangeorzan, BJ Beskin, JL Britt, SM Brage, M Holt, S Kadel, NJ Legro, MW Sands, AK SooHoo, NF Stroud, CC AF Sangeorzan, BJ Beskin, JL Britt, SM Brage, M Holt, S Kadel, NJ Legro, MW Sands, AK SooHoo, NF Stroud, CC TI Issues of importance to patients seeking care from members of the AOFAS: A preliminary report of the outcomes committee of the AOFAS SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE AOFAS members; outcomes ID OSTEOARTHRITIS; QUALITY; TRIALS; ANKLE; WANT AB Background. The purpose of this multi-center study was to examine the outcomes of importance for patients seeking treatment for foot and ankle disorders. An improved understanding of patient outcome preferences will assist surgeons in improving patient satisfaction. Methods: An open-ended priority function questionnaire was administered to 235 patients presenting as new patients to five different outpatient locations. The questionnaire was designed to identify activities of importance to patients and was based on the McMaster Toronto Arthritis (MACTAR) patient preference disability questionnaire. Subjects were asked to list the specific activities that were limited by their condition. Open-ended answers were written on five blank spaces and then ranked as to their importance. The visual analog pain scale was recorded as a measure of the severity of the patient's symptoms at the time the response was made. The outpatient settings were two university hospitals, two private offices with academic affiliation, and one private office. Two hundred thirty-five surveys were collected between September and November of 2000; 227 surveys were acceptable for analysis. The respondents included 132 females (58.1%), 94 males (41.4%) and one patient who did not specify his gender (0.4%). The mean age was 45.8 (range 18 to 83) years. Results: Average pain at the time of assessment was 2.7 on a scale of 0 to 9 and was reported to increase to 4.8 in a typical day. The most frequently ranked limitations were difficulty with walking (1159), running (73), standing (55), and exercise (54). Walking also was the issue ranked as the highest priority (77 of 159), while running (111 of 73), standing (110 of 55) and exercise (3 of 54) were assigned lesser priority values. Only 68 of 227 respondents failed to list walking as an issue. Work, sleep, and social activities were not commonly cited as issues of importance. Conclusion: Patients presenting to off ice practices identified as specializing in foot and ankle disorders are predominantly middle-aged women in mild to moderate pain. Walking is the function most frequently identified as a problem and ranked as the highest priority for improvement. Social limitations were unlikely to be named as a limitation in this population. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98109 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. Peachtree Orthopaed Clin, Atlanta, GA USA. Univ Calif San Diego, San Diego, CA 92103 USA. St Vincents Med Ctr, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Orthopaed & Spine Surg Troy, Troy, MI USA. RP Britt, SM (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,MS 151, Seattle, WA 98109 USA. EM sarah.britt@med.va.gov NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD AUG PY 2005 VL 26 IS 8 BP 638 EP 644 PG 7 WC Orthopedics SC Orthopedics GA 949SI UT WOS:000230808000012 PM 16115422 ER PT J AU Satoh, A Gukovskaya, AS Edderkaoui, M Daghighian, MS Reeve, JR Shimosegawa, T Pandol, SJ AF Satoh, A Gukovskaya, AS Edderkaoui, M Daghighian, MS Reeve, JR Shimosegawa, T Pandol, SJ TI Tumor necrosis factor-alpha mediates pancreatitis responses in acinar cells via protein kinase C and proline-rich tyrosine kinase 2 SO GASTROENTEROLOGY LA English DT Article ID KAPPA-B ACTIVATION; INDUCED APOPTOSIS; HUMAN NEUTROPHILS; PKC-DELTA; IN-VIVO; CHOLECYSTOKININ; PYK2; CYTOSKELETON; RAT; SRC AB Background & Aims: Although tumor necrosis factor alpha is implicated as an important mediator of the inflammatory response in acute pancreatitis, its role in other pathologic features of the disease remains unknown. We investigated the role for tumor necrosis factor alpha in cytoskeletal responses and the underlying signaling mechanisms in pancreatic acinar cells. Methods: In isolated rat pancreatic acini and AR42J cells, we determined the effect of tumor necrosis factor (x on the actin cytoskeleton by rhodamine-phalloidin. Using pharmacological and molecular approaches, we assessed the involvement of protein kinase C, Src kinases, and proline-rich tyrosine kinase 2 in the process. We also studied the involvement of these signaling pathways in tumor necrosis factor-alpha-induced nuclear factor-kappa B activation and apoptosis. Results: Tumor necrosis factor-alpha increased the tyrosine phosphorylation of proline-rich tyrosine kinase 2 in acinar cells. The broad-spectrum protein kinase C inhibitor and the Src kinase inhibitor both inhibited tumor necrosis factor-alpha-induced proline-rich tyrosine kinase 2 phosphorylation, but at different tyrosine residues. Using protein kinase C isoform-specific inhibitors and the antisense approach, we showed that protein kinase C delta and epsilon mediate proline-rich tyrosine kinase 2 tyrosine phosphorylation. Tumor necrosis factor-alpha caused disorganization of the actin cytoskeleton by a mechanism dependent on protein kinase C, Src kinases, and proline-rich tyrosine kinase 2. Inhibition of protein kinase C, but not Src kinases, decreased tumor necrosis factor-alpha-induced apoptosis. Furthermore, with antisense transfections, we showed that protein kinase C delta and epsilon, but not proline-rich tyrosine kinase 2, mediate tumor necrosis factor alpha-induced nuclear factor-kappa B activation. Conclusions: Tumor necrosis factor-alpha activates proline-rich tyrosine kinase 2 to cause cytoskeletal disorganization and nuclear factor-kappa B to cause inflammatory response, and it triggers cell death signaling through divergent mechanisms mediated by protein kinase C. The results provide insights into the mechanisms in pancreatic acinar cells that link tumor necrosis factor alpha to critical processes in acute pancreatitis. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, W Los Angeles Healthcare Ctr, Bldg 258,Room 340,11301 Willshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIAAA NIH HHS [1 U56 AA 0114643]; NIDDK NIH HHS [DK-59508]; PHS HHS [P50-A11999] NR 51 TC 34 Z9 37 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2005 VL 129 IS 2 BP 639 EP 651 DI 10.1053/j.gastro.2005.05.005 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 953IU UT WOS:000231070600025 PM 16083718 ER PT J AU Baden, HP Champliaud, MF Sundberg, JP Viel, A AF Baden, HP Champliaud, MF Sundberg, JP Viel, A TI Targeted deletion of the sciellin gene resulted in normal development and maturation SO GENESIS LA English DT Article DE cornified envelope; sciellin; targeted deletion ID CORNIFIED CELL-ENVELOPE; KERATIN INTERMEDIATE-FILAMENTS; EPIDERMAL PERMEABILITY BARRIER; STRATUM-CORNEUM; TRANSGENIC MICE; CULTURED KERATINOCYTES; STRUCTURAL PROTEINS; HUMAN LORICRIN; CROSS-LINKING; LIM DOMAIN AB Sciellin, together with other precursor proteins, was cross-linked by transglutaminase I to form the cornified envelope, an essential component of the physical barrier of the epidermis and stratified squamous epithelia. To more fully understand the function of sciellin in cornified envelope formation, we generated sciellin null mice. The mice appeared normal in their development and maturation and there were no structural features that distinguished them from littermate controls. Isolated cornified envelopes appeared normal in structure and were not more fragile to mechanical stress. There was no evidence of decreased barrier function or altered expression of other cornified envelope components. Transgenic mice expressing the repeat domain appeared to have a normal phenotype, like the null, and did not alter endogenous sciellin expression. We conclude that sciellin null mice had no structural anomalies and the transgenic mice did not act as a dominant-negative mutation. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp,Dept Dermatol, Charlestown, MA 02129 USA. Univ Strasbourg 1, Lab Physiopathol Cellulaire & Mol Retine, Strasbourg, France. Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Baden, HP (reprint author), Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp,Dept Dermatol, 13th St Bldg 149, Charlestown, MA 02129 USA. EM hbaden@partners.org FU NCRR NIH HHS [RR 173] NR 50 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD AUG PY 2005 VL 42 IS 4 BP 219 EP 228 DI 10.1002/gene.20133 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 957DE UT WOS:000231348900001 PM 16028229 ER PT J AU Kwong, KY Bloom, GC Yang, I Boulware, D Coppola, D Haseman, J Chen, E McGrath, A Makusky, AJ Taylor, J Steiner, S Zhou, J Yeatman, TJ Quackenbush, J AF Kwong, KY Bloom, GC Yang, I Boulware, D Coppola, D Haseman, J Chen, E McGrath, A Makusky, AJ Taylor, J Steiner, S Zhou, J Yeatman, TJ Quackenbush, J TI Synchronous global assessment of gene and protein expression in colorectal cancer progression SO GENOMICS LA English DT Article ID TWO-DIMENSIONAL ELECTROPHORESIS; MESSENGER-RNA; SKELETAL-MUSCLE; TUMOR-INDUCTION; COLON-CANCER; MICE; IDENTIFICATION; MICROARRAY; CAVEOLIN-1; CARCINOMA AB Well-established models of colorectal cancer progression are based on the idea that the disease evolves through a multistep process involving sequential genetic mutations, suggesting that progression through clinically defined stages should correlate with well-defined patterns of gene expression. The majority of studies to date, however, have assessed these processes one gene and one protein at a time. We report the first comprehensive assessment of both gene and protein expression performed in parallel across progressive stages of human colorectal neoplasia. Remarkably, despite the global nature of the gene expression assessment, very few genes could be linked with certainty to specific proteins through currently available annotations. Furthermore, the correlation of expression between identified genes and proteins was poor. Nevertheless, both produced expression signatures that differentiated normal mucosa and nonmalignant adenomas from each other and from the malignant carcinomas and both produced fairly consistent subclasses of the malignancies, suggesting that a molecular staging might be more appropriate provided that these profiles can be tied to clinical outcome. This is potentially important as clinical staging is widely used as a prognostic indicator and used in the decision to pursue adjuvant therapies. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Dept Surg & Interdisciplinary Onocl, Tampa, FL 33612 USA. Inst Genom Res, Rockville, MD 20850 USA. Large Scale Biol Corp, Germantown, MD USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Yeatman, TJ (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Dept Surg & Interdisciplinary Onocl, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Yeatman@moffitt.usf.edu; johnq@jimmy.harvard.edu NR 44 TC 41 Z9 43 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 2005 VL 86 IS 2 BP 142 EP 158 DI 10.1016/j.ygeno.2005.03.012 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 947QU UT WOS:000230662000003 PM 15951154 ER PT J AU Clemmons, DR Moses, AC Sommer, A Jacobson, W Rogol, AD Sleevi, MR Allan, G AF Clemmons, DR Moses, AC Sommer, A Jacobson, W Rogol, AD Sleevi, MR Allan, G TI Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE insulin sensitivity obesity; pharmacokinetics; insulin action ID GROWTH-FACTOR-I; IGF-BINDING PROTEIN-3; DUAL HORMONAL REPLACEMENT; GLYCEMIC CONTROL; FACTOR (IGF)-I; THERAPY; ADULTS; RESISTANCE; SERUM; HUMANS AB Administration of insulin-like growth factor-I to patients with diabetes enhances insulin action and reduces the degree of hyperglycemia but it is associated with a high rate of adverse events. Infusion of the combination of rhiGFBP-3 (the principal binding protein for IGF-I in plasma) with rhIGF-I to patients with type I diabetes improved insulin sensitivity and was associated with a low incidence in side effects. In this study, 52 patients with insulin-treated type 2 diabetes received recombinant human IGF-I plus rhIGFBP-3 in one of four dosage regimens for 14 days. The four groups were: (1) continuous subcutaneous infusion of 2 mg/kg/day; (2) the same 2 mg/kg dose infused subcutaneously over 6 h between 2000 and 0200 h; (3) 1 mg/kg twice a day by bolus subcutaneous injection; (4) a single bedtime subcutaneous injection of I mg/kg. Across these four groups rhlGF-1/rhlGFBP-3 decreased insulin requirements between 54 % and 82 %. Fasting glucose decreased by 32-37 %. Mean daily blood glucose (4 determinations per day) declined in all 4 groups (range 9-23 % decrease). Frequent sampling for total IGF-I, free IGF-I and IGFBP-3 was performed on days 0, 1, 7,14 and 15. The peak total IGF-I values were increased to 4.0-4.8-fold at 16-24 h. For free IGF-I the increase varied between 7.1 and 8.2-fold and peak values were attained at 16-20 h after administration. Both the time to maximum concentration (Tmax) and the maximum free IGF-I levels (Cmax) on day I for all groups were substantially less than previously published studies, wherein lower doses of rhIGF-I were given without IGFBP-3. The improvement in glucose values and the degree of reduction in insulin requirement were the greatest in groups 2 and 3 and the patients in those groups had the highest free IGF-I levels. The frequency of side effects such as edema, jaw pain and arthralgias was 4 % which is less than that has been reported in previous studies wherein IGF-I was administered without IGFBP-3. We conclude that rhlGF-1/rhlGFBP-3 significantly lowers insulin requirements yet improves glucose values and these changes may reflect improvement in insulin sensitivity. Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Dept Med, Div Endocrinol, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Insmed Inc, Glen Allen, VA USA. RP Clemmons, DR (reprint author), Univ N Carolina, Dept Med, Div Endocrinol, 6111A Thurston Bowles,CB 7170, Chapel Hill, NC 27599 USA. EM endo@med.unc.edu NR 37 TC 40 Z9 40 U1 1 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 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD AUG PY 2005 VL 15 IS 4 BP 265 EP 274 DI 10.1016/j.ghir.2005.05.002 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 959BS UT WOS:000231492500004 PM 16005252 ER PT J AU Rao, GG Skinner, EN Gehrig, PA Duska, LR Miller, DS Schorge, JO AF Rao, GG Skinner, EN Gehrig, PA Duska, LR Miller, DS Schorge, JO TI Fertility-sparing surgery for ovarian low malignant potential tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE fertility-sparing surgery; ovarian borderline tumor ID REPRODUCTIVE-AGE WOMEN; BORDERLINE TUMORS; CONSERVATIVE-MANAGEMENT; FROZEN-SECTION; INTESTINAL-TYPE; DIAGNOSIS; ACCURACY; RECURRENCE; CARCINOMA AB Objective. Ovarian low malignant potential (LMP) tumors have an excellent prognosis when treated by surgical resection. Conservative management usually involves leaving behind the uterus and contralateral adnexa to allow future childbearing. The purpose of this study was to determine the outcome of women treated with fertility-sparing surgery. Methods. All patients diagnosed with ovarian LMP tumors between 1984 and 2003 were identified at three institutions. Data were retrospectively extracted from clinical records. Results. Thirty-eight (15%) of 249 women with LMP tumors underwent fertility-sparing surgery. Twenty-three were nulliparous and four primiparous. Thirty-three (87%) underwent unilateral salpingo-ophorectomy and five (13%) cystectomy. Fourteen patients also had contralateral cystectomy or biopsy. Thirty-four (89%) were stage I, one (3%) stage II and three (8%) stage III. Most tumors had serous (55%) or mucinous (42%) histology. No patients received adjuvant therapy. Six (16%) of 38 recurred after a median follow-up of 26 months: five in the remaining ovary were salvaged with surgical resection alone, and none died from recurrent LMP tumor. Five women delivered six term infants during post-treatment surveillance. Conclusion. Fertility-sparing surgery for ovarian LMP tumors is an option for motivated patients. Preservation of the contralateral adnexa increases the risk of recurrence, but surgical resection is usually curative. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schorge, JO (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 5323 Harry Hines Blvd,J7-124, Dallas, TX 75390 USA. EM john.schorge@utsouthwestern.edu RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 20 TC 26 Z9 28 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2005 VL 98 IS 2 BP 263 EP 266 DI 10.1016/j.ygyno.2005.04.025 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 952TP UT WOS:000231028700013 PM 15964063 ER PT J AU Tavakolian, JD Jupiter, JB AF Tavakolian, JD Jupiter, JB TI Dorsal plating for distal radius fractures SO HAND CLINICS LA English DT Article ID DISPLACED INTRAARTICULAR FRACTURES; TITANIUM PI PLATE; INTERNAL-FIXATION; OPEN REDUCTION; END; COMPLICATIONS; MULTICENTER; WRIST AB Dorsal plating of distal radius fractures is the preferred technique for certain fracture patterns. Historically, dorsal plating has reliably supported the radiocarpal joint, leading to low rates of arthrosis at the expense of wrist stiffness and problems with extensor tendons. New, smaller implants may prove capable of buttressing the joint with a lower incidence of extensor irritation. The authors outline the history of dorsal plating, describing early experiences, advances in implant design and application, and the current state of the art. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Union Mem Hosp, Curtis Natl Hand Ctr, Baltimore, MD 21218 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, ACC 525,15 Parkman St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 20 TC 15 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2005 VL 21 IS 3 BP 341 EP + DI 10.1016/j.hcl.2005.02.001 PG 7 WC Orthopedics SC Orthopedics GA 958HB UT WOS:000231434200008 PM 16039445 ER PT J AU Ring, D AF Ring, D TI Nonunion of the distal radius SO HAND CLINICS LA English DT Article ID FRACTURES; OSTEOMYELITIS; DEFORMITY; WRIST AB Nonunion of the distal radius-long considered to be extremely rare-has been noted more frequently in recent years. While some have speculated that the advent of external fixation and other techniques for maintaining the length of the radius has created bony defects that can lead to nonunion, nonunion is also seen after internal fixation or non-operative treatment. While the cause and incidence of nonunion of the distal radius are uncertain, the need for operative treatment is clear. The majority of nonunions are synovial. The wrist is usually deformed, unstable, and painful. Operative treatment can improve upper limb function in patients with nonunion of the distal radius by either fusing the wrist or healing the fracture. Improved implants and operative techniques have improved the ability to gain healing of the fracture, thereby preserving some wrist motion. C1 Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkee Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Yawkee Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkee Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 10 Z9 11 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2005 VL 21 IS 3 BP 443 EP + DI 10.1016/j.hcl.2005.01.005 PG 6 WC Orthopedics SC Orthopedics GA 958HB UT WOS:000231434200018 PM 16039455 ER PT J AU Fung, CH Elliott, MN Hays, RD Kahn, KL Kanouse, DE McGlynn, EA Spranca, MD Shekelle, PG AF Fung, CH Elliott, MN Hays, RD Kahn, KL Kanouse, DE McGlynn, EA Spranca, MD Shekelle, PG TI Patients' preferences for technical versus interpersonal quality when selecting a primary care physician SO HEALTH SERVICES RESEARCH LA English DT Article DE quality; health care; primary care; physician profiling ID PLAN PERFORMANCE INFORMATION; HEALTH-CARE; CONSUMER ASSESSMENT; PSYCHOMETRIC PROPERTIES; DIFFERENCE; PRIORITIES; RATINGS; IMPACT AB Objective. To assess patients' use of and preferences for information about technical and interpersonal quality when using simulated, computerized health care report cards to select a primary care provider (PCP). Data Sources/Study Setting. Primary data collected from 304 adult consumers living in Los Angeles County in January and February 2003. Study Design/Data Collection.We constructed computerized report cards for seven pairs of hypothetical individual PCPs (two internal validity check pairs included). Participants selected the physician that they preferred. A questionnaire collected demographic information and assessed participant attitudes towards different sources of report card information. The relationship between patient characteristics and number of times the participant selected the physician who excelled in technical quality are estimated using an ordered logit model. Principal Findings. Ninety percent of the sample selected the dominant physician for both validity checks, indicating a level of attention to task comparable with prior studies. When presented with pairs of physicians who varied in technical and interpersonal quality, two-thirds of the sample (95 percent CI: 62, 72 percent) chose the physician who was higher in technical quality at least three out of five times (one-sample binomial test of proportion). Age, gender, and ethnicity were not significant predictors of choosing the physician who was higher in technical quality. Conclusions. These participants showed a strong preference for physicians of high technical quality when forced to make tradeoffs, but a substantial proportion of the sample preferred physicians of high interpersonal quality. Individual physician report cards should contain ample information in both domains to be most useful to patients. C1 RAND Corp, Santa Monica, CA 90407 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Fung, CH (reprint author), RAND Corp, 1776 Main St,M5N, Santa Monica, CA 90407 USA. RI Hays, Ronald/D-5629-2013 NR 43 TC 51 Z9 51 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2005 VL 40 IS 4 BP 957 EP 977 DI 10.1111/j.1475-6773.2005.00395.x PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 942OT UT WOS:000230292400002 PM 16033487 ER PT J AU Volpp, KGM Ketcham, JD Epstein, AJ Williams, SV AF Volpp, KGM Ketcham, JD Epstein, AJ Williams, SV TI The effects of price competition and reduced subsidies for uncompensated care on hospital mortality SO HEALTH SERVICES RESEARCH LA English DT Article DE quality of health care; health care markets; hospital competition; mortality ID MARKET-STRUCTURE; MANAGED CARE; NEW-JERSEY; COST; QUALITY; PROGRAM AB Objective. To determine whether hospital mortality rates changed in New Jersey after implementation of a law that changed hospital payment from a regulated system based on hospital cost to price competition with reduced subsidies for uncompensated care and whether changes in mortality rates were affected by hospital market conditions. Data Source/Study Setting. State discharge data for New Jersey and New York from 1990 to 1996. Study Design. We used an interrupted time series design to compare risk-adjusted in-hospital mortality rates between states over time. We compared the effect sizes in markets with different levels of health maintenance organization penetration and hospital market concentration and tested the sensitivity of our results to different approaches to defining hospital markets. Data Collection/Extraction Methods. The study sample included all patients under age 65 admitted to New Jersey or New York hospitals with stroke, hip fracture, pneumonia, pulmonary embolism, congestive heart failure, hip fracture, or acute myocardial infarction (AMI). Principal Findings. Mortality among patients in New Jersey improved less than in New York by 0.4 percentage points among the insured (p=.07) and 0.5 percentage points among the uninsured (p=.37). There was a relative increase in mortality for patients with AMI, congestive heart failure, and stroke, especially for uninsured patients with these conditions, but not for patients with the other four conditions we studied. Less competitive hospital markets were significantly associated with a relative decrease in mortality among insured patients. Conclusions. Market-based reforms may adversely affect mortality for some conditions but it appears the effects are not universal. Insured patients in less competitive markets fared better in the transition to price competition. C1 Philadelphia Vet Affairs Med Ctr Univ & Woodlands, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Arizona State Univ, Casey Sch Business, Tempe, AZ 85287 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Volpp, KGM (reprint author), Philadelphia Vet Affairs Med Ctr Univ & Woodlands, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. NR 38 TC 16 Z9 16 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2005 VL 40 IS 4 BP 1056 EP 1077 DI 10.1111/j.1475-6773.2005.00396.x PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 942OT UT WOS:000230292400007 PM 16033492 ER PT J AU Mims, MP Prchal, JT AF Mims, MP Prchal, JT TI Divalent metal transporter 1 SO HEMATOLOGY LA English DT Article DE iron metabolism; microcytic anemia; alternative splicing; tissue specific mRNA processing; Nramp2 ID DUODENAL IRON TRANSPORTERS; BELGRADE B RAT; MICROCYTIC ANEMIA; HEREDITARY HEMOCHROMATOSIS; SUBCELLULAR-LOCALIZATION; DEPENDENT REGULATION; MEDIATED REGULATION; DMT1 NRAMP2/DCT1; ERYTHROID-CELLS; ION TRANSPORTER AB In the last few years, the field of iron metabolism has exploded with the discovery of many new proteins including ferroportin, hephaestin, hepcidin, duodenal cytochrome b and the topic of this review, divalent metal ion transporter 1 (DMT1). DMT1 fimctions in transport of ferrous iron, and some, but not all divalent metal ions across the plasma membrane and/or out of the endosomal compartment. DMT1 mRNA has been found in every cell type in which it has been sought and its structure is highly conserved in evolution with similar proteins expressed in plants, insects, microorganisms and vertebrate animals. Rodents with defects in iron absorption and utilization were identified long before it was determined that the defect was due to a single nucleotide mutation in DMT1. Study of these animals reveals that transport of iron and other divalent metal ions by DMT1 is pH dependent, but the exact manner in which pH exerts its effect is unknown. The structure of the DMT1 gene is complex. Alternative usage of 3' exons, results in forms with and without iron responsive elements (IREs), while alternative usage of 5' exons and less well defined products of alternative splicing results in an array of isoforms with incompletely defined function. Expression of some isoforms is tissue specific and appears to affect subcellular targeting of the protein. At least one signal for DMT1 expression appears to be intracellular iron status,, however, other, as yet undefined signals may also contribute to DMT1 expression. Interestingly, DMT1 function may differ subtly between humans and other animals; the spontaneous DMT1 mutation found in mice and rats appears to limit iron uptake in the intestine and iron utilization in red cell precursors, whereas the only known human mutation has its primary effect on iron utilization by erythroid cells. The importance of DMT1 function at the level of the whole organism and the individual cell and mechanisms of its regulation on a molecular scale are only beginning to be understood; an appreciation of these process will lead to an understanding of the role of iron in various cellular processes and improved treatments for both anemia and iron-overload. C1 Baylor Coll Med, Dept Med, Div Hematol Oncol, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. RP Mims, MP (reprint author), Baylor Coll Med, Dept Med, Div Hematol Oncol, 1 Baylor Plaza Room 802E, Houston, TX 77030 USA. EM mmims@bcm.tmc.edu FU NHLBI NIH HHS [R01 HL 50077-11] NR 61 TC 60 Z9 62 U1 2 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1024-5332 J9 HEMATOLOGY JI Hematology PD AUG PY 2005 VL 10 IS 4 BP 339 EP 345 DI 10.1080/10245330500093419 PG 7 WC Hematology SC Hematology GA 956KO UT WOS:000231298800012 PM 16085548 ER PT J AU Fitzsimmons, A Upchurch, K Batchelor, T AF Fitzsimmons, A Upchurch, K Batchelor, T TI Clinical features and diagnosis of primary central nervous system lymphoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY CNS LYMPHOMA; POLYMERASE-CHAIN-REACTION; STEREOTAXIC BRAIN BIOPSY; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CEREBROSPINAL-FLUID CELLS; AIDS PATIENTS; B-CELL; IMMUNOCYTOCHEMICAL ANALYSIS AB This article reviews the clinical features of primary central nervous system lymphoma (PCNSL) in immunocompetent and immunocompromised patients. Clinical presentation, differential diagnosis, diagnostic testing, and staging evaluation in both immunocompetent and AIDS patients who have PCNSL are discussed. The differing role of biopsy in these two populations also is addressed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Batchelor, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 70 TC 19 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2005 VL 19 IS 4 BP 689 EP + DI 10.1016/j.hoc.2005.05.009 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 959BL UT WOS:000231491800007 PM 16083830 ER PT J AU Lok, ASF Ghany, MG Goodman, ZD Wright, EC Everson, GT Sterling, RK Everhart, JE Lindsay, KL Bonkovsky, HL Di Bisceglie, AM Lee, WM Morgan, TR Dienstag, JL Morishima, C AF Lok, ASF Ghany, MG Goodman, ZD Wright, EC Everson, GT Sterling, RK Everhart, JE Lindsay, KL Bonkovsky, HL Di Bisceglie, AM Lee, WM Morgan, TR Dienstag, JL Morishima, C CA HALT-C Trial Grp TI Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: Results of the HALT-C cohort SO HEPATOLOGY LA English DT Article ID LIVER FIBROSIS; VIRUS-INFECTION; ASPARTATE-AMINOTRANSFERASE; BIOCHEMICAL MARKERS; AST/ALT RATIO; VALIDATION; BIOPSY; COMPLICATIONS; RIBAVIRIN; MODEL AB Knowledge of the presence of cirrhosis is important for the management of patients with chronic hepatitis C (CHC). Most models for predicting cirrhosis were derived from small numbers of patients and included subjective variables or laboratory tests that are not readily available. The aim of this study was to develop a predictive model of cirrhosis in patients with CHC based on standard laboratory tests. Data from 1,141 CHC patients including 429 with cirrhosis were analyzed. All biopsies were read by a panel of pathologists (blinded to clinical features), and fibrosis stage was determined by consensus. The cohort was divided into a training set (n = 783) and a validation set (n = 358). Variables that were significantly different between patients with and without cirrhosis in univariate analysis were entered into logistic regression models, and the performance of each model was compared. The area under the receiver-operating characteristic curve of the final model comprising platelet count, AST/ALT ratio, and INR in the training and validation sets was 0.78 and 0.81, respectively. A cutoff of less than 0.2 to exclude cirrhosis would misclassify only 7.8 % of patients with cirrhosis, while a cutoff of greater than 0.5 to confirm cirrhosis would misclassify 14.8 % of patients without cirrhosis. The model performed equally well in fragmented and nonfragmented biopsies and in biopsies of varying lengths. Use of this model might obviate the requirement for a liver biopsy in 50 % of patients with CHC. In conclusion, a model based on standard laboratory test results can be used to predict histological cirrhosis with a high degree of accuracy in 50 % of patients with CHC. C1 Univ Michigan, Med Ctr, Div Gastroenterol, Taubman Ctr 3912, Ann Arbor, MI 48109 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Vet Adm Special Reference Lab Pathol, Washington, DC 20306 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. Virginia Commonwealth Univ, Hlth Syst, Div Gastroenterol Hepatol & Nutr, Hepatol Sect, Richmond, VA USA. Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Gen Clin Res Ctr, Farmington, CT USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Lok, ASF (reprint author), Univ Michigan, Med Ctr, Div Gastroenterol, Taubman Ctr 3912, Ann Arbor, MI 48109 USA. EM aslok@umich.edu RI Lok, Anna /B-8292-2009 FU NCRR NIH HHS [M01 RR 00042, M01 RR 00043, M01 RR 00051, M01 RR 00065, M01 RR 00633, M01 RR 00827, M01 RR 01066, M01 RR 06192]; NIDDK NIH HHS [N01 DK 92320, N01 DK 92318, N01 DK 92319, N01 DK 92321, N01 DK 92322, N01 DK 92323, N01 DK 92324, N01 DK 92325, N01 DK 92326, N01 DK 92327, N01 DK 92328] NR 37 TC 167 Z9 178 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2005 VL 42 IS 2 BP 282 EP 292 DI 10.1002/hep.20772 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 950NU UT WOS:000230864900007 PM 15986415 ER PT J AU Fisher, SA Abecasis, GR Yashar, BM Zareparsi, S Swaroop, A Iyengar, SK Klein, BEK Klein, R Lee, KE Majewski, J Schultz, DW Klein, ML Seddon, JM Santangelo, SL Weeks, DE Conley, YP Mah, TS Schmidt, S Haines, JL Pericak-Vance, MA Gorin, MB Schulz, HL Pardi, F Lewis, CM Weber, BHF AF Fisher, SA Abecasis, GR Yashar, BM Zareparsi, S Swaroop, A Iyengar, SK Klein, BEK Klein, R Lee, KE Majewski, J Schultz, DW Klein, ML Seddon, JM Santangelo, SL Weeks, DE Conley, YP Mah, TS Schmidt, S Haines, JL Pericak-Vance, MA Gorin, MB Schulz, HL Pardi, F Lewis, CM Weber, BHF TI Meta-analysis of genome scans of age-related macular degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID BEAVER DAM EYE; STARGARDT-DISEASE GENE; COMPLEX HUMAN-DISEASES; SUSCEPTIBILITY LOCI; FAMILIAL AGGREGATION; LINKAGE ANALYSIS; EXTENDED FAMILIES; BIPOLAR DISORDER; OXIDATIVE STRESS; APOLIPOPROTEIN-E AB A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies. Results from non-parametric analysis for a broad AMD clinical phenotype (including two studies with quantitative traits) were extracted. For each study, 120 genomic bins of similar to 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted according to study size and summed across all studies; the summed rank (SR) for each bin was assessed empirically for significance using permutation methods. A high SR indicates a region with consistent evidence for linkage across studies. The strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 where genome-wide significant linkage was observed (P=0.00025). Several other regions met the empirical significance criteria for bins likely to contain linked loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several of the regions identified here showed only weak evidence for linkage in the individual studies. These results will help prioritize regions for future positional and functional candidate gene studies in AMD. C1 Univ London Kings Coll, Guys Kings & St Thomas Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Dept Ophthalmol, Portland, OR USA. Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Ophthalmol Epidemiol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15261 USA. Duke Univ, Med Ctr, Ctr Human Genet, Dept Med, Durham, NC USA. Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. Univ Wurzburg, Bioctr, Inst Human Genet, Wurzburg, Germany. Univ Regensburg, Inst Human Genet, D-8400 Regensburg, Germany. RP Fisher, SA (reprint author), Univ London Kings Coll, Guys Hosp, Guys Kings & St Thomas Sch Med, Dept Med & Mol Genet, 8th Floor,Guys Tower, London SE1 9RT, England. EM sheila.fisher@genetics.kcl.ac.uk RI Lewis, Cathryn/A-5225-2010; Abecasis, Goncalo/B-7840-2010; Weeks, Daniel/B-2995-2012; Haines, Jonathan/C-3374-2012 OI Abecasis, Goncalo/0000-0003-1509-1825; Lewis, Cathryn/0000-0002-8249-8476; Swaroop, Anand/0000-0002-1975-1141; Weeks, Daniel/0000-0001-9410-7228; FU NCRR NIH HHS [M01 RR-00095, RR03655]; NEI NIH HHS [EY10605, EY012203, EY015216, EY015288, EY03279, EY08247, EY10572, EY11309, EY12118, EY12562, F32-EY014085, R01-EY 09859, R01-EY10605, R01-EY11309, R01-U10-EY06594, U10-EY06594, U10-EY11309]; NHGRI NIH HHS [HG00008]; NHLBI NIH HHS [HL07567]; NIA NIH HHS [AG11268]; NIGMS NIH HHS [GM28356] NR 55 TC 145 Z9 149 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2005 VL 14 IS 15 BP 2257 EP 2264 DI 10.1093/hmg/ddi230 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 948OG UT WOS:000230725000017 PM 15987700 ER PT J AU Altug-Teber, O Dufke, A Poths, S Mau-Holzmann, UA Bastepe, M Colleaux, L Cormier-Daire, V Eggermann, T Gillessen-Kaesbach, G Bonin, M Riess, O AF Altug-Teber, O Dufke, A Poths, S Mau-Holzmann, UA Bastepe, M Colleaux, L Cormier-Daire, V Eggermann, T Gillessen-Kaesbach, G Bonin, M Riess, O TI A rapid microarray based whole genome analysis for detection of uniparental disomy SO HUMAN MUTATION LA English DT Article DE uniparental disomy; microarray; SNP; Prader-Willi; PWS; Angelman; AS; Silver-Russell; SRS; Beckwith-Wiedemann; pseudohypoparathyroidism; PHP ID PATERNAL DISOMY; CHROMOSOME; ISODISOMY; COMPLEX; UPD; ABNORMALITIES; RETARDATION; DISEASE; LINKAGE; FEMALE AB To date, uniparental disomy (UPD) with phenotypic relevance is described for different chromosomes and it is likely that additional as yet unidentified UPD phenotypes exist. Due to technical difficulties and limitations of time and resources, molecular analyses for UPD using microsatellite markers are only performed in cases with specific phenotypic features. In this study, we carried out a whole genome UPD screening based on a microarray genotyping technique. Six patients with the diagnosis of both complete or segmental UPD including Prader-Willi syndrome (PWS; matUPD15), Angelman syndrome (AS; patUPD15), Silver-Russell syndrome (SRS; matUPD7), Beckwith-Wiedemann syndrome (BWS; patUPD11p), pseudohypoparathyroidism (PHP; patUPD20q) and a rare chromosomal rearrangement (patUPD2p, matUPD2q), were genotyped using the GeneChip (R) Human Mapping 10K Array. Our results demonstrate the presence of UPD in the patients with high efficiency and reveal clues about the mechanisms of UPD formation. We thus conclude that array based SNP genotyping is a fast, cost-effective, and reliable approach for whole genome UPD screening. C1 Univ Klinikum Tubingen, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hop Necker Enfants Malad, INSERM, U393, Paris, France. Univ Aachen, Inst Human Genet, D-5100 Aachen, Germany. Univ Klinikum Essen, Inst Human Genet, Essen, Germany. RP Bonin, M (reprint author), Univ Klinikum Tubingen, Calwerstr 7, D-72076 Tubingen, Germany. EM michael.bonin@med.uni-tuebingen.de; olaf.riess@med.uni-tuebingen.de RI Eggermann, Thomas/F-3807-2014 NR 24 TC 40 Z9 41 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD AUG PY 2005 VL 26 IS 2 BP 153 EP 159 DI 10.1002/humu.20198 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 948TQ UT WOS:000230739000012 PM 15968682 ER PT J AU Shoda, LKM Young, DL Ramanujan, S Whiting, CC Atkinson, MA Bluestone, JA Eisenbarth, GS Mathis, D Rossini, AA Campbell, SE Kahn, R Kreuwel, HT AF Shoda, LKM Young, DL Ramanujan, S Whiting, CC Atkinson, MA Bluestone, JA Eisenbarth, GS Mathis, D Rossini, AA Campbell, SE Kahn, R Kreuwel, HT TI A comprehensive review of interventions in the NOD mouse and implications for translation SO IMMUNITY LA English DT Review ID NONOBESE DIABETIC MICE; ANTI-CD3 MONOCLONAL-ANTIBODY; REGULATORY T-CELLS; NECROSIS-FACTOR-ALPHA; ORAL INSULIN; GENE-TRANSFER; IN-VIVO; ENDOGENOUS INTERLEUKIN-12; NEONATAL INJECTION; SELF-TOLERANCE AB Type 1 diabetes (T1D) animal models such as the non-obese diabetic (NOD) mouse have improved our understanding of disease pathophysiology, but many candidate therapeutics identified therein have failed to prevent/cure human disease. We have performed a comprehensive evaluation of disease-modifying agents tested in the NOD mouse based on treatment timing, duration, study length, and efficacy. Interestingly, some popular tenets regarding NOD interventions were not confirmed: all treatments do not prevent disease, treatment dose and timing strongly influence efficacy, and several therapies have successfully treated overtly diabetic mice. The analysis provides a unique perspective on NOD interventions and suggests that the response of this model to therapeutic interventions can be a useful predictor of the human response as long as careful consideration is given to treatment dose, timing, and protocols; more thorough investigation of these parameters should improve clinical translation. C1 Entelos Inc, Foster City, CA 94404 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Diabet Div, Worcester, MA 01605 USA. Amer Diabet Assoc, Alexandria, VA 22311 USA. RP Shoda, LKM (reprint author), Entelos Inc, 110 Marsh Dr, Foster City, CA 94404 USA. EM shoda@entelos.com NR 112 TC 186 Z9 192 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2005 VL 23 IS 2 BP 115 EP 126 DI 10.1016/j.immuni.2005.08.002 PG 12 WC Immunology SC Immunology GA 962HM UT WOS:000231721700003 PM 16111631 ER PT J AU Anderson, MS Venanzi, ES Chen, ZB Berzins, SP Benoist, C Mathis, D AF Anderson, MS Venanzi, ES Chen, ZB Berzins, SP Benoist, C Mathis, D TI The cellular mechanism of Aire control of T cell tolerance SO IMMUNITY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; PROMISCUOUS GENE-EXPRESSION; TRANSCRIPTION FACTOR FOXP3; THYMIC EPITHELIAL-CELLS; NEGATIVE SELECTION; POSITIVE SELECTION; DEFICIENT MICE; ANTIGEN; AUTOIMMUNITY; THYMOCYTES AB Aire promotes the tolerization of thymocytes by inducing the expression of a battery of peripheral-tissue antigens in thymic medullary epithelial cells. We demonstrate that the cellular mechanism by which Aire exerts its tolerance-promoting function is not primarily positive selection of regulatory T cells, but rather negative selection of T effector cells. Surprisingly, supplementing its influence on the transcription of genes encoding peripheral-tissue antigens, Aire somehow enhances the antigen-presentation capability of medullary epithelial cells. Thus, this transcriptional control element promotes central tolerance both by furnishing a specific thymic stromal cell type with a repertoire of self antigens and by better arming such cells to present these antigens to differentiating thymocytes. In Aire's absence, autoimmunity and ultimately overt autoimmune disease develops. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. EM cb@joslin.harvard.edu; dm@joslin.harvard.edu FU NIDDK NIH HHS [1 R01 DK60027, K08 DK059958] NR 43 TC 350 Z9 366 U1 1 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2005 VL 23 IS 2 BP 227 EP 239 DI 10.1016/j.immuni.2005.07.005 PG 13 WC Immunology SC Immunology GA 962HM UT WOS:000231721700012 PM 16111640 ER PT J AU Smith, PD Ochsenbauer-Jambor, C Smythies, LE AF Smith, PD Ochsenbauer-Jambor, C Smythies, LE TI Intestinal macrophages: unique effector cells of the innate immune system SO IMMUNOLOGICAL REVIEWS LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR-BETA; LAMINA PROPRIA LYMPHOCYTES; REGULATORY T-CELLS; CROHNS-DISEASE; QUANTITATIVE-ANALYSIS; TARGETED DISRUPTION; MUCOSAL MACROPHAGES; NEGATIVE REGULATION AB The gastrointestinal mucosa is the largest reservoir of macrophages in the body. These important effector cells are derived from blood monocytes that are recruited to the lamina propria by endogenous chemoattractants in the non-inflamed mucosa and by inflammatory chemokines and bacterial products during inflammation. In the non-inflamed mucosa, newly recruited pro-inflammatory monocytes are exposed to lamina propria stromal (extracellular matrix) factors that induce phenotypic and functional differentiation into non-inflammatory macrophages. As a consequence of this differentiation, resident lamina propria macrophages are strikingly downregulated for the expression of innate response receptors, such as the receptors for lipopolysaccharide, immunoglobulin G (IgG), and IgA, and the production of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-alpha. Despite downregulated pro-inflammatory function, strong phagocytic and bactericidal activities remain intact. Thus, in the non-inflamed intestinal mucosa, lamina propria macrophages are non-inflammatory but retain avid scavenger and host defense functions, a unique but ideal phenotype and functional profile for effector cells in close proximity to immunostimulatory microorganisms and products. C1 Univ Alabama, Dept Med Gastroenterol & Hepatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Smith, PD (reprint author), Univ Alabama, Dept Med Gastroenterol & Hepatol, 703,19th St S, Birmingham, AL 35294 USA. EM pdsmith@uab.edu FU NICHD NIH HHS [HD-41361]; NIDCR NIH HHS [DE-16005]; NIDDK NIH HHS [DK-64400, DK-47322, DK-54495] NR 66 TC 129 Z9 138 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2005 VL 206 BP 149 EP 159 DI 10.1111/j.0105-2896.2005.00288.x PG 11 WC Immunology SC Immunology GA 949VW UT WOS:000230817200010 PM 16048547 ER PT J AU Liu, DX Cramer, CC Scafidi, J Davis, AE AF Liu, DX Cramer, CC Scafidi, J Davis, AE TI N-linked glycosylation at Asn(3) and the positively charged residues within the amino-terminal domain of the C1 inhibitor are required for interaction of the C1 inhibitor with Salmonella enterica serovar Typhimurim lipopolysaccharide and lipid A SO INFECTION AND IMMUNITY LA English DT Article ID LPS BINDING-PROTEIN; ESTER TRANSFER PROTEIN; HUMAN CD14; ANTIMICROBIAL PEPTIDES; ANTIBACTERIAL ACTIVITY; FUNCTIONAL DOMAINS; HUMAN LACTOFERRIN; ENDOTOXIN-SHOCK; ACID-RESIDUES; POLYMYXIN-B AB The C1 inhibitor (C1INH), a plasma complement regulatory protein, prevents endotoxin shock, at least partially via the direct interaction of its amino-terminal heavily glycosylated nonserpin region with gram-negative bacterial lipopolysaccharide (LPS). To further characterize the potential LPS-binding site(s) within the amino-terminal domain, mutations were introduced into C1INH at the three N-linked glycosylation sites and at the four positively charged amino acid residues. A mutant in which Asn(3) was replaced with Ala was markedly less effective in its binding to LPS, while substitution of Asn(47) or Asn(59) had little effect on binding. The mutation of C1INH at all four positively charged amino acid residues (Arg(18), Lys(22) Lys(30), and Lys(55)) resulted in near-complete failure to interact with LPS. The C1INH mutants that did not bind to LPS also did not suppress LPS binding or LPS-induced up-regulation of tumor necrosis factor alpha mRNA expression in RAW 264.7 macrophages. In addition, the binding of C1INH mutants to diphosphoryl lipid A was decreased in comparison with that of recombinant wild-type C1INH. Therefore, the interaction of C1INH with gram-negative bacterial LPS is dependent both on the N-linked carbohydrate at Asn(3) and on the positively charged residues within the amino-terminal domain. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu FU NICHD NIH HHS [R37 HD022082, R01 HD033727, HD33727, HD22082] NR 60 TC 20 Z9 21 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4478 EP 4487 DI 10.1128/IAI.73.8.4478-4487.2005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600003 PM 16040958 ER PT J AU LaRocque, RC Harris, JB Dziejman, M Li, XM Khan, AI Faruque, ASG Faruque, SM Nair, GB Ryan, ET Qadri, F Mekalanos, JJ Calderwood, SB AF LaRocque, RC Harris, JB Dziejman, M Li, XM Khan, AI Faruque, ASG Faruque, SM Nair, GB Ryan, ET Qadri, F Mekalanos, JJ Calderwood, SB TI Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection SO INFECTION AND IMMUNITY LA English DT Article ID TOXIN-COREGULATED PILI; PATHOGENICITY ISLANDS; GENE-EXPRESSION; CTX-PHI; VIRULENCE; REGULON; PATHOGENESIS; HEMOLYSIN; EPIDEMIC; O1 AB Understanding gene expression by bacteria during the actual course of human infection may provide important insights into microbial pathogenesis. In this study, we evaluated the transcriptional profile of Vibrio cholerae, the causative agent of cholera, in clinical specimens from cholera patients. We collected samples of human stool and vomitus that were positive by dark-field microscopy for abundant vibrios and used a microarray to compare gene expression in organisms recovered directly from specimens collected during the early and late stages of human infection. Our results reveal that V. cholerae gene expression within the human host environment differs from patterns defined in in vitro models of pathogenesis. tcpA, the major subunit of the essential V. cholerae colonization factor, was significantly more highly expressed in early than in late stages of infection; however, the genes encoding cholera toxin were not highly expressed in either phase of human infection. Furthermore, expression of the virulence regulators toxRS and tcpPH was uncoupled. Interestingly, the pattern of gene expression indicates that the human upper intestine may be a uniquely suitable environment for the transfer of genetic elements that are important in the evolution of pathogenic strains of V. cholerae. These findings provide a more detailed assessment of the transcriptome of V. cholerae in the human host than previous studies of organisms in stool alone and have implications for cholera control and the design of improved vaccines. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Dept Biostat, Cambridge, MA 02138 USA. Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org FU FIC NIH HHS [K01 TW007144, TW07144]; NIAID NIH HHS [R01 AI040725, AI40725, T32 AI007061, U01 AI058935, U01-AI58935]; NICHD NIH HHS [K12 HD000850, K12-HD00850]; NIGMS NIH HHS [GM068851, R01 GM068851] NR 26 TC 71 Z9 75 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4488 EP 4493 DI 10.1128/IAI.73.8.4488-4493.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600004 PM 16040959 ER PT J AU Cullen, PA Xu, XY Matsunaga, J Sanchez, Y Ko, AI Haake, DA Adler, B AF Cullen, PA Xu, XY Matsunaga, J Sanchez, Y Ko, AI Haake, DA Adler, B TI Surfaceome of Leptospira spp. SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEINS; PATHOGENIC LEPTOSPIRA; LIPOPOLYSACCHARIDE ANTIGENS; MONOCLONAL-ANTIBODIES; MAMMALIAN INFECTION; EXPOSED LIPOPROTEIN; MASS-SPECTROMETRY; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; INTERROGANS AB The identification of the subset of outer membrane proteins exposed on the surface of a bacterial cell (the surfaceome) is critical to understanding the interactions of bacteria with their environments and greatly narrows the search for protective antigens of extracellular pathogens. The surfaceome of Leptospira was investigated by biotin labeling of viable leptospires, affinity capture of the biotinylated proteins, two-dimensional gel electrophoresis, and mass spectrometry (MS). The leptospiral surfaceome was found to be predominantly made up of a small number of already characterized proteins, being in order of relative abundance on the cell surface: LipL32 > LipL21 > LipL41. Of these proteins, only LipL32 had not been previously identified as surface exposed. LipL32 surface exposure was subsequently verified by three independent approaches: surface immunofluorescence, whole-cell enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Three other proteins, Q8F8Q0 (a putative transmembrane outer membrane protein) and two proteins of 20 kDa and 55 kDa that could not be identified by MS, one of which demonstrated a high degree of labeling potentially representing an additional, as-yet-uncharacterized, surface-exposed protein. Minor labeling of p31(LipL45), GroEL, and FlaB1 was also observed. Expression of the surfaceome constituents remained unchanged under a range of conditions investigated, including temperature and the presence of serum or urine. Immunization of mice with affinity-captured surface components stimulated the production of antibodies that bound surface proteins from heterologous leptospiral strains. The surfaceomics approach is particularly amenable to protein expression profiling using small amounts of sample (< 10(7) cells) offering the potential to analyze bacterial surface expression during infection. C1 Monash Univ, Dept Microbiol, Victorian Bioinformat Consortium, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. Cornell Univ, Weil Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Victorian Bioinformat Consortium, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia. EM Ben.Adler@med.monash.edu.au RI Ko, Albert/P-2343-2015 FU NIAID NIH HHS [AI-01605, AI-34431, R01 AI034431, R01 AI034431-08, R21 AI034431, R29 AI034431] NR 42 TC 114 Z9 123 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4853 EP 4863 DI 10.1128/IAI.73.8.4853-4863.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600044 PM 16040999 ER PT J AU Nielsen, K Cox, GM Litvintseva, AP Mylonakis, E Malliaris, SD Benjamin, DK Giles, SS Mitchell, TG Casadevall, A Perfect, JR Heitman, J AF Nielsen, K Cox, GM Litvintseva, AP Mylonakis, E Malliaris, SD Benjamin, DK Giles, SS Mitchell, TG Casadevall, A Perfect, JR Heitman, J TI Cryptococcus neoformans alpha strains preferentially disseminate to the central nervous system during coinfection SO INFECTION AND IMMUNITY LA English DT Article ID RAT ALVEOLAR MACROPHAGES; HUMAN-IMMUNODEFICIENCY-VIRUS; MATING-TYPE LOCUS; A MATA STRAIN; AIDS PATIENTS; MOLECULAR EPIDEMIOLOGY; CAENORHABDITIS-ELEGANS; CELL IDENTITY; UNITED-STATES; HIV-INFECTION AB Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests differences in epidemiology and disease, and var. grubii strains are responsible for the vast majority of human disease. In previous studies, alpha strains were more virulent than congenic a strains in var. neoformans, whereas var. grubii congenic a and alpha strains exhibited equivalent levels of virulence. Here the role of mating type in the virulence of var. grubii was further characterized in a panel of model systems. Congenic var. grubii a and alpha strains had equivalent survival rates when cultured with amoebae, nematodes, and macrophages. No difference in virulence was observed between a and alpha congenic strains in multiple inbred-mouse genetic backgrounds, and there was no difference in accumulations in the central nervous system (CNS) late in infection. In contrast, during coinfections, a and alpha strains are equivalent in peripheral tissues but alpha cells have an enhanced predilection to penetrate the CNS. These studies reveal the first virulence difference between congenic a and a strains in the most common pathogenic variety and suggest an explanation for the prevalence of alpha strains in clinical isolates. C1 Duke Univ, Ctr Med, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Duke Univ, Howard Hughes Med Inst, Durham, NC 27710 USA. Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10461 USA. Albert Einstein Coll Med, Div Microbiol & Immunol, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Heitman, J (reprint author), Duke Univ, Ctr Med, Dept Mol Genet & Microbiol, 322 CARL Bldg,Res Dr, Durham, NC 27710 USA. EM heitm001@duke.edu RI Mitchell, Thomas/A-2356-2008 FU NIAID NIH HHS [R56 AI028388, R01 AI28388, R01 AI50113, R01 AI028388, R01 AI050113]; NICHD NIH HHS [K23 HD044799, HD044799-01] NR 80 TC 78 Z9 88 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4922 EP 4933 DI 10.1128/IAI.73.8.4922-4933.2005 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600051 PM 16041006 ER PT J AU Menzies, BE Kenoyer, A AF Menzies, BE Kenoyer, A TI Staphylococcus aureus infection of epidermal keratinocytes promotes expression of innate antimicrobial peptides SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; BETA-DEFENSINS; GENE; DIFFERENTIATION; CALCIUM; HBD-2; ACID AB Keratinocytes upregulate expression of endogenous antimicrobial peptides in response to inflammatory stimuli. We show that both viable and heat-inactivated Staphylococcus aureus and lipoteichoic acid differentially alter expression of these peptides upon contact with human keratinocytes. The findings indicate a diversity of staphylococcal factors involved in upregulation of antimicrobial peptide expression in cutaneous epithelia. C1 Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. RP Menzies, BE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, S-111-ID,1660 S Columbian Way, Seattle, WA 98108 USA. EM bmenzies@u.washington.edu NR 15 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 5241 EP 5244 DI 10.1128/IAI.73.8.5241-5244.2005 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600093 PM 16041048 ER PT J AU Harisinghani, MG AF Harisinghani, MG TI MRI colonography for IBD: Do magnets spin a tale of the inflamed colon? SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2005 VL 11 IS 8 BP 778 EP 778 DI 10.1097/01.MIB.0000171283.71468.92 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952KA UT WOS:000231001200012 PM 16043995 ER PT J AU Bigatello, LM Stelfox, HT Hess, D AF Bigatello, LM Stelfox, HT Hess, D TI Inhaled nitric oxide therapy in adults - opinions and evidence SO INTENSIVE CARE MEDICINE LA English DT Editorial Material C1 Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM lbigatello@partners.org NR 9 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD AUG PY 2005 VL 31 IS 8 BP 1014 EP 1016 DI 10.1007/s00134-005-2674-5 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 951CD UT WOS:000230905600003 PM 15973522 ER PT J AU Elmaleh, DR Brown, NV Geiben-Lynn, R AF Elmaleh, DR Brown, NV Geiben-Lynn, R TI Anti-viral activity of human antithrombin III SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE antithrombin III; CD8(+) T-cells; HIV infection ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; KAPPA-B ACTIVATION; CD8(+) T-CELLS; REVERSE TRANSCRIPTION; MEDIATED SUPPRESSION; HIV-1 INFECTION; HEPARIN-BINDING; SERPIN ANTITHROMBIN; BETA-CHEMOKINES AB Soluble inhibitory factors produced by CD8(+) T-cells have been shown to inhibit HIV-1 replication and may play a critical role in vivo in anti-viral host defense. CD8(+) T-cell-modified antithrombin III (ATIII) accounts for some of the described CD8(+) T-cell anti-viral activity. We demonstrate that CD4(+) T-cells, CD8(+) T-cells, and natural killer cells react to an ATIII gradient by cell migration. Furthermore, exogenously added ATIII induced a G-protein-coupled signal transduction process in CD4(+) T-cells and inhibited TNF-alpha-induced NF-kappa B activation. Heat and/or heparin treatment prior to the anti-viral inhibition test increased the anti-HIV activity up to 1000-fold. Our data indicate that anti-viral inactive ATIII can be activated having promising anti-viral properties as complementary candidate for the treatment of HIV infection. C1 Accelerat BioPharmaceut Inc, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Geiben-Lynn, R (reprint author), Accelerat BioPharmaceut Inc, 25 Hawthorne St,2, Watertown, MA 02472 USA. EM delmaieh@partners.org; acceleration@rcn.com NR 60 TC 12 Z9 12 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD AUG PY 2005 VL 16 IS 2 BP 191 EP 200 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 946DR UT WOS:000230553000001 PM 16012749 ER PT J AU Plan, Y Hlatky, L Hahnfeldt, P Sachs, R Loucas, B Cornforth, M AF Plan, Y Hlatky, L Hahnfeldt, P Sachs, R Loucas, B Cornforth, M TI Full-color painting reveals an excess of radiation-induced dicentrics involving homologous chromosomes SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE DNA repair; dicentric chromosome aberrations; proximity dependent DNA misrepair; homologous repair ID NORMAL HUMAN-FIBROBLASTS; HUMAN-LYMPHOCYTES; IONIZING-RADIATION; HUMAN-CELLS; ABERRATIONS; REPAIR; REARRANGEMENTS; RECOMBINATION; INVOLVEMENT; FREQUENCY AB Purpose: To determine the ratio of homologous to heterologous dicentric chromosomes induced in human cells by ionizing radiation. This ratio is influenced by, and thus potentially informative about, underlying DNA damage/repair/misrepair processes and also the geometry of individual chromosome domains within the interphase nucleus. Materials and methods: 24-color mFISH (multiplex fluorescent in situ hybridization) was used to determine the ratio of 1-color (homologous) to 2-color (heterologous) dicentrics produced in human lymphocytes or fibroblasts by gamma-rays, alpha particles, or iron ions at various doses. Assuming that randomness independent of homology holds, the expected homologue: heterologue ratio for diploid human male cells is similar to 0.024, as shown by deriving a formula applicable to simple interchanges and then extending the result, via Monte Carlo simulation, to the general situation where complex aberrations are also considered. Results and conclusions: There was a substantial excess of homologous dicentrics, with probability of occurrence by chance less than 0.02 for each of the three radiations and only about 10(-8) for all the data combined. Overall, approximately 18 homologous dicentrics were expected but 47 were found, including 11 involving chromosome 1. Observed excesses were similar for both sparsely and densely ionizing radiations. Geometric proximity of homologues is a possible explanation for the overabundance; in that case more extensive statistics should eventually uncover a linear energy transfer (LET) dependence. An alternative possibility, not ruled out by the present data, is homology-dependent misrepair. C1 Univ Calif Berkeley, Dept Math, Grad Sch, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Texas, Med Branch, Dept Radiat Oncol, Galveston, TX 77550 USA. RP Sachs, R (reprint author), Univ Calif Berkeley, Dept Math, Grad Sch, 970 Evans Hall,MC 3840, Berkeley, CA 94720 USA. EM sachs@math.berkeley.edu FU NIGMS NIH HHS [GM68423] NR 25 TC 6 Z9 8 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD AUG PY 2005 VL 81 IS 8 BP 613 EP 620 DI 10.1080/09553000500331881 PG 8 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 986IQ UT WOS:000233443700006 PM 16298942 ER PT J AU Cohen, SJ Dobelbower, R Lipsitz, S Catalano, PJ Sischy, B Smith, TJ Haller, DG AF Cohen, SJ Dobelbower, R Lipsitz, S Catalano, PJ Sischy, B Smith, TJ Haller, DG TI A randomized Phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern cooperative oncology group study E8282 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE pancreatic cancer; locally advanced; radiotherapy; chemotherapy; 5-fluorouracil ID COMBINED-MODALITY THERAPY; SQUAMOUS-CELL CARCINOMA; CANCER; RADIATION; CHEMOTHERAPY; TRIAL; COMBINATION; GEMCITABINE; CONCURRENT AB Purpose: The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8-10 months. Radiation therapy has been used to improve local control and palliate symptoms. This randomized study was undertaken to determine whether the addition of 5-fluorouracil (5-FU) find mitomycin-C (MMC) to radiation therapy improves outcome in this patient population. Patients and Methods: One hundred fourteen patients were randomized to receive 59.4 Gy external beam radiotherapy in 1.8 Gy fractions alone or in combination with 5-FU (1,000 mg/m(2)/day for 4 days by continuous infusion Days 2-5 and 28-31) and MMC (10 mg/m(2) on Day 2). Results: One hundred four patients were evaluable for efficacy. Hematologic and nonhematologic toxicities were more common in the combination arm. The response rates were 6% in the radiation therapy arm and 9% in the combination arm. There were no differences in median disease-free survival time (DFS) or overall survival time (OS) between the combination and radiation therapy alone arms: 5.1 vs. 5.0 months, respectively, for DFS (p = 0.19) and 8.4 vs. 7.1 months, respectively, for OS (p = 0.16). Conclusion: The addition of 5-FU and MMC to radiotherapy increased toxicity without improving DFS or OS in patients with locally advanced pancreatic cancer. Alternative drugs for radiosensitization may improve outcome. (c) 2005 Elsevier Inc. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Med Coll Ohio, Dept Radiat Oncol, Toledo, OH 43699 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Rochester, Rochester, NY USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Everett Clin, Everett, WA USA. Univ Penn, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM S_Cohen@fccc.edu FU NCI NIH HHS [CA15488, CA21115, CA11083, CA66636, CA07190, CA27525, CA23318] NR 21 TC 89 Z9 96 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2005 VL 62 IS 5 BP 1345 EP 1350 DI 10.1016/j.ijrobp.2004.12.074 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 949EI UT WOS:000230767300012 PM 16029791 ER PT J AU Chang, SM Wen, P Cloughesy, T Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI De Angelis, L Raizer, J Hess, K Aldape, K Lamborn, KR Kuhn, J Dancey, J Prados, MD AF Chang, SM Wen, P Cloughesy, T Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI De Angelis, L Raizer, J Hess, K Aldape, K Lamborn, KR Kuhn, J Dancey, J Prados, MD CA N Amer Brain Tumor Consortium Natl Canc Inst TI Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE chemotherapy; CCI-779; rapamycin; glioblastoma multiforme; recurrent; efficacy ID GROWTH-FACTOR RECEPTOR; MAMMALIAN TARGET; CANCER-CELLS; MALIGNANT GLIOMA; RAPAMYCIN; PTEN; EXPRESSION; RESISTANCE; PATHWAY; AMPLIFICATION AB Purpose: Loss of PTEN, which is common in glioblastoma multiforme (GBM), results in activation of the mammalian target of rapapmycin (mTOR), thereby increasing mRNA translation of a number of key proteins required for cell-cycle progression. CCI-779 is an inhibitor of mTOR. The primary objectives of this study were to determine the efficacy of CCI-779 in patients with recurrent GBM and to further assess the toxicity of the drug. Experimental Design: CCI-779 was administered weekly at a dose of 250 mg intravenously for patients on enzyme-inducing anti-epileptic drugs (EIAEDs). Patients not on EIAEDs were initially treated at 250 mg; however, the dose was reduced to 170 mg because of intolerable side effects. Treatment was continued until unacceptable toxicity, tumor progression, or patient withdrawal. The primary endpoint was 6-month progression-free survival. Results: Forty-three patients were enrolled; 29 were not on EIAEDs. The expected toxicity profile of increased lipids, lymphopenia, and stomatitis was seen. There were no grade IV hematological toxicities and no toxic deaths. One patient was progression free at 6 months. Of the patients assessable for response, there were 2 partial responses and 20 with stabilization of disease. The median time to progression was 9 weeks. Conclusions: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM. Despite initial disease stabilization in approximately 50% of patients, the durability of response was short. Because of the low toxicity profile, CCI-779 may merit exploration in combination with other modalities. C1 Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Texas San Antonio, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas San Antonio, Austin, TX 78712 USA. Univ Wisconsin, Madison, WI 53706 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Neurooncol Serv, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu FU NCI NIH HHS [CA62399, 5-U01CA62399-09, CA16672, CA62412, CA62422, CA62426, CA62455-08, U01 CA62399, U01 CA62407-08, U01CA62421-08]; NCRR NIH HHS [M01 RR03186, M01-RR00042, M01-RR00079, M01-RR00633, M01-RR0865] NR 21 TC 247 Z9 253 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2005 VL 23 IS 4 BP 357 EP 361 DI 10.1007/s10637-005-1444-0 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 945GG UT WOS:000230490400009 PM 16012795 ER PT J AU Barabino, S Shen, LL Chen, L Rashid, S Rolando, M Dana, MR AF Barabino, S Shen, LL Chen, L Rashid, S Rolando, M Dana, MR TI The controlled-environment chamber: A new mouse model of dry eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OCULAR SURFACE DISEASE; KERATOCONJUNCTIVITIS SICCA; TEAR FILM; PREVALENCE; SYMPTOMS; NASAL; MUCIN AB PURPOSE. To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. METHODS. Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber ( CEC) where relative humidity ( RH), temperature ( T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions ( RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21 - 23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment ( RH = 50% - 80%, no AF, T = 21 - 23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining ( score, 0 - 15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. RESULTS. No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. CONCLUSIONS. This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lab Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Cornea Serv, Boston, MA USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lab Immunol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 23 TC 80 Z9 81 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2005 VL 46 IS 8 BP 2766 EP 2771 DI 10.1167/iovs.04-1326 PG 6 WC Ophthalmology SC Ophthalmology GA 949AB UT WOS:000230756100019 PM 16043849 ER PT J AU Schumacher, HR AF Schumacher, HR TI Why I do research SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID REITERS-SYNDROME; EARLY ARTHRITIS; CHLAMYDIA-TRACHOMATIS; IDENTIFICATION; SYNOVITIS; CRYSTALS; ANTIGEN; DISEASE; JOINTS C1 Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), VA Med Ctr, 151-K Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacher@mail.med.upenn.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2005 VL 11 IS 4 BP 228 EP 232 DI 10.1097/01.rhu.0000173617.98775.8d PG 5 WC Rheumatology SC Rheumatology GA 956CM UT WOS:000231276500011 PM 16357764 ER PT J AU Kafkala, C Hynes, A Choi, J Topalkara, A Foster, CS AF Kafkala, C Hynes, A Choi, J Topalkara, A Foster, CS TI Ahmed valve implantation for uncontrolled pediatric uveitic glaucoma SO JOURNAL OF AAPOS LA English DT Article ID CHRONIC CHILDHOOD UVEITIS; CHILDREN; MANAGEMENT; SECONDARY AB Purpose: We sought to evaluate the safety and efficacy of Ahmed valve implantation for the management of glaucoma associated with chronic uveitis in pediatric patients. Methods: A retrospective chart review was conducted of 6 pediatric patients (7 eyes) who underwent Ahmed valve implantation because of refractory uveitic glaucoma. Intraocular pressure (IOP) reduction, preoperative and postoperative visual acuities, the number of hypotensive medications required, and complications associated with the operation were evaluated. Results: Mean follow-up was 36.8 months (range, 6-60). At the last visit, all 7 eyes had IOPs between 9 and 18 mm Hg (average, 12.1). IOP reduction averaged 69.6% (P = 0.0005, paired t-test). The number of hypotensive agents was reduced from an average of 3 to an average of 0.71 medicines per eye (P = 0.001). The only complication was hemorrhagic choroidal detachment postoperatively in two eyes; both resolved within one month. Conclusions: For children with good immunomodulatory control of their inflammation and appropriate follow-up, Ahmed valve implantation can be an effective and safe procedure for treating pediatric uveitic glaucoma. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Massachusetts Eye Res & Surg Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Foster, CS (reprint author), Ocular Immunol & Uveitis Fdn, 348 Glen Rd, Weston, MA 02790 USA. EM fosters@uveitis.org NR 23 TC 21 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD AUG PY 2005 VL 9 IS 4 BP 336 EP 340 DI 10.1016/j.jaapos.2005.04.006 PG 5 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 958DZ UT WOS:000231426200007 PM 16102483 ER PT J AU Marcus, SM Young, EA Kerber, KB Kornstein, S Farabaugh, AH Mitchell, J Wisniewski, SR Balasubramani, GK Trivedi, MH Rush, AJ AF Marcus, SM Young, EA Kerber, KB Kornstein, S Farabaugh, AH Mitchell, J Wisniewski, SR Balasubramani, GK Trivedi, MH Rush, AJ TI Gender differences in depression: Findings from the STAR*D study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depression; women; gender; comorbidity ID NATIONAL-COMORBIDITY-SURVEY; CHRONIC MAJOR DEPRESSION; SEX-DIFFERENCES; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; UNITED-STATES; RATING SCALE; INVENTORY; LIFETIME; QUESTIONNAIRE AB Background: Epidemiologic research consistently reports gender differences in the rates and course of major depressive disorder (MDD). The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) multicenter trial provides a unique opportunity to explore gender differences in outpatients with nonpsychotic MDD. Methods: This sample included the first 1500 outpatients with MDD who enrolled in STAR*D. Nearly two-thirds of the sample (62.8%) were women. Baseline sociodemographic factors, comorbidities, and illness characteristics were analyzed by gender. Results: Women (62.8% of the sample) had a younger age at onset of the first major depressive episode. They commonly reported concurrent symptoms consistent with anxiety disorders, somatoform disorder, and bulimia as well as atypical symptoms. Alcohol and drug abuses were more common in men. Limitations: This report is a subpopulation of the entire STAR*D sample. These exploratory analyses aimed to identify potential gender differences for further hypothesis testing. Conclusions: The gender-specific rate of MDD in this study population is proportional to rates found in community samples with a 1.7:1 prevalence of MDD in women vs. men which argues against increased treatment seeking in women. (c) 2004 Published by Elsevier B.V. C1 Univ Michigan, Dept Psychiat, Sch Med, Ann Arbor, MI 48105 USA. Univ Michigan, Mental Hlth Res Ctr, Ann Arbor, MI 48105 USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Laureate Psychiat Clin & Hosp, Tulsa, OK USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. RP Marcus, SM (reprint author), Univ Michigan, Dept Psychiat, Sch Med, 2101 Commonwealth Blvd,Suite B, Ann Arbor, MI 48105 USA. EM smmarcus@umich.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 NR 33 TC 161 Z9 164 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG PY 2005 VL 87 IS 2-3 BP 141 EP 150 DI 10.1016/j.jad.2004.09.008 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 956TA UT WOS:000231321500001 PM 15982748 ER PT J AU Kolasinski, SL Garfinkel, M Tsai, AG Matz, W Van Dyke, A Schumacher, HR AF Kolasinski, SL Garfinkel, M Tsai, AG Matz, W Van Dyke, A Schumacher, HR TI Iyengar yoga for treating symptoms of osteoarthritis of the knees: A pilot study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID IMPACT MEASUREMENT SCALES; HEALTH-STATUS; CLINICAL-TRIALS; EXERCISE; ARTHRITIS; HIP; THERAPY; RECOMMENDATIONS; INTERVENTION; DISABILITY AB Objectives: The American College of Rheumatology (ACR) Guidelines for the medical management of osteoarthritis (OA) emphasize the use of nonpharmacologic interventions including exercise. Implementation of an exercise program can be difficult for patients, and little is known about the benefits of alternative therapies such as yoga. The aim of this pilot study was to assess the feasibility of using yoga in the tradition of B.K.S. Iyengar to treat the symptoms of osteoarthritis of the knee. Design: Participants were instructed in modified Iyengar yoga postures during 90-minute classes once weekly for 8 weeks. Subjects: Participants met ACR criteria for osteoarthritis of the knee and completed a medical history and physical examination, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Arthritis Impact Measurement Scale 2 (AIMS2), Patient Global Assessment (GA) by Visual Analog Scale (VAS), Physician GA by VAS, and 50-foot Walk Time before and following an 8-week course of yoga instruction. Eleven (11) subjects enrolled, nine completed at least one session and seven (six of whom were obese) had data from pre- and post-course time points available for analysis. Results: Statistically significant reductions in WOMAC Pain, WOMAC Physical Function, and AIMS2 Affect were observed when participants' status were compared to their pre-course status. WOMAC Stiffness, AIMS2 Symptoms, Social and Role, Physician GA, and Patient GA measured trends in improvement of symptoms. No adverse events from treatment were reported. Conclusions: This pilot study suggests that yoga may provide a feasible treatment option for previously yoga-naive, obese patients > 50 years of age and offers potential reductions in pain and disability caused by knee OA. Future studies should compare yoga to other nonpharmacologic interventions for knee OA, such as patient education or quadriceps-strengthening exercises. C1 Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. BKS Iyengar Yoga Studio Philadelphia, Philadelphia, PA USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kolasinski, SL (reprint author), Univ Penn, Sch Med, Div Rheumatol, 504 Maloney Bldg,36th & Spruce Bldg, Philadelphia, PA 19104 USA. EM sharonk@mail.med.upenn.edu NR 23 TC 69 Z9 72 U1 0 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD AUG PY 2005 VL 11 IS 4 BP 689 EP 693 DI 10.1089/acm.2005.11.689 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 961SE UT WOS:000231681300017 PM 16131293 ER PT J AU Trautner, BW Hull, RA Darouiche, RO AF Trautner, BW Hull, RA Darouiche, RO TI Colicins prevent colonization of urinary catheters SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE bacteriocins; UTIs; uropathogens ID INFECTION; BACTERIOCINS AB Objectives: Natural microbial defence systems, such as bacteriocins, may be a novel means to prevent catheter-associated urinary tract infection. We investigated in vitro whether a colicin-expressing strain of Escherichia, coli could prevent urinary catheter colonization by a colicin-susceptible, uropathgenic strain of E. coli. Methods: Segments of urinary catheter were inoculated with colicin-producing E. coli K-12 and then exposed to either colicin-susceptible E. coli (a uropathogenic clinical isolate) or colicin-resistant E. coli (derived from the susceptible clinical isolate). Catheters were then incubated overnight, rinsed and sonicated. Results: The presence of colicin-producing E. coli K-12 on the catheter surface completely prevented catheter colonization by colicin-susceptible E. coli but not by resistant E. coli. The colicin-susceptible strain but not the colicin-resistant strain also disappeared from broth cultures in the presence of colicin-producing E. coli K-12. Conclusions: The observed inhibition of catheter colonization by the uropathogenic clinical isolate of E. coli can be attributed to the presence of a colicin-producing strain of E. coli on the catheter surface. Bacteriocin production by a non-pathogenic organism may have clinical applicability as a means to prevent catheter-associated urinary tract infection. C1 Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Trautner, BW (reprint author), MEDVAMC, Spinal Cord Injury 128, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.tmc.edu FU NICHD NIH HHS [K23 HD042014-02, HD42014, K23 HD042014, K23 HD042014-01, K23 HD042014-03] NR 10 TC 20 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD AUG PY 2005 VL 56 IS 2 BP 413 EP 415 DI 10.1093/jac/dki228 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 953QK UT WOS:000231094000030 PM 15980093 ER PT J AU Beversdorf, DQ Manning, SE Hillier, A Anderson, SL Nordgren, RE Walters, SE Nagaraja, HN Cooley, WC Gaelic, SE Bauman, ML AF Beversdorf, DQ Manning, SE Hillier, A Anderson, SL Nordgren, RE Walters, SE Nagaraja, HN Cooley, WC Gaelic, SE Bauman, ML TI Timing of prenatal stressors and autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE autism; prenatal; stress; development ID PERINATAL RISK-FACTORS; INFANTILE-AUTISM; MATERNAL STRESS; RAT PUPS; PREGNANCY; EXPOSURE; CHILDREN; BRAIN; SUSCEPTIBILITY; ABNORMALITIES AB Recent evidence supports a role for genetics in autism, but other findings are difficult to reconcile with a purely genetic cause. Pathological changes in the cerebellum in autism are thought to correspond to an event before 30-32 weeks gestation. Our purpose was to determine whether there is an increased incidence of stressors in autism before this time period. Surveys regarding incidence and timing of prenatal stressors were distributed to specialized schools and clinics for autism and Down syndrome, and to mothers of children without neurodevelopmental diagnoses in walk-in clinics. Incidence of stressors during each 4-week block of pregnancy was recorded. Incidence of stressors in the blocks prior to and including the predicted time period (21-32 weeks gestation) in each group of surveys was compared to the other prenatal blocks. A higher incidence of prenatal stressors was found in autism at 21-32 weeks gestation, with a peak at 25-28 weeks. This does support the possibility of prenatal stressors as a potential contributor to autism, with the timing of stressors consistent with the embryological age suggested by neuroanatomical findings seen in the cerebellum in autism. Future prospective studies would be needed to confirm this finding. C1 Ohio State Univ, Dept Neurol, Med Ctr, Columbus, OH 43210 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. Ohio State Univ, Dept Stat, Columbus, OH 43210 USA. Child Hlth Associates, Ann Arbor, MI USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA USA. RP Beversdorf, DQ (reprint author), Ohio State Univ, Dept Neurol, Med Ctr, Means Hall 469,1654 Upham Dr, Columbus, OH 43210 USA. EM beversdorf-1@medctr.osu.edu RI Beversdorf, David/M-2786-2016 OI Beversdorf, David/0000-0002-0298-0634 FU NCRR NIH HHS [M01RR00034] NR 44 TC 125 Z9 133 U1 7 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD AUG PY 2005 VL 35 IS 4 BP 471 EP 478 DI 10.1007/s10803-005-5037-8 PG 8 WC Psychology, Developmental SC Psychology GA 960NU UT WOS:000231601200007 PM 16134032 ER PT J AU Lieberman, J Song, EW Zhu, PC Palliser, D AF Lieberman, J Song, EW Zhu, PC Palliser, D TI Silencing the messenger: Harnessing RNA interference for therapy SO JOURNAL OF BIOTECHNOLOGY LA English DT Meeting Abstract CT 12th European Congress on Biotechnology (ECB 12) CY AUG 21-24, 2005 CL Copenhagen, DENMARK C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD AUG PY 2005 VL 118 SU 1 BP S68 EP S69 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 954ZV UT WOS:000231195200233 ER PT J AU Doornberg, JN Ring, D Fabian, LM Malhotra, L Zurakowski, D Jupiter, JB AF Doornberg, JN Ring, D Fabian, LM Malhotra, L Zurakowski, D Jupiter, JB TI Pain dominates measurements of elbow function and health status SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID QUALITY-OF-LIFE; ROTATOR CUFF; SHOULDER; DISABILITY; VALIDITY; QUESTIONNAIRE; RELIABILITY; FRACTURE; SYSTEM; WRIST AB Background: Elbow function can be quantified with use of physician-based elbow-rating systems and health status questionnaires. Our hypothesis was that pain has a strong influence on these scores, which overwhelms the influence of objective factors such as motion. Methods: One hundred and four patients were evaluated, at a minimum of six months (average, forty-six months) after the latest surgery for an intra-articular fracture of the elbow, with use of three physician-based evaluation instruments (Mayo Elbow Performance Index [MEPI], Broberg and Morrey rating system, and American Shoulder and Elbow Surgeons Elbow Evaluation Instrument [ASES]), an upper-extremity-specific health status questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]), and a general health status questionnaire (Short Form-36 [SF-36]). Multivariate analysis of variance and regression modeling were used to identify the factors that account for the variability in scores derived with these measures-in other words, which factors have the strongest influence on the final score. Results: Pain alone accounted for 66% of the variability in the MEPI scores, 59% of the variability in the Broberg and Morrey scores, and 57% of the variability in the ASES scores. Models that included other factors accounted for only slightly more variability (73%, 79%, and 79%, respectively), and those that did not include pain accounted for only 22%, 41%, and 41% of the variability. Thirty-six percent of the variability in the DASH scores could be accounted for by pain alone, and 45% could be accounted for by pain and range of motion. Models not including pain accounted for only 17% of the variability in the DASH scores. Conclusions: Pain has a very strong influence on both physician-rated and patient-rated quantitative measures of elbow function. Consequently, these measures may be strongly influenced by the psychosocial aspects of illness that have a strong relationship with pain, and objective measures of elbow function such as mobility may be undervalued. It may be advisable to evaluate pain separately from objective measures of elbow function in physician-based elbow ratings. C1 Massachusetts Gen Hosp, Yawkee Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Doornberg, JN (reprint author), Massachusetts Gen Hosp, Yawkee Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 25 TC 49 Z9 51 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2005 VL 87A IS 8 BP 1725 EP 1731 DI 10.2106/JBJS.D.027145 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 951RZ UT WOS:000230949800009 PM 16085611 ER PT J AU Ring, D Holovacs, T AF Ring, D Holovacs, T TI Brachial plexus palsy after intramedullary fixation of a clavicular fracture - A report of three cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MIDSHAFT; NONUNION; PIN C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 27 Z9 30 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2005 VL 87A IS 8 BP 1834 EP 1837 DI 10.2106/JBJS.D.02919 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 951RZ UT WOS:000230949800025 PM 16085627 ER PT J AU Baker, DW Asch, SM Keesey, JW Brown, JA Chan, KS Joyce, G Keeler, EB AF Baker, DW Asch, SM Keesey, JW Brown, JA Chan, KS Joyce, G Keeler, EB TI Differences in education, knowledge, self-management activities, and health outcomes for patients with heart failure cared for under the chronic disease model: The improving chronic illness care evaluation SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE chronic care; quality improvement; self-management ID HOSPITAL READMISSION; CONTROLLED-TRIAL; COMMUNICATION; QUESTIONNAIRE; FRAMEWORK AB Background: The objective of this study was to determine whether participation in a quality improvement (QI) collaborative for heart failure (HF) was associated with better interpersonal aspects of care and health outcomes. Methods and Results: We conducted a cross-sectional telephone survey of patients in 6 organizations who participated in a QI collaborative for HF (participants, n = 387) and 6 comparable control organizations (controls, n = 414) and measured provider-patient communication, education received, knowledge of HE, self-management behaviors, satisfaction, and quality of life. The participant group patients were more likely to report their doctor and nurse discussed treatment options and reviewed self-management (P <.01 for both). A total of 88% of participants were told to weigh themselves daily and record their weight compared with 34% of controls (P <.01). Participants were more likely to know how often to check their weight (P <.01), recognize symptoms of worsening HF (P <=.01 for all), have a scale (P =.002), and monitor their weight daily (P <.001). Participants had similar quality of life but fewer emergency department visits and hospitalizations. Conclusion: Participation in a QI collaborative for HF was associated with better communication, education, and knowledge, and lower health care use. Collaboratives may be a useful method for disseminating quality improvement strategies. C1 Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Dept Med, Chicago, IL 60611 USA. RAND Corp, Hlth Program, Santa Monica, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. RP Baker, DW (reprint author), Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Dept Med, 676 N St Clair,Suite 200, Chicago, IL 60611 USA. NR 23 TC 36 Z9 40 U1 0 U2 8 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 BP 405 EP 413 DI 10.1016/j.cardfail.2005.03.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 961DZ UT WOS:000231643400001 PM 16105630 ER PT J AU Luther, SA McCullough, PA Havranek, EP Rumsfeld, JS Jones, PG Heidenreich, PA Peterson, ED Rathore, SS Krumholz, HM Weintraub, WS Spertus, JA Masoudi, FA AF Luther, SA McCullough, PA Havranek, EP Rumsfeld, JS Jones, PG Heidenreich, PA Peterson, ED Rathore, SS Krumholz, HM Weintraub, WS Spertus, JA Masoudi, FA CA Cardiovascular Outcomes Res Consor TI The relationship between B-type natriuretic peptide and health status in patients with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; natriuretic peptides; health status ID QUALITY-OF-LIFE; 6-MINUTE WALK TEST; FUNCTIONAL-CAPACITY; MORTALITY; IMPACT; QUESTIONNAIRE; RELIABILITY; PREDICTOR; MORBIDITY; PRESSURE AB Background: Although B-type natriurefic peptide (BNP) levels have been proposed as a means of assessing disease severity in patients with heart failure. it is not known if BNP levels are correlated with health status (symptom burden, functional limitation, and quality of life), Methods and Results: We studied 342 outpatients with systolic heart failure from 14 centers at baseline and 6 +/- 2 weeks with BNP levels and the Kansas City Cardioniyopathy Questionaire (KCCQ). a heart-failure-specific health status instrument. We assessed the correlation between KCCQ scores and BNP at baseline and changes in KCCQ according to changes in BNP levels between baseline and follow-up, Mean baseline BNP levels were 379 +/- 387 pg/mL and mean KCCQ summary,cores were 62 2 23 points. Although baseline BNP and KCCQ were both associated with New York Heart Association classification (P <.001 for both), BNP and KCCQ were not correlated (r(2) - 0,008, P = .15). There was no significant relationship between changes in BNP and KCCQ regardless of the threshold used to define a clinically meaningful BNP change. For example, using > 50% BNP change threshold, KCCQ improved by 3.7 +/- 14.2 in patients with decreasing BNR improved by 1.7 +/- 13.6 in patients with no BNP change. and improved by 1.0 +/- 13.4 in patients with increasing BNP (P =.6). Conclusion: BNP and health status are not correlated in outpatients with heart failure in the short term, This suggests that these measures may assess different aspects of heart failure severity, and that physiologic measures do not reflect patients ' perceptions of the impact of heart failure on their health status. C1 Denver Hlth Med Ctr, Div Cardiol MC 0960, Dept Med, Denver, CO 80204 USA. Denver VA Med Ctr, Dept Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. William Beaumont Hosp, Dept Med, Royal Oak, MI 48072 USA. Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, MD PhD Training Program, New Haven, CT 06510 USA. Yale Univ, Sch Med, Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Masoudi, FA (reprint author), Denver Hlth Med Ctr, Div Cardiol MC 0960, Dept Med, 777 Bannock St, Denver, CO 80204 USA. OI Heidenreich, Paul/0000-0001-7730-8490 FU NIA NIH HHS [AG01011, K08-AG01011]; NIGMS NIH HHS [GM07205] NR 35 TC 27 Z9 30 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 BP 414 EP 421 DI 10.1016/j.cardfail.2005.02.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 961DZ UT WOS:000231643400002 PM 16105631 ER PT J AU Corvera-Tindel, TE Doering, LV Dracup, K AF Corvera-Tindel, TE Doering, LV Dracup, K TI Impact of age on functional status, moods and quality of life in patients with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 9th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 18-21, 2005 CL Boca Raton, FL SP Heart Failure Soc Amer C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 SU S MA 318 BP S174 EP S175 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PV UT WOS:000231745600319 ER PT J AU Devi, S Kennedy, RH Joseph, L Melchert, RB Shekhawat, NS Joseph, J AF Devi, S Kennedy, RH Joseph, L Melchert, RB Shekhawat, NS Joseph, J TI Hyperhomocysteinemia leads to reactive interstitial fibrosis and systolic dysfunction in spontaneously hypertensive rats SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 9th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 18-21, 2005 CL Boca Raton, FL SP Heart Failure Soc Amer C1 Boston Univ, Sch Med, VA Boston Healthcare, Boston, MA 02215 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Loyola Univ, Maywood, IL 60153 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 SU S MA 093 BP S115 EP S115 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PV UT WOS:000231745600094 ER PT J AU Devi, S Burke, B Joseph, L Kennedy, RH Joseph, J AF Devi, S Burke, B Joseph, L Kennedy, RH Joseph, J TI Collagen phenotype alterations in hyperhomocysteinemia-induced cardiac remodeling SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 9th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 18-21, 2005 CL Boca Raton, FL SP Heart Failure Soc Amer C1 Boston Univ, Sch Med, VA Boston Healthcare, Boston, MA 02118 USA. Loyola Univ, Chicago Stritch Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 SU S MA 095 BP S115 EP S115 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PV UT WOS:000231745600096 ER PT J AU Grazette, LP Kerkela, R Patten, R Rosenzweig, A Durand, JB Force, T AF Grazette, LP Kerkela, R Patten, R Rosenzweig, A Durand, JB Force, T TI Imatinib mesylate (Gleevec) induces mitochondrial dysfunction and caspase activation in cardiac myocytes SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 9th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 18-21, 2005 CL Boca Raton, FL SP Heart Failure Soc Amer C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, MD Anderson Canc Ctr, Houston, TX 77030 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 SU S MA 130 BP S126 EP S126 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PV UT WOS:000231745600131 ER PT J AU Sayers, SL Hanrahan, N Kutney, AM Clark, S Reis, B Riegel, B AF Sayers, SL Hanrahan, N Kutney, AM Clark, S Reis, B Riegel, B TI Comorbid mental disorder among patients hospitalized with heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 9th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 18-21, 2005 CL Boca Raton, FL SP Heart Failure Soc Amer C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Widener Univ, Inst Grad Clin Psychol, Chester, PA 19013 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2005 VL 11 IS 6 SU S MA 283 BP S165 EP S165 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PV UT WOS:000231745600284 ER PT J AU Luo, J Field, SJ Lee, JY Engelman, JA Cantley, LC AF Luo, J Field, SJ Lee, JY Engelman, JA Cantley, LC TI The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR-I; INCREASED INSULIN SENSITIVITY; ACTIVATED PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; MICE LACKING; SH2 DOMAINS; RECEPTOR SUBSTRATE-1; CATALYTIC SUBUNIT; 3T3-L1 ADIPOCYTES; P85-ALPHA SUBUNIT AB Phosphoinositide (PI) 3-kinase is required for most insulin and insulin-like growth factor (IGF) 1-dependent cellular responses. The p85 regulatory subunit of PI 3-kinase is required to mediate the insulin-dependent recruitment of PI 3-kinase to the plasma membrane, yet mice with reduced p85 expression have increased insulin sensitivity. To further understand the role of p85, we examined IGF-1-dependent translocation of p85 alpha by using a green fluorescence protein (GFP)-tagged p85 alpha (EGFP-p85 alpha). In response to IGF-1, but not to PDGF signaling, EGFP-p85 alpha translocates to discrete foci in the cell. These foci contain the insulin receptor substrate (IRS) 1 adaptor molecule, and their formation requires the binding of p85 to IRS-1. Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85-p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production. Ultrastructural analysis reveals that p85-IRS-1 foci are cytosolic protein complexes devoid of membrane. These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA089021, P01 CA089021]; NIDDK NIH HHS [K08 DK065108, K08 DK065108-01]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 52 TC 94 Z9 95 U1 0 U2 8 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 AUG 1 PY 2005 VL 170 IS 3 BP 455 EP 464 DI 10.1083/jcb.200503088 PG 10 WC Cell Biology SC Cell Biology GA 951AR UT WOS:000230901600014 PM 16043515 ER PT J AU Stuart, LM Deng, JS Silver, JM Takahashi, K Tseng, AA Hennessy, EJ Ezekowitz, RAB Moore, KJ AF Stuart, LM Deng, JS Silver, JM Takahashi, K Tseng, AA Hennessy, EJ Ezekowitz, RAB Moore, KJ TI Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR; FALCIPARUM-PARASITIZED ERYTHROCYTES; PROTEIN-TYROSINE KINASES; LIPOTEICHOIC ACID; MEDIATES CYTOADHERENCE; SIGNAL-TRANSDUCTION; INNATE IMMUNITY; ANTIGEN CD36; RECOGNITION; CELLS AB Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-alpha and IL-12 production. As a result, Cd36-/- mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, Boston, MA 02114 USA. Univ Edinburgh, MRC, Ctr Inflammat Res, Edinburgh EH8 9AG, Midlothian, Scotland. RP Moore, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. EM kmoore@molbio.mgh.harvard.edu OI Moore, kathryn/0000-0003-2505-2547 FU NIA NIH HHS [R01 AG020255, R01AG20255]; Wellcome Trust NR 39 TC 233 Z9 240 U1 2 U2 15 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 AUG 1 PY 2005 VL 170 IS 3 BP 477 EP 485 DI 10.1083/jcb.200501113 PG 9 WC Cell Biology SC Cell Biology GA 951AR UT WOS:000230901600016 PM 16061696 ER PT J AU Hainsworth, AH Bermpohl, D Webb, TE Darwish, R Fiskum, G Qiu, JH McCarthy, D Moskowitz, MA Whalen, MJ AF Hainsworth, AH Bermpohl, D Webb, TE Darwish, R Fiskum, G Qiu, JH McCarthy, D Moskowitz, MA Whalen, MJ TI Expression of cellular FLICE inhibitory proteins (cFLIP) in normal and traumatic murine and human cerebral cortex SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE caspases; human; mice; neuronal cell death; programmed cell death; reactive astrocytes; trauma; traumatic brian injury ID SPINAL-CORD-INJURY; TRAIL-INDUCED APOPTOSIS; BRAIN-INJURY; DEATH RECEPTOR; MEDIATED APOPTOSIS; FAS RECEPTOR; TNF-ALPHA; C-FLIP; ALZHEIMERS-DISEASE; UP-REGULATION AB Cellular Fas-associated death domain-like interleukin-1-beta converting enzyme (FLICE) inhibitory proteins (cFLIPs) are endogenous caspase homologues that inhibit programmed cell death. We hypothesized that cFLIPs are differentially expressed in response to traumatic brain injury (TBI). cFLIP-alpha and cFLIP-delta mRNA were expressed in normal mouse brain-specifically cFLIP-delta (but not cFLIP-alpha) protein was robustly expressed. After controlled cortical impact (CCl), cFLIP-alpha expression increased initially then decreased to control levels at 12 h, increasing again at 24-72 h (P<0.05). cFLIP-delta expression was decreased in brain homogenates by 12 h after CCl, then increased again at 24 to 72 h (P<0.05). cFLIP-delta immunostaining was markedly reduced in injured cortex, but not hippocampus, at 3 to 72 h after CCl. In cortex, reduced cFLIP-delta staining was found in TUNEL-positive cells, but in hippocampus TUNEL-positive cells expressed cFLIP-delta immunoreactivity. cFLIP-delta was increased in a subset of reactive astrocytes in pericontusional cortex and hippocampus at 48 to 72 h. Low levels of both cFLIP isoforms were detected in human cortical tissue with no TBI, from four patients undergoing brain surgery for epilepsy and <24 h post mortem from three patients without CNS pathologic assessment. In cortical tissue surgically removed <18 h after severe TBI (n=3), cFLIP-alpha expression was increased relative to epilepsy controls (P<0.05) but not relative to post-mortem controls. The data suggest differential spatial and temporal regulation of cFLIP-alpha and cFLIP-delta expression that may influence the magnitude of cell death and further implicate programmed mechanisms of cell death after TBI. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Neurosci, Sch Med, Charlestown, MA 02129 USA. De Montfort Univ, Pharmacol Res Grp, Leicester Sch Pharm, Leicester, Leics, England. Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Whalen, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Neurosci, Sch Med, Charlestown, MA 02129 USA. EM mwhalen@bics.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU Biotechnology and Biological Sciences Research Council [C17893]; NINDS NIH HHS [K08 NS041969, KO8NS41969, R01 NS037141, R01NS37141] NR 54 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2005 VL 25 IS 8 BP 1030 EP 1040 DI 10.1038/sj.jcbfm.9600104 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 950SL UT WOS:000230877600010 PM 15815586 ER PT J AU Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Rauf, A Scott, M Pollack, M Rosenbaum, JE AF Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Rauf, A Scott, M Pollack, M Rosenbaum, JE TI Childhood antecedents to panic disorder in referred and nonreferred adults SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SEPARATION ANXIETY HYPOTHESIS; REGRESSION TREES CART; EARLY-ONSET; CHILDREN; CLASSIFICATION; ASSOCIATION; AGORAPHOBIA; HISTORY; RISK AB Objective: We used a recursive partitioning method to examine antecedent childhood anxiety disorders in large samples of referred and nonreferred subjects with and without panic disorder. Methods: Referred subjects included adults treated for panic disorder (n = 131) and comparison adults with neither major anxiety nor mood disorders (n = 61). The nonreferred adult group derived from an opportunistic sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD), yielding 58 adults with panic disorder and 587 who were free of major anxiety, and mood disorders. Results: The majority of referred (65%) and nonreferred, (52%), adults, with panic disorder had antecedent childhood anxiety or disruptive behavior disorders. Classification and Regression Trees (CART) analysis showed that both, separation anxiety disorder and overanxious disorder were independent predictors of subsequent panic disorder in, both referred and nonreferred samples. Conclusions: These results confirm and extend previously reported findings by documenting that childhood anxiety disorders are important antecedent risk, factors for panic disorder, independently of referral bias. C1 Massachusetts Gen Hosp, Pediat Psychopharm Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Syracuse, Upstate Med Univ, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharm Clin, 15 Parkman St,WACC 725, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD36317]; NIMH NIH HHS [5R01MH50657, 2 R01 MH47077] NR 38 TC 16 Z9 16 U1 2 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2005 VL 15 IS 4 BP 549 EP 561 DI 10.1089/cap.2005.15.549 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 973EZ UT WOS:000232507000004 PM 16190787 ER PT J AU Faraone, SV Biederman, J Spencer, T Michelson, D Adler, L Reimherr, F Seidman, L AF Faraone, SV Biederman, J Spencer, T Michelson, D Adler, L Reimherr, F Seidman, L TI Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; NEUROPSYCHOLOGICAL PERFORMANCE; CHILDREN; ADHD; METHYLPHENIDATE; ADOLESCENTS; SAMPLE; BRAIN AB Objective: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD). Method: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task. Results: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop color-word score. Conclusions: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Behav Sci, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Lilly Res Labs, Indianapolis, IN USA. NYU, Sch Med, New York, NY USA. Univ Utah, Salt Lake City, UT USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 23 TC 43 Z9 44 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2005 VL 15 IS 4 BP 664 EP 670 DI 10.1089/cap.2005.15.664 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 973EZ UT WOS:000232507000014 PM 16190797 ER PT J AU Yoshii, A Takeoka, M Kelly, PJ Krishnamoorthy, KS AF Yoshii, A Takeoka, M Kelly, PJ Krishnamoorthy, KS TI Focal status epilepticus as atypical presentation of pyridoxine-dependent epilepsy SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID SEIZURES AB Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report air infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med,Boston Childrens Hosp, Dept Neurol, Div Epilepsy & Neurophysiol, Boston, MA 02115 USA. RP Krishnamoorthy, KS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, VBK731,55 Fruit St, Boston, MA 02114 USA. EM kkrishnamoorthy@partners.org NR 12 TC 8 Z9 9 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2005 VL 20 IS 8 BP 696 EP 698 DI 10.1177/08830738050200081301 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 006XL UT WOS:000234930900013 PM 16225819 ER PT J AU Kitz, RJ AF Kitz, RJ TI Leroy Vandam: an editorial tribute SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kitz, RJ (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM richard_kitz@hms.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2005 VL 17 IS 5 BP 327 EP 327 DI 10.1016/j.jclinane.2005.06.001 PG 1 WC Anesthesiology SC Anesthesiology GA 961JG UT WOS:000231657700001 ER PT J AU Acquadro, MA Borodic, GE AF Acquadro, MA Borodic, GE TI Botutinum toxin efficacy for the treatment of pain SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material ID TENSION-TYPE HEADACHE; BOTULINUM-A TOXIN; DOUBLE-BLIND; PROPHYLACTIC TREATMENT; MIGRAINE; MANAGEMENT; INJECTIONS; STATES; TRIAL; CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Acquadro, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM macquadro@partners.org NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2005 VL 17 IS 5 BP 328 EP 330 DI 10.1016/j.jclinane.2005.02.006 PG 3 WC Anesthesiology SC Anesthesiology GA 961JG UT WOS:000231657700002 PM 16102679 ER PT J AU Battantyne, JC Kupelnick, B McPeek, B Lau, J AF Battantyne, JC Kupelnick, B McPeek, B Lau, J TI Does the evidence support the use of spinal and epidural anesthesia for surgery? SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Review DE analgesia; neuraxial; anesthesia; epidural; neuraxial; regional; spinal ID PATIENT-CONTROLLED ANALGESIA; ABDOMINAL AORTIC-SURGERY; TOTAL HIP-REPLACEMENT; MOLECULAR-WEIGHT HEPARIN; HEALTH-RELATED QUALITY; GENERAL-ANESTHESIA; REGIONAL ANESTHESIA; RANDOMIZED TRIAL; VASCULAR-SURGERY; ELDERLY PATIENTS AB When spinal and epidural anesthesia were introduced into clinical practice, their primary use was as an alternative to general anesthesia. Later, largely as a result of the realization that opioids could be safely and effectively used to produce selective spinal analgesia, spinal and epidural (neuraxial) analgesia began to be used specifically for the treatment of perioperative pain. We present a systematic review of the literature on neuraxial anesthesia and analgesia, new meta-analyses that illustrate the powerful effect of improvements in perioperative safety in general on the ability of neuraxial techniques to make a difference, and a consideration of why a literature analysis does not provide clear answers. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Pain Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. RP Battantyne, JC (reprint author), Massachusetts Gen Hosp, Div Pain Med, Boston, MA 02114 USA. EM jballantyne@partners.org NR 111 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2005 VL 17 IS 5 BP 382 EP 391 DI 10.1016/j.jclinane.2004.10.005 PG 10 WC Anesthesiology SC Anesthesiology GA 961JG UT WOS:000231657700015 ER PT J AU Mantzoros, CS Li, T Manson, JE Meigs, JB Hu, FB AF Mantzoros, CS Li, T Manson, JE Meigs, JB Hu, FB TI Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; PRIOR MYOCARDIAL-INFARCTION; PLASMA ADIPONECTIN; INSULIN-RESISTANCE; PROTEIN ADIPONECTIN; JAPANESE POPULATION; FAT DISTRIBUTION; HDL-CHOLESTEROL; ADIPOSE-TISSUE; RISK-FACTOR AB Context: Low adiponectin levels, by regulating insulin resistance and metabolic profile, may contribute to the markedly increased risk of atherosclerosis in diabetic subjects. Objective: The complex interrelationships between adiponectin and metabolic abnormalities have not yet been fully assessed in diabetic women. Design/Setting/Patients: We performed a cross-sectional evaluation of the association between circulating adiponectin and glycemia, lipid-lipoprotein levels, and inflammatory markers in 925 women with type 2 diabetes enrolled in the Nurses' Health Study. Results: Circulating adiponectin levels were significantly and positively associated with high-density lipoprotein (HDL) cholesterol and physical activity levels, and inversely with body mass index and plasma concentrations of hemoglobin A(1c) (HgbA(1c)), triglycerides, non-HDL cholesterol, apolipoprotein B-100, C-reactive protein, fibrinogen, soluble E-selectin, and soluble intercellular adhesion molecule-1. The above associations were not appreciably altered after adjusting for lifestyle factors, existing medical conditions, obesity, and body fat distribution, with the exception of HgbA1c and soluble intercellular adhesion molecule-1 (which became nonsignificant). Associations between adiponectin and inflammatory markers persisted after control for the potential confounding effects of HgbA(1C) and HDL cholesterol, suggesting that the antiinflammatory properties of adiponectin are not mediated by its effect on glycemia and lipidemia. With the exception of the associations with triglycerides and apolipoprotein B(100), which were significant only in subjects with body mass index less than 30, all other associations observed herein were consistent among obese and nonobese diabetic women. Conclusions: In summary, higher adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in diabetic women. C1 Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr,Dept Med, 330 Brookline Ave,ST 816, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu FU NHLBI NIH HHS [HL-34594, HL-65582]; NIDDK NIH HHS [DK-58785, DK-58845] NR 46 TC 118 Z9 121 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2005 VL 90 IS 8 BP 4542 EP 4548 DI 10.1210/jc.2005-037 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953HZ UT WOS:000231068500019 PM 15914524 ER PT J AU Goodarzi, MO Wong, H Quinones, MJ Taylor, KD Guo, XQ Castellani, LW Antoine, HJ Yang, HY Hsueh, WA Rotter, JI AF Goodarzi, MO Wong, H Quinones, MJ Taylor, KD Guo, XQ Castellani, LW Antoine, HJ Yang, HY Hsueh, WA Rotter, JI TI The 3 ' untranslated region of the lipoprotein lipase gene: Haplotype structure and association with post-heparin plasma lipase activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-ARTERY-DISEASE; 3'-UNTRANSLATED REGION; INSULIN-RESISTANCE; TRANSLATIONAL REGULATION; MYOCARDIAL-INFARCTION; MEXICAN-AMERICANS; BLOOD-PRESSURE; MESSENGER-RNA; LPL GENE; POPULATION AB Context: Haplotypes comprising six single nucleotide polymorphisms (SNPs) (intron 7 to intron 9) of the lipoprotein lipase (LPL) gene appear to influence risk for atherosclerosis and insulin resistance in Mexican-Americans. Objective: Based on rodent studies, we hypothesized that these haplotypes are in linkage disequilibrium with functional variants in the 3' untranslated region of LPL, which is encoded by exon 10, and that these variants influence phenotype by altering LPL expression. Design: We sequenced exon 10 in subjects with divergent insulin sensitivity and divergent haplotypes. We also sequenced the other common LPL haplotypes. Variants identified by sequencing were genotyped in a large, family-based population along with the six SNPs spanning intron 7 to intron 9. We tested the potential functional significance of variation in exon 10 by evaluating association of haplotypes with post-heparin plasma LPL activity. Setting: The study took place within the general community, with the Mexican-American Coronary Artery Disease Project cohort. Participants: Participants included 847 subjects from 163 families. Main Outcome Measures: We determined LPL haplogenotype and post-heparin plasma LPL activity. Results: Exon 10 sequencing identified 15 variants. Thirteen of these variants were genotyped in large-scale along with the six SNPs spanning intron 7 to intron 9. LPL haplotypes and their relative frequencies in Mexican-Americans were determined. The fourth most common haplotype based on 19 SNPs (haplotype 19-4) was associated with increased LPL activity as well as multiple phenotypes related to the metabolic syndrome. Conclusions: These results support the possibility that variation in the 3' untranslated region of LPL affects LPL expression and activity, consequently influencing risk of atherosclerosis and insulin resistance, and provides important tools for further dissection of LPL regulation. C1 Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Lipid Res Lab, Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Endocrinol, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Div Diabet & Hypertens, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Div Cardiol, Dept Med, David Geffen Sch Med, Los Angeles, CA 90025 USA. RP Goodarzi, MO (reprint author), Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, 8700 Beverly Blvd,Becker B-128, Los Angeles, CA 90048 USA. EM mark.goodarzi@cshs.org OI Antoine, Heath/0000-0002-1914-3576 FU NHLBI NIH HHS [HL-28481, HL-60030] NR 40 TC 22 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2005 VL 90 IS 8 BP 4816 EP 4823 DI 10.1210/jc.2005-0389 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953HZ UT WOS:000231068500058 PM 15928243 ER PT J AU Santoro, N Torrens, J Crawford, S Allsworth, JE Finkelstein, JS Gold, EB Korenman, S Lasley, WL Luborsky, JL McConnell, D Sowers, MF Weiss, G AF Santoro, N Torrens, J Crawford, S Allsworth, JE Finkelstein, JS Gold, EB Korenman, S Lasley, WL Luborsky, JL McConnell, D Sowers, MF Weiss, G TI Correlates of circulating androgens in mid-life women: The study of women's health across the nation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIMENOPAUSAL WOMEN; MENOPAUSAL TRANSITION; SEXUAL FUNCTION; SURVEY SF-36; DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; ENDOCRINE PROFILES; INSULIN-RESISTANCE; METABOLIC SYNDROME; BODY-COMPOSITION AB Context: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. Objective: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. Design: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. Main Outcome Measures: Correlations of androgen measures with each other and with body mass index, waist circumference, and waist-hip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, self-reported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. Results: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR = 0.32; 95% confidence interval = 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR = 1.09; 95% confidence interval = 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. Conclusions: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being. C1 Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Div Reprod Endocrinol, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Univ, Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Michigan, Ann Arbor, MI 48104 USA. New England Res Inst, Watertown, MA 02472 USA. RP Santoro, N (reprint author), Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Div Reprod Endocrinol, 1300 Morris Pk Ave,Mazer 316, Bronx, NY 10461 USA. EM glicktoro@aol.com RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Allsworth, Jenifer/0000-0001-6559-8638 FU NIA NIH HHS [AG012531, AG012495, AG012505, AG012535, AG012539, AG012546, AG012553, AG012554]; NICHD NIH HHS [K12 HD01457, K24 HD419782]; NIDDK NIH HHS [K24 DK02759]; NINR NIH HHS [NR004061] NR 55 TC 138 Z9 142 U1 3 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2005 VL 90 IS 8 BP 4836 EP 4845 DI 10.1210/jc.2004-2063 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953HZ UT WOS:000231068500061 PM 15840738 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI How to predict the future - (Outcome of gastrointestinal disease) SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE confidence interval; epidemiology; prognosis; risk factors; statistics AB This short review is aimed to illustrate three simple rules to predict the outcome of a gastrointestinal disease. The first rule relates to the principle of WYSIWYG, that is, "what you see is what you get." To predict the future of a given digestive disease, the gastroenterologist needs to pay close attention to its present appearance and develop clear understanding of its pathophysiology. To delineate future trends, as a second rule, the gastroenterologist needs to delineate past trends and try to extrapolate them into the near future. Third, the length of the past medical history also provides a reliable estimate for the expected future lifetime of a gastrointestinal disease. These rules enable gastroenterologists to enlighten themselves, as well as their patients, about the future outcome of a given gastrointestinal disease. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2005 VL 39 IS 7 BP 570 EP 571 DI 10.1097/01.mcg.0000170738.36263.7b PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 950NK UT WOS:000230863900003 PM 16000922 ER PT J AU Nagoshi, T Matsui, T Aoyama, T Leri, A Anversa, P Li, L Ogawa, W del Monte, F Gwathmey, JK Grazette, L Hemmings, B Kass, DA Champion, HC Rosenzweig, A AF Nagoshi, T Matsui, T Aoyama, T Leri, A Anversa, P Li, L Ogawa, W del Monte, F Gwathmey, JK Grazette, L Hemmings, B Kass, DA Champion, HC Rosenzweig, A TI PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-FACTOR-I; ISCHEMIA-REPERFUSION INJURY; PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3-BETA; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORT; SENSITIVE PATHWAY; TRANSGENIC MICE AB Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI). However, less is known about the chronic effects of Akt activation in the heart, and, paradoxically, Akt is activated in samples from patients with chronic heart failure. We generated Tg mice with cardiac-specific expression of either activated (myristoylated [myr]) or dominant-negative (dn) Akt and assessed their response to IRI in an ex vivo model. While dn-Akt hearts demonstrated a moderate reduction in functional recovery after IRI, no function was restored in any of the myr-Akt-Tg hearts. Moreover, infarcts were dramatically larger in myr-Akt-Tg hearts. Biochemical analyses demonstrated that chronic Akt activation induces feedback inhibition of PI3K activity through both proteasome-dependent degradation of insulin receptor substrate-1 (IRS-1) and inhibition of transcription of IRS-1 as well as that of IRS-2. To test the functional significance of these signaling changes, we performed in vivo cardiac gene transfer with constitutively active PI3K in myr-Akt-Tg mice. Restoration of PI3K rescued function and reduced injury after IRI. These data demonstrate that PI3K-dependent but Akt-independent effectors are required for full cardioprotection and suggest a mechanism by which chronic Akt activation can become maladaptive. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Program Cardiovasc Gene Therapy, Charlestown, MA 02129 USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. Kobe Univ, Dept Clin Mol Med, Div Daibet Digest & Kidney Dis, Grad Sch Med, Kobe, Hyogo, Japan. Gwathmey Inc, Cambridge, MA USA. Friedrich Miescher Inst Biomed Res, Basel, Switzerland. Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. RP Rosenzweig, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Program Cardiovasc Gene Therapy, 114 16th St,Room 2600, Charlestown, MA 02129 USA. EM arosenzweig@partners.org FU NCRR NIH HHS [RR-016362]; NHLBI NIH HHS [K08 HL004250, R43 HL067516, HL-04250, R44 HL067516, HL-67516, HL-49574, HL-59521, R01 HL059521] NR 53 TC 145 Z9 147 U1 0 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2005 VL 115 IS 8 BP 2128 EP 2138 DI 10.1172/JCI23073 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951OJ UT WOS:000230939800027 PM 16007268 ER PT J AU Huang, FW Pinkus, JL Pinkus, GS Fleming, MD Andrews, NC AF Huang, FW Pinkus, JL Pinkus, GS Fleming, MD Andrews, NC TI A mouse model of juvenile hemochromatosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; IRON OVERLOAD; HEREDITARY HEMOCHROMATOSIS; HEPCIDIN; GENE; MUTATION; SLC11A3; MICE; FERROPORTIN AB Hereditary hemochromatosis is an iron-overload disorder resulting from mutations in proteins presumed to be involved in the maintenance of iron homeostasis. Mutations in hemojuvelin (HJV) cause severe, early-onset juvenile hemochromatosis. The normal function of HJV is unknown. Juvenile hemochromatosis patients have decreased urinary levels of hepcidin, a peptide hormone that binds to the cellular iron exporter ferroportin, causing its internalization and degradation. We have disrupted the murine Hjv gene and shown that Hjv(-/-) mice have markedly increased iron deposition in liver, pancreas, and heart but decreased iron levels in tissue macrophages. Hepcidin mRNA expression was decreased in Hjv(-/-) mice. Accordingly, ferroportin expression detected by immunohistochemistry was markedly increased in both intestinal epithelial cells and macrophages. We propose that excess, unregulated ferroportin activity in these cell types leads to the increased intestinal iron absorption and plasma iron levels characteristic of the juvenile hemochromatosis phenotype. C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Karp Family Res Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Karp Family Res Labs, 300 Longwood Ave,RM 8-125, Boston, MA 02115 USA. EM nancy_andrews@hms.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 FU NICHD NIH HHS [P30 HD018655, P30 HD18655]; NIDDK NIH HHS [R01 DK 066373, R01 DK066373, R01 DK 062474, R01 DK066373-02, R01 DK062474] NR 32 TC 219 Z9 228 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2005 VL 115 IS 8 BP 2187 EP 2191 DI 10.1172/JCI25049 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951OJ UT WOS:000230939800033 PM 16075059 ER PT J AU Moore, KJ Kunjathoor, VV Koehn, SL Manning, JJ Tseng, AA Silver, JM McKee, M Freeman, MW AF Moore, KJ Kunjathoor, VV Koehn, SL Manning, JJ Tseng, AA Silver, JM McKee, M Freeman, MW TI Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; FOAM CELL-FORMATION; MACROPHAGE-SPECIFIC EXPRESSION; MARROW-DERIVED CELLS; APOE-DEFICIENT MICE; TRANSGENIC MICE; CHOLESTEROL LEVELS; IMMUNE-COMPLEXES; LESIONS; ACCUMULATION AB Macrophage internalization of modified lipoproteins is thought to play a critical role in the initiation of atherogenesis. Two scavenger receptors, scavenger receptor A (SR-A) and CD36, have been centrally implicated in this lipid uptake process. Previous studies showed that these receptors mediated the majority of cholesterol ester accumulation in macrophages exposed to oxidized LDL and that mice with deletions of either receptor exhibited marked reductions in atherosclerosis. This work has contributed to an atherosclerosis paradigm: scavenger receptor-mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis. In this study, Apoe(-/-) mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks. Hyperlipidemic Cd36(-/-)Apoe(-/-) and Msr1(-/-)Apoe(-/-) mice showed significant reductions in peritoneal macrophage lipid accumulation in vivo; however, in contrast with previous reports, this was associated with increased aortic sinus lesion areas. Characterization of aortic sinus lesions by electron microscopy and immunohistochemistry showed abundant macrophage foam cells, indicating that lipid uptake by intimal macrophages occurs in the absence of CD36 or SR-A. These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, 55 Fruit St,GRJ1328, Boston, MA 02114 USA. EM freeman@molbio.mgh.harvard.edu OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [R01 HL045098, HL45098]; NIA NIH HHS [AG20255, R01 AG020255] NR 47 TC 243 Z9 254 U1 1 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2005 VL 115 IS 8 BP 2192 EP 2201 DI 10.1172/JCI24061 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951OJ UT WOS:000230939800034 PM 16075060 ER PT J AU Sun, WJ Lipsitz, S Catalano, P Mailliard, JA Haller, DG AF Sun, WJ Lipsitz, S Catalano, P Mailliard, JA Haller, DG TI Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NEUROENDOCRINE TUMORS; ITALIAN TRIALS; II TRIAL; OCTREOTIDE; 5-FLUOROURACIL; CHEMOTHERAPY; COMBINATION; EPIRUBICIN; INTERFERON; MANAGEMENT AB Purpose Optimal treatments for metastatic carcinoid tumor remain undefined, and the role of chemotherapy for symptomatic patients with progressive disease is uncertain. Patients and Methods Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function. Results In the randomized group, there was no difference between FU/DOX and FU/STZ in response rates (15.9% v 16%) and progression-free survival (4.5 v 5.3 months). FU/STZ (24.3 months) was superior to FU/DOX (15.7 months; P =.0267) in median survival. The response rate of crossover DTIC treatment was 8.2%, with a median survival of 11.9 months. Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ, and mild to moderate renal toxicity was reported in 40 (34.8%) of 115 patients in the FU/STZ arm. Conclusion Response to all three treatment regimens were modest. FU/STZ improved survival compared with the doxorubicin-based regimen, suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors. C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Creighton Univ, Omaha, NE 68178 USA. RP Sun, WJ (reprint author), Univ Penn, Abramson Canc Ctr, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM weijing.sun@uphs.upenn.edu FU NCI NIH HHS [CA13650, CA21115, CA233818, CA15488, CA66636] NR 20 TC 182 Z9 185 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 AUG 1 PY 2005 VL 23 IS 22 BP 4897 EP 4904 DI 10.1200/JCO.2005.01616 PG 8 WC Oncology SC Oncology GA 952CL UT WOS:000230979300023 PM 16051944 ER PT J AU Coleman, RE Major, P Lipton, A Brown, JE Lee, KA Smith, M Saad, F Zheng, M Hei, YJ Seaman, J Cook, R AF Coleman, RE Major, P Lipton, A Brown, JE Lee, KA Smith, M Saad, F Zheng, M Hei, YJ Seaman, J Cook, R TI Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID LONG-TERM EFFICACY; STAGE OCCUPATION PROBABILITIES; INTEGRATED TRANSITION HAZARDS; PLACEBO-CONTROLLED TRIAL; SKELETAL COMPLICATIONS; PROSTATE-CANCER; BREAST-CANCER; DOUBLE-BLIND; PAMIDRONATE DISODIUM; BIOCHEMICAL MARKERS AB Purpose Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. Patients and Methods Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (>= 100 nmol/mmol creatinine), and BAP as low (< 146 U/U or high (? 146 U/U. The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates. Results Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P <.001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P <.001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes. Conclusion The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates. C1 Weston Pk Hosp, Yorkshire Canc Res Acad Unit Clin Oncol, Ctr Canc Res, Sheffield S10 2SJ, S Yorkshire, England. McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Ctr Hosp Univ Montreal, Hop Notre Dame, Montreal, PQ, Canada. Penn State Univ Hosp, Milton S Hershey Med Ctr, Div Oncol, Hershey, PA 17033 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Nova Pharmaceut Corp, E Hanover, NJ USA. RP Coleman, RE (reprint author), Weston Pk Hosp, Yorkshire Canc Res Acad Unit Clin Oncol, Ctr Canc Res, Whitham Rd, Sheffield S10 2SJ, S Yorkshire, England. EM r.e.coleman@sheffield.ac.uk NR 32 TC 319 Z9 338 U1 1 U2 6 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 AUG 1 PY 2005 VL 23 IS 22 BP 4925 EP 4935 DI 10.1200/JCO.2005.06.091 PG 11 WC Oncology SC Oncology GA 952CL UT WOS:000230979300026 PM 15983391 ER PT J AU D'Amico, AV Chen, MH Roehl, KA Catalona, WJ AF D'Amico, AV Chen, MH Roehl, KA Catalona, WJ TI Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; MITOXANTRONE; RADIOTHERAPY; PREDNISONE; DOCETAXEL; DISEASE; GLANDS; BIOPSY AB Purpose We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. Patients and Methods A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than, 12 months or no PSA failure were identified using logistic regression. Results A preoperative PSA velocity more than 2.0 ng/mL/yr (P =.001) and biopsy Gleason score 7 (P=.006) or 8 to 10 (P=.003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P =.005), a nonpalpable cancer (P =.001) with a Gleason score <= 6 (P =.0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P=.03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. Conclusion A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NW Feinberg Sch Med, Dept Urol, Chicago, IL USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu NR 20 TC 78 Z9 78 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 AUG 1 PY 2005 VL 23 IS 22 BP 4975 EP 4979 DI 10.1200/JCO.2005.08.904 PG 5 WC Oncology SC Oncology GA 952CL UT WOS:000230979300031 PM 16051949 ER PT J AU Punglia, RS Kuntz, KM Winer, EP Weeks, JC Burstein, HJ AF Punglia, RS Kuntz, KM Winer, EP Weeks, JC Burstein, HJ TI Optimizing adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer: A decision analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED-TRIAL; TAMOXIFEN THERAPY; ANASTROZOLE; RECURRENCE; LETROZOLE AB Purpose The optimal adjuvant endocrine strategy for postmenopausal breast cancer is unknown. Options include the antiestrogen tamoxifen, estrogen deprivation with aromatase inhibitors, and sequential therapy with tamoxifen and then an aromatase inhibitor. Methods We developed Markov models to simulate 10-year disease-free survival among postmenopausal women with hormone receptor-positive breast cancer. The treatment strategies analyzed were 5 years of tamoxifen alone, 5 years of an aromatase inhibitor alone, and sequential treatment consisting of tamoxifen with cross over to an aromatase inhibitor at 2.5 or 5 years. Risk estimates were derived from reported randomized clinical trials. Results Sequential therapy with tamoxifen followed by cross over to an aromatase inhibitor at 2.5 years yielded a modest improvement in disease-free survival compared with planned aromatase inhibitor monotherapy. At 10 years, the cross-over strategy yielded absolute disease-free survival rates of 83.7% and 67.6% for node-negative and node-positive patients, respectively, compared with 82.6% and 65.5%, respectively, for aromatase inhibitor monotherapy, which is a 6% relative risk reduction. Sequential therapy improved disease-free survival estimates by year 6 after treatment initiation. Later cross over from tamoxifen to an aromatase inhibitor at 5 years did not further. improve 10-year disease-free survival estimates. Sensitivity analyses suggest that sequential treatment strategies optimized 10-year disease-free and distant disease-free survival independent of the degree of the beneficial carryover effect after aromatase inhibitor therapy or the ratio of local to distant tumor recurrence. Conclusion Modeling estimates suggest that sequential adjuvant therapy with tamoxifen followed by an aromatase inhibitor after 2.5 years yields improved outcomes compared with either drug alone or cross-over treatment after 5 years of tamoxifen. C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 16 TC 65 Z9 69 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2005 VL 23 IS 22 BP 5178 EP 5187 DI 10.1200/JCO.2005.02.964 PG 10 WC Oncology SC Oncology GA 952CL UT WOS:000230979300055 PM 15998905 ER PT J AU Iosifescu, DV Nierenberg, AA Mischoulon, D Perlis, RH Papakostas, GI Ryan, JL Alpert, JE Fava, M AF Iosifescu, DV Nierenberg, AA Mischoulon, D Perlis, RH Papakostas, GI Ryan, JL Alpert, JE Fava, M TI An open study of triiodothyronine augmentation of selective serotonin Reuptake inhibitors in treatment-resistant major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc ID TRICYCLIC ANTIDEPRESSANT RESPONSE; HIGH-DOSE THYROXINE; REFRACTORY DEPRESSION; POTENTIATION; FAILURE; T3 AB Objective: In an open trial, we investigated the efficacy of triiodothyronine (T,) adjuvant to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder (MDD) resistant to SSRI treatment. Method. Twenty subjects who met DSM-IV criteria for MDD (mean +/- SD age = 44.3 +/- 10.3 years; 55% [N = I I] women) and had failed to respond to a course of treatment of at least 8 weeks with an SSRI antidepressant were enrolled in a 4-week open-label augmentation treatment with T-3 50 mu g/day. Atypical and melancholic subtypes of MDD were diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders criteria. We administered the 17-item Hamilton Rating Scale for Depression (HAM-D-17) 4 times during the study (which was conducted between 2001 and 2003). Results: During T3 augmentation, the severity of depression decreased from an initial mean SD HAM-D-17 score of 20.5 +/- 3.6 to a final HAM-D-17 score of 14.0 +/- 7.1 (p < .001). Seven subjects (35.0%) were treatment responders (HAM-D-17 reduction >= 50%), and 6 subjects (30.0%) achieved clinical remission (final HAM-D-17 : 7). The 5 subjects with atypical depression experienced significantly (p < .01) greater clinical improvement (final HAM-D-17 scores 6.6 +/- 1.8 vs. 16.4 +/- 4.5), and higher rates of treatment response (100% [5/5] vs. 13.3% [2/15]) and remission (80.0% [4/5] vs. 13.3% [2/15]), compared to subjects with nonatypical MDD. The 8 subjects with melancholic MDD experienced significantly (p < .05) greater depression severity at the end of the study compared to nonmelancholic MDD subjects (final HAM-D-17 scores = 18.3 +/- 6.6 vs. 11.1 +/- 6.1). Conclusion: Triiodothyronine augmentation of SSRIs may be a promising treatment strategy in SSRI-resistant MDD, particularly in subjects with the atypical MDD subtype. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 16 TC 33 Z9 34 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2005 VL 66 IS 8 BP 1038 EP 1042 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 957AK UT WOS:000231341400012 PM 16086620 ER PT J AU Dombrovski, AY Mulsant, BH Haskett, RF Prudic, J Begley, AE Sackeim, HA AF Dombrovski, AY Mulsant, BH Haskett, RF Prudic, J Begley, AE Sackeim, HA TI Predictors of remission after electroconvulsive therapy in unipolar major depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; SHORT-TERM RESPONSE; MEDICATION RESISTANCE; CONTINUATION PHARMACOTHERAPY; CLINICAL-RESPONSE; MENTAL-HEALTH; RATING-SCALE; ECT RESPONSE; FOLLOW-UP AB Context: Electroconvulsive therapy (ECT) is the most effective biological treatment for major depression. However, there is little agreement about clinically useful predictors of acute ECT outcomes. Objective: To assess whether age, sex, burden of comorbid physical illness, age at onset, history of recurrence, episode duration, chronic depression or comorbid dysthymia, melancholic features, episode severity, and medication resistance are predictors of remission after an acute course of ECT. Design: We performed an analysis using data gathered prospectively in 328 patients with unipolar major depression (according to Research Diagnostic Criteria) treated with ECT. The study was conducted from 1993 through 1999. Patients had a pretreatment score of 21 or higher on the 24-item Hamilton Rating Scale for Depression (HAM-D). Treatment history was assessed using the Antidepressant Treatment History Form. Remission was defined as a 24-item HAM-D score of 10 or less and a 60% or more relative reduction of the HAM-D score. Results: On univariate logistic regression, statistically significant predictors of nonremission were chronic depression/dysthymia, medication resistance, longer episode duration, and younger age. On backward elimination logistic regression, only medication resistance (OR = 1.67, 95% CI = 1.05 to 2.67) and chronic depression/dysthymia (OR = 1.84, 95% CI = 1.06 to 3.21) were statistically significant predictors of nonremission. Conclusions: In patients with major depression, lower rates of remission after acute ECT are associated with medication resistance and chronicity, but not with age or burden of physical illness. C1 Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, GRECC, Pittsburgh, PA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Mulsant, BH (reprint author), Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, 3811 OHara St,E837, Pittsburgh, PA 15213 USA. EM mulsantbh@upmc.edu OI Dombrovski, Alexandre/0000-0002-2054-4772 FU NIMH NIH HHS [MH48512, MH52247, MH01613, MH30915] NR 62 TC 64 Z9 66 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2005 VL 66 IS 8 BP 1043 EP 1049 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 957AK UT WOS:000231341400013 PM 16086621 ER PT J AU Petersen, T Papakostas, GI Posternak, MA Kant, A Guyker, WM Iosifescu, DV Yeung, AS Nierenberg, AA Fava, M AF Petersen, T Papakostas, GI Posternak, MA Kant, A Guyker, WM Iosifescu, DV Yeung, AS Nierenberg, AA Fava, M TI Empirical testing of two models for staging antidepressant treatment resistance SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID MAJOR DEPRESSION; FOLLOW-UP; STRATEGIES; REMISSION; AUGMENTATION; NONRESPONSE; DISORDERS; RECOVERY; SYMPTOMS AB Background: An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission and one's degree of resistance is not clearly known at this time. This study was undertaken to empirically test 2 recent models for staging treatment resistance. Materials and Methods: Psychiatrists from 2 academic sites reviewed charts of patients on their caseloads. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales were used to measure severity of depression and response to treatment, and 2 treatment-resistant staging scores were classified for each patient using the Massachusetts General Hospital staging method (MGH-S) and the Thase and Rush staging method (TR-S). Results: Out of the 115 patient records reviewed, 58 (49.6%) patients remitted at some point during treatment. There was a significant positive correlation between the 2 staging scores, and logistic regression results indicated that greater MGH-S scores, but not TR-S scores, predicted nonremission. Conclusions: This study suggests that the hierarchical manner in which the field has typically gauged levels of treatment resistance may not be strongly supported by empirical evidence. This study suggests that the NIGH staging model may offer some advantages over the staging method by Thase and Rush, as it generates a continuous score that considers both number of trials and intensity/optimization of each trial. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM tpetersen@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 26 TC 69 Z9 70 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2005 VL 25 IS 4 BP 336 EP 341 DI 10.1097/01.jcp.0000169036.40755.16 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 950SD UT WOS:000230876800008 PM 16012276 ER PT J AU Beresford, TP Clapp, L Martin, B Wiberg, JL Alfers, J Beresford, HF AF Beresford, TP Clapp, L Martin, B Wiberg, JL Alfers, J Beresford, HF TI Aripiprazole in schizophrenia with cocaine dependence - A pilot study SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SUBSTANCE-ABUSE; RELIABILITY; HALOPERIDOL; OLANZAPINE; PSYCHOSIS; ALCOHOL; SYSTEM AB The debilitation of schizophrenia (SCHZ) worsens markedly with comorbid cocaine dependence (CD) and alcohol abuse. To date, no medications have conclusively demonstrated effects against both SCHZ and CD (SCHZ + CD) simultaneously. Because of its dopamine-modulating properties, we hypothesized that aripiprazole would alleviate cocaine craving in patients with SCHZ + CD. We conducted a prospective, 8-week, open-label trial in poorly compliant SCHZ + CD subjects. Each received aripiprazole as their sole neuroleptic agent at a maximum dose of 15 mg/d. The Brief Psychiatric Rating Scale (BPRS) and the Brief Substance Craving Scale (BSCS) measured psychosis and subjective cocaine and alcohol cravings. Urine tests for cocaine provided data on actual use. Of 10 male subjects entered, 6 (60%) completed the 8-week trial. In those cases, positive urine tests dropped significantly (P < 0.001) after 2 weeks, when aripiprazole had reached steady state. Mean cocaine craving scores declined significantly (P = 0.026) as did mean alcohol craving scores (P = 0.006). Declining psychosis scores were associated with declining cocaine craving (r = 0.87, P < 0.01) and alcohol craving (r = 0.88, P < 0.01), respectively. This experience suggests possible aripiprazole effects in lowering both desire for and the use of cocaine in comorbid SCHZ subjects. These data suggest double-blind, randomized, comparison study in this severely ill, comorbid patient group. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Med Ctr, Dept Vet Affairs, Denver Res Inst, Denver, CO USA. RP Beresford, TP (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.beresford@uchsc.edu FU NIAAA NIH HHS [AA 014010] NR 32 TC 68 Z9 69 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2005 VL 25 IS 4 BP 363 EP 366 DI 10.1097/01.jcp.0000169419.38899.5b PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 950SD UT WOS:000230876800012 PM 16012280 ER PT J AU Bersani, G Gherardelli, S Clemente, R Di Giannantonio, M Grilli, A Conti, CMV Exton, MS Conti, P Doyle, R Paneheri, P AF Bersani, G Gherardelli, S Clemente, R Di Giannantonio, M Grilli, A Conti, CMV Exton, MS Conti, P Doyle, R Paneheri, P TI Neurologic soft signs in schizophrenic patients treated with conventional and atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PSYCHIATRIC-PATIENTS; NEUROLEPTIC-NAIVE; PSYCHOPATHOLOGY; ABNORMALITIES; PERFORMANCE; DYSFUNCTION; INSTRUMENT; STABILITY; SIBLINGS AB Neurologic soft signs (NSS) are considered a somatic feature associated with schizophrenia (DSM-IV) that are present in neuroleptic-treated, as well as untreated or first-episode patients. The aim of this study was to determine the incidence and severity of NSS in groups of schizophrenic patients treated with either a conventional neuroleptic medication, haloperidol (n = 37), or atypical antipsychotic medications, risperidone (n = 19), clozapine (n = 34), and olanzapine (n = 18). NSS were assessed with the Neurological Evaluation Scale (NES), whereas extrapyramidal symptoms (EPS), which occur more commonly with conventional neuroleptic treatment, were evaluated using the Simpson-Angus Scale. NES scores were not significantly different between groups. Slight differences were found for 2 items only. The haloperidol group showed higher scores for the "Romberg test," whereas the clozapine group showed higher scores for "short-term memory. " There were significant correlations between EPS and NES total score in the haloperidol and risperidone groups. These results demonstrate an overall overlapping of NSS among the groups, confirming their substantial independence from neurologic implications of neuroleptic treatment. C1 Univ Roma La Sapienza, Psychiat Clin 3, Dept Psychiat Sci & Psychol Med, I-00100 Rome, Italy. Univ Chieti, Sch Psychol, Chieti, Italy. Univ Urbino, Sch Psychol, Urbino, Italy. Eli Lilly Australia Pty Ltd, Sydney, NSW, Australia. Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. Univ Chieti, Div Immunol, Chieti, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Bersani, G (reprint author), Univ Roma La Sapienza, Psychiat Clin 3, Dept Psychiat Sci & Psychol Med, Via Torre Argentina 21, I-00100 Rome, Italy. EM bersani@uniromal.it OI grilli, alfredo/0000-0002-5746-5007 NR 42 TC 26 Z9 26 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2005 VL 25 IS 4 BP 372 EP 375 DI 10.1097/01.jcp.0000169268.44421.cf PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 950SD UT WOS:000230876800014 PM 16012282 ER PT J AU Pozner, CN Levine, M Zane, R AF Pozner, CN Levine, M Zane, R TI The cardiovascular effects of cocaine SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE cocaine; myocardial infarction; chest pain; drug; intoxication ID INDUCED CORONARY VASOCONSTRICTION; ACUTE MYOCARDIAL-INFARCTION; INDUCED CHEST PAIN; ARTERY VASOCONSTRICTION; CRACK COCAINE; DRUG-ABUSE; TROPONIN-I; COMPLICATIONS; NITROGLYCERIN; EMERGENCY AB Cocaine use continues to be prevalent among all races and socioeconomic groups in the United States. Patients presenting to emergency departments after cocaine ingestion frequently present with a chief complaint of chest pain. Although acute myocardial infarction is perhaps the most concerning diagnosis in this setting, there are many other potential causes of chest pain after cocaine ingestion. This article reviews the pharmacology of cocaine, as well as the etiologies and treatment of cocaine-associated chest pain, with an emphasis on this drug's range of cardiovascular effects. (c) 2005 Elsevier Inc. C1 Harvard Univ, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA USA. RP Pozner, CN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 77 TC 24 Z9 29 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2005 VL 29 IS 2 BP 173 EP 178 DI 10.1016/j.jemermed.2005.01.019 PG 6 WC Emergency Medicine SC Emergency Medicine GA 949FT UT WOS:000230771200011 PM 16029829 ER PT J AU Thomas, SH Rago, O Harrison, T Biddinger, PD Wedel, SK AF Thomas, SH Rago, O Harrison, T Biddinger, PD Wedel, SK TI Fentanyl trauma analgesia use in air medical scene transports SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Associational-of-EMS-Physicians CY JAN 13-15, 2005 CL Naples, FL SP Natl Assoc EMS Phys DE fentanyl; prehospital; analgesia; helicopter; air medical transport ID ACUTE PAIN MANAGEMENT; PEDIATRIC TRAUMA; ABDOMINAL-PAIN; EMERGENCY; CARE; MORPHINE; PROGRAM AB This study assessed frequency, safety and efficacy of prehospital fentanyl analgesia during 6 months' adult and pediatric helicopter trauma scene transports (213 doses in 177 patients). We reviewed flight records for pain assessment and analgesia provision, effect, and complications. Analgesia was administered to 46/49 (93.9%) intubated patients. In non-intubated patients, pain assessment was documented in 112 of 128 (87.5%), and analgesia was offered, or there was no pain, in 97/128 (75.8%). Of the 67 non-intubated patients to whom analgesia was administered, post-analgesia pain assessment was documented in 62 (92.5%) and pain improved in 53 (79.1% of 67). Post-analgesia blood pressure dropped below 90 torr in 2/177 cases (1.1%, 95% confidence interval [CI] 0.1-4.0%). Post-analgesia SpO2 did not drop below 90% in any patients (95% CI 0-2.3%). In this study, prehospital providers performed well with respect to pain assessment and treatment. Fentanyl was provided frequently, with good effect and minimal cardiorespiratory consequence. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Boston MedFlight, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Boston Univ, Dept Surg, Sch Med, Boston, MA 02215 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Clin Bldg 115,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2005 VL 29 IS 2 BP 179 EP 187 DI 10.1016/j.jemermed.2005.02.007 PG 9 WC Emergency Medicine SC Emergency Medicine GA 949FT UT WOS:000230771200012 PM 16029830 ER PT J AU Shewakramani, S McCann, DJ Thomas, SH Nadel, ES Brown, DFM AF Shewakramani, S McCann, DJ Thomas, SH Nadel, ES Brown, DFM TI Sixth cranial nerve palsy SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID MULTIPLE-SCLEROSIS; PATIENT; ARTERY C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2005 VL 29 IS 2 BP 207 EP 211 DI 10.1016/j.jemermed.2005.04.006 PG 5 WC Emergency Medicine SC Emergency Medicine GA 949FT UT WOS:000230771200016 PM 16029834 ER PT J AU Alvarez, GA Horowitz, TS Arsenio, HC DiMase, JS Wolfe, JM AF Alvarez, GA Horowitz, TS Arsenio, HC DiMase, JS Wolfe, JM TI Do multielement visual tracking and visual search draw continuously on the same visual attention resources? SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article DE tracking; search; attention; dual task; attention operating characteristic ID PSYCHOPHYSICS; MULTIPLE; INDEXES; TASKS; MODEL AB Multielement visual tracking and visual search are 2 tasks that are held to require visual-spatial attention. The authors used the attentional operating characteristic (AOC) method to determine whether both tasks draw continuously on the same attentional resource (i.e., whether the 2 tasks are mutually exclusive). The authors found that observers can search and track within the same trial significantly better than would be predicted if the 2 tasks were mutually exclusive. In fact, the AOC for tracking and search is similar to that for tracking and auditory monitoring. The results of additional experiments support an attention-switching account for this high level of dual-task performance in which a single attentional resource is efficiently switched between the tracking and search. The results provide important constraints for architectures of visual selective attention and the mechanisms of multielement tracking. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Ophthalmol, Boston, MA USA. Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Alvarez, GA (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,7th Floor, Cambridge, MA 02138 USA. EM geoalvarez@wjh.harvard.edu RI Wolfe, Jeremy/C-1621-2012; Horowitz, Todd/J-3376-2013; Wolfe, Jeremy/A-9248-2016 OI Wolfe, Jeremy/0000-0002-6475-1984; Wolfe, Jeremy/0000-0002-6475-1984 NR 25 TC 37 Z9 40 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-1523 J9 J EXP PSYCHOL HUMAN JI J. Exp. Psychol.-Hum. Percept. Perform. PD AUG PY 2005 VL 31 IS 4 BP 643 EP 667 DI 10.1037/0096-1523.31.4.643 PG 25 WC Psychology; Psychology, Experimental SC Psychology GA 959TS UT WOS:000231542800001 PM 16131240 ER PT J AU Hayward, RA Asch, SM Hogan, MM Hofer, TP Kerr, EA AF Hayward, RA Asch, SM Hogan, MM Hofer, TP Kerr, EA TI Sins of omission - Getting too little medical care may be the greatest threat to patient safety SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality of care; adverse events; patient safety; medical errors ID ADVERSE DRUG EVENTS; QUALITY-OF-CARE; DIABETES CARE; HOSPITALIZED-PATIENTS; HEALTH; ERRORS; CHOICE; MODEL; APPROPRIATENESS; PREVENTABILITY AB BACKGROUND: Little is known about the relative incidence of serious errors of omission versus errors of commission. OBJECTIVE: To identify the most common substantive medical errors identified by medical record review. DESIGN: Retrospective cohort study. SETTING: Twelve Veterans Affairs health care systems in 2 regions. PARTICIPANTS: Stratified random sample of 621 patients receiving care over a 2-year period. MAIN OUTCOME MEASURE: Classification of reported quality problems. METHODS: Trained physicians reviewed the full inpatient and outpatient record and described quality problems, which were then classified as errors of omission versus commission. RESULTS: Eighty-two percent of patients had at least 1 error reported over a 13-month period. The average number of errors reported per case was 4.7 (95% confidence intervals [CI]: 4.4, 5.0). Overall, 95.7% ( 95% CI: 94.9%, 96.4%) of errors were identified as being problems with under-use. Inadequate care for people with chronic illnesses was particularly common. Among errors of omission, obtaining insufficient information from histories and physicals (25.3%), inadequacies in diagnostic testing (33.9%), and patients not receiving needed medications (20.7%) were all common. Out of the 2,917 errors identified, only 27 were rated as being highly serious, and 26 (96%) of these were errors of omission. CONCLUSIONS: While preventing iatrogenic injury resulting from medical errors is a critically important part of quality improvement, we found that the overwhelming majority of substantive medical errors identifiable from the medical record were related to people getting too little medical care, especially for those with chronic medical conditions. C1 Vet Affairs Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA USA. Rand Hlth Program, Santa Monica, CA USA. RP Hayward, RA (reprint author), POB 130170, Ann Arbor, MI 48113 USA. EM rhayward@umich.edu FU PHS HHS [P60-972573] NR 55 TC 44 Z9 44 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 686 EP 691 DI 10.1111/j.1525-1497.2005.0152.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900003 PM 16050875 ER PT J AU Shrank, WH Kutner, JS Richardson, T Mularski, RA Fischer, S Kagawa-Singer, M AF Shrank, WH Kutner, JS Richardson, T Mularski, RA Fischer, S Kagawa-Singer, M TI Focus group findings about the influence of culture on communication preferences in end-of-life care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE end-of-life; communication; cultural sensitivity; focus groups; ethnicity ID NOT-RESUSCITATE ORDERS; ILL HOSPITALIZED ADULTS; NURSING-HOME RESIDENTS; ADVANCE DIRECTIVES; AFRICAN-AMERICANS; SUSTAINING TREATMENTS; DECISION-MAKING; ETHNICITY; RACE; PERSPECTIVES AB BACKGROUND: Little guidance is available for health care providers who try to communicate with patients and their families in a culturally sensitive way about end-of-life care. OBJECTIVE: To explore the content and structure of end-of-life discussions that would optimize decision making by conducting focus groups with two diverse groups of patients that vary in ethnicity and socioeconomic status. DESIGN: Six focus groups were conducted; 3 included non-Hispanic white patients recruited from a University hospital (non- Hispanic white groups) and 3 included African-American patients recruited from a municipal hospital (African-American groups). A hypothetical scenario of a dying relative was used to explore preferences for the content and structure of communication. PARTICIPANTS: Thirty-six non-Hispanic white participants and 34 African-American participants. APPROACH: Content analysis of focus group transcripts. RESULTS: Non-Hispanic white participants were more exclusive when recommending family participants in end-of-life discussions while African-American participants preferred to include more family, friends and spiritual leaders. Requested content varied as non-Hispanic white participants desired more information about medical options and cost implications while African-American participants requested spiritually focused information. Underlying values also differed as non-Hispanic white participants expressed more concern with quality of life while African-American participants tended to value the protection of life at all costs. CONCLUSIONS: The groups differed broadly in their preferences for both the content and structure of end-of-life discussions and on the values that influence those preferences. Further research is necessary to help practitioners engage in culturally sensitive end-of-life discussions with patients and their families by considering varying preferences for the goals of end-of-life care communication. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Boulder, CO 80309 USA. Kaiser Permanente, Denver, CO USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, Denver, CO USA. Asian Amer Studies, Los Angeles, CA USA. RP Shrank, WH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM William.Shrank@med.va.gov NR 34 TC 46 Z9 47 U1 3 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 703 EP 709 DI 10.1111/j.1525-1497.2005.0151.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900006 PM 16050878 ER PT J AU Nicolaidis, C Curry, M Gerrity, M AF Nicolaidis, C Curry, M Gerrity, M TI Measuring the impact of the Voices of survivors program on health care workers' attitudes toward survivors of intimate partner violence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE intimate partner violence; continuing medical education; survey instrument; provider attitudes; measurement ID DOMESTIC VIOLENCE; FAMILY-VIOLENCE; CLINICAL CHARACTERISTICS; MEDICAL-EDUCATION; PUBLIC-HEALTH; WOMEN; ABUSE; KNOWLEDGE; PRACTITIONERS; CONSEQUENCES AB BACKGROUND: Most continuing medical education programs on intimate partner violence (IPV) use an expert-driven approach and focus on changing knowledge and screening behaviors. The Voices of Survivors program aims to also improve attitudes and empathy. OBJECTIVES: To test the Attitudes Toward Survivors of IPV (ATSI) survey psychometrically. To assess the effectiveness of the Voices of Survivors program in changing health care workers' responsibility to assess for and counsel about IPV, respect for patient autonomy, empathy toward patients in abusive relationships, barriers, confidence, knowledge, and self-reported assessment behaviors. SETTING: Thirty-one unaffiliated primary care practices in Washington County, Ore. DESIGN: Comparison of ATSI survey results before and after a two-hour workshop including a 30-minute video and an advocate-led discussion. PARTICIPANTS: Convenience sample of primary care providers, medical support staff, and other clinic employees. RESULTS: Two hundred and eighty-four health care workers participated in the training. Two hundred and sixty-seven (94%) completed workshop evaluations and 187 (66%) completed both pre- and postintervention surveys. Cronbach's alpha for all scales ranged from 0.68 to 0.92. Postintervention, participants' summary scores improved for responsibility to assess for IPV (3.96 vs 3.64; P < .0001), respect for patient autonomy (2.78 vs 2.41; P < . 0001), empathy (3.24 vs. 2.99; P = .002), confidence (2.33 vs 2.07; P < .0001), knowledge (2.08 vs 1.64; P < .0001), and self-reported behaviors (3.08 vs 2.53; P = .0001). Barriers related to availability of resources and referrals also improved. CONCLUSIONS: The ATSI scales demonstrated good internal reliability and responsiveness to change in all domains except responsibility to counsel. The Voices of Survivors documentary, along with a workshop based on its companion guide, improved clinic employees' knowledge, attitudes, empathy, and self-reported assessment behaviors about IPV. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. RP Nicolaidis, C (reprint author), Oregon Hlth Sci Univ, Dept Med, L475,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM nicolaid@ohsu.edu NR 38 TC 6 Z9 6 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 731 EP 737 DI 10.1111/j.1525-1497.2005.0141.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900011 PM 16050883 ER PT J AU Morrill, JA Shrestha, M Grant, RW AF Morrill, JA Shrestha, M Grant, RW TI Barriers to the treatment of hepatitis C SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE hepatitis C virus infection; interferon and ribavirin therapy; barriers to treatment; substance abuse ID INJECTION-DRUG USERS; VIRUS-INFECTION; PLUS RIBAVIRIN; UNITED-STATES; THERAPY; STAY; CARE AB BACKGROUND: Hepatitis C virus (HCV) infection is both prevalent and undertreated. OBJECTIVE: To identify barriers to HCV treatment in primary care practice. DESIGN:Cross-sectional study. SETTING AND PARTICIPANTS: A cohort of 208 HCV-infected patients under the care of a primary care physician (PCP) between December 2001 and April 2004 at a single academically affiliated community health center. MEASUREMENTS: Data were collected from the electronic medical record (EMR), the hospital clinical data repository, and interviews with PCPs. MAIN RESULTS: Our cohort consisted of 208 viremic patients with HCV infection. The mean age was 47.6 (+/- 9.7) years, 56% were male, and 79% were white. Fifty-seven patients (27.4% of the cohort) had undergone HCV treatment. Independent predictors of not being treated included: unmarried status (adjusted odds ratio [aOR] for treatment 0.36, P=.02), female gender (aOR 0.31, P=.01), current alcohol abuse (aOR 0.08, P=.0008), and a higher ratio of no-shows to total visits (aOR 0.005 per change of 1.0 in the ratio of no-shows to total visits, P=.002). The major PCP-identified reasons not to treat included: substance abuse (22.5%), patient preference (16%), psychiatric comorbidity (15%), and a delay in specialist input (12%). For 13% of the untreated patients, no reason was identified. CONCLUSION: HCV treatment was infrequent in our cohort of outpatients. Barriers to treatment included patient factors (patient preference, alcohol use, missed appointments), provider factors (reluctance to treat past substance abusers), and system factors (referral-associated delays). Multimodal interventions may be required to increase HCV treatment rates. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. MGH Revere HealthCare Ctr, Revere, MA USA. RP Morrill, JA (reprint author), MGH Charlestown HealthCare Ctr, Adult Med Unit, 73 High St, Charlestown, MA 02139 USA. EM jmorrill@partners.org NR 26 TC 110 Z9 110 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 754 EP 758 DI 10.1111/j.1525-1497.2005.0161.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900015 PM 16050887 ER PT J AU Atlas, SJ McDermott, SM Mannone, C Barry, MJ AF Atlas, SJ McDermott, SM Mannone, C Barry, MJ TI The role of point of care testing for patients with acute pharyngitis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT New England Regional Meeting of the Society-of-General-Internal-Medicine CY MAR 05, 2004 CL Boston, MA SP Soc Gen Internal Med DE pharyngitis; point of care testing; diagnostic accuracy; guideline ID SORE THROAT; STREPTOCOCCAL PHARYNGITIS; PRESCRIBING STRATEGIES; STREP THROAT; ADULTS; MANAGEMENT; DIAGNOSIS; TRIAL; GUIDELINES AB BACKGROUND: There is no consensus favoring a particular strategy for evaluating patients with pharyngitis. OBJECTIVE: To compare a clinical decision aid and a rapid office-based point of care (POC) test with routine culture for group A beta-hemolytic streptococcus (GAS). DESIGN: Prospective observational study. PARTICIPANTS: Among 179 patients enrolled, 150 were eligible and 148 had POC testing and cultures initially performed. MEASUREMENTS: An encounter form included eligibility criteria, clinical information based upon the Centor rule, and treatment provided. Sensitivity and specificity of POC test compared to routine culture for GAS. RESULTS: Thirty-eight patients (25.7%) had a positive GAS culture. The POC test was 92.1% sensitive (95% confidence interval [CI] 80% to 98%) and 100% specific (95% CI 97% to 100%). Although the Centor rule did not adequately discriminate among symptomatic patients with or without GAS (receiver operating curve area 0.63), the 3 patients with a false-negative POC test had a Centor score of less than 2. Among patients with a negative POC test, 26% initially received antibiotics. CONCLUSION: For patients with a Centor score of >= 2, a POC test was highly sensitive for GAS. Future studies should confirm these results and assess whether implementation of POC testing as part of a local practice guideline can decrease variability in testing and treatment. C1 Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Med Serv, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org NR 18 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 759 EP 761 DI 10.1111/j.1525-1497.2005.0143.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900016 PM 16050888 ER PT J AU Jha, AK Perlin, JB Steinman, MA Peabody, JW Ayanian, JZ AF Jha, AK Perlin, JB Steinman, MA Peabody, JW Ayanian, JZ TI Quality of ambulatory care for women and men in the veterans affairs health care system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE gender; quality; veterans; prevention; diabetes mellitus ID ACUTE MYOCARDIAL-INFARCTION; SERVICES-TASK-FORCE; OF-CARE; FEMALE VETERANS; MEDICAL-CENTER; HEART-DISEASE; MANAGED CARE; RISK; RACE; OUTCOMES AB BACKGROUND: Gender differences in inpatient quality of care are well known. However, whether men and women receive equivalent ambulatory care is less well understood. OBJECTIVE: To study gender differences in quality of care for patients receiving primary care in the Veterans Affairs (VA) Health Care System. DESIGN: Cross-sectional samples of VA enrollees during fiscal years 1999 to 2000. PARTICIPANTS: Samples of 6,442 to 86,405 men and women treated at VA facilities for whom at least 1 of 9 quality measures was available. MEASUREMENTS: Appropriate general preventive services (pneumococcal vaccination, influenza vaccination, colorectal cancer screening), and specific services for diabetes (annual hemoglobin A1c [HbA1c] testing, good glycemic control, annual diabetic eye exam), hypertension (good blood pressure control), or prior myocardial infarction (use of beta-blockers or aspirin). RESULTS: In adjusted analyses, there were no substantial gender differences in rates of appropriate care. For women compared with men, the adjusted relative risk for appropriate care ranged from 0.96 for blood pressure control (95% confidence interval: 0.93 to 0.99; P=.02) to 1.05 for HbA1c <= 8.0% (95% confidence interval: 1.03 to 1.07; P <.01). Analyses stratified by age demonstrated equivalent care between men and women in 9 of the 14 subgroups evaluated. CONCLUSION: In this large national health care system that predominantly serves men, the quality of ambulatory care is equivalent for women and men on numerous measures. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Boston VA Hlth Care Syst, Boston, MA USA. Vet Hlth Adm, Off Undersecretary, Washington, DC USA. San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. Inst Global Hlth, San Francisco, CA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU AHRQ HHS [5T32HS00020-16, T32 HS000020] NR 27 TC 32 Z9 32 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 762 EP 765 DI 10.1111/j.1525-1497.2005.0160.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900017 PM 16050889 ER PT J AU Zipkin, DA Steinman, MA AF Zipkin, DA Steinman, MA TI Interactions between pharmaceutical representatives and doctors in training SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE medical students; interns and residents; medical education; drug industry ID PHYSICIAN PRESCRIBING PATTERNS; SALES REPRESENTATIVES; MEDICINE RESIDENTS; COMPANY REPRESENTATIVES; DRUG COMPANIES; INDUSTRY; ATTITUDES; PROGRAMS; FACULTY; GIFTS AB OBJECTIVE: Medical school and residency are formative years in establishing patterns of prescribing. We aimed to review the literature regarding the extent of pharmaceutical industry contact with trainees, attitudes about these interactions, and effects on trainee prescribing behavior, with an emphasis on points of potential intervention and policy formation. DESIGN: We searched MEDLINE from 1966 until May 2004 for English language articles. All original articles were included if the abstract reported content relevant to medical training and the pharmaceutical industry. Editorials, guidelines, and policy recommendations were excluded. MEASUREMENTS AND RESULTS: Contact with pharmaceutical representatives was common among residents. The majority of trainees felt that the interactions were appropriate. A minority felt that their own prescribing could be influenced by contact or gifts, but were more likely to believe that others' prescribing could be influenced. Resident prescribing was associated with pharmaceutical representative visits and the availability of samples. A variety of policy and educational interventions appear to influence resident attitudes toward interactions with industry, although data on the long-term effects of these interventions are limited. Overall, residents reported insufficient training in this area. CONCLUSION: The pharmaceutical industry has a significant presence during residency training, has gained the overall acceptance of trainees, and appears to influence prescribing behavior. Training programs can benefit from policies and curricula that teach residents about industry influence and ways in which to critically evaluate information that they are given. Recommendations for local and national approaches are discussed. C1 Calif Pacific Med Ctr, Dept Internal Med, San Francisco, CA USA. San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Zipkin, DA (reprint author), 3801 Sacramento St,306, San Francisco, CA 94118 USA. EM zipkind@sutterhealth.org NR 58 TC 77 Z9 79 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2005 VL 20 IS 8 BP 777 EP 786 DI 10.1111/j.1525-1497.2005.0134.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 946VR UT WOS:000230601900021 PM 16050893 ER PT J AU Baratelli, F Lin, Y Zhu, L Yang, SC Heuze-Vourc'h, N Zeng, G Reckamp, K Dohadwala, M Sharma, S Dubinett, SM AF Baratelli, F Lin, Y Zhu, L Yang, SC Heuze-Vourc'h, N Zeng, G Reckamp, K Dohadwala, M Sharma, S Dubinett, SM TI Prostaglandin E-2 induces FOXP3 gene expression and T regulatory cell function in human CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN DENDRITIC CELLS; PERIPHERAL-BLOOD; LUNG-CANCER; DOWN-REGULATION; CUTTING EDGE; TGF-BETA; IN-VITRO; PROLIFERATION; IL-2; INDUCTION AB Naturally occurring CD4(+)CD25(+) regulatory T cells (T reg) are pivotal in suppressing immune responses and maintaining tolerance. The identification of molecules controlling T reg differentiation and function is important in understanding host immune responses in malignancy and autoimmunity. In this study we show that PGE(2) enhances the in vitro inhibitory function of human purified CD4(+)CD25(+) T reg cells. Moreover, PGE(2) induces a regulatory phenotype in CD4(+)CD25(-) T cells. PGE(2)-treated T cell-mediated inhibition of anti-CD3-stimulated lymphocyte proliferation did not require cell contact. Phenotypic analysis revealed that PGE(2) diminished CD25 expression in both CD4(+)CD2(dim) T cells and CD4(+)CD25(bright) T reg cells. PGE(2) exposure induced the T reg cell-specific transcription factor forkhead/winged helix transcription factor gene (FOXP3) in CD4(+)CD25(-) T cells and significantly up-regulated its expression in CD4(+)CD25(+) T reg cells. Similarly, 24-h incubation with supernatants from cyclooxygenase-2-overexpressing lung cancer cells that secrete high levels of PGE(2) significantly induced FOXP3 in CD4(+)CD25(-) T cells. Finally, PGE(2) up-regulated FOXP3 at both mRNA and protein levels and enhanced FOXP3 promoter activity. This is the first report indicating that PGE(2) can modulate FOXP3 expression and T reg function in human lymphocytes. C1 Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Room 37-131 Ctr Hlth Sci,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016; OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [P50CA90388, R01CA85686] NR 50 TC 304 Z9 323 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2005 VL 175 IS 3 BP 1483 EP 1490 PG 8 WC Immunology SC Immunology GA 989BN UT WOS:000233648000016 PM 16034085 ER PT J AU Dardalhon, V Schubart, AS Reddy, J Meyers, JH Monney, L Sabatos, CA Ahuja, R Nguyen, K Freeman, GJ Greenfield, EA Sobel, RA Kuchroo, VK AF Dardalhon, V Schubart, AS Reddy, J Meyers, JH Monney, L Sabatos, CA Ahuja, R Nguyen, K Freeman, GJ Greenfield, EA Sobel, RA Kuchroo, VK TI CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN PROTEOLIPID PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD4(+) T-CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; CUTTING EDGE; TRANSCRIPTION FACTOR; ADHESION MOLECULE; SIGNAL TRANSDUCER; DNAM-1 CD226; RECEPTOR AB Surface molecules that are differentially expressed on Th1 and Th2 cells may be useful in regulating specific immune responses in vivo. Using a panel of mAbs, we have identified murine CD226 as specifically expressed on the surface of differentiated Th1 cells but not Th2 or Th0 cells. Although CD226 is constitutively expressed on CD8 cells, it is up-regulated on CD4 cells upon activation. Th1 differentiation results in enhanced CD226 expression, whereas expression is down-regulated upon Th2 polarization. We demonstrate that CD226 is involved in the regulation of T cell activation; in vivo treatment with anti-CD226 results insignificant reduction of Th1 cell expansion and in the induction of APCs that inhibit T cell activation. Furthermore, anti-CD226 treatment delays the onset and reduces the severity of a Th1-mediated autoinmume disease, experimental autoimmune encephalomyelitis. Our data suggest that CD226 is a costimulatory molecule that plays an important role in activation and effector functions of Th1 cells. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Inst Med,Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. Vet Adm Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 95305 USA. RP Kuchroo, VK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Inst Med,Dept Neurol, Room 786,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vkuchroo@rics.bwh.harvard.edu RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 FU NIAID NIH HHS [2PO1AI39671-07, 1R01AI44880-03]; NIGMS NIH HHS [1F31GM20927-01]; NINDS NIH HHS [1PO1NS38037-04, 1R01NS045937-01, 2R01NS35685-06, 2R37NS30843-11] NR 43 TC 75 Z9 78 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2005 VL 175 IS 3 BP 1558 EP 1565 PG 8 WC Immunology SC Immunology GA 989BN UT WOS:000233648000025 PM 16034094 ER PT J AU O'Connor, KC Appel, H Bregoli, L Call, ME Catz, I Chan, JA Moore, NH Warren, KG Wong, SJ Hafler, DA Wucherpfennig, KW AF O'Connor, KC Appel, H Bregoli, L Call, ME Catz, I Chan, JA Moore, NH Warren, KG Wong, SJ Hafler, DA Wucherpfennig, KW TI Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; B-CELL RESPONSE; CEREBROSPINAL-FLUID; CLONAL EXPANSION; BASIC-PROTEIN; MYELIN/OLIGODENDROCYTE GLYCOPROTEIN; FINE SPECIFICITY; IMMUNOGLOBULIN-G; DEMYELINATION AB Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading. C1 Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Alberta, Multiple Sclerosis Patient Care & Res Clin, Edmonton, AB, Canada. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. RP O'Connor, KC (reprint author), Harvard Univ, Sch Med, Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM koconnor@rics.bwh.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI44447, R01 AI39229, P01 AI045757] NR 61 TC 104 Z9 109 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2005 VL 175 IS 3 BP 1974 EP 1982 PG 9 WC Immunology SC Immunology GA 989BN UT WOS:000233648000073 PM 16034142 ER PT J AU McInturff, JE Wang, SJ Machleidt, T Lin, TR Oren, A Hertz, CJ Krutzik, SR Hart, S Zeh, K Anderson, DH Gallo, RL Modlin, RL Kim, J AF McInturff, JE Wang, SJ Machleidt, T Lin, TR Oren, A Hertz, CJ Krutzik, SR Hart, S Zeh, K Anderson, DH Gallo, RL Modlin, RL Kim, J TI Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against Propionibacterium acnes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE acne; antimicrobial peptide; inflammation; innate immunity; skin ID INFLAMMATORY ACNE; DEFENSINS; ACTIVATION; INDUCTION; RESPONSES; IMMUNITY; INNATE; CELLS; BETA AB Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium has become resistant to standard antibiotic agents. We investigated whether the human antimicrobial protein granulysin is a potential candidate for the treatment of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix-loop-helix motif killed P. acnes in vitro. Modi. cation of a helix-loop-helix peptide, 31-50, by substitution of a tryptophan for the valine at amino acid 44 (peptide 31-50v44w) to increase its interaction with bacterial surfaces also increased its antimicrobial activity. Moreover, when synthesized with D- rather than L-type amino acids, this peptide (D-31-50v44w) became less susceptible to degradation by proteases and more effective in killing P. acnes. Granulysin peptides were bactericidal, demonstrating an advantage over standard bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide D-31-50v44w killed P. acnes in isolated human microcomedone preparations. Importantly, peptides 31-50, 31-50v44w, and D-31-50v44w also have potential anti-inflammatory effects, as demonstrated by suppression of P. acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies. C1 Univ Calif Los Angeles, Inst Mol Biol, Inst Genom & Prote, Dept Dermatol,DOE, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA USA. Ansata Therapeut Inc, La Jolla, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol, Los Angeles, CA USA. Howard Hughes Med Inst, Los Angeles, CA USA. Univ Calif San Diego, Div Dermatol, San Diego, CA 92103 USA. Vet Adm San Diego Healthcare Syst, San Diego, CA USA. RP Kim, J (reprint author), Univ Calif Los Angeles, Inst Mol Biol, Inst Genom & Prote, Dept Dermatol,DOE, 52-121 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM JeKim@mednet.ucla.edu RI Gallo, Richard/A-8931-2009; OI Modlin, Robert/0000-0003-4720-031X FU NIAMS NIH HHS [K08 AR048551, K08 AR48551-01] NR 26 TC 40 Z9 44 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2005 VL 125 IS 2 BP 256 EP 263 DI 10.1111/j.0022-202X.2005.23805.x PG 8 WC Dermatology SC Dermatology GA 945HI UT WOS:000230493200012 PM 16098035 ER PT J AU Anand, S Chakrabarti, E Kawamura, H Taylor, CR Maytin, EV AF Anand, S Chakrabarti, E Kawamura, H Taylor, CR Maytin, EV TI Ultraviolet light (UVB and UVA) induces the damage-responsive transcription factor CHOP/gadd153 in murine and human epidermis: Evidence for a mechanism specific to intact skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT International Investigative Dermatology Meeting CY APR 30-MAY 04, 2003 CL Miami Beach, FL DE epidermis; keratinocyte; transcription factor; ultraviolet rays ID UNFOLDED PROTEIN RESPONSE; SOLAR-SIMULATED IRRADIATION; FACTOR CHOP GADD153; ENDOPLASMIC-RETICULUM; DNA-DAMAGE; HUMAN KERATINOCYTES; MYXOID LIPOSARCOMA; INDUCED APOPTOSIS; STRESS-RESPONSE; INHIBITS TRANSLATION AB C/EBP-homologous protein ( CHOP)/gadd153 ( or CHOP) is a transcription factor induced by endoplasmic reticulum ( ER) stress. Forcible overexpression of CHOP causes apoptosis in keratinocytes in culture. Here, we asked whether CHOP might be increased in the skin after UVB (280-320 nm) exposure, thus implicating CHOP in sunburn cell (SBC) formation. SKH-1 hairless mice were exposed to a ultraviolet (UV) source ( 80 mJ per cm(2); similar to 74% UVB, similar to 16% UVA), and skin biopsies examined by immunohistology and immunoprecipitation. Compared with non-irradiated epidermis, CHOP expression was significantly increased at 30 min, and reached maximal levels by 24 h. Similar increases in CHOP following UVB exposure were observed in human buttock skin. The time course of CHOP expression preceded SBC formation and another marker of apoptosis, caspase-3 cleavage. Intracellular CHOP accumulated mainly in cytoplasmic and perinuclear locations, with little remaining in the nucleus. To examine mechanisms, cultured keratinocytes were irradiated in vitro and examined by western blotting. Under conditions that eliminated ER stress because of cell handling, CHOP did not accumulate ( and was in fact decreased) in the cells. Thus, induction of CHOP in keratinocytes requires factors present only in the native skin. Overall, the data suggest that CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo. C1 Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Dermatol, Cleveland, OH 44195 USA. RP Maytin, EV (reprint author), Cleveland Clin Fdn, Dept Biomed Engn, ND-20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU NCI NIH HHS [P01-CA84203]; NIAMS NIH HHS [5R29-AR45430, P30-AR39750] NR 51 TC 25 Z9 27 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2005 VL 125 IS 2 BP 323 EP 333 DI 10.1111/j.0022-202X.2005.23784.x PG 11 WC Dermatology SC Dermatology GA 945HI UT WOS:000230493200021 PM 16098044 ER PT J AU Baratelli, F Krysan, K Heuze-Vourc'h, N Zhu, L Escuadro, B Sharma, S Reckamp, K Dohadwala, M Dubinett, SM AF Baratelli, F Krysan, K Heuze-Vourc'h, N Zhu, L Escuadro, B Sharma, S Reckamp, K Dohadwala, M Dubinett, SM TI PGE(2) confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE lipid mediators; immune cells; antiapoptotic proteins ID ACTIVATION-INDUCED APOPTOSIS; NORMAL CORD BLOOD; LUNG-CANCER; PROSTAGLANDIN E-2; PROTEIN SURVIVIN; UP-REGULATION; DOWN-REGULATION; CD34(+) CELLS; T-CELLS; EXPRESSION AB Control of apoptosis is fundamental for dendritic cell (DC) homeostasis. Numerous factors maintain DC viability throughout their lifespan, including inhibitor of apoptosis proteins. Among them, survivin is overexpressed in many human malignancies, but its physiological function in normal cells has not been fully delineated. Prostaglandin E-2 (PGE(2)), also overproduced in several malignancies, has shown to induce proapoptotic and antiapoptotic effects in different cell types, including immune cells. In DC, PGE(2) predominantly affects maturation and modulates immune functions. Here, we show that exposure of monocyte-derived DC to PGE(2) (10(-5) M) for 72 h significantly increased DC survivin mRNA and protein expression. In contrast, DC, matured with lipopolysaccharide or tumor necrosis factor alpha, did not reveal survivin induction in response to PGE(2). Following exposure to apoptotic stimuli, DC treated with PGE(2) exhibited an overall increased viability compared with control DC, and this effect was correlated inversely with caspase-3 activation. Moreover, PGE(2)-treated, survivin-deficient DC demonstrated reduced viability in response to apoptotic stimuli. Further analysis indicated that PGE(2) induced DC survivin expression in an E prostanoid (EP)(2)/EP4 receptor and phosphatidylinositol-3 kinase-dependent manner. These findings suggest that PGE(2)-dependent regulation of survivin is important in modulating apoptosis resistance in human DC. C1 Univ Calif Los Angeles, Lung Canc Res Program, Div Pulm & Crit Care Med,Dept Med, Geffen Sch Med,Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Lung Canc Res Program, Div Pulm & Crit Care Med,Dept Med, Geffen Sch Med,Jonsson Comprehens Canc Ctr, 37-131 CHS,10833 Le Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016; OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [CA-16042, P50 CA 90388, R01 CA85686]; NIAID NIH HHS [AI-28697] NR 55 TC 34 Z9 34 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2005 VL 78 IS 2 BP 555 EP 564 DI 10.1189/jlb.1004569 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 950MG UT WOS:000230860700026 PM 15908458 ER PT J AU Maung, AA Fujimi, S Miller, ML MacConmara, MP Mannick, JA Lederer, JA AF Maung, AA Fujimi, S Miller, ML MacConmara, MP Mannick, JA Lederer, JA TI Enhanced TLR4 reactivity following injury is mediated by increased p38 activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE monocytes; macrophages; inflammation; signal transduction ID PROINFLAMMATORY CYTOKINE PRODUCTION; BLOOD MONONUCLEAR-CELLS; MAP KINASE ACTIVATION; GOLGI-APPARATUS; FLOW-CYTOMETRY; BACTERIAL LIPOPOLYSACCHARIDE; ISCHEMIA/REPERFUSION INJURY; SIGNAL-TRANSDUCTION; THERMAL-INJURY; EXPRESSION AB Severe injury primes the innate-immune system for increased Toll-like receptor 4 (TLR4)induced proinflammatory cytokine production by macrophages. In this study, we examined changes in TLR4 signaling pathways in splenic macrophages from burn-injured or sham mice to determine the molecular mechanism(s) responsible for the increased TLR4 responsiveness. Using flow cytometry and specific antibodies, we first looked for injury-induced changes in the expression levels of several TLR-associated signaling molecules. We found similar levels of myeloid differentiation primary-response protein 88 (MyD88) and interleukin-1 receptor-associated kinase-M (IRAK-M) and somewhat lower levels of total p38, extracellular signal-regulated kinase (ERK), mid stress-activated protein kinase (SAPK)/c-jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) in burn compared with sham macrophages. However, with the use of antibodies specific for the phosphorylated (activated) forms of the three MAPKs, we found that macrophages from burn mice showed a twofold increase in purified lipopolysaccharide (LPS)-stimulated p38 activation as compared with cells from sham mice on days 1 and 7 post-injury, whereas ERK and SAPK/JNK activation was increased by burn injury only on day 1. Using the specific p38 inhibitor (SB203580), we confirmed that the increase in tumor necrosis factor alpha production by LPS-stimulated burn macrophages requires p38 activation. Although we demonstrated that injury increases niacropliage TLR4 mRNA expression and intracellular expression of TLR4-myeloid differentiation protein-2 (MD-2) protein, macrophage cell-surface expression of TLR4-MD-2 was not changed by burn injury. Our results suggest that the injury-induced increase in TLR4 reactivity is mediated, at least in part, by enhanced activation of the p38 signaling pathway. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lederer, JA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Franics St, Boston, MA 02115 USA. EM jlederer@rics.bwh.harvard.edu FU NIGMS NIH HHS [GM35633, GM57664] NR 35 TC 56 Z9 59 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2005 VL 78 IS 2 BP 565 EP 573 DI 10.1189/jlb.1204698 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 950MG UT WOS:000230860700027 PM 15857937 ER PT J AU Gnerre, C Schuster, GU Roth, A Handschin, C Johansson, L Looser, R Parini, P Podvinec, M Robertsson, K Gustafsson, JA Meyer, UA AF Gnerre, C Schuster, GU Roth, A Handschin, C Johansson, L Looser, R Parini, P Podvinec, M Robertsson, K Gustafsson, JA Meyer, UA TI LXR deficiency and cholesterol feeding affect the expression and phenobarbital-mediated induction of cytochromes P450 in mouse liver SO JOURNAL OF LIPID RESEARCH LA English DT Article DE liver X receptor; pregnane X receptor; constitutive androstane receptor; metabolism; cytochrome P450 3a11; cytochrome P450 2b10 ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; ORPHAN NUCLEAR RECEPTOR; BILE-ACID BIOSYNTHESIS; ANTIEPILEPTIC DRUGS; DIETARY-CHOLESTEROL; EPILEPTIC CHILDREN; LITHOCHOLIC ACID; GENE-EXPRESSION; SERUM-LIPIDS AB Metabolic transformation by the superfamily of cytochromes P450 ( CYPs) plays an important role in the detoxification of xenobiotics such as drugs, environmental pollutants, and food additives. Endogenous substrates of CYPs include fatty acids, sterols, steroids, and bile acids. Induction of CYPs via transcriptional activation by substrates and other xenobiotics is an important adaptive mechanism that increases the organism's defense capability against toxicity. Numerous in vivo and in vitro data have highlighted the concept that the molecular mechanism of hepatic drug induction is linked to endogenous regulatory pathways. In particular, in vitro data suggest that oxysterols via the liver X receptor (LXR) inhibit phenobarbital (PB)-mediated induction of CYPs. To study the link between LXR, cholesterol homeostasis, and drug induction in vivo, we designed experiments in wild-type, LXR alpha-, LXR beta-, and LXR alpha/beta-deficient mice. Our data expose differential regulatory patterns for Cyp2b10 and Cyp3a11 dependent on the expression of LXR isoforms and on challenge of cholesterol homeostasis by excess dietary cholesterol. Our results suggest that, in the mouse, liver cholesterol status significantly alters the pattern of expression of Cyp3a11, whereas the absence of LXR leads to an increase in PB-mediated activation of Cyp2b10. C1 Univ Basel, Biozentrum, Div Pharmacol Neurobiol, CH-4056 Basel, Switzerland. Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Huddinge Univ Hosp, Karolinska Inst, Novum, Ctr Metab & Endocrinol,Dept Med, S-14186 Huddinge, Sweden. RP Meyer, UA (reprint author), Univ Basel, Biozentrum, Div Pharmacol Neurobiol, CH-4056 Basel, Switzerland. EM urs-a.meyer@unibas.ch RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 NR 50 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2005 VL 46 IS 8 BP 1633 EP 1642 DI 10.1194/jlr.M400453-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946UB UT WOS:000230597400008 PM 15930522 ER PT J AU Ruiz, J Kouiavskaia, D Migliorini, M Robinson, S Saenko, EL Gorlatova, N Li, DH Lawrence, D Hyman, BT Weisgraber, KH Strickland, DK AF Ruiz, J Kouiavskaia, D Migliorini, M Robinson, S Saenko, EL Gorlatova, N Li, DH Lawrence, D Hyman, BT Weisgraber, KH Strickland, DK TI The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoprotein E; low density lipoprotein; very low density lipoprotein; low density lipoprotein receptor-related protein ID DENSITY-LIPOPROTEIN RECEPTOR; HUMAN APOLIPOPROTEIN-E; AMYLOID PRECURSOR PROTEIN; FACTOR PATHWAY INHIBITOR; ALPHA-2-MACROGLOBULIN RECEPTOR; III HYPERLIPOPROTEINEMIA; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; LIGAND-BINDING; TYROSINE PHOSPHORYLATION AB Apolipoprotein E ( apoE) associates with lipoproteins and mediates their interaction with members of the LDL receptor family. ApoE exists as three common isoforms that have important distinct functional and biological properties. Two apoE isoforms, apoE3 and apoE4, are recognized by the LDL receptor, whereas apoE2 binds poorly to this receptor and is associated with type III hyperlipidemia. In addition, the apoE4 isoform is associated with the common late-onset familial and sporadic forms of Alzheimer's disease. Although the interaction of apoE with the LDL receptor is well characterized, the specificity of other members of this receptor family for apoE is poorly understood. In the current investigation, we have characterized the binding of apoE to the VLDL receptor and the LDL receptor-related protein (LRP). Our results indicate that like the LDL receptor, LRP prefers lipid-bound forms of apoE, but in contrast to the LDL receptor, both LRP and the VLDL receptor recognize all apoE isoforms. Interestingly, the VLDL receptor does not require the association of apoE with lipid for optimal recognition and avidly binds lipid-free apoE. It is likely that this receptor-dependent specificity for various apoE isoforms and for lipid-free versus lipid-bound forms of apoE is physiologically significant and is connected to distinct functions for these receptors. C1 Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Biochem, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimer Dis Res Lab, Charlestown, MA 02129 USA. Univ Calif San Francisco, Dept Pathol, Cardiovasc Res Inst, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Pathol, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Pathol, Gladstone Inst Neurol Dis, San Francisco, CA 94141 USA. RP Strickland, DK (reprint author), Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. EM dstrickland@som.umaryland.edu FU NHLBI NIH HHS [2P01 HL-41633, HL-50784, HL-54710, HL-72929]; NIA NIH HHS [AG-12406] NR 61 TC 83 Z9 85 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2005 VL 46 IS 8 BP 1721 EP 1731 DI 10.1194/jlr.M5000114-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946UB UT WOS:000230597400017 PM 15863833 ER PT J AU Kim, HG Herrick, SR Lemyre, E Kishikawa, S Salisz, JA Seminara, S MacDonald, ME Bruns, GAP Morton, CC Quade, BJ Gusella, JF AF Kim, HG Herrick, SR Lemyre, E Kishikawa, S Salisz, JA Seminara, S MacDonald, ME Bruns, GAP Morton, CC Quade, BJ Gusella, JF TI Hypogonadotropic hypogonadism and cleft lip and palate caused by a balanced translocation producing haploinsufficiency for FGFR1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CELL MYELOPROLIFERATIVE DISORDER; FACTOR RECEPTOR 1; KALLMANN-SYNDROME; GENE; MUTATION; PATIENT; DIMERIZATION; GENOME; FUSES; KAL1 C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Genet, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Montreal, Hop St Justine, Med Genet Serv, Montreal, PQ H3T 1C5, Canada. W Shore Urol, Muskegon, MI USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Genet Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Gusella, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Genet, Ctr Human Genet Res,Mol Neurogenet Unit, CNY149-6214,13th St, Boston, MA 02129 USA. EM gusella@helix.mgh.harvard.edu FU NICHD NIH HHS [HD28138]; NIGMS NIH HHS [GM061354, P01 GM061354] NR 29 TC 33 Z9 34 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2005 VL 42 IS 8 BP 666 EP 672 DI 10.1136/jmg.2004.026989 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 950ZB UT WOS:000230896900008 PM 16061567 ER PT J AU Ogino, S Kawasaki, T Brahmandam, M Yan, LY Cantor, M Namgyal, C Mino-Kenudson, M Lauwers, GY Loda, M Fuchs, CS AF Ogino, S Kawasaki, T Brahmandam, M Yan, LY Cantor, M Namgyal, C Mino-Kenudson, M Lauwers, GY Loda, M Fuchs, CS TI Sensitive Sequencing method for KRAS mutation detection by pyrosequencing SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID K-RAS MUTATIONS; WHOLE-GENOME AMPLIFICATION; MULTIPLE DISPLACEMENT AMPLIFICATION; SINGLE NUCLEOTIDE POLYMORPHISM; TUMOR-SUPPRESSOR GENE; TOF MASS-SPECTROMETRY; POINT MUTATIONS; DETECTION PLATFORM; DNA ANALYSIS; PCR AB Both benign and malignant tumors represent heterogenous tissue containing tumor cells and non-neoplastic mesenchymal and inflammatory cells. To detect a minority of mutant KRAS alleles among abundant wild-type alleles, we developed a sensitive DNA sequencing assay using Pyrosequencing, ie, nucleotide extension sequencing with an allele quantification capability. We designed our Pyrosequencing assay for use with whole-genome-amplified DNA from paraffin-embedded tissue. Assessing various mixtures of DNA from mutant KRAS cell lines and DNA from a wild-type KRAS cell line, we found that mutation detection rates for Pyrosequencing were superior to dideoxy sequencing. In addition, Pyrosequencing proved superior to dideoxy sequencing in the detection of KRAS mutations from DNA mixtures of paraffin-embedded colon cancer and normal tissue as well as from paraffin-embedded pancreatic cancers. Quantification of mutant alleles by Pyrosequencing was precise and useful for assay validation, monitoring, and quality assurance. Our Pyrosequencing method is simple, robust, and sensitive, with a detection limit of approximately 5% mutant alleles. It is particularly useful for tumors containing abundant non-neoplastic cells. In addition, the applicability of this assay for DNA amplified by whole-genome amplification technique provides an expanded source of DNA for large-scale studies. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Biotage AB & Biosyst, Foxboro, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU PHS HHS [P01-9467802, P01-9483703, R01-9485602] NR 36 TC 356 Z9 367 U1 1 U2 13 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD AUG PY 2005 VL 7 IS 3 BP 413 EP 421 DI 10.1016/S1525-1578(10)60571-5 PG 9 WC Pathology SC Pathology GA 953CU UT WOS:000231054600012 PM 16049314 ER PT J AU Henderson, DC Mollica, RF Tor, S Lavelle, J Culhane, MA Hayden, D AF Henderson, DC Mollica, RF Tor, S Lavelle, J Culhane, MA Hayden, D TI Building primary care practitioners' attitudes and confidence in mental health skills in a post-conflict society - A Cambodian example SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE primary care practitioners (PCPs); psychiatric symptoms; depression; confidence; folk diagnosis; categories of emotional distress ID POSTTRAUMATIC-STRESS-DISORDER; AMBULATORY PROCEDURES; DEPRESSION; GUIDELINES; RESIDENTS; TRAUMA; INSTRUMENT; SERVICES; REFUGEES; TORTURE AB Our program attempted to integrate community mental health in primary care settings in Cambodia and to evaluate the effects of training on local providers. The training program underwent an extensive evaluation to determine its impact on the mental health knowledge, confidence in performing medical and psychiatric procedures, skills and attitudes of its trainees. One hundred four Cambodian primary care practitioners (PCPs) were trained in a primary care setting in Siem Reap, Cambodia, over a 2-year period. There was a significant improvement in PCPs ' confidence in all clusters of medical and psychiatric procedures (counseling, medical evaluation, prescribing medications, psychiatric diagnosis, assessing risk for violence, traditional treatments, and treating trauma victims) comparing baseline to posttraining and baseline to 2-year follow-up (p < 0.05). Only confidence in prescribing psychotropic medications improved from posttraining to 2-year follow-up. This study supports the feasibility of training PCPs in a culturally effective manner in a postconflict society. C1 Harvard Univ, Massachusetts Gen Hosp, Program Refugee Trauma, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Harvard Program Refugee Trauma, 22 Putnam St, Cambridge, MA 02138 USA. NR 26 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 2005 VL 193 IS 8 BP 551 EP 559 DI 10.1097/01.nmd.0000172869.01711.33 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 954TK UT WOS:000231177600008 PM 16082300 ER PT J AU Sweadner, KJ Donnet, C Wetzel, RK Arystarkhova, E Ivanov, A AF Sweadner, KJ Donnet, C Wetzel, RK Arystarkhova, E Ivanov, A TI FXYD proteins: Specialized regulators of Na, K-ATPase in the brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 20th Biennial Meeting of the International-Society-for-Neurochemistry/European-Society-for-Neurochemi stry CY AUG 21-26, 2005 CL Innsbruck, AUSTRIA SP Int Soc Neurochem, European Soc Neurochem C1 Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2005 VL 94 SU 2 BP 158 EP 158 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 961PD UT WOS:000231673401033 ER PT J AU Nath, N Giri, S Prasad, R Salem, ML Singh, AK Singh I AF Nath, N Giri, S Prasad, R Salem, ML Singh, AK Singh, I TI 5-aminoimidazole-4-carboxamide ribonucleoside: A novel immunomodulator in experimental autoimmune encephalomyelitis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 20th Biennial Meeting of the International-Society-for-Neurochemistry/European-Society-for-Neurochemi stry CY AUG 21-26, 2005 CL Innsbruck, AUSTRIA SP Int Soc Neurochem, European Soc Neurochem C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2005 VL 94 SU 2 BP 182 EP 182 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 961PD UT WOS:000231673401103 ER PT J AU White, AR Du, T Hill, AF Sharples, R Barnham, KJ Holsinger, D Ciccotosto, G Hoke, D Evin, G Laughton, K Li, QX Volitakis, I Cherny, RA Bush, AI Cappai, R Masters, CL AF White, AR Du, T Hill, AF Sharples, R Barnham, KJ Holsinger, D Ciccotosto, G Hoke, D Evin, G Laughton, K Li, QX Volitakis, I Cherny, RA Bush, AI Cappai, R Masters, CL TI Modulation of APP and A beta metabolism by metal chelators SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Mental Hlth Res Inst, Melbourne, Vic, Australia. Univ Melbourne, Dept Biochem, Melbourne, Vic, Australia. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Genet & Aging Unit, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RI Cappai, Roberto/B-3347-2010; Holsinger, R. M. Damian/B-4650-2012; Evin, Genevieve/E-5891-2013; Hill, Andrew/B-4527-2009; Bush, Ashley/A-1186-2007 OI Cappai, Roberto/0000-0002-9505-8496; Hill, Andrew/0000-0001-5581-2354; Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2005 VL 94 SU 2 BP 223 EP 223 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 961PD UT WOS:000231673401215 ER PT J AU Le, SS Loucks, FA Udo, H Richardson-Burns, S Phelps, RA Bouchard, RJ Barth, H Aktories, K Tyler, KL Kandel, ER Heidenreich, KA Linseman, DA AF Le, SS Loucks, FA Udo, H Richardson-Burns, S Phelps, RA Bouchard, RJ Barth, H Aktories, K Tyler, KL Kandel, ER Heidenreich, KA Linseman, DA TI Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial apoptotic cascade in cerebellar granule neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Bax; BH3-only; c-jun N-terminal protein kinase; neuronal survival; Rho GTPase ID RHO FAMILY GTPASES; N-TERMINAL KINASE; GROWTH-FACTOR-I; CELL-DEATH; SIGNALING PATHWAY; CLOSTRIDIAL CYTOTOXINS; BH3-ONLY PROTEIN; LETHAL TOXIN; ACTIVATION; SURVIVAL AB Rho GTPases are key transducers of integrin/extracellular matrix and growth factor signaling. Although integrin-mediated adhesion and trophic support suppress neuronal apoptosis, the role of Rho GTPases in neuronal survival is unclear. Here, we have identified Rac as a critical pro-survival GTPase in cerebellar granule neurons (CGNs) and elucidated a death pathway triggered by its inactivation. GTP-loading of Rac1 was maintained in CGNs by integrin-mediated ( RGDdependent) cell attachment and trophic support. Clostridium difficile toxin B ( ToxB), a specific Rho family inhibitor, induced a selective caspase-mediated degradation of Rac1 without affecting RhoA or Cdc42 protein levels. Both ToxB and dominant-negative N17Rac1 elicited CGN apoptosis, characterized by cytochrome c release and activation of caspase-9 and -3, whereas dominant - negative N19RhoA or N17Cdc42 did not cause significant cell death. ToxB stimulated mitochondrial translocation and conformational activation of Bax, c-Jun activation, and induction of the BH3-only protein Bim. Similarly, c-Jun activation and Bim induction were observed with N17Rac1. A c-jun N-terminal protein kinase (JNK)/p38 inhibitor, SB203580, and a JNK-specific inhibitor, SP600125, significantly decreased ToxB-induced Bim expression and blunted each subsequent step of the apoptotic cascade. These results indicate that Rac acts downstream of integrins and growth factors to promote neuronal survival by repressing c-Jun/Bim-mediated mitochondrial apoptosis. C1 Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Ulm, Dept Pharmacol & Toxicol, Ulm, Germany. Univ Freiburg, Inst Expt & Klin Pharmakol & Toxikol, Freiburg, Germany. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO USA. RP Linseman, DA (reprint author), Denver Vet Affairs Med Ctr, Res Serv, 111H,1055 Clermont St, Denver, CO 80220 USA. EM Dan.Linseman@UCHSC.edu RI Barth, Holger/E-7920-2013; OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS051403, R01 NS051403-03, R01 NS050138-04, R01 NS050138] NR 65 TC 36 Z9 36 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2005 VL 94 IS 4 BP 1025 EP 1039 DI 10.1111/j.1471-4159.2005.03252.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 950WA UT WOS:000230888200016 PM 16092944 ER PT J AU Lane, CC Delgutte, B AF Lane, CC Delgutte, B TI Neural correlates and mechanisms of spatial release from masking: Single-unit and population responses in the inferior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE FIBERS; TIME DIFFERENCE DISCRIMINATION; INTERAURAL PHASE DISPARITY; AMPLITUDE-MODULATED TONES; LOW-FREQUENCY NEURONS; BINAURAL INTERACTION; INHIBITORY INPUTS; LEVEL DIFFERENCES; PHYSIOLOGICAL-MECHANISMS AB Spatial release from masking (SRM), a factor in listening in noisy environments, is the improvement in auditory signal detection obtained when a signal is separated in space from a masker. To study the neural mechanisms of SRM, we recorded from single units in the inferior colliculus (IC) of barbiturate-anesthetized cats, focusing on low-frequency neurons sensitive to interaural time differences. The stimulus was a broadband chirp train with a 40-Hz repetition rate in continuous broadband noise, and the unit responses were measured for several signal and masker ( virtual) locations. Masked thresholds ( the lowest signal-to-noise ratio, SNR, for which the signal could be detected for 75% of the stimulus presentations) changed systematically with signal and masker location. Single-unit thresholds did not necessarily improve with signal and masker separation; instead, they tended to reflect the units' azimuth preference. Both how the signal was detected ( through a rate increase or decrease) and how the noise masked the signal response ( suppressive or excitatory masking) changed with signal and masker azimuth, consistent with a cross-correlator model of binaural processing. However, additional processing, perhaps related to the signal's amplitude modulation rate, appeared to influence the units' responses. The population masked thresholds ( the most sensitive unit's threshold at each signal and masker location) did improve with signal and masker separation as a result of the variety of azimuth preferences in our unit sample. The population thresholds were similar to human behavioral thresholds in both SNR value and shape, indicating that these units may provide a neural substrate for low-frequency SRM. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, England. MIT, Elect Res Lab, Cambridge, England. RP Lane, CC (reprint author), Rice Univ, Dept Elect & Comp Engn, MS 380,POB 1892, Houston, TX 77251 USA. EM court@rice.edu OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [R01 DC002258, DC-02258, DC-00038, T32 DC000038, DC-00361, DC-05209, P30 DC005209] NR 77 TC 18 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2005 VL 94 IS 2 BP 1180 EP 1198 DI 10.1152/jn.01112.2004 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 950UA UT WOS:000230882300030 PM 15857966 ER PT J AU Kaban, LB Guralnick, WC AF Kaban, LB Guralnick, WC TI Massachusetts General Hospital/Harvard MD oral and maxillofacial surgery program SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2005 VL 63 IS 8 BP 1069 EP 1072 DI 10.1016/j.joms.2005.04.033 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 951EM UT WOS:000230911900002 PM 16094570 ER PT J AU Steinbacher, DM Kaban, LB Troulis, MJ AF Steinbacher, DM Kaban, LB Troulis, MJ TI Mandibular advancement by distraction osteogenesis for tracheostomy-dependent children with severe micrognathia SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-of-Oral-Maxillofacial-Surgeons CY SEP, 2003 CL Orlando, FL SP Amer Assoc Oral & Maxillofacial Surg ID UPPER AIRWAY-OBSTRUCTION; PIERRE-ROBIN-SEQUENCE; SLEEP-APNEA SYNDROME; EARLY DECANNULATION; HYPOPLASIA; EXPERIENCE AB Purpose: The purpose of this study was to evaluate mandibular lengthening by distraction osteogenesis (DO) to achieve decannulation of micrognathic children with "permanent" tracheostomies. Patients and Methods: Using a retrospective chart review, patients were included who had 1) airway compromise/tracheostomy, 2) micrognathia, 3) polysomnography-documented obstructive apnea, and 4) mandibular advancement using DO. Excluded were 1) adults, 2) neonates without tracheostomy, and 3) patients with central apnea. Patient age, past medical history, age at tracheostomy, and distraction protocol were documented. Oxygen saturation, posterior airway space (in millimeters), and sella-nasion-B point (SNB) angle were recorded. The distraction protocol consisted of a latency of 48 hours and a rate of 1 mm/day. Results: There were 5 children, aged 2 to 14 years, who received a tracheostomy between ages 2 and 36 months for airway obstruction. All patients underwent bilateral mandibular distraction using semiburied, unidirectional devices. The average latency was 58 hours, the rate was 1 mm/day, the duration of fixation was 40 to 60 days, and the magnitude of advancement was 23 mm. Healing was evaluated by clinical, radiologic, and ultrasound examinations. No complications were experienced. Mean follow-up was 3.2 years. Postdistraction sleep studies demonstrated no obstructive apneic events and a mean oxygen saturation of 98% (preoperative, 76%, P <.005). Cephalometric values improved: posterior airway space 4 to 14 mm; SNB 66 degrees to 72 degrees (P <.005 for both variables). Four of the 5 patients have been successfully decannulated to date. Conclusions: The results of this preliminary study indicate that mandibular advancement by DO is a potentially viable treatment option for tracheostomy-dependent children with upper airway obstruction secondary to micrognathia. (c) 2005 American Association of Oral and Maxillofacial Surgeons C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02112 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02112 USA. EM mtroulis@partners.org NR 36 TC 26 Z9 31 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2005 VL 63 IS 8 BP 1072 EP 1079 DI 10.1016/j.joms.2005.04.013 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 951EM UT WOS:000230911900003 PM 16094571 ER PT J AU Susarla, SM Lam, NP Donoff, RB Kaban, LB Dodson, TB AF Susarla, SM Lam, NP Donoff, RB Kaban, LB Dodson, TB TI A comparison of patient satisfaction and objective assessment of neurosensory function after trigeminal nerve repair SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID LINGUAL NERVE; INFERIOR ALVEOLAR; SURGERY; PAIN AB Purpose: The purpose of this study was to compare objective and subjective assessments of neurosensory function after trigeminal nerve repair. Methods: This was a retrospective cohort study using a sample of patients who underwent surgical repair of trigeminal nerve injuries. The primary study variables were categorized as objective or subjective. The objective variable was the change in neurosensory examination between preoperative and 1-year postoperative visits. Neurosensory status was measured using an ordinal scale ranging from anesthetic (0) to normal (4). Subjective variables included patient satisfaction with the nerve repair and patient assessment of injury-related oral dysfunction. Demographic, anatomic, and operative variables were also collected. Appropriate univariate and bivariate statistics were computed. Results: The sample was composed of 19 patients (14 female, 17 Caucasian) who had trigeminal nerve repair (17 lingual, 2 inferior alveolar). The mean duration between injury and repair was 4.5 +/- 2.3 months; between repair and postoperative assessment was 11.9 +/- 0.9 months. The mean change in neurosensory status was 1.3 +/- 1.0 levels. The majority of patients (63.1%) rated their satisfaction with the outcome of treatment as "good" to "excellent." There was a statistically significant correlation between change in neurosensory status and patient satisfaction (rho = 0.86; P < .01). Conclusion: There is evidence of a strong correlation between improvement in the neurosensory examination following trigeminal nerve repair and patient satisfaction with the surgical outcome 1-year postoperatively. Patients who experience greater neurosensory improvement also report lower frequencies of related oral dysfunction. (c) 2005 American Association of Oral and Maxillofacial Surgeons C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Growth Dev, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU NIDCR NIH HHS [K24-DE000448] NR 16 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2005 VL 63 IS 8 BP 1138 EP 1144 DI 10.1016/j.joms.2005.04.021 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 951EM UT WOS:000230911900013 PM 16094581 ER PT J AU Subramanian, S West, RB Marinelli, RJ Nielsen, TO Rubin, BP Goldblum, JR Patel, RM Zhu, S Montgomery, K Ng, TL Corless, CL Heinrich, MC van de Rijn, M AF Subramanian, S West, RB Marinelli, RJ Nielsen, TO Rubin, BP Goldblum, JR Patel, RM Zhu, S Montgomery, K Ng, TL Corless, CL Heinrich, MC van de Rijn, M TI The gene expression profile of extraskeletal myxoid chondrosarcoma SO JOURNAL OF PATHOLOGY LA English DT Article DE extraskeletal myxoid chondrosarcoma; expressing profile; lipid metabolism; Neuromedin B gene; tissue microarray ID ACTIVATED-RECEPTOR-GAMMA; GASTROINTESTINAL STROMAL TUMORS; FINE-NEEDLE-ASPIRATION; SOFT-TISSUE TUMORS; NEUROENDOCRINE DIFFERENTIATION; FUSION PROTEIN; FATTY-ACIDS; PPAR-GAMMA; DERMATOFIBROSARCOMA PROTUBERANS; MOLECULAR CHARACTERIZATION AB Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42 000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Stanford Univ, Ctr Med, Dept Pathol, Stanford, CA 94035 USA. Stanford Univ, Ctr Med, Dept Biochem, Stanford, CA USA. Vancouver Gen Hosp, Dept Pathol & Genet Pathol, Evaluat Ctr, Vancouver, BC, Canada. Univ Washington, Ctr Med, Dept Anat Pathol, Seattle, WA USA. Cleveland Clin Fdn, Dept Pathol Anat, Cleveland, OH USA. Oregon Hlth Sci Univ, OHSU Canc Inst, Dept Pathol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. RP van de Rijn, M (reprint author), Stanford Univ, Ctr Med, Dept Pathol, 300 Pasteur Dr,L-235, Stanford, CA 94035 USA. EM mrijn@stanford.edu FU NCI NIH HHS [CA85129] NR 97 TC 36 Z9 37 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD AUG PY 2005 VL 206 IS 4 BP 433 EP 444 DI 10.1002/path.1792 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 947QV UT WOS:000230662100009 PM 15920699 ER PT J AU Markowitz, J Markowitz, TE Bousvaros, A Crandall, W Faubion, I Kirschner, BS Perrault, J Rosh, J Winter, H AF Markowitz, J Markowitz, TE Bousvaros, A Crandall, W Faubion, I Kirschner, BS Perrault, J Rosh, J Winter, H TI Workshop report: Prevention of postoperative recurrence in Crohn's disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; PLACEBO-CONTROLLED TRIAL; INTESTINAL INFLAMMATION; MAINTENANCE TREATMENT; ILEOCOLIC RESECTION; FECAL CALPROTECTIN; RISK-FACTORS; MESALAMINE; RELAPSE; 6-MERCAPTOPURINE C1 Schneider Childrens Hosp, Div Pediat Gastroenterol, New Hyde Pk, NY 11040 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Columbus, OH 43205 USA. Mayo Clin Rochester, Rochester, MN USA. Univ Chicago, Chicago, IL 60637 USA. McGill Univ, Montreal, PQ, Canada. Morristown Mem Hosp, Morristown, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Markowitz, J (reprint author), Schneider Childrens Hosp, Div Pediat Gastroenterol, N Shore LIJ Hlth Syst,269-01 76 Ave, New Hyde Pk, NY 11040 USA. EM jmarkowi@nshs.edu NR 49 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2005 VL 41 IS 2 BP 145 EP 151 DI 10.1097/01.mpg.0000172746.86973.ef PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 950VA UT WOS:000230885000001 PM 16056092 ER PT J AU Deal, L Gold, TD Gremse, DA Winter, HS Peters, SB Fraga, PD Mack, ME Gaylord, SM Tolia, I Fitzgerald, JF AF Deal, L Gold, TD Gremse, DA Winter, HS Peters, SB Fraga, PD Mack, ME Gaylord, SM Tolia, I Fitzgerald, JF TI Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: Development and initial validation SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; PREVALENCE; CHILDHOOD; VALIDITY AB Two gastroesophageal reflux disease (GERD) symptom questionnaires were developed and tested prospectively in a pilot study conducted in infants (1 through 11 months) and young children (1 through 4 years) with and without a clinical diagnosis of GERD. A pediatric gastroenterologist made the clinical diagnosis of GERD. Parents or guardians at 4 study sites completed the questionnaires, providing information on the frequency and severity of symptoms appropriate to the 2 age cohorts. In infants, symptoms assessed were back arching, choking or gagging, hiccups, irritability, refusal to feed and vomiting or regurgitation. In young children, symptoms assessed were abdominal pain, burping or belching, choking when eating, difficulty swallowing, refusal to eat and vomiting or regurgitation. Respondents were asked to describe additional symptoms. Symptom frequency was the number of occurrences of each symptom in the 7 days before completion of the questionnaire. Symptom severity was rated from 1 (not at all severe) to 7 (most severe). An individual symptom score was calculated as the product of symptom frequency and severity scores. The composite symptom score was the sum of the individual symptom scores. The mean composite symptom and individual symptom scores were higher in infants (P < 0.001 and P < 0.05, respectively) and young children (P < 0.001 and P < 0.05, respectively) with GERD than controls. Vomiting/regurgitation was particularly prevalent in infants with GERD (90%). Both groups with GERD were more likely to experience greater severity of symptoms. We found the GERD Symptom Questionnaire useful in distinguishing infants and young children with symptomatic GERD from healthy children. C1 Wyeth Ayerst Res, Collegeville, PA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ S Alabama, Mobile, AL 36688 USA. MassGen Hosp Children, Boston, MA USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Indiana Sch Med, Indianapolis, IN USA. James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. RP Deal, L (reprint author), Wyeth Global Hlth Outcomes Assessment, 500 Arcola Rd, Collegeville, PA 19426 USA. EM deall@wyeth.com NR 15 TC 48 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2005 VL 41 IS 2 BP 178 EP 185 DI 10.1097/01.mpg.0000172885.77795.0f PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 950VA UT WOS:000230885000005 PM 16056096 ER PT J AU Smith, SR Blais, MA Vangala, M Masek, BJ AF Smith, SR Blais, MA Vangala, M Masek, BJ TI Exploring the hand test with medically ill children and adolescents SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Society-for-Personality-Assessment CY MAR, 2002 CL SAN ANTONIO, TX SP Soc Personality Assessment ID INCREMENTAL VALIDITY; PAIN; MULTIMETHOD; RELIABILITY; INFORMANTS; ADJUSTMENT; DISORDERS; VARIABLES; RESPONSES; SCALE AB Pediatric psychologists use the tools of assessment to evaluate the psychological functioning of youth with chronic and acute medical illnesses. This study is an exploration of the use of a performance-based measure, the Hand Test (HT; Wagner, 1983), with pediatric medical patients. A sample of medical inpatients (n = 27) and psychiatric outpatients (n = 24) were administered the HT, a self-report measure, and a parent-report behavior rating scale. Results indicate that the psychiatric group scored higher than the medical group on HT Aggression, Withdrawal, and Pathological scores. The Aggression (d = 0.90) and Pathological (d = 0.80) variables were particularly robust in differentiating between groups, but the Crippled variable did not differ between groups. Hierarchical logistic regression demonstrated the incremental validity of the HT over behavior ratings alone in the classification of clinical groups. Analyses indicated that the HT can add important information in the differentiation of medically ill children from those with psychological disturbance. C1 Univ Calif Santa Barbara, Grad Sch Educ, Counseling Clin & Sch Psychol Program, Santa Barbara, CA 93106 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Smith, SR (reprint author), Univ Calif Santa Barbara, Grad Sch Educ, Counseling Clin & Sch Psychol Program, Santa Barbara, CA 93106 USA. EM ssmith@education.ucsb.edu NR 40 TC 2 Z9 2 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD AUG PY 2005 VL 85 IS 1 BP 82 EP 91 DI 10.1207/s15327752jpa8501_08 PG 10 WC Psychology, Clinical; Psychology, Social SC Psychology GA 949QR UT WOS:000230803700008 PM 16083387 ER PT J AU Chan, PLS Nutt, JG Holford, NHG AF Chan, PLS Nutt, JG Holford, NHG TI Importance of within subject variation in levodopa pharmacokinetics: A 4 year cohort study in Parkinson's disease SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE levodopa; within subject variability; pharmacokinetics; Parkinson's disease; population approach ID ON-OFF FLUCTUATIONS; L-DOPA THERAPY; POPULATION PHARMACOKINETICS; ORAL LEVODOPA; MOTOR FLUCTUATIONS; PHARMACODYNAMICS; 1ST; BIOAVAILABILITY; 3-O-METHYLDOPA; EVOLUTION AB The purpose of the study was to describe the population pharmacokinetics of levodopa in patients with Parkinson's disease studied in 5 trials (10 occasions) over 4 years. Twenty previously untreated Parkinsonian patients were investigated. Each trial consisted of a 2-hr IV infusion of levodopa (1 mg/kg/h) with concomitant oral carbidopa given on two occasions separated by 72hr with no levodopa in between. This trial design was repeated at 6, 12, 24 and 48 months. A two-compartment pharmacokinetic model with central volume (V-1), peripheral volume (V-2), clearance (CL) and inter-compartmental clearance (CLic) was used to fit plasma levodopa concentrations. The model accounted for levodopa dosing prior to each trial and endogenous levodopa synthesis. Population parameter estimates (geometric mean) and population parameter variability (PPV; SD of normal distribution) were V-1 11.4 l/70 kg (0.44), CL 30.9 l/h/70 kg (0.25), V-2 27.3 l/70 kg (0.27), and CLic 34.6 l/h/70 kg (0.48). PPV was partitioned into between subject variability (BSV) which was 0.12 V-1, 0.13 CL, 0.15 V-2, 0.28 CLic, within trial variability (WTV) which was 0.16 V-1, 0.13 CL, 0.08 V-2, 0.18 CLic and between trial variability (BTV) which was 0.40 V-1, 0.17 CL, 0.21 V-2, 0.34 CLic. Neither structural nor random levodopa pharmacokinetic parameters were associated with the time course of development of fluctuation in motor response. Variability in levodopa pharmacokinetic parameters (particularly V-1) may result in variability in plasma levodopa concentrations that could contribute to fluctuations in motor response. C1 Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Neurobiol Physiol & Pharmacol, Portland, OR USA. Pfizer Inc, Ann Arbor, MI 48105 USA. RP Chan, PLS (reprint author), Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. EM Phylinda.Chan@pfizer.com OI Holford, Nick/0000-0002-4031-2514 NR 40 TC 11 Z9 12 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD AUG PY 2005 VL 32 IS 3-4 BP 307 EP 331 DI 10.1007/s10928-005-0039-x PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 990DT UT WOS:000233724100001 PM 16320098 ER PT J AU Chan, PLS Nutt, JG Holford, NHG AF Chan, PLS Nutt, JG Holford, NHG TI Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE levodopa; pharmacokinetics; pharmacodynamics; disease progression; Parkinson's disease; fluctuations ID LONG-DURATION RESPONSES; MOTOR FLUCTUATIONS; SLEEP BENEFIT; ORAL LEVODOPA; L-DOPA; THERAPY; MECHANISMS; DYSKINESIAS; EVOLUTION; TIME AB The purpose of this analysis is to describe how levodopa pharmacokinetic and pharmacodynamic parameters change over the first 4 years of long-term levodopa treatment in patients with Parkinson's disease. Twenty previously untreated Parkinsonian patients were admitted to the general clinical research center (GCRC) for 4 days at the beginning of long-term levodopa therapy and 6, 12, 24 and 48 months later. On each GCRC admission, patients received a 2 hr IV infusion of levodopa on day 1 and day 4 with no oral levodopa between the infusions. After the first GCRC admission patients were treated with oral levodopa dosed for optimal control of Parkinsonism. Motor function was measured by finger tapping rate. A pharmacokinetic-pharmacodynamic model incorporating 3 effect compartments was used to fit the individual plasma levodopa concentrations and tapping rates. Motor function before the first levodopa infusion (E0(1)) improved over the first 20 months and subsequently returned to the initial baseline at the start of the study. A similar pattern was seen in motor function before the second infusion (E0(2)) after the 3 days levodopa withdrawal, with a decline predicted to fall below the initial baseline at the start of the study by 6 years. Eight patients showed an increase in maximum tapping rate with levodopa (E-max) approaching a steady state after 16 months. Ten patients showed an increase in E-max with a peak at 31 months. One patient showed a linear decrease and another patient did not change over the 48 months. Longitudinal progress models were used to describe the time course of pharmacokinetic and pharmacodynamic parameters over 4 years. Peak treatment benefit, defined as the difference between E-max and E0(1) or E0(2) (D-max1 or D-max2), increased with time particularly after the 3-day levodopa withdrawal. Deterioration of pre-dose motor function (E0) as disease progresses coupled with a greater amplitude of response due to levodopa (D-max) could be a key factor contributing to motor fluctuations associated with long-term levodopa treatment. C1 Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. Portland VA Med Ctr, Dept Neurol & Physiol & Pharmacol, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Pfizer Inc, Ann Arbor, MI 48105 USA. RP Chan, PLS (reprint author), Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. EM Phylinda.Chan@pfizer.com OI Holford, Nick/0000-0002-4031-2514 NR 39 TC 15 Z9 15 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD AUG PY 2005 VL 32 IS 3-4 BP 459 EP 484 DI 10.1007/s10928-005-0055-x PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 990DT UT WOS:000233724100008 PM 16320101 ER PT J AU Maudsley, S Martin, B Luttrell, LM AF Maudsley, S Martin, B Luttrell, LM TI The origins of diversity and specificity in G protein-coupled receptor signaling SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BETA(2) ADRENERGIC-RECEPTOR; A-MEDIATED PHOSPHORYLATION; TERNARY COMPLEX MODEL; MU-OPIOID RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; EFFECTOR PATHWAY; KINASE-A; CONSTITUTIVE ACTIVATION; ANTAGONISTS PROMOTE; PERTUSSIS-TOXIN AB The modulation of transmembrane signaling by G protein-coupled receptors ( GPCRs) constitutes the single most important therapeutic target in medicine. Drugs acting on GPCRs have traditionally been classified as agonists, partial agonists, or antagonists based on a two- state model of receptor function embodied in the ternary complex model. Over the past decade, however, many lines of investigation have shown that GPCR signaling exhibits greater diversity and "texture" than previously appreciated. Signal diversity arises from numerous factors, among which are the ability of receptors to adopt multiple "active" states with different effector-coupling profiles; the formation of receptor dimers that exhibit unique pharmacology, signaling, and trafficking; the dissociation of receptor "activation" from desensitization and internalization; and the discovery that non-G protein effectors mediate some aspects of GPCR signaling. At the same time, clustering of GPCRs with their downstream effectors in membrane microdomains and interactions between receptors and a plethora of multidomain scaffolding proteins and accessory/ chaperone molecules confer signal preorganization, efficiency, and specificity. In this context, the concept of agonist-selective trafficking of receptor signaling, which recognizes that a bound ligand may select between a menu of active receptor conformations and induce only a subset of the possible response profile, presents the opportunity to develop drugs that change the quality as well as the quantity of efficacy. As a more comprehensive understanding of the complexity of GPCR signaling is developed, the rational design of ligands possessing increased specific efficacy and attenuated side effects may become the standard mode of drug development. C1 NIA, Neurosci Lab, Intramural Res Program, Gerontol Res Ctr,Johns Hopkins Med Ctr, Baltimore, MD USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Maudsley, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, Gerontol Res Ctr,Johns Hopkins Med Ctr, 5600 Nathan Shock Dr, Baltimore, MD USA. EM maudsleyst@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000318-01]; NIDDK NIH HHS [DK 55524, DK 58283, DK 64353, R01 DK055524, R01 DK058283, R01 DK064353, R56 DK055524] NR 95 TC 128 Z9 130 U1 0 U2 15 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 2005 VL 314 IS 2 BP 485 EP 494 DI 10.1124/jpet.105.083121 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946CS UT WOS:000230550300001 PM 15805429 ER PT J AU Meltzner, GS Hillman, RE AF Meltzner, GS Hillman, RE TI Impact of aberrant acoustic properties on the perception of sound quality in electrolarynx speech SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE electrolarynx speech; alaryngeal speech; laryngectomy speech rehabilitation; speech quality; artificial larynx speech ID LARYNGECTOMEE REHABILITATION; COMMUNICATION; MODEL AB A large percentage of patients who have undergone laryngectomy to treat advanced laryngeal cancer rely on an electrolarynx (EL) to communicate verba Although serviceable, EL speech is plagued by shortcomings in both sound quality This study sought to better quantify the relative contributions of and intelligibility. previously identified acoustic abnormalities to the perception of degraded quality in EL speech. Ten normal listeners evaluated the sound quality of EL speech tokens that had been acoustically enhanced by (a) increased low-frequency energy, (b) EL-noise reduction, and (c) fundamental frequency variation to mimic normal pitch intonation in relation to nonenhanced EL speech, normal speech, and normal monotonous speech (fundamental frequency variation removed). In comparing all possible combinations of token pairs, listeners were asked to identify which one of each pair sounded most like normal natural speech, and then to rate on a visual analog scale how different the chosen token was from normal speech. The results indicate that although EL speech can be most improved by removing the EL noise and providing proper pitch information, the resulting quality is still well below that of normal natural speech or even that of monotonous natural speech. This suggests that, in addition to the widely acknowledged acoustic abnormalities examined in this investigation, there are other attributes that contribute significantly to the unnatural quality of EL speech. Such additional factors need to be clearly identified and remedied before EL speech can be made to more closely approximate the sound quality of normal natural speech. C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Meltzner, GS (reprint author), BAE Syst, 6 New England Execut Pk, Burlington, MA 01803 USA. EM geoffrey.meltzner@baesystems.com NR 39 TC 18 Z9 18 U1 2 U2 6 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD AUG PY 2005 VL 48 IS 4 BP 766 EP 779 DI 10.1044/1092-4388(2005/053) PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 993SI UT WOS:000233974900005 PM 16378472 ER PT J AU Banta, S Yokoyama, T Berthiaume, F Yarmush, ML AF Banta, S Yokoyama, T Berthiaume, F Yarmush, ML TI Effects of dehydroepiandrosterone administration on rat hepatic metabolism following thermal injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE liver perfusion; metabolic flux analysis; dehydroepiandrosterone; burn injury; antioxidants ID SEVERE SURGICAL ILLNESS; BURN INJURY; LIPID-PEROXIDATION; TRAUMA-HEMORRHAGE; OXIDATIVE STRESS; LIVER PERFUSION; DHEA TREATMENT; SEVERE SEPSIS; MODEL; INDUCTION AB Background. Severe burns cause dramatic alterations in liver and whole-body metabolism. Recently, there has been interest in using dehydroepiandrosterone (DHEA) as a treatment for trauma patients, and enhanced survival and immune function have been reported using DHEA in animal trauma models. The specific effects of DHEA on hepatic metabolism following burn injury have not been explored. Materials and methods. Male rats received either (1) a burn covering similar to 20% of the total body surface area or a sham burn or (2) burn injury followed by two intraperitoneal injections of DHEA or vehicle. After 4 days, the livers were isolated and perfused in vitro, and 28 metabolite fluxes were measured. Metabolic flux analysis was used to obtain the intracellular metabolic flux distribution and provide an overview of the metabolic state of the livers in each experimental group. Results. Burn injury decreased the uptake of lactate and the production of beta-hydroxybutyrate and increased the deamination of glutamine to glutamate and asparagine to aspartate. DHEA, compared to vehicle treatment, decreased pentose phosphate pathway (PPP) fluxes and the uptake of several amino acids in burned rats. Furthermore, DHEA treatment restored liver metabolism in burned rats to a state that was very similar to that of the sham control group. Conclusions. DHEA administration appears to normalize hepatocellular metabolism in burned rats but also decreases the PPP flux, which may impair the liver's ability to recycle endogenous antioxidants. DHEA treatment combined with exogenous antioxidants should receive further consideration in the management of burn and trauma patients. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Shriners Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yarmush, ML (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK 59766] NR 62 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2005 VL 127 IS 2 BP 93 EP 105 DI 10.1016/j.jss.2005.01.001 PG 13 WC Surgery SC Surgery GA 953DN UT WOS:000231056700006 PM 15882877 ER PT J AU Hanifin, JM Paller, AS Eichenfield, L Clark, RA Korman, N Weinstein, G Caro I Jaracz, E Rico, MJ AF Hanifin, JM Paller, AS Eichenfield, L Clark, RA Korman, N Weinstein, G Caro, I Jaracz, E Rico, MJ CA US Tacrolimus Ointment Study Grp TI Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 61st Meeting of the American-Academy-of-Dermatology CY MAR 21, 2003 CL SAN FRANCISCO, CA SP Amer Acad Dermatol ID HERPES-SIMPLEX; VARICELLIFORM ERUPTION; ECZEMA HERPETICUM; SEVERITY INDEX; ADULT PATIENTS; INFECTIONS; PIMECROLIMUS; PREVENTION; AREA AB Objective: This study was designed to evaluate the long-term safety and efficacy of 0.1 % tacrolimus ointment in adult and pediatric patients with atopic dermatitis (AD). Methods. A total of 408 adult and 391 pediatric patients with AD who had participated in a previous clinical trial of tacrolimus ointment were enrolled in this long-term, open-label, noncomparative trial. Tacrolimus ointment 0.1 % was applied twice daily either intermittently or continuously to the affected areas. Efficacy and safety assessments included percent body surface area affected, Eczema Area and Severity Index score, individual signs of AD, and the incidence of adverse events. Results: A total of 799 patients were evaluated, of whom 300 (37.5 %) were followed for more than 3 years (maximum 49 months). Improvements in efficacy parameters were observed within I week of treatment and continued for the duration of the Study. Common adverse events included skin burning, pruritus, skin infection, skin erythema, flu-like symptoms, and headache. The incidence of adverse events, including Cutaneous infections, did not increase with time on study. Conclusion: Tacrolimus ointment therapy is a rapidly effective and safe treatment for the management of AD in pediatric and adult patients for up to 4 years. C1 Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp, San Diego, CA USA. Ctr Hlth, San Diego, CA USA. SUNY, New York, NY USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Astellas Pharma US Inc, Deerfield, IL USA. RP Hanifin, JM (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, OP06,3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hanifinj@ohsu.edu NR 27 TC 56 Z9 60 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2005 VL 53 IS 2 SU S BP S186 EP S194 DI 10.1016/j.jaad.2005.04.062 PN 2 PG 9 WC Dermatology SC Dermatology GA 953NE UT WOS:000231082300004 PM 16021174 ER PT J AU Pugh, MJV Fincke, BG Bierman, AS Chang, BH Rosen, AK Cunningham, FE Amuan, ME Burk, ML Berlowitz, DR AF Pugh, MJV Fincke, BG Bierman, AS Chang, BH Rosen, AK Cunningham, FE Amuan, ME Burk, ML Berlowitz, DR TI Potentially inappropriate prescribing in elderly veterans: Are we using the wrong drug, wrong dose, or wrong duration? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pharmacoepidemiology; patient safety; prescribing; appropriateness; geriatrics ID NURSING-HOME RESIDENTS; MEDICATION USE; BENZODIAZEPINE USE; EXPLICIT CRITERIA; BEERS CRITERIA; UNITED-STATES; OLDER-ADULTS; POPULATION; RISK; PRESCRIPTIONS AB OBJECTIVES: To identify the extent of inappropriate prescribing using criteria for proper use developed by the Agency for Healthcare Research and Quality (AHRQ) and dose-limitation criteria defined by Beers, as well as to describe duration of use and patient characteristics associated with inappropriate prescribing for older people. DESIGN: Retrospective national Veterans Health Administration (VA) administrative database analysis. SETTING: VA outpatient facilities during fiscal year 2000 (FY00). PARTICIPANTS: Veterans aged 65 and older having at least one VA outpatient visit in FY00 (N=1,265,434). MEASUREMENTS: Operational definitions of appropriate use were developed based on recommendations of an expert panel convened by the AHRQ (Zhan criteria). Inappropriate use was identified based on these criteria and inappropriate use of drugs per Beers criteria for dose-limitations in older people. Furthermore, duration of use and patient characteristics associated with inappropriate use were described. RESULTS: After adjusting for diagnoses, dose, and duration, inappropriate prescribing decreased from 33% to 23%. Exposure to inappropriate drugs was prolonged. Pain relievers, benzodiazepines, antidepressants, and musculoskeletal agents constituted 61% of inappropriate prescribing. Whites, patients with psychiatric comorbidities, and patients receiving more medications were most likely to receive inappropriate drugs. Women were more likely to receive Zhan criteria drugs; men were more likely to receive dose-limited drugs CONCLUSION: For the most part, the Zhan criteria did not explain inappropriate prescribing, which includes problems related to dose and duration of prescriptions. Interventions targeted at prescriptions for pain relievers, benzodiazepines, antidepressants, and musculoskeletal agents may dramatically decrease inappropriate prescribing and improve patient outcomes. C1 S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, Audie L Murphy Div, San Antonio, TX USA. Dept Vet Affairs Hosp, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Inner City Hlth Res Unit, Toronto, ON M5B 1W8, Canada. US Dept Vet Affairs, Pharm Benefits Management Strateg Hlth Grp, Hines, IL 60141 USA. Univ Illinois, Coll Pharm, Chicago, IL 60680 USA. RP Pugh, MJV (reprint author), STVHCS, VERDICT, ALMD, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763 NR 39 TC 48 Z9 50 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2005 VL 53 IS 8 BP 1282 EP 1289 DI 10.1111/j.1532-5415.2005.53402.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 948OY UT WOS:000230726800002 PM 16078952 ER PT J AU Ullian, ME Gelasco, AK Fitzgibbon, WR Beck, CN Morinelli, TA AF Ullian, ME Gelasco, AK Fitzgibbon, WR Beck, CN Morinelli, TA TI N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth muscle cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Nephrology CY OCT 30-NOV 06, 2002 CL PHILADELPHIA, PA SP Amer Soc Nephrol ID ALPHA-LIPOIC ACID; OXIDATIVE STRESS; EXTRACELLULAR DOMAINS; SUPEROXIDE-PRODUCTION; DISULFIDE BRIDGES; TYPE-1 RECEPTOR; GENE-EXPRESSION; LIGAND-BINDING; PROTEIN-KINASE; MESSENGER-RNA AB Antioxidants seem to inhibit angiotensin II (Ang II) actions by consuming stimulated reactive oxygen species. An alternative hypothesis was investigated: Antioxidants that are also strong reducers of disulfide bonds inhibit the binding of Ang II to its surface receptors with consequent attenuation of signal transduction and cell action. Incubation of cultured vascular smooth muscle cells, which possess Ang II type 1 alpha receptors, with the reducing agent n-acetylcysteine (NAC) for 1 h at 37 degrees C resulted in decreased Ang II radioligand binding in a concentration-dependent pattern. NAC removal restored Ang II binding within 30 min. Incubation with n-acetylserine, a nonreducing analogue of NAC, did not lower Ang II binding, and oxidized NAC was less effective than reduced NAC in lowering Ang II binding. NAC did not decrease Ang II type 1 alpha receptor protein content. Other antioxidants regulated Ang II receptors differently: alpha-Lipoic acid lowered Ang II binding after 24 h, and vitamin E did not lower Ang II binding at all. NAC inhibited Ang II binding in cell membranes at 21 or 37 but not VC. Dihydrolipoic acid (the reduced form of alpha-lipoic acid), which contains free sulfhydryl groups as NAC does, decreased Ang II receptor binding in cell membranes, whereas alpha-lipoic acid, which does not contain free sulfhydryl groups, did not. Ang II-stimulated inositol phosphate formation was decreased by preincubation with NAC (1 h) or alpha-lipoic acid (24 h) but not vitamin E. In conclusion, certain antioxidants that are reducing agents lower Ang II receptor binding, and Ang II-stimulated signal transduction is decreased in proportion to decreased receptor binding. C1 Med Univ S Carolina, Div Nephrol, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. RP Ullian, ME (reprint author), Med Univ S Carolina, Div Nephrol, Ralph H Johnson Vet Adm Hosp, CSB 829,96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM ullianme@musc.edu NR 48 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2005 VL 16 IS 8 BP 2346 EP 2353 DI 10.1681/ASN.2004060458 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 949HC UT WOS:000230774700013 PM 15944340 ER PT J AU Weisbord, SD Fried, LF Arnold, RM Fine, MJ Levenson, DJ Peterson, RA Switzer, GE AF Weisbord, SD Fried, LF Arnold, RM Fine, MJ Levenson, DJ Peterson, RA Switzer, GE TI Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; AMBULATORY AIDS PATIENTS; ERECTILE DYSFUNCTION; DIALYSIS PATIENTS; BEHAVIORAL COMPLIANCE; PSYCHOSOCIAL FACTORS; MEDICAL-CENTER; DEPRESSION; PAIN AB The prevalence, severity, and clinical significance of physical and emotional symptoms in patients who are on maintenance hemodialysis remain incompletely characterized. This study sought to assess symptoms and their relationship to quality of life and depression. The recently developed Dialysis Symptom Index was used to assess the presence and the severity of 30 symptoms. The Illness Effects Questionnaire and Beck Depression Inventory were used to evaluate quality of life and depression, respectively. Correlations among symptom burden, symptom severity, quality of life, and depression were assessed using Spearman correlation coefficient. A total of 162 patients from three dialysis units were enrolled. Mean age was 62 y, 48% were black, 62% were men, and 48% had diabetes. The median number of symptoms was 9.0 (interquartile range 6 to 13). Dry skin, fatigue, itching, and bone/joint pain each were reported by >= 50% of patients. Seven additional symptoms were reported by > 33% of patients. Sixteen individual symptoms were described as being more than "somewhat bothersome." Overall symptom burden and severity each were correlated directly with impaired quality of life and depression. In multivariable analyses adjusting for demographic and clinical variables including depression, associations between symptoms and quality of life remained robust. Physical and emotional symptoms are prevalent, can be severe, and are correlated directly with impaired quality of life and depression in maintenance hemodialysis patients. Incorporating a standard assessment of symptoms into the care provided to maintenance hemodialysis patients may provide a means to improve quality of life in this patient population. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc,Inst Performance Improvement, Div Gen Internal Med,Ctr Bioeth & Hlth Law, Dept Med,Sect Palliat Care & Med Eth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Med, Ctr Hlth Equ Res & Promot,VA Pittsburgh Healthcar, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. George Washington Univ, Dept Psychol, Washington, DC 20052 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, 7E,Room 120,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM steven.weisbord@med.va.gov FU NHLBI NIH HHS [T32HL07820-05] NR 48 TC 170 Z9 184 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2005 VL 16 IS 8 BP 2487 EP 2494 DI 10.1681/ASN.2005020157 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 949HC UT WOS:000230774700029 PM 15975996 ER PT J AU Salusky, IB Goodman, WG Sahney, S Gales, B Perilloux, A Wang, HJ Elashoff, RM Juppner, H AF Salusky, IB Goodman, WG Sahney, S Gales, B Perilloux, A Wang, HJ Elashoff, RM Juppner, H TI Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; INTERMITTENT CALCITRIOL THERAPY; AMBULATORY PERITONEAL-DIALYSIS; CHRONIC KIDNEY-DISEASE; FREE PHOSPHATE BINDER; HEMODIALYSIS-PATIENTS; SECONDARY HYPERPARATHYROIDISM; PEDIATRIC-PATIENTS; YOUNG-ADULTS; CHILDREN AB Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism (2 degrees HPT). The effects of calcium carbonate (CaCO3) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT. Twenty-nine patients were randomly assigned to CaCO3 (n = 14) or sevelamer (n = 15), concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2 degrees HPT improved with both binders, and bone formation rates reached the normal range in approximately 75% of the patients. Overall, serum phosphorus levels were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS) with CaCO3 and sevelamer, respectively. Serum calcium levels and the Ca x P ion product increased with CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus 8.9 +/- 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (> 10.2 mg/dl) occurred more frequently with CaCO3 (P < 0.01). Baseline PTH levels were 980 +/- 112 and 975 +/- 174 pg/ml (NS); these values decreased to 369 +/- 92 (P < 0.01) and 562 +/- 164 pg/ml (P < 0.01) in the CaCO3 and the sevelamer groups, respectively (NS between groups). Serum alkaline phosphatase levels also diminished in both groups (P < 0.01). Thus, treatment with either CaCO3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT. Sevelamer, however, maintained serum calcium concentrations closer to the lower end of the normal physiologic range, thereby increasing the safety of treatment with active vitamin D sterols. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Biomath, Los Angeles, CA 90095 USA. Loma Linda Med Ctr, Dept Pediat, Loma Linda, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Salusky, IB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Dept Pediat, 10833 Le Conte Blvd,Box 951752, Los Angeles, CA 90095 USA. EM isalusky@mednet.ucla.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 49 TC 58 Z9 59 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2005 VL 16 IS 8 BP 2501 EP 2508 DI 10.1681/ASN.2004100885 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 949HC UT WOS:000230774700031 PM 15944337 ER PT J AU Johnston, DR Muniappan, A Hoerbelt, R Guenther, DA Shoji, T Houser, SL Sachs, DH Madsen, JC AF Johnston, DR Muniappan, A Hoerbelt, R Guenther, DA Shoji, T Houser, SL Sachs, DH Madsen, JC TI Heart and en-bloc thymus transplantation in miniature swine SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MISMATCHED BARRIERS; TOLERANCE; ALLOGRAFT; INDUCTION; DEPENDENCE; MECHANISMS; ANTIGEN AB Background: Donor-specific tolerance to organ allografts might be induced by cotransplantation of a sufficient amount of vascularized donor thymus. To facilitate donor thymus-induced cardiac allograft tolerance, we have developed a novel technique for heart and en-bloc thymus transplantation in swine. Methods: Donor heart and en-bloc thymus grafts were prepared by a technique that preserves the entire arterial supply and venous drainage of the right thymic lobe. En-bloc grafts (n = 4) were transplanted heterotopically into the abdomens of major histocompatibility complex-matched miniature swine. Recipients received 12 days of cyclosporine intravenously. Grafts were monitored by palpation, electrocardiographic monitoring, and periodic open biopsy. Engraftment of the donor thymus was demonstrated by measuring the proportion of recipient-type thymocytes in the donor thymus with flow cytometry. Results: All of the heart and en-bloc thymus grafts had normal cardiac contractility and immediate perfusion of the thymus. All en-bloc grafts were accepted for more than 200 days without significant acute cellular rejection or cardiac allograft vasculopathy. Thymic tissue of en-bloc grafts displayed normal architecture and supported thymopoiesis of recipient-type cells. Conclusion: We have validated a new technique of donor thymus transplantation that could have utility in human heart transplantation. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [F32HL074671-02, R01 HL54211, R01 HL67110, F32HL74519-02, P01 HL18646] NR 15 TC 8 Z9 9 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD AUG PY 2005 VL 130 IS 2 BP 554 EP 559 DI 10.1016/j.jtcvs.2005.03.036 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 953IL UT WOS:000231069700048 PM 16077427 ER PT J AU Polgar, J Matuskova, J Wagner, DD AF Polgar, J Matuskova, J Wagner, DD TI The P-selectin, tissue factor, coagulation triad SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article; Proceedings Paper CT 20th Congress of the International Society-on-Thrombosis-and-Haemostasis CY AUG 06-12, 2005 CL Sydney, AUSTRALIA SP Int Soc Thrombosis & Haemostasis DE coagulation; microparticles; P-selectin; P-selectin glycoprotein ligand 1; thrombosis; tissue factor ID VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; FACTOR PATHWAY INHIBITOR; HUMAN-ENDOTHELIAL CELLS; IN-VIVO; DEFICIENT MICE; LEUKOCYTE MICROPARTICLES; GLYCOPROTEIN LIGAND-1; ADHERENT PLATELETS; CYTOPLASMIC DOMAIN AB The primary importance of tissue factor (TF) in blood coagulation and thrombus propagation has been recognized for many years. Nevertheless, our view about the origin of TF activity, necessary for normal hemostasis and found in pathologic conditions, needs to be revised in the light of recent observations. Pioneering work by Yale Nemerson's group showed that circulating TF on microparticles (MPs), could promote thrombus growth. The origin and characteristics of this 'blood-borne' TF are targets of intense research as well as intense debate. Surprising observations now implicate the adhesion receptor P-selectin (P-sel), known for its role in inflammation, in these MPs' generation. P-sel, translocated from granules to the cell surfaces of activated platelets and endothelial cells, was recently found to play multiple roles in hemostasis. Expressed on endothelium, it can mediate platelet rolling. Signaling by P-sel through its receptor on leukocytes, P-selectin glycoprotein ligand 1 (PSGL-1), induces the generation of TF-positive, highly procoagulant MPs. In addition, P-sel on activated platelets helps to recruit these MPs specifically to thrombi. In this review, we discuss the roles of P-sel and TF-positive MPs and highlight strategies to modulate hemostasis by modulating the P-sel, TF, coagulation triad. C1 Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R37 HL041002, P01 HL056949, P01 HL56949, R01 HL053756, R01 HL53756, R37 HL41002] NR 69 TC 166 Z9 171 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2005 VL 3 IS 8 BP 1590 EP 1596 DI 10.1111/j.1538-7836.2005.01373.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 949HO UT WOS:000230776000006 PM 16102023 ER PT J AU Schulze, H Shivdasani, RA AF Schulze, H Shivdasani, RA TI Mechanisms of thrombopoiesis SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article; Proceedings Paper CT 20th Congress of the International Society-on-Thrombosis-and-Haemostasis CY AUG 06-12, 2005 CL Sydney, AUSTRALIA SP Int Soc Thrombosis & Haemostasis DE bone marrow cell interactions; megakaryocytes; platelet biogenesis; platelet release; transcription factors ID TRANSCRIPTION FACTOR NF-E2; BERNARD-SOULIER-SYNDROME; ZINC-FINGER PROTEIN; HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION PROFILE; BONE-MARROW; DOWN-SYNDROME; HUMAN MEGAKARYOCYTES; ACTIVATED PLATELETS; PROPLATELET FORMATION AB Megakaryocytes (MKs) expand and differentiate over several days in response to thrombopoietin (Tpo) before releasing innumerable blood platelets. The final steps in platelet assembly and release represent a unique cellular transformation that is orchestrated by a range of transcription factors, signaling molecules, and cytoskeletal elements. Here we review recent advances in the physiology and molecular basis of MK differentiation. Genome-wide approaches, including transcriptional profiling and proteomics, have been used to identify novel platelet products and differentiation markers. The extracellular factors, stromal-derived factor (SDF)-1 chemokine and fibroblast growth factor (FGF)-4 direct MK interactions with the bone marrow stroma and regulate cytokine-independent cell maturation. An abundance of bone marrow MKs induce pathologic states, including excessive bone formation and myelofibrosis, and the basis for these effects is now better appreciated. We review the status of transcription factors that control MK differentiation, with special emphasis on nuclear factor-erythroid 2 (NF-E2) and its two putative target genes, beta 1-tubulin and 3-beta-hydroxysteroid reductase. MKs express steroid receptors and some estrogen ligands, which may constitute an autocrine loop in formation of proplatelets, the cytoplasmic protrusions within which nascent blood platelets are assembled. Finally, we summarize our own studies on cellular and molecular facets of proplatelet formation and place the findings within the context of outstanding questions about mechanisms of thrombopoiesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NHLBI NIH HHS [R01HL63143] NR 86 TC 66 Z9 69 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2005 VL 3 IS 8 BP 1717 EP 1724 DI 10.1111/j.1538-7836.2005.01426.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 949HO UT WOS:000230776000021 PM 16102038 ER PT J AU Ring, D Rhini, RD Carpenter, C Jupiter, JB AF Ring, D Rhini, RD Carpenter, C Jupiter, JB TI Comminuted diaphyseal fractures of the radius and ulna: Does bone grafting affect nonunion rate? SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE radius; ulna; forearm; fracture; bone graft; nonunion; plate; screws ID COMPRESSION-PLATE FIXATION; FOREARM FRACTURES; LONG BONES; ADULTS AB Background: The recommendation of Anderson and colleagues to bone graft even relatively minor amounts of comminution (a third of the bone diameter) in the treatment of diaphyseal forearm fractures with plate-and-screw fixation has been questioned. This study examines factors related to nonunion in adult patients with comminuted diaphyseal fractures of both the radius and the ulna to determine the relative influence of bone grafting. Methods: Over a 15-year period at two hospitals, 41 patients with diaphyseal fractures of both forearm bones satisfied the following criteria: comminution (Orthopaedic Trauma Association grade IV or higher) of at least one fracture; treatment with 3.5- or 4.5-mm dynamic compression plates at least six holes in length; and minimum 12-month follow-up. Multiple logistic regression was used to determine the contribution of the following factors to the risk of nonunion: multiple injuries; ipsilateral upper extremity injury; open wound; and the application of cancellous bone graft at the fracture site. Results: Five patients had nonunion of one or both bones (12%). According to the multiple logistic regression model, none of the factors studied had a statistically significant association with nonunion (p > 0.40 for all). The odds ratios were as follows: multiple injuries, 2.1 (95% confidence interval [CI], 0.34-12.9); ipsilateral injury, 0.68 (95% CI, 0.058-7.84); open fracture, 1.46 (95% CI, 0.21-9.89); and bone graft, 0.98 (95% CI, 0.15-6.42). Conclusion: Nonunion occurred in 12% of comminuted, diaphyseal fractures of both bones of the forearm treated with dynamic compression plates. No single factor was associated with nonunion. In particular, the use of bone graft was not associated with a higher rate of union. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg Hand & Upper Extrem Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 2005 VL 59 IS 2 BP 436 EP 439 DI 10.1097/01.ta.0000174839.23348.43 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 014BX UT WOS:000235454800037 ER PT J AU Patten, LC Awad, SS Berger, DH Fagan, SP AF Patten, LC Awad, SS Berger, DH Fagan, SP TI Rectus abdominus myonecrosis: An unrecognized complication of rectus sheath hematoma SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Southwestern-Surgical-Congress CY APR 07-10, 2002 CL CORONADO, CA SP Southwestern Surg Congress C1 Houston Vet Affairs Med Ctr, Surg Serv VA 112, Houston, TX 77030 USA. Baylor Coll Med, Michael E Debakey Dept Surg, Houston, TX 77030 USA. RP Fagan, SP (reprint author), Houston Vet Affairs Med Ctr, Surg Serv VA 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM shawnp.fagan@med.va.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 2005 VL 59 IS 2 BP 473 EP 475 DI 10.1097/01.TA.0000068991.11522.2E PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 014BX UT WOS:000235454800045 ER PT J AU Cook, JM Elhai, JD Arean, PA AF Cook, JM Elhai, JD Arean, PA TI Psychometric properties of the PTSD checklist with older primary care patients SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHIATRIC INTERVIEW MINI; WAR-II VETERANS; VALIDATION; VALIDITY; SAMPLE; ADULTS AB In this article the authors evaluated the posttraumatic stress disorder (PTSD) Checklist's (PCL) psychometric properties in 142 older adult primary care patients screened for several psychiatric disorders. Several established PCL scoring rules were assessed. Receiver operating characteristic analyses revealed a PCL score of 37 achieving optimal sensitivity and specificity, when compared to the PCL's algorithm-derived PTSD diagnosis (based on whether at least one reexperiencing, three avoidance/numbing, and two hyperarousal symptoms were endorsed with a rating of 3 or higher, indicating at least moderate severity). Among depressed, anxious, and substance abusing older adults, the PCL demonstrated adequate internal consistency. It also revealed similar convergence with the Center for Epidemiological Studies-Depression scale, found in previous research. Implications for using the PTSD Checklist with community-dwelling older adults in primary care are discussed. C1 Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ S Dakota, Philadelphia Vet Affairs Med Ctr, Vermillion, SD USA. Univ S Dakota, Disaster Mental Hlth Inst, Vermillion, SD USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. RP Cook, JM (reprint author), Columbia Univ, New York State Psychiat Inst, 1051 Riverside Dr,Box 69, New York, NY 10032 USA. EM cook_j@mail.trc.upenn.edu NR 39 TC 44 Z9 45 U1 5 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2005 VL 18 IS 4 BP 371 EP 376 DI 10.1002/jts.20038 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 986JS UT WOS:000233446500010 PM 16281234 ER PT J AU Hernandez, J Syed, S Weiss, G Fernandes, G von Merveldt, D Troyer, DA Basler, JW Thompson, IM AF Hernandez, J Syed, S Weiss, G Fernandes, G von Merveldt, D Troyer, DA Basler, JW Thompson, IM TI The modulation of prostate cancer risk with alpha-tocopherol: A pilot randomized, controlled clinical trial SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; alpha-tocopherol; prostate-specific antigen; tumor markers; biological ID GROWTH-FACTOR-I; VITAMIN-E; BETA-CAROTENE; SELECT; CELLS; MEN AB Purpose: Studies suggest that vitamin E may decrease the risk of prostate cancer. The Prevention Research Veteran Affairs E-vitamin Nutrition Trial is a randomized, double-blind, placebo controlled study designed to assess the effects of vitamin E supplementation on biomarkers associated with prostate cancer risk in peripheral blood and prostate tissue. Materials and Methods: A total of 44 patients with increased prostate specific antigen (PSA) and/or abnormal digital rectal examination on initial evaluation were randomized to receive 400 IU vitamin E (22) vs placebo (22). Serum vitamin E, PSA, dehydroepiandrosterone, testosterone and insulin-like growth factor-1 (IGF-1) were measured in the 2 groups at baseline and then at 3-month intervals. Results are reported in 28 patients (placebo in 14 and vitamin E in 14) who completed the treatment as specified by the protocol. Results: Serum Vitamin E was significantly higher in patients on vitamin E supplementation. a-Tocopherol supplementation did not affect the levels of PSA, serum androgens (testosterone and dehydroepiandrosterone) or (IGF-1). Conclusions: Serum a-tocopherol is increased by oral supplementation of vitamin E. We found that a-tocopherol supplementation has no effect on serum androgens, IGF-1 or PSA. The lack of an effect of vitamin supplementation on PSA avoids any bias in the diagnosis of prostate cancer in vitamin E treated patients. Our results suggest that a decrease in prostate cancer risk with alpha-tocopherol is likely to occur through a mechanism that is nonhormonal and independent of IGF-1. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, Div Urol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med Clin Immunol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med Med Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Canc Therapy Res Ctr, Inst Drug Dev, San Antonio, TX USA. S Texas Vet Healthcare Syst, Audie L Murphy Div, San Antonio, TX USA. RP Thompson, IM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, Div Urol, 7703 Floyd Curl Dr,MC7845, San Antonio, TX 78229 USA. EM thompsoni@uthscsa.edu NR 19 TC 9 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2005 VL 174 IS 2 BP 519 EP 522 DI 10.1097/01.ju.0000165151.08560.6a PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 946WP UT WOS:000230604300031 PM 16006884 ER PT J AU Barry, MJ AF Barry, MJ TI Prognostic features in men who died of prostate cancer - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barry, MJ (reprint author), 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 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 2005 VL 174 IS 2 BP 556 EP 556 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 946WP UT WOS:000230604300042 ER PT J AU Laird, J Jaff, MR Biamino, G McNamara, T Scheinert, D Zetterlund, P Moen, E Joye, JD AF Laird, J Jaff, MR Biamino, G McNamara, T Scheinert, D Zetterlund, P Moen, E Joye, JD TI Cryoplasty for the treatment of femoropopliteal arterial disease: Results of a prospective, multicenter registry SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID BALLOON ANGIOPLASTY; ATHEROSCLEROTIC RABBIT; BLOOD VESSELS; RESTENOSIS; EXPERIENCE; APOPTOSIS; STENTS; TRIAL; PLACEMENT; GRAFTS AB PURPOSE: Despite suboptimal results, angioplasty of femoropopliteal arterial lesions has been a mainstay of endovascular therapy for many years. The recent introduction of cryoplasty marks a potential advance in the ability to effectively treat peripheral arterial atherosclerotic stenoses. This article presents the results of a prospective, multicenter trial that evaluated the efficacy of cryoplasty for femoropopliteal disease. MATERIALS AND METHODS: One hundred two patients with claudication and lesions of the superficial femoral and popliteal arteries of no greater than 10 cm were studied. All patients were treated with a primary strategy of stand-alone cryoplasty with use of the PolarCath cryoplasty system. The primary endpoints of the study were acute technical success and clinical patency at 9 months. Technical success was defined as the ability to achieve residual angiographic stenosis no greater than 30% and residual stenosis less than 50% by duplex ultrasound (US) imaging. Clinical patency was defined as freedom from target lesion revascularization within 9 months. Primary patency was defined by a duplex US systolic velocity ratio no greater than 2.0. RESULTS: A total of 102 patients were enrolled at 16 centers. Of those treated, 31% had diabetes and 31% were active cigarette smokers. The majority of the lesions were confined to the superficial femoral artery (84.3%) and 14.7% presented with total occlusions. The mean vessel diameter treated was 5.5 mm +/- 0.5, the mean stenosis diameter was 87% +/- 10%, and the mean lesion length was 4.7 cm +/- 2.6. The technical success rate was 85.3% with a mean residual stenosis after cryoplasty of 11.2% +/- 11.2% (P < .05 vs baseline). Clinical patency in this group was 82.2%, as only 16 patients required target lesion revascularization during the 9-month surveillance period. Primary patency determined by duplex US was 70.1%. CONCLUSIONS: Cryoplasty demonstrated a high degree of acute angiographic success and a low frequency of target lesion revascularization. The patency rate observed compares favorably to that previously documented with conventional angioplasty. C1 Washington Hosp Ctr, Div Cardiol, Washington, DC 20010 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Leipzig, Herzzentrum, Dept Angiol, D-7010 Leipzig, Germany. Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. Salinas Valley Mem Hosp, Dept Med, Salinas, CA USA. El Camino Hosp, Dept Med, Mountain View, CA USA. St Vincents Hosp, Div Cardiol, Indianapolis, IN USA. RP Joye, JD (reprint author), Inst Cardiovasc, 2660 Grant Rd, Mountain View, CA 94040 USA. EM jimjoye@aol.com NR 39 TC 80 Z9 84 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2005 VL 16 IS 8 BP 1067 EP 1073 DI 10.1097/01.RVI.0000167866.86201.4E PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 956IH UT WOS:000231292900004 PM 16105918 ER PT J AU Hua, HT Al-Badawi, H Entabi, F Stoner, MC Diamond, RE Bonheur, JA Houser, S Watkins, MT AF Hua, HT Al-Badawi, H Entabi, F Stoner, MC Diamond, RE Bonheur, JA Houser, S Watkins, MT TI CXC chemokine expression and synthesis in skeletal muscle during ischemia/reperfusion SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 17-19, 2004 CL Whitefield, NH SP New England Soc Vasc Surg ID ISCHEMIA-REPERFUSION INJURY; NEUTROPHIL PMN PHAGOCYTOSIS; RENAL-DISEASE; LUNG INJURY; IN-VIVO; RECEPTOR; RAT; LIPOPOLYSACCHARIDE; TRANSPLANTATION; CHEMOTAXIS AB Background. The chemokines keratinocyte-Derived Cytokine (KC) and macrophage inflammatory protein (MIP)-2, murine equivalents of human interleukin 8, have been implicated in remote injury after acute hind limb ischemia/ reperfusion (I/R). These studies were designed to determine whether the cytokines responsible for remote tissue injury are also synthesized and accumulate in the ischemic or reperfused hind limb. Methods. B6, 129SF2/J mice were subjected to either 3 hours of unilateral hind limb ischemia alone (IA) or 3 hours of ischemia followed by 4 or 24 hours of reperfusion (I/R). After IA or I/R, experimental and control (nonischemic) contralateral hind limbs were harvested for analysis of protein content, messenger RNA (mRNA), tissue edema, and viability. Results. IA did not increase KC or MIP-2 mRNA or protein levels. In contrast, I/R resulted in a 15- and 10-fold increase in KC mRNA after 4 and 24 hours of reperfusion, respectively. KC protein levels were increased 10-fold after 4 hours of reperfusion and 30-fold after 24 hours (vs IA or sham; P <.001). MIP-2 mRNA transiently increased 42-fold after 4 hours of reperfusion but decreased to basal levels after 24 hours of reperfusion. Despite the relative increase in MIP-2 mRNA by 4 hours of reperfusion, significantly increased (8- to 10 fold) MIP-2 protein levels were not detected until 24 hours of reperfusion only in the reperfused limbs. Tissue edema was increased significantly (P <.01) compared with sham after just 4 hours of reperfusion and remained increased at 24 hours. Tissue viability decreased 52% after 4 hours of reperfusion and did not change significantly by 24 hours. Conclusions. Skeletal muscle is a site of significant ongoing chemokine synthesis during reperfusion. The persistent increase in muscle chemokine levels at 24 hours of reperfusion was not associated with increased edema or injury. The role of these chemokines during reperfusion may be further investigated by local or oral administration of chemokines or chemokine receptor antagonists. C1 Harvard Univ, Div Vasc & Endovasc Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Vet Adm Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Harvard Univ, Div Vasc & Endovasc Surg, Sch Med, Massachusetts Gen Hosp, 15 Parkman Sr,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 31 TC 15 Z9 16 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2005 VL 42 IS 2 BP 337 EP 343 DI 10.1016/j.jvs.2005.04.046 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 953RW UT WOS:000231099200029 PM 16102636 ER PT J AU Pancera, M Lebowitz, J Schon, A Zhu, P Freire, E Kwong, PD Roux, KH Sodroski, J Wyatt, R AF Pancera, M Lebowitz, J Schon, A Zhu, P Freire, E Kwong, PD Roux, KH Sodroski, J Wyatt, R TI Soluble mimetics of human immunodeficiency virus type 1 viral spikes produced by replacement of the native trimerization domain with a heterologous trimerization motif: Characterization and ligand binding analysis SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; HIV-1 GP120; NEUTRALIZATION SENSITIVITY; TRANSMEMBRANE GLYCOPROTEIN; OLIGOMERIC STRUCTURE; IMMUNE-RESPONSES; MEMBRANE-FUSION; INFLUENZA-VIRUS; LEUCINE-ZIPPER AB The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, mediates binding to the viral receptors and, along with the transmembrane glycoprotein gp41, is a major target for neutralizing antibodies. We asked whether replacing the gp41 fusion/trimerization domain with a stable trimerization motif might lead to a more stable gp120 trimer that would be amenable to structural and immunologic analysis. To obtain stable gp120 trimers, a heterologous trimerization motif, GCN4, was appended to the C terminus of YU2gp120. Biochemical analysis indicated that the gp120-GCN4 trimers were superior to gp140 molecules in their initial homogeneity, and trilobed structures were observable by electron microscopy. Biophysical analysis of gp120-GCN4 trimers by isothermal titration calorimetry (ITC) and ultracentrifugation analyses indicated that most likely two molecules of soluble CD4 could bind to one gp120-GCN4 trimer. To further examine restricted CD4 stoichiometric binding to the gp120-GCN4 trimers, we generated a low-affinity CD4 binding trimer by introducing a D457V change in the CD4 binding site of each gp120 monomeric subunit. The mutant trimers could definitively bind only one soluble CD4 molecule, as determined by ITC and sedimentation equilibrium centrifugation. These data indicate that there are weak interactions between the gp120 monomeric subunits of the GCN4-stabilized trimers that can be detected by low-affinity ligand sensing. By similar analysis, we also determined that removal of the variable loops V1, V2, and V3 in the context of the gp120-GCN4 proteins allowed the binding of three CD4 molecules per trimer. Interestingly, both the gp120-GCN4 variants displayed a restricted stoichiometry for the CD4-induced antibody 17b of one antibody molecule binding per trimer. This restriction was not evident upon removal of the variable loops V1 and V2 loops, consistent with conformational constraints in the wild-type gp120 trimers and similar to those inherent in the functional Env spike. Thus, the gp120-GCN4 trimers demonstrate several properties that are consistent with some of those anticipated for gp120 in the context of the viral spike. C1 NIH, Vaccine Res Ctr, Struct Virol Sect, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Vaccine Res Ctr, Struct Virol Sect, 40 Convent Dr, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov NR 75 TC 58 Z9 60 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2005 VL 79 IS 15 BP 9954 EP 9969 DI 10.1128/JVI.79.15.9954-9969.2005 PG 16 WC Virology SC Virology GA 946MC UT WOS:000230575300057 PM 16014956 ER PT J AU Poon, B Hsu, JF Gudeman, V Chen, ISY Grovit-Ferbas, K AF Poon, B Hsu, JF Gudeman, V Chen, ISY Grovit-Ferbas, K TI Formaldehyde-treated, heat-inactivated virions with increased human immunodeficiency virus type 1 Env can be used to induce high-titer neutralizing antibody responses SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; EXPERIMENTAL VACCINE PROTECTION; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; HIV TYPE-1; INTERNALIZATION SIGNAL; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; SUBUNIT VACCINES; RHESUS-MONKEYS AB The lack of success of subunit human immunodeficiency virus (HIV) type I vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Grovit-Ferbas, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11-934 Factor Bldg, Los Angeles, CA 90095 USA. EM kferbas@ucla.edu FU NCI NIH HHS [CA016042, P30 CA016042]; NIAID NIH HHS [1R01AI052012, AI028697, P30 AI028697, R01 AI052012, R21AI42687] NR 55 TC 22 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2005 VL 79 IS 16 BP 10210 EP 10217 DI 10.1128/JVI.79.16.10210-10217.2005 PG 8 WC Virology SC Virology GA 950UX UT WOS:000230884700012 PM 16051814 ER PT J AU Frahm, N Adams, S Kiepiela, P Linde, CH Hewitt, HS Lichterfeld, M Sango, K Brown, NV Pae, E Wurcel, AG Altfeld, M Feeney, ME Allen, TM Roach, T St John, MA Daar, ES Rosenberg, E Korber, B Marincola, F Walker, BD Goulder, PJR Brander, C AF Frahm, N Adams, S Kiepiela, P Linde, CH Hewitt, HS Lichterfeld, M Sango, K Brown, NV Pae, E Wurcel, AG Altfeld, M Feeney, ME Allen, TM Roach, T St John, MA Daar, ES Rosenberg, E Korber, B Marincola, F Walker, BD Goulder, PJR Brander, C TI HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HIV-1 INFECTION; HLA-B; TYPE-1 INFECTION; ESCAPE MUTATION; POLYMORPHISM; SPECIFICITY; REVERSION; VIREMIA; AIDS AB Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B*1516 and HLA-B*1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. NIH, Ctr Clin, HLA Typing Lab, Bethesda, MD 20892 USA. Univ Natal, UHIV Pathogenesis Program, ZA-4001 Durban, South Africa. Fenway Community Hlth Ctr, Boston, MA 02115 USA. Lemuel Shattuck Hosp, Jamaica Plain, MA 02130 USA. Queen Elizabeth Hosp, Bridgetown, Barbados. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Brander, C (reprint author), AIDS Res Ctr, 5th Floor,MGH E,5214,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI-067077, AI-043638, N01-AI-15422, R01 AI067077, U01 AI043638] NR 34 TC 57 Z9 57 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2005 VL 79 IS 16 BP 10218 EP 10225 DI 10.1128/JVI.79.16.10218-10225.2005 PG 8 WC Virology SC Virology GA 950UX UT WOS:000230884700013 PM 16051815 ER PT J AU Lu, R Ghory, HZ Engelman, A AF Lu, R Ghory, HZ Engelman, A TI Genetic analyses of conserved residues in the carboxyl-terminal domain of human immunodeficiency virus type 1 integrase SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING DOMAIN; TARGET SITE SELECTION; PHOTO-CROSS-LINKING; AVIAN-SARCOMA VIRUS; HIV-1 INTEGRASE; NUCLEAR-LOCALIZATION; IN-VITRO; CORE DOMAIN; RETROVIRAL INTEGRASE; CATALYTIC CORE AB Results of in vitro assays identified residues in the C-terminal domain (CTD) of human immunodeficiency virus type 1 (HIV-1) integrase (IN) important for IN-IN and IN-DNA interactions, but the potential roles of these residues in virus replication were mostly unknown. Sixteen CTD residues were targeted here, generating 24 mutant viruses. Replication-defective mutants were typed as class I (blocked at integration) or class II (additional reverse transcription and/or assembly defects). Most defective viruses (15 of 17) displayed reverse transcription defects. In contrast, replication-defective HIV-1(E246K) synthesized near-normal cDNA levels but processing of Pr55(gag) was largely inhibited in virus-producing cells. Because single-round HIV-1(E246K.Luc(R-)) transduced cells at approximately 8% of the wild-type level, we concluded that the late-stage processing defect contributed significantly to the overall replication defect of HIV-1(E246K). Results of complementation assays revealed that the CTD could function in trans to the catalytic core domain (CCD) in in vitro assays, and we since determined that certain class I and class II mutants defined a novel genetic complementation group that functioned in cells independently of IN domain boundaries. Seven of eight novel Vpr-IN mutant proteins efficiently trans-complemented class I active-site mutant virus, demonstrating catalytically active CTD mutant proteins during infection. Because most of these mutants inefficiently complemented a class II CCD mutant virus, the majority of CTD mutants were likely more defective for interactions with cellular and/or viral components that affected reverse transcription and/or preintegration trafficking than the catalytic activity of the IN enzyme. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI39394, AI28691, AI52014, P30 AI028691, R01 AI039394, R01 AI052014, R37 AI039394] NR 87 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2005 VL 79 IS 16 BP 10356 EP 10368 DI 10.1128/JVI.79.16.10356-10368.2005 PG 13 WC Virology SC Virology GA 950UX UT WOS:000230884700026 PM 16051828 ER PT J AU Melnychuk, RA Smith, P Kreklywich, CN Ruchti, F Vomaske, J Hall, L Loh, L Nelson, JA Orloff, SL Streblow, DN AF Melnychuk, RA Smith, P Kreklywich, CN Ruchti, F Vomaske, J Hall, L Loh, L Nelson, JA Orloff, SL Streblow, DN TI Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration SO JOURNAL OF VIROLOGY LA English DT Article ID COUPLED RECEPTOR HOMOLOG; BETA-CHEMOKINE RECEPTOR; APOE KNOCKOUT MICE; FRAME U12 ENCODES; MURINE CYTOMEGALOVIRUS; INDUCED ATHEROSCLEROSIS; DEFICIENT MICE; PROTEIN; INFECTION; CMV AB Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically knock down M33 expression in the context of viral infection. The knockdown of M33 resulted in the specific reduction of M33 protein expression and ablation of MCMV-mediated SMC migration but failed to reduce viral growth in cultured cells. Adenovirus vector expression of M33 was sufficient to promote SMC migration, which was enhanced in the presence of recombinant mouse RANTES (mRANTES). In addition, M33 promoted the activation of Rac1 and extracellular signal-related kinase 1/2 upon stimulation with mRANTES. These findings demonstrate that mRANTES is a ligand for this chemokine receptor and that the activation of M33 occurs in a ligand-dependent manner. Thus, M33 is a functional homologue of US28 that is required for MCMV-induced vascular SMC migration. C1 Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Dept Surg, Beaverton, OR 97006 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Univ Saskatchewan, Dept Microbiol, Saskatoon, SK 57N 5E5, Canada. RP Streblow, DN (reprint author), Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. EM streblow@ohsu.edu FU NHLBI NIH HHS [R01 HL065754, HL71695, R01 HL071695, HL65754, R01 HL066238, HL 66238-01] NR 37 TC 31 Z9 34 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2005 VL 79 IS 16 BP 10788 EP 10795 DI 10.1128/JVI.79.16.10788-10795.2005 PG 8 WC Virology SC Virology GA 950UX UT WOS:000230884700068 PM 16051870 ER PT J AU Gibney, EM Casebeer, AW Schooley, LM Cunningham, F Grover, FL Bell, MR McDonald, GO Shroyer, AL Parikh, CR AF Gibney, EM Casebeer, AW Schooley, LM Cunningham, F Grover, FL Bell, MR McDonald, GO Shroyer, AL Parikh, CR TI Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: A National Veterans Administration study SO KIDNEY INTERNATIONAL LA English DT Article DE cardiovascular disease; cardiac surgery; mortality ID CONVERTING-ENZYME-INHIBITOR; ACUTE MYOCARDIAL-INFARCTION; PLACEBO-CONTROLLED TRIAL; DIALYSIS PATIENTS; HEART-FAILURE; SERUM CREATININE; KIDNEY-DISEASE; BETA-BLOCKER; OUTCOMES; RISK AB Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: A national Veterans Administration study. Background. Chronic kidney disease is now recognized as an independent risk factor for cardiovascular events. We sought to determine if cardiovascular medications were utilized less in patients with renal dysfunction following coronary artery bypass grafting (CABG) and if the association of decreased medication use was independent of comorbid conditions. We also examined associations between cardiovascular medication use and mortality at 6 months. Methods. Data from the National Veterans Adminstration (VA) Continuous Improvement in Cardiac Surgery Program were merged with the national VA pharmacy database. Prescription rates within 6 months of discharge for CABG were obtained for four classes of medicines: beta blockers, lipid-lowering agents, antiplatelet agents, and angiotensin antagonists. Utilization of medications in patients with estimated glomerular filtration rate (GFR) 60 to 90, 30 to 60, and < 30 were compared with the reference group of GFR > 90. Results. In a retrospective analysis of 19,411 patients, the frequency of nonprescription increased with declining GFR. Decreased utilization for patients with GFR 30 to 60 and < 30 remained highly significant after adjustment for age, race, hypertension, diabetes, and prior myocardial infarction. In patients with more advanced renal dysfunction (GFR < 60), cardiovascular medication use for all medication classes was associated with survival at 6 months after adjusting for demographic and clinical variables. Cumulative protection was seen with use of medication from each additional class. Conclusion. In a large VA population undergoing CABG, renal disease is associated with highly significant decreases in utilization of cardiovascular medications. Nonprescription of medications was associated with adverse outcomes in those with renal dysfunction. C1 Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO USA. Dept Vet Affairs, Chicago, IL USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Continuous Improvement Cardiac Surg Program, Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Denver, CO USA. Dept Vet Affairs, Off Patient Care Serv, Cent Off, Washington, DC USA. RP Gibney, EM (reprint author), 1101 E Marshall St,POB 980160, Richmond, VA 23298 USA. EM chirag.parikh@yale.edu FU NIDDK NIH HHS [T32-DK007135-30, K23-DK064689-01] NR 31 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2005 VL 68 IS 2 BP 826 EP 832 DI 10.1111/j.1523-1755.2005.00463.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 943GW UT WOS:000230342500043 PM 16014062 ER PT J AU Partridge, AH AF Partridge, AH TI Young women's preferences about adjuvant endocrine therapy for breast cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID CHEMOTHERAPY C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2005 VL 6 IS 8 BP 542 EP 544 DI 10.1016/S1470-2045(05)70260-6 PG 3 WC Oncology SC Oncology GA 955MF UT WOS:000231229300005 PM 16054565 ER PT J AU Kawano, N Ishikawa, F Shimoda, K Yasukawa, M Nagafuji, K Miyamoto, T Baba, E Tanaka, T Yamasaki, S Gondo, H Otsuka, T Ohshima, K Shultz, LD Akashi, K Harada, M AF Kawano, N Ishikawa, F Shimoda, K Yasukawa, M Nagafuji, K Miyamoto, T Baba, E Tanaka, T Yamasaki, S Gondo, H Otsuka, T Ohshima, K Shultz, LD Akashi, K Harada, M TI Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD/SCID/beta 2-microglobulin(null) mice SO LEUKEMIA LA English DT Article DE NOD; SCID; beta 2-microglobulin(null) mice; ATL; HTLV-I; xenotransplantation ID COMBINED IMMUNODEFICIENT MICE; IN-VIVO; VIRUS; LYMPHOMA; MODEL; LINES; TRANSPLANTATION; INTEGRATION; PROVIRUS; CARRIERS AB Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe-combined immunodeficiency (SCID)/beta 2-microglobulin(null) (NOD/SCID/beta 2m(null)) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV-I integration identical to those of donors by Southern blot analysis. These cells infiltrated into recipients' liver, and formed nodular lesions, recapitulating the clinical feature of each patient. In contrast, in smoldering-type ATL cases, multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta 2m(null) mice. When smoldering-type ATL cells were retransplanted into secondary NOD/SCID/beta 2m(null) recipients, single HTLV-I-infected clones became predominant, suggesting that clones with dominant proliferative activity can be competitively selected in this xenogeneic system. Taken together, the NOD/SCID/beta 2m(null) newborn system is useful to understand kinetics, metastasis, and disease progression of ATL in vivo. C1 Kyushu Univ, Grad Shc Med, Dept Med & Biosyst Sci, Higashi Ku, Fukuoka 8128582, Japan. Ehime Univ, Sch Med, Dept Internal Med 1, Matsuyama, Ehime 790, Japan. SRL Inc, Dept Infect & Immunol, Hachioji, Tokyo, Japan. Dept Pathol 1, Fukuoka, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. RP Ishikawa, F (reprint author), Kyushu Univ, Grad Shc Med, Dept Med & Biosyst Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM f_ishika@intmed1.med.kyushu-u.ac.jp RI 石川, 文彦/L-4488-2014 FU NIAID NIH HHS [AI30389] NR 24 TC 21 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2005 VL 19 IS 8 BP 1384 EP 1390 DI 10.1038/sj.leu.2403829 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 947LN UT WOS:000230646300016 PM 15959532 ER PT J AU Kennedy, TC Franklin, WA Prindiville, SA Cooka, R Dempsey, EC Keith, RL Hirsch, FR Merrick, TA Shroyer, KR Petty, TL Byers, T Bunn, PA Miller, YE AF Kennedy, TC Franklin, WA Prindiville, SA Cooka, R Dempsey, EC Keith, RL Hirsch, FR Merrick, TA Shroyer, KR Petty, TL Byers, T Bunn, PA Miller, YE TI High prevalence of occult endobronchial malignancy in high risk patients with moderate sputum atypia SO LUNG CANCER LA English DT Article DE sputum cytology; bronchoscopy; autofluorescence bronchoscopy; lung cancer; early detection; risk assessment; biomarkers ID LUNG-CANCER DETECTION; SQUAMOUS-CELL CARCINOMA; AIR-FLOW OBSTRUCTION; CYTOLOGY; FLUORESCENCE; BRONCHOSCOPY; LESIONS AB Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of Lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects. C1 Denver Vet Affairs Med Ctr, Pulm Sect 111A, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Ctr Comprehens Canc, Denver, CO USA. Lung Canc Inst Colorado HealthOne, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Med Oncol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biostat, Denver, CO USA. RP Miller, YE (reprint author), Denver Vet Affairs Med Ctr, Pulm Sect 111A, 1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu FU NCI NIH HHS [P50 CA58187]; PHS HHS [P30 46934] NR 22 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD AUG PY 2005 VL 49 IS 2 BP 187 EP 191 DI 10.1016/j.lungcan.2005.02.009 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 955UO UT WOS:000231253300006 PM 16022912 ER PT J AU Robine, S Fre, S Huyghe, M Artavanis-Tsakonas, S Louvard, D AF Robine, S Fre, S Huyghe, M Artavanis-Tsakonas, S Louvard, D TI Notch signals control the fate of immature progenitor cells in the intestine SO M S-MEDECINE SCIENCES LA French DT Article ID RECOMBINATION C1 Inst Curie, CNRS, UMR 144, F-75248 Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cell Biol,Canc Ctr, Charlestown, MA 02129 USA. RP Robine, S (reprint author), Inst Curie, CNRS, UMR 144, 26,Rue Ulm, F-75248 Paris, France. EM Sylvie.Robine@curie.fr RI Fre, Silvia/C-7540-2017 OI Fre, Silvia/0000-0002-7209-7636 NR 8 TC 5 Z9 6 U1 1 U2 10 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD AUG-SEP PY 2005 VL 21 IS 8-9 BP 780 EP 781 DI 10.1051/medsci/2005218-9780 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 966BS UT WOS:000231995200025 PM 16115467 ER PT J AU Lin, FH Huang, TY Chen, NK Wang, FN Stufflebeam, SM Belliveau, JW Wald, LL Kwong, KK AF Lin, FH Huang, TY Chen, NK Wang, FN Stufflebeam, SM Belliveau, JW Wald, LL Kwong, KK TI Functional MRI using regularized parallel imaging acquisition SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fMRI; SENSE; EPI; parallel MRI; brain ID SINGLE-SHOT; SENSE-EPI; FMRI; OXYGENATION; UNFOLD; SMASH; ARTIFACTS; CORTEX; NOISE AB Parallel MRI techniques reconstruct full-FOV images from undersampled k-space data by using the uncorrelated information from RF array coil elements. One disadvantage of parallel MRI is that the image signal-to-noise ratio (SNR) is degraded because of the reduced data samples and the spatially correlated nature of multiple RF receivers. Regularization has been proposed to mitigate the SNR loss originating due to the latter reason. Since it is necessary to utilize static prior to regularization, the dynamic contrast-to-noise ratio (CNR) in parallel MRI will be affected. In this paper we investigate the CNR of regularized sensitivity encoding (SENSE) acquisitions. We propose to implement regularized parallel MRI acquisitions in functional MRI (fMRI) experiments by incorporating the prior from combined segmented echo-planar imaging (EPI) acquisition into SENSE reconstructions. We investigated the impact of regularization on the CNR by performing parametric simulations at various BOLD contrasts, acceleration rates, and sizes of the active brain areas. As quantified by receiver operating characteristic (ROC) analysis, the simulations suggest that the detection power of SENSE fMRl can be improved by regularized reconstructions, compared to unregularized reconstructions. Human motor and visual fMRI data acquired at different field strengths and array coils also demonstrate that regularized SENSE improves the detection of functionally active brain regions. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, MIT,HMS, Charlestown, MA 02129 USA. Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Lin, FH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, MIT,HMS, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM fhlin@nmr.mgh.harvard.edu RI Teng-Yi, Huang/C-7433-2011; Lin, Fa-Hsuan/G-6988-2012; Chen, Nan-kuei/E-7791-2016; Wald, Lawrence/D-4151-2009 OI Lin, Fa-Hsuan/0000-0002-9539-1731; Chen, Nan-kuei/0000-0001-6564-4219; FU NCRR NIH HHS [P41 RR014075, P41 RR14075]; NICHD NIH HHS [R01 HD040712]; NIMH NIH HHS [K08 MH067966, K08 MH067966-01A2, K08 MH067966-02, K08 MH067966-03, K08 MH067966-04, K08 MH067966-05]; NINDS NIH HHS [R01 NS037462] NR 41 TC 34 Z9 34 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD AUG PY 2005 VL 54 IS 2 BP 343 EP 353 DI 10.1002/mrm.20565 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 949DS UT WOS:000230765700012 PM 16032694 ER PT J AU Abel, GA Hays, JT Decker, PA Croghan, GA Kuter, DJ Rigotti, NA AF Abel, GA Hays, JT Decker, PA Croghan, GA Kuter, DJ Rigotti, NA TI Effects of biochemically confirmed smoking cessation on white blood cell count SO MAYO CLINIC PROCEEDINGS LA English DT Article ID CORONARY-HEART-DISEASE; CIGARETTE-SMOKING; LEUKOCYTE COUNT; EPIC-NORFOLK; ASSOCIATION; MEN; MORTALITY; NICOTINE; POPULATION; PRESSURE AB OBJECTIVES: To determine the relationship between white blood cell (WBC) indices and several baseline variables in a large cohort of healthy smokers and to assess whether these changed after biochemically confirmed smoking cessation. SUBJECTS AND METHODS: The study consisted of 784 healthy smokers enrolled in a trial of sustained-release bupropion, 300 mg/d, for relapse prevention after smoking cessation from 1995 to 1998. Both WBC counts and absolute neutrophil counts (ANCs) were measured at baseline, week 7, and week 52. Smoking status was assessed at weeks 7 and 52 by self-report and biochemically confirmed with expired air carbon monoxide levels. Multivariate analyses compared changes in WBC count and ANC between smokers who did and did not stop smoking, adjusting for treat ment group, age, sex, and body mass index. RESULTS: Of 784 smokers enrolled, 461 had biochemically confirmed tobacco abstinence after 7 weeks of bupropion; 429 were randomly assigned to receive continued bupropion therapy or placebo until week 52. Between baseline and week 7, there was a significantly larger decrease in WBC count in continuously abstinent subjects compared with continuing smokers (adjusted P=.03). At 52 weeks, continuously abstinent subjects, compared with continuing smokers, had a greater decline from baseline in WBC count (1.2 +/- 1.9 x 10(9)/L vs 0.1 +/- 1.9 x 10(9)/L; P <.001) and ANC (1.0 +/- 1.6 x 10(9)/L vs 0.2 +/- 1.5 x 10(9)/L; P <.001). CONCLUSION: Biochemically confirmed tobacco abstinence leads to a rapid and sustained decrease in WBC and ANC, possibly reflecting a decrease in an underlying state of tobacco-induced Inflammation. C1 Mayo Clin & Mayo Fdn, Coll Med, Div Gen Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Coll Med, Div Biostat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Coll Med, Div Med Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Coll Med, Nicotine Dependence Ctr, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02115 USA. RP Hays, JT (reprint author), Mayo Clin & Mayo Fdn, Coll Med, Div Gen Internal Med, 200 1st St SW, Rochester, MN 55905 USA. EM hays.taylor@mayo.edu NR 33 TC 23 Z9 23 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2005 VL 80 IS 8 BP 1022 EP 1028 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 952BZ UT WOS:000230978100008 PM 16092581 ER PT J AU Paganetti, H AF Paganetti, H TI Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution SO MEDICAL PHYSICS LA English DT Article DE proton therapy; relative biological effectiveness; lethal lesion; lesion repair ID LOW-ENERGY PROTONS; POTENTIALLY LETHAL DAMAGE; HEAVY ION BOMBARDMENT; TRACK-STRUCTURE; IONIZING-RADIATIONS; EFFECTIVENESS RBE; BEAM THERAPY; DNA-DAMAGE; V79 CELLS; INACTIVATION AB Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological "track structure" model and the more mechanistic "lethal lesion/potentially lethal lesion" (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values. (c) 2005 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NCI NIH HHS [CA 21239] NR 44 TC 15 Z9 16 U1 1 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2005 VL 32 IS 8 BP 2548 EP 2556 DI 10.1118/1.1949807 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 958VM UT WOS:000231476300015 PM 16193785 ER PT J AU Frimmel, H Nappi, J Yoshida, H AF Frimmel, H Nappi, J Yoshida, H TI Centerline-based colon segmentation for CT colonography SO MEDICAL PHYSICS LA English DT Article DE CT colonography; segmentation; centerline; colon ID COMPUTERIZED DETECTION; VIRTUAL COLONOSCOPY; POLYPS; CANCER; WALLS AB We have developed a fully automated algorithm for colon segmentation, centerline-based segmentation (CBS), which is faster than any of the previously presented segmentation algorithms, but also has high sensitivity as well as high specificity. The algorithm first thresholds a set of unprocessed CT slices. Outer air is removed, after which a bounding box is computed. A centerline is computed for all remaining regions in the thresholded volume, disregarding segments related to extracolonic structures. Centerline segments are connected, after which the anatomy-based removal of segments representing extracolonic structures occurs. Segments related to the remaining centerline are locally region grown, and the colonic wall is found by dilation. Shape-based interpolation provides an isotropic mask. For 38 CT datasets, CBS was compared with the knowledge-guided segmentation (KGS) algorithm for sensitivity and specificity. With use of a 1.5 GHz AMD Athion-based PC, the average computation time for the segmentation was 14.8 s. The sensitivity was, on average, 96%, and the specificity was 99%. A total of 21% of the voxels segmented by KGS, of which 96% represented extracolonic structures and 4% represented the colon, were removed. (c) 2005 American Association of Physicists in Medicine. C1 Univ Uppsala Hosp, Sect Radiol, Dept ORKI, Uppsala, Sweden. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Univ Uppsala Hosp, Sect Radiol, Dept ORKI, Uppsala, Sweden. EM frimmel@it.uu.se FU NCI NIH HHS [CA095279] NR 14 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2005 VL 32 IS 8 BP 2665 EP 2672 DI 10.1118/1.1990288 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 958VM UT WOS:000231476300027 PM 16193797 ER PT J AU Duncan, GE Li, SM Zhou, XH AF Duncan, GE Li, SM Zhou, XH TI Cardiovascular fitness among US adults: NHANES 1999-2000 and 2001-2002 SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE maximal oxygen consumption; race; epidemiology; body mass index ID CARDIORESPIRATORY FITNESS; MEN; MORTALITY; HEALTH; WOMEN; AMERICAN; CAPACITY AB Purpose: To present information on cardiovascular fitness (estimated maximal oxygen uptake [VO(2)max] and cardiovascular fitness levels based on sex- and age-specific cut-points of estimated VO2max among U.S. adults. Methods: Analysis of data on 1978 adults (20-49 yr) who had completed a submaximal exercise test, from the National Health and Nutrition Examination Survey (1999-2000 and 2001-2002), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized U.S. population Results: Estimated VO2max was significantly lower (P < 0.01) in non-Hispanic black ([mean +/- standard error] 38.2 +/- 0.7 mL(.)min(-1)center dot-kg(-1)) than Mexican-American and non-Hispanic white adults (41.5 +/- 0.6 and 40.6 +/- 0.4 mL(.)min(-1.)kg(-1), respectively). Estimated VO2max was also significantly lower (P < 0.001) in non-Hispanic black females (33.1 +/- 0.6 mL(.)min(-1.)kg(-1)) than in Mexican-American and non-Hispanic white females (37.0 +/- 0.7 and 36.4 +/- 0.4 mL(.)min(-1.)kg(-1), respectively). The proportion of low, moderate, and high cardiovascular fitness differed (P < 0.001) among race and race-sex groups. This difference was most striking among females, where 30.9% [95% confidence interval = 23.6-38.2%] of non-Hispanic black women had a low cardiovascular fitness level, compared with only 13.5% [10.0-17.0%] of non-Hispanic white and 18.9% [14.0-23.8%] of Mexican-American women. Conclusions: Adults of non-Hispanic black race have lower cardiovascular fitness than other major race groups in the United States. Nearly one third of non-Hispanic black women had a low cardiovascular fitness level, suggesting that this group in particular may be at increased health risk due to low cardiovascular fitness. C1 Univ Washington, Dept Epidemiol, Interdisciplinary Grad Program Nutrit Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA USA. RP Duncan, GE (reprint author), Univ Washington, Dept Epidemiol, Interdisciplinary Grad Program Nutrit Sci, 305 Raitt Hall,Box 353410, Seattle, WA 98195 USA. EM duncag@u.washington.edu RI Duncan, Glen/A-3771-2008 OI Duncan, Glen/0000-0001-6909-1869 FU NIDDK NIH HHS [K01 DK61999, K01 DK061999-03, K01 DK061999] NR 17 TC 21 Z9 23 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD AUG PY 2005 VL 37 IS 8 BP 1324 EP 1328 DI 10.1249/01.mss.0000174893.74326.11 PG 5 WC Sport Sciences SC Sport Sciences GA 958VJ UT WOS:000231476000011 PM 16118579 ER PT J AU Gragnoli, C Stanojevic, V Gorini, A Von Preussenthal, GM Thomas, MK Habener, JF AF Gragnoli, C Stanojevic, V Gorini, A Von Preussenthal, GM Thomas, MK Habener, JF TI IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and gestational diabetes SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PROMOTER FACTOR-I; BETA-CELL FUNCTION; HOMEOSTASIS MODEL ASSESSMENT; ORAL GLUCOSE-TOLERANCE; HOMEODOMAIN PROTEIN; BIRTH-WEIGHT; PANCREAS DEVELOPMENT; INSULIN SENSITIVITY; MELLITUS; EXPRESSION AB Maturity-onset diabetes of the young (MODY) is a monogenic autosomal-dominant form of diabetes mellitus with onset before 25 years of age. Genetic variation in insulin promoter factor-1 (IPF1) (MODY4) is uncommon but may contribute to early- or late-onset diabetes as part of a polygenic background. IPF1 is a homeodomain transcription factor required for pancreas development. Our aim was to identify whether IPF1 gene mutations play a role in Italian early-onset type 2 diabetic (T2D) patients and what functional impact mutations may have in the beta cell. We screened 40 Italian early-onset type 2 diabetic probands for IPF1 mutations, performed oral glucose tolerance tests in the unaffected family members, and performed in vitro functional studies of the mutant variant. In an extended family (Italy-6) of 46 members with clinical phenotypes of gestational diabetes, MODY, and T2D, a single nucleotide change of CCT to ACT was identified at codon 33 resulting in a Pro to Thr substitution (P33T) in the IPF1 transactivation domain that also contributes to an altered metabolic status in the unaffected NM subjects. Of the 22 genotyped Italy-6 members, 9 carried the P33T allele (NM), of whom 5 have either T2D or elevated fasting glucose levels. Oral glucose tolerance tests showed higher glucose levels at 90 minutes in unaffected NM compared with unaffected NN subjects. Of the 5 female pregnant carriers of the IPF1 mutation, 4 had pregnancies complicated by reduced birth weights, miscarriages, or early postnatal deaths. In studies in vitro, the IPF1 mutant protein (P33T) showed a reduction in DNA-binding and transcriptional activation functions as compared to the wild-type IPF1 protein. Our findings suggest that the P33T IPF1 mutation may provide an increased susceptibility to the development of gestational diabetes and MODY4 in the Italy-6 pedigree. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Roma Tor Vergata, Policlin Tor Vergata, I-00133 Rome, Italy. Howard Hughes Med Inst, Boston, MA 02114 USA. Univ Roma La Sapienza, Policlin Umberto I, I-00161 Rome, Italy. RP Gragnoli, C (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. EM cgragnoli@partners.org FU NIDDK NIH HHS [DK 55365] NR 29 TC 24 Z9 27 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2005 VL 54 IS 8 BP 983 EP 988 DI 10.1016/j.metabol.2005.01.037 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955TU UT WOS:000231251300001 PM 16092045 ER PT J AU Klaustermeyer, WB Gowda, VC AF Klaustermeyer, WB Gowda, VC TI Penicillin skin testing: A 20-year study at the west Los Angeles Veterans Affairs Medical Center SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Allergy-Asthma-and-Immunology CY NOV 07-12, 2003 CL New Orleans, LA SP Amer Coll Allergy, Asthma & Immunol ID BETA-LACTAM ANTIBIOTICS; IMMEDIATE HYPERSENSITIVITY REACTIONS; CLINICAL-EXPERIENCE; CROSS-REACTIVITY; ORAL CHALLENGE; ALLERGY; AZTREONAM; DESENSITIZATION; ANAPHYLAXIS; AMOXICILLIN AB Penicillin (PCN) may cause a reaction in up to 10% of the population. No study has examined PCN skin testing longitudinally over a 20-year period. A total of 122 patients underwent PCN skin testing between September 1978 and May 1998. Patients were skin tested with the major determinant, penicilloyl polylysine, and three minor determinants, PCN, benzylpenilloate, and benzylpenicilloate. Ten of a total of 122 patients had positive skin test reactions. Nine reactions were to penicilloyl polylysine and one reaction was to the minor determinant benzylpenilloate. There was a total of four patients (3.6%) with false-negative results on skin testing. PCN skin testing with both the major and minor determinants should be performed when there is a history of PCN allergy, a serious illness, and no suitable alternatives. If either the major or minor determinants are positive without suitable alternative antibiotics, then the patient should undergo desensitization. C1 Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Div Allergy & Immunol,Dept Med, Los Angeles, CA 90073 USA. RP Klaustermeyer, WB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Div Allergy & Immunol,Dept Med, 111R,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 39 TC 6 Z9 6 U1 0 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD AUG PY 2005 VL 170 IS 8 BP 701 EP 704 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 019JP UT WOS:000235831700014 PM 16173213 ER PT J AU King, R Googe, PB Page, RN Mihm, MC AF King, R Googe, PB Page, RN Mihm, MC TI Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ SO MODERN PATHOLOGY LA English DT Article DE dermatofibromas; melanoma; nevus ID BASAL-CELL CARCINOMA; HYPERPLASIA OVERLYING DERMATOFIBROMA; DESMOPLASTIC MELANOMA; BLUE NEVUS AB Dermatofibromas are common lesions that are often associated with epidermal hyperplasia and basal layer hyperpigmentation. A single case of lentiginous melanocytic hyperplasia overlying a dermatofibroma has been reported, however, nevi and melanoma have to the best of our knowledge, not been previously reported. We present 14 cases of melanocytic lesions associated with dermatofibromas. The clinical data and hematoxylin- and eosin-stained sections were obtained and formalin-fixed, paraffin-embedded tissue was immunostained with antibodies against S-100, Mart-1, Factor XIIIa, and CD117. There were nine females and five males ranging in age from 30 to 64 years and anatomic sites included back ( five), arm ( six), flank ( two), and leg ( one). The clinical diagnosis ranged from dermatofibroma to desmoplastic melanoma. Histologically, the melanocytic lesions included junctional, compound, and dermal nevi, and malignant melanoma in situ. In four cases the dermal component appeared to merge with the dermatofibroma. In the case of the melanoma in situ, the dermatofibroma abutted the epidermis. Immunohistochemically, the melanocytic lesions were S-100/ Mart-1+, FXIIIa-, and the dermatofibromas were S-100/ Mart-1-, FXIIIa+. Melanocytic neoplasia may appear in association with dermatofibromas. The fibrohistiocytic proliferation may be misinterpreted as a spindle or pleomorphic melanocytic process. Awareness of this association will aid in the correct diagnosis, and immunohistochemical studies will help in the differentiation of these two cell populations. C1 Knoxville Dermatopathol Lab, Knoxville, TN 37919 USA. Univ Tennessee, Dept Pathol, Knoxville, TN USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA USA. RP King, R (reprint author), Knoxville Dermatopathol Lab, 315 Erin Dr, Knoxville, TN 37919 USA. EM rking@labpath.com OI Googe, Paul/0000-0002-9185-3548 NR 21 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD AUG PY 2005 VL 18 IS 8 BP 1043 EP 1047 DI 10.1038/modpathol.3800384 PG 5 WC Pathology SC Pathology GA 947LK UT WOS:000230646000005 PM 15803191 ER PT J AU Lynch, M Chen, L Ravitz, MJ Mehtani, S Korenblat, K Pazin, MJ Schmidt, EV AF Lynch, M Chen, L Ravitz, MJ Mehtani, S Korenblat, K Pazin, MJ Schmidt, EV TI hnRNP K binds a core polypyrimidine element in the eukaryotic translation initiation factor 4E (eIF4E) promoter, and its regulation of eIF4E contributes to neoplastic transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID HUMAN C-MYC; NUCLEAR RIBONUCLEOPROTEIN-K; SINGLE-STRANDED-DNA; TATA-LESS PROMOTERS; MESSENGER-RNA; TRANSCRIPTION INITIATION; PROTEIN-SYNTHESIS; GENE-EXPRESSION; FACTOR EIF-4E; HELA-CELLS AB Translation initiation factor eukaryotic translation initiation factor 4E (eIF4E) plays a key role in regulation of cellular proliferation. Its effects on the m(7) GpppN mRNA cap are critical because overexpression of eIF4E transforms cells, and eIF4E function is rate-limiting for G, passage. Although we identified eIF4E as a c-Myc target, little else is known about its transcriptional regulation. Previously, we described an element at position -25 (TTACCCCCCCTT) that was critical for eIF4E promoter function. Here we report that this sequence (named 4EBE, for eIF4E basal element) functions as a basal promoter element that binds hnRNP K. The 4EBE is sufficient to replace TATA sequences in a heterologous reporter construct. Interactions between 4EBE and upstream activator sites are position, distance, and sequence dependent. Using DNA affinity chromatography, we identified hnRNP K as a 4EBE-binding protein. Chromatin immunoprecipitation, siRNA interference, and hnRNP K overexpression demonstrate that hnRNP K can regulate eIF4E mRNA. Moreover, hnRNP K increased translation initiation, increased cell division, and promoted neoplastic transformation in an eIF4E-dependent manner. hnRNP K binds the TATA-binding protein, explaining how the 4EBE might replace TATA in the eIF4E promoter. hnRNP K is an unusually diverse regulator of multiple steps in growth regulation because it also directly regulates c-myc transcription, mRNA export, splicing, and translation initiation. C1 Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Washington Univ, Sch Med, Div Gastroenterol, St Louis, MO 63110 USA. NIA, NIH, LCMB, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM Schmidt@helix.mgh.harvard.edu OI Pazin, Michael/0000-0002-7561-3640 FU NCI NIH HHS [5T32 CA009216-24, R01 CA063117, R01-CA63117, T32 CA009216]; NIDDK NIH HHS [T32 DK007191] NR 108 TC 72 Z9 79 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2005 VL 25 IS 15 BP 6436 EP 6453 DI 10.1128/MCB.25.15.6436-6453.2005 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947YY UT WOS:000230684400013 PM 16024782 ER PT J AU Boehm, JS Hession, MT Bulmer, SE Hahn, WC AF Boehm, JS Hession, MT Bulmer, SE Hahn, WC TI Transformation of human and murine fibroblasts without viral oncoproteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NORMAL HUMAN-CELLS; PROSTATE EPITHELIAL-CELLS; HUMAN-DIPLOID FIBROBLASTS; RAS-INDUCED SENESCENCE; LI-FRAUMENI-SYNDROME; SMALL-T ANTIGEN; TELOMERASE ACTIVITY; C-MYC; ONCOGENIC TRANSFORMATION; CELLULAR-TRANSFORMATION AB Murine embryo fibroblasts are readily transformed by the introduction of specific combinations of oncogenes; however, the expression of those same oncogenes in human cells fails to convert such cells to tumorigenicity. Using normal human and murine embryonic fibroblasts, we show that the transformation of human cells requires several additional alterations beyond those required to transform comparable murine cells. The introduction of the c-Myc and H-RAS oncogenes in the setting of loss of p53 function efficiently transforms murine embryo fibroblasts but fails to transform human cells constitutively expressing hTERT, the catalytic subunit of telomerase. In contrast, transformation of multiple strains of human fibroblasts requires the constitutive expression of c-Myc, H-RAS, and hTERT, together with loss of function of the p53, RB, and PTEN tumor suppressor genes. These manipulations permit the development of transformed human fibroblasts with genetic alterations similar to those found associated with human cancers and define specific differences in the susceptibility of human and murine fibroblasts to experimental transformation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu FU NCI NIH HHS [K01 CA094223, P01 CA050661] NR 59 TC 88 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2005 VL 25 IS 15 BP 6464 EP 6474 DI 10.1128/MCB.25.15.6464-6474.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947YY UT WOS:000230684400015 PM 16024784 ER PT J AU King, IFG Emmons, RB Francis, NJ Wild, B Muller, J Kingston, RE Wu, CT AF King, IFG Emmons, RB Francis, NJ Wild, B Muller, J Kingston, RE Wu, CT TI Analysis of a polycomb group protein defines regions that link repressive activity on nucleosomal templates to in vivo function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POSTERIOR-SEX COMBS; HISTONE METHYLTRANSFERASE ACTIVITY; DROSOPHILA-MELANOGASTER; GROUP GENES; BITHORAX COMPLEX; ZESTE; CHROMATIN; BMI-1; SUPPRESSOR-2; EXPRESSION AB Polycomb group (PcG) genes propagate patterns of transcriptional repression throughout development. The products of several such genes are part of Polycomb repressive complex 1 (PRO), which inhibits chromatin remodeling and transcription in vitro. Genetic and biochemical studies suggest the product of the Posterior sex combs (Psc) gene plays a central role in both PcG-mediated gene repression in vivo and PRC1 activity in vitro. To dissect the relationship between the in vivo and in vitro activities of Psc, we identified the lesions associated with 11 genetically characterized Psc mutations and asked how the corresponding mutant proteins affect Psc activity on nucleosomal templates in vitro. Analysis of both single-mutant Psc proteins and recombinant complexes containing mutant protein revealed that Psc encodes at least two functions, complex formation and the inhibition of remodeling and transcription, which require different regions of the protein. There is an excellent correlation between the in vivo phenotypes of mutant Psc alleles and the structure and in vitro activities of the corresponding proteins, suggesting that the in vitro activities of PRC1 reflect essential functions of Psc in vivo. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Gene Express Programme, D-69120 Heidelberg, Germany. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Welman 10,50 Blossom St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu; twu@genetics.med.harvard.edu NR 62 TC 40 Z9 41 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2005 VL 25 IS 15 BP 6578 EP 6591 DI 10.1128/MCB.25.15.6578-6591.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947YY UT WOS:000230684400025 PM 16024794 ER PT J AU Xu, DS Hemler, ME AF Xu, DS Hemler, ME TI Metabolic activation-related CD147-CD98 complex SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID AMINO-ACID TRANSPORTER; MATRIX-METALLOPROTEINASE INDUCER; T-CELL-ACTIVATION; THYROID-HORMONE TRANSPORTER; SYSTEM L; ANTIGEN; PROTEINS; FAMILY; CD98; EXPRESSION AB Cell surface CD147 protein promotes production of matrix metalloproteinases and hyaluronan, associates with monocarboxylate transporters and integrins, and is involved in reproductive, neural, inflammatory, and tumor functions. Here we combined covalent cross-linking, mass spectrometric protein identification, and co-immunoprecipitation to show selective CD147 association with three major types of transporters (CD98 heavy chain (CD98hc)-L-type amino acid transporter, ASCT2, and monocarboxylate transporters) as well as a regulator of cell proliferation ( epithelial cell adhesion molecule). In the assembly of these multicomponent complexes, CD147 and CD98hc play a central organizing role. RNA interference knock-down experiments established a strong connection between CD147 and CD98hc expression and a strong positive association of CD147 ( and CD98hc) with cell proliferation. As the CD147-CD98hc complex and proliferation diminished, AMP-activated protein kinase ( a cellular "fuel gauge") became activated, indicating a disturbance of cellular energy metabolism. Our data point to a CD147-CD98 cell surface supercomplex that plays a critical role in energy metabolism, likely by coordinating transport of lactate and amino acids. Furthermore we showed how covalent cross-linking, together with mass spectrometry, can be used to identify closely associated transmembrane proteins. This approach should also be applicable to many other types of transmembrane proteins besides those associated with CD98hc and CD147. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. EM Martin_hemler@dfci.harvard.edu FU NCI NIH HHS [CA102034, R01 CA102034] NR 59 TC 85 Z9 93 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 BP 1061 EP 1071 DI 10.1074/mcp.M400207-MCP200 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954SY UT WOS:000231176300004 PM 15901826 ER PT J AU Bandera, C Dos Reis, FC Qin, S Hasselblatt, K Schorge, J Skates, S Mok, S AF Bandera, C. Dos Reis, F. Candido Qin, S. Hasselblatt, K. Schorge, J. Skates, S. Mok, S. TI M2PK is an ovarian cancer biomarker identified through proteomic evaluation of pre- and post-treatment serum samples SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Bandera, C.; Dos Reis, F. Candido] Brown Univ, Sch Med, Women & Infants Hosp, Providence, RI 02912 USA. [Qin, S.; Hasselblatt, K.] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. [Schorge, J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Skates, S.] Massachusetts Gen Hosp, Dept Stat, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S101 EP S101 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300271 ER PT J AU Kam, SY Lidov, HGW Cox, GA Brown, RH Ho, MMF AF Kam, S. -Y. Lidov, H. G. W. Cox, G. A. Brown, R. H., Jr. Ho, M. M. F. TI Proteomic analysis of dysferlin-mediated cell membrane repair pathway SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Kam, S. -Y.; Ho, M. M. F.] Natl Canc Ctr, Singapore, Singapore. [Lidov, H. G. W.] Childrens Hosp, Boston, MA 02115 USA. [Cox, G. A.] Jackson Lab, Bar Harbor, ME 04609 USA. [Brown, R. H., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S203 EP S203 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300525 ER PT J AU Krueger, M Kratchmarova, I Blagoev, B Kahn, R Mann, M AF Krueger, M. Kratchmarova, I. Blagoev, B. Kahn, R. Mann, M. TI Temporal analysis of insulin-induced changes in the tyrosine-phosphoproteom of brown adipocytes SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Krueger, M.; Kratchmarova, I.; Blagoev, B.; Mann, M.] Univ So Denmark, Odense, Denmark. [Kahn, R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S36 EP S36 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300103 ER PT J AU Lu, X Lu, A Carter, E Avruch, J Burke, J Fischman, A Tompkins, R AF Lu, X. Lu, A. Carter, E. Avruch, J. Burke, J. Fischman, A. Tompkins, R. TI Insulin-dependent tyrosine-phosphorylated IRS-1 characterized with CAPLC-Q-TOF mass spectrometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Lu, X.; Lu, A.; Carter, E.; Avruch, J.; Burke, J.; Fischman, A.; Tompkins, R.] Massachusetts Gen Hosp, Shriners Burns Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S280 EP S280 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300720 ER PT J AU Manor, A Richmond, T Sutton, J Gerszten, R Liu, E Shi, X Bonilla, L AF Manor, A. Richmond, T. Sutton, J. Gerszten, R. Liu, E. Shi, X. Bonilla, L. TI The biomarker sieve; a computational framework for label-free MS-based proteomic biomarker discovery SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Manor, A.; Richmond, T.; Sutton, J.; Bonilla, L.] Thermo Electron Corp, Cambridge, MA USA. [Gerszten, R.; Liu, E.; Shi, X.] Massachusetts Gen Hosp, Cambridge, MA USA. [Gerszten, R.; Liu, E.; Shi, X.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S27 EP S27 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300076 ER PT J AU Sutton, J Shi, X Askenazi, M Richmond, T Bonilla, L Guerra, C Gerszten, R AF Sutton, J. Shi, X. Askenazi, M. Richmond, T. Bonilla, L. Guerra, C. Gerszten, R. TI Comparative analysis of biomarker discovery workflows utilizing labeled versus non-labeled differential strategies SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Sutton, J.; Askenazi, M.; Richmond, T.; Bonilla, L.] Thermo Electron BRIMS Ctr, Cambridge, MA USA. [Shi, X.; Gerszten, R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shi, X.; Gerszten, R.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Shi, X.; Gerszten, R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Guerra, C.] Agilix Corp, Woodbridge, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S322 EP S322 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300829 ER PT J AU Pettus, BJ Kitatani, K Chalfant, CE Taha, TA Kawamori, T Bielawski, J Obeid, LM Hannun, YA AF Pettus, BJ Kitatani, K Chalfant, CE Taha, TA Kawamori, T Bielawski, J Obeid, LM Hannun, YA TI The coordination of prostaglandin E-2 production by sphingosine-1-phosphate and ceramide-1-phosphate SO MOLECULAR PHARMACOLOGY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); SPHINGOSINE; KINASE AB The ability of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) to induce the major inflammatory mediator prostaglandin (PG) E-2 depends on the activation of two rate-limiting enzymes, phospholipase A(2) (PLA(2)) and cyclooxygenase 2 (COX-2). PLA(2) acts to generate arachidonic acid, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to PGE(2) production. However, less is known about the mechanisms that coordinate the regulation of these two enzymes. We have provided prior evidence that sphingosine kinase 1 and its bioactive lipid product sphingosine-1-phosphate (S1P) mediate the effects of cytokines on COX-2 induction, whereas ceramide kinase and its distinct product, ceramide-1-phosphate (C1P), are required for the activation and translocation of cPLA(2) (FASEB J 17: 1411 - 1421. 2003; J Biol Chem 278: 38206 - 38213, 2003; J Biol Chem 279: 11320 - 11326, 2004). Herein, we show that these two pathways are independent but coordinated, resulting in synergistic induction of PGE(2). Moreover, the combination of both S1P and C1P recapitulates the temporal and spatial activation of cPLA(2) and COX-2 seen with IL-1 beta. Taken together, the results provide, for the first time, a mechanism that assures the coordinate expression and activation in time and space of COX-2 and cPLA(2), assuring maximal production of PGE(2). C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Virginia Commonwealth Univ, Dept Biochem, Richmond, VA USA. Ralph Johnson H Vet Affairs Med Ctr, Charleston, SC USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Room 501,BAsic Sci Bldg,173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hannun@musc.edu RI Kawamori, Toshihiko/G-7636-2012; OI Kitatani, Kazuyuki/0000-0002-8516-6135; obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA87584]; NHLBI NIH HHS [HL072925]; NIGMS NIH HHS [GM08716, GM62887] NR 12 TC 86 Z9 87 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2005 VL 68 IS 2 BP 330 EP 335 DI 10.1124/mol.104.008722 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946CO UT WOS:000230549900009 PM 15900018 ER PT J AU Swarztrauber, K Anau, J Peters, D AF Swarztrauber, K Anau, J Peters, D TI Identifying and distinguishing cases of parkinsonism and Parkinson's disease using ICD-9 CM codes and pharmacy data SO MOVEMENT DISORDERS LA English DT Article DE sensitivity and specificity; prevalence; Parkinson's disease; ICD-9 CM codes; administrative data ID INTERNATIONAL CLASSIFICATION; CLINICAL-DIAGNOSIS; ACCURACY; NEUROLOGISTS; VETERANS; FEATURES; RECORDS; RATES C1 Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Gen Clin Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Swarztrauber, K (reprint author), P-3 PADRECC,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM swarztra@ohsu.edu NR 25 TC 36 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2005 VL 20 IS 8 BP 964 EP 970 DI 10.1002/mds.20479 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 958JM UT WOS:000231440600008 PM 15834854 ER PT J AU Jang, IK AF Jang, IK TI Can angiographically silent coronary atherosclerosis predict mortality after cardiac transplantation? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE atherosclerosis; cardiac transplantation; intravascular ultrasound ID VASCULOPATHY C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bigelow 800 55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD AUG PY 2005 VL 2 IS 8 BP 386 EP 387 DI 10.1038/ncpcardio0269 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962NS UT WOS:000231740100005 PM 16119696 ER PT J AU Campbell, CD Ogburn, EL Lunetta, KL Lyon, HN Freedman, ML Groop, LC Altshuler, D Ardlie, KG Hirschhorn, JN AF Campbell, CD Ogburn, EL Lunetta, KL Lyon, HN Freedman, ML Groop, LC Altshuler, D Ardlie, KG Hirschhorn, JN TI Demonstrating stratification in a European American population SO NATURE GENETICS LA English DT Article ID GENETIC ASSOCIATION; STRUCTURED POPULATIONS; QUANTITATIVE TRAITS; GENOMIC CONTROL; DISEQUILIBRIUM; INFERENCE; VARIANTS; MARKERS; DISEASE; CANCER AB Population stratification occurs in case-control association studies when allele frequencies differ between cases and controls because of ancestry. Stratification may lead to false positive associations, although this issue remains controversial(1-4). Empirical studies have found little evidence of stratification in European-derived populations, but potentially significant levels of stratification could not be ruled out(5-7). We studied a European American panel discordant for height, a heritable trait that varies widely across Europe(8). Genotyping 178 SNPs and applying standard analytical methods(6,9-11) yielded no evidence of stratification. But a SNP in the gene LCT that varies widely in frequency across Europe(12) was strongly associated with height (P < 10(-6)). This apparent association was largely or completely due to stratification; rematching individuals on the basis of European ancestry greatly reduced the apparent association, and no association was observed in Polish or Scandinavian individuals. The failure of standard methods to detect this stratification indicates that new methods may be required. C1 Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Genom Collaborat Inc, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Lund Univ, Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. RP Hirschhorn, JN (reprint author), Childrens Hosp, Program Genom, 300 Longwood Ave, Boston, MA 02115 USA. EM joelh@broad.mit.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Lunetta, Kathryn/0000-0002-9268-810X NR 29 TC 263 Z9 269 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2005 VL 37 IS 8 BP 868 EP 872 DI 10.1038/ng1607 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 950TK UT WOS:000230880400017 PM 16041375 ER PT J AU Hu, M Yao, J Cai, L Bachman, KE van den Brule, F Velculescu, V Polyak, K AF Hu, M Yao, J Cai, L Bachman, KE van den Brule, F Velculescu, V Polyak, K TI Distinct epigenetic changes in the stromal cells of breast cancers SO NATURE GENETICS LA English DT Article ID HUMAN COLON-CARCINOMA; CPG ISLANDS; ALTERED METHYLATION; PROTEOGLYCAN GENE; DNA METHYLATION; HYPOMETHYLATION; EXPRESSION; HIN-1; TRANSCRIPTOME; EPIGENOMICS AB Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. Although epigenetic modifications of the neoplastic cells in tumors have been firmly implicated in tumorigenesis(1), it is not known whether epigenetic modifications occur in the non-neoplastic stromal cells. To address this question in an unbiased and genome-wide manner, we developed a new method, methylation-specific digital karyotyping, and applied it to epithelial and myoepithelial cells, stromal fibroblasts from normal breast tissue, and in situ and invasive breast carcinomas. Our analyses showed that distinct epigenetic alterations occur in all three cell types during breast tumorigenesis in a tumor stage- and cell type-specific manner, suggesting that epigenetic changes have a role in the maintenance of the abnormal cellular microenvironment in breast cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Liege, Lab Biol & Dev Biol, B-4000 Liege, Belgium. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu NR 29 TC 301 Z9 317 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2005 VL 37 IS 8 BP 899 EP 905 DI 10.1038/ng1596 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 950TK UT WOS:000230880400023 PM 16007089 ER PT J AU Gounari, F Chang, R Cowan, J Guo, ZY Dose, M Gounaris, E Khazaie, K AF Gounari, F Chang, R Cowan, J Guo, ZY Dose, M Gounaris, E Khazaie, K TI Loss of adenomatous polyposis coli gene function disrupts thymic development SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; COMMON LYMPHOID PROGENITORS; GERM-LINE MUTATIONS; BETA-CATENIN; APC GENE; PRE-TCR; CHROMOSOMAL INSTABILITY; TUMOR-SUPPRESSOR; DESMOID TUMORS; BONE-MARROW AB Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated beta-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) beta, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and alpha beta TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of beta-catenin signaling and is essential for T cell differentiation. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Pediat, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Khazaie, K (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM khashayarsha_khazaie@dfci.harvard.edu RI Gounaris, Elias/B-3184-2011; OI Dose, Marei/0000-0001-5394-9779; Gounaris, Elias/0000-0001-8679-9711 FU NCI NIH HHS [R01 CA104547, R01 CA104547-01A1]; NIAID NIH HHS [R01 AI059676, R01 AI059676-01, R01 AI059676-02] NR 50 TC 70 Z9 72 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2005 VL 6 IS 8 BP 800 EP 809 DI 10.1038/ni1228 PG 10 WC Immunology SC Immunology GA 947LM UT WOS:000230646200021 PM 16025118 ER PT J AU Tanzi, RE AF Tanzi, RE TI The synaptic A beta hypothesis of Alzheimer disease SO NATURE NEUROSCIENCE LA English DT Editorial Material ID LONG-TERM POTENTIATION; AMYLOID-PROTEIN; IN-VIVO; OLIGOMERS AB A beta peptide is linked to Alzheimer pathology, but its toxic mechanism remains unclear. New work shows that A leads to internalization of NMDA receptors, reducing their availability at synapses. The authors also suggest a molecular mechanism for this endocytosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 15 TC 128 Z9 131 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2005 VL 8 IS 8 BP 977 EP 979 DI 10.1038/nn0805-977 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 949BP UT WOS:000230760200003 PM 16047022 ER PT J AU Salat, DH Tuch, DS Greve, DN van der Kouwe, AJW Hevelone, ND Zaleta, AK Rosen, BR Fischl, B Corkin, S Rosas, HD Dale, AM AF Salat, DH Tuch, DS Greve, DN van der Kouwe, AJW Hevelone, ND Zaleta, AK Rosen, BR Fischl, B Corkin, S Rosas, HD Dale, AM TI Age-related alterations in white matter microstructure measured by diffusion tensor imaging SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; white matter; prefrontal; motor; corticospinal; internal capsule; myelin ID MULTIPLE-SCLEROSIS; OLDER-ADULTS; CORPUS-CALLOSUM; IN-VIVO; DIFFERENTIAL VULNERABILITY; ALZHEIMER-DISEASE; PREFRONTAL GRAY; CEREBRAL-CORTEX; SEX-DIFFERENCES; BLOOD-PRESSURE AB Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosurn (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration. (c) 2004 Published by Elsevier Inc. C1 MIT, MGH, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Salat, DH (reprint author), MIT, MGH, HMS Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mail Code 149 2301, Charlestown, MA 02129 USA. EM salat@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; OI Hevelone, Nathanael/0000-0003-4740-2085 FU NCRR NIH HHS [P41:RR14075, RR14075]; NIA NIH HHS [AG05886, 5:P50:AG05134, AG14432]; NINDS NIH HHS [NS39581] NR 65 TC 429 Z9 442 U1 4 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD AUG-SEP PY 2005 VL 26 IS 8 BP 1215 EP 1227 DI 10.1016/j.neurobiolaging.2004.09.017 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 935XO UT WOS:000229816900011 PM 15917106 ER PT J AU Albert, ML AF Albert, ML TI Subcortical dementia: Historical review and personal view SO NEUROCASE LA English DT Review C1 Boston Univ, Sch Med, Dept Neurol, Res Ctr, Boston, MA 02130 USA. VA Boston Healthcare Syst, Med Res Serv, Boston, MA 02130 USA. RP Albert, ML (reprint author), Boston Univ, Sch Med, Dept Neurol, Res Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM malbert@bu.edu NR 13 TC 5 Z9 5 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PD AUG PY 2005 VL 11 IS 4 BP 243 EP 245 DI 10.1080/13554790590963040 PG 3 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 957LG UT WOS:000231370700001 PM 16093223 ER PT J AU Lev, MH AF Lev, MH TI Stroke II: Imaging techniques and future directions SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Emergency Neuroradiol & Neurovasc Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Emergency Neuroradiol & Neurovasc Lab, 32 Fruit St, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP XV EP XVI DI 10.1016/j.nic.2005.09.002 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800001 ER PT J AU Shetty, SK Lev, MH AF Shetty, SK Lev, MH TI CT perfusion in acute stroke SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE ISCHEMIC-STROKE; CEREBRAL-BLOOD-FLOW; TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE HEMISPHERIC STROKE; SUSCEPTIBILITY CONTRAST MRI; 3-DIMENSIONAL FUNCTIONAL CT; HIGH-RESOLUTION MEASUREMENT; ANGIOGRAPHY SOURCE IMAGES; DIFFUSION-WEIGHTED MRI; FINAL INFARCT VOLUME AB As new treatments are developed for stroke, the potential clinical applications of CT perfusion (CTP) imaging in the diagnosis, triage, and therapeutic monitoring of these diseases are certain to increase. Technical advances in scanner hardware and software should no doubt continue to increase the speed, coverage, and resolution of CTP imaging. CTP offers the promise of efficient use of imaging resources and, potentially, of decreased morbidity. Most importantly, current CT technology already permits the incorporation of CTP as part of an all-in-one acute stroke examination to answer the four fundamental questions of stroke triage quickly and accurately, further increasing the contribution of imaging to the diagnosis and treatment of acute stroke. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shetty, SK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM sshetty@partners.org NR 134 TC 24 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 481 EP + DI 10.1016/j.nic.2005.08.004 PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800003 PM 16360585 ER PT J AU Schaefer, PW Copen, WA Lev, MH Gonzalez, RG AF Schaefer, PW Copen, WA Lev, MH Gonzalez, RG TI Diffusion-weighted imaging in acute stroke SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; CEREBRAL VENOUS THROMBOSIS; TRANSIENT GLOBAL AMNESIA; ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; RECEIVING INTRAARTERIAL THROMBOLYSIS; ANISOTROPIC WATER DIFFUSION; MAGNETIC-RESONANCE; APPARENT DIFFUSION; HEMORRHAGIC TRANSFORMATION AB In magnetic resonance diffusion-weighted imaging (DWI), regions of the brain are depicted not only on the basis of physical properties, such as T2 relaxation and spin density, which influence image contrast in conventional MRI, but also by local characteristics of water molecule diffusion. The diffusion of water molecules is altered in a variety of disease processes, including ischemic stroke. The changes that occur in acute infarction enable DWI to detect very early ischemia. Also, because predictable progression of diffusion findings occurs during the evolution of ischemia, DWI enables more precise estimation of the time of stroke onset than does conventional imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schaefer, PW (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St,Gray B285, Boston, MA 02114 USA. EM pschaefer@partners.org NR 166 TC 26 Z9 29 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 503 EP + DI 10.1016/j.nic.2005.08.011 PG 30 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800004 PM 16360586 ER PT J AU Gupta, R Jovin, TG Yonas, H AF Gupta, R Jovin, TG Yonas, H TI Xenon CT cerebral blood flow in acute stroke SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE ISCHEMIC-STROKE; POSITRON-EMISSION-TOMOGRAPHY; TISSUE-PLASMINOGEN ACTIVATOR; COMPUTED-TOMOGRAPHY; INTRAARTERIAL THROMBOLYSIS; BRAIN ISCHEMIA; ENHANCED CT; CEREBROVASCULAR-DISEASE; VESSEL RECANALIZATION; ARTERY INFARCTION AB Acute stroke therapy is evolving rapidly as research moves toward extending the time window for treatment so that more patients can benefit. As physiology-based imaging increasingly is used in patient selection, it is becoming evident that rigid time windows are not applicable to individual patients. Xenon CT has an important role in acute stroke therapeutic intervention as a quantitative, reproducible, rapid, and safe modality, which can provide valuable physiologic data that can optimize patient triage and aid in management. C1 Univ Pittsburgh, Med Ctr, Stroke Inst, Dept Neurol, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ New Mexico, Hlth Sci Ctr, Dept Neurosurg, Albuquerque, NM 87131 USA. RP Jovin, TG (reprint author), Univ Pittsburgh, Med Ctr, Stroke Inst, Dept Neurol, 200 Lothrop St,Suite C-400, Pittsburgh, PA 15213 USA. EM colejl2@upmc.edu NR 62 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 531 EP + DI 10.1016/j.nic.2005.08.007 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800005 PM 16360587 ER PT J AU Brobeck, BR Grant, PE AF Brobeck, BR Grant, PE TI Pediatric stroke: The child is not merely a small adult SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID SICKLE-CELL-DISEASE; ARTERIAL ISCHEMIC-STROKE; CEREBRAL VENOUS THROMBOSIS; FAMILIAL MOYAMOYA-DISEASE; VARICELLA-ZOSTER-VIRUS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE RISK-FACTORS; MITOCHONDRIAL MYOPATHY; LACTIC-ACIDOSIS; SINOVENOUS THROMBOSIS AB Arterial ischemic stroke and sinovenous thrombosis are significant yet under-recognized causes of mortality and morbidity in the pediatric population. With increasingly complex etiologies yet urgency for rapid diagnosis and treatment, pediatric stroke teams likely will become the standard of care. A common terminology must be developed to avoid confusing types of acute cerebral insults-such as focal arterial ischemic stroke and global hypoxia and ischemia-that have different causes and pathophysiologic mechanisms of injury. Increased awareness of unique pediatric stroke subtypes, their clinical presentation, and their imaging findings will facilitate early identification and development of optimal treatment strategies. C1 Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ellen@nmr.mgh.harvard.edu NR 101 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 589 EP + DI 10.1016/j.nic.2005.08.013 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800009 PM 16360591 ER PT J AU Chen, JW Wasserman, BA AF Chen, JW Wasserman, BA TI Vulnerable plaque imaging SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID CORONARY-ARTERY-DISEASE; HUMAN ATHEROSCLEROTIC LESIONS; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; ACUTE MYOCARDIAL-INFARCTION; RISK-ASSESSMENT STRATEGIES; UNSTABLE CAROTID PLAQUES; IN-VIVO DETECTION; CONTRAST AGENT; INTRAVASCULAR ULTRASOUND AB The concept of vulnerable plaque is well established with increasing evidence from clinical and basic research. The paradigm has shifted from focusing exclusively on the hemodynamic effects of plaque (ie, resulting lumenal stenosis alone as a predictor of stroke risk) to assessment of the structure and composition of plaque (eg, denuded endothelium with inflammatory elements as a nidus for platelet-fibrin clumping). It is increasingly evident that methods to detect and characterize vulnerable plaque must be developed and optimized. Although MRI, CT, and ultrasound provide data regarding single lesions, future investigations relying heavily on nuclear medicine techniques may offer functional assessment of the entire cardiovascular system. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Neuroradiol Div, Baltimore, MD 21205 USA. RP Chen, JW (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 32 Fruit St, Boston, MA 02114 USA. EM chenjo@helix.mgh.harvard.edu NR 125 TC 15 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 609 EP + DI 10.1016/j.nic.2005.08.005 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800010 PM 16360592 ER PT J AU Singhal, AB Lo, EH Dalkara, T Moskowitz, MA AF Singhal, AB Lo, EH Dalkara, T Moskowitz, MA TI Advances in stroke neuroprotection: Hyperoxia and beyond SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN-ACTIVATOR; NITRIC-OXIDE SYNTHASE; RANDOMIZED CONTROLLED-TRIAL; CLOMETHIAZOLE ACUTE STROKE; PERFUSION COMPUTED-TOMOGRAPHY; HYPERBARIC-OXYGEN THERAPY; CUZN-SUPEROXIDE-DISMUTASE; RADICAL-TRAPPING AGENT; BRAIN-INJURY AB Refinements in patient selection, improved methods of drug delivery, use of more clinically relevant animal stroke models, and the use of combination therapies that target the entire neurovascular unit make stroke neuroprotection an achievable goal. This article provides an overview of the major mechanisms of neuronal injury and the status of neuroprotective drug trials and reviews emerging strategies for treatment of acute ischemic stroke. Advances in the fields of stem cell transplantation, stroke recovery, molecular neuroimaging, genomics, and proteomics will provide new therapeutic avenues in the near future. These and other developments over the past decade raise expectations that successful stroke neuroprotection is imminent. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey. Massachusetts Gen Hosp, Dept Radiol, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802, Boston, MA 02114 USA. EM asinghal@partners.org RI Moskowitz, Michael/D-9916-2011 NR 195 TC 11 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 697 EP + DI 10.1016/j.nic.2005.08.014 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800016 PM 16360598 ER PT J AU Lev, MH AF Lev, MH TI Stroke I: Imaging techniques and future directions (vol 15, pg xv, 2005) SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Correction C1 Massachusetts Gen Hosp, Dept Radiol, Emergency Neuroradiol & Neurovasc Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Emergency Neuroradiol & Neurovasc Lab, 32 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2005 VL 15 IS 3 BP 721 EP 721 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 998FK UT WOS:000234303800017 ER PT J AU Katz, IR Morales, K Datto, C Streim, J Oslin, D DiFilippo, S Ten Have, T AF Katz, IR Morales, K Datto, C Streim, J Oslin, D DiFilippo, S Ten Have, T TI Probing for affective side effects of drugs used in geriatric practice: Use of daily diaries to test for effects of metoclopramide and naproxen SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE mood disorders; daily diaries; metoclopramide; naproxen; randomized clinical trial; affect ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RELIABILITY; VALIDITY; EVENTS; LIFE; AGE AB The aim of this study was to develop the use of daily diaries of affects and events as measures of pharmacological effects on affective processes and to apply them to evaluate the possible affective toxicity of metoclopramide and naproxen, two medications commonly used in geriatric practice. In all, 105 adults aged 65 years or older were randomized to receive metoclopramide (up to 40 mg/day), naproxen (up to 1000 mg/day), or placebo under double-blind conditions for a period of 5 weeks. Patients were seen weekly for evaluations of affective and cognitive outcomes as well as safety. In addition, patients kept diaries with daily records of positive and negative affect and reports of significant daily events. Findings included mixed model analyses of drug assignment, time, events, and interactions for both positive affect and days with significant negative affect. Subjects exhibited high levels of adherence in completing daily diaries. Neither the pattern of dropouts nor the weekly assessments demonstrated significant drug effects on mood or affect. However, diary data demonstrated that metoclopramide increased the apparent impact of negative events on both positive and negative affect relative to placebo, and that naproxen increased the apparent impact of positive events on positive affect and, possibly, of negative events on negative affect relative to placebo. The findings confirm the utility of diary methods for studying drug effects on affective processes in normal elderly subjects. They suggest that both metoclopramide and naproxen can affect the associations between daily events and affects. If replicated, they would demonstrate that drug effects can extend beyond the intensity of affect and/or the emergence of full-fledged psychiatric disorders to include moderation of the interactions between daily events and affect. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Katz, IR (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Room 3001, Philadelphia, PA 19104 USA. EM katzi@mail.med.upenn.edu NR 30 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2005 VL 30 IS 8 BP 1568 EP 1575 DI 10.1038/sj.npp.1300751 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 946QJ UT WOS:000230586900017 PM 15856076 ER PT J AU Herbert, MR Ziegler, DA AF Herbert, MR Ziegler, DA TI Volumetric neuroirnaging and low-dose early-life exposures: Loose coupling of pathogenesis-brain-behavior links SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 21st International Neurotoxicology Conference CY FEB 10-14, 2004 CL Honolulu, HI DE brain morphometry; developmental disorder; autism; toxicology; scaling; network ID DEVELOPMENTAL LANGUAGE DISORDER; CEREBRAL WHITE-MATTER; TOPOGRAPHIC PARCELLATION; AUTISM; MRI; IMPAIRMENT; CHILDREN; PRINCIPLES; CORTEX; TIME AB The interface of developmental neuroimaging with developmental neurotoxicology can, broadly speaking, address two complementary concerns. The first is to study the impact (of specific exposures (in brain development. The second is to study known neurobehavioral disorders with an eye to discerning toxicological contributions to pathogenesis. Pathogenesis targets brain based upon physical properties (receptors, growth factors, etc.) while behavior is modulated by regional and neural systems alterations. The distribution of pathogenesis-brain relationships overlaps only partially with that of brain-behavior relationships. The goal of this paper is to highlight methodological issues involved in designing and interpreting volumetric neuroimaging studies in the light of this loose coupling. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA. MIT, Cambridge, MA 02139 USA. RP Herbert, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, 149 13th St,Room 6012, Charlestown, MA 02129 USA. EM mherbert1@partners.org NR 35 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD AUG PY 2005 VL 26 IS 4 BP 565 EP 572 DI 10.1016/j.neuro.2005.01.002 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 961VH UT WOS:000231689400009 PM 16112322 ER PT J AU Evins, AE Cather, C Culhane, M AF Evins, AE Cather, C Culhane, M TI Predictors of smoking cessation in patients with schizophrenia SO NICOTINE & TOBACCO RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD AUG PY 2005 VL 7 IS 4 BP 680 EP 680 PG 1 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 972SY UT WOS:000232474700063 ER PT J AU Yu, MX Tueckmantel, W Wang, XK Zhu, AJ Kozikowski, AP Brownell, AL AF Yu, MX Tueckmantel, W Wang, XK Zhu, AJ Kozikowski, AP Brownell, AL TI Methoxyphenylethynyl, methoxypyridylethynyl and phenylethynyl derivatives of pyridine: synthesis, radiolabeling and evaluation of new PET ligands for metabotropic glutamate subtype 5 receptors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE MgluR5; PET; MPEP; M-MPEP; M-PEPy; carbon-11 ID PARKINSONS-DISEASE; SELECTIVE RADIOLIGAND; SEROTONIN TRANSPORTER; ALZHEIMERS-DISEASE; MGLU5 RECEPTOR; ANTAGONIST; POTENT; 2-METHYL-6-(PHENYLETHYNYL)-PYRIDINE; DISORDERS AB We have synthesized three different PET ligands to investigate the physiological function of metabotropic glutamate subtype 5 receptors (mGluR5) in vivo: 2-[C-11]methyl-6-(2-phenylethynyl)pyridine ([C-11]MPEP), 2-(2-(3-[C-11]methoxyphenyl)ethynyl)pyridine ([C-11]M-MPEP) and 2-(2-(5-[C-11]methoxypyridin-3-yl)ethynyl)pyridine([C-11]M-PEPy). [C-11]Methyl iodide was used to label the compounds under basic conditions, and a Pd(0) catalyst was applied to label [C-11]MPEP in a Stille coupling reaction. In vivo microPET imaging studies of the functional accumulation of radiolabeled ligands were conducted in 35 rats (Sprague-Dawley, 8 weeks old male, weight of 300 g). Specific binding was tested using pre-administration of unlabeled mGluR5 antagonist 2-methyl-6-(2-phenylethynyl)pyridine (MPEP) (10 mg/kg iv 5 min before radioactivity injection). In the radiolabeling of [C-11]MPEP, [C-11]M-MPEP and [C-11]M-PEPy, a specific radioactivity of 700-1200 mCi/mu mol and over 97% radiochemical purity were obtained. The microPET studies showed these three radiolabeled mGIuR5 antagonists having the highest binding in the olfactory bulb followed by striatum, hippocampus and cortex. Pre-administration of the mGluR5 antagonist MPEP induced a 45.1% decrease in [C-11]MPEP binding, a 59.7% decrease in [C-11]M-MPEP binding and an 84.6% decrease in [C-11]M-PEPy binding in the olfactory bulb at 5 min. The feasibility of synthesizing high-affinity and high-selectivity ligands for mGluR5 receptors and their suitability as PET imaging ligands for mGluR5 receptors in vivo are demonstrated. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Boston, MA 02114 USA. Acenta Discovery Inc, Tucson, AZ 85747 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Boston, MA 02114 USA. EM myu@utmck.edu; abrownell@partners.org FU NIBIB NIH HHS [EB01850] NR 41 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 2005 VL 32 IS 6 BP 631 EP 640 DI 10.1016/j.nucmedbio.2005.05.004 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 955KZ UT WOS:000231226100009 PM 16026710 ER PT J AU Young, TA Seddon, JM AF Young, TA Seddon, JM TI Choroidal and cutaneous melanoma: Distinctly different cousins SO OPHTHALMIC EPIDEMIOLOGY LA English DT Editorial Material ID UVEAL MELANOMA; METASTASIS; RISK C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Ophthalm Oncol Ctr, Los Angeles, CA USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. EM johanna_seddon@meei-harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD AUG PY 2005 VL 12 IS 4 BP 221 EP 222 DI 10.1080/092865805001863989 PG 2 WC Ophthalmology SC Ophthalmology GA 951ZY UT WOS:000230972100001 PM 16033742 ER PT J AU Richardson, DT Dodson, TB AF Richardson, DT Dodson, TB TI Risk of periodontal defects after third molar surgery: An exercise in evidence-based clinical decision-making SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID 3RD MOLAR SURGERY; SURGICAL REMOVAL AB Objective. The object of this study was to apply evidence-based principles to answer the question, What is the risk of having periodontal defects on the distal aspect of the mandibular second molar (M2) following third molar (M3) removal? Study design. To identify relevant articles for review, we completed a computerized literature search of Medline. The inclusion criteria for articles included prospective cohort studies or randomized clinical trials with follow-up periods of 6 months or more, and preoperative and postoperative measurements of periodontal probing depths (PDs) or attachment levels (ALs). Results. Eight articles met the inclusion criteria. Overall, the reported mean changes in ALs or PDs on the distal of M2 6 months after M3 removal were clinically insignificant, ie, less than 2 mm. Six months after M3 removal, 52% to 100% of subjects had no change or improvement in ALs or PDs. Given periodontal disease present preoperatively, the number needed to treat (NNT) ranged from 3 to 10. Given healthy periodontal status preoperatively, 48% had worsening of their periodontal measures after M3 removal and the number needed to harm (NNH) was 2. Conclusion. Commonly, the second molar periodontal probing depth or attachment levels either remain unchanged or improve after third molar removal. For subjects with healthy second molar periodontium preoperatively, the indication for third molar removal needs to be evaluated carefully as these subjects have an increased risk for worsening of probing depths or attachment levels after third molar removal. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Richardson, DT (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM dtrichardson@partners.org FU NIDCR NIH HHS [K24 DE00048] NR 12 TC 21 Z9 22 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD AUG PY 2005 VL 100 IS 2 BP 133 EP 137 DI 10.1016/j.tripleo.2005.02.063 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 951PY UT WOS:000230944100002 PM 16037768 ER PT J AU Ao, Y Wu, SY Go, VLW Toy, N Yang, H AF Ao, Y Wu, SY Go, VLW Toy, N Yang, H TI Maintaining euglycemia prevents insulin-induced Fos expression in brain autonomic regulatory circuits SO PANCREAS LA English DT Article DE dorsal motor nucleus of the vagus; nucleus tractus solitarii; paraventricular nucleus of the hypothalamus; hypoglycemia; vagus ID EXTRACELLULAR GLUCOSE-CONCENTRATIONS; SOLITARY TRACT NUCLEUS; CENTRAL-NERVOUS-SYSTEM; SENSITIVE K+ CHANNELS; PORTAL-VEIN AREA; GASTRIC-MOTILITY; ACID-SECRETION; VAGAL COMPLEX; VAGUS NERVE; RAT-BRAIN AB Objective: Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply. Methods: Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion ( control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry. Results: The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus ( DMV, 26 6 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats. Conclusion: These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range. C1 Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Room 203, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-41301] NR 43 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD AUG PY 2005 VL 31 IS 2 BP 142 EP 147 DI 10.1097/01.mpa.0000172562.96168.59 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 950YN UT WOS:000230895300007 PM 16025001 ER PT J AU Cote, CJ AF Cote, CJ TI Strategies for preventing sedation accidents SO PEDIATRIC ANNALS LA English DT Article ID PEDIATRIC-PATIENTS; THERAPEUTIC PROCEDURES; NON-ANESTHESIOLOGISTS; PROCEDURAL SEDATION; PRACTICE GUIDELINES; ADVERSE SEDATION; PULSE OXIMETRY; SINGLE-BLIND; CHILDREN; ANALGESIA C1 Massachusetts Gen Hosp, Div Pediat Anesthesiol, Childrens Hosp, Boston, MA 02114 USA. RP Cote, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Childrens Hosp, Boston, MA 02114 USA. NR 36 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD AUG PY 2005 VL 34 IS 8 BP 625 EP 633 PG 9 WC Pediatrics SC Pediatrics GA 970UO UT WOS:000232336900007 PM 16149751 ER PT J AU Chetty, A Manzo, N Waxman, AB Nielsen, HC AF Chetty, A Manzo, N Waxman, AB Nielsen, HC TI Modulation of IGF-binding protein-2 and -3 in hyperoxic injury in developing rat lung SO PEDIATRIC RESEARCH LA English DT Article ID GROWTH-FACTOR-I; ALVEOLAR EPITHELIAL-CELLS; VITAMIN-A SUPPLEMENTATION; RETINOIC ACID; BRONCHOPULMONARY DYSPLASIA; PRIMARY CULTURES; GENE-EXPRESSION; NEWBORN RATS; FACTOR-BETA; INSULIN AB Retinoids play an important role in lung development and repair. We showed that retinoic acid (RA) inhibits O-2-induced fibroblast proliferation in rat lung explants. IGF-1, which enhances the proliferation of human fetal lung fibroblasts and stimulates collagen production during lung injury, has an important role in the lung injury/repair process. Interactions of IGF-1 with its receptor are modulated by IGF-binding proteins IGFBPs. We hypothesized that RA alters IGFBP-2 and -3 in hyperoxia-exposed neonatal lung and alters collagen production. Neonatal rat lungs were cultured in room air or 95% O-2 and 5% CO2 for 3 d with or without RA. IGFBP-2 and -3 were measured both in culture medium and in lung tissue. Type I collagen and procollagen propeptide were analyzed in the lung tissue. Hyperoxia induced an increase in type I collagen that was significantly inhibited in the presence of RA. IGFBP-2 and IGFBP-3 in the lungs were decreased in hyperoxia but significantly increased in hyperoxia plus RA. In the culture medium, IGFBP-2 and -3 were not increased with hyperoxia but significantly increased in the presence of RA plus hyperoxia. There was no increase in IGFBP-3 RNA transcript after RA treatment in either room air or O-2 exposure. In conclusion, RA modulates the secreted IGFBP-2 and -3 during O-2 exposure and inhibits the increase in collagen that occurs during lung injury. We speculate that RA protects against O-2-induced neonatal lung injury through modulation of the IGFBPs. C1 Tufts Univ New England Med Ctr, Floating Hosp Children, Boston, MA 02111 USA. Tufts Med Sch, Boston, MA 02111 USA. Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chetty, A (reprint author), Tufts Univ New England Med Ctr, Dept Pediat, Box 044,750 Washington St, Boston, MA 02111 USA. EM achetty@tufts-nemc.org OI Nielsen, Heber/0000-0002-9382-0539 FU NHLBI NIH HHS [R01 HL037930, HL 67089, HL 37930, HL 074859] NR 57 TC 8 Z9 10 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 2005 VL 58 IS 2 BP 222 EP 228 DI 10.1203/01.PDR.0000169973.42653.68 PG 7 WC Pediatrics SC Pediatrics GA 952HV UT WOS:000230995500009 PM 16055936 ER PT J AU Field, AE Austin, SB Camargo, CA Taylor, CB Striegel-Moore, RH Loud, KJ Colditz, GA AF Field, AE Austin, SB Camargo, CA Taylor, CB Striegel-Moore, RH Loud, KJ Colditz, GA TI Exposure to the mass media, body shape concerns, and use of supplements to improve weight and shape among male and female adolescents SO PEDIATRICS LA English DT Article DE adolescents; creatine; steroids; body image; male and female ID ANABOLIC-ANDROGENIC STEROIDS; EATING-DISORDERS; NONOVERWEIGHT ADOLESCENTS; RISK-FACTOR; BEHAVIORS; GIRLS; BOYS; PREADOLESCENT; OVERWEIGHT; PEER AB Objective. To assess the prevalence and correlates of products used to improve weight and shape among male and female adolescents. Methods. A cross-sectional study was conducted of 6212 girls and 4237 boys who were 12 to 18 years of age and enrolled in the ongoing Growing Up Today Study. The outcome measure was at least weekly use of any of the following products to improve appearance, muscle mass, or strength: protein powder or shakes, creatine, amino acids/hydroxy methylbutyrate (HMB), dehydroepiandrosterone, growth hormone, or anabolic/injectable steroids. Results. Approximately 4.7% of the boys and 1.6% of the girls used protein powder or shakes, creatine, amino acids/HMB, dehydroepiandrosterone, growth hormone, or anabolic/injectable steroids at least weekly to improve appearance or strength. In multivariate models, boys and girls who thought a lot about wanting more defined muscles (boys: odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.1-2.2; girls: OR: 2.3; 95% CI: 1.2-3.2) or were trying to gain weight (boys: OR: 3.0; 95% CI: 2.0-4.6; girls: OR: 4.3; 95% CI: 1.6-11.4) were more likely than their peers to use these products. In addition, boys who read men's, fashion, or health/fitness magazines (OR: 2.3; 95% CI: 1.1-4.9) and girls who were trying to look like women in the media (OR: 2.9; 95% CI: 1.4-4.0) were significantly more likely than their peers to use products to improve appearance or strength, but hours per week watching television, watching sports on television, and participation in team sports were not independently associated with using products to improve appearance or muscle mass. Conclusions. Girls and boys who frequently thought about wanting toned or well-defined muscles were at increased risk for using potentially unhealthful products to enhance their physique. These results suggest that just as girls may resort to unhealthful means to achieve a low body weight, girls and boys may also resort to unhealthful means to achieve other desired physiques. C1 Childrens Hosp, Div Adolescent Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Wesleyan Univ, Dept Psychol, Middletown, CT USA. RP Field, AE (reprint author), Childrens Hosp, Div Adolescent Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Alison.Field@childrens.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK 46200, DK-46834, DK-59570] NR 25 TC 51 Z9 52 U1 2 U2 28 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 AUG PY 2005 VL 116 IS 2 BP E214 EP E220 DI 10.1542/peds.2004-2022 PG 7 WC Pediatrics SC Pediatrics GA 951FU UT WOS:000230915600006 PM 16061574 ER PT J AU Cronise, K Finn, DA Metten, P Crabbe, JC AF Cronise, K Finn, DA Metten, P Crabbe, JC TI Scheduled access to ethanol results in motor impairment and tolerance in female C57BL/6J mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE intoxication; alcohol; consumption; tolerance; motor incoordination; self-administration; mouse; rotarod ID ALCOHOL-PREFERRING RATS; FREE-CHOICE DRINKING; WATER RESTRICTION; LOW-LEVEL; CONSUMPTION; INTOXICATION; SENSITIVITY; DEPENDENCE; EXPOSURE; MODEL AB We recently reported a method where water-restricted mice were given scheduled access to ethanol followed by access to water. C57BL/ 6J mice would repeatedly self-administer ethanol in amounts that produced high and stable blood ethanol concentrations (BEC) [Finn DA, Belknap JK, Cronise K, Yoneyama N, Murillo A, Crabbe X. A procedure to produce high alcohol intake in mice. Psychopharmacol 2005;178:471-480]. The studies reported here demonstrate that behavioral signs of motor impairment result from these high alcohol intakes, and that there was some evidence of tolerance development across repeated sessions. Female C57BL/6J mice were allowed 30 min access to ethanol (5% v/v) followed by 2.5 h access to water either: every 3rd day for 12 days-, every 2nd day for 28 days; or every 2nd day for 9 days. On intervening days, mice had 3 h access to water. A control group had daily access to water only. Mice consumed 2-2.5 g/kg ethanol in 30 min, resulting in BECs of 1.4-1.5 mg/ml. Motor impairment was assessed using the accelerating or fixed speed rotarod, balance beam or screen test. In all studies, mice were tested for motor impairment immediately after 30 min access to ethanol or water. In Experiment 1, ethanol-exposed mice had shorter latencies to fall from the fixed speed rotarod and more foot slips on the balance beam than the control group, indicating motor impairment. After drinking ethanol, mice also fell from a screen more quickly than during sober pretraining. In Experiment 2, mice tested (without prior training) for motor impairment and tolerance on the fixed speed rotarod at 6.5 and 10 RPM showed repeated motor impairment in the ethanol group, but did not develop tolerance. In Experiment 3, mice were first given rotarod training at 10 RPM. Following each fluid access period, performance was impaired in mice self-administering ethanol at 10, but not 15 RPM, when compared to control mice. There was no evidence of tolerance across days. However, on the last day, all mice were tested at both RPM following an i.p. injection of 2 g/kg ethanol. Ethanol-experienced mice were less impaired at both RPM than the ethanol-naive mice, indicating tolerance development according to this between-groups index. These results suggest that C57BL/6J mice will repeatedly consume alcohol in amounts that produce motor impairment under these scheduled fluid access conditions, and that a modest degree of tolerance can be detected using appropriate tests. Published by Elsevier Inc. C1 Portland VA Med Ctr, R&D 12, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Crabbe, JC (reprint author), Portland VA Med Ctr, R&D 12, Portland Alcohol Res Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kcronise@middlebury.edu; crabbe@ohsu.edu FU NIAAA NIH HHS [AA10760, AA13478, P60 AA010760, AA13519, AA07468] NR 44 TC 17 Z9 17 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 2005 VL 81 IS 4 BP 943 EP 953 DI 10.1016/j.pbb.2005.07.005 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 965AQ UT WOS:000231922500032 PM 16099022 ER PT J AU Rajakumar, A Michael, HM Rajakumar, PA Shibata, E Hubel, CA Karumanchi, SA Thadhani, R Wolf, M Harger, G Markovic, N AF Rajakumar, A Michael, HM Rajakumar, PA Shibata, E Hubel, CA Karumanchi, SA Thadhani, R Wolf, M Harger, G Markovic, N TI Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFit-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women SO PLACENTA LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Invest DE preeclampsia; hypoxia; placenta; villous explants; VEGF-receptor-1; Flt-1; sFlt-1; peripheral blood mononuclear cells (PBMCs) ID INFLAMMATORY RESPONSE; HYPERTENSION; HYPOXIA; HIF-2-ALPHA AB The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has been previously demonstrated to produce high levels of the soluble VEGF receptor. Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may also represent an additional source for circulating sF1t-1 during normal and preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and sFlt-1 levels arc eight-fold higher in precclamptic placentae if we collect biopsies without rinsing them in saline to remove excess blood. Cultured villous explants from women with preeclampsia failed to show the increased amount of Flt-1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in the cxplants Nvere 3.11 +/- 0.6 fold in normal pregnancy and 3.6 +/- 0.4 fold in women with preeclampsia (p = NS by ANOVA). However, the same villous explants showed hypoxic induction of Flt-1 mRNA (NP 3.96 +/- 0.4 fold, p = NS and PE 5.24 +/- 0.6 fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra-placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant women exposed to hypoxia show up-regulation of HIF-1 alpha and Flt-1 proteins. PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher amounts of sFIt-1 under normal tissue culture conditions (104.6 +/- 14.3 pg/ml vs. 46.23 +/- 5.03 pg/ml, p < 0.05 T ANOVA) and much higher concentrations under hypoxia (196.74 +/- 26.3 pg/ml vs. 83.3 +/- 13.6 pg/ml, p < 0.05 by ANOVA) than PBMCs from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different group of women with a history of preeclampsia showed persistent abnormality of Flt-1 women one year post-partum. The present study indicates that Flr-1 dysregulation in PBMCs of pregnant women resulting in over-expression of sFIt-1 could be an additional (extra-placental) source of sFlt-1 that contributes to the pathogenesis of preeclampsia. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Lab 640, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02115 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Rajakumar, A (reprint author), Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Lab 640, 204 Craft Ave, Pittsburgh, PA 15213 USA. EM rsiar@mwri.magee.edu FU NHLBI NIH HHS [HL 64144]; NICHD NIH HHS [P01-HD30367] NR 29 TC 110 Z9 114 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD AUG PY 2005 VL 26 IS 7 BP 563 EP 573 DI 10.1016/j.placenta.2004.09.001 PG 11 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 946WL UT WOS:000230603900006 PM 15993706 ER PT J AU Jian-Wei, X Randolph, MA Peretti, GM Nazzal, JA Roses, RE Morse, KR Yaremchuk, MJ AF Jian-Wei, X Randolph, MA Peretti, GM Nazzal, JA Roses, RE Morse, KR Yaremchuk, MJ TI Producing a flexible tissue-engineered cartilage framework using expanded polytetrafluoroethylene membrane as a pseudoperichondrium SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 3rd Biennial Tissue-Engineering-Society International Meeting CY NOV 30-DEC 03, 2000 CL ORLANDO, FL SP Tissue Engn Soc ID GORE-TEX; CHONDROCYTES; RECONSTRUCTION; PERICHONDRIUM; GRAFTS; EAR; EXPERIENCE; DEFECTS; MATRIX AB Background: Both native and engineered cartilage is brittle and fractures easily without perichondrium. The aim of this study was to understand the role of the perichondrium and try to enhance the flexible properties of tissue-engineered cartilage using expanded polytetrafluoroethylene (ePTFE) membrane as a pseudoperichondrium. Methods: The study was conducted in two phases. In phase I, native swine auricular cartilage of different thicknesses was studied by histologic evaluation and failure testing. Next, isolated perichondrium was bonded to native cartilage slices using fibrin glue or Dermabond and tested to failure. In phase II, swine auricular chondrocytes were suspended in fibrin glue. The chondrocyte-fibrin glue composites were then bound to expanded polytetrafluoroethylene membrane in two trilaminar configurations: In group EC-1, the membrane was in the center, whereas it was on the surfaces in group EC-2. Specimens were implanted into nude mice for 4 weeks, 8 weeks, 12 weeks, and 8 months and subjected to histologic evaluation and failure testing. Results: In phase I, the results demonstrated that perichondrium securely bonded to the cartilage plays an important role in maintaining the flexible nature of elastic cartilage. In phase II, failure testing revealed that specimens in group EC-1 (expanded polytetrafluoroethylene core) were fractured during bending and destroyed after torsion, whereas those in group EC-2 (cartilage core) returned to their original shape without fracturing even after rigorous torsion. Histologic analysis demonstrated that transplanted chondrocytes penetrated into the microporous structure of expanded polytetrafluoroethylene and created a bond to it. Conclusion: It is possible to engineer flexible cartilage using expanded polytetrafluoroethylene as a pseudoperichondrium. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Plast Surg, Boston, MA 02114 USA. Fudan Univ, Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Plast Surg, WACC 453,15 Parkman St, Boston, MA 02114 USA. EM randolph.mark@mgh.harvard.edu RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 32 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 2005 VL 116 IS 2 BP 577 EP 589 DI 10.1097/01.prs.0000172985.81897.dc PG 13 WC Surgery SC Surgery GA 951NM UT WOS:000230937400039 PM 16079694 ER PT J AU Thomson, CC Siegel, M Winickoff, J Biener, L Rigotti, NA AF Thomson, CC Siegel, M Winickoff, J Biener, L Rigotti, NA TI Household smoking bans and adolescents' perceived prevalence of smoking and social acceptability of smoking SO PREVENTIVE MEDICINE LA English DT Article DE household smoking bans; adolescents; smoking ID ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; NORMATIVE EXPECTATIONS; ETS EXPOSURE; CHILDREN; HOME; RESTRICTIONS; BEHAVIOR; NONSMOKERS; IMPACT AB Objectives. Household smoking bans might decrease the visibility of cigarette smoking and communicate nonsmoking social norms and parental attitudes to youths, which may serve as mediators to reduce smoking initiation. Whether they have these effects even if parents smoke or do not otherwise communicate strong disapproval of smoking to their children is not clear. We tested these hypotheses in multilevel analyses. Methods. A telephone survey of a random sample of 3831 Massachusetts adolescents (12-17 years) assessed respondents' perceptions of smoking prevalence and attitudes about the social acceptability of smoking in their community. The association of these outcomes with the presence of a smoking ban in the youths' home was tested in multivariate analyses that adjusted for town-level clustering and individual and envirommental characteristics. Results. A household smoking ban was reported by 71% of all youths and 49% of youths who lived with smokers. In multivariate models, youths who had a household smoking ban were more likely to perceive a lower adult smoking prevalence (OR 2.1; 95% CI 1.7-2.5; P < 0.001), greater adult disapproval of adult smoking (OR 2.0; 1.5-2.6; P < 0.001) and of teen smoking (OR 1.5; 95% Cl 1.2-1.9; P = 0.001). Conclusions. Among adolescents, a household smoking ban was associated with a lower perceived prevalence of adult smoking in their communities and more negative attitudes about the social acceptability of smoking, two factors that affect the likelihood of smoking initiation. Household smoking bans had these effects even in the presence of two parental factors known to encourage adolescent smoking initiation (parental smoking and lack of perceived parental disapproval of youth tobacco use). This provides an additional rationale for promoting household smoking bans to parents. C 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy, Boston, MA 02115 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Thomson, CC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Tobacco Res & Treatment Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM cthomson@partners.org OI Biener, Lois/0000-0002-4130-8138 NR 33 TC 36 Z9 36 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG PY 2005 VL 41 IS 2 BP 349 EP 356 DI 10.1016/j.ypmed.2004.12.003 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 938MR UT WOS:000230008000001 ER PT J AU Sorensen, G Gupta, PC Sinha, DN Shastri, S Kamat, M Pednekar, MS Ramakrishnan, S AF Sorensen, G Gupta, PC Sinha, DN Shastri, S Kamat, M Pednekar, MS Ramakrishnan, S TI Teacher tobacco use and tobacco use prevention in two regions in India: Results of the Global School Personnel Survey SO PREVENTIVE MEDICINE LA English DT Article DE tobacco use prevention; India; developing countries; school teachers; Global School Personnel Survey ID MORTALITY; BIHAR AB Background. This paper compares tobacco use patterns and tobacco use prevention efforts among teachers in two Indian states with high versus low prevalence of tobacco use. Methods. Data from the Global School Personnel Survey compared tobacco use patterns and tobacco use prevention activities among teachers from the Indian states of Maharashtra (N = 954) and Bihar (N = 524). Results. 78% of teachers in Bihar and 31% from Maharashtra were current tobacco users. Tobacco control policies were virtually nonexistent in schools in Bihar, while in Maharashtra, over one-fourth of teachers reported that tobacco use was prohibited among both students and teachers. Few teachers in Bihar taught their students about tobacco use prevention, while such teaching was more common in Maharashtra. In Maharashtra, teaching about tobacco use prevention was significantly associated with not currently using tobacco (P < 0.0001), having a policy specifically prohibiting tobacco use among students (P < 0.0001), and having a policy specifically prohibiting tobacco use among school personnel (P < 0.0001). Conclusions. This study has clear implications for implementation of tobacco control policies in Indian schools and further underscores the need for infrastructure support for tobacco use prevention in developing countries such as India, where tobacco use threatens to contribute to a growing proportion of the burden of disease worldwide. (c) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Tata Inst Fundamental Res, Epidemiol Res Unit, Bombay, Maharashtra, India. Sch Prevent Oncol, Patna, Bihar, India. Tata Mem Hosp, Dept Prevent Oncol, Bombay, Maharashtra, India. KJ Somaiya Med Coll, Dept Prevent & Social Med, Bombay, Maharashtra, India. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM Glorian_Sorensen@dfci.harvard.edu NR 14 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG PY 2005 VL 41 IS 2 BP 417 EP 423 DI 10.1016/j.ypmed.2004.09.048 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 938MR UT WOS:000230008000008 PM 15917036 ER PT J AU Sorensen, G Gupta, PC Sinha, DN Shastri, S Kamat, M Pednekar, MS Ramakrishnan, S AF Sorensen, G Gupta, PC Sinha, DN Shastri, S Kamat, M Pednekar, MS Ramakrishnan, S TI Teacher tobacco use and tobacco use prevention in two regions in India: qualitative research findings SO PREVENTIVE MEDICINE LA English DT Article DE tobacco use prevention; India; developing countries; school teachers; qualitative research ID ORAL-CANCER; INTERVENTION; WORKSITE AB Background. This paper uses qualitative data to explore differences in tobacco use patterns and tobacco use prevention efforts among teachers in two Indian states with high versus low prevalence of tobacco use. Methods. We conducted a series of 12 focus groups with teachers in 12 schools in Maharashtra and Bihar following a standardized script, and analyzed data using standard qualitative methods. Results. Teachers in Bihar reported higher levels of tobacco use and stronger social norms promoting tobacco use compared to those in Maharashtra; nonetheless, teachers in both states reported strong social prescriptions about teachers' not using tobacco, Few supports were available for cessation. Although focus group participants were generally aware that tobacco use has deleterious health effects, not all were knowledgeable of specific health consequences, in particular resulting from the use of smokeless tobacco. Key barriers to teaching about tobacco use prevention were reported, including the lack of its inclusion in standard curricula and large class sizes, these results also underscore the importance of support for tobacco control policies. Conclusions. These findings point to the need for a multi-pronged approach to tobacco use prevention that involves die government, school administration, as well as teachers, parents, and the broader community, and including support to tobacco use cessation. (c) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Tata Inst Fundamental Res, Epidemiol Res Unit, Bombay 400005, Maharashtra, India. Sch Prevent Oncol, Patna, Bihar, India. Tata Mem Hosp, Dept Prevent Oncol, Bombay 400012, Maharashtra, India. KJ Somaiya Med Coll, Dept Prevent & Social Med, Bombay, Maharashtra, India. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM Glorian_Sorensen@dfci.harvard.edu NR 21 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG PY 2005 VL 41 IS 2 BP 424 EP 432 DI 10.1016/j.ypmed.2004.09.047 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 938MR UT WOS:000230008000009 PM 15917037 ER PT J AU Zhang, M Mukherjee, N Bermudez, RS Latham, DE Delaney, MA Zietman, AL Shipley, WU Chakravarti, A AF Zhang, M Mukherjee, N Bermudez, RS Latham, DE Delaney, MA Zietman, AL Shipley, WU Chakravarti, A TI Adenovirus-mediated inhibition of survivin expression sensitizes human prostate cancer cells to paclitaxel in vitro and in vivo SO PROSTATE LA English DT Article DE survivin; paclitaxel; prostate cancer; chemotherapy ID ANTI-APOPTOSIS GENE; HUMAN OVARIAN-CANCER; DOWN-REGULATION; HUMAN-MELANOMA; MESSENGER-RNA; RESISTANCE; INDUCTION; CARCINOMA; PROTEIN; PHOSPHORYLATION AB BACKGROUND. Improvements in the response rates to chemotherapy would represent an important advancement in the care of patients with metastatic prostate cancer. There is accumulating evidence that Survivin, a member of the inhibitor of apoptosis (IAP) family, is associated with both cancer progression and drug resistance. The purpose of this study is to investigate the role of Survivin in paclitaxel-resistance and whether the targeting of Survivin sensitizes prostate cancer cells to paclitaxel. METHODS. Human prostate cell lines PC-3, DU-145, and LNCaP were infected with replication-deficient adenoviruses encoding either wild-type Survivin [pAd-S(WT)], to examine Survivin overexpression effects, or a phosphorylation-defective Survivin Thr34 -> Ala dominant negative mutant [pAd-S(T34A)], to examine Survivin inactivation effects. The effects of wild-type or mutant Survivin on spontaneous and paclitaxel-induced apoptosis were investigated both in vitro and in vivo. RESULTS. Forced overexpression of wild-type Survivin with pAd-S(WT) increased resistance to paclitaxel in all cell lines, both in vitro and in vivo. Inhibition of Survivin using pAd-S(T34A) resulted in a significant increase in the rate of spontaneous and paclitaxel-induced apoptosis in all cell lines, both in vitro and in vivo. This effect was abolished by co-treatment with VAD-CHO (Calbiochem, San Diego, CA), a pan-caspase inhibitor, indicating that Survivin normally mediates resistance to paclitaxel through suppression of caspase-mediated apoptosis. CONCLUSIONS. Survivin mediates paclitaxel-resistance in prostate cancer cells. The inhibition of Survivin sensitizes prostate cancer cells to paclitaxel-induced apoptosis through a caspase-dependant mechanism in vitro and in vivo. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org OI Mukherjee, Neelanjan/0000-0003-0017-1400 NR 53 TC 53 Z9 67 U1 0 U2 3 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 AUG 1 PY 2005 VL 64 IS 3 BP 293 EP 302 DI 10.1002/pros.20263 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 943RE UT WOS:000230371000009 PM 15754318 ER PT J AU Ping, PP Vondriska, TM Creighton, CJ Gandhi, TKB Yang, ZP Menon, R Kwon, MS Cho, SY Drwal, G Kellmann, M Peri, S Suresh, S Gronborg, M Molina, H Chaerkady, R Rekha, B Shet, AS Gerszten, RE Wu, HF Raftery, M Wasinger, V Schulz-Knappe, P Hanash, SM Paik, YK Hancock, WS States, DJ Omenn, GS Pandey, A AF Ping, PP Vondriska, TM Creighton, CJ Gandhi, TKB Yang, ZP Menon, R Kwon, MS Cho, SY Drwal, G Kellmann, M Peri, S Suresh, S Gronborg, M Molina, H Chaerkady, R Rekha, B Shet, AS Gerszten, RE Wu, HF Raftery, M Wasinger, V Schulz-Knappe, P Hanash, SM Paik, YK Hancock, WS States, DJ Omenn, GS Pandey, A TI A functional annotation of subproteomes in human plasma SO PROTEOMICS LA English DT Article DE annotation; bioinformatics; MS; proteomics; serum ID PERIPHERAL-BLOOD MONOCYTES; HUMAN SERUM PROTEOME; THROMBOTIC THROMBOCYTOPENIC PURPURA; FACTOR-CLEAVING PROTEASE; ACTIVATOR INHIBITOR 2; HEPATOCELLULAR-CARCINOMA; MASS-SPECTROMETRY; GENE-EXPRESSION; LIVER-CIRRHOSIS; RECEPTOR AB The data collected by Human Proteome Organization' s Plasma Proteome Pilot project phase was analyzed by members of our working group. Accordingly, a functional annotation of the human plasma proteome was carried out. Here, we report the findings of our analyses. First, bioinformatic analyses were undertaken to determine the likely sources of plasma proteins and to develop a protein interaction network of proteins identified in this project. Second, annotation of these proteins was performed in the context of functional subproteomes involved in the coagulation pathway, the mononuclear phagocytic system, the inflammation pathway, the cardiovascular system, and the liver, as well as the subset of proteins associated with DNA binding activities. Our analyses contributed to the Plasma Proteome Database (http://www.plasmaproteomedatabase.org), an annotated database of plasma proteins identified by HPPP as well as from other published studies. In addition, we address several methodological considerations including the selective enrichment of post-translationally modified proteins by the use of multi-lectin chromatography as well as the use of peptidomic techniques to characterize the low molecular weight proteins in plasma. Furthermore, we have performed additional analyses of peptide identification data to annotate cleavage of signal peptides, sites of intra-membrane proteolysis and post-translational modifications. The HPPP-organized, multi-laboratory effort, as described herein, resulted in much synergy and was essential to the success of this project. C1 Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. Rockefeller Univ, Lab Blood & Vasc Biol, University, NY USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Univ New S Wales, Bioanalyt Mass Spectrometry Facil, Sydney, NSW, Australia. Univ Michigan, Bioinformat Program, Ann Arbor, MI 48109 USA. BioVisioN AG, Hannover, Germany. Ohio State Univ, Dept Pathol, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Yonsei Univ, Dept Biochem, Biomed Proteome Res Ctr, Seoul 120749, South Korea. Yonsei Univ, Yonsei Proteome Res Ctr, Seoul 120749, South Korea. Northeastern Univ, Barnett Inst, Chem & Chem Biol Dept, Boston, MA 02215 USA. Inst Bioinformat, Bangalore, Karnataka, India. Univ Michigan, Dept Pediat 12, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med 13, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Dept Physiol, Div Cardiol, Cardiovasc Res Labs, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Div Cardiol, Cardiovasc Res Labs, Los Angeles, CA 90024 USA. RP Pandey, A (reprint author), Johns Hopkins Univ, McKusick Nathans Inst Genet Med, 733 N Broadway,BRB 569, Baltimore, MD 21205 USA. EM pandey@jhmi.edu RI Pandey, Akhilesh/B-4127-2009; Chaerkady, Raghothama/D-5718-2011; Wu, Haifeng/E-4329-2011; OI Pandey, Akhilesh/0000-0001-9943-6127; Omenn, Gilbert S./0000-0002-8976-6074; Ping, Peipei/0000-0003-3583-3881 NR 75 TC 43 Z9 51 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD AUG PY 2005 VL 5 IS 13 BP 3506 EP 3519 DI 10.1002/pmic.200500140 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958VZ UT WOS:000231477600026 PM 16104058 ER PT J AU Lesser, IM Leuchter, AF Trivedi, MH Davis, LL Wisniewski, SR Balasubramani, GK Petersen, T Stegman, D Rush, AJ AF Lesser, IM Leuchter, AF Trivedi, MH Davis, LL Wisniewski, SR Balasubramani, GK Petersen, T Stegman, D Rush, AJ TI Characteristics of insured and noninsured outpatients with depression in STAR*D SO PSYCHIATRIC SERVICES LA English DT Article ID QUALITY-OF-LIFE; SEQUENCED TREATMENT ALTERNATIVES; MEDICATION ALGORITHM PROJECT; PRIMARY-CARE PATIENTS; ILLNESS RATING-SCALE; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; SYMPTOMATOLOGY IDS; CONTROLLED-TRIAL; MOOD DISORDERS AB Objective: This study examined data from the first 1,500 patients with major depressive disorder who were entered into the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and compared baseline characteristics of outpatients on the basis of their insurance status. Methods: We compared the demographic and clinical characteristics and the features of the presenting symptoms of outpatients with private insurance, public insurance, Medicaid and Medicare, or no insurance who were seeking treatment for depression. Results: Valid insurance data were available for 1,452 patients. Compared with patients with private insurance, patients with public or no insurance were more likely to be members of a racial or ethnic minority group, unmarried, less educated, and unemployed. Patients were more likely to attend primary care clinics if they had public insurance (46 percent) compared with private insurance (34 percent) or no insurance (30 percent). Compared with the other groups, patients with public insurance had the greatest number and severity of comorbid medical conditions. In general, compared with patients with private insurance, those with public or no insurance had greater severity of depression, more comorbid psychiatric symptoms, lower life satisfaction scores, and greater functional impairment. These findings remained after the analyses adjusted for gender, employment, comorbid medical conditions, race, and duration of illness. Conclusions: Compared with patients with private insurance, those with public or no insurance had a more chronic, more severe, and more disabling form of depression. C1 Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Alabama, Dept Psychiat, Birmingham, AL USA. Tuscaloosa Vet Adm Med Ctr, Dept Res & Dev, Tuscaloosa, AL USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Lesser, IM (reprint author), Harbor UCLA Med Ctr, Dept Psychiat, Box 8,1000 W Carson St, Torrance, CA 90509 USA. EM ilesser@labiomed.org OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-900-03] NR 46 TC 21 Z9 21 U1 1 U2 2 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 AUG PY 2005 VL 56 IS 8 BP 995 EP 1004 DI 10.1176/appi.ps.56.8.995 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 953JK UT WOS:000231072300016 PM 16088018 ER PT J AU Sharf, BF Stelljes, LA Gordon, HS AF Sharf, BF Stelljes, LA Gordon, HS TI 'A little bitty spot and I'm a big man': Patients' perspectives on refusing diagnosis or treatment for lung cancer SO PSYCHO-ONCOLOGY LA English DT Article DE treatment refusal; lung neoplasms; patient acceptance of health care; decision-making rationale; physician-patient relationship; coping; uncertainty; problematic integration ID INDIVIDUAL PATIENTS; DECISION-MAKING; BREAST-CANCER; CHEMOTHERAPY; SURVIVAL; THERAPY AB Patient refusal of physicians' recommendations may partially account for variations in lung cancer treatment affecting survival. Reasons for refusal have not been well researched, and patients who refuse are often labeled derogatorily as irrational or enigmatically non-compliant. This study explored why patients refused recommendations for further diagnosis or treatment of lung cancer. We conducted in-depth interviews with nine patients, identified and recruited over a 2-year period, with documented refusal of doctors' recommendations. Recruiting was hampered by deaths, logistics, and refusal to participate. Questions focused on participants' understanding of disease, medical recommendations, and perceptions of decision-making. Transcripts were analyzed using a grounded theory approach. Participants emphasized selfefficacy, minimizing threat, fatalism or faith, and distrust of medical authority; explanations were often multidimensional. Comments included complaints about communication with physicians, health system discontinuities, and impact of social support. Explanations of participants' decisions reflected several ways of coping with an undesirable situation, including strategies for reducing, sustaining, and increasing uncertainty. Problematic Integration Theory helps to explain patients' difficulties in managing uncertainty when assessments of disease outcomes and treatment recommendations diverge. Implications for clinical communication include increasing trust while delivering bad news, understanding the source of resistance to recommendations, and discussing palliative care. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Sharf, BF (reprint author), Texas A&M Univ, Dept Commun, MS 4234, College Stn, TX 77843 USA. EM bsharf@tamu.edu RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU AHRQ HHS [5PO1 HS10876] NR 30 TC 37 Z9 37 U1 2 U2 7 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 AUG PY 2005 VL 14 IS 8 BP 636 EP 646 DI 10.1002/pons.885 PG 11 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 954QF UT WOS:000231168900003 PM 15744761 ER PT J AU Doyle, AE Biederman, J Seidman, LJ Reske-Nielsen, JJ Faraone, SV AF Doyle, AE Biederman, J Seidman, LJ Reske-Nielsen, JJ Faraone, SV TI Neuropsychological functioning in relatives of girls with and without ADHD SO PSYCHOLOGICAL MEDICINE LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 14-19, 2003 CL Miami, FL SP Amer Acad Child & Adolescent Psychiat ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; LONGITUDINAL DATA-ANALYSIS; DUAL PATHWAY MODEL; RESPONSE-INHIBITION; READING-DISABILITY; WORKING-MEMORY; CHILDREN; PARENTS; FAMILY AB Background. A limited number of studies have examined neuropsychological functioning in the family members of ADHD youth, and none have focused exclusively on relatives of females. Method. Structured diagnostic interviews and neuropsychological batteries were administered to parents and siblings enrolled in a family study of girls with and without ADHD. Relatives were stratified into three groups: relatives of DSM-IV ADHD probands with ADHD (n = 106), relatives of ADHD probands without ADHD (n = 189) and relatives of controls without ADHD (it = 243). Analyses were also conducted on a subgroup of families in which more than one member had ADHD. Results. The neuropsychological battery as a whole distinguished affected and unaffected ADHD relatives from controls. The Wechsler Oral Arithmetic subtest, the Stroop Word, Color and Color-Word subscales were impaired in affected ADHD relatives, as were the WRAT-R Arithmetic and Reading subtests. Only the Stroop Color-Word and Interference subtests and the WRAT-R Arithmetic subtest showed significant impairments in unaffected relatives. In multiplex families, additional impairments were found in unaffected relatives on the Stroop Color subtest and the Wechsler Oral Arithmetic subtest. Analyses based on DSM-III-R diagnoses produced nearly identical results. Minor differences emerged across relatives of probands with different DSM-IV subtypes. Conclusions. Data were consistent with our previous study of relatives of boys with ADHD. Neuropsychological impairments in relatives of female ADHD probands were primarily associated with the diagnosis of ADHD, but subtle cognitive impairments that index familial vulnerability to the disorder may exist. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. RP Doyle, AE (reprint author), Massachusetts Gen Hosp, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM doylea@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1R01MH41314, K08MH66072] NR 63 TC 17 Z9 18 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2005 VL 35 IS 8 BP 1121 EP 1132 DI 10.1017/S0033291705004496 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 961AV UT WOS:000231635200003 PM 16116938 ER PT J AU Yehuda, R Golier, JA Harvey, PD Stavitsky, K Kaufman, S Grossman, RA Tischler, L AF Yehuda, R Golier, JA Harvey, PD Stavitsky, K Kaufman, S Grossman, RA Tischler, L TI Relationship between cortisol and age-retated memory impairments in Holocaust survivors with PTSD SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE posttraumatic stress disorder (PTSD); Holocaust survivors; memory performance; cortisol; circadian rhythm; aging ID POSTTRAUMATIC-STRESS-DISORDER; PITUITARY-ADRENAL AXIS; DEHYDROEPIANDROSTERONE-SULFATE DHEAS; HEALTHY ELDERLY-MEN; ALZHEIMERS-DISEASE; HIPPOCAMPAL ATROPHY; DECLARATIVE MEMORY; BASAL CORTISOL; DEXAMETHASONE SUPPRESSION; FEEDBACK INHIBITION AB Rationale: Holocaust survivors with PTSD appear to show an accelerated aging effect as evidenced by their performance on tests of explicit memory, and also show more exaggerated patterns on age-related alterations in cortisol release over the diurnal cycle than Holocaust survivors without PTSD and nonexposed subjects. To investigate the implications of age-related HPA axis alterations on cognition, we examined correlations between parameters reflecting circadian cortisol release and implicit and explicit memory performance. Methods: Nineteen Holocaust survivors with PTSD (7 men, 12 women), 16 Holocaust survivors without PTSD (7 men, 9 women), and 28 non-exposed healthy comparison subjects (13 men, 15 women) collected salivary samples at six times over the diurnal cycle, and were tested with Paired Associates and Word Stem Completion Tests. Results: Negative correlations were observed between several measures of salivary cortisol concentrations and explicit memory in Holocaust survivors with PTSD after adjusting for IQ, years of education and current age reflecting poorer performance in association with higher cortisol levels. This relationship was absent in Holocaust survivors without PTSD and in demographically-comparable subjects who were not exposed to the Holocaust or other extremely traumatic events. Conclusion: The significantly different relationship between cortisol and memory performance in these groups suggests that the neuropsychological impairments observed in Holocaust survivors with PTSD may reflect an interaction of PTSD and aging effects. (c) 2005 Elsevier Ltd. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat OOMH, Div Traumat Stress Studies, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, Dept Psychiat OOMH, Div Traumat Stress Studies, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@med.va.gov FU NIMH NIH HHS [R01 MH64675-01] NR 59 TC 31 Z9 31 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 2005 VL 30 IS 7 BP 678 EP 687 DI 10.1016/j.psyneuen.2005.02.007 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 928BO UT WOS:000229246300007 PM 15854784 ER PT J AU Chen, YCI Choi, JK Andersen, SL Rosen, BR Jenkins, BG AF Chen, YCI Choi, JK Andersen, SL Rosen, BR Jenkins, BG TI Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging SO PSYCHOPHARMACOLOGY LA English DT Article DE dopamine; autoreceptor; MRI; amphetamine; Nucleus accumbens; microdialysis; eticlopride; quinpirole; relative cerebral blood volume; D2 ID CEREBRAL BLOOD-VOLUME; IN-VIVO; NUCLEUS-ACCUMBENS; RAT STRIATUM; D-3 RECEPTORS; D-AMPHETAMINE; HUMAN BRAIN; DRUG DISCRIMINATION; IRON-OXIDE; RELEASE AB Rationale: Regulation of dopamine release and. synthesis occurs via pre-synaptic dopamine (DA) D2/D3 autoreceptors (DARs). Mapping of DAR function in vivo is difficult and is usually best assessed using invasive measures of DA release, such as microdialysis at discrete sites. We wished to show that pharmacological magnetic resonance imaging (phMRI) may prove useful for this purpose. Objective: To demonstrate that the relative cerebral blood volume (rCBV) changes induced by amphetamine can be modulated by DA D2 receptor antagonists and agonists in a manner consistent with modulation of DAR function and to compare these effects with microdialysis. Methods: We used phMRI with iron oxide contrast agents to map changes in rCBV in response to an amphetamine challenge, pre-treatment and post-treatment with varying doses of the D2 antagonist eticlopride and the D2 agonist quinpirole. We also compared the effects of D2 antagonism using microdialysis measurements of DA release. Results: Antagonism of D2 receptors with eticlopride potentiated rCBV changes induced by amphetamine in the nucleus accumbens and caudate putamen in a dose-dependent manner. The amphetamine-induced increase in rCBV in the accumbens in animals pre-treated with eticlopride was paralleled by a similar percentage increase in DA release measured by means of microdialysis. Conversely, agonism of D2 receptors using quinpirole reduced amphetamine-induced rCBV changes in the caudate putamen and nucleus accumbens. The effects of both quinpirole and eticlopride on amphetamine-induced rCBV changes were largest in the nucleus accumbens. Conclusions: These results suggest that phMRI may potentially prove useful to map DAR function non-invasively in multiple brain regions simultaneously. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, MGH, NMR, Charlestown, MA 02129 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. RP Chen, YCI (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM bgj@nmr.mgh.harvard.edu FU NIDA NIH HHS [5PO1DA09467, R01 DA16187] NR 64 TC 46 Z9 48 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2005 VL 180 IS 4 BP 705 EP 715 DI 10.1007/s00213-004-2034-0 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 962KN UT WOS:000231731800014 PM 15536545 ER PT J AU Bloomfield, HE Nelson, DB van Ryn, M Neil, BJ Koets, NJ Basile, JN Samaha, FF Kaul, R Mehta, JL Bouland, D AF Bloomfield, HE Nelson, DB van Ryn, M Neil, BJ Koets, NJ Basile, JN Samaha, FF Kaul, R Mehta, JL Bouland, D TI A trial of education, prompts, and opinion leaders to improve prescription of lipid modifying therapy by primary care physicians for patients with ischemic heart disease SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; PREVENTIVE CARE; INTERVENTIONS; REMINDERS; BEHAVIOR AB Background: Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease (IHD) and low levels of high density lipoprotein (HDL) cholesterol. The results of these trials, however, have not been widely implemented in clinical practice. Objectives: To develop and test an intervention designed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts ( progress notes, patient letters, or computer chart reminders). Methods: The study was conducted in 11 US Department of Veterans Affairs Medical Centers. The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design. Additionally, 92 providers within the intervention clinics were randomized to receive one of the three prompts. Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data. Results: At the intervention sites the prescription rate increased from 8.3% during the pre-intervention period to 39.1% during the intervention ( OR = 6.5, 95% CI 5.2 to 8.2, p < 0.0001) but remained unchanged at the control sites. The interaction between group ( control v intervention) and time period was highly significant (p < 0.0001). The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites ( 95% CI 2.1 to 4.7). Overall, there was no significant difference in prescription rates among the three prompt groups. However, there was a significant interaction between prompt group and site, indicating that the efficacy of the prompts differed by site. Conclusion: An intervention for primary care providers consisting of an educational workshop, opinion leader influence, and prompts substantially increased the prescription rate of lipid modifying therapy. C1 VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Charleston, SC USA. Philadelphia VA Med Ctr, Cardiovasc Sect, Philadelphia, PA USA. VA Med Ctr, Fargo, ND USA. Univ Arkansas, Div Cardiovasc, Little Rock, AR 72204 USA. VA Pacific Isl Hlth Care Syst, Honolulu, HI USA. RP Bloomfield, HE (reprint author), VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. EM hanna.bloomfield@med.va.gov RI VAN RYN, MICHELLE/B-1664-2010; OI bloomfield, hanna/0000-0002-0756-7064 NR 20 TC 13 Z9 13 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD AUG PY 2005 VL 14 IS 4 BP 258 EP 263 DI 10.1136/qshc.2004.012617 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 950YT UT WOS:000230896000007 PM 16076789 ER PT J AU Kho, ME Carbone, JM Lucas, J Cook, DJ AF Kho, ME Carbone, JM Lucas, J Cook, DJ TI Safety Climate Survey: reliability of results from a multicenter ICU survey SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID TEAMWORK AB Background: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit ICU). Methods: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. Results: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. Conclusions: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives. C1 McMaster Univ, Dept Clin Epidemiol & Biostat, Fac Hlth Sci, Hamilton, ON L8S 4L8, Canada. Hamilton Hlth Sci, Hamilton, ON, Canada. RP Kho, ME (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. EM khome@mcmaster.ca NR 9 TC 50 Z9 51 U1 1 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD AUG PY 2005 VL 14 IS 4 BP 273 EP 278 DI 10.1136/qshc.2005.014316 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 950YT UT WOS:000230896000010 PM 16076792 ER PT J AU Thrall, JH AF Thrall, JH TI Reinventing radiology in the digital age - Part I. The all-digital department SO RADIOLOGY LA English DT Editorial Material ID PRODUCTIVITY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 13 TC 14 Z9 14 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 AUG PY 2005 VL 236 IS 2 BP 382 EP 385 DI 10.1148/radiol.2362050257 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200003 PM 16040896 ER PT J AU Glazer, GM Margulis, AR Wolf, KJ Ringertz, HG Frija, GG Thrall, JH Golding, SJ Krestin, GP AF Glazer, GM Margulis, AR Wolf, KJ Ringertz, HG Frija, GG Thrall, JH Golding, SJ Krestin, GP TI The International Society of Strategic Studies in Radiology SO RADIOLOGY LA English DT Editorial Material C1 Erasmus Med Ctr, NL-3000 CA Rotterdam, Netherlands. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Free Univ Berlin, D-1000 Berlin, Germany. Karolinska Sch Med, Stockholm, Sweden. Univ Paris, Fac Med, F-75252 Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England. RP Krestin, GP (reprint author), Erasmus Med Ctr, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM g.p.krestin@erasmusmc.nl NR 3 TC 1 Z9 2 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 AUG PY 2005 VL 236 IS 2 BP 386 EP 388 DI 10.1148/radiol.2362050516 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200004 ER PT J AU Kassarjian, A Yoon, LS Belzile, E Connolly, SA Millis, MB Palmer, WE AF Kassarjian, A Yoon, LS Belzile, E Connolly, SA Millis, MB Palmer, WE TI Triad of MR arthrographic findings in patients with cam-type femoroacetabular impingement SO RADIOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY MAY 07, 2004 CL Chicago, IL SP Radiol Soc N Amer ID ACETABULAR LABRUM; HIP; LESIONS AB PURPOSE: To retrospectively analyze magnetic resonance (MR) arthrographic findings in patients with clinical cam-type femoroacetabular impingement. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was waived. Study was compliant with the Health Insurance Portability and Accountability Act. Forty-two MR arthrograms obtained in 40 patients with clinical femoroacetabular impingement were analyzed retrospectively by two radiologists. Quantitative analysis by using alpha angle measurement was performed to assess anterosuperior femoral head-neck morphology. Presence of labral tears, articular cartilage lesions, paralabral cysts, os acetabuli, and synovial herniation pits was recorded. Presence of the typical triad of anterosuperior labral tear, anterosuperior cartilage lesion, and abnormal alpha angle was recorded. Surgical comparison was available for 11 patients. RESULTS: At imaging, in 40 patients (22 male, 18 female) with a mean age of 36.5 years, 39 of 42 hips (93%) had an abnormal alpha angle, with a mean angle of 69.7 degrees; 40 of 42 (95%) had an anterosuperior cartilage abnormality; and 42 of 42 (100%) had an anterosuperior labral tear. Thirty-seven of 42 hips (88%) had the triad. Six had paralabral cysts, 17 had an os acetabuli, and two had synovial herniation pits. Surgical comparison for 11 hips led to confirmation of all labral and cartilage abnormalities seen at imaging. CONCLUSION: MR arthrography demonstrated a triad of abnormal head-neck morphology, anterosuperior cartilage abnormality, and anterosuperior labral abnormality in 37 of 42 patients with cam-type femoroacetabular impingement. (c) RSNA, 2005 C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Ctr Hosp Univ Quebec, Dept Orthoped Surg, Quebec City, PQ, Canada. Boston Childrens Hosp, Dept Radiol, Boston, MA USA. Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA USA. RP Kassarjian, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 55 Fruit St,Yawkey Ctr,6th Floor, Boston, MA 02114 USA. EM akassarjian@partners.org NR 13 TC 172 Z9 181 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2005 VL 236 IS 2 BP 588 EP 592 DI 10.1148/radiol.2362041987 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200029 PM 15972331 ER PT J AU Torriani, M Thomas, BJ Halpern, EF Jensen, ME Rosenthal, DI Palmer, WE AF Torriani, M Thomas, BJ Halpern, EF Jensen, ME Rosenthal, DI Palmer, WE TI Intramyocellular lipid quantification: Repeatability with H-1 MR spectroscopy SO RADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN SKELETAL-MUSCLE; PROTON NMR-SPECTRA; INSULIN-RESISTANCE; IN-VIVO; TRIGLYCERIDE CONTENT; FAT; SENSITIVITY; HUMANS; QUANTITATION AB PURPOSE: To prospectively determine the repeatability and variability of tibialis anterior intramyocellular lipid (IMCL) quantifications performed by using 1.5-T hydrogen 1(H-1) magnetic resonance (MR) spectroscopy in healthy subjects. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. The authors examined the anterior tibial muscles of 27 healthy subjects aged 19-48 years (12 men, 15 women; mean age, 25 years) by using single-voxel short-echo-time point-resolved H-1 MR spectroscopy. During a first visit, the subjects underwent H-1 MR spectroscopy before and after being repositioned in the magnet bore, with voxels carefully placed on the basis of osseous landmarks. Measurements were repeated after a mean interval of 12 days. All spectra were fitted by using lava-based MR user interface (jMRUI) and LCModel software, and lipid peaks were scaled to the unsuppressed water peak (at 4.7 ppm) and the total creatine peak (at approximately 3.0 ppm). A one-way random-effects variance components model was used to determine intraday and intervisit coefficients of variation (CVs). A power analysis was performed to determine the detectable percentage change in lipid measurements for two subject sample sizes. RESULTS: Measurements of the IMCL methylene protons peak at a resonance of 1.3 ppm scaled to the unsuppressed water peak (IMCLW) that were obtained by using jMRUI software yielded the lowest CVs overall (intraday and intervisit CVs, 13.4% and 14.4%, respectively). The random-effects variance components model revealed that nonbiologic factors (equipment and repositioning) accounted for 50% of the total variability in IMCL quantifications. Power analysis for a sample size of 20 subjects revealed that changes in IMCLW of greater than 15% could be confidently detected between H-1 MR spectroscopic measurements obtained on different days. CONCLUSION: H-1 MR spectroscopy is feasible for repeatable quantification of IMCL concentrations in longitudinal studies of muscle metabolism. (c) RSNA, 2005 C1 Massachusetts Gen Hosp, Div Musculoskeletal Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging, 15 Parkman St,WACC 515, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu NR 24 TC 38 Z9 42 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 AUG PY 2005 VL 236 IS 2 BP 609 EP 614 DI 10.1148/radiol.2362041661 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200032 PM 16040916 ER PT J AU Dalal, T Kalra, MK Rizzo, SMR Schmidt, B Suess, C Flohr, T Blake, MA Saini, S AF Dalal, T Kalra, MK Rizzo, SMR Schmidt, B Suess, C Flohr, T Blake, MA Saini, S TI Metallic prosthesis: Technique to avoid increase in CT radiation dose with automatic tube current modulation in a phantom and patients SO RADIOLOGY LA English DT Article ID MULTIDETECTOR BODY CT; OPTIMIZATION; ARTIFACTS AB The institutional review board approved this Health Insurance Portability and Accountability Act-compliant study protocol, with waiver of informed consent. The purpose of the study was to retrospectively evaluate the combined automatic tube current modulation technique in patients with orthopedic metallic prostheses. Five hundred abdominal-pelvic computed tomographic (CT) studies performed with combined modulation technique were reviewed to identify nine patients with metallic prostheses (mean age, 66 years; range, 35-86 years; male-female ratio, 5:4). On the basis of age and transverse abdominal images, these patients were matched with nine others with no metallic prostheses (mean age, 56 years; range, 36-72 years; male-female ratio, 4:5) who were control patients. Images were graded for extent and severity of streak artifacts (grade 1, streak artifact present but not substantially compromising evaluation of adjacent structures; grade 2, streak artifact present and slightly compromising evaluation of adjacent structures; and grade 3, streak artifact present and severely compromising evaluation of adjacent structures). Student t test was performed for statistical analysis. There was no difference in mean effective tube current-time product between study and control patients (P >.49). With automatic tube current modulation, an increase in CT dose caused by metallic prostheses can be successfully avoided.(c) RSNA, 2005. C1 Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Siemens Med Solut, Forchheim, Germany. RP Kalra, MK (reprint author), Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. EM mkalra@emory.edu NR 12 TC 13 Z9 15 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2005 VL 236 IS 2 BP 671 EP 675 DI 10.1148/radiol.2362041565 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200043 PM 16040924 ER PT J AU Varghese, JC Hahn, PF Harisinghani, MG Hayat, SM Gervais, DA Hooper, DC Mueller, PR AF Varghese, JC Hahn, PF Harisinghani, MG Hayat, SM Gervais, DA Hooper, DC Mueller, PR TI Fungus-infected fluid collections in thorax or abdomen: Effectiveness of percutaneous catheter drainage SO RADIOLOGY LA English DT Article; Proceedings Paper CT 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2001 CL CHICAGO, IL SP Radiol Soc N Amer ID SURGICAL PATIENTS; TORULOPSIS-GLABRATA; ABSCESS DRAINAGE; INTRAABDOMINAL ABSCESSES; ABDOMINAL ABSCESSES; GUIDED DRAINAGE; HEPATIC-ABSCESS; FUNGEMIA; DIAGNOSIS; FAILURE AB PURPOSE: To retrospectively evaluate the effectiveness of percutaneous catheter drainage in the treatment of fungus-infected fluid collections in the thorax or abdomen and to identify any factor that may be predictive of a poor clinical outcome. MATERIALS AND METHODS: Approval for this study was obtained from the hospital ethics subcommittee on human studies. Because the study was retrospective, patient informed consent was not required. This study was compliant with the Health Insurance Portability and Accountability Act. Retrospective analysis was performed of cases of fungus-infected fluid collections in the thorax or abdomen treated by using percutaneous catheter drainage in 60 patients (36 male and 24 female patients; mean age, 57 years; range, 2 months to 91 years) during 5 years. The patient medical records were reviewed to identify recognized factors for predisposition to fungal infection. The details of percutaneous catheter drainage and microbiologic findings were recorded. The technical success (ability of catheters placed to drain collections treated) and the clinical success (ability of patients to recover fully without surgery) of percutaneous catheter drainage were determined. A multifactor logistic regression analysis was performed to identify any clinical or microbiologic factor predictive of a poor clinical outcome. RESULTS: Seventy-three fungus-infected fluid collections were drained in 60 patients. The collections originated from the pleura (n = 6), mediastinum (n = 2), liver (n = 3), pancreas (n = 5), obstructed biliary or urinary tract (n = 9), gallbladder (n 1), and abdominopelvic area (n = 47). The technical success rate for catheter drainage was 79% (41 of 52 patients); the clinical success rate, 57% (34 of 60 patients). Twenty (33%) patients died from all causes during hospital admission. Multifactor logistic regression analysis was used to identify predictors of a poor clinical outcome; complexity of collection, history of malignancy, and admission to intensive care unit were significant (P <.03) and independent predictors. CONCLUSION: Despite a moderately high technical success rate with percutaneous catheter drainage of fungus-infected fluid collections, clinical success rate was much lower. Both imaging appearance (complexity of collection) and clinical factors (history of malignancy, admission to intensive care unit) influenced prognosis. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Infect Control Unit, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270-E, Boston, MA 02114 USA. EM phahn@partners.org NR 34 TC 5 Z9 5 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2005 VL 236 IS 2 BP 730 EP 738 DI 10.1148/radiol.2362031044 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947TM UT WOS:000230670200051 PM 16040928 ER PT J AU Fischer, KA Van Leyen, K Lovercamp, KW Manandhar, G Sutovsky, M Feng, D Safranski, T Sutovsky, P AF Fischer, KA Van Leyen, K Lovercamp, KW Manandhar, G Sutovsky, M Feng, D Safranski, T Sutovsky, P TI 15-Lipoxygenase is a component of the mammalian sperm cytoplasmic droplet SO REPRODUCTION LA English DT Article ID BOAR SPERM; ORGANELLE DEGRADATION; DEPENDENT PROTEOLYSIS; SPERMATOZOA; LIPOXYGENASE; RETICULOCYTES; MITOCHONDRIA; EPIDIDYMIS; IMMUNOFLUORESCENCE; SPERMATOGENESIS AB Lipoxygenases (LOXs) are a family of enzymes capable of peroxidizing phospholipids. A member of the LOX family of enzymes, 15-LOX, participates in the degradation of mitochondria and other organelles within differentiating red blood cells, the reticulocytes. The present study provides biochemical and immunocytochemical evidence for the presence of 15-LOX in the sperm cytoplasmic droplet (CD). Testicular, epididymal and ejaculated spermatozoa were evaluated for the presence of 15-LOX using an affinity-purified immune serum raised against a synthetic peptide corresponding to the C-terminal sequence of rabbit reticulocyte 15-LOX. Western blotting revealed an appropriate single band of similar to 81 kDa in boar spermatozoa but not in boar seminal plasma. When ejaculated boar spermatozoa were subjected to separation on a 45/90% Percoll gradient, 15-LOX co-migrated with the immotile sperm and cellular debris/CD fractions, but not with the motile sperm fraction containing morphologically normal spermatozoa without CDs. Varied levels of 15-LOX were expressed in ejaculated sperm samples from boars with varied semen quality. By immunofluorescence, prominent 15-LOX immunoreactivity was found within the residual body in the testis and within the CDs from caput, corpus and cauda epididymal and ejaculated spermatozoa. Components of the ubiquitin-dependent proteolytic pathway, which is thought to facilitate both spermiogenesis and reticulocyte organelle degradation, were also detected in the sperm CD. These included ubiquitin, the ubiquitin-conjugating enzyme E2, the ubiquitin C-terminal hydrolase PGP 9.5, and various 20S proteasomal core subunits of the alpha- and beta-type. The 15-LOX and various components of the ubiquitin-proteasome pathway were also detected in sperm CDs of other mammalian species, including the human, mouse, stallion and wild babirusa boar. We conclude that 15-LOX is prominently present in the mammalian sperm CD and thus may contribute to spermiogenesis, CD function or CD removal. C1 Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Clin Obstet & Gynecol, Columbia, MO 65211 USA. Univ Missouri, Dept Obstet & Gynecol, Columbia, MO 65211 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. RP Sutovsky, P (reprint author), Univ Missouri, Div Anim Sci, S141 ASRC,920 E Campus Dr, Columbia, MO 65211 USA. EM sutovskyp@missouri.edu RI van Leyen, Klaus/C-9126-2013 NR 26 TC 33 Z9 40 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD AUG PY 2005 VL 130 IS 2 BP 213 EP 222 DI 10.1530/rep.1.00646 PG 10 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 958PT UT WOS:000231460900009 PM 16049159 ER PT J AU Kulkarni, RN AF Kulkarni, RN TI New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell mass SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Review DE insulin; IGF; islet beta-cells; insulin resistance; replication; knockout ID GROWTH-FACTOR-I; EPITHELIAL-MESENCHYMAL TRANSITIONS; MICE LACKING INSULIN; TYPE-1 IGF RECEPTOR; TRANSGENIC MICE; GLUCOSE-HOMEOSTASIS; PHOSPHOINOSITIDE 3-KINASE; MOLECULAR-MECHANISMS; PANCREATIC-ISLETS; TRANSCRIPTION FACTORS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU NIDDK NIH HHS [DKR0168721, K08 DK 02885, R01 DK67536, R03 DK66207] NR 144 TC 59 Z9 61 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD AUG PY 2005 VL 6 IS 3 BP 199 EP 210 DI 10.1007/s11154-005-3051-y PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980GS UT WOS:000233003200005 PM 16151624 ER PT J AU Sharpe, PT Young, CS AF Sharpe, PT Young, CS TI Test-tube teeth SO SCIENTIFIC AMERICAN LA English DT Article AB Tissue engineers working toward creating living replacement teeth take cues from nature as they coax disparate cell types to form a functional organ. Alternative methods include building teeth from existing dental cells or growing them from progenitor tissues. Both approaches have already produced structurally correct teeth. Remaining challenges include growing roots and identifying ideal raw materials for bioengineered human teeth, but progress has been rapid andtest-tube teeth may become the first engineered organs. C1 Guys Hosp, Dept Craniofacial Biol, London SE1 9RT, England. Univ London Kings Coll, London WC2R 2LS, England. Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Forsyth Inst, Boston, MA USA. RP Sharpe, PT (reprint author), Guys Hosp, Dept Craniofacial Biol, London SE1 9RT, England. NR 5 TC 50 Z9 57 U1 0 U2 8 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 AUG PY 2005 VL 293 IS 2 BP 34 EP 41 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946AZ UT WOS:000230545600029 PM 16053135 ER PT J AU Schipani, E AF Schipani, E TI Hypoxia and HIF-1 alpha in chondrogenesis SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE hypoxia; HIF-1 alpha; VHL; VEGF; chondrocytes ID TUMOR-SUPPRESSOR PROTEIN; ENDOCHONDRAL BONE-FORMATION; INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; GROWTH-PLATE; EPIPHYSEAL CHONDROCYTES; PROLYL HYDROXYLATION; SKELETAL DEVELOPMENT; CELL-PROLIFERATION; VEGF ISOFORMS AB In endochondral bone development chondrocytes undergo well-ordered and controlled phases of proliferation, hypertrophic differentiation, mineralization of the surrounding matrix, death, blood vessel invasion, and finally replacement of cartilage with bone. The chondrocytic growth plate is a unique mesenchymal tissue, as it is avascular but it requires blood vessel invasion, i.e. the angiogenic switch, in order to be replaced by bone. We have recently provided evidence that the growth plate is hypoxic during fetal development. Adaptation to hypoxia is a critical event in numerous pathological settings, such as tumor progression and survival of tissues in which blood flow has been suddenly interrupted. One of the hallmarks of the response to hypoxia is activation of the transcription factor HIF-1 alpha. The von Hippel Lindau tumor suppressor protein VHL is a component of a ubiquitin ligase promoting proteolysis of HIF-1 alpha. By using a genetic approach, we have demonstrated the essential role of the hypoxia/VHL/HIF-1 alpha pathway in endochondral bone development. Hypoxia-dependent up regulation of HIF-1 alpha transcriptional activity is critical for survival of hypoxic chondrocyte, and it shapes up the fetal growth plate by inhibiting chondrocyte proliferation, increasing matrix accumulation and probably modulating cell size. The findings overall highlight the usefulness of studying fetal growth plate development as a model to address issues such as adaptation of normal tissues to hypoxia, survival of hypoxic cells, and regulation of the angiogenic switch. They also demonstrate a crucial role of hypoxia and HIF-1 alpha in development and differentiation. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR 048191] NR 54 TC 62 Z9 66 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD AUG-OCT PY 2005 VL 16 IS 4-5 BP 539 EP 546 DI 10.1016/j.semcdb.2005.03.003 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 969UK UT WOS:000232260300009 PM 16144691 ER PT J AU Hirschkowitz, M Schmidt, MH AF Hirschkowitz, M Schmidt, MH TI Sleep-related erections: Clinical perspectives and neural mechanisms SO SLEEP MEDICINE REVIEWS LA English DT Review DE sleep-related erections; nocturnal penile tumescence; erectile dysfunction; mechanisms of erection ID NOCTURNAL PENILE TUMESCENCE; FOREBRAIN INHIBITORY MECHANISMS; MEDIAL PREOPTIC AREA; MALE-RATS; COPULATORY-BEHAVIOR; PARADOXICAL SLEEP; HYPOGONADAL MEN; BASAL FOREBRAIN; SEXUAL-BEHAVIOR; NUCLEUS PARAGIGANTOCELLULARIS AB Involuntary sleep-related erections (SREs) occur naturally during REM sleep in sexually potent men and other mammals. The regularity of their pattern and non-volitional nature made SREs useful clinically for differentiating psychogenic and organic erectile dysfunction (ED) in candidates for surgical intervention. Normative data available for different age groups added to the attractiveness of SRE measurement for clinical decision-making. Clinical SIRE testing is less commonly applied today with the advent of minimally invasive medical therapies for ED. Nonetheless, as an objective measure of erectile function, SRE recording for research provides a precise technique for examining the mechanisms of erection and is still conducted to resolve legal disputes. SIRE alterations provoked hormonally and pharmacologically are discussed. Different SIRE patterns are associated with comorbid factors and some of these are illustrated, described, or both. Recording techniques developed for rats have proved extremely valuable for furthering our understanding of brain centers mediating erectile response. Data from lesion and stimulation studies are examined in the present review, moving us a step closer to understanding the underpinnings of erectile function. Published by Elsevier Ltd. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Sleep Ctr, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Sleep Ctr, Dept Med, Houston, TX 77030 USA. Ohio Sleep Med & Neurosci Inst, Dublin, OH 43017 USA. RP Hirschkowitz, M (reprint author), VAMC, Sleep Ctr 1111, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM maxh@bcm.tmc.edu NR 121 TC 33 Z9 37 U1 1 U2 12 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD AUG PY 2005 VL 9 IS 4 BP 311 EP 329 DI 10.1016/j.smrv.2005.03.001 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 954QQ UT WOS:000231170000006 PM 15994100 ER PT J AU Fuchs, JR Hannouche, D Terada, S Zand, S Vacanti, JP Fauza, DO AF Fuchs, JR Hannouche, D Terada, S Zand, S Vacanti, JP Fauza, DO TI Cartilage engineering from ovine umbilical cord blood mesenchymal progenitor cells SO STEM CELLS LA English DT Article DE cord blood cells; differentiation; fetal stem cells; in vitro differentiation; stem/progenitor cell; stromal cells; TGF-beta 1; tissue regeneration ID STEM-CELLS; BONE-MARROW; IN-UTERO; TRACHEAL AUGMENTATION; FETAL CELLS; DIFFERENTIATION; TRANSPLANTATION; IDENTIFICATION; CORDOCENTESIS; CHONDROCYTES AB We aimed to determine whether three-dimensional (3D) cartilage could be engineered from umbilical cord blood (CB) cells and compare it with both engineered fetal cartilage and native tissue. Ovine mesenchymal progenitor cells were isolated from CB samples (n = 4) harvested at 80-120 days of gestation by low-density fractionation, expanded, and seeded onto polyglycolic acid scaffolds. Constructs (n = 28) were maintained in a rotating bioreactor with serum-free medium supplemented with transforming growth factor-beta 1 for 4-12 weeks. Similar constructs seeded with fetal chondrocytes (n = 13) were cultured in parallel for 8 weeks. All specimens were analyzed and compared with native fetal cartilage samples (n = 10). Statistical analysis was by analysis of variance and Student's t-test (p < .01). At 12 weeks, CB constructs exhibited chondrogenic differentiation by both standard and matrix-specific staining. In the CB constructs, there was a significant time-dependent increase in extracellular matrix levels of glycosaminoglycans (GAGS) and type-II collagen (C-II) but not of elastin (EL). Fetal chondrocyte and CB constructs had similar GAG and C-II contents, but CB constructs had less EL. Compared with both hyaline and elastic native fetal cartilage, C-II and EL levels were, respectively, similar and lower in the CB constructs, which had correspondingly lower and similar GAG levels than native hyaline and elastic fetal cartilage. We conclude that CB mesenchymal progenitor cells can be successfully used for the engineering of 3D cartilaginous tissue in vitro, displaying select histological and functional properties of both native and engineered fetal cartilage. Cartilage engineered from CB may prove useful for the treatment of select congenital anomalies. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Minimally Invas Surg, Boston, MA 02115 USA. RP Fauza, DO (reprint author), Childrens Hosp, Dept Surg, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. EM dario.fauza@childrens.harvard.edu NR 29 TC 46 Z9 53 U1 0 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD AUG PY 2005 VL 23 IS 7 BP 958 EP 964 DI 10.1634/stemcells.2004-0310 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 957MN UT WOS:000231374000011 PM 16043460 ER PT J AU Parmar, K Burdick, D Ethier, M Clyne, J Mauch, P AF Parmar, K Burdick, D Ethier, M Clyne, J Mauch, P TI Murine side population cells contain cobblestone area-forming cell activity in mobilized blood SO STEM CELLS AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Keystone Symposium from Stem Cells to Therapy CY MAR 29-APR 03, 2003 CL Steamboat Springs, CO ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; IN-VIVO; FUNCTIONAL-PROPERTIES; CYTOTOXIC AGENTS; PROGENITOR CELLS; DYE EFFLUX; MICE AB Primitive hematopoietic stem cells ( HSCs) can be purified from murine bone marrow by sorting Hoechst 33342- effluxing side population ( SP) cells. The aim of this study was to establish whether SP cells from peripheral blood contain primitive HSCs and whether this is altered in mice following mobilization. SP cells were analyzed and isolated from bone marrow and blood of mice after mobilization; the HSC content of isolated SP cells was determined through surrogate cobblestone area- forming cell ( CAFC) assays. SP cells in normal blood were not found in the high Hoechst dye effluxing portion of the SP tail, did not express the stem cell markers c- Kit and CD34, and did not have measurable CAFC activity. In contrast, SP cells in mobilized blood expressed both stem cell markers, contained cells in the high dye efflux portion of the SP tail, and displayed significant day28 to day- 35 CAFC activity with 165- to 334- fold enrichment. In comparison to mobilized blood SP cells, normal marrow SP cells contained a higher proportion of cells expressing c- Kit and CD34 and had a greater percentage of cells in the high Hoechst dye- effluxing portion of the SP tail. Analysis of SP cells in the bone marrow after mobilization revealed a decrease in the frequency of SP cells, in expression of c- Kit and Sca (+) CD34(+)/ CD34(-), and in day- 7 to day- 35 CAFC activity, consistent with mobilization into blood. We conclude that murine SP cells mobilized into blood contain primitive hematopoietic stem cell activity ( day- 28 to day- 35 CAFC activity). This model offers a means to study the mechanisms of mobilization of primitive stem cells directly in a murine model. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Mauch, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM pmauch@partners.org FU NCI NIH HHS [R01 CA10941-30] NR 49 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD AUG PY 2005 VL 14 IS 4 BP 452 EP 461 DI 10.1089/scd.2005.14.452 PG 10 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 961WF UT WOS:000231691800013 PM 16137234 ER PT J AU Studenski, S Duncan, PW Perera, S Reker, D Lai, SM Richards, L AF Studenski, S Duncan, PW Perera, S Reker, D Lai, SM Richards, L TI Daily functioning and quality of life in a randomized controlled trial of therapeutic exercise for subacute stroke survivors SO STROKE LA English DT Article DE disability; exercise; quality of life; rehabilitation; stroke ID POST-STROKE; REHABILITATION; PERFORMANCE; COMMUNITY AB Background and Purpose - The ability of therapeutic exercise after stroke to improve daily functioning and quality of life (QOL) remains controversial. We examined treatment effects on these outcomes in a randomized controlled trial (RCT) of exercise in subacute stroke survivors. Methods - This is a secondary analysis of a single-blind RCT of a 12-week program versus usual care. Baseline, post-treatment and 6-month post-treatment daily functioning and QOL were assessed by Barthel index, Functional Independence Measure, instrumental activities of daily living, Medical Outcomes Study short-form 36-item questionnaire (SF-36), and Stroke Impact Scale (SIS). Results - Of 100 randomized subjects, 93 completed the postintervention assessment, ( mean age 70; 54% male; 81% white; mean Orpington Prognostic Score 3.4), and 80 had 6-month post-treatment assessment. Immediately after intervention, the intervention group improved more than usual care in SF-36 social function ( 14.0 points; P = 0.0051) and in SIS ( strength [9.2 points; P = 0.0003], emotion [5.6 points; P = 0.0240], social participation [6.6 points; P = 0.0488], and physical function [5.0 points; P = 0.0145]). Treatment was marginally more effective on Barthel score (3.3 points; P = 0.0510), SF-36 ( physical function [6.8 points; P = 0.0586], physical role function [14.4 points; P = 0.0708]), and SIS upper extremity function (7.2 points; P = 0.0790). Effects were diluted 6 months after treatment ended. Conclusion - This rehabilitation exercise program led to more rapid improvement in aspects of physical, social, and role function than usual care in persons with subacute stroke. Adherence interventions to promote continued exercise after treatment might be needed to continue benefit. C1 Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Florida, Dept Hlth Serv Res, Gainesville, FL USA. Univ Florida, Brooks Ctr Rehabil Studies, Gainesville, FL USA. Univ Kansas, N Florida S Georgia Vet Hlth Syst, Gainesville Dept Hlth Policy & Adm, Lawrence, KS 66045 USA. Kansas City VA Med Ctr, Kansas City, KS USA. Univ Kansas, Dept Prevent Med & Publ Hlth, Lawrence, KS 66045 USA. Univ Florida, Dept Occupat Therapy, Gainesville, FL USA. RP Studenski, S (reprint author), 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM sas33@pitt.edu RI Perera, Subashan/D-7603-2014 FU NIA NIH HHS [P60AG14635] NR 25 TC 72 Z9 82 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2005 VL 36 IS 8 BP 1764 EP 1770 DI 10.1161/01.STR.0000174192.87887.70 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 949WA UT WOS:000230817600026 PM 16040590 ER PT J AU Stone, DH Al-Badawi, H Conrad, ME Stoner, MC Entabi, F Cambria, RP Watkins, MT AF Stone, DH Al-Badawi, H Conrad, ME Stoner, MC Entabi, F Cambria, RP Watkins, MT TI PJ34, a poly-ADP-ribose polymerase inhibitor, modulates renal injury after thoracic aortic ischemia/reperfusion SO SURGERY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 2005 CL Nashville, TN SP Soc Univ Surg ID THORACOABDOMINAL ANEURYSM REPAIR; SPINAL-CORD ISCHEMIA; SWINE FEVER VIRUS; ADHESION MOLECULE-1; POTENT INHIBITOR; RISK-FACTOR; SYNTHETASE; FAILURE; REPLACEMENT; EXPERIENCE AB Background. These experiments sought to evaluate the effects of PJ34, a poly-ADP-ribose polymerase inhibitor, on molecular indices of renal injury, mitochondrial function, tissue thrombosis, and fibrinolysis after thoracic aortic ischemia/reperfusion (TAR). Methods. Forty-three 129S1/SvImj mice were subjected to 11 minutes of TAR followed by 48 hours of reperfusion. Experimental groups included untreated normal saline (NS) controls (UC), (n = 15, 0.5 mL NS ip) or PJ34 (PJ) (n = 17, PJ34 10 mg/kg ip, I hour before and after TAR). Sham (SH) mice (n = 11) underwent median sternotomy (heparin, NS ip) without TAR. Forty-eight hours after TAR or sham operation, kidney mitochondrial activity (using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium [MM), D-dimer and thrombin-antithrombin III (TAT) complex levels were measured. Levels of messenger RNA for neutrophil gelatinase-associated lipocalin (NGAL), a marker for renal injury, were also measured by reverse transcriptase-polymerase chain reaction. Results. PJ34 improves renal mitochondrial activity after 48 hours of TAR, compared with untreated control animals (UC, 87.6 +/- 2.2 %; PJ, 151.4 +/- 9.5 %; P <. 001). PJ34 did not alter the increase in renal D-dimer levels by 48 hours reperfusion (UC, 1.37 +/- 0.09 U; PJ, 1.1 +/- 0. 14 U; SH, 0.82 +/- 0.06 U; P <.05). TAR did not alter renal levels of TAT expression among groups (UC, 0. 103 +/- 0.034; PJ, 0. 067 +/- 0.008; SH, 0.106 +/- 0.027; P =. 619). The incidence of significantly increased NGAL among UC mice was 1415 +/- 823.6 (n = 12), compared with 29.6 +/- 20.8 (n = 10) in the PJ34-treated group (P <.014). Conclusions. PJ34 preserves renal mitochondrial activity and decreases steady-state levels of NGAL after TAR. TAR did increase markers of fibrinolysis in renal tissue but their increase did not correlate with renal injury or PJ34 treatment. These studies indicate that PJ34 confers protection against TAR and suggest that PARP may represent a novel target for reducing perioperative renal injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Vasc & Endovasc Surg, Cambridge, MA USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 27 TC 8 Z9 10 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2005 VL 138 IS 2 BP 368 EP 374 DI 10.1016/j.surg.2005.06.004 PG 7 WC Surgery SC Surgery GA 966KY UT WOS:000232019800033 PM 16153449 ER PT J AU Conrad, MF Stone, DH Albadawi, H Hua, HT Entabi, F Stoner, MC Watkins, MT AF Conrad, MF Stone, DH Albadawi, H Hua, HT Entabi, F Stoner, MC Watkins, MT TI Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion SO SURGERY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 2005 CL Nashville, TN SP Soc Univ Surg ID ISCHEMIA-REPERFUSION INJURY; LOWER-EXTREMITY ISCHEMIA; CHEMOKINES; MUSCLE; INTERLEUKIN-1; ANGIOGENESIS; CYTOKINES AB Background. These experiments were designed to quantitatively compare the Patterns of tissue thrombosis, cytokine response, and tissue viability in a murine model of partial (PI) versus complete hindlimb ischemia (CI), alone or with reperfusion (RE). Methods. The control tension tourniquet was used to establish either PI or CI in the unilateral mouse hindlimb for 3 hours followed by 0, 4, and 24 hours of RE. Muscle viability, local neutrophil chemoattractant protein, interleukin 6, interleukin I beta, D-dimer, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, and. tissue plasminogen activator levels were measured in protein extracts for each experimental interval. Results. Tissue viability after CI and. 24 hours of RE was significantly less than tissue subjected to PI and 24 hours of RE (96% +/- 16 PI, 64% +/- 4 CI, P =. 02). The local cytokine response was initially elevated in the PI group but dissipated by 24RE. In contrast, the local cytokine response to CI alone was small but greatly increased by 24RE. The thrombotic response to PI was increased throughout ischemia/reperfusion. While thrombosis during CI alone was negligible, reperfusion led to a significant thrombotic response. Conclusions. Biochemical markers for tissue viability, thrombosis, and cytokine mediated inflammation differ signficantly in mice subjected to moderate and severe hindlimb ischemia/reperfusion. These biochemical markers may facilitate stratification of patients in clinical trials for treatment of ischemia/reperfusion injury and contribute to interpretation of their outcomes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Vasc & Endovasc Surg, Cambridge, MA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 25 TC 11 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2005 VL 138 IS 2 BP 375 EP 381 DI 10.1016/j.surg.2005.06.005 PG 7 WC Surgery SC Surgery GA 966KY UT WOS:000232019800034 PM 16153450 ER PT J AU Dzik, WH AF Dzik, WH TI The impact of the National Blood Foundation SO TRANSFUSION LA English DT Article ID WHITE CELLS WBCS; PLATELETS C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2005 VL 45 IS 2 SU S BP 41S EP 43S DI 10.1111/j.1537-2995.2005.00532.x PG 3 WC Hematology SC Hematology GA 954KS UT WOS:000231154600006 PM 16086786 ER PT J AU Masland, RH AF Masland, RH TI The many roles of starburst amacrine cells SO TRENDS IN NEUROSCIENCES LA English DT Article ID RABBIT RETINA; DIRECTIONAL SELECTIVITY; CHOLINERGIC NEURONS; GABA; ACETYLCHOLINE; MECHANISMS; LIGHT AB Starburst amacrine cells release two classical neurotransmitters, ACh and GABA. In a tour de force of paired-cell recording, Zheng et al. now show that the starburst cells are mutually excitatory during early development but mutually inhibitory in adult animals. The change occurs by remodeling of both the cholinergic and the GABAergic synapses between starburst cells. The finding gives a precise mechanistic basis for the developmental waves of activity in the retina. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM masland@helix.mgh.harvard.edu NR 18 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD AUG PY 2005 VL 28 IS 8 BP 395 EP 396 DI 10.1016/j.tins.2005.06.002 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 957AU UT WOS:000231342400001 PM 15979167 ER PT J AU Guzzo, TJ Vira, M Hwang, WT D'Amico, A Tomaszewski, J Whittington, R Wein, AJ VanArsdalen, K Malkowicz, SB AF Guzzo, TJ Vira, M Hwang, WT D'Amico, A Tomaszewski, J Whittington, R Wein, AJ VanArsdalen, K Malkowicz, SB TI Impact of multiple biopsy cores on predicting final tumor volume in prostate cancer detected by a single microscopic focus of cancer on biopsy SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; NEEDLE-BIOPSY; CLINICALLY IMPORTANT; SYSTEMATIC BIOPSIES; PATHOLOGICAL STAGE; SPECIMENS; ADENOCARCINOMA; CARCINOMA; OUTCOMES; ANTIGEN AB Objectives. To compare the impact that the number of biopsy cores have on final pathologic findings when minimal disease is detected at biopsy. Discordance has been noted between transrectal ultrasound-guided biopsy results and tumor volume even when minimal amounts of tumor are found on biopsy. Methods. We identified patients who had undergone radical retropubic prostatectomy for a single microscopic focus of adenocarcinoma from a prospectively maintained surgical database. Patients were stratified into two groups: those with six biopsies or less and those with seven or more. The Gleason score, margin status, presence of extracapsular extension, and percentage of tumor volume were compared. Results. A total of 102 patients in our database had a single microscopic focus of adenocarcinoma detected by needle biopsy. Of these patients, 65 underwent six or fewer biopsies and 37 underwent seven or more at transrectal ultrasonography. Of the 37 patients in group 2, 27 (73%) had a final tumor volume of less than 5% compared with 24 (37%) of 65 patients in group I (P = 0.002). Of the group 2 patients, 15 (75%) with Stage T1c had an estimated tumor volume of less than 5% compared with only 11 (34%) in group 1 (P = 0.01). No statistically significant difference was noted between the two groups for margin status, presence of extracapsular extension, or Gleason score. Conclusions. A single microscopic focus of cancer obtained after multiple cores predicts for a significantly lower tumor volume on final pathologic examination across clinical stages. In the context of greater tissue sampling, the minimal disease designation may carry more predictive value and be a useful parameter in stratifying patients with Stage T1c and other good-risk factors with regard to surgical outcome. C1 Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Guzzo, TJ (reprint author), Hosp Univ Penn, Dept Urol, 3400 Spruce St,9 Penn Tower, Philadelphia, PA 19104 USA. EM t.guzzo@att.net NR 15 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2005 VL 66 IS 2 BP 361 EP 365 DI 10.1016/j.urology.2005.02.029 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 968JB UT WOS:000232157600028 PM 16098364 ER PT J AU Taplin, ME George, DJ Halabi, S Sanford, B Febbo, PG Hennessy, KT Mihos, CG Vogelzang, NJ Small, EJ Kantoff, PW AF Taplin, ME George, DJ Halabi, S Sanford, B Febbo, PG Hennessy, KT Mihos, CG Vogelzang, NJ Small, EJ Kantoff, PW TI Prognostic significance of plasma chromogranin A levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study SO UROLOGY LA English DT Article ID DISEASE-SPECIFIC SURVIVAL; ENDOTHELIAL GROWTH-FACTOR; NEUROENDOCRINE DIFFERENTIATION; RADICAL PROSTATECTOMY; ENDOCRINE THERAPY; FOLLOW-UP; CARCINOMA; PROGRESSION; PREDICTORS; ADENOCARCINOMA AB Objectives. To test the hypothesis that chromogranin A (CgA) levels are prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC). The extent of neuroendocrine differentiation in prostate cancer correlates with aggressive disease and with progression to HRPC. Plasma CgA levels in patients with prostate cancer may reflect the extent of the tumor neuroendocrine phenotype. Methods. Pretreatment plasma was collected from 390 patients with metastatic HRPC enrolled in the Cancer and Leukemia Group B (CALGB) 9480 trial, a study of three different doses of suramin. Plasma CgA levels were determined in 321 samples in duplicate using a quantitative sandwich immunoassay. The proportional hazards model was used to assess the prognostic significance of CgA in predicting overall survival. Results. The median plasma CgA level was 12 U/L (interquartile range 7.7 to 19.3). In univariate analysis, plasma CgA correlated inversely with survival times, with a survival time of 17 months for low CgA (less than 12 U/L, 95% CI 14 to 19) compared with 11 months for high CgA (95% CI 8 to 14, P = 0.014) and at all exploratory cutpoints, including CgA of 9.5 U/L or less versus greater than 9.5 U/L, with survival of 19 months compared with 12 months (P = 0.0015). In multivariate models (adjusting for performance status, prostate-specific antigen, and lactate dehydrogenase), the plasma CgA levels remained predictive of overall survival. Conclusions. These results support the hypothesis that serum CgA levels correlate with outcome in patients with HRPC, although the clinical significance needs to be established in confirmatory studies before incorporation of CgA measurements in clinical practice. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Nevada Canc Inst, Las Vegas, NV USA. Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94143 USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 1230 Dana Bldg,44 Binney St, Boston, MA 02115 USA. EM mtaplin@partners.org NR 28 TC 58 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2005 VL 66 IS 2 BP 386 EP 391 DI 10.1016/j.urology.2005.03.040 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 968JB UT WOS:000232157600033 PM 16098367 ER PT J AU Nimsky, C Grummich, P Sorensen, AG Fahlbusch, R Ganslandt, O AF Nimsky, C Grummich, P Sorensen, AG Fahlbusch, R Ganslandt, O TI Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation SO ZENTRALBLATT FUR NEUROCHIRURGIE LA English DT Article DE diffusion tensor imaging; functional neuronavigation; functional magnetic resonance imaging; white matter tracts ID SPACE-OCCUPYING LESIONS; WHITE-MATTER TRACTS; MAGNETIC-RESONANCE; BRAIN-TUMORS; FIBER TRACKING; MOTOR CORTEX; INITIAL-EXPERIENCE; GRADE GLIOMAS; IN-VIVO; MAGNETOENCEPHALOGRAPHY AB Object: The aim of this study was to investigate whether diffusion tensor imaging (DTI) can be integrated into functional navigation for the intraoperative visualization of the pyramidal tract. Methods: A single-shot spin-echo diffusion-weighted echo planar imaging sequence on a 1.5 T magnetic resonance (MR) scanner was used for DTI. One null image and six diffusion-weighted,images (high B value 1000 mm/s(2)) were obtained. Color-encoded fractional anisotropy maps of the principal eigenvector rendered as a boxoid within each voxel were used for segmentation of the pyramidal tract. The segmented images were rigidly registered with a T(1)-weighted gradient echo 3D dataset for navigation in 16 patients with gliomas. In tumors adjacent to the motor cortex (n = 6) data from functional MR imaging were co-registered. Results: The whole DTI processing lasted about 25-30 minutes in each case. In all cases DTI could be integrated into the navigational dataset resulting in an intraoperative visualization of the pyramidal tract by microscope-based navigation. Navigational accuracy measured as the target registration error was 1.2 +/- 0.46 mm. Registration of fractional anisotropy maps with the 3D navigational dataset was possible with an error of less than 2 mm. Co-registration with fMRI was consistent with DTI data. A neurological deterioration was observed only in one patient. Conclusions: DTI can be reliably integrated into navigational datasets. Thus, microscope-based neuronavigation can be used for an intraoperative visualization of the course of the pyramidal tract. However, a possible shifting of the pyramidal tract has to be taken into account after major tumor parts are removed. C1 Univ Erlangen Nurnberg, Dept Neurosurg, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Boston, MA 02114 USA. RP Nimsky, C (reprint author), Univ Erlangen Nurnberg, Dept Neurosurg, Schwabachanlage 6, D-91054 Erlangen, Germany. EM nimsky@nch.imed.uni-erlangen.de RI Nimsky, Christopher/E-3702-2014 NR 39 TC 48 Z9 53 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0044-4251 J9 ZBL NEUROCHIR JI Zent.bl. Neurochir. PD AUG PY 2005 VL 66 IS 3 BP 133 EP 141 DI 10.1055/s-2005-836606 PG 9 WC Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA 959YN UT WOS:000231555600005 PM 16116556 ER PT J AU Heuze-Vourc'h, N Liu, M Dalwadi, H Baratelli, FE Zhu, L Goodglick, L Pold, M Sharma, S Ramirez, RD Shay, JW Minna, JD Strieter, RM Dubinett, SM AF Heuze-Vourc'h, N Liu, M Dalwadi, H Baratelli, FE Zhu, L Goodglick, L Pold, M Sharma, S Ramirez, RD Shay, JW Minna, JD Strieter, RM Dubinett, SM TI IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE interleukin-20; cyclooxygenase-2; prostaglandin-E-2; lung cancer; angiogenesis; NSCLC; human bronchial epithelial cells ID CELL LUNG-CANCER; CYCLOOXYGENASE-2; INTERLEUKIN-10; PREVENTION; RECEPTOR; TARGET AB COX-2 overexpression and subsequent PGE(2) production are frequently associated with non-small cell lung cancer and are implicated in tumor-mediated angiogenesis. Here, we report for the first time that IL-20 downregulates COX-2 and PGE(2) in human bronchial epithelial and endothelial cells. Flow cytometry analysis suggests that IL-20-dependent inhibition of COX-2/PGE(2) occurs through the IL-22R1/IL-2OR2 dimers. In addition, we report that IL-20 exerts anti-angiogenic effects, inhibiting experimental angiogenesis. IL-20-mediated inhibition of PMA-induced angiogenesis occurs through the COX-2 regulatory pathway. Altogether our findings revealed that IL-20 is a negative modulator of COX-2/PGE(2) and inhibits angiogenesis. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapuet Oncol Res, Dallas, TX USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90024 USA. EM sdubinett@mednet.ucla.edu RI Shay, Jerry/F-7878-2011; HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [R01 CA85686, CA-16042, P50 CA90388]; NIAID NIH HHS [AI-28697] NR 21 TC 30 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 29 PY 2005 VL 333 IS 2 BP 470 EP 475 DI 10.1016/j.bbrc.2005.05.122 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 944HU UT WOS:000230418700026 PM 15950941 ER PT J AU Johnson, J Bagley, J Skaznik-Wikiel, M Lee, HJ Adams, GB Niikura, Y Tschudy, KS Tilly, JC Cortes, ML Forkert, R Spitzer, T Iacomini, J Scadden, DT Tilly, JL AF Johnson, J Bagley, J Skaznik-Wikiel, M Lee, HJ Adams, GB Niikura, Y Tschudy, KS Tilly, JC Cortes, ML Forkert, R Spitzer, T Iacomini, J Scadden, DT Tilly, JL TI Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood SO CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MURINE HOMOLOG; PROPHASE I; MOUSE; EXPRESSION; GENE; MICE; FOLLICULOGENESIS; DEFICIENCY; PLASTICITY AB It has been suggested that germline stem cells maintain oogenesis in postnatal mouse ovaries. Here we show that adult mouse ovaries rapidly generate hundreds of oocytes, despite a small premeiotic germ cell pool. In considering the possibility of an extragonadal source of germ cells, we show expression of germline markers in bone marrow (BM). Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. Donor-derived oocytes are also observed in female mice following peripheral blood transplantation. Although the fertilizability and developmental competency of the BM and peripheral blood-derived oocytes remain to be established, their morphology, enclosure within follicles, and expression of germ-cell- and oocyte-specific markers collectively support that these cells are bona fide oocytes. These results identify BM as a potential source of germ cells that could sustain oocyte production in adulthood. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstetr & Gynecol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstetr & Gynecol, Boston, MA 02114 USA. EM jtilly@partners.org FU NIA NIH HHS [R01-AG012279, R01-AG024999]; NICHD NIH HHS [L50 HD048367]; NIEHS NIH HHS [R01-ES08430] NR 65 TC 399 Z9 434 U1 4 U2 38 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 29 PY 2005 VL 122 IS 2 BP 303 EP 315 DI 10.1016/j.cell.2005.06.031 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 951CR UT WOS:000230907000016 PM 16051153 ER PT J AU Lee, JT AF Lee, JT TI Regulation of X-chromosome counting by Tsix and Xite sequences SO SCIENCE LA English DT Article ID INACTIVATION CENTER; XIST GENE AB In mammals, X-inactivation establishes X-chromosome dosage parity between mates and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation "blocking factor" nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding Tsix and Xite genes as numerators. Homozygous deficiency of Tsix resulted in "chaotic choice" and a variable number of inactive X's, whereas overdosage of TsixlXite inhibited X-inactivation. Thus, counting was affected by specific TsixlXite mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one "blocking factor," but by both a "blocking" and a "competence" factor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Howard Hughes Med Inst,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Howard Hughes Med Inst,Dept Genet, Boston, MA 02114 USA. EM tee@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01-GM58839] NR 14 TC 93 Z9 98 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 29 PY 2005 VL 309 IS 5735 BP 768 EP 771 DI 10.1126/science.1113673 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 951NU UT WOS:000230938200049 PM 16051795 ER PT J AU Sieburth, D Ch'ng, Q Dybbs, M Tavazoie, M Kennedy, S Wang, D Dupuy, D Rual, JF Hill, DE Vidal, M Ruvkun, G Kaplan, JM AF Sieburth, D Ch'ng, Q Dybbs, M Tavazoie, M Kennedy, S Wang, D Dupuy, D Rual, JF Hill, DE Vidal, M Ruvkun, G Kaplan, JM TI Systematic analysis of genes required for synapse structure and function SO NATURE LA English DT Article ID PROTEIN-KINASE-C; CAENORHABDITIS-ELEGANS; NEUROMUSCULAR-JUNCTIONS; ACETYLCHOLINE-RELEASE; ACTIN CYTOSKELETON; DENDRITIC SPINES; NERVOUS-SYSTEM; UNC-13; TRANSMISSION; EXPRESSION AB Chemical synapses are complex structures that mediate rapid intercellular signalling in the nervous system. Proteomic studies suggest that several hundred proteins will be found at synaptic specializations. Here we describe a systematic screen to identify genes required for the function or development of Caenorhabditis elegans neuromuscular junctions. A total of 185 genes were identified in an RNA interference screen for decreased acetylcholine secretion; 132 of these genes had not previously been implicated in synaptic transmission. Functional profiles for these genes were determined by comparing secretion defects observed after RNA interference under a variety of conditions. Hierarchical clustering identified groups of functionally related genes, including those involved in the synaptic vesicle cycle, neuropeptide signalling and responsiveness to phorbol esters. Twenty-four genes encoded proteins that were localized to presynaptic specializations. Loss-of-function mutations in 12 genes caused defects in presynaptic structure. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu RI Ch'ng, QueeLim/C-5348-2009; Hill, David/B-6617-2011; OI Ch'ng, QueeLim/0000-0003-1941-3828; Rual, Jean-Francois/0000-0003-4465-8819; Dupuy, Denis/0000-0002-4781-5595 FU NIDDK NIH HHS [R01 DK070147] NR 54 TC 218 Z9 293 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 28 PY 2005 VL 436 IS 7050 BP 510 EP 517 DI 10.1038/nature03809 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 949LE UT WOS:000230788800052 PM 16049479 ER PT J AU Wang, D Kennedy, S Conte, D Kim, JK Gabel, HW Kamath, RS Mello, CC Ruvkun, G AF Wang, D Kennedy, S Conte, D Kim, JK Gabel, HW Kamath, RS Mello, CC Ruvkun, G TI Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants SO NATURE LA English DT Article ID C-ELEGANS; CAENORHABDITIS-ELEGANS; VULVAL DEVELOPMENT; LIN-35 RB; COMPLEX; PROTEIN; GENE; DROSOPHILA; HOMOLOG; LINE AB Caenorhabditis elegans homologues of the retinoblastoma (Rb) tumour suppressor complex specify cell lineage during development(1,2). Here we show that mutations in Rb pathway components enhance RNA interference (RNAi) and cause somatic cells to express genes and elaborate perinuclear structures normally limited to germline-specific P granules. Furthermore, particular gene inactivations that disrupt RNAi reverse the cell lineage transformations of Rb pathway mutants. These findings suggest that mutations in Rb pathway components cause cells to revert to patterns of gene expression normally restricted to germ cells. Rb may act by a similar mechanism to transform mammalian cells. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu NR 30 TC 165 Z9 209 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 28 PY 2005 VL 436 IS 7050 BP 593 EP 597 DI 10.1038/nature04010 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 949LE UT WOS:000230788800069 PM 16049496 ER PT J AU Kleinschmidt-DeMasters, BK Tyler, KL AF Kleinschmidt-DeMasters, BK Tyler, KL TI Brief report - Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN POLYOMAVIRUSES; DISEASE; ENCEPHALOMYELITIS; INTEGRIN; ANTIBODY AB A 46-year-old woman with relapsing-remitting multiple sclerosis died from progressive multifocal leukoencephalopathy (PM) after having received 37 doses of natalizumab (300 mg every four weeks) as part of a clinical trial of natalizumab and interferon beta-1a. PML was diagnosed on the basis of the finding of JC viral DNA in cerebrospinal fluid on polymerase-chain-reaction assay and was confirmed at autopsy. Nearly every tissue section from bilateral cerebral hemispheres contained either macroscopic or microscopic PML lesions. There was extensive tissue destruction and cavitation in the left frontoparietal area, large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes, which were positive for JC virus DNA on in situ hybridization. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kleinschmidt-DeMasters, BK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, B-216,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 13 TC 631 Z9 654 U1 2 U2 16 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 JUL 28 PY 2005 VL 353 IS 4 BP 369 EP 374 DI 10.1056/NEJMoa051782 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 949JW UT WOS:000230782800009 PM 15947079 ER PT J AU Tanabe, KK Blaszkowsky, LS Chung, RT Blake, MA Lauwers, GY AF Tanabe, KK Blaszkowsky, LS Chung, RT Blake, MA Lauwers, GY TI Case 23-2005: A 57-year-old man with a mass in the liver - Hepatocellular carcinoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PERCUTANEOUS ETHANOL INJECTION; RANDOMIZED CONTROLLED TRIAL; 2ND PRIMARY TUMORS; HEPATITIS-B; POSTOPERATIVE RECURRENCE; INTRAHEPATIC RECURRENCE; PROGNOSTIC INDEX; RESECTION; SURVIVAL; CIRRHOSIS C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. NR 47 TC 1 Z9 1 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 JUL 28 PY 2005 VL 353 IS 4 BP 401 EP 410 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 949JW UT WOS:000230782800015 PM 16049213 ER PT J AU D'Amico, AV Renshaw, AA Sussman, B Chen, MH AF D'Amico, AV Renshaw, AA Sussman, B Chen, MH TI Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID III RANDOMIZED TRIAL; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; ANTIGEN LEVELS; TRENDS AB Context Men with localized prostate cancer and a preoperative prostate-specific antigen (PSA) velocity greater than 2.0 ng/mL per year experience a 10-fold increase in prostate cancer-specific mortality despite surgery. Objective To assess whether a greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis was significantly associated with prostate cancer-specific mortality following radiation therapy (RT). Design, Setting, and Patients Between January 1, 1989, and December 1, 2002, 358 men treated with RT for localized prostate cancer formed the study cohort (median age at treatment, 71.2 (range, 43.2-83.5] years). A Cox regression multivariable analysis was used to evaluate whether a PSA velocity greater than 2.0 ng/mL per year was significantly associated with prostate cancer-specific mortality and all-cause mortality after controlling for prognostic factors available at diagnosis. Main Outcome Measure Time to prostate cancer-specific mortality for the 125 men with low-risk prostate cancer (clinical tumor category T1c or T2a and PSA level <10.0 ng/mL and Gleason score :56) and the 233 men with higher-risk disease, stratified by the PSA velocity. Results A PSA velocity greater than 2.0 ng/mL per year was significantly associated with a shorter time to prostate cancer-specific mortality (adjusted hazard ratio [HR], 12.0; 95% confidence interval [CI], 3.0-54.0; P=.001) and all-cause mortality (adjusted HR, 2.1; 95% Cl, 1.3-3.6; P=.005) when compared with men whose PSA velocity was 2.0 ng/mL per year or less. Men presenting with low-risk disease and a PSA velocity greater than 2.0 ng/mL per year had a 7-year estimate of prostate cancer-specific mortality of 19% (95% Cl, 2%-39%) compared with 0% for men whose PSA velocity was 2.0 ng/mL per year or less. The corresponding values for men with higher-risk disease were 24% (95% Cl, 12%-37%) and 4% (95% Cl, 0%-11%), respectively. Conclusions A greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis is associated with a significantly higher risk of death due to prostate cancer following RT despite having low-risk disease. Such men who are planning to undergo RT and are in good health could be considered for RT combined with androgen suppression therapy because this approach improves survival in men with higher-risk disease. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu NR 22 TC 217 Z9 221 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 27 PY 2005 VL 294 IS 4 BP 440 EP 447 DI 10.1001/jama.294.4.440 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 948RM UT WOS:000230733400018 PM 16046650 ER PT J AU Blaha, P Bigenzahn, S Koporc, Z Sykes, M Muehlbacher, F Wekerle, T AF Blaha, P Bigenzahn, S Koporc, Z Sykes, M Muehlbacher, F Wekerle, T TI Short-term immunosuppression facilitates induction of mixed chimerism and tolerance after bone marrow transplantation without cytoreductive conditioning SO TRANSPLANTATION LA English DT Article DE co-stimulation blockade; mixed chimerism; tolerance ID CELL-MEDIATED ALLORESISTANCE; LYMPHOHEMATOPOIETIC CHIMERISM; HEMATOPOIETIC CHIMERISM; COSTIMULATORY BLOCKADE; GRAFT-REJECTION; ENGRAFTMENT; ANTI-CD40L; ANTIBODY; LIGAND; IRRADIATION AB Background. Induction of mixed chimerism and tolerance usually requires cytoreduction or transplantation of high numbers of bone marrow cells (BMC). However, such protocols have only a suboptimal success rate and, more importantly, equivalent numbers of BMC cannot be routinely obtained in the clinical setting. The authors therefore evaluated whether a short-course of immunosuppression (IS) given in addition to co-stimulation blockade would facilitate chimerism induction and allow reduction of the minimally required number of BMC without cytoreduction. Methods. B6 mice received 200, 100, or 50 X 106 unseparated BMC from Balb/c donors plus an anti-CD40L monoclonal antibody (mAb) and CTLA4Ig (without irradiation or cytotoxic drugs). Some groups were treated additionally with IS (rapamycin, methylprednisolone, and mycophenolate mofetil for 4 weeks after bone marrow transplantation), donor-specific transfusion (DST), or anti-OX40L mAb, as indicated. Results. IS led to long-term multilineage chimerism in 9 of 10 mice receiving 200X10(6) BMC (without IS, 1 of 4; P < 0.05), in all mice (n= 10) receiving 100 X 106 (without IS, 6 of 9; P < 0.05), and notably in 9 of 10 mice treated with 50X 10(6) BMC (without IS, 4 of 10; P < 0.05). With transient IS, donor skin grafts were accepted longer than 170 days in 9 of 10 mice receiving 200X 106 (without IS, 0 of 5 mice; P < 0.05), all mice receiving 100X 106 (without IS, 6 of 9; P < 0.05), and 6 of 11 mice receiving 50X 106 BMC (without IS, 4 of 10). The use of DST or anti-OX40L mAb had no beneficial effect. Conclusions. Transient IS significantly improves rates of chimerism and donor skin graft survival, and allows lasting mixed chimerism after transplantation of only 50 X 106 BMC. Thus, IS might help in the further development of noncytoreductive chimerism protocols. C1 Med Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, A-1090 Vienna, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Wekerle, T (reprint author), Med Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, 21-A,Waehringer Guertel 18, A-1090 Vienna, Austria. EM thomas.wekerle@meduniwien.ac.at OI Wekerle, Thomas/0000-0001-5159-2796 NR 23 TC 37 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2005 VL 80 IS 2 BP 237 EP 243 DI 10.1097/01.TP.0000164510.25625.70 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 950TQ UT WOS:000230881100012 PM 16041269 ER PT J AU Song, YL Jones, JE Beppu, H Keaney, JF Loscalzo, J Zhang, YY AF Song, YL Jones, JE Beppu, H Keaney, JF Loscalzo, J Zhang, YY TI Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice SO CIRCULATION LA English DT Article DE inflammation; hypertension; pulmonary; vasoconstriction; bone morphogenetic proteins; thromboxane ID ARTERIAL-HYPERTENSION; THROMBOXANE SYNTHASE; GERMLINE MUTATIONS; SMOOTH-MUSCLE; BETA FAMILY; INFLAMMATION; RECEPTOR; BONE; 5-LIPOXYGENASE; PROSTACYCLIN AB Background - Bone morphogenetic protein receptor-2 (BMPR2)-heterozygous, mutant (BMPR2(+/-)) mice have a genetic trait similar to that of certain patients with idiopathic pulmonary arterial hypertension (IPAH). To understand the role of BMPR2 in the development of IPAH, we examined the phenotype of BMPR2(+/-) mice and their response to inflammatory stress. Methods and Results - BMPR2(+/-) mice were found to have the same life span, right ventricular systolic pressure (RVSP), and lung histology as those of wild-type mice under unstressed conditions. However, when treated with recombinant adenovirus expressing 5-lipoxygenase (Ad5LO), BMPR2(+/-) mice exhibited significantly higher RVSP than wild-type mice. The increase of RVSP occurred in the first 2 weeks after Ad5LO delivery. Modest but significant muscularization of distal pulmonary arterioles appeared in BMPR2(+/-) mice 4 weeks after Ad5LO treatment. Measurement of urinary metabolites of vasoactive molecules showed that cysteinyl leukotrienes, prostacyclin metabolites, and PGE(2) were all increased to a similar degree in both BMPR2(+/-) and wild-type mice during 5LO transgene expression, whereas urinary endothelin-1 remained undetectable. Urinary thromboxane A(2) metabolites, in contrast, were significantly higher in BMPR2(+/-) than in wild-type mice and paralleled the increase in RVSP. Platelet activation markers, serotonin, and soluble P-selectin showed a trend toward higher concentrations in BMPR2(+/-) than wild-type mice. Cell culture studies found that BMP treatment reduced interleukin-1 beta-stimulated thromboxane A(2) production in the pulmonary epithelial cell line A549. Conclusions - BMPR2(+/-) mice do not develop pulmonary hypertension spontaneously; however, under inflammatory stress, they are more susceptible to an increase in RVSP, thromboxane A(2) production, and vascular remodeling than wild-type mice. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. RP Zhang, YY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Res Lab, NRB 0630,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yyzhang@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL58976, HL55993, HL61795, P50 HL055993, R01 HL058976, R01 HL061795, R37 HL061795] NR 39 TC 121 Z9 122 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 26 PY 2005 VL 112 IS 4 BP 553 EP 562 DI 10.1161/CIRCULATIONAHA.104.492488 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 949AC UT WOS:000230756200016 PM 16027259 ER PT J AU Heller, EA Liu, E Tager, AM Sinha, S Roberts, JD Koehn, SL Libby, P Aikawa, ER Chen, JQ Huang, P Freeman, MW Moore, KJ Luster, AD Gerszten, RE AF Heller, EA Liu, E Tager, AM Sinha, S Roberts, JD Koehn, SL Libby, P Aikawa, ER Chen, JQ Huang, P Freeman, MW Moore, KJ Luster, AD Gerszten, RE TI Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment SO CIRCULATION LA English DT Article DE atherosclerosis; inflammation; leukotrienes; muscle, smooth ID LEUKOTRIENE B-4 RECEPTOR; HUMAN ATHEROSCLEROTIC PLAQUES; INTEGRIN-LINKED KINASE; DOUBLE-KNOCKOUT MICE; REDUCES ATHEROSCLEROSIS; SIGNAL-TRANSDUCTION; LESION FORMATION; DEFICIENT MICE; 5-LIPOXYGENASE; ACTIVATION AB Background - It is known that 5-lipoxygenase and its product, leukotriene B4 (LTB4), are highly expressed in several human pathologies, including atherosclerotic plaque. LTB4 signals primarily through its high-affinity G protein - coupled receptor BLT1, which is expressed on specific leukocyte subsets. BLT1 receptor expression and function on other atheroma-associated cell types is unknown. Methods and Results - To directly assess the role of the LTB4-BLT1 pathway in atherogenesis, we bred BLT1(-/-) mice into the atherosclerosis-susceptible apoE(-/-) strain. Compound-deficient apoE(-/-)/Blt1(-/-) mice fed a Western-type diet had a marked reduction in plaque formation compared with apoE(-/-) controls. Immunohistochemical analysis of atherosclerotic lesions in compound-deficient mice revealed a striking decrease in smooth muscle cells (SMCs) and significant decreases in macrophages and T cells. We report here novel evidence of the expression and function of BLT1 on vascular SMCs. LTB4 triggered SMC chemotaxis, which was pertussis toxin sensitive in Blt1(-/-) SMCs and absent in Blt1(-/-) cells, suggesting that BLT1 was the dominant receptor mediating effector functions through a G protein - coupled signaling pathway. Furthermore, BLT1 colocalized with SMCs in human atherosclerotic lesions. Conclusions - These new findings extend the role of inducible BLT1 to nonleukocyte populations and suggest an important target for intervention to modulate the response to vascular injury. C1 Massachusetts Gen Hosp, Div Cardiol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. Brigham & Womens Hosp, Vasc Med & Atherosclerosis Unit, Div Cardiovasc, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Ctr Immunol & Inflammatory Dis, E 8307,149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org FU NHLBI NIH HHS [K08 HL004237, K08 HL004237-05] NR 44 TC 91 Z9 95 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 26 PY 2005 VL 112 IS 4 BP 578 EP 586 DI 10.1161/CITCULATIONAHA.105.545616 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 949AC UT WOS:000230756200019 PM 16043658 ER PT J AU Goh, S Kwiatkowski, DJ Dorer, DJ Thiele, EA AF Goh, S Kwiatkowski, DJ Dorer, DJ Thiele, EA TI Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex SO NEUROLOGY LA English DT Article ID RANDOMIZED TRIAL; WEST-SYNDROME; VIGABATRIN AB Objective: To assess intellectual outcomes in a clinic-based population of patients with tuberous sclerosis complex (TSC) who also have a history of infantile spasms (IS) and to identify clinical risk factors for mental retardation in these patients. Methods: This is a retrospective study of 50 patients with TSC and IS seen consecutively at the Massachusetts General Hospital Tuberous Sclerosis Comprehensive Clinic from December 2001 to October 2003. Data were obtained by chart review and by interview with patients' parents. Results: Thirty-two (64%) of 50 patients with TSC with IS were found to have mental retardation (IQ or developmental quotient < 70). Three clinical variables showed an association with mental retardation: increased duration of IS from clinical onset to cessation ( odds ratio [ OR] per 1-month interval 1.09, 95% CI: 1.03 to 1.15, p = 0.004), increased time from treatment initiation until IS cessation ( OR 1.07, 95% CI: 1.01 to 1.14, p = 0.020), and poor control of other seizures after IS (OR 17.76, 95% CI: 3.47 to 129.1, p = 0.00004). The following variables did not show an association with intellectual outcome: gender, initial seizure type, age at IS onset, or time from IS onset to treatment initiation. Conclusions: In patients with tuberous sclerosis complex who also have a history of infantile spasms ( IS), the rate of mental retardation may be lower than previously reported. The risk of mental retardation increases significantly with prolonged duration of IS, prolonged time from treatment initiation until the cessation of IS, and poor control of subsequent seizures after IS. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU NINDS NIH HHS [P01 NS024279, NS31535] NR 10 TC 76 Z9 79 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 26 PY 2005 VL 65 IS 2 BP 235 EP 238 DI 10.1212/01.wnl.0000168908.78118.99 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 949AD UT WOS:000230756300011 PM 16043792 ER PT J AU Puri, BK Leavitt, BR Hayden, MR Ross, CA Rosenblatt, A Greenamyre, JT Hersch, S Vaddadi, KS Sword, A Horrobin, DF Manku, M Murck, H AF Puri, BK Leavitt, BR Hayden, MR Ross, CA Rosenblatt, A Greenamyre, JT Hersch, S Vaddadi, KS Sword, A Horrobin, DF Manku, M Murck, H TI Ethyl-EPA in Huntington disease - A double-blind, randomized, placebo-controlled trial SO NEUROLOGY LA English DT Article ID RATING-SCALE; EICOSAPENTAENOIC ACID; MULTIPLE IMPUTATION; FATTY-ACIDS; PROGRESSION; APOPTOSIS; PATHWAY AB Background: Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD). Methods: A total of 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy of 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. The primary end point was outcome at 12 months on the Total Motor Score 4 subscale (TMS-4). Analysis of covariance (ANCOVA) and a chi(2) test on response, defined as absence of increase in the TMS-4, were performed. Results: A total of 121 patients completed 12 months, and 83 did so without protocol violations (PP cohort). Intent-to-treat (ITT) analysis revealed no significant difference between ethyl-EPA and placebo for TMS-4. In the PP cohort, ethyl-EPA proved better than placebo on the chi(2) test on TMS-4 (p < 0.05), but missed significance on ANCOVA (p = 0.06). Secondary end points (ITT cohort) showed no benefit of ethyl-EPA but a significantly worse outcome in the behavioral severity and frequency compared with placebo. Exploring moderators of the efficacy of ethyl-EPA on TMS-4 showed a significant interaction between treatment and a factor defining patients with high vs low CAG repeats. Reported adverse events were distributed equally between treatment arms. Conclusions: Ethyl-eicosapentaenoate (ethyl-EPA) (purity > 95%) had no benefit in the intent-to-treat cohort of patients with Huntington disease, but exploratory analysis revealed that a significantly higher number of patients in the per protocol cohort, treated with ethyl-EPA, showed stable or improved motor function. Further studies of the potential efficacy of ethyl-EPA are warranted. C1 Amarin Neurosci Ltd, Stirling FK7 9JQ, Scotland. Hammersmith Hosp, Imperial Coll, MRC Clin Sci Ctr, Imaging Sci Dept,MRI Unit, London, England. Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Sch Med, Baltimore Huntingtons Dis Ctr, Dept Psychiat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Baltimore Huntingtons Dis Ctr, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Baltimore Huntingtons Dis Ctr, Dept Neurosci, Baltimore, MD 21218 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Monash Univ, Dept Med Psychol, Monash Med Ctr, Clayton, Vic 3168, Australia. Centum Ltd, Stirling, Scotland. RP Murck, H (reprint author), Amarin Neurosci Ltd, Kings Pk House,Laurelhill Business Pk, Stirling FK7 9JQ, Scotland. EM hmurck@amarin-neuro.com RI Greenamyre, J. Timothy/B-4049-2011; Leavitt, Blair/G-1934-2012; Ross, Christopher/H-8395-2013; Hayden, Michael/D-8581-2011 OI Greenamyre, J. Timothy/0000-0003-3468-7878; Hayden, Michael/0000-0001-5159-1419 NR 34 TC 78 Z9 83 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 26 PY 2005 VL 65 IS 2 BP 286 EP 292 DI 10.1212/01.wnl.0000169025.09670.6d PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 949AD UT WOS:000230756300020 PM 16043801 ER PT J AU Milad, MR Quinn, BT Pitman, RK Orr, SP Fischl, B Rauch, SL AF Milad, MR Quinn, BT Pitman, RK Orr, SP Fischl, B Rauch, SL TI Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cortical thickness; fear conditioning; orbitofrontal cortex ID POSTTRAUMATIC-STRESS-DISORDER; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; COORDINATE SYSTEM; FEAR EXTINCTION; BRAIN ACTIVITY; AMYGDALA; VOLUME AB The ventromedial prefrontal cortex (vmPFC) has been implicated in fear extinction [Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. (2004) Neuron 43, 897-905; Herry, C. & Garcia, R. (2003) Behav. Brain Res. 146, 89-96]. Here, we test the hypothesis that the cortical thickness of vmPFC regions is associated with how well healthy humans retain their extinction memory a day after having been conditioned and then extinguished. Fourteen participants underwent a 2-day fear conditioning and extinction protocol. The conditioned stimuli (CSs) were pictures of virtual lights, and the unconditioned stimulus (US) was an electric shock. On day 1, participants received 5 CS+US pairings (conditioning), followed by 10 CS trials with no US (extinction). On day 2, the CS was presented alone to test for extinction memory. Skin conductance response (SCR) was the behavioral index of conditioning and extinction. Participants underwent MRI scans to obtain structural images, from which cortical thickness was measured. We performed a vertex-based analysis across the entire cortical surface and a region-of-interest analysis of a priori hypothesized territories to measure cortical thickness and map correlations between this measure and SCR. We found significant, direct correlation between thickness of the vmPFC, specifically medial orbitofrontal cortex, and extinction retention. That is, thicker medial orbitofrontal cortex was associated with lower SCR to the conditioned stimulus during extinction recall (i.e., greater extinction memory). These results suggest that the size of the vmPFC might explain individual differences in the ability to modulate fear among humans. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH 03104 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY 2618, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu NR 56 TC 214 Z9 221 U1 4 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 26 PY 2005 VL 102 IS 30 BP 10706 EP 10711 DI 10.1073/pnas.050441102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 950JL UT WOS:000230853300054 PM 16024728 ER PT J AU Braunstein, GD Sundwall, DA Katz, M Shifren, JL Buster, JE Simon, JA Bachman, G Aguirre, OA Lucas, JD Rodenberg, C Buch, A Watts, NB AF Braunstein, GD Sundwall, DA Katz, M Shifren, JL Buster, JE Simon, JA Bachman, G Aguirre, OA Lucas, JD Rodenberg, C Buch, A Watts, NB TI Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women - A randomized, placebo-controlled trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POSTMENOPAUSAL WOMEN; OOPHORECTOMIZED WOMEN; DYSFUNCTION; ANDROGEN; PREMENOPAUSAL; HYSTERECTOMY; PREVALENCE; THERAPY; PROFILE; AROUSAL AB Background: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women. Methods: A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n = 119) or testosterone patches in dosages of 150 mu g/d (n= 107),300 mu g/d (n= 110), or 450 mu g/d (n = 111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures. Results: Of the 447 women randomized, 318 (71%) completed the trial. Compared with placebo, women receiving the 300-mu g/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P=.05) and in frequency of satisfying sexual activity (79% vs 43%; P =. 049). The 150-mu g/d group showed no evidence of a treatment effect. The 450-mu g/d group also was not statistically different from the 300-mu g/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P=.06 and.06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed. Conclusions: The 300-mu g/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause. C1 Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. Phys Res Opt, Sandy, UT USA. Hewitt Inc, Cincinnati, OH USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX USA. Womens Hlth Res Ctr, Laurel, MD USA. Univ Med & Dent New Jersey, Womens Hlth Inst, New Brunswick, NJ USA. Urogynecol Associates Colorado, Denver, CO USA. Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH USA. Univ Cincinnati, Osteoporosis Ctr, Cincinnati, OH 45221 USA. RP Braunstein, GD (reprint author), Cedars Sinai Med Ctr, Dept Med, Room 2119 Plaza Level,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM Glenn.Braunstein@cshs.org NR 27 TC 210 Z9 220 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 25 PY 2005 VL 165 IS 14 BP 1582 EP 1589 DI 10.1001/archinte.165.14.1582 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 948BT UT WOS:000230691700003 PM 16043675 ER PT J AU Pierce, MC Shishkov, M Park, BH Nassif, NA Bouma, BE Tearney, GJ de Boer, JF AF Pierce, MC Shishkov, M Park, BH Nassif, NA Bouma, BE Tearney, GJ de Boer, JF TI Effects of sample arm motion in endoscopic polarization-sensitive optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID IN-VIVO; BIOLOGICAL TISSUE; AXIS ORIENTATION; TURBID MEDIA; BIREFRINGENCE; CATHETER; INTERFEROMETER AB Motion of the sample arm fiber in optical coherence tomography (OCT) systems can dynamically alter the polarization state of light incident on tissue during imaging, with consequences for both conventional and polarization-sensitive (PS-)OCT. Endoscopic OCT is particularly susceptible to polarization-related effects, since in most cases, the transverse scanning mechanism involves motion of the sample arm optical fiber to create an image. We investigated the effects of a scanning sample arm fiber on the polarization state of light in an OCT system, and demonstrate that by referencing the state backscattered from within a sample to the measured state at the surface, changes in polarization state due to sample fiber motion can be isolated. The technique is demonstrated by high-speed PS-OCT imaging at 1 frame per second, with both linear and rotary scanning fiberoptic probes. Measurements were made on a calibrated wave plate, and endoscopic PS-OCT images of ex-vivo human tissues are also presented, allowing comparison with features in histologic sections. (C) 2005 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR 714, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 29 TC 24 Z9 24 U1 1 U2 7 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 JUL 25 PY 2005 VL 13 IS 15 BP 5739 EP 5749 DI 10.1364/OPEX.13.005739 PG 11 WC Optics SC Optics GA 949FO UT WOS:000230770700020 PM 19498576 ER PT J AU Lichterfeld, M Pantaleo, G Altfeld, M AF Lichterfeld, M Pantaleo, G Altfeld, M TI Loss of HIV-1-specific T cell proliferation in chronic HIV-1 infection: cause or consequence of viral replication? SO AIDS LA English DT Editorial Material ID IMMUNODEFICIENCY VIRUS-INFECTION; LYMPHOCYTE RESPONSE; ESCAPE; CD4(+); VIREMIA; SELECTION; EPITOPE; LOAD; AIDS C1 Harvard Univ, Partners AIDS Res Ctr, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Div Aids, Sch Med, Boston, MA 02129 USA. CHU Vaudois, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland. RP Altfeld, M (reprint author), Harvard Univ, Partners AIDS Res Ctr, Sch Med, Massachusetts Gen Hosp, Rm 6625, Boston, MA 02129 USA. EM maltfeld@partners.org RI Pantaleo, Giuseppe/K-6163-2016 NR 24 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 22 PY 2005 VL 19 IS 11 BP 1225 EP 1227 DI 10.1097/01.aids.0000176224.56108.fb PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 948BX UT WOS:000230692100014 PM 15990577 ER PT J AU Chemaly, ER Gianni, D Lebeche, D Pomerantseva, I Yoneyama, R Kawase, Y Hoshino, K Hayase, M del Monte, F Hajjar, RJ AF Chemaly, ER Gianni, D Lebeche, D Pomerantseva, I Yoneyama, R Kawase, Y Hoshino, K Hayase, M del Monte, F Hajjar, RJ TI Tracking and gene expression profile of bone marrow mesenchymal stem cells injected into pig myocardium SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 042 BP E16 EP E16 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900054 ER PT J AU Gianni, D Padmanabhan, PA Lezoualch, F Lompre, AM Macgillivray, TE Semigran, MJ Dec, GW Gwathmey, JK Hajjar, RJ del Monte, F AF Gianni, D Padmanabhan, PA Lezoualch, F Lompre, AM Macgillivray, TE Semigran, MJ Dec, GW Gwathmey, JK Hajjar, RJ del Monte, F TI Insoluble deposits in cardiac myocytes from human dilated cardiomyopathy SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Charlestown, MA USA. INSERM, Chatenay Malabry, France. INSERM, Paris, France. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI LOMPRE, Anne-Marie/H-2872-2013 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 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 187 BP E45 EP E45 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900191 ER PT J AU Kerkela, R Grazette, L Force, T AF Kerkela, R Grazette, L Force, T TI Cardiotoxic effects of imatinib mesylate SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Tufts New England Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, 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 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 079 BP E23 EP E23 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900089 ER PT J AU Lebeche, D Kaprielian, R Haijar, R AF Lebeche, D Kaprielian, R Haijar, R TI Modulation of action potential duration on myocyte hypertrophic pathways SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 123 BP E31 EP E31 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900129 ER PT J AU Lompre, M del Monte, F Hajjar, RJ Lipskaia, L AF Lompre, M del Monte, F Hajjar, RJ Lipskaia, L TI Importance of sarcoplasmic reticulum calcium handling in vascular smooth muscle proliferation SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 INSERM, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 086 BP E24 EP E24 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900095 ER PT J AU Padmanabhan, PA Sato, T Doud, K Macgillivray, TE Semigran, MJ Hajjar, RJ Gwathmey, JK del Monte, F AF Padmanabhan, PA Sato, T Doud, K Macgillivray, TE Semigran, MJ Hajjar, RJ Gwathmey, JK del Monte, F TI Differentially expressed sarcoplasmic reticulum proteins in human heart failure SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 061 BP E19 EP E19 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900071 ER PT J AU Petroff, MGV Palomeque, J Sapia, L AF Petroff, MGV Palomeque, J Sapia, L TI Angiotensin II-induced negative inotropy in rat ventricular myocytes: Role of reactive oxygen species and P38 MAPK SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Ctr Invest Cardiovasc, La Plata, Argentina. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 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 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 141 BP E35 EP E35 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900147 ER PT J AU Pyo, R Sui, JL Logothetes, D AF Pyo, R Sui, JL Logothetes, D TI CXCR4: A new functional receptor on the myocardium that modulates cardiac contractility SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Mt Sinai Sch Med, New York, NY USA. Univ Rochester, Rochester, NY 14627 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 135 BP E34 EP E34 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900141 ER PT J AU Yoneyama, R Hoshino, K Pomerantseva, I Kushibiki, T Kawase, Y Hayase, M Hajjar, RJ AF Yoneyama, R Hoshino, K Pomerantseva, I Kushibiki, T Kawase, Y Hayase, M Hajjar, RJ TI Labeling of mesenchymal stem cells with gadolinium using biodegradable gelatin as a transfection agent SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kyoto Univ, Inst Frontier Med Sci, Kyoto, Japan. 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 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 043 BP E16 EP E16 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900055 ER PT J AU Bali, P Pranpat, M Bradner, J Balasis, M Fiskus, W Guo, F Rocha, K Kumaraswamy, S Boyapalle, S Atadja, P Seto, E Bhalla, K AF Bali, P Pranpat, M Bradner, J Balasis, M Fiskus, W Guo, F Rocha, K Kumaraswamy, S Boyapalle, S Atadja, P Seto, E Bhalla, K TI Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90 - A novel basis for antileukemia activity of histone deacetylase inhibitors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELOGENOUS LEUKEMIA-CELLS; BCR-ABL; MOLECULAR CHAPERONES; BREAST-CANCER; MUTANT FLT-3; IN-VIVO; PROTEIN; HSP90; APOPTOSIS; LAQ824 AB The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated alpha-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and alpha-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and alpha-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Interdisciplinary Oncol Program, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut Inc, Cambridge, MA 02139 USA. RP Bhalla, K (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Interdisciplinary Oncol Program, Dept Interdisciplinary Oncol, 12902 Magnolia Dr,MRC 3 E,Rm 3056, Tampa, FL 33612 USA. EM bhallakn@moffitt.usf.edu NR 40 TC 490 Z9 510 U1 5 U2 40 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 JUL 22 PY 2005 VL 280 IS 29 BP 26729 EP 26734 DI 10.1074/jbc.C500186200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946RI UT WOS:000230589500013 PM 15937340 ER PT J AU Javanbakht, H Diaz-Griffero, F Stremlau, M Si, ZH Sodroski, J AF Javanbakht, H Diaz-Griffero, F Stremlau, M Si, ZH Sodroski, J TI The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SIMIAN CELLS; POSTENTRY RESTRICTION; REVERSE TRANSCRIPTION; B30.2(SPRY) DOMAIN; OLD-WORLD; HIV-1; REPLICATION; PROTEIN; REF1 AB TRIM5 alpha is a cytoplasmic protein that mediates a post-entry block to infection by some retroviruses. TRIM5 alpha contains a tripartite motif ( TRIM), which includes RING, B-box 2, and coiled-coil domains, and a C-terminal B30.2 ( SPRY) domain. We investigated the contribution of the RING and B- box 2 domains to the antiretroviral activity of rhesus monkey TRIM5 alpha (TRIM5 alpha(rh)), which potently restricts infection by human immunodeficiency virus, type 1 (HIV-1) and simian immunodeficiency virus of African green monkeys (SIVagm). Disruption of the RING domain caused mislocalization of TRIM5 alpha(rh) so that the cytoplasmic level of the protein was decreased compared with that of the wild-type protein. Nonetheless, partial ability to restrict HIV-1 and SIVagm was retained by the RING domain mutants. By contrast, although TRIM5 alpha(rh) mutants with disrupted B- box 2 domains were efficiently expressed and correctly localized to the cytoplasm, antiretroviral activity was absent. The B- box 2 mutants colocalized and associated with wild-type TRIM5 alpha(rh) and exerted dominant-negative effects on the antiretroviral activity of the wild-type protein. Taken together with other data, these results indicate that functionally defective TRIM5 alpha(rh) molecules that retain a coiled coil can act as dominant-negative inhibitors of wild-type TRIM5 alpha(rh) function. The RING domain of TRIM5 alpha(rh) is not absolutely required for retrovirus restriction. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI28691, AI063987] NR 35 TC 135 Z9 141 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 JUL 22 PY 2005 VL 280 IS 29 BP 26933 EP 26940 DI 10.1074/jbc.M502145200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946RI UT WOS:000230589500037 PM 15897199 ER PT J AU Lleo, A Waldron, E von Arnim, CAF Herl, L Tangredi, MM Peltan, ID Strickland, DK Koo, EH Hyman, BT Pietrzik, CU Berezovska, O AF Lleo, A Waldron, E von Arnim, CAF Herl, L Tangredi, MM Peltan, ID Strickland, DK Koo, EH Hyman, BT Pietrzik, CU Berezovska, O TI Low density lipoprotein receptor-related protein (LRP) interacts with presenilin 1 and is a competitive substrate of the amyloid precursor protein (APP) for gamma-secretase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; C-TERMINAL FRAGMENTS; ALPHA-2-MACROGLOBULIN RECEPTOR; PLASMINOGEN-ACTIVATOR; INTRACELLULAR DOMAIN; ALZHEIMERS-DISEASE; DOCKING SITE; COMPLEX; NOTCH1; FE65 AB Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, which is involved in the cleavage of several substrates including the amyloid precursor protein (APP) and the Notch receptor. Recently, the low density receptor-related protein (LRP) has been shown to be cleaved by a gamma-secretase-like activity. We postulated that LRP may interact with PS1 and tested its role as a competitive substrate for gamma-secretase. In this report we show that LRP colocalizes and interacts with endogenous PS1 using coimmunoprecipitation and fluorescence lifetime imaging microscopy. In addition, we found that gamma-secretase active site inhibitors do not disrupt the interaction between LRP and PS1, suggesting that the substrate associates with a gamma-secretase docking site located in close proximity to PS1. This is analogous to APP-gamma-secretase interactions. Finally, we show that LRP competes with APP for gamma-secretase activity. Overexpression of a truncated LRP construct consisting of the C terminus, the transmembrane domain, and a short extracellular portion leads to a reduction in the levels of the A beta(40), A beta(42), and p3 peptides without changing the total level of APP expression. In addition, transfection with the beta-chain of LRP causes an increase in uncleaved APP C-terminal fragments and a concomitant decrease in the signaling effects of the APP intracellular domain. In conclusion, LRP is a PS1 interactor and can compete with APP for gamma-secretase enzymatic activity. C1 Univ Mainz, Inst Physiol Chem & Pathobiochem, Dept Mol Neurodegenerat, D-55099 Mainz, Germany. Massachusetts Gen Hosp, Massachusetts Inst Neurodgenerat Disorders, Alzheimer Res Unit, Charlestown, MA 02129 USA. Univ Maryland, Sch Med, Dept Surg, Rockville, MD 20855 USA. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD 20855 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Pietrzik, CU (reprint author), Univ Mainz, Inst Physiol Chem & Pathobiochem, Dept Mol Neurodegenerat, Rm 04-128, D-55099 Mainz, Germany. EM Pietrzik@uni-mainz.de; oberezovska@partners.org OI Peltan, Ithan/0000-0003-1730-234X FU NHLBI NIH HHS [HL50784]; NIA NIH HHS [AG12376, AG12406, AG15379] NR 55 TC 45 Z9 46 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 22 PY 2005 VL 280 IS 29 BP 27303 EP 27309 DI 10.1074/jbc.M413969200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946RI UT WOS:000230589500080 PM 15917251 ER PT J AU Chou, S Hollander, H Schaefer, PW Harris, NL Singhal, A Daskalakis, DC Hedley-Whyte, ET AF Chou, S Hollander, H Schaefer, PW Harris, NL Singhal, A Daskalakis, DC Hedley-Whyte, ET TI Case 22-2005: An 81-year-old man with cough, fever, and altered mental status - Encephalomyelitis due to West Nile virus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; PCR ASSAY; ENCEPHALITIS; INFECTION; DIAGNOSIS; PATHOLOGY C1 Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chou, S (reprint author), Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 21 PY 2005 VL 353 IS 3 BP 287 EP 295 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 946YH UT WOS:000230608700011 PM 16034015 ER PT J AU Cummings, DE AF Cummings, DE TI Gastric bypass and nesidioblastosis - Too much of a good thing for islets? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TYPE-2 DIABETES-MELLITUS; GLUCAGON-LIKE PEPTIDE-1; BARIATRIC SURGERY; WEIGHT-LOSS; GHRELIN; OBESITY C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Cummings, DE (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. NR 16 TC 54 Z9 58 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 JUL 21 PY 2005 VL 353 IS 3 BP 300 EP 302 DI 10.1056/NEJMe058170 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 946YH UT WOS:000230608700013 PM 16034017 ER PT J AU Kliethermes, CL Cronise, K Crabbe, JC AF Kliethermes, CL Cronise, K Crabbe, JC TI Home cage activity and ingestive behaviors in mice following chronic ethanol vapor inhalation SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE alcohol withdrawal; mice; anxiety-like behaviors; home cage ID ELEVATED PLUS-MAZE; WITHDRAWAL-INDUCED ANXIETY; ALCOHOL-WITHDRAWAL; RATS; DEPENDENCE; EXPOSURE; NITRENDIPINE; ANTAGONISTS; MANAGEMENT; RESPONSES AB Although drug withdrawal may induce an anxiety-like state, decreased locomotion in tests of anxiety-like behavior is an almost universal finding in rodent studies of ethanol withdrawal. Decreased locomotion in many behavioral apparatus, either as a result of a withdrawal-induced lethargy, malaise, or reduced motivation to explore confounds interpreting the effects of withdrawal as specifically increasing an anxiety-like state. To address this issue, we measured home cage activity levels as well as food and water intake for 3 days prior to and up to 5 days after chronic ethanol vapor exposure in genetically heterogeneous mice. In the first experiment, ethanol-withdrawing WSC-2 mice drank less water than controls, but did not differ from controls on any other behavioral measure during the withdrawal assessments. When the dose of ethanol was elevated in a subsequent experiment in WSC-2 mice, a similar temporary decrease in food and water intake, but not in locomotion, was observed during withdrawal. These results differed from those of mice placed into activity monitors during peak withdrawal, which exhibited profoundly reduced activity levels compared to controls. Finally, home cage activity levels during withdrawal were only transiently decreased in a mouse line that has been selectively bred to display high ethanol withdrawal handling-induced convulsion severity (WSP mice). The reduction in food and water consumption seen in most experiments suggests that withdrawal may induce a temporary malaise-like state, but this state is not reflected in altered home cage activity levels. Further, even in a relatively severe mouse model of alcohol withdrawal, any decreases in general home cage activity are short-lived. Published by Elsevier Inc. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. RP Kliethermes, CL (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, R&D 12,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kliether@ohsu.edu FU NIAAA NIH HHS [P60 AA010760, AA10760, AA015015] NR 39 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUL 21 PY 2005 VL 85 IS 4 BP 479 EP 488 DI 10.1016/j.physbeh.2005.05.009 PG 10 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 953UJ UT WOS:000231105800013 PM 16005034 ER PT J AU McKee, AE Minet, E Stern, C Riahi, S Stiles, CD Silver, PA AF McKee, AE Minet, E Stern, C Riahi, S Stiles, CD Silver, PA TI A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; SYNAPTIC PLASTICITY; CELLS; MEMORY; ROLES; TRANSLATION; DISRUPTION; TRANSPORT; PROFILES AB Background: In eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized. Results: Here we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Using in situ hybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues. Conclusion: Our data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Fac Univ Notre Dame Paix, URBC, B-5000 Namur, Belgium. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM adrienne_mckee@student.hms.harvard.edu; emmanuel.minet@fundp.ac.be; cstern@foleyhoag.com; shervin@gmail.com; charles_stiles@dfci.harvard.edu; pamela_silver@dfci.harvard.edu FU NCI NIH HHS [T32 CA009361, T32CA09361] NR 49 TC 93 Z9 95 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD JUL 20 PY 2005 VL 5 AR 14 DI 10.1186/1471-213X-5-14 PG 9 WC Developmental Biology SC Developmental Biology GA 997WC UT WOS:000234278500001 PM 16033648 ER PT J AU Salvesen, HB Kumar, R Stefansson, I Angelini, S MacDonald, N Smeds, J Jacobs, IJ Hemminki, K Das, S Alkslen, LA AF Salvesen, HB Kumar, R Stefansson, I Angelini, S MacDonald, N Smeds, J Jacobs, IJ Hemminki, K Das, S Alkslen, LA TI Low frequency of BRAF and CDKN2A mutations in endometrial cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE BRAF; K-ras; CDKN2A (p16); endometrial cancer; prognosis ID SPORADIC PRIMARY MELANOMAS; POPULATION-BASED SERIES; MICROSATELLITE INSTABILITY; PROMOTER METHYLATION; MISMATCH-REPAIR; KRAS MUTATIONS; CARCINOMAS; EXPRESSION; P16(INK4); P53 AB Several pathways have been implicated in the pathogenesis of endometrial carcinoma. Based on recent reports, BRAF mutations provide an alternative route for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor gene is also altered in several tumour types. We therefore wanted to assess the pattern and prognostic impact of BRAF mutations and p16 alterations in endometrial carcinomas. Only 1 of 48 tumours (2%) was found to have a BRAF mutation in exon 15, whereas 8 of 45 tumours (18%) had a K-ras mutation. Homozygous deletion, amplification, promoter region methylation or mutation of the p16 gene was seen in 6 cases (13%), and 18 cases (38%) carried polymorphisms in the p16 gene. All tumours with presence of p16 methylation, non-sense mutation, deletion or amplification exhibited loss of p16 expression as evaluated by immunohistochemistry. Presence of a p16 hit was significantly correlated with high FIGO stage (p = 0.04), high histologic grade (p = 0.02), estrogen receptor negativity (p = 0.05), pathologic expression of p53 (p = 0.02), pathologic expression of p16 (p = 0.05) and poor survival (p 0.02). There was also a significant correlation between loss of p16 expression and K-ras mutations, pathologic p53 expression and serous papillary/clear cell histologic types (p = 0.05/p = 0.001/p = 0.002). In. conclusion, BRAF mutation is an infrequent finding in endometrial carcinomas. Loss of p16 expression is seen in all cases with alterations of the p16 gene. The presence of a p16 hit might be important in a subset of endometrial carcinomas with aggressive clinical behaviour. However, the mechanism of p16 inactivation remains unclear for the majority of cases exhibiting loss of expression, but the interactions with K-ras and p53 should be further studied. (c) 2005 Wiley-Liss, Inc. C1 Univ Bergen, Haukeland Hosp, Gade Inst, Dept Pathol, N-5021 Bergen, Norway. Univ Bergen, Haukeland Hosp, Dept Clin Med, Sect Obstet & Gynceol, N-5021 Bergen, Norway. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. Ctr Nutr & Toxicol, Karolinska Inst, Dept Biosci, Novum, Sweden. Royal London Hosp, Sch Med & Dent, London E1 1BB, England. St Bartholomews Hosp, Gynaecol Canc Res Unit, Dept Gynaecol Oncol, London, England. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. RP Salvesen, HB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, D720,44 Binney St, Boston, MA 02115 USA. EM helga.salvesen@gades.uib.no RI Jacobs, Ian/F-1743-2013; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017; OI Jacobs, Ian/0000-0002-8112-4624; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831; Kumar, Rajiv/0000-0002-6093-0395; Angelini, Sabrina/0000-0002-1609-0421 FU NCI NIH HHS [CA81652-01] NR 27 TC 29 Z9 30 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 20 PY 2005 VL 115 IS 6 BP 930 EP 934 DI 10.1002/ijc.20702 PG 5 WC Oncology SC Oncology GA 934EM UT WOS:000229689700011 PM 15723290 ER PT J AU Canellos, GP AF Canellos, GP TI Chemotherapy alone for early Hodgkin's lymphoma: An emerging option SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INVOLVED-FIELD RADIOTHERAPY; LONG-TERM SURVIVORS; RADIATION-THERAPY; STAGE-I; 2ND MALIGNANCY; DISEASE; TRIAL; VINBLASTINE; DOXORUBICIN; RISK C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 TC 19 Z9 19 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 JUL 20 PY 2005 VL 23 IS 21 BP 4574 EP 4576 DI 10.1200/JCO.2005.01.911 PG 3 WC Oncology SC Oncology GA 950QK UT WOS:000230872000003 PM 15837972 ER PT J AU Lamont, EB Herndon, JE Weeks, JC Henderson, IC Lilenbaum, R Schilsky, RL Christakis, NA AF Lamont, EB Herndon, JE Weeks, JC Henderson, IC Lilenbaum, R Schilsky, RL Christakis, NA CA Canc Leukemia Grp B TI Criterion validity of medicare chemotherapy claims in cancer and leukemia group B breast and lung cancer trial participants SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID III COLON-CANCER; ADJUVANT CHEMOTHERAPY; ELDERLY-PATIENTS; CLINICAL-TRIALS; OLDER PATIENTS; STAGE-II; AGE; OUTCOMES; EPIDEMIOLOGY; SURVEILLANCE AB To determine the accuracy with which Medicare claims data measure chemotherapy use in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We compared gold-standard clinical trial data for 175 elderly cancer patients treated in two Cancer and Leukemia Group B (CALGB) breast and lung cancer trials (i.e., 45 from trial 9344 and 130 from trial 9730) with contemporaneous ambulatory and in-patient Medicare health insurance claims data from Centers for Medicare and Medicaid Services (CMS). The breast trial participants studied were those elderly enrolled between 1995 and 1997 and treated with doxorubicin and cyclophosphamide or this combination with paclitaxel. The lung trial participants studied were those elderly enrolled between 1998 and 2000 and treated with paclitaxel and carboplatin or paclitaxel alone. Comparing CALGB data with Medicare claims, we found the crude sensitivity for chemotherapy administration was 93% (95% confidence interval [CI] = 88% to 96%). Individual chemotherapy agents had similarly high sensitivities, ranging from 81% (95% CI = 70% to 89%) for carboplatin to 91% (95% CI = 79% to 98%) for cyclophosphamide. Agentspecific specificities were 100%. CMS data reliably captured repeat administration of chemotherapy to within one cycle. Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. CALGB, Ctr Stat, Durham, NC USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Mt Sinai Canc Ctr, Dept Med, Miami Beach, FL USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Lamont, EB (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM elamont@partners.org RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU NCI NIH HHS [CA93892, K07 CA093892, CA47577, CA33601, CA41287, U10 CA033601, CA60138, CA32291, CA31946, CA45564] NR 20 TC 49 Z9 49 U1 0 U2 2 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 JUL 20 PY 2005 VL 97 IS 14 BP 1080 EP 1083 DI 10.1093/jnci/dji189 PG 4 WC Oncology SC Oncology GA 945SV UT WOS:000230523400013 PM 16030306 ER PT J AU Mische, CC Yuan, W Strack, B Craig, S Farzan, M Sodroski, J AF Mische, CC Yuan, W Strack, B Craig, S Farzan, M Sodroski, J TI An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor SO VIROLOGY LA English DT Article DE HIV; gp4l; trimer; prefusion state ID VIRAL MEMBRANE-FUSION; TYPE-1 GP41; TRANSMEMBRANE GLYCOPROTEIN; LEUCINE-ZIPPER; INFLUENZA HEMAGGLUTININ; ENDOPLASMIC-RETICULUM; MUTATIONAL ANALYSIS; CONSERVED RESIDUES; SYNTHETIC PEPTIDE; ATOMIC-STRUCTURE AB The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp4l coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate. (C) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI42848, AI39420, AI40895, AI24755] NR 48 TC 13 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 20 PY 2005 VL 338 IS 1 BP 133 EP 143 DI 10.1016/j.virol.2005.05.001 PG 11 WC Virology SC Virology GA 944ZR UT WOS:000230470400013 PM 15950253 ER PT J AU Herrera, C Klasse, PJ Michael, E Kake, S Bames, K Kibler, CW Campbell-Gardener, L Si, ZH Sodroski, J Moore, JP Beddows, S AF Herrera, C Klasse, PJ Michael, E Kake, S Bames, K Kibler, CW Campbell-Gardener, L Si, ZH Sodroski, J Moore, JP Beddows, S TI The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type I particles SO VIROLOGY LA English DT Article DE gp160 Env; HIV-1; cleavage; antigenicity; neutralizing antibodies; mutants ID HUMAN MONOCLONAL-ANTIBODY; CELL-SURFACE EXPRESSION; CROSS-CLADE NEUTRALIZATION; GP41 CYTOPLASMIC TAIL; NONNEUTRALIZING ANTIBODIES; PRECURSOR CLEAVAGE; EPITOPE EXPOSURE; HIV-1 INFECTION; PLASMA-MEMBRANE; VIRIONS AB Endoproteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins is an obligate part of the biosynthetic pathway that generates functional, fusion-competent Env complexes, which are then incorporated into infectious virions. We have examined the influence of cleavage on Env-specific antibody reactivity, Env incorporation into pseudovirions, and the infectivity and neutralization sensitivity of Env-pseudotyped viruses. To do so, we have used both incompletely processed wild-type (Wt) Env and engineered, cleavage-defective Env mutants. We find that there is no simple association between antibody reactivity to cell surface-expressed Env, and the ability of the same antibody to neutralize virus pseudotyped with the same Env proteins. One explanation for the absence of such an association is the diverse array of Env species present on the surface of transiently transfected cells. We also confirm that cleavage-defective mutants are antigenically different from Wt Env. These findings have implications for the use of Env binding assays as predictors of neutralizing activity, and for the development of cleavage-defective Env trimers for use as subunit immunogens. (C) 2005 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave,Room W-805, New York, NY 10021 USA. EM jpm2003@med.cornell.edu FU NIAID NIH HHS [N01 AI30030, R01 AI39420, R37 AI036082-13, R37 AI36082] NR 88 TC 55 Z9 55 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 20 PY 2005 VL 338 IS 1 BP 154 EP 172 DI 10.1016/j.virol.2005.05.002 PG 19 WC Virology SC Virology GA 944ZR UT WOS:000230470400015 PM 15932765 ER PT J AU Mahon, NG Murphy, RT MacRae, CA Caforio, ALP Elliott, PM McKenna, WJ AF Mahon, NG Murphy, RT MacRae, CA Caforio, ALP Elliott, PM McKenna, WJ TI Echocardiographic evaluation in asymptornatic relatives of patients with dilated cardiomyopathy reveals preclinical disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONDUCTION-SYSTEM DISEASE; LAMIN A/C GENE; HEART-FAILURE; MUTATION; ASSOCIATION; GUIDELINES; ADULT; LOCUS; MAPS AB Background: idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease. Objective: To determine the prevalence and natural history of asymptomatic cardiac abnormalities among sampled relatives of unselected patients referred for management of dilated cardiomyopathy. Design: Prospective cohort study. Patients: 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy. Measurements: Clinical evaluation, including history, physical examination, electrocardiography, and echocardiography, was performed. Participants were classified in accordance with published echocardiographic criteria. Sampled relatives who did not have evidence of dilated cardiomyopathy at the initial evaluation were followed for a median of 57 months (range, 1 to 133 months). Results: Of the 767 patients evaluated, 592 (77.2%) were assessed as healthy, 35 (4.6% [95% CI, 3.7% to 7.6%]) had dilated cardiomyopathy, 119 (15.5% [CI, 12.5% to 18.8%]) had left ventricular enlargement without systolic dysfunction, and 21 (2.7% [CI, 1.9% to 4.9%]) had depressed fractional shortening without ventricular dilatation. At follow-up, progression to dilated cardiomyopathy occurred in 13 (10%) relatives with left ventricular enlargement or depressed fractional shortening versus 3 (1.3%) healthy relatives. In a multivariate model, only left ventricular enlargement or depressed fractional shortening independently predicted progression to dilated cardiomyopathy (hazard ratio, 10.0 [CI, 2.8 to 35.5]; P < 0.001). Limitations: Because relatives had to be willing to participate and be available geographically, selection bias may have occurred. Conclusion: Treatable asymptomatic dilated cardiomyopathy was identified in 4.6% of asymptomatic relatives. In addition, left ventricular enlargement and depressed fractional shortening were common in asymptomatic relatives of patients with dilated cardiomyopathy and were associated with a statistically significant medium-term risk for disease progression. Evaluation of relatives of patients with cardiomyopathy is recommended. C1 St George Hosp, Sch Med, London, England. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Padua, Padua, Italy. RP McKenna, WJ (reprint author), Heart Hosp, Westmoreland St, London W1G 8PH, England. EM william.mckenna@uclh.org RI McKenna, William/C-3243-2008 OI McKenna, William/0000-0001-7994-2460 FU NHLBI NIH HHS [R01 HL075431] NR 34 TC 63 Z9 64 U1 0 U2 1 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 JUL 19 PY 2005 VL 143 IS 2 BP 108 EP 115 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 946YG UT WOS:000230608600003 PM 16027452 ER PT J AU Roy, CL Poon, EG Karson, AS Ladak-Merchant, Z Johnson, RE Maviglia, SM Gandhi, TK AF Roy, CL Poon, EG Karson, AS Ladak-Merchant, Z Johnson, RE Maviglia, SM Gandhi, TK TI Patient safety concerns arising from test results that return after hospital discharge SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FOLLOW-UP; CARE; IMPLEMENTATION; OUTCOMES; SERVICE AB Background: Failure to relay information about test results pending when patients are discharged from the hospital may pose an important patient-safety problem. Few data are available on the epidemiology of test results pending at discharge or on physician awareness of these results. Objective: To determine the prevalence, characteristics, and physician awareness of potentially actionable laboratory and radiologic test results returning after hospital discharge. Design: Cross-sectional study. Setting: Two tertiary care academic hospitals. Patients: 2644 consecutive patients discharged from hospitalist services from February to June 2004. Measurements: The main outcomes were the prevalence and characteristics of potentially actionable test results returning after hospital discharge, awareness of these results by inpatient and primary care physicians, and satisfaction of inpatient physicians with current systems for follow-up on test results. The authors prospectively collected data on test results pending at the time of discharge and, as results returned after discharge, surveyed hospitalists, junior residents, and primary care physicians about those results that were potentially actionable according to a physician-reviewer. Results: A total of 1095 patients (41%) had 2033 test results return after discharge. Of these results, 191 (9.4% [95% CI, 8.0% to 11.0%]) were potentially actionable. Surveys were sent regarding 155 results, and 105 responses were returned. Of the 105 results in the surveys with responses, physicians had been unaware of 65 (61.6% [CI, 51.3% to 70.9%]); of these 65, they agreed with physician-reviewers that 24 (37.1% [CI, 25.7% to 50.2%]) were actionable and 8 (12.6% [CI, 6.4% to 23.3%]) required urgent action. Inpatient physicians were dissatisfied with their systems for following up on test results returning after discharge. Limitations: The authors were unable to determine whether physicians' lack of awareness of test results returning after discharge Conclusions: Many patients are discharged from hospitals with test results still pending, and physicians are often unaware of potentially actionable test results returning after discharge. Further work is needed to design better follow-up systems for test results returning after hospital discharge. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roy, CL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM croy@partners.org NR 17 TC 181 Z9 182 U1 0 U2 2 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 JUL 19 PY 2005 VL 143 IS 2 BP 121 EP 128 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 946YG UT WOS:000230608600005 PM 16027454 ER PT J AU Kawaguchi, K Hickey, RW Rose, ME Zhu, L Chen, J Graham, SH AF Kawaguchi, K Hickey, RW Rose, ME Zhu, L Chen, J Graham, SH TI Cyclooxygenase-2 expression is induced in rat brain after kainate-induced seizures and promotes neuronal death in CA3 hippocampus SO BRAIN RESEARCH LA English DT Article DE cyclooxygenase; kainate; cell death; seizure ID PENTYLENETETRAZOL-INDUCED SEIZURES; SUSTAINED ELECTRICAL-STIMULATION; KAINIC ACID; CELL-DEATH; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); ANTIINFLAMMATORY AGENTS; SELECTIVE-INHIBITION; INDUCED CONVULSIONS; ALZHEIMERS-DISEASE; PILOCARPINE MODEL AB Cyclooxygenase-2 (COX-2) is the predominant isoform of cyclooxygenase in brain. COX-2 activity produces oxidative stress and results in the production of prostaglandins that have many injurious effects. COX-2 transcription is induced by synaptic activity; therefore, COX-2 activity could contribute to epileptic neuronal injury. To address this hypothesis, COX-2 protein expression and PGE(2) production were determined after kainate-induced limbic seizures in rats. The effects of a specific COX-2 inhibitor, SC58125, on neuronal survival and PGE2 concentration in the hippocampus were also determined. COX-2 protein expression was increased in CA3, dentate gyrus, and cortex at 18-24 h after seizures. Hippocampal PGE(2) levels were increased at 24 h following seizures, and treatment with the selective COX-2 inhibitor SC58125, 3 mg/kg p.o., attenuated the increase in PGE(2) concentration. The survival of CA3 neurons at 7 days after seizures was increased in rats treated with SC58125 compared to vehicle controls. There was no effect of drug treatment on body or brain temperature, nor on the duration or rate of Type IV EEG activity. These results suggest that COX-2 activity can contribute to epileptic neuronal injury and that selective COX-2 inhibitors are neuroprotective. C1 Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res & Educ Ctr 151, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. RP Graham, SH (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res & Educ Ctr 151, Univ Dr C, Pittsburgh, PA 15240 USA. EM sgra@pitt.edu FU NICHD NIH HHS [K08 HD040848, K08 HD40848]; NINDS NIH HHS [R01 NS037459-05, R01 NS37459, R01 NS037459] NR 59 TC 62 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 19 PY 2005 VL 1050 IS 1-2 BP 130 EP 137 DI 10.1016/j.brainres.2005.05.038 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 954AT UT WOS:000231127200017 PM 15979590 ER PT J AU Sleeper, LA Ramanathan, K Picard, MH LeJemtel, TH White, HD Dzavik, V Tormey, D Avis, NE Hochman, JS AF Sleeper, LA Ramanathan, K Picard, MH LeJemtel, TH White, HD Dzavik, V Tormey, D Avis, NE Hochman, JS CA SHOCK Invest TI Functional status and quality of life after emergency revascularization for cardiogenic shock complicating acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DISEASE AB OBJECTIVES Our goal was to describe the functional status of cardiogenic shock survivors, identify the correlates of cardiogenic shock, and compare global quality of life and functional status of patients randomly assigned to treatment with emergency revascularization (ERV) versus initial medical stabilization (IMS). BACKGROUND Historically, the hospital survival rate of patients with cardiogenic shock complicating acute myocardial infarction (MI) has been very low. Shock survivors are salvaged from a critically ill state, and their later functional status is not well documented. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial showed significantly improved one-year survival after ERV compared with IMS. METHODS The SHOCK trial survivors completed interviews at 2 weeks after discharge and at 6 and 12 months after MI. Functional status assessment included the Multidimensional Index of Life Quality and New York Heart Association (NYHA) congestive heart failure functional class. RESULTS Eighty-seven percent of one-year survivors of the SHOCK trial were in NYHA functional. class I or II. Between two weeks after discharge and one year after MI, improvement was similar in the two treatment groups (18% overall), but fewer patients remained stable (44% vs. 71%), and more patients worsened or died (34% vs. 15%) in the IMS group compared with those assigned to ERV. Assignment to ERV was the only independent predictor of outcome at one year. CONCLUSIONS Although one-year mortality after ERV is still high (54%), most survivors have good functional status. The ERV patients have a lower rate of deterioration than IMS patients. The level of recovery for shock patients undergoing ERV is similar to that of historical controls not in cardiogenic shock undergoing elective revascularization. (c) 2005 by the American College of Cardiology Foundation. C1 New England Res Inst, Watertown, MA 02472 USA. NYU, Sch Med, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Albert Einstein Coll Med, Div Cardiol, Bronx, NY 10467 USA. Auckland Hosp, Dept Cardiol, Auckland, New Zealand. Toronto Gen Hosp, Toronto, ON, Canada. St Lukes Roosevelt Hosp, New York, NY USA. Wake Forest Univ, Winston Salem, NC USA. RP Sleeper, LA (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM lsleeper@neriscience.com OI Picard, Michael/0000-0002-9264-3243; Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [R01 HL49970, R01 HL50020] NR 14 TC 39 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 19 PY 2005 VL 46 IS 2 BP 266 EP 273 DI 10.1016/j.jacc.2005.01.061 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947RR UT WOS:000230664500008 PM 16022953 ER PT J AU Luo, J Sobkiw, CL Logsdon, NM Watt, JM Signoretti, S O'Connell, F Shin, E Shim, Y Pao, L Neel, BG DePinho, RA Loda, M Cantley, LC AF Luo, J Sobkiw, CL Logsdon, NM Watt, JM Signoretti, S O'Connell, F Shin, E Shim, Y Pao, L Neel, BG DePinho, RA Loda, M Cantley, LC TI Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE intestinal polyps; prostate intraepithelial neoplasia; AKT ID INCREASED INSULIN SENSITIVITY; PIK3CA GENE; HUMAN CANCER; EMBRYONIC LETHALITY; CATALYTIC SUBUNIT; P85-ALPHA SUBUNIT; SUPPRESSOR GENE; PTEN(+/-) MICE; MUTATION; PATHWAY AB Mice with heterozygous deletion of the PTEN tumor suppressor gene develop a range of epithelial neoplasia as well as lymphoid hyperplasia. Previous studies suggest that PTEN suppresses tumor formation by acting as a phosphoinositide phosphatase to limit signaling by phosphoinositide 3-kinase (PI3K). Here, we examined the effect of deleting various regulatory subunits of PI3K(p85 alpha and p85 beta) on epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice. Interestingly, we found the loss of one p85a allele with or without the loss of p85 beta led to increased incidence of intestinal polyps. Signaling downstream of PI3K was enhanced in the PTEN(+/-)p85 alpha(+/-)p85 beta(-/-) polyps, as judged by an increased fraction of both cells with cytoplasmic staining of the transcription factor WHIR and cells with positive staining for the proliferation marker Ki-67. In contrast, the incidence of prostate intraepithelial neoplasia was not significantly altered in PTEN+/- mice heterozygous for p85 alpha or null for p85 beta, whereas the fraction of proliferating cells in prostate intraepithelial neoplasia was reduced in mice lacking p85 beta. Finally, there was no significant change in T lymphocyte hyperplasia in the PTEN+/- mice with various p85 deletions, although anti-CD3-stimulated AKT activation was somewhat reduced in the p85 alpha(+/-) background. These results indicate that decreasing the levels of different p85 regulatory subunits can result in enhanced PI3K signaling in some tissues and decreased PI3K signaling in others, supporting the model that, although p85 proteins are essential for class I-A PI3K signaling, they can function as inhibitors of PI3K signaling in some tissues and thus suppress tumor formation. C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P01 CA089021, P01-CA089021]; NIGMS NIH HHS [R01 GM041890] NR 35 TC 27 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 2005 VL 102 IS 29 BP 10238 EP 10243 DI 10.1073/pnas.0504378102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 947SE UT WOS:000230665800046 PM 16006513 ER PT J AU Hirano, AA Brandstatter, JH Brecha, NC AF Hirano, AA Brandstatter, JH Brecha, NC TI Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE SNARE complex; exocytosis; GABA; amacrine cells; immunocytochemistry ID GAMMA-AMINOBUTYRIC-ACID; GABA-LIKE IMMUNOREACTIVITY; SYNAPTIC VESICLE PROTEINS; OUTER PLEXIFORM LAYER; CONE BIPOLAR CELLS; MOUSE RETINA; MAMMALIAN RETINA; RIBBON SYNAPSES; GLUTAMIC-ACID; CAT RETINA AB The mechanism underlying transmitter release from retinal horizontal cells is poorly understood. We investigated the possibility of vesicular transmitter release from mammalian horizontal cells by examining the expression of synaptic proteins that participate in vesicular transmitter release at chemical synapses. Using immunocytochemistry, we evaluated the cellular and subcellular distribution of complexin I/II, syntaxin-1, and synapsin I in rabbit retina. Strong labeling for complexin I/II, proteins that regulate a late step in vesicular transmitter release, was found in both synaptic layers of the retina, and in somata of A- and B-type horizontal cells, of gamma-aminobutyric acid (GABA)- and glycinergic amacrine cells, and of ganglion cells. Immunoelectron microscopy demonstrated the presence of complexin I/II in horizontal cell processes postsynaptic to rod and cone ribbon synapses. Syntaxin-1, a core protein of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) complex known to bind to complexin, and synapsin 1, a synaptic vesicle-associated protein involved in the Ca(2+)-dependent recruitment of synaptic vesicles for transmitter release, were also present in the horizontal cells and their processes at photoreceptor synapses. Photoreceptors and bipolar cells did not express any of these proteins at their axon terminals. The presence of complexin I/II, syntaxin-1, and synapsin I in rabbit horizontal cell processes and tips suggests that a vesicular mechanism may underlie transmitter release from mammalian horizontal cells. Published 2005 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Ctr Ulcer Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Educ Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Max Planck Inst Brain Res, Dept Neuroanat, D-60528 Frankfurt, Germany. Univ Erlangen Nuernberg, Inst Zool, D-91058 Erlangen, Germany. RP Hirano, AA (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave,Box 951763, Los Angeles, CA 90095 USA. EM ahirano@mednet.ucla.edu FU NEI NIH HHS [EY 04067, R01 EY004067, R01 EY015573, R01 EY015573-01A1, R56 EY004067] NR 105 TC 33 Z9 33 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 18 PY 2005 VL 488 IS 1 BP 70 EP 81 DI 10.1002/cne.20577 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 932MH UT WOS:000229557300006 PM 15912504 ER PT J AU Muljo, SA Ansel, KM Kanellopoulou, C Livingston, DM Rao, A Rajewsky, K AF Muljo, SA Ansel, KM Kanellopoulou, C Livingston, DM Rao, A Rajewsky, K TI Aberrant T cell differentiation in the absence of Dicer SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RNA INTERFERENCE; DNA METHYLATION; TH1 DEVELOPMENT; MICRORNAS; EXPRESSION; MECHANISMS; GATA-3 AB Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production. A severe block in peripheral CD8(+) T cell development was observed upon dcr-1 deletion in the thymus. However, Dicerdeficient CD4(+) T cells, although reduced in numbers, were viable and could be analyzed further. These cells were defective in microRNA processing, and upon stimulation they proliferated poorly and underwent increased apoptosis. Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Canc Biol, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu RI Muljo, Stefan/F-5671-2015 OI Muljo, Stefan/0000-0003-1013-446X FU NIAID NIH HHS [AI64345, AI44432, AI56900, R01 AI044432, R01 AI064345, U19 AI056900] NR 33 TC 375 Z9 397 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 18 PY 2005 VL 202 IS 2 BP 261 EP 269 DI 10.1084/jem.20050678 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 946UE UT WOS:000230597800009 PM 16009718 ER PT J AU Biederman, J Faraone, SV AF Biederman, J Faraone, SV TI Attention-deficit hyperactivity disorder SO LANCET LA English DT Review ID LOW-BIRTH-WEIGHT; SPONTANEOUSLY HYPERTENSIVE-RAT; STRIATAL DOPAMINE TRANSPORTER; HEALTH MULTIMODAL TREATMENT; PRENATAL ALCOHOL EXPOSURE; SUBSTANCE USE DISORDERS; SCHOOL-AGE-CHILDREN; DSM-IV ADHD; DEFICIT/HYPERACTIVITY-DISORDER; FOLLOW-UP AB Attention-deficit hyperactivity disorder (ADHD) is a disorder of inattention, impulsivity, and hyperactivity that affects 8-12% of children worldwide. Although the rate of ADHD falls with age, at least half of children with the disorder will have impairing symptoms in adulthood. Twin, adoption, and molecular genetic studies show ADHD to be highly heritable, and other findings have recorded obstetric complications and psychosocial adversity as predisposing risk factors. Converging evidence from animal and human studies implicates the dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits in the pathophysiology of ADHD, and molecular imaging studies suggest that abnormalities of the dopamine transporter lead to impaired neurotransmission. Studies during the past decade have shown the safety and effectiveness of new non-stimulant drugs and long-acting formulations of methylphenidate and amfetamine. Other investigations have also clarified the appropriate role of targeted psychosocial treatments in the context of ongoing pharmacotherapy. C1 Massachusetts Gen Hosp, Pediat Psychophamracol Unit, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychophamracol Unit ACC 725, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 179 TC 877 Z9 906 U1 50 U2 310 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 16 PY 2005 VL 366 IS 9481 BP 237 EP 248 DI 10.1016/S0140-6736(05)66915-2 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 945RG UT WOS:000230519200034 PM 16023516 ER PT J AU Todaro, JF Con, A Niaura, R Spiro, A Ward, KD Roytberg, A AF Todaro, JF Con, A Niaura, R Spiro, A Ward, KD Roytberg, A TI Combined effect of the metabolic syndrome and hostility on the incidence of myocardial infarction (the Normative Aging Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PSYCHOLOGICAL RISK-FACTORS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; HEALTH BEHAVIORS; YOUNG-ADULTS; PREVALENCE; MORTALITY; OLDER AB A growing body of evidence suggests that the metabolic syndrome and hostility are independent risk factors for the development of coronary heart disease. However, few studies have examined the combined effect of the metabolic syndrome and hostility on the incidence of myocardial infarction (MI). We examined prospectively the relation among the metabolic syndrome, hostility, and the incidence of MI in healthy, older men (mean +/- SD 59.7 +/- 7.2 years) who participated in the Normative Aging Study. Seven hundred fifty-four men who were diagnosed as not having coronary heart disease and diabetes mellitus were included in the present study. Men were assigned to 1 of 4 risk-factor groups based on the presence or absence of the metabolic syndrome and low or high hostility. Hierarchical logistic regression was used to assess the multivariate risk of developing a MI. The incidence of MI was 11.3% (n = 85) over an average follow-up period of 13.8 years. After adjusting for potential covariates, risk-factor group significantly predicted the incidence of MI (odds ratio 1.59, 95% confidence interval 1.29 to 1.96, p < 0.0001). The effect was strongest among patients who had the metabolic syndrome and high levels of hostility, with this subgroup showing a fourfold increase in the odds of developing a MI (odds ratio 4.21, 95% confidence interval 2.21 to 8.04, p = 0.0001). In conclusion, it appears that hostility may provide additional prognostic information to the assessment of coronary heart disease risk in patients with the metabolic syndrome and should routinely be evaluated as part of a comprehensive risk factor assessment. (c) 2005 Elsevier Inc. All rights reserved. C1 Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI USA. Miriam Hosp, Providence, RI USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Memphis, Dept Hlth & Sport Sci, Memphis, TN 38152 USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. RP Todaro, JF (reprint author), Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI USA. EM john_todaro@brown.edu OI Spiro III, Avron/0000-0003-4080-8621 FU NHLBI NIH HHS [HL 004473, HL 37871]; NIA NIH HHS [AG 02287] NR 31 TC 16 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 2005 VL 96 IS 2 BP 221 EP 226 DI 10.1016/j.amjcard.2005.03.049 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 945WF UT WOS:000230532500013 PM 16018847 ER PT J AU Sakhuja, R Chen, AA Anwaruddin, S Baggish, AL Januzzi, JL AF Sakhuja, R Chen, AA Anwaruddin, S Baggish, AL Januzzi, JL CA PRIDE Study Grp TI Combined use of amino terminal-pro-brain natriuretic peptide levels and QRS duration to predict left ventricular systolic dysfunction in patients with dyspnea SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; NT-PROBNP; ELECTROCARDIOGRAM; ECHOCARDIOGRAPHY; MARKER AB The combination of elevated amino-terminal pro-brain natriuretic peptide levels and wide QRS duration was highly sensitive and specific for the prediction of impaired left ventricular systolic function among a group of patients presenting with dyspnea to the emergency department. This strategy can be used to predict depressed function and target more formal evaluation with echocardiography in patients with dyspnea. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Januzzi, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. EM JJanuzzi@Partners.org NR 13 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 2005 VL 96 IS 2 BP 263 EP 266 DI 10.1016/j.amjcard.2005.03.056 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 945WF UT WOS:000230532500020 PM 16018854 ER PT J AU Kostis, JB Jackson, G Rosen, R Barrett-Connor, E Billups, K Burnett, AL Carson, C Cheitlin, M Debusk, R Fonseca, V Ganz, P Goldstein, I Guay, A Hatzichristou, D Hollander, JE Hutter, A Katz, S Kloner, RA Mittleman, M Montorsi, F Montorsi, P Nehra, A Sadovsky, R Shabsigh, R AF Kostis, JB Jackson, G Rosen, R Barrett-Connor, E Billups, K Burnett, AL Carson, C Cheitlin, M Debusk, R Fonseca, V Ganz, P Goldstein, I Guay, A Hatzichristou, D Hollander, JE Hutter, A Katz, S Kloner, RA Mittleman, M Montorsi, F Montorsi, P Nehra, A Sadovsky, R Shabsigh, R TI Sexual dysfunction and cardiac risk (The Second Princeton Consensus Conference) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Review ID LIFE-STYLE CHANGES; ERECTILE-DYSFUNCTION; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; SILDENAFIL-CITRATE; HEART-FAILURE; NITRIC-OXIDE; DOUBLE-BLIND; MEN; TADALAFIL AB Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. St Thomas Hosp, Nashville, TN USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ N Carolina, Chapel Hill, NC USA. Stanford Univ, Sch Med, Stanford, CA USA. Tulane Univ, Med Ctr, New Orleans, LA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA USA. Lahey Clin Fdn, Ctr Sexual Funct Endocrinol, Peabody, MA USA. Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. Hosp Univ Philadelphia, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Good Samaritan Hosp, Inst Heart, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA USA. Univ Vita Salute, S Raffaele Hosp, Milan, Italy. Univ Milan, Inst Cardiol, Milan, Italy. Mayo Clin, Rochester, MN USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Columbia Univ, Sch Med, New York, NY USA. RP Kostis, JB (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. EM kostis@umdnj.edu OI Hollander, Judd/0000-0002-1318-2785 NR 53 TC 166 Z9 182 U1 1 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 2005 VL 96 IS 2 BP 313 EP 321 DI 10.1016/j.amjcard.2005.03.065 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 945WF UT WOS:000230532500030 PM 16018863 ER PT J AU Vives, S Loucas, B Vazquez, M Brenner, DJ Sachs, RK Hlatky, L Cornforth, M Arsuaga, J AF Vives, S Loucas, B Vazquez, M Brenner, DJ Sachs, RK Hlatky, L Cornforth, M Arsuaga, J TI SCHIP: statistics for chromosome interphase positioning based on interchange data SO BIOINFORMATICS LA English DT Article ID HUMAN-CELLS; ABERRATIONS; PROXIMITY AB The position of chromosomes in the interphase nucleus is believed to be associated with a number of biological processes. Here, we present a web-based application that helps analyze the relative position of chromosomes during interphase in human cells, based on observed radiogenic chromosome aberrations. The inputs of the program are a table of yields of pairwise chromosome interchanges and a proposed chromosome geometric cluster. Each can either be uploaded or selected from provided datasets. The main outputs are P-values for the proposed chromosome clusters. SCHIP is designed to be used by a number of scientific communities interested in nuclear architecture, including cancer and cell biologists, radiation biologists and mathematical/computational biologists. C1 Univ Calif San Francisco, Comprehens Canc Ctr, Canc Res Inst, Balmain Lab, San Francisco, CA 94115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Univ Calif Berkeley, Math Dept, Berkeley, CA 94720 USA. Univ Texas, Med Branch, Radiat Oncol Dept, Galveston, TX 77555 USA. Univ Barcelona, Dept Estadistica, Barcelona 08028, Spain. RP Arsuaga, J (reprint author), Univ Calif San Francisco, Comprehens Canc Ctr, Canc Res Inst, Balmain Lab, San Francisco, CA 94115 USA. EM jarsuaga@cc.ucsf.edu FU NCI NIH HHS [CA76260]; NIDCR NIH HHS [DE-PG-02-98ER62686]; NIGMS NIH HHS [GM68423] NR 11 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 15 PY 2005 VL 21 IS 14 BP 3181 EP 3182 DI 10.1093/bioin/bti470 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 941GX UT WOS:000230204400021 PM 15886279 ER PT J AU Rodrigues, NP Janzen, V Forkert, R Dombkowski, DM Boyd, AS Orkin, SH Enver, T Vyas, P Scadden, DT AF Rodrigues, NP Janzen, V Forkert, R Dombkowski, DM Boyd, AS Orkin, SH Enver, T Vyas, P Scadden, DT TI Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; FETAL LIVER HEMATOPOIESIS; CYCLE ENTRY; ERYTHROID DEVELOPMENT; MICE LACKING; IN-VIVO; C-MYB; GENE; EXPRESSION; APOPTOSIS AB The zinc finger transcription factor GATA-2 plays a fundamental role in generating hematopoietic stem-cells in mammalian development. Less well defined is whether GATA-2 participates in adult stem-cell regulation, an issue we addressed using GATA-2 heterozygote mice that express reduced levels of GATA-2 in hematopoietic cells. While GATA-2(+/-) mice demonstrated decreases in some colony-forming progenitors, the most prominent changes were observed within the stem-cell compartment. Heterozygote bone marrow had a lower abundance of Lin(-) c-kit(+)Sca-1(+)CD34(-) cells and performed poorly in competitive transplantation and quantitative week-5 cobblestone area-forming cell (CAFC) assays. Furthermore, a stem-cell-enriched population from GATA1(+/-) marrow was more quiescent and exhibited a greater frequency of apoptotic cells associated with decreased expression of the antiapoptotic gene Bcl-xL. Yet the self-renewal potential of the +/- stem-cell compartment, as judged by serial transplantations, was unchanged. These data indicate compromised primitive cell proliferation and survival in the setting of a lower GATA-2 gene dose without a change in the differentiation or self-renewal capacity of the stem-cells that remain. Thus, GATA-2 dose regulates adult stem-cell homeostasis by affecting select aspects of stem cell function. C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Dept Haematol, Oxford OX3 9DS, England. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Weatherall Inst Mol Med,MRC,Haematol Unit, Oxford OX3 9DS, England. RP Scadden, DT (reprint author), Massachusetts Gen Hosp East, Ctr Regenerat Med & Technol, Rm 5212D,Bldg 149,13th St, Boston, MA 02129 USA. EM paresh.vyas@imm.ox.ac.uk OI Vyas, Paresh/0000-0003-3931-0914 FU Wellcome Trust NR 53 TC 125 Z9 129 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 477 EP 484 DI 10.1182/blood-2004-08-2989 PG 8 WC Hematology SC Hematology GA 945AG UT WOS:000230472100025 PM 15811962 ER PT J AU Growney, JD Shigematsu, H Li, Z Lee, BH Adeisperger, J Rowan, R Curley, DP Kutok, JL Akashi, K Williams, IR Speck, NA Gilliland, DG AF Growney, JD Shigematsu, H Li, Z Lee, BH Adeisperger, J Rowan, R Curley, DP Kutok, JL Akashi, K Williams, IR Speck, NA Gilliland, DG TI Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FETAL LIVER HEMATOPOIESIS; MRC AML TRIALS; STEM-CELLS; TEL/AML1 FUSION; IN-VIVO; DEFINITIVE HEMATOPOIESIS; AML1/PEBP2-ALPHA-B GENE AB Homozygous loss of function of Runx1 (Runt-related transcription factor 1 gene) during murine development results in an embryonic lethal phenotype characterized by a complete lack of definitive hematopoiesis. In light of recent reports of disparate requirements for hematopoietic transcription factors during development as opposed to adult hematopoiesis, we used a conditional gene-targeting strategy to effect the loss of Runx1 function in adult mice. in contrast with the critical role of Runx1 during development, Runx1 was not essential for hematopoiesis in the adult hematopoietic compartment, though a number of significant hematopoietic abnormalities were observed. Runx1 excision had lineage-specific effects on B- and T-cell maturation and pronounced inhibition of common lymphocyte progenitor production. Runx1 excision also resulted in inefficient platelet production. Of note, Runx1-deficient mice developed a mild myeloproliferative phenotype characterized by an increase in peripheral blood neutrophils, an increase in myeloid progenitor populations, and extramedullary hematopoiesis composed of maturing myeloid and erythroid elements. These findings indicate that Runx1 deficiency has markedly different consequences during development compared with adult hematopoiesis, and they provide insight into the phenotypic manifestations of Runx1 deficiency in hematopoietic malignancies. C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. RP Growney, JD (reprint author), Brigham & Womens Hosp, Div Hematol, 1Blackfan Circle, Boston, MA 02115 USA. EM jgrowney@rics.bwh.harvard.edu; ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NCI NIH HHS [CA66996, R01 CA058343, R01CA58343]; PHS HHS [50564] NR 63 TC 240 Z9 244 U1 1 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 494 EP 504 DI 10.1182/blood-2004-08-3280 PG 11 WC Hematology SC Hematology GA 945AG UT WOS:000230472100027 PM 15784726 ER PT J AU Battle, TE Arbiser, J Frank, DA AF Battle, TE Arbiser, J Frank, DA TI The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells SO BLOOD LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MAGNOLIA-OFFICINALIS; IN-VITRO; INTRINSIC PATHWAY; CYTOCHROME-C; DEATH; EXPRESSION; BCL-2; MCL-1; MODULATION AB B-cell chronic lymphocytic leukemia (B-CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Hlonokiol is a natural product known to possess potent antineoplastic and antiangiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspase-3, -8, and -9 and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP). Exposure of B-CLL cells to honokiol resulted in upregulation of Bcl2-associated protein (Bax) and down-regulation of the expression of the key survival protein myeloid-cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pretreated with interleukin-4 (IL-4), a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the prosurvival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 522B,44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 46 TC 127 Z9 137 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 690 EP 697 DI 10.1182/blood-2004-11-4273 PG 8 WC Hematology SC Hematology GA 945AG UT WOS:000230472100052 PM 15802533 ER PT J AU Yasui, H Hideshima, T Hamasaki, M Roccaro, AM Shiraishi, N Kumar, S Tassone, P Ishitsuka, K Raje, N Tai, YT Podar, K Chauhan, D Leoni, LM Kanekal, S Elliott, G Munshi, NC Anderson, KC AF Yasui, H Hideshima, T Hamasaki, M Roccaro, AM Shiraishi, N Kumar, S Tassone, P Ishitsuka, K Raje, N Tai, YT Podar, K Chauhan, D Leoni, LM Kanekal, S Elliott, G Munshi, NC Anderson, KC TI SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma SO BLOOD LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; BONE-MARROW MICROENVIRONMENT; CHRONIC LYMPHOCYTIC-LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; NECROSIS-FACTOR-ALPHA; CELL-GROWTH; UP-REGULATION; COMBINATION CHEMOTHERAPY; KINASE ACTIVATION AB In this study we report that R-etodolac (SDX-101), at clinically relevant concentrations, induces potent cytotoxicity in drug-sensitive multiple myeloma (MM) cell lines, as well as in dexamethasone (MM.1R)-, doxorubicin (Dox40/RPMI8226)-, and bortezomib (DHL4)-resistant cell lines. Immunoblot analysis demonstrates that R-etodolac induces apoptosis characterized by caspase-8, -9, and -3 and PARP (poly-ADP [adenosine diphosphate]-ribose polymerase) cleavage and down-regulation of cyclin D1 expression. Subcytotoxic doses of R-etodolac up-regulate myeloid cell leukemia-1 proapoptotic variant (Mcl-1(s)), while enhancing dexamethasone (Dex)-induced caspase activation and apoptosis. The combination of R-etodolac with Dex results in a highly synergistic cytotoxic effect. R-etodolac also induces apoptosis against primary cells isolated from patients with MM refractory to chemotherapy. Although interleukin 6 (IL-6) and insulin-like growth factor-1 (IGF-1) abrogate Dex-induced MM cell cytotoxicity, neither IL-6 nor IGF-1 protects against R-etodolac-induced cytotoxicity in MM cells. R-etodolac also inhibits viability Of MM cells adherent to bone marrow stromal cells (BMSCs), thereby overcoming a mechanism of drug resistance commonly observed with other conventional chemotherapeutic agents. Our data, therefore, indicate that R-etodolac circumvents drug resistance in MM cells at clinically relevant concentrations, targets Mcl-1, and can be synergistically combined with Dex. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Salmedix Inc, San Diego, CA USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [P0-1 CA78378, R0-1 CA50947, IP50 CA10070-01] NR 77 TC 38 Z9 41 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 706 EP 712 DI 10.1182/blood-2005-02-0838 PG 7 WC Hematology SC Hematology GA 945AG UT WOS:000230472100054 PM 15802527 ER PT J AU Tassone, P Neri, P Carrasco, DR Burger, R Goldmacher, VS Fram, R Munshi, V Shammas, MA Catley, L Jacob, GS Venuta, S Anderson, KC Munshi, NC AF Tassone, P Neri, P Carrasco, DR Burger, R Goldmacher, VS Fram, R Munshi, V Shammas, MA Catley, L Jacob, GS Venuta, S Anderson, KC Munshi, NC TI A clinically relevant SCID-hu in vivo model of human multiple myeloma SO BLOOD LA English DT Article ID HUMAN BONE-MARROW; MICE; CELLS; THERAPY; DISEASE; GROWTH; MOUSE; RECEPTOR; BIOLOGY AB We developed a novel in vivo multiple myeloma (MM) model by engrafting the interleukin 6 (IL-6)-dependent human MM cell line INA-6 into severe combined immunodeficiency (SCID) mice previously given implants of a human fetal bone chip (SCID-hu mice). INA-6 cells require either exogenous human IL-6 (huIL-6) or bone marrow stromal cells (BMSCs) to proliferate in vitro. In this model, we monitored the in vivo growth of INA-6 cells stably transduced with a green fluorescent protein (GFP) gene (INA-6(GFP+) cells). INA-6 MM cells engrafted in SCID-hu mice but not in SCID mice that had not been given implants of human fetal bone. The level of soluble human IL-6 receptor (shuIL-6R) in murine serum and fluorescence imaging of host animals were sensitive indicators of tumor growth. Dexamethasone as well as experimental drugs, such as Atiprimod and B-B4-DM1, were used to confirm the utility of the model for evaluation of anti-MM agents. We report that this model is highly reproducible and allows for evaluation of investigational drugs targeting IL-6-dependent MM cells in the human bone marrow (huBM) milieu. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia, Catanzaro, Italy. ImmunoGen Inc, Cambridge, MA USA. Callisto Pharmaceut Inc, New York, NY USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [R01-50947, P50-100707, P01-78378] NR 22 TC 87 Z9 89 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 713 EP 716 DI 10.1182/blood-2005-01-0373 PG 4 WC Hematology SC Hematology GA 945AG UT WOS:000230472100055 PM 15817674 ER PT J AU Growney, JD Clark, JJ Adelsperger, J Stone, R Fabbro, D Griffin, JD Gilliland, DG AF Growney, JD Clark, JJ Adelsperger, J Stone, R Fabbro, D Griffin, JD Gilliland, DG TI Activation mutations of human c-KIT resistant to imatinib, mesylate are sensitive to the tyrosine kinase inhibitor PKC412 SO BLOOD LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; MAST-CELL DISEASE; WILD-TYPE; DOMAIN MUTATIONS; HUMAN MASTOCYTOSIS; HUMAN LEUKEMIA; STI571; PROLIFERATION AB Constitutively activated forms of the transmembrane receptor tyrosine kinase c-KIT have been associated with systemic mast cell disease, acute myeloid leukemia, and gastrointestinal stromal tumors. Reports of the resistance of the kinase domain mutation D816V to the adenosine triphosphate (ATP)-competitive kinase inhibitor imatinib mesylate prompted us to characterize 14 c-KIT mutations reported in association with human hematologic malignancies for transforming activity in the murine hematopoietic cell line Ba/F3 and for sensitivity to the tyrosine kinase inhibitor PKC412. Ten of 14 c-KIT mutations conferred interleukin 3 (IL-3)-independent growth. c-KIT D816Y and D816V transformed cells were sensitive to PKC412 despite resistance to imatinib mesylate. In these cells, PKC412, but not imatinib mesylate, inhibited autophosphorylation of c-KIT and activation of downstream effectors signal transducer and transcriptional activator 5 (Stat5) and Stat3. Variable sensitivities to PKC412 or imatinib mesylate were observed among other mutants. These findings suggest that PKC412 may be a useful therapeutic agent for c-KIT-positive malignancies harboring the imatinib mesylate-resistant D816V or D816Y activation mutations. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Karp Family Res Bldg,1 Blackfan Circle,5th Fl, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu FU NCI NIH HHS [CA-66996]; NIDDK NIH HHS [DK50564] NR 25 TC 150 Z9 154 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2005 VL 106 IS 2 BP 721 EP 724 DI 10.1182/blood-2004-12-4617 PG 4 WC Hematology SC Hematology GA 945AG UT WOS:000230472100057 PM 15790786 ER PT J AU Chan, JA Krichevsky, AM Kosik, KS AF Chan, JA Krichevsky, AM Kosik, KS TI MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells SO CANCER RESEARCH LA English DT Article ID LOCKED NUCLEIC-ACIDS; CAENORHABDITIS-ELEGANS; RNA; DIFFERENTIATION; EXPRESSION; GENES; BRAIN; ACCUMULATION; INHIBITION AB MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for either cleavage or repression of translation. The roles of miRNAs in lineage determination and proliferation as well as the location of several miRNA genes at sites of translocation breakpoints or deletions has led to the speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state. Here we show that the highly malignant human brain tumor, glioblastoma, strongly overexpresses a specific miRNA, miR-21. Our studies show markedly elevated miR-21 levels in human glioblastoma tumor tissues, early-passage glioblastoma cultures, and in six established glioblastoma cell lines (A172, U87, U373, LN229, LN428, and LN308) compared with nonneoplastic fetal and adult brain tissues and compared with cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. RP Krichevsky, AM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 4 Blackfan Circle HIM 760, Boston, MA 02115 USA. EM krichevsky@cnd.bwh.harvard.edu FU NINDS NIH HHS [NS46569] NR 24 TC 1517 Z9 1706 U1 20 U2 136 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 JUL 15 PY 2005 VL 65 IS 14 BP 6029 EP 6033 DI 10.1158/0008-5472.CAN-05-0137 PG 5 WC Oncology SC Oncology GA 947HG UT WOS:000230633400010 PM 16024602 ER PT J AU Krysan, K Reckamp, KL Dalwadi, H Sharma, S Rozengurt, E Dohadwala, M Dubinett, SM AF Krysan, K Reckamp, KL Dalwadi, H Sharma, S Rozengurt, E Dohadwala, M Dubinett, SM TI Prostaglandin E-2 activates mitogen-activated protein kinase/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an epidermal growth factor receptor-independent manner SO CANCER RESEARCH LA English DT Article ID EGF RECEPTOR; COUPLED RECEPTORS; EPITHELIAL-CELLS; CARCINOMA-CELLS; CYCLOOXYGENASE-2; PHOSPHORYLATION; MUTATIONS; GEFITINIB; THERAPY; GENE AB Cyclooxygenase 2 (COX-2) overexpression is found in a wide variety of human cancers and is linked to all stages of tumorigenesis. Elevated tumor COX-2 expression is associated with increased angiogenesis, tumor invasion, suppression of host immunity and promotes tumor cell resistance to apoptosis. Previous reports have linked the COX-2 product prostaglandin E-2 (PGE(2)) to the abnormal activation of the mitogen-activated protein kinase/Erk kinase pathway. Here we show that PGE(2) is able to rapidly stimulate Erk phosphorylation in a subset of non-small cell lung cancer (NSCLC) cell lines. This effect is not evident in bronchial epithelial cells. In contrast to previous reports in colon cancer, we found that Erk activation as well as cellular proliferation induced by PGE2 was not inhibited by pretreatment of the cells with epidermal growth factor receptor (EGFR) inhibitors. Activation of the Erk pathway by PGE2 was also resistant to src kinase inhibitors but sensitive to the protein kinase C inhibition. PGE2 effects are mediated through four G protein-coupled receptors. Selective inhibition of EP receptors revealed the possible involvement of Ca2+-dependent signaling in PGE(2)-mediated activation of Erk. Our data indicate the presence of an EGFR-independent activation of the mitogen-activated protein kinase/Erk pathway by PGE2 in NSCLC cells. These findings provide evidence for the possible link between tumor COX-2 overexpression and elevated Erk-mediated cancer cell proliferation and migration. Importantly, these findings suggest that COX-2 overexpression may contribute to EGFR inhibitor resistance in NSCLC. C1 Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [P50 CA90388] NR 49 TC 149 Z9 157 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 JUL 15 PY 2005 VL 65 IS 14 BP 6275 EP 6281 DI 10.1158/0008-5472.CAN-05-0216 PG 7 WC Oncology SC Oncology GA 947HG UT WOS:000230633400037 PM 16024629 ER PT J AU Montet, X Ntziachristos, V Grimm, J Weissleder, R AF Montet, X Ntziachristos, V Grimm, J Weissleder, R TI Tomographic fluorescence mapping of tumor targets SO CANCER RESEARCH LA English DT Article ID FLUOROCHROME-LABELED ANTIBODIES; LASER-SCANNING MICROSCOPY; IN-VIVO; OPTICAL TOMOGRAPHY; GENE-EXPRESSION; MONOCLONAL-ANTIBODY; BREAST-CARCINOMA; ANGIOGENESIS; CANCER; VISUALIZATION AB Methods that allow robust imaging of specific molecular targets and biological processes in vivo should have widespread applications in biology and clinical medicine. Here we use a quantitative, three-dimensional fluorescence-mediated tomographic technique (FMT) that enables rapid measurements of fluorochrome-based affinity tags in live xenograft models. We validate the method by showing its sensitivity in quantitating tumor angiogenesis and therapeutic modulation using an anti-vascular endothelial growth factor antibody. Furthermore, we show the feasibility of simultaneous multichannel measurements of distinct biological phenomena such as receptor tyrosine kinase expression and angiogenesis. FMT measurements can be done serially, with short imaging times and within the same live animal. The described method should be valuable for rapidly profiling biological phenomena in vivo. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM weisleder@helix.mgh.harvard.edu RI Grimm, Jan/B-1937-2008; OI Montet, Xavier/0000-0003-2442-5866 NR 42 TC 136 Z9 142 U1 0 U2 8 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 JUL 15 PY 2005 VL 65 IS 14 BP 6330 EP 6336 DI 10.1158/0008-5472.CAN-05-0382 PG 7 WC Oncology SC Oncology GA 947HG UT WOS:000230633400043 PM 16024635 ER PT J AU Shimamura, T Lowell, AM Engelman, JA Shapiro, GI AF Shimamura, T Lowell, AM Engelman, JA Shapiro, GI TI Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; CYCLIN-D EXPRESSION; HSP90 FUNCTION; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR CHAPERONE; SIGNAL-TRANSDUCTION; TYROSINE KINASES; ANTITUMOR AGENT; EGFR MUTATIONS; BRAF GENE AB Somatic mutations in the kinase domain of the epidermal growth factor receptor (EGFR), including L858R and exon 19 deletions, underlie responsiveness to gefitinib and erlotinib in non-small cell lung cancer (NSCLC). Acquired resistance to these tyrosine kinase inhibitors is in some cases mediated by a second mutation, T790M. Ansamycin antibiotics, such as geldanamycin, potently inhibit heat shock protein 90 (Hsp90), promoting ubiquitin-mediated degradation of oncogenic kinases that require the chaperone for proper conformational folding. Here, we show that L858R and deletion mutant EGFR proteins found in NSCLC interact with the chaperone and are sensitive to degradation following Hsp90 inhibition. In NIH/3T3 cells expressing either wild-type or mutant EGFR, diminution of expression of both L85SR and EGFR deIL747-S752, P753S occurred following exposure to 50 nmol/L geldanamycin over 24 hours, whereas partial diminution of wild-type EGFR required a minimum of 200 nmol/L drug. In time course experiments, mutant EGFR expression was depleted after only 4 hours of exposure to 1 mu mol/L geldanamycin, whereas diminution of wild-type EGFR was less substantial and seen only following 12 hours. Similarly, EGFR proteins in NSCLC cell lines harboring EGFR mutations, including NCI-H1650, NCI-H3255, and NO-H1975, were also more sensitive to geldanamycin-induced degradation compared with the protein in wild-type cells. Exposure of EGFR-mutant cell lines to geldanamycin induced marked depletion of phospho-Akt and cyclin D1 as well as apoptosis. These data suggest mutational activation of EGFR is associated with dependence on Hsp90 for stability and that Hsp90 inhibition may represent a novel strategy for the treatment of EGFR-mutant NSCLC. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, DAna 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [P20 CA90578, T32 CA009172] NR 55 TC 173 Z9 181 U1 4 U2 10 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 JUL 15 PY 2005 VL 65 IS 14 BP 6401 EP 6408 DI 10.1158/0008-5472.CAN-05-0933 PG 8 WC Oncology SC Oncology GA 947HG UT WOS:000230633400052 PM 16024644 ER PT J AU Arlotta, P Macklis, JD AF Arlotta, P Macklis, JD TI Archeo-cell biology: Carbon dating is not just for pots and dinosaurs SO CELL LA English DT Editorial Material ID SUBVENTRICULAR ZONE; ADULT MICE; NEUROGENESIS; PROLIFERATION; NEURONS; FOREBRAIN; NEOCORTEX; RAT AB Defining the life span of specific human cell populations is limited by our inability to mark the exact time when cells are born in a way that can be detected over many years. In this issue of Cell, Spalding et al. (2005) describe a clever strategy for retrospectively birth dating human cells in vivo, based on their incorporation of C-14 during a peak in atmospheric levels of this isotope resulting from above-ground nuclear arms testing in the 1950s. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg,Pr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurol,Progr, Boston, MA 02114 USA. RP Arlotta, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg,Pr, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 15 PY 2005 VL 122 IS 1 BP 4 EP 6 DI 10.1016/j.cell.2005.06.037 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 950EC UT WOS:000230839400003 PM 16009125 ER PT J AU Carroll, JS Liu, XS Brodsky, AS Li, W Meyer, CA Szary, AJ Eeckhoute, J Shao, WL Hestermann, EV Geistlinger, TR Fox, EA Silver, PA Brown, M AF Carroll, JS Liu, XS Brodsky, AS Li, W Meyer, CA Szary, AJ Eeckhoute, J Shao, WL Hestermann, EV Geistlinger, TR Fox, EA Silver, PA Brown, M TI Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1 SO CELL LA English DT Article ID BREAST-CANCER CELLS; BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR; CHROMATIN-IMMUNOPRECIPITATION; RESPONSIVE ELEMENT; GENE-EXPRESSION; ALPHA; ACTIVATION; IDENTIFICATION; MICROARRAY AB Estrogen plays an essential physiologic role in reproduction and a pathologic one in breast cancer. The completion of the human genome has allowed the identification of the expressed regions of protein-coding genes; however, little is known concerning the organization of their cis-regulatory elements. We have mapped the association of the estrogen receptor (ER) with the complete nonrepetitive sequence of human chromosomes 21 and 22 by combining chromatin immunoprecipitation (ChIP) with tiled microarrays. ER binds selectively to a limited number of sites, the majority of which are distant from the transcription start sites of regulated genes. The unbiased sequence interrogation of the genuine chromatin binding sites suggests that direct ER binding requires the presence of Forkhead factor binding in close proximity. Furthermore, knockdown of FoxA1 expression blocks the association of ER with chromatin and estrogen-induced gene expression demonstrating the necessity of FoxA1 in mediating an estrogen response in breast cancer cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Furman Univ, Dept Biol, Greenville, SC 29613 USA. RP Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Li, Wei/A-8544-2009; OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NCI NIH HHS [F32 CA108380-02]; NHGRI NIH HHS [K22 HG02488-01A1]; NIDDK NIH HHS [T90 DK070078-01] NR 50 TC 774 Z9 791 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 15 PY 2005 VL 122 IS 1 BP 33 EP 43 DI 10.1016/j.cell.2005.05.008 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 950EC UT WOS:000230839400009 PM 16009131 ER PT J AU Ross, RW Manola, J Hennessy, K Galsky, M Scher, H Small, E Kelly, WK Kantoff, PW AF Ross, RW Manola, J Hennessy, K Galsky, M Scher, H Small, E Kelly, WK Kantoff, PW TI Prognostic significance of baseline reverse transcriptase-PCR for prostate-specific antigen in men with hormone-refractory prostate cancer treated with chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL ID POLYMERASE-CHAIN-REACTION; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; CELLS; RECURRENCE; CARCINOMA; BLOOD; ASSAY AB Purpose: Methods accurately categorizing the diverse biology of prostate cancer are needed. A positive baseline reverse transcriptase-PCR for prostate-specific antigen (RT-PCR PSA) in the androgen-independent setting is an independent prognostic marker of survival. The objectives of the current study were to examine the prognostic implication of baseline RT-PCR PSA positivity during treatment with an active chemotherapeutic agent and explore whether an RT-PCR PSA "response" provides prognostic information. Materials and Methods: In a combined analysis of a phase I and a randomized phase II trial of BMS-247550 (an epothilone B analogue), 104 patients with hormone-refractory prostate cancer had whole blood samples collected at baseline, then with each cycle of therapy. RT-PCR PSA was assessed and related to time to progression (TTP). Results: From 100 evaluable patients, 368 samples were received, of which 90.8% were evaluable for RT-PCR PSA status. Baseline RT-PCR PSA status was significantly associated with TTP (hazard ratio, 2.22; 95% confidence interval, 1.40-3.52). Twenty-six of 38 patients positive at first assessment had at least one follow-up RT-PCR PSA that was negative ("response"). In univariate analysis, RT-PCR PSA response was not significantly associated with TTP, but in multivariate analysis, RT-PCR PSA response was of borderline statistical significance in predicting TTP (hazard ratio, 0.41; 95% confidence interval, 0.16-1.01). Conclusion: These results provide further confirmation that baseline RT-PCR PSA is a statistically significant predictor of TTP in hormone-refractory prostate cancer. Moreover, this is the first report to suggest that RT-PCR PSA response during chemotherapy treatment may predict TTR. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Ross, RW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith 353,44 Binney St, Boston, MA 02115 USA. EM rwross@partners.org NR 13 TC 11 Z9 11 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 JUL 15 PY 2005 VL 11 IS 14 BP 5195 EP 5198 DI 10.1158/1078-0432.CCR-05-0431 PG 4 WC Oncology SC Oncology GA 945VG UT WOS:000230529800020 PM 16033836 ER PT J AU Febbo, PG Richie, JP George, DJ Loda, M Manola, J Shankar, S Barnes, AS Tempany, C Catalona, W Kantoff, PW Oh, WK AF Febbo, PG Richie, JP George, DJ Loda, M Manola, J Shankar, S Barnes, AS Tempany, C Catalona, W Kantoff, PW Oh, WK TI Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; HORMONAL-THERAPY; ESTRAMUSTINE PHOSPHATE; CHEMOTHERAPY; ANTIGEN; EXPRESSION; MITOXANTRONE; MONOTHERAPY; PREDNISONE; MANAGEMENT AB Purpose: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Experimental Design: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels > 20 ng/mL, and/or clinical stage T-3 disease received weekly docetaxel (36 mg/m(2)) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. Results: The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of > 50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Conclusions: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of > 50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med 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 FU NCI NIH HHS [K23 CA089031-03, K23 CA089031, K23 CA89031] NR 41 TC 131 Z9 134 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 JUL 15 PY 2005 VL 11 IS 14 BP 5233 EP 5240 DI 10.1158/1078-0432.CCR-05-0299 PG 8 WC Oncology SC Oncology GA 945VG UT WOS:000230529800025 PM 16033841 ER PT J AU Fox, RK Currie, SL Evans, J Wright, TL Tobler, L Phelps, B Busch, MP Page-Shafer, K AF Fox, RK Currie, SL Evans, J Wright, TL Tobler, L Phelps, B Busch, MP Page-Shafer, K TI Hepatitis C virus infection among prisoners in the California State correctional system SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTI-D IMMUNOGLOBULIN; GENDER-DIFFERENCES; RISK-FACTORS; HETEROSEXUAL TRANSMISSION; PLUS RIBAVIRIN; HIV; PREVALENCE; WOMEN AB Background. Incarcerated populations are at high risk for hepatitis C virus (HCV) infection, yet prisoners are not routinely screened or treated for HCV infection. Understanding the risk factors of HCV infection among prisoners could help improve HCV interventions. Methods. Prevalence and risk of HCV infection among 469 prisoners entering California State correctional facilities were assessed using HCV antibody screening, HCV RNA measurement, and structured interviews. Multivariate logistic regression analysis was used to identify independent correlates of HCV infection. Results. The prevalence of HCV infection was 34.3% overall (95% confidence interval [CI], 30% - 38%) and was 65.7% among those with a history of injection drug use (IDU), compared with 10.2% among those with no history of IDU (odds ratio [OR], 17.24; 95% CI, 10.52 - 28.25). Significant differences in HCV antibody positivity were found in association with age at first detention but not with the nature of the crime. Independent correlates of HCV infection included age, history of IDU, cumulative time of incarceration, biological sex ( OR for females subjects compared with males subjects, 0.35; 95% CI, 0.13 - 0.96), and a history of having sex with a male IDU (OR, 4.42; 95% CI, 1.46 - 13.37). We identified significant differences in risk factors between male and female subjects - notably, that the risk of HCV infection was significantly elevated among female non-IDUs who reported having sexual partners with a history of IDU. Among non-IDUs, correlates of HCV infection included history of receipt of blood products and cumulative years of incarceration. Conclusions. HCV infection is pervasive among the California prison population, including prisoners who are non-IDUs and women with high-risk sexual behavior. These results should promote consideration of routine HCV antibody screening and behavioral interventions among incarcerated men and women. C1 Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94105 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94105 USA. San Francisco Vet Adm Med Ctr, Div Gastroenterol, San Francisco, CA USA. Blood Syst Res Inst, San Francisco, CA USA. Chiron Corp, Emeryville, CA 94608 USA. RP Page-Shafer, K (reprint author), Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, 74 New Montgomery,Ste 600, San Francisco, CA 94105 USA. EM kshafer@psg.ucsf.edu OI Page, Kimberly/0000-0002-7120-1673 FU NIDDK NIH HHS [R03 DK065113] NR 38 TC 62 Z9 65 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 JUL 15 PY 2005 VL 41 IS 2 BP 177 EP 186 DI 10.1086/430913 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 936YF UT WOS:000229890800006 PM 15983913 ER PT J AU Sethi, S AF Sethi, S TI Moxifloxacin for the treatment of acute exacerbations of chronic obstructive pulmonary disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; REQUIRING MECHANICAL VENTILATION; CHRONIC-BRONCHITIS; ANTIBIOTIC-TREATMENT; COPD; FLUOROQUINOLONES; LEVOFLOXACIN; MANAGEMENT; INFECTION; HEALTH AB Background/purpose. The significant impact of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is now recognized. This recognition has led to increased efforts to provide evidence-based, appropriate treatment of AECOPD, to minimize its negative impact. This article reviews the bacterial etiology of AECOPD and clinical trials (both placebo-controlled and antibiotic comparison trials) that support the use of antibiotics for AECOPD, with an emphasis on the role of newer fluoroquinolones for the treatment of patients with this condition. A discussion of patient stratification that permits identification of those who require initial aggressive antibiotic therapy is presented. Main findings. Among the treatment modalities for exacerbations, the role and choice of antibiotics is hotly debated. Current evidence supports the use of antibiotics in the treatment of AECOPD, because bacterial pathogens cause approximately half the exacerbations, and because empirical antibiotics have a significant benefit in most exacerbations. Several recent investigations have aided in the development of a rational antibiotic strategy for AECOPD. These include outcome studies that have identified patients who are likely to have a poor outcome of their exacerbation and, therefore, are candidates for aggressive initial antibiotic therapy. Studies of the new fluoroquinolone agents have shown superior short- and long-term clinical results among patients with AECOPD who are at risk of a poor outcome. Conclusions. Theoretical concerns about the emergence of resistance to the fluoroquinolones dictate not only the appropriate use of these drugs but, also, the use of the most-potent agents available in this class, to sustain their usefulness over time. Such selected use of the new fluoroquinolones balances individual benefit with societal concerns regarding the use of these agents for the treatment of AECOPD. C1 SUNY Buffalo, Div Pulm Crit Care & Sleep Med, Buffalo, NY USA. US Dept Vet Affairs, Western New York Healthcare Syst, Buffalo, NY USA. RP Sethi, S (reprint author), VA Med Res, 151,3495 Bailey Ave, Buffalo, NY 14215 USA. EM ssethi@buffalo.edu NR 42 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2005 VL 41 SU 2 BP S177 EP S185 DI 10.1086/428058 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 936YI UT WOS:000229891100009 PM 15942884 ER PT J AU Albertson, RC Yelick, PC AF Albertson, RC Yelick, PC TI Roles for fgf8 signaling in left-right patterning of the visceral organs and craniofacial skeleton SO DEVELOPMENTAL BIOLOGY LA English DT Article DE asymmetry; Kupffer's vesicle; craniofacial; visceral organ; fgf8; zebrafish ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; NO TAIL; HEMIFACIAL MICROSOMIA; EMBRYONIC-DEVELOPMENT; TRANSGENIC MOUSE; DANIO-RERIO; ZEBRAFISH; HEART; BRAIN AB Laterality is fundamental to the vertebrate body plan. Here, we investigate the roles of fgf8 signaling in LR patterning of the zebrafish embryo. We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. When fgf8 is absent, nodal signaling is randomized in the lateral plate mesoderm, leading to aberrant LR orientation of the brain and visceral organs. We also show that fgf8 is necessary for proper symmetric development of the pharyngeal skeleton. Attenuated fgf8 signaling results in consistently biased LR asymmetric development of the pharyngeal arches and craniofacial skeleton. Approximately 1/3 of zebrafish ace/fgf8 mutants are missing Kupffer's vesicle (KV), a ciliated structure similar to Hensen's node. We correlate fgf8 deficient laterality defects in the brain and viscera with the absence of KV, supporting a role for KV in proper LR patterning of these structures. Strikingly, we also correlate asymmetric craniofacial development in ace/fgf8 mutants with the presence of KV, suggesting roles for KV in lateralization of the pharyngeal skeleton when fgf8 is absent. These data provide new insights into vertebrate laterality and offer the zebrafish ace/fgf8 mutant as a novel molecular tool to investigate tissue-specific molecular laterality mechanisms. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Albertson, RC (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, 140 The Fenway, Boston, MA 02115 USA. EM calbertson@forsyth.org; pyelick@forsyth.org FU NIDCR NIH HHS [DE12076, T32 DE08327, DE12024] NR 65 TC 51 Z9 53 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 BP 310 EP 321 DI 10.1016/j.ydbio.2005.04.025 PG 12 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800004 PM 15932752 ER PT J AU Vidal, M AF Vidal, M TI Interactome networks. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 24 BP 579 EP 579 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800045 ER PT J AU Jette, CA Langenau, DM Stewart, RA Kanki, JP Look, AT AF Jette, CA Langenau, DM Stewart, RA Kanki, JP Look, AT TI Genetic modifiers of the anti-apoptotic functions of BCL-2. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 127 BP 600 EP 601 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800148 ER PT J AU Stewart, RA Arduini, BL Jette, CA Kanki, JP Henion, PD Look, AT AF Stewart, RA Arduini, BL Jette, CA Kanki, JP Henion, PD Look, AT TI Zebrafish foxd3 is selectively required for neural crest sublineage determination, migration and survival. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 413 BP 659 EP 659 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800430 ER PT J AU Feng, YY Chen, MH Mendonza, AM Kwiatkowsk, DJ Walsh, CA AF Feng, YY Chen, MH Mendonza, AM Kwiatkowsk, DJ Walsh, CA TI Filamin A is required in endothelial cells for cardiovascular development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Harvard Univ, Sch Med, Dept Neurol, BIDMC,HHMI, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Cardiovasc, BWH, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol, BWH, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 491 BP 675 EP 676 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800508 ER PT J AU Nagy, N Allan, GM AF Nagy, N Allan, GM TI Chick-quail intestinal transplants - A new method for studying enteric nervous system development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 550 BP 687 EP 688 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800566 ER PT J AU Kim, S Dunn, NR Malicki, J Walsh, CA AF Kim, S Dunn, NR Malicki, J Walsh, CA TI A polarity gene, Pals1 (Stardust), is essential for normal gastrulation in mice. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Harvard Univ, Sch Med, HHMI, BIDMC, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. ES Cell Int, Singapore 138667, Singapore. Harvard Univ, Sch Med, MEEI, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 611 BP 701 EP 701 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800627 ER PT J AU Jagsi, R Raad, RA Goldberg, S Sullivan, T Michaelson, J Powell, SN Taghian, AG AF Jagsi, R Raad, RA Goldberg, S Sullivan, T Michaelson, J Powell, SN Taghian, AG TI Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: Implications for postmastectomy radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol DE breast cancer; radiation therapy; node negative; local failure; mastectomy ID BREAST-CANCER PATIENTS; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; CLINICAL-ONCOLOGY; TRIALS; IRRADIATION; TAMOXIFEN; PATTERNS AB Purpose: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) of breast cancer. Survival appears improved in patients at higher risk for LRR. This study addresses whether subsets of node-negative patients with sufficiently high risk of LRR might benefit from PMRT. Methods: Retrospective analysis of a cohort of 877 cases of node-negative breast cancer treated with mastectomy, without adjuvant radiation, from 1980 to 2000. Results: Median follow-up was 100 months. Ten-year cumulative incidence of LRR as first event was 6.0%. Size greater than 2 cm, margin less than 2 mm, premenopausal status, and lymphovascular invasion (LVI) were independently significant prognostic factors. Ten-year LRR was 1.2% for those with 0 risk factors, 10.0% for those with 1 risk factor, 17.9% for those with 2 risk factors, and 40.6% for those with 3 risk factors. The chest wall was the site of failure in 80% of patients. Conclusion: Postmastectomy radiation therapy has not been recommended for node-negative patients because the LRR rate is low in that population overall. This study suggests, however, that node-negative patients with multiple risk factors, including close margins, T2 or larger tumors, premenopausal status, and LVI, are at higher risk for LRR and might benefit from PMRT. Because the chest wall is the most common site of failure, treating the chest wall alone in these patients to minimize toxicity is reasonable. (c) 2005 Elsevier Inc. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM ataghian@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 16 TC 72 Z9 73 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2005 VL 62 IS 4 BP 1035 EP 1039 DI 10.1016/j.ijrobp.2004.12.014 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 941SF UT WOS:000230233800015 PM 15990006 ER PT J AU Rubio, MT Saito, TI Kattleman, K Zhao, GL Buchli, J Sykes, M AF Rubio, MT Saito, TI Kattleman, K Zhao, GL Buchli, J Sykes, M TI Mechanisms of the antitumor responses and host-versus-graft reactions induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: A critical role for recipient CD4(+) T cells and recipient leukocyte infusion-derived IFN-gamma-producing CD8(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; IMMUNOLOGICAL SELF-TOLERANCE; NATURAL-KILLER-CELLS; STAGE RENAL-DISEASE; LYMPHOHEMATOPOIETIC CHIMERISM; MYELOABLATIVE THERAPY; ALLOGRAFT TOLERANCE; MULTIPLE-MYELOMA; NKG2D RECEPTOR AB Surprisingly, antitumor responses can occur in patients who reject donor grafts following nonmyeloablative hemopoietic cell transplantation. In murine mixed chimeras prepared with nonmyeloablative conditioning, we previously showed that recipient leukocyte infusions (RLI) induced loss of donor chimerism, IFN-gamma production, and antitumor responses against host-type tumors. However, the mechanisms behind this phenomenon remain to be determined. We now demonstrate that the effects of RLI are mediated by distinct and complex mechanisms. Donor marrow rejection is induced by RLI-derived alloactivated T cells, which activate non-RLI-derived, recipient WN-gamma-producing cells. RLI-derived CD8 T cells induce the production of IFN-gamma by both RLI and non-RLI-derived recipient cells. The antitumor responses of RLI involve mainly RLI-derived IFN-gamma-producing CD8 T cells and recipient-derived CD4 T cells and do not involve donor T cells. The pathways of donor marrow and tumor rejection lead to the development of tumor-specific cell-mediated cytotoxic responses that are not due to bystander killing by alloreactive T cells. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM Sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA 79989] NR 43 TC 33 Z9 34 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 665 EP 676 PG 12 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600005 PM 16002661 ER PT J AU Sharma, S Zhu, L Yang, SC Zhang, L Lin, J Hillinger, S Gardner, B Reckamp, K Strieter, RM Huang, M Batra, RK Dubinett, SM AF Sharma, S Zhu, L Yang, SC Zhang, L Lin, J Hillinger, S Gardner, B Reckamp, K Strieter, RM Huang, M Batra, RK Dubinett, SM TI Cyclooxygenase 2 inhibition promotes IFN-gamma-dependent enhancement of antitumor responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER CELLS; LUNG-CANCER; DENDRITIC CELLS; PROSTAGLANDIN E(2); SOLUBLE MEDIATORS; ANTICANCER AGENTS; TUMOR-DEVELOPMENT; T-LYMPHOCYTES; UP-REGULATION AB In previous studies, we demonstrated an immune suppressive network in non-small cell lung cancer that is due to overexpression of tumor cyclooxygenase 2 (COX-2). In this study, we assessed the vaccination response to tumor challenge following either pharmacological or genetic inhibition of COX-2 in a murine lung cancer model. Treatment of naive mice with the COX-2 inhibitor, SC-58236, skewed splenocytes toward a type I cytokine response, inducing IFN-gamma, IL-12, and IFN-gamma-inducible protein 10, whereas the type 2 cytokines IL-4, IL-5, and IL-10 remained unaltered. Fifty percent of mice receiving SC-58236 and an irradiated tumor cell vaccine completely rejected tumors upon challenge. Those mice that did form tumors following challenge demonstrated a reduced tumor growth. In contrast, all mice either vaccinated with irradiated tumor cells alone or receiving SC-58236 alone showed progressive tumor growth. Studies performed in CD4 and CD8 knockout mice revealed a requirement for the CD4 T lymphocyte subset for the complete rejection of tumors. To determine the role of host COX-2 expression on the vaccination responses, studies were performed in COX-2 gene knockout mice. Compared with control littermates, COX-2(-/-) mice showed a significant tumor growth reduction, whereas heterozygous COX-2(-/+) mice had an intermediate tumor growth reduction following vaccination. In vivo depletion of IFN-gamma abrogated the COX-2 inhibitor-mediated enhancement of the vaccination effect. These findings provide a strong rationale for additional evaluation of the capacity of COX-2 inhibitors to enhance vaccination responses against cancer. C1 Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare, Mol Gene Med Lab, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Dept Med, 37-131 Ctr Hlth Sci,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU NCI NIH HHS [R01 CA 78654, CA 85686, P50 CA 90388] NR 57 TC 57 Z9 65 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 813 EP 819 PG 7 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600022 PM 16002678 ER PT J AU Saraiva, M Christensen, JR Tsytsykova, AV Goldfeld, AE Ley, SC Kioussis, D O'Garra, A AF Saraiva, M Christensen, JR Tsytsykova, AV Goldfeld, AE Ley, SC Kioussis, D O'Garra, A TI Identification of a macrophage-specific chromatin signature in the IL-10 locus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; ALPHA GENE; BINDING-SITES; DIFFERENTIATION; ACTIVATION; INTERLEUKIN-10; PROMOTER; INDUCTION AB The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-kappa B binding site. In support of a function for this site, NF-kappa B p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages. C1 Natl Inst Med Res, Div Immunoregulat, London NW7 1AA, England. Natl Inst Med Res, Div Immune Cell Biol, London NW7 1AA, England. Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England. Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. RP Saraiva, M (reprint author), Natl Inst Med Res, Div Immunoregulat, The Ridgeway, London NW7 1AA, England. EM msaraiv@nimr.mrc.ac.uk RI Saraiva, Margarida/E-8781-2011; OI Saraiva, Margarida/0000-0002-8180-1293; O'Garra, Anne/0000-0001-9845-6134 FU Medical Research Council [MC_U117512796, MC_U117565642]; NHLBI NIH HHS [HL 59838] NR 36 TC 73 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 1041 EP 1046 PG 6 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600048 PM 16002704 ER PT J AU Rhee, SJ Walker, WA Cherayil, BJ AF Rhee, SJ Walker, WA Cherayil, BJ TI Developmentally regulated intestinal expression of IFN-gamma and its target genes and the age-specific response to enteric Salmonella infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPITHELIAL-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; TYPHIMURIUM INFECTION; FUNGAL MICROBIOTA; MICROARRAY DATA; ANTIBIOTIC USE; MICE; IMMUNITY; DISEASE; COLONIZATION AB Young infants are highly susceptible to systemic dissemination of enteric pathogens such as Salmonella typhimurium when compared with older individuals. The mechanisms underlying this differential susceptibility have not been defined clearly. To better understand this phenomenon, we examined the responses of adult mice and preweaned pups to oral infection by S. typhimurium. We found clear age-specific differences, namely, an attenuated intestinal inflammatory response and a higher systemic bacterial burden in the pups compared with the adults. To elucidate the molecular basis for these differences, we obtained a microarray-based profile of gene expression in the small intestines of uninfected adult and preweaned animals. The results indicated a striking age-dependent increase in the intestinal expression of a number of IFN-gamma-regulated genes involved in antimicrobial defense. This finding was confirmed by real-time quantitative PCR, which also demonstrated an age-dependent increase in intestinal expression of IFN-gamma. The developmental up-regulation of the IFN-gamma-regulated genes was dependent on both IFN-gamma and a normal commensal microflora, as indicated by experiments in IFN-gamma-knockout mice and germfree mice, respectively. However, the increase in expression of IFN-gamma itself was independent of the commensal flora. The functional importance of IFN-gamma in the immunological maturation of the intestine was confirmed by the observation that the response of adult IFN-gamma-knockout animals to S. typhimurium infection resembled that of the wild-type pups. Our findings thus reveal a novel role for IFN-gamma in the developmental regulation of antimicrobial responses in the intestine. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Pediat Gastroenterol & Nutr Unit, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Pediat Gastroenterol & Nutr Unit, Bldg 114,Room 3400,16th St, Charlestown, MA 02139 USA. EM cherayil@helix.mgh.harvard.edu FU NIAID NIH HHS [R01 AI 48815]; NIDDK NIH HHS [R01 DK 070260, T32 DK 07477] NR 62 TC 50 Z9 53 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 1127 EP 1136 PG 10 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600058 PM 16002714 ER PT J AU Lutskiy, MI Rosen, FS Remold-O'Donnell, E AF Lutskiy, MI Rosen, FS Remold-O'Donnell, E TI Genotype-proteotype linkage in the Wiskott-Aldrich syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Article ID WASP GENE-MUTATIONS; SYNDROME PROTEIN; N-WASP; LINKED THROMBOCYTOPENIA; MISSENSE MUTATIONS; IDENTIFICATION; PHENOTYPE; ACTIVATION; MECHANISM; COMPLEX AB Wiskott-Aldrich syndrome (WAS) is a platelet/immunodeficiency disease arising from mutations of WAS protein (WASP), a hemopoietic cytoskeletal protein. Clinical symptoms vary widely from mild (X-linked thrombocytopenia) to life threatening. In this study, we examined the molecular effects of individual mutations by quantifying WASP in peripheral lymphocytes of 44 patients and identifying the molecular variant (collectively called proteotype). Nonpredicted proteotypes were found for 14 genotypes. These include WASP-negative lymphocytes found for five missense genotypes and WASP-positive lymphocytes for two nonsense, five frameshift, and two splice site genotypes. Missense mutations in the Ena/VASP homology 1 (EVH1) domain lead to decreased/absent WASP but normal mRNA levels, indicating that proteolysis causes the protein deficit. Because several of the EVH1 missense mutations alter WIP binding sites, the findings suggest that abrogation of WIP binding induces proteolysis. Whereas platelets of most patients were previously shown to lack WASP, WASP-positive platelets were found for two atypical patients, both of whom have mutations outside the EVH1 domain. WASP variants with alternative splicing and intact C-terminal domains were characterized for eight nonsense and frameshift genotypes. One of these, a nonsense genotype in a mild patient, supports expression of WASP lacking half of the proline-rich region. With one notable exception, genotype and proteotype were linked, indicating that a genotype-proteotype registry could be assembled to aid in predicting disease course and planning therapy for newly diagnosed infants. Knowledge of the molecular effect of mutations would aid also in identifying disease-modifying genes. C1 CBR Biomed Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), CBR Biomed Res Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NHLBI NIH HHS [HL 59561]; NIAID NIH HHS [AI 39574] NR 43 TC 37 Z9 40 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 1329 EP 1336 PG 8 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600082 PM 16002738 ER PT J AU Blackard, JT Smeaton, L Hiasa, Y Horiike, N Onji, M Jamieson, DJ Rodriguez, I Mayer, KH Chung, RT AF Blackard, JT Smeaton, L Hiasa, Y Horiike, N Onji, M Jamieson, DJ Rodriguez, I Mayer, KH Chung, RT TI Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-2A PLUS RIBAVIRIN; HIV-INFECTED PATIENTS; NEGATIVE-STRAND RNA; EXTRAHEPATIC REPLICATION; IN-VITRO; INTERFERON THERAPY; VIRAL REPLICATION; HUMAN MACROPHAGES AB It has been speculated that hepatitis C virus (HCV) replicates in peripheral-blood mononuclear cells (PBMCs), which, therefore, may be a site for interaction with human immunodeficiency virus (HIV). We used strand-specific real-time polymerase chain reaction to detect HCV RNA in 28 HCV-monoinfected and 20 HIV/HCV coinfected women. At the first visit, positive-strand HCV RNA was detected in serum samples from 89% of the women, whereas positive-strand HCV RNA was detected in PBMC samples from 32% and 55% of the HCV-monoinfected and HIV/HCV-coinfected women, respectively. After initiation of antiretroviral therapy, the HIV/HCV-coinfected women were significantly more likely to have detectable positive-and negative-strand HCV RNA in the PBMC compartment than were the HCV-monoinfected women. HIV and HCV RNA levels were not correlated. Serum HCV RNA levels were correlated over time; HCV RNA levels in the serum and PBMC compartments were not. These data suggest differential regulation of HCV RNA in the serum and PBMC compartments and may partially explain the limited HCV antiviral response rates observed in coinfected persons. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Brown Univ, Dept Med, Providence, RI 02912 USA. Ehime Univ, Dept Internal Med 3, Sch Med, Matsuyama, Ehime 790, Japan. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [P30-AI42851]; ODCDC CDC HHS [U64/CCU106795] NR 43 TC 52 Z9 53 U1 0 U2 5 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 JUL 15 PY 2005 VL 192 IS 2 BP 258 EP 265 DI 10.1086/430949 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 943WX UT WOS:000230387300009 PM 15962220 ER PT J AU Burns, JC Shimizu, C Gonzalez, E Kulkarni, H Patel, S Shike, H Sundel, RS Newburger, JW Ahuja, SK AF Burns, JC Shimizu, C Gonzalez, E Kulkarni, H Patel, S Shike, H Sundel, RS Newburger, JW Ahuja, SK TI Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 2004 CL San Francisco, CA SP Pediat Acad Soc ID HIV-1 DISEASE; IMMUNODEFICIENCY-VIRUS; LINKAGE ANALYSIS; TRANSMISSION; PROGRESSION; ALLELE; FREQUENCY; CHILDREN; DELETION; DISEQUILIBRIUM AB Kawasaki disease (KD) is an enigmatic, self-limited vasculitis of childhood that is complicated by development of coronary-artery aneurysms. The high incidence of KD in Asian versus European populations prompted a search for genetic polymorphisms that are differentially distributed among these populations and that influence KD susceptibility. Here, we demonstrate a striking, inverse relationship between the worldwide distribution of CCR5-Delta 32 allele and the incidence of KD. In 164 KD patient-parent trios, 4 CCR5 haplotypes including the CCR5-Delta 32 allele were differentially transmitted from heterozygous parents to affected children. However, the magnitude of the reduced risk of KD associated with the CCR5-Delta 32 allele and certain CCR5 haplotypes was significantly greater in individuals who also possessed a high copy number of the gene encoding CCL3L1, the most potent CCR5 ligand. These findings, derived from the largest genetic study of any systemic vasculitis, suggest a central role of CCR5-CCL3L1 gene-gene interactions in KD susceptibility and the importance of gene modifiers in infectious diseases. C1 Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV1 Infect, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Cardiol, Boston, MA 02115 USA. RP Ahuja, SK (reprint author), Univ Calif San Diego, Sch Med, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM ahujas@uthscsa.edu RI Burns, Jane/J-6167-2015; Shimizu, Chisato/J-6516-2015; OI Sundel, Robert/0000-0002-0083-5695 FU NHLBI NIH HHS [HL69413, R01 HL069413, R01 HL069413-08]; NIAID NIH HHS [AI043279, AI046326, R01 AI043279, R01 AI046326, R21 AI046326, R37 AI046326] NR 42 TC 67 Z9 71 U1 1 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 JUL 15 PY 2005 VL 192 IS 2 BP 344 EP 349 DI 10.1086/430953 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 943WX UT WOS:000230387300020 PM 15962231 ER PT J AU Montalbetti, N Li, Q Timpanaro, GA Gonzalez-Perrett, S Dai, XQ Chen, XZ Cantiello, HF AF Montalbetti, N Li, Q Timpanaro, GA Gonzalez-Perrett, S Dai, XQ Chen, XZ Cantiello, HF TI Cytoskeletal regulation of calcium-permeable cation channels in the human syncytiotrophoblast: role of gelsolin SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT 8th Clincopathological Conference on Renal Allograft Pathology CY JUL 10, 2004 CL Tokyo, JAPAN ID POLYCYSTIC KIDNEY-DISEASE; HUMAN PLACENTAL MICROVILLI; ACTIN-FILAMENT ORGANIZATION; EPITHELIAL SODIUM-CHANNELS; HUMAN TERM PLACENTA; HUMAN TROPHOBLAST; CHLORIDE CHANNEL; ALPHA-ACTININ; BRUSH-BORDER; CELL-VOLUME AB The human syncytiotrophoblast (hST) is the most apical epithelial barrier that covers the villous tree of the human placenta. An intricate and highly organized network of cytoskeletal structures supports the hST. Recently, polycystin-2 (PC2), a TRP-type nonselective cation channel, was functionally observed in hST, where it may be an important player to Ca2+ transport. Little is known, however, about channel regulation in hST. In this report, the regulatory role of actin dynamics on PC2 channels reconstituted from hST apical membranes was explored. Acute addition of cytochalasin D (CD, 5 mu g ml(-1)) to reconstituted hST apical membranes transiently increased K+-permeable channel activity. The actin-binding proteins alpha-actinin and gelsolin, as well as PC2, were observed by Western blot and immunofluorescence analyses in hST vesicles. CD treatment of hST vesicles resulted in a re-distribution of actin filaments, in agreement with the effect of CD on K+ channel activity. In contrast, addition of exogenous monomeric actin, but not prepolymerized actin, induced a rapid inhibition of channel function in hST. This inhibition was obliterated by the presence of CD in the medium. The acute (<15 min) CD stimulation of K+ channel activity was mimicked by addition of the actin-severing protein gelsolin in the presence, but not in the absence, of micromolar Ca2+. Ca2+ transport through PC2 triggers a regulatory feedback mechanism, which is based on the severing and re-formation of filamentous actin near the channels. Cytoskeletal structures may thus be relevant to ion transport regulation in the human placenta. C1 Univ Alberta, Dept Physiol, Edmonton, AB, Canada. Massachusetts Gen Hosp, Renal Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales Ion, Dept Fis Quim Fis & Quim Analit, RA-1113 Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp E, Renal Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 65 TC 23 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 2005 VL 566 IS 2 BP 309 EP 325 DI 10.1113/jphysiol.2005.087072 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 951DL UT WOS:000230909200003 PM 15845576 ER PT J AU Shammas, MA Koley, H Batchu, RB Bertheau, RC Protopopov, A Munshi, NC Goyal, RK AF Shammas, Masood A. Koley, Hemanta Batchu, Ramesh B. Bertheau, Robert C. Protopopov, Alexei Munshi, Nikhil C. Goyal, Raj K. TI Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential SO MOLECULAR CANCER LA English DT Article ID IMMORTAL CELLS; GROWTH ARREST; IN-VIVO; CANCER; EXPRESSION; REPAIR; AGENT; P73 AB Background: In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. Results: We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-I cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bc110 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed. Conclusion: These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma. C1 VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, Boston, MA 02132 USA. VA Boston Healthcare Syst, Boston, MA 02132 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goyal, RK (reprint author), VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, Boston, MA 02132 USA. EM masood_shammas@hms.harvard.edu; Hemanta_Koley@hms.harvard.edu; Ramesh_Batchu@hms.harvard.edu; Robert_Bertheau@dfci.harvard.edu; Alexei_Protopopov@dfci.harvard.edu; Nikhil_Munshi@dfci.harvard.edu; Raj_Goyal@hms.harvard.edu FU NIDDK NIH HHS [R01 DK031092, DK031092]; PHS HHS [NIH-P50-100007, P01-78378, P050-100007] NR 31 TC 57 Z9 74 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD JUL 15 PY 2005 VL 4 AR 24 DI 10.1186/1476-4598-4-24 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 076NO UT WOS:000239965200001 PM 16022731 ER PT J AU Rimol, LM Specht, K Weis, S Savoy, R Hugdahl, K AF Rimol, LM Specht, K Weis, S Savoy, R Hugdahl, K TI Processing of sub-syllabic speech units in the posterior temporal lobe: An fMRI study SO NEUROIMAGE LA English DT Article DE speech processing; laterality; middle temporal gyrus; sub-syllabic; consonant-vowel ID EVENT-RELATED FMRI; DEVELOPMENTAL APHASIA; AUDITORY-CORTEX; TIME-SERIES; HEMISPHERIC-SPECIALIZATION; PERCEPTION; LATERALIZATION; LANGUAGE; ANATOMY; MEMORY AB The objective of this study was to investigate phonological processing in the brain by using sub-syllabic speech units with rapidly changing frequency spectra. We used isolated stop consonants extracted from natural speech consonant-vowel (CV) syllables, which were digitized and presented through headphones in a functional magnetic resonance imaging (fMRI) paradigm. The stop consonants were contrasted with CV syllables. In order to control for general auditory activation, we used duration- and intensity-matched noise as a third stimulus category. The subjects were seventeen right-handed, healthy male volunteers. BOLD activation responses were acquired on a 1.5-T MR scanner. The auditory stimuli were presented through MR compatible headphones, using an fMRI paradigm with clustered volume acquisition and 12 s repetition time. The consonant vs. noise comparison resulted in unilateral left lateralized activation in the posterior part of the middle temporal gyrus and superior temporal sulcus (MTG/STS). The CV syllable vs. noise comparison resulted in bilateral activation in the same regions, with a leftward asymmetry. The reversed comparisons, i.e., noise vs. speech stimuli. resulted in right hemisphere activation in the supramarginal and superior temporal gyros, as well as right prefrontal activation. Since the consonant stimuli are unlikely to have activated a semantic-lexical processing system, it seems reasonable to assume that the MTG/STS activation represents phonetic/phonological processing. This may involve the processing of both spectral and temporal features considered important for phonetic encoding. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Bergen, Dept Biol & Med Psychol, Div Cognit Neurosci, N-5009 Bergen, Norway. Univ Bonn, Dept Epileptol, D-5300 Bonn, Germany. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Rimol, LM (reprint author), Univ Bergen, Dept Biol & Med Psychol, Div Cognit Neurosci, BBB 9 Etg,Jonas Lies Vei 91, N-5009 Bergen, Norway. EM lars.rimol@psybp.uib.no RI Specht, Karsten/C-3762-2009; OI Rimol, Lars M./0000-0002-1243-0396 NR 54 TC 61 Z9 63 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 15 PY 2005 VL 26 IS 4 BP 1059 EP 1067 DI 10.1016/j.neuroimage.2005.03.028 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 939KK UT WOS:000230071300009 PM 15894493 ER PT J AU Yelin, D Yun, SH Bouma, BE Tearney, GJ AF Yelin, D Yun, SH Bouma, BE Tearney, GJ TI Three-dimensional imaging using spectral encoding heterodyne interferometry SO OPTICS LETTERS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; DELAY-LINE; ENDOSCOPY AB We present a novel heterodyne approach for performing fast, three-dimensional spectrally encoded imaging. Volumetric data of a volunteer's finger and of coin surfaces were acquired at a rate of 5 volume sets per second with a depth resolution of 145 mu m. (c) 2005 Optical Society of America. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM dyelin@partners.org NR 10 TC 14 Z9 14 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 15 PY 2005 VL 30 IS 14 BP 1794 EP 1796 DI 10.1364/OL.30.001794 PG 3 WC Optics SC Optics GA 944EJ UT WOS:000230408700010 PM 16092348 ER PT J AU SantaCruz, K Lewis, J Spires, T Paulson, J Kotilinek, L Ingelsson, M Guimaraes, A DeTure, M Ramsden, M McGowan, E Forster, C Yue, M Orne, J Janus, C Mariash, A Kuskowski, M Hyman, B Hutton, M Ashe, KH AF SantaCruz, K Lewis, J Spires, T Paulson, J Kotilinek, L Ingelsson, M Guimaraes, A DeTure, M Ramsden, M McGowan, E Forster, C Yue, M Orne, J Janus, C Mariash, A Kuskowski, M Hyman, B Hutton, M Ashe, KH TI Tau suppression in a neurodegenerative mouse model improves memory function SO SCIENCE LA English DT Article ID PAIRED HELICAL FILAMENTS; NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; PROTEIN-TAU; P301L TAU; A-BETA; ASSOCIATION; EXPRESSION; PATHOLOGY; PLAQUES AB Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating, neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy. C1 Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Grad Program Neurosci, Minneapolis, MN 55455 USA. Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Minneapolis VA Hosp, Ctr Geriatr Res Educ & Clin, Minneapolis, MN 55417 USA. RP Ashe, KH (reprint author), Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. EM hsiao005@umn.edu FU NIA NIH HHS [P01 AG015453, P01-AG15453, P50 AG005134, R01 AG008487, R01 AG026249, R01 AG026252, R01-AG08487, R01-AG26249, T31-AG00277]; NINDS NIH HHS [R01 NS033249, R01 NS046355, R01 NS082672, R01-NS46355]; PHS HHS [R01-026252] NR 26 TC 879 Z9 911 U1 11 U2 69 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 15 PY 2005 VL 309 IS 5733 BP 476 EP 481 DI 10.1126/science.1113694 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946LY UT WOS:000230574900050 PM 16020737 ER PT J AU Yu, PB Parker, W Nayak, JV Platt, JL AF Yu, PB Parker, W Nayak, JV Platt, JL TI Sensitization with xenogeneic tissues alters the heavy chain repertoire of human anti-Ga1 alpha 1-3Ga1 antibodies SO TRANSPLANTATION LA English DT Article DE antibodies; repertoire; heavy chain; hapten; xenotransplantation ID ANTI-GAL ANTIBODY; ALPHA-GALACTOSYL IGG; INFLUENZAE TYPE-B; IMMUNE-RESPONSE; NATURAL ANTIBODIES; STRUCTURAL CHARACTERIZATION; SOMATIC HYPERMUTATION; RHEUMATOID FACTORS; GENE CONVERSION; HEPATIC-FAILURE AB Background. Antigen sensitization alters the use of genes encoding the variable and constant regions of immunoglobulin, changing avidity, and function. Alterations in variable region genes induced by carbohydrate antigens have been studied extensively in animals but are incompletely characterized in humans. We asked how sensitization with the carbohydrate Gal alpha 1-3Gal modifies antibody heavy chain use. Methods. To overcome limited access to B cells, we analyzed anti-Gal alpha 1-3Gal antibodies from the serum of naive and sensitized human subjects with anti-sera specific for VH families. Results. We find that in preimmune subjects, heavy chains of IgM anti-Gal alpha 1-3Gal derived primarily from VH3 family members, whereas the heavy chains of IgG are from diverse VH families. After sensitization, heavy chains of IgM and IgG antibodies both derived from diverse VH families. Conclusions. The preimmune repertoire of IgM antibodies to Gal alpha 1-3Gal is thus more restricted than the antibody repertoire after sensitization, suggesting an antigen-induced shift in the repertoire. C1 Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Mayo Clin Coll Med, Dept Immunol & Pediat, Rochester, MN USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Platt, JL (reprint author), Mayo Clin Coll Med, Dept Surg, 200 1st St SW,Med Sci 2-66, Rochester, MN 55905 USA. EM Platt.jeffrey@mayo.edu FU NHLBI NIH HHS [HL52297] NR 57 TC 5 Z9 5 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 JUL 15 PY 2005 VL 80 IS 1 BP 102 EP 109 DI 10.1097/01.TP.0000163976.07023.6D PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 945AX UT WOS:000230473800018 PM 16003240 ER PT J AU Andrews, NC Anupindi, S Harris, NL Buie, TM Badizadegan, K AF Andrews, NC Anupindi, S Harris, NL Buie, TM Badizadegan, K TI Case 21-2005: A four-week-old male infant with jaundice and thrombocytopenia - Neonatal giant-cell hepatitis with bridging fibrosis and early regenerative nodules, with iron deposition in hepatocytes and Kupffer cells (consistent with - but not diagnostic of - neonatal hemochromatosis). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DELTA(4)-3-OXOSTEROID 5-BETA-REDUCTASE; LIVER-FAILURE; INBORN ERROR; METABOLISM; GENE; MUTATIONS; OVERLOAD C1 Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. OI Andrews, Nancy/0000-0003-0243-4462 NR 22 TC 1 Z9 1 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 JUL 14 PY 2005 VL 353 IS 2 BP 189 EP 198 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 944OP UT WOS:000230438800012 PM 16014889 ER PT J AU Wu, SV Chen, MC Rozengurt, E AF Wu, SV Chen, MC Rozengurt, E TI Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat SO PHYSIOLOGICAL GENOMICS LA English DT Article DE calcium flux; neuroendocrine cells; gustducin; transducin ID CELL-LINE AR42J; ALPHA-GUSTDUCIN; IDENTIFICATION; FAMILY; GENES; PHENYLTHIOCARBAMIDE; SENSITIVITY; PERCEPTION; SECRETION; EVOLUTION AB Mammalian type 2 taste receptors (T2R) are a family of G protein-coupled receptors that mediate bitter signals in taste cells. In the present study, we compared the genomic organization of rodent T2R genes based on the recently completed mouse and rat genomes and examined tissue-and cell-specific expression of T2Rs. Both mouse and rat T2R families consist of 36 intact genes and at least 7 pseudogenes that are mapped to mouse chromosomes 15, 2, and 6 and to rat chromosomes 2, 3, and 4, respectively. All but two T2R genes are clustered on mouse chromosome 6 and rat chromosome 4 with virtually identical genomic organization. The orthologs of the first human T2R gene identified, mT2R119 and rT2R1, are located on mouse chromosome 15 and rat chromosome 2, whereas the novel rodent-specific T2R genes, mT2R134 and rT2R34, are located on mouse chromosome 2 and rat chromosome 3, respectively. Our results, using RT-PCR, demonstrate the presence of transcripts corresponding to the putative denatonium benzoate (DB) and phenylthiocarbamide (PTC) receptors in the antrum, fundus, and duodenum as well as in STC-1 and AR42J cells. The novel rodent-specific T2R gene (mT2R134 and rT2R34) was also expressed in these tissues and cell lines. The addition of DB, PTC, or cycloheximide to AR42J cells induced a rapid increase in the intracellular Ca2+ concentration. The specificity of these effects is shown by the fact that these bitter stimuli did not induce any detectable Ca2+ signaling in many other rodent or human cells that do not express receptors or G proteins implicated in bitter taste signaling. These results demonstrate that mouse and rat T2R genes are highly conserved in terms of genomic organization and tissue expression, suggesting that rodent T2Rs are evolved under similar dietary pressure and share bitter sensing functions in the lingual and gastrointestinal systems. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med,David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Rozengurt, E (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med,David Geffen Sch Med, 900 Vet Ave,Rm 11-115, Los Angeles, CA 90095 USA. EM erozengurt@mednet.ucla.edu FU NIDDK NIH HHS [R01 DK-17294, R01 DK-41301, R01 DK-55003, R01 DK-56930] NR 29 TC 74 Z9 82 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUL 14 PY 2005 VL 22 IS 2 BP 139 EP 149 DI 10.1152/physiolgenomics.00030.2005 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 952FD UT WOS:000230987900003 PM 15886333 ER PT J AU Casarett, D Karlawish, J Morales, K Crowley, R Mirsch, T Asch, DA AF Casarett, D Karlawish, J Morales, K Crowley, R Mirsch, T Asch, DA TI Improving the use of hospice services in nursing homes - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-LIFE CARE; ADVANCE DIRECTIVES; HEALTH-CARE; PALLIATIVE CARE; END; PREFERENCES; COMPLETION; PATIENT; PAIN; ILL AB Context Hospice care may improve the quality of end-of-life care for nursing home residents, but hospice is underutilized by this population, at least in part because physicians are not aware of their patients' preferences. Objective To determine whether it is possible to increase hospice utilization and improve the quality of end-of-life care by identifying residents whose goals and preferences are consistent with hospice care. Design, Setting, and Participants Randomized controlled trial (December 2003-December 2004) of nursing home residents and their surrogate decision makers (N=205) in 3 US nursing homes. Intervention A structured interview identified residents whose goals for care, treatment preferences, and palliative care needs made them appropriate for hospice care. These residents' physicians were notified and asked to authorize a hospice informational visit. Main Outcome Measures The primary outcome measures were (1) hospice enrollment within 30 days of the intervention and (2) families' ratings of the quality of care for residents who died during the 6-month follow-up period. Results Of the 205 residents in the study sample, 107 were randomly assigned to receive the intervention, and 98 received usual care. Intervention residents were more likely than usual care residents to enroll in hospice within 30 days (21/107 [20%] vs 1/98 [1%]; P<.001 [Fisher exact test]) and to enroll in hospice during the follow-up period (27/207 [25%] vs 6/98 [6%]; P<.001). Intervention residents had fewer acute care admissions (mean: 0.28 vs 0.49; P=.04 [Wilcoxon rank sum test]) and spent fewer days in an acute care setting (mean: 1.2 vs 3.0; P=.03 [Wilcoxon rank sum test]). Families of intervention residents rated the resident's care more highly than did families of usual care residents (mean on a scale of 1-5: 4.1 vs 2.5; P=.04 [Wilcoxon rank sum test]). Conclusion A simple communication intervention can increase rates of hospice referrals and families' ratings of end-of-life care and may also decrease utilization of acute care resources. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Temple Univ, Sch Law, Philadelphia, PA 19122 USA. Holy Redeemer Home Hlth & Hospice Care, Philadelphia, PA USA. RP Casarett, D (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 51 TC 108 Z9 109 U1 3 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 13 PY 2005 VL 294 IS 2 BP 211 EP 217 DI 10.1001/jama.294.2.211 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 944DO UT WOS:000230406100025 PM 16014595 ER PT J AU Lin, B Jakobs, TC Masland, RH AF Lin, B Jakobs, TC Masland, RH TI Different functional types of bipolar cells use different gap-junctional proteins SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mouse; GFP; retina; Cx36; ON bipolar cell; gap junctions ID AII AMACRINE CELLS; INNER PLEXIFORM LAYER; RABBIT RETINA; MAMMALIAN RETINA; MOUSE RETINA; VISUAL TRANSMISSION; ROD; CONNEXIN36; EXPRESSION; PATHWAYS AB Rod signals are transmitted to ON retinal ganglion cells by means of gap junctions between AII amacrine cells and ON bipolars. The AII amacrine cells are known to express connexin36 (Cx36), but previous studies of Cx36 in ON cone bipolars have been ambiguous. Here, we studied bipolar cells in a transgenic mouse line that expresses high levels of green fluorescent protein (GFP) in one type of ON cone bipolar cell. We found strong Cx36 immunostaining in the axon terminals of the GFP-labeled type 357 bipolar cells in both vertical sections and whole mounts of the retina. This finding was confirmed by single-cell immunostaining and single-cell reverse transcription-PCR (RT-PCR). As reported previously (Maxeiner et al., 2005), Cx45 was found in some ON bipolar cells, but RT-PCR showed Cx36 and not Cx45 to be expressed by the type 357 bipolar cells. Some of the remaining GFP-negative bipolar cells expressed Cx45 but not Cx36. It appears that different types of ON cone bipolar cells express different connexins at their gap junctions with AII amacrine cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lin, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. EM blin@helix.mgh.harvard.edu RI Lin, Bin/E-9871-2010; OI Jakobs, Tatjana/0000-0002-8104-9206 NR 27 TC 34 Z9 34 U1 1 U2 2 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 JUL 13 PY 2005 VL 25 IS 28 BP 6696 EP 6701 DI 10.1523/JNEUROSCI.1894-05.2005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 945CD UT WOS:000230478100023 PM 16014731 ER PT J AU Chao, MY Larkins-Ford, J Tucey, TM Hart, AC AF Chao, MY Larkins-Ford, J Tucey, TM Hart, AC TI lin-12 Notch functions in the adult nervous system of C-elegans SO BMC NEUROSCIENCE LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; GLR-1 GLUTAMATE-RECEPTOR; GENE SERRATE ENCODES; LONG-TERM-MEMORY; CAENORHABDITIS-ELEGANS; TRANSMEMBRANE PROTEIN; SYNAPTIC PLASTICITY; REVERSAL FREQUENCY; SEL-12 PRESENILIN; ALAGILLE-SYNDROME AB Background: Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. Results: The spontaneous reversal rate of C. elegans during normal locomotion is constant. Both lin-12 gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by lin-12 activity, because the loss of function defect could be rescued by a wild type lin-12 transgene. Furthermore, overexpression of lin-12 recapitulated the gain-of-function defect. Increasing or decreasing lin-12 activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for lin-12. Although lin-12 is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering lin-12 activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical lin-12 signaling cascade, including the ligand lag-2 and the transcriptional effector lag-1. Finally, the C. elegans AMPA/kainate glutamate receptor homolog glr-1 shows strong genetic interactions with lin-12, suggesting that glr-1 and/or other glutamate gated channels may be targets of lin-12 regulation. Conclusion: Our results demonstrate a neuronal role for lin-12 Notch in C. elegans and suggest that lin-12 acutely regulates neuronal physiology to modulate animal behavior, without altering neuronal cell fate specification or neurite outgrowth. This is consistent with a role for Notch signaling in neurological disease with late onset symptoms. C1 Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. RP Hart, AC (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. EM chao@helix.mgh.harvard.edu; j_lford@yahoo.com; ttucey@partners.org; hart@helix.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM057918-05, R01 GM057918] NR 57 TC 21 Z9 26 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD JUL 12 PY 2005 VL 6 AR 45 DI 10.1186/1471-2202-6-45 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 951BD UT WOS:000230902900001 PM 16011804 ER PT J AU Finn, AV Kolodgie, FD Harnek, J Guerrero, LJ Acampado, E Tefera, K Skorija, K Weber, DK Gold, HK Virmani, R AF Finn, AV Kolodgie, FD Harnek, J Guerrero, LJ Acampado, E Tefera, K Skorija, K Weber, DK Gold, HK Virmani, R TI Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents SO CIRCULATION LA English DT Article DE drugs; pathology; restenosis; stents ID CORONARY-ARTERY; NEOINTIMAL HYPERPLASIA; IMPLANTATION; RESTENOSIS; DELIVERY; LESIONS; SIRIUS; THROMBOSIS; RELEASE; HUMANS AB Background - Although effective coverage of challenging coronary lesions has warranted the use of overlapping drug-eluting stents, the histopathological response to stent overlap is unknown. Methods and Results - The arterial reaction to overlapping Cypher or Taxus drug-eluting stents was examined in rabbits with bare metal stents, BxVelocity or Express, serving as controls. Single iliac artery balloon injury was followed by placement of 2 overlapping 3.0-mm-diameter drug-eluting stents or bare metal stents in 60 animals ( mean length of overlap, 9.8 +/- 3.6 mm). Stented arteries were harvested at 28 and 90 days for histology. Overlapped segments exhibited delayed healing compared with proximal and distal nonoverlapping sites at 28 days. Overlapped segments in Taxus stents induced significantly more luminal heterophils/eosinophils and fibrin deposition than Cypher; peristrut giant cell infiltration, however, was more frequent in the latter. Overlapping bare metal stents also showed mild delayed healing compared with nonoverlapped segments, but not to the same extent as drug-eluting stents. Although neointimal thickness within the overlap was similar in 28- and 90-day Cypher stents, there was a significant increase with Taxus (P = 0.03). Conclusions - Compared with bare metal stents, drug-eluting stents further delay arterial healing and promote inflammation at sites of overlap. Taxus stents induced greater fibrin deposition, medial cell loss, heterophils/eosinophils, and late neointimal hyperplasia. Patients receiving overlapping drug-eluting stents need more frequent follow-up than patients with nonoverlapping stents. C1 CVPath, Int Registry Pathol, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Internal Med, Boston, MA 02114 USA. Univ Lund Hosp, Heart Lung Div, S-22185 Lund, Sweden. RP CVPath, Int Registry Pathol, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 27 TC 334 Z9 350 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUL 12 PY 2005 VL 112 IS 2 BP 270 EP 278 DI 10.1161/CIRCULATIONAHA.104.508937 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 944KQ UT WOS:000230427300019 PM 15998681 ER PT J AU Mikaelian, BJ Malchano, ZJ Neuzil, P Weichet, J Doshi, SK Ruskin, JN Reddy, VY AF Mikaelian, BJ Malchano, ZJ Neuzil, P Weichet, J Doshi, SK Ruskin, JN Reddy, VY TI Integration of 3-dimensional cardiac computed tomography images with real-time electroanatomic mapping to guide catheter ablation of atrial fibrillation SO CIRCULATION LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Homolce Hosp, Prague, Czech Republic. Boston Med Ctr, Dept Internal Med, Boston, MA USA. RP Reddy, VY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org NR 0 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 12 PY 2005 VL 112 IS 2 BP E35 EP E36 DI 10.1161/01.CIR.0000161085.58945.1C PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 944KQ UT WOS:000230427300027 PM 16009803 ER PT J AU Mehta, KM Yin, M Resendez, C Yaffe, K AF Mehta, KM Yin, M Resendez, C Yaffe, K TI Ethnic differences in acetylcholinesterase inhibitor use for Alzheimer disease SO NEUROLOGY LA English DT Article ID DEMENTIA; PREVALENCE; HEALTH AB Acetylcholinesterase inhibitors (AChIs) have been demonstrated to improve Alzheimer disease symptoms. Whether the use of AChIs varies by ethnicity is unknown. More than 2500 ethnically diverse patients (6% African American, 14% Latino, and 7% Asian patients) from the Alzheimer's Disease Research Centers in California were studied. Compared with white patients with AD, minority patients had 40% lower odds of AChI use (odds ratio 0.6, 95% confidence interval: 0.5 to 0.7). C1 Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol & Epidemiol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Mehta, KM (reprint author), 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM kala@itsa.ucsf.edu FU NIA NIH HHS [P30 AG015272, R01 AG021918, P30 AG 15272, K01 AG025444-01A1, R-01 AG021918-02]; NIMH NIH HHS [R25 MH060482, R25 MH 60482] NR 10 TC 24 Z9 24 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 12 PY 2005 VL 65 IS 1 BP 159 EP 162 DI 10.1212/01.wnl.0000167545.38161.48 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 944KP UT WOS:000230427200036 PM 16009909 ER PT J AU Penson, RT Seiden, MV Matulonis, UA Appleman, LJ Fuller, AF Goodman, A Campos, SM Clark, JW Roche, M Eder, JP AF Penson, RT Seiden, MV Matulonis, UA Appleman, LJ Fuller, AF Goodman, A Campos, SM Clark, JW Roche, M Eder, JP TI A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours SO BRITISH JOURNAL OF CANCER LA English DT Article DE sequential; palliative; chemotherapy; rational; topoisomerase ID CELL LUNG-CANCER; 24-HOUR CONTINUOUS-INFUSION; COLONY-STIMULATING FACTOR; DNA TOPOISOMERASE-II; ORAL ETOPOSIDE; OVARIAN-CANCER; RANDOMIZED TRIAL; IRINOTECAN; INHIBITORS; CAMPTOTHECIN AB The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m(-2) b.i.d. days (D) 1-5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m(-2) day(-1) with a dose escalation of 0.1, then at 0.05 mg m(-2) day(-1). Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22-78) years, received a median 8 (2-19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m(-2) b.i.d. D1-5 and 1.8 mg m(-2) 96 h (total dose) infusional topotecan D8-11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02114 USA. Dept Med, Div Adult Oncol, Boston, MA 02114 USA. Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gynecol & Obstet, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org OI Appleman, Leonard/0000-0003-4951-7388 NR 38 TC 1 Z9 1 U1 0 U2 2 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 JUL 11 PY 2005 VL 93 IS 1 BP 54 EP 59 DI 10.1038/sj.bjc.6602671 PG 6 WC Oncology SC Oncology GA 942EF UT WOS:000230265000009 PM 15986034 ER PT J AU De Venecia, RK Liberman, MC Guinan, JJ Brown, MC AF De Venecia, RK Liberman, MC Guinan, JJ Brown, MC TI Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: A kainic acid lesion study in guinea pigs SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE hearing; outer hair cell; otoacoustic emission; superior olive ID AUDITORY-NERVE FIBERS; PRODUCT OTOACOUSTIC EMISSION; INFERIOR COLLICULUS; RESPONSE PROPERTIES; EFFERENT NEURONS; ELECTRICAL-STIMULATION; HAIR-CELLS; CAT; PROJECTIONS; ADAPTATION AB The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(1)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the posteroventral cochlear nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons. J. Comp. Neurol. 487:345-360, 2005. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcb@epl.meei.harvard.edu FU NIDCD NIH HHS [T32 DC000020, R01 DC001089, R01 DC 01089, P30 DC05209, P30 DC005209, R01 DC 00188, R01 DC000188, T32 DC00020-11] NR 83 TC 25 Z9 25 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 11 PY 2005 VL 487 IS 4 BP 345 EP 360 DI 10.1002/cne.20550 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 931AH UT WOS:000229457700001 PM 15906311 ER PT J AU Vakoc, BJ Yun, SH de Boer, JF Tearney, GJ Bouma, BE AF Vakoc, BJ Yun, SH de Boer, JF Tearney, GJ Bouma, BE TI Phase-resolved optical frequency domain imaging SO OPTICS EXPRESS LA English DT Article ID TO-NOISE RATIO; 1.3 MU-M; COHERENCE TOMOGRAPHY; SPECTRAL-DOMAIN; BLOOD-FLOW; DOPPLER TOMOGRAPHY; SWEPT-SOURCE; SPEED; WAVELENGTH; VELOCITY AB Phase-resolved Doppler optical coherence tomography has been used to image blood flow dynamics in various tissues using both time-domain and spectral-domain optical coherence tomography techniques. In this manuscript, we present phase-resolved Doppler imaging with a highspeed optical frequency domain imaging system. We demonstrate that by correcting for spurious timing-induced phase errors, excellent flow sensitivity can be achieved, limited only by the imaging signal-to-noise ratio. Conventional and Doppler images showing flow in an Intralipid phantom and in human skin are presented. Additionally, we demonstrate the ability of phase-resolved OFDI to measure high flow rates without the deleterious effects of fringe washout. (C) 2005 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Vakoc, BJ (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR-712, Boston, MA 02114 USA. EM bvakoc@partners.org RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769, R01 CA103769-02, R33 CA110130, R33 CA110130-01]; NCRR NIH HHS [R01 RR019768-02]; NHLBI NIH HHS [R01 HL070039, R01 HL070039-02, R01 HL076398, R01 HL076398-03] NR 31 TC 192 Z9 195 U1 0 U2 10 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 JUL 11 PY 2005 VL 13 IS 14 BP 5483 EP 5493 DI 10.1364/OPEX.13.005483 PG 11 WC Optics SC Optics GA 945RF UT WOS:000230519100035 PM 19498543 ER PT J AU Willett, CG Czito, BG Bendell, JC Ryan, DP AF Willett, CG Czito, BG Bendell, JC Ryan, DP TI Locally advanced pancreatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID COOPERATIVE-ONCOLOGY-GROUP; PHASE-I TRIAL; CONCURRENT RADIATION-THERAPY; INFUSION FLUOROURACIL; WEEKLY GEMCITABINE; BEAM IRRADIATION; ADENOCARCINOMA; RADIOTHERAPY; 5-FLUOROURACIL; CARCINOMA AB Of the 32,180 patients diagnosed with pancreatic carcinoma in the United States this year, approximately 40% will present with locally advanced disease. Radiotherapeutic approaches are often employed because these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil-based chemotherapy, intraoperative irradiation, and, more recently, external-beam irradiation with new systemic targeted agents. (c) 2005 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. EM willett@radonc.duke.edu NR 44 TC 111 Z9 118 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 10 PY 2005 VL 23 IS 20 BP 4538 EP 4544 DI 10.1200/JCO.2005.23.911 PG 7 WC Oncology SC Oncology GA 945LX UT WOS:000230505100010 PM 16002845 ER PT J AU Brugge, WR AF Brugge, WR TI Endoscopic techniques to diagnose and manage biliary tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID BILE-DUCT STRICTURES; FINE-NEEDLE-ASPIRATION; INTRADUCTAL ULTRASONOGRAPHY; BRUSH CYTOLOGY; CHOLANGIOCARCINOMA; PANCREATICODUODENECTOMY; ULTRASOUND; CANCER; YIELD; ERCP AB Malignancies of the bile duct are often suspected in patients with abnormal serum hepatic enzyme levels and obstruction of the biliary system. Although cross-sectional imaging can provide evidence for biliary obstruction and a malignancy arising from the bile duct, a definitive diagnosis is often obtained through the use of endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP), the most commonly performed procedure for cholangiocarcinoma, can provide a tissue diagnosis through brush cytology of the bile duct. Relief from biliary obstruction can be provided with temporary plastic stenting or permanent metal stenting. Photodynamic therapy guided by ERCP may provide improved palliation from biliary obstruction in the future. Endoscopic ultrasonography complements the role of ERCP and may provide a tissue diagnosis through fine-needle aspiration and staging through ultrasound imaging. High-resolution ultrasound images can provide detailed information regarding the relationship between a mass and the bile duct wall. Despite these advances in endoscopic techniques and imaging of the bile duct, a tissue diagnosis often remains elusive in many patients. In the future, molecular markers will be employed to improve the sensitivity for the detection of malignancy in bile duct samples obtained through brushing, aspiration, and biopsy. (c) 2005 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Blake 452C, Boston, MA 02114 USA. EM WBrugge@partners.org NR 25 TC 25 Z9 36 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 JUL 10 PY 2005 VL 23 IS 20 BP 4561 EP 4565 DI 10.1200/JCO.2005.19.729 PG 5 WC Oncology SC Oncology GA 945LX UT WOS:000230505100013 PM 16002848 ER PT J AU Mager, DL Haffajee, AD Devlin, PM Norris, CM Posner, MR Goodson, JM AF Mager, DL Haffajee, AD Devlin, PM Norris, CM Posner, MR Goodson, JM TI The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; STREPTOCOCCUS-ANGINOSUS; EXPERIMENTAL GINGIVITIS; PERIODONTAL-DISEASE; MUCOUS-MEMBRANES; MUCOSAL SURFACES; UNITED-STATES; YOUNG-ADULTS; CAVITY; DNA AB Background: The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC- free) controls. Methods: Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history. Results: Counts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively. Conclusion: High salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC. C1 Forsyth Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mager, DL (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM dmager@forsyth.org; ahaffajee@forsyth.org; pdevlin@lroc.harvard.edu; Charles_Norris@dfci.harvard.edu; marshall_posner@dfci.harvard.edu; mgoodson@forsyth.org NR 56 TC 17 Z9 17 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUL 7 PY 2005 VL 3 DI 10.1186/1479-5876-3-27 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KP UT WOS:000232161700001 ER PT J AU Garraway, LA Widlund, HR Rubin, MA Getz, G Berger, AJ Ramaswamy, S Beroukhim, R Milner, DA Granter, SR Du, JY Lee, C Wagner, SN Li, C Golub, TR Rimm, DL Meyerson, ML Fisher, DE Sellers, WR AF Garraway, LA Widlund, HR Rubin, MA Getz, G Berger, AJ Ramaswamy, S Beroukhim, R Milner, DA Granter, SR Du, JY Lee, C Wagner, SN Li, C Golub, TR Rimm, DL Meyerson, ML Fisher, DE Sellers, WR TI Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma SO NATURE LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; ANTICANCER DRUG SCREEN; CANCER-CELL LINES; HETEROZYGOSITY ANALYSIS; EXPRESSION PATTERNS; PROSTATE-CANCER; COPY NUMBER; MELANOCYTES; GENE; MICROPHTHALMIA AB Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer(1-5). Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification. We found that MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. BRAF mutation and p16 inactivation accompanied MITF amplification in melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression. C1 Dana Farber Canc Inst, Dept Med Oncol, Pediat Oncol Biostat Sci & Melonam Program Med On, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Broad Inst Harvard, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Austrian Acad Sci, Ctr Mol Med, A-1090 Vienna, Austria. Med Univ Vienna, Dept Dermatol, DIAID, A-1090 Vienna, Austria. RP Dana Farber Canc Inst, Dept Med Oncol, Pediat Oncol Biostat Sci & Melonam Program Med On, 44 Binney St, Boston, MA 02115 USA. EM William_Sellers@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Wagner, Stephan/0000-0003-4941-7029; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [T32 CA009172] NR 29 TC 761 Z9 777 U1 6 U2 54 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 JUL 7 PY 2005 VL 436 IS 7047 BP 117 EP 122 DI 10.1038/nature03664 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942QJ UT WOS:000230296600050 PM 16001072 ER PT J AU Wu, LZ Liu, JX Gao, P Nakamura, M Cao, Y Shen, HX Griffin, JD AF Wu, LZ Liu, JX Gao, P Nakamura, M Cao, Y Shen, HX Griffin, JD TI Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation SO EMBO JOURNAL LA English DT Article DE CREB; MECT1-MAML2 fusion; mucoepidermoid carcinoma; transformation; Warthin's tumor ID BINDING-PROTEIN; MUCOEPIDERMOID CARCINOMA; WARTHINS TUMOR; CELL-CYCLE; CAMP; TRANSCRIPTION; EXPRESSION; FAMILY; PHOSPHORYLATION; IDENTIFICATION AB Salivary gland tumors, a group of histologically diverse benign and malignant neoplasms, represent a challenging problem for diagnosis and treatment. A specific recurring t(11; 19)(q21; p13) translocation is associated with two types of salivary gland tumors, mucoepidermoid carcinomas and Warthin's tumors. This translocation generates a fusion protein comprised of the N-terminal CREB ( cAMP response element-binding protein)-binding domain of the CREB regulator MECT1 ( Mucoepidermoid carcinoma translocated-1) and the C-terminal transcriptional activation domain of the Notch coactivator Mastermind-like 2 (MAML2). Here, we demonstrate that the MECT1-MAML2 fusion protein induces expression of multiple genes known to be CREB transcriptional targets. MECT1-MAML2 was found to bind to CREB, recruit p300/CBP into the CREB complex through a binding domain on MAML2, and constitutively activate CREB-dependent transcription. The transforming activity of MECT1-MAML2 was markedly reduced by blocking CREB DNA binding. Thus, this fusion oncogene mimics constitutive activation of cAMP signaling, by activating CREB directly. This study has identified a novel, critical mechanism of transformation for an oncogene associated very specifically with salivary gland tumors, and identified potential targets for the development of novel therapies. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wu, LZ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Mayer 540,44 Binney St, Boston, MA 02115 USA. EM lizi_wu@dfci.harvard.edu FU NCI NIH HHS [R01 CA036167, R01 CA097148] NR 37 TC 67 Z9 68 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD JUL 6 PY 2005 VL 24 IS 13 BP 2391 EP 2402 DI 10.1038/sj.emboj.7600719 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 951UI UT WOS:000230956500014 PM 15961999 ER PT J AU Talcott, JA AF Talcott, JA TI Employment after therapy for localized prostate cancer: Widening the perspective SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; FOLLOW-UP; MEN; ABSENTEEISM; EXPERIENCE; OUTCOMES C1 Massachusetts Gen Hosp, Ctr Outcomes Res, Boston, MA 02114 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, HO1-107,55 Fruit St, Boston, MA 02114 USA. EM jtalcott@partners.org NR 15 TC 4 Z9 4 U1 0 U2 3 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 JUL 6 PY 2005 VL 97 IS 13 BP 948 EP 949 DI 10.1093/jnci/dji182 PG 2 WC Oncology SC Oncology GA 942QF UT WOS:000230296200001 PM 15998940 ER PT J AU do Rosario-Campos, MC Leckman, JF Curi, M Quatrano, S Katsovitch, L Miguel, EC Pauls, DL AF do Rosario-Campos, MC Leckman, JF Curi, M Quatrano, S Katsovitch, L Miguel, EC Pauls, DL TI A family study of early-onset obsessive-compulsive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive compulsive disorder; childhood onset; family study; genetics; comorbid tic disorders ID LA-TOURETTE-SYNDROME; PSYCHIATRIC-DISORDERS; 1ST-DEGREE RELATIVES; CHILDREN; EPIDEMIOLOGY; ADOLESCENTS; SCALE; AGE; RELIABILITY; VALIDITY AB Results from family studies have suggested that obsessive-compulsive disorder (OCD) is a genetically heterogeneous disorder and have emphasized the importance of identifying valid subgroups of patients. The current study focused on early-onset OCD probands and examined the recurrence risks of OCD and tics among first-degree family members. One hundred six children and adolescents with OCD were recruited from a specialty clinic for OCD and 44 control individuals without OCD were identified by random-digit dialing. These 150 probands and their 465 first-degree relatives were assessed by trained interviewers, using standardized semi-structured interviews. Diagnoses were assigned according to DSM-IV criteria by two experts blind to the proband's diagnosis, through the best-estimate process. These data were analyzed using chi(2) tests, t-tests, logistic regression, and generalized estimating equations (GEE). Case probands had a mean age of onset of OC symptoms of 6.7 years (SD = 2.8), and high comorbid rates with Tourette syndrome (33%) and chronic tics (13.2%). Compared to control relatives, case relatives had higher age-corrected recurrence risks of OCD (22.7% vs. 0.9%, odds ratio (OR)= 32.5, 95% confidence interval (CI) = 4.5-230.8, P = 0.0005), and chronic tics (11.6% vs. 1.7%, OR = 7.9, 95% CI = 1.9-33.1, P = 0.005). A comorbid diagnosis of ties in the relatives was the best predictor of their diagnosis of OCD (OR = 7.35, 95% CI = 3.79-14.25, P < 0.0001). There was a significant correlation between the ages of onset of OCD in probands and their affected relatives. Childhood onset OCD is a highly familial disorder. Some early-onset cases may represent a valid subgroup, with higher genetic loading and shared vulnerability with chronic tic disorders. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 149 13th St, Charlestown, MA 02129 USA. EM dpauls@partners.org RI Miguel, Euripedes/B-2871-2008; Curi, Mariana/E-8468-2011; do Rosario, Maria Conceicao/E-5213-2012 OI do Rosario, Maria Conceicao/0000-0002-9687-0072 FU NIMH NIH HHS [MH00508]; NINDS NIH HHS [NS40024, NS16648] NR 35 TC 93 Z9 94 U1 6 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 5 PY 2005 VL 136B IS 1 BP 92 EP 97 DI 10.1002/ajmg.b.30149 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 939DN UT WOS:000230052700016 PM 15892140 ER PT J AU Dec, GW AF Dec, GW TI Acute decompensated heart failure - The shrinking role of inotropic therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID HOSPITALIZATION; MANAGEMENT; MILRINONE C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,Mailstop 847,Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 9 TC 8 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 5 PY 2005 VL 46 IS 1 BP 65 EP 67 DI 10.1016/j.jacc.2005.04.007 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 941LJ UT WOS:000230216000011 PM 15992637 ER PT J AU Singh, JP Houser, S Heist, EK Ruskin, JN AF Singh, JP Houser, S Heist, EK Ruskin, JN TI The coronary venous anatomy - A segmental approach to aid cardiac resynchronization therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ELECTRON-BEAM CT; COMPUTED-TOMOGRAPHY; HEART-FAILURE; SINUS; CATHETER; VEIN; TRIBUTARIES; DRAINAGE AB The coronary sinus is the gateway for left ventricular (LV) epicardial lead placement for cardiac resynchronization therapy. The implanting electrophysiologist is usually challenged by a high degree of variability in the coronary venous anatomy, making it important to have a more consistent and uniform segmental approach to describe the coronary venous tree and its branches. Classifying the coronary sinus branches and tributaries by the segment of their location rather than by conventional anatomic names (i.e., middle cardiac vein, great cardiac vein, and so on), would provide more relevant anatomic and functional information at the time of LV lead placement. This would enable the implanting physician to proactively correlate the venous anatomy with the segmental wall motion abnormalities or dyssynchrony, as defined by echocardiography and other imaging modalities. The current viewpoint calls for a more systematic segmental approach for describing the coronary venous anatomy. (J Am Coll Cardiol 2005-,46:68-74) (c) 2005 by the American College of Cardiology Foundation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Caradiac Pathol Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 24 TC 94 Z9 99 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 5 PY 2005 VL 46 IS 1 BP 68 EP 74 DI 10.1016/j.jacc.2005.04.017 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 941LJ UT WOS:000230216000012 PM 15992638 ER PT J AU Uemura, T Otsuji, Y Nakashiki, K Yoshifuku, S Maki, Y Yu, B Mizukami, N Kuwahara, E Hamasaki, S Biro, S Kisanuki, A Minagoe, S Levine, RA Tei, C AF Uemura, T Otsuji, Y Nakashiki, K Yoshifuku, S Maki, Y Yu, B Mizukami, N Kuwahara, E Hamasaki, S Biro, S Kisanuki, A Minagoe, S Levine, RA Tei, C TI Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients with localized basal inferior left ventricular remodeling - Insights from tissue Doppler strain imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; PROGNOSTIC IMPLICATIONS; MECHANISM; DETERMINANTS; DYNAMICS; GEOMETRY; FLOW AB OBJECTIVES The purpose of this research was to test whether Papillary muscle (PM) dysfunction attenuates ischemic mitral regurgitation (MR) in patients with left ventricular (LV) remodeling of a similar location and extent. BACKGROUND Papillary muscle dysfunction could attenuate tethering and MR because of PM elongation. However, variability in the associated LV remodeling, which exaggerates tethering, can influence the relationship between PM dysfunction and MR. METHODS In 40 patients with a previous inferior myocardial infarction but without other lesions, the LV volume, sphericity, PM tethering distance, PM longitudinal systolic strain, and MR fraction were quantified by echocardiography. The patients were divided into two groups: group 1 with significant basal inferoposterior LV bulging but without advanced LV bulging involving other territories, therefore with a similar location and extent of LV remodeling, and group 2 without significant LV bulging. RESULTS The medial PM tethering distance was significantly correlated with the %MR fraction (r(2) = 0.64, p < 0.01), and multiple regression analysis identified an increase in the tethering distance as the only independent determinant of the MR fraction in all subjects and also in group 1. The PM longitudinal systolic strain had no significant relationships with MR fraction in all subjects with variable degrees of LV remodeling, but it had a significant inverse correlation with the MR fraction (r(2) = 0.33, p < 0.01) in group 1 with LV remodeling of a similar location and extent, indicating that PM dysfunction is associated with less MR. CONCLUSIONS Papillary muscle dysfunction, reducing its longitudinal contraction to induce leaflet tethering, attenuates ischemic MR in patients with basal inferior LV remodeling. (J Am Coll Cardiol 2005;46:113-9) (c) 2005 by the American College of Cardiology Foundation. C1 Kagoshima Univ, Grad Sch Med, Dept Internal Med 1, Kagoshima 8908520, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Otsuji, Y (reprint author), Kagoshima Univ, Grad Sch Med, Dept Internal Med 1, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM yutaka@m.kufm.kagoshima-u.ac.jp NR 37 TC 39 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 5 PY 2005 VL 46 IS 1 BP 113 EP 119 DI 10.1016/j.jacc.2005.003.049 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 941LJ UT WOS:000230216000018 PM 15992644 ER PT J AU Tonon, G Wong, KK Maulik, G Brennan, C Feng, B Zhang, YY Khatry, DB Protopopov, A You, MJ Aguirre, AJ Martin, ES Yang, ZH Ji, HB Chin, L DePinho, RA AF Tonon, G Wong, KK Maulik, G Brennan, C Feng, B Zhang, YY Khatry, DB Protopopov, A You, MJ Aguirre, AJ Martin, ES Yang, ZH Ji, HB Chin, L DePinho, RA TI High-resolution genomic profiles of human lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE array comparative genomic hybridization; expression profiling; lung adenocarcinoma; squamous-cell lung carcinoma; TP73L ID SQUAMOUS-CELL CARCINOMAS; ACUTE MYELOID-LEUKEMIA; DOMAIN-CONTAINING GENE; CHROMOSOMAL IMBALANCES; MICROARRAY ANALYSIS; ADENOCARCINOMA; HYBRIDIZATION; P63; MULTIPLE; REVEALS AB Lung cancer is the leading cause of cancer mortality worldwide, yet there exists a limited view of the genetic lesions driving this disease. In this study, an integrated high-resolution survey of regional amplifications and deletions, coupled with gene-expression profiling of non-small-cell lung cancer subtypes, adenocarcinoma and squamous-cell carcinoma (SCC), identified 93 focal copy-number alterations, of which 21 span < 0.5 megabases and contain a median of five genes. Whereas all known lung cancer genes/loci are contained in the dataset, most of these recurrent copy-number alterations are previously uncharacterized and include high-amplitude amplifications and homozygous deletions. Notably, despite their distinct histopathological phenotypes, adenocarcinoma and SCC genomic profiles showed a nearly complete overlap, with only one clear SCC-specific amplicon. Among the few genes residing within this amplicon and showing consistent overexpression in SCC is p63, a known regulator of squamous-cell differentiation. Furthermore, intersection with the published pancreatic cancer comparative genomic hybridization dataset yielded, among others, two focal amplicons on 8p12 and 20q11 common to both cancer types. Integrated DNA-RNA analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kwong1@partners.org; ron_depinho@dfci.harvard.edu OI Khatry, Deepak/0000-0002-2388-9434; Brennan, Cameron/0000-0003-4064-8891; wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [R01 CA084628, R01 CA084628-12, R01 CA099041, U01 CA084313, U01-CA084313-07]; NIA NIH HHS [K08AG 2400401] NR 34 TC 261 Z9 272 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2005 VL 102 IS 27 BP 9625 EP 9630 DI 10.1073/pnas.0504126102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944DN UT WOS:000230406000034 PM 15983384 ER PT J AU Sabbagh, Y Carpenter, TO Demay, MB AF Sabbagh, Y Carpenter, TO Demay, MB TI Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Phex gene; vitamin D receptor ID VITAMIN-D-RECEPTOR; MINERAL ION HOMEOSTASIS; SKELETAL PHENOTYPE; ABLATED MICE; CELL-DEATH; PHOSPHATE; MUTATIONS; IDENTIFICATION; TRANSPORT; ALOPECIA AB Rickets is seen in association with vitamin D deficiency and in several genetic disorders associated with abnormal mineral ion homeostasis. Studies in vitamin D receptor (VDR)-null mice have demonstrated that expansion of the late hypertrophic chondrocyte layer, characteristic of rickets, is secondary to impaired apoptosis of these cells. The observation that normalization of mineral ion homeostasis in the VDR-null mice prevents rachitic changes suggests that rickets is secondary to hypocalcemia, hypophosphatemia, or hyperparathyroidism, rather than impaired VDR action. To determine which of these abnormalities is responsible for impaired chondrocyte apoptosis and subsequent rachitic changes, two additional models were examined: diet-induced hypophosphatemia/hypercalcemia and hypophosphatemia secondary to mutations in the Phex gene. The former model is associated with suppressed parathyroid hormone levels as a consequence of hypercalcemia. The latter model demonstrates normal calcium and parathyroid hormone levels, but 1,25-dihydroxyvitamin D levels that are inappropriately low for the degree of hypophosphatemia. Our studies demonstrate that normal phosphorus levels are required for growth plate maturation and implicate a critical role for phosphate-regulated apoptosis of hypertrophic chondrocytes via activation of the caspase-9-mediated mitochondrial pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu OI Sabbagh, Yves/0000-0001-5339-6705 FU NIDDK NIH HHS [R01 DK046974, DK46974] NR 31 TC 95 Z9 96 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2005 VL 102 IS 27 BP 9637 EP 9642 DI 10.1073/pnas.0502249102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944DN UT WOS:000230406000036 PM 15976027 ER PT J AU Cho, S Knox, KS Kohli, LM He, JJ Exley, MA Wilson, SB Brutkiewicz, RR AF Cho, S Knox, KS Kohli, LM He, JJ Exley, MA Wilson, SB Brutkiewicz, RR TI Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complex SO VIROLOGY LA English DT Article DE CD1d; human; murine; HIV-1; Nef; cell surface expression; complex ID KILLER T-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; CLASS-I MHC; ANTIGEN-PRESENTING MOLECULES; BACILLUS-CALMETTE-GUERIN; NKT CELLS; DENDRITIC CELLS; CYTOPLASMIC TAIL; IFN-GAMMA; ALPHA-GALACTOSYLCERAMIDE AB The HIV-1 Nef protein causes a decrease in major histocompatibility complex (MHC) class 1 and CD4 molecule expression on the cell surface. To determine if Nef can affect components of the innate immune response, we assessed the ability of Nef to alter the cell surface expression of human CD1d. In cells co-expressing CD1d and Nef, a Substantial reduction in the cell surface level of CD1d was observed, with a concomitant reduction in the activation of CD1d-restricted NKT cells. Nef had a minimal effect on the cell surface expression of a mutant CD1d molecule in which the last 6 or 10 amino acids of the cytoplasmic tail were deleted. Additionally, it was found that Nef physically interacted with wild-type (but not tail-deleted) CD1d. Therefore, one means by which HIV-1 may be able to establish a foothold in an infected individual is by directly interfering with the functional cell surface expression of CD1d. (c) 2005 Elsevier Inc. All rights reserved. C1 Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Div Pulm Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Walther Oncol Ctr, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN 46208 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Biol Program,Div Hematol & Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Diabet Res Labs, Cambridge, MA 02139 USA. RP Brutkiewicz, RR (reprint author), Indiana Univ, Sch Med, Dept Microbiol & Immunol, 950 W Walnut St,R2-302, Indianapolis, IN 46202 USA. EM rbrutkie@iupui.edu NR 71 TC 60 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2005 VL 337 IS 2 BP 242 EP 252 DI 10.1016/j.virol.2005.04.020 PG 11 WC Virology SC Virology GA 940PB UT WOS:000230155300005 PM 15916790 ER PT J AU Chang, JH Javier, JAD Chang, GY Oliveira, HB Azar, DT AF Chang, JH Javier, JAD Chang, GY Oliveira, HB Azar, DT TI Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen SO FEBS LETTERS LA English DT Article DE endostatin; neostatin-7; neostatin-14; matrix metalloproteinas; MMP-7; MMP-14 ID HEPARAN-SULFATE PROTEOGLYCAN; KERATECTOMY WOUNDS; ENDOTHELIAL-CELLS; DEFICIENT MICE; ENDOSTATIN; ANGIOGENESIS; MATRILYSIN; EXPRESSION; DOMAIN; GENERATION AB Several anti-angiogenic factors are derived from proteolytic processing of large molecules including endostatin from type XVIII collagen and angiostatin from plasminogen. In previous studies we showed that neostatin-7, the C-terminal 28 kDa endostatin-spanning proteolytic fragment, is generated from the proteolytic action of matrix metalloproteinase matrilysin (MMP)-7 on type XVIII collagen. Now, we report a second member of the neostatin family of proteins, neostatin-14. Given the small quantities of neostatin-7 and -14 generated by the breakdown of naturally occurring collagen XVIII (using MMP-7 and -14, respectively), we used two other approaches to characterize the anti-angiogenic properties of these molecules: murine recombinant neostatin in vitro, and gene therapy. We demonstrate that murine recombinant neostatin-7 inhibits calf pulmonary artery endothelial cell proliferation and that microinjection of neostatin-7 and neostatin-14 naked DNA into the corneal stroma of mice results in significant reduction of basic fibroblast growth factor-induced corneal neovascularization. These results provide supportive evidence of the possible antiangiogenic effect of neostatins. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, External Dis & Refract Surg Serv, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Sch Med, External Dis & Refract Surg Serv, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU PHS HHS [NEI 14048, NEI 10101] NR 40 TC 51 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 2005 VL 579 IS 17 BP 3601 EP 3606 DI 10.1016/j.febslet.2005.05.043 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 943EQ UT WOS:000230335600022 PM 15978592 ER PT J AU Barnich, N Aguirre, JE Reinecker, HC Xavier, R Podolsky, DK AF Barnich, N Aguirre, JE Reinecker, HC Xavier, R Podolsky, DK TI Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-kappa B activation in muramyl dipeptide recognition SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CROHNS-DISEASE; FAMILY-MEMBER; CARD15 GENE; INNATE; SUSCEPTIBILITY; PEPTIDOGLYCAN; RESPONSES; VARIANTS; MUTATION; PROTEIN AB Nucleotide oligomerization domain ( NOD) 2 functions as a mammalian cytosolic pathogen recognition molecule, and mutant forms have been genetically linked to Crohn's disease ( CD). NOD2 associates with the caspase activation and recruitment domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase (RICK)/RIP2 and activates nuclear factor (NF)-kappa B in epithelial cells and macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an impaired ability to activate NF-kappa B. To gain insight into the molecular mechanisms of NOD2 function, we performed a functional analysis of deletion and substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with cell surface membranes of intestinal epithelial cells. Membrane targeting and subsequent NF-kappa B activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane targeting of NOD2 is required for NF-kappa B activation after the recognition of bacterial muramyl dipeptide in intestinal epithelial cells. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK043351, DK069344, DK07191, DK33506, DK54429, P01 DK033506, P30 DK043351, R01 DK068181, R01 DK069344, T32 DK007191] NR 24 TC 167 Z9 173 U1 1 U2 2 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 JUL 4 PY 2005 VL 170 IS 1 BP 21 EP 26 DI 10.1083/jcb.200502153 PG 6 WC Cell Biology SC Cell Biology GA 943XK UT WOS:000230388700004 PM 15998797 ER PT J AU Medoff, BD Seung, E Wain, JC Means, TK Campanella, GSV Islam, SA Thomas, SY Ginns, LC Grabie, N Lichtman, AH Tager, AM Luster, AD AF Medoff, BD Seung, E Wain, JC Means, TK Campanella, GSV Islam, SA Thomas, SY Ginns, LC Grabie, N Lichtman, AH Tager, AM Luster, AD TI BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID B-4 RECEPTOR ANTAGONIST; LEUKOTRIENE B-4; ALLOGRAFT-REJECTION; BRONCHIAL HYPERREACTIVITY; AIRWAY INFLAMMATION; IN-VIVO; EXPRESSION; PATHOGENESIS; LYMPHOCYTES; CXCL10 AB Leukotriene B 4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8(+) T cell trafficking into the lung and that disruption of BLT1 signaling in CD8(+) T cells reduces lung inflammation and mortality in the model. In addition, we used BLT1-deficient mice and a BLT1 antagonist in two tracheal transplant models of lung transplantation to demonstrate the importance of BLT1 for the recruitment of T cells into tracheal allografts. We also show that BLT1-mediated CD8(+) T cell recruitment plays an important role in the development of airway fibroproliferation and obliteration. Finally, in human studies of lung transplant recipients, we found that BLT1 is up-regulated on T lymphocytes isolated from the airways of patients with obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the development of lung rejection and obliterative bronchiolitis by mediating effector T lymphocyte trafficking into the lung. This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NHLBI NIH HHS [K08 HL072775]; NIAID NIH HHS [K08 AI055663, R01 AI050892] NR 50 TC 38 Z9 42 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 4 PY 2005 VL 202 IS 1 BP 97 EP 110 DI 10.1084/jem.20042481 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 941LA UT WOS:000230215100010 PM 15998790 ER PT J AU Sarmento, LM Huang, H Limon, A Gordon, W Fernandes, J Tavares, MJ Miele, L Cardoso, AA Classon, M Carlesso, N AF Sarmento, LM Huang, H Limon, A Gordon, W Fernandes, J Tavares, MJ Miele, L Cardoso, AA Classon, M Carlesso, N TI Notch1 modulates timing of G(1)-S progression by inducing SKP2 transcription and p27(Kip1) degradation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MEDIATED GROWTH ARREST; INHIBITOR P27; IN-VIVO; J-KAPPA; CELLS; DIFFERENTIATION; FATE; DISRUPTION; INDUCTION; NEOPLASMS AB Cyclin-dependent kinase inhibitors (CKIs) and Notch receptor activation have been shown to influence adult stem cells and progenitors by altering stem cell self-renewal and proliferation. Yet, no interaction between these molecular pathways has been defined. Here we show that ligand-independent and ligand-dependent activation of Notch1 induces transcription of the S phase kinase-associated protein 2 (SKP2), the F-box subunit of the ubiquitin-ligase complex SCFSKP2 that targets proteins for degradation. Up-regulation of SKP2 by Notch signaling enhances proteasome-mediated degradation of the CKIs, p27(Kip1) and p21(Cip1), and causes premature entry into S phase. Silencing of SKP2 by RNA interference in G(1) stabilizes p27(Kip1) and p21(Cip1) and abolishes Notch effect on G(1)-S progression. Thus, SKP2 serves to link Notch1 activation with the cell cycle machinery. This novel pathway involving Notch/SKP2/CKIs connects a cell surface receptor with proximate mediators of cell cycle activity, and suggests a mechanism by which a known physiologic mediator of cell fate determination interfaces with cell cycle control. C1 Harvard Univ, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02129 USA. Univ Lisbon, IMM, P-1649028 Lisbon, Portugal. Sci Res Lab Inc, Somerville, MA 02143 USA. Univ Illinois, Dept Pharmacodynam, Chicago, IL 60612 USA. RP Carlesso, N (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02129 USA. EM carlesso.nadia@mgh.harvard.edu OI Sarmento, Leonor/0000-0002-3692-0592 FU NHLBI NIH HHS [R01 HL68256-01, R01 HL068256] NR 44 TC 125 Z9 141 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 4 PY 2005 VL 202 IS 1 BP 157 EP 168 DI 10.1084/jem.20050559 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 941LA UT WOS:000230215100015 PM 15998794 ER PT J AU Schiller, JD Gervais, DA Mueller, PR AF Schiller, JD Gervais, DA Mueller, PR TI Radiofrequency ablation of renal cell carcinoma SO ABDOMINAL IMAGING LA English DT Article DE radiofrequency ablation; kidney tumors; renal tumors ID NEPHRON SPARING SURGERY; TISSUE ABLATION; CLINICAL-EXPERIENCE; THERMAL ABLATION; TUMOR ABLATION; CANCER; TEMPERATURE; MALIGNANCY; MANAGEMENT; ELECTRODE C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dgervais@partners.org NR 38 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JUL-AUG PY 2005 VL 30 IS 4 BP 442 EP 450 DI 10.1007/s00261-004-0259-3 PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 949AM UT WOS:000230757300009 PM 16132440 ER PT J AU Metlay, JP Camargo, CA Bos, K Gonzales, R AF Metlay, JP Camargo, CA Bos, K Gonzales, R TI Assessing the suitability of intervention sites for quality improvement studies in emergency departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT National Meeting of the Agency-for-Healthcare-Research-and-Quality CY JUL, 2004 CL Washington, DC SP Agency Healthcare Res Quality DE emergency medical services; data collection; quality improvement ID CARE AB Objectives: As an initial step in disseminating an emergency department (ED)-based quality improvement program (QIP) to improve antibiotic prescribing for patients 0 with acute respiratory infections, the authors conducted a nationwide survey to assess the value and feasibility of the QIP. Methods: Directors of EDs at 119 Veterans Administration hospitals and 160 non-Veterans Administration hospitals (identified based on the existence of accredited emergency medicine training programs and/or participation in an existing ED-based research network) were surveyed. The survey included questions on the current existence of an antibiotic QIP in the ED, enthusiasm for an antibiotic QIP program, and the existence of physical features in the ED that would support the QIP intervention. Results: Overall, 77% of ED directors reported they did not have an existing antibiotic QIP and 84% reported they would benefit from having such a program (either new or in addition to their current program). In addition, 63% of respondents indicated that improving antibiotic prescribing was an intermediate to high priority in the ED. Forty-five percent reported that they did not cave a suitable location for a key component of the intervention (an interactive computer kiosk), and 26% reported that they could not display educational posters on the walls of the examination room. Conclusions: Many EDs identify barriers to implementing an antibiotic QIP. Perceived and real barriers are important factors to consider in translating successful QIPs into routine clinical practice. C1 VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Metlay, JP (reprint author), 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM imetlay@cceb.med.upenn.edu FU AHRQ HHS [R01 HS13915] NR 5 TC 10 Z9 10 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 2005 VL 12 IS 7 BP 667 EP 670 DI 10.1197/j.aem.2005.01.012 PG 4 WC Emergency Medicine SC Emergency Medicine GA 942MW UT WOS:000230287500016 PM 15995102 ER PT J AU Jackson, VA Sullivan, AM Gadmer, NM Seltzer, D Mitchell, AM Lakoma, MD Arnold, RM Block, SD AF Jackson, VA Sullivan, AM Gadmer, NM Seltzer, D Mitchell, AM Lakoma, MD Arnold, RM Block, SD TI "It was haunting...": Physicians' descriptions of emotionally powerful patient deaths SO ACADEMIC MEDICINE LA English DT Article ID PALLIATIVE CARE; QUALITATIVE RESEARCH; MEDICAL-EDUCATION; HEALTH-CARE; DOCTORS; ONCOLOGISTS; EXPERIENCES; AWARENESS; STUDENTS; BURNOUT AB Purpose To understand the emotional experiences of physicians who care for dying patients and to identify educational opportunities for improving patient care and physician well-being. Method Between 1999-2001, physicians at two quaternary care medical centers in Boston, Massachusetts, and Pittsburgh, Pennsylvania, participated in 90-minute, semistructured personal interviews on their most emotionally powerful patient death. Quantitative data was obtained through face-to-face surveys rated on ten-point scales that asked physicians about emotional characteristics of and emotional responses to the death. In the qualitative portion of the survey, physicians were asked to describe the details of the most emotionally powerful patient death, the types and sequence of their emotional reactions, their methods. of coping, and subsequent changes in behavior. Results Physicians had powerful experiences with death during all stages of their careers. Experiences with patient death generally fit into one of three types: "good," "overtreated," or "shocking/unexpected." Housestaff often described coping in isolation with the disturbing emotions generated in the care of dying patients. Physicians learned how to care for and cope with dying patients from their experiences with patients whose deaths were most emotionally powerful and reported changes in their clinical behavior and career paths as a result. Conclusions Physicians' emotional reactions to patient death can affect patient care and the personal lives of physicians. Supervising physicians have an opportunity to improve both the care of dying patients and house-staff coping with these deaths by using the "teachable moments" that are present for trainees as they care for the dying. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, VA (reprint author), Massachusetts Gen Hosp, 55 Fruit St Founders 600, Boston, MA 02114 USA. EM vjackson@partners.org NR 31 TC 56 Z9 56 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2005 VL 80 IS 7 BP 648 EP 656 DI 10.1097/00001888-200507000-00007 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 939FT UT WOS:000230058600006 PM 15980081 ER PT J AU Sullivan, AM Lakoma, MD Billings, JA Peters, AS Block, SD AF Sullivan, AM Lakoma, MD Billings, JA Peters, AS Block, SD CA PCEP Core Faculty TI Teaching and learning end-of-life care: Evaluation of a faculty development Program in Palliative Care SO ACADEMIC MEDICINE LA English DT Article ID CONTINUING MEDICAL-EDUCATION; PHYSICIAN; OPPORTUNITIES; CHALLENGES; BURNOUT; COMPETENCE; PRINCIPLES; TEACHERS; OUTCOMES AB Purpose To evaluate the effectiveness of the Program in Palliative Care Education and Practice (PCEP), an intensive faculty development program at Harvard Medical School. Method PCEP is a two-week program offered annually with two on-site sessions in Boston, MA, and an interim period distance-learning component. Training integrates palliative care clinical skill development, learning theory and teaching methods, and leadership and organizational change. Longitudinal surveys (preprogram, retrospective preprogram, and postprogram) of participants from 2000-03 assessed self-reported preparation in providing and teaching palliative care;, teaching and patient care practices; and satisfaction with program. Results The response rate was 96% (n = 149) for Session 1 and 72% for both Session 1 and 11 (n = 113). Questionnaire responses demonstrated statistically significant improvements with large effect sizes (range 0.7-1.8) on nearly all measures. Preparation increased from 3.0 +/- 1.1 to 4.2 +/- 0.7 for providing end-of-life care (1 = not well prepared, 5 = very well prepared), and from 2.6 +/- 1.0 to 4.3 +/- 0.7 for teaching this topic. Respondents reported behavioral changes in patient care and teaching; e.g., after the program, 63% noted that, specifically as a result of attending the course, they encouraged learners to reflect on their emotional responses to dying patients, and 57% conducted experiential exercises (e.g., role-play). Eighty-two percent rated the experience as "transformative," and many responses to open-ended items described powerful learning experiences. Participants rated the program highly (4.9 +/- 0.1, 1 = lowest, 5 = highest rating). Conclusions integrating clinical content with learning about educational methods is an efficient and effective approach to enhancing clinical faculty's capacity to model and teach clinical care. This program offers an educational model that engages practitioners, stimulates changes in practice, and offers opportunities for reflection and professional revitalization. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sullivan, AM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM amy_sullivan@dfci.harvard.edu NR 58 TC 52 Z9 53 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2005 VL 80 IS 7 BP 657 EP 668 DI 10.1097/00001888-200507000-00008 PG 12 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 939FT UT WOS:000230058600007 PM 15980082 ER PT J AU Belkin, GS Fricchione, GL AF Belkin, GS Fricchione, GL TI Internationalism and the future of academic psychiatry SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID MENTAL-HEALTH-SERVICES C1 Massachusetts Gen Hosp, Dept Psychiat, Div Int Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Dept Psychiat, Boston, MA USA. NYU, Sch Med, Bellevue Hosp Ctr, Dept Psychiat, New York, NY 10012 USA. RP Fricchione, GL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Int Psychiat, Warren Bldg,6th Floor,275 Charles St, Boston, MA 02114 USA. EM gfricchione@partners.org NR 20 TC 13 Z9 13 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2005 VL 29 IS 3 BP 240 EP 243 DI 10.1176/appi.ap.29.3.240 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 960MH UT WOS:000231596700002 PM 16141117 ER PT J AU Wilbur, DC AF Wilbur, DC TI The annual Pap test - Baseline data to allow informed decisions about future screening programs SO ACTA CYTOLOGICA LA English DT Editorial Material DE papanicolaou smear; cervical cancer; mass screening C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wilbur, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 120, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 2005 VL 49 IS 4 BP 351 EP 353 DI 10.1159/000326165 PG 3 WC Pathology SC Pathology GA 948BO UT WOS:000230691200001 PM 16124161 ER PT J AU Soldani, F Ghaemi, SN Baldessarini, RJ AF Soldani, F Ghaemi, SN Baldessarini, RJ TI Research reports on treatments for bipolar disorder: preliminary assessment of methodological quality SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; journal article; epidemiologic research design; randomized controlled trials; control groups; reproducibility of results; confidence intervals; bibliometrics ID JOURNALS AB Objective: To assess frequencies of types of publications about bipolar disorder ( BD) and evaluate methodological quality of treatment studies. Method: We classified 100 randomly selected articles (1998-2002) from five psychiatric journals with highest impact ratings, by topic areas, and assessed methods employed in treatment studies. Results: Topics ranked: treatment (41%; 37% on pharmacotherapy) > biology (31%) > psychopathology (14%) = miscellaneous (14%). Of treatment studies, only 19% of original articles were randomized, 15% were relatively large (n >= 50) but non-randomized, 65% were small non-randomized, case-series or -reports, and 53% relied on baseline-to-endpoint contrasts without a control group. Patient dropout rates were >= 40% in 43% of prospective studies. Only two reports provided confidence intervals; one included a power analysis, and 53% included no references on study design or statistical methods. Conclusion: Even in highly respected journals, the typical methodological quality of recent reports on therapeutics for BD was unexpectedly limited, and psychopathology and psychotherapies were little studied. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Bipolar & Psychot Disorders Program, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Soldani, F (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Bipolar & Psychot Disorders Program, 115 Mill St, Belmont, MA 02478 USA. EM federico@post.harvard.edu FU NIMH NIH HHS [MH-64189] NR 9 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 2005 VL 112 IS 1 BP 72 EP 74 DI 10.1111/j.1600-0447.2005.00575.x PG 3 WC Psychiatry SC Psychiatry GA 933MS UT WOS:000229634500010 PM 15952948 ER PT J AU Siegel, CA Sands, BE AF Siegel, CA Sands, BE TI Review article: practical management of inflammatory bowel disease patients taking immunomodulators SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID SEVERE ULCERATIVE-COLITIS; LOW-DOSE METHOTREXATE; HUMAN THIOPURINE METHYLTRANSFERASE; 6-THIOGUANINE METABOLITE LEVELS; ISRAELI MULTICENTER TRIAL; REFRACTORY CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; LONG-TERM TOXICITY; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND AB Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists - azathioprine and mercaptopurine - the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors - ciclosporin and tacrolimus - can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations. C1 Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, 100 Charles River Plaza,9th Floor,Cambridge St, Boston, MA 02114 USA. EM bsands@partners.org NR 134 TC 69 Z9 73 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 2005 VL 22 IS 1 BP 1 EP 16 DI 10.1111/j.1365-2036.2005.02520.x PG 16 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 937GK UT WOS:000229912400001 PM 15963074 ER PT J AU Gupta, S Volpp, H Klaustermeyer, WB AF Gupta, S Volpp, H Klaustermeyer, WB TI Demographics and long-term follow-up in a Veterans Affairs Allergy/Immunology Center: A 10-year analysis SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 18-23, 2004 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol ID PREVALENCE; SYMPTOMS; ASTHMA AB Between 1985 and 1992, patients were evaluated as new outpatient consultations in the Allergy/Immunology Center at the Veterans Affairs Greater Los Angeles Health Care System (VAGLAHS). Data collected included age, gender, ethnicity, and diagnosis. After 10 years, patient follow-up status was determined and classified into five categories: gender, ethnic distribution, age distribution, disorders seen, and follow-up pattern. A total of 1116 patients were evaluated. The gender of our population was 7.8% women and 92.2% men. The ethnic distribution was 59.5% white, 32.2% black, 6.5% Hispanic, and 1.9% other. Neither age nor ethnic distribution was significantly different from the general veterans affairs population. Age of patients ranged from 20 to 90 years old. The largest peak for age at initial presentation was 60 years. The three most common disorders seen in the clinic were rhinitis (36.6%), asthma (24.5%), and sinusitis (12.3%). The 10-year follow-up pattern of patients revealed that 6% were seen in the past year, 6.2% of patients were seen longer than I year ago but within the 5 past years, 29% of patients who were still seen at VAGLAHS but were no longer patients of the allergy clinic, 32.7% of patients who were no longer seen at VAGLAHS, and 26.2% died. Women and patients who were 50-60 years old were more likely to follow-up. There was no difference in follow-up visits among ethnic groups. C1 Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Div Allergy & Immunol, Los Angeles, CA 90073 USA. RP Klaustermeyer, WB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Div Allergy & Immunol, 11301 Wilshire Blvd,111R, Los Angeles, CA 90073 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 2005 VL 26 IS 4 BP 310 EP 315 PG 6 WC Allergy SC Allergy GA 960UL UT WOS:000231618600010 PM 16270725 ER PT J AU Ohman, EM Van de Werf, F Antman, EM Califf, RM de Lemos, JA Gibson, CM Oliverio, RL Harrelson, L McCabe, C DiBattiste, P Braunwald, E AF Ohman, EM Van de Werf, F Antman, EM Califf, RM de Lemos, JA Gibson, CM Oliverio, RL Harrelson, L McCabe, C DiBattiste, P Braunwald, E CA FASTER (TIMI 24) Investigators TI Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: Results of a randomized trial SO AMERICAN HEART JOURNAL LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; GLYCOPROTEIN IIB/IIIA INHIBITION; COMBINATION REPERFUSION THERAPY; TIMI 14 TRIAL; PLATELET-AGGREGATION; FIBRINOLYTIC THERAPY; DOSE RETEPLASE; ABCIXIMAB; THROMBOLYSIS; INTEGRILIN AB Background The combination of older reduced-dose fibrinolytic agents and platelet glycoprotein IIb/IIIa inhibitors has shown modest improvements in reperfusion and more striking improvements in ST-segment resolution after acute myocardial infarction. We performed a multicenter dose-ranging study of reduced doses of a newer fibrinolytic (tenecteplase) combined with tirofiban, a glycoprotein IIb/IIIa inhibitor. Methods The first goal of the trial was to identify a dose or closes,of tirofiban that, when combined with reduced-dose tenecteplase, would result in a higher incidence of Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 60 minutes versus full-dose tenecteplase alone. The second goal was to assess whether the optimum close(s) from the first stage also would result in greater resolution of ST-segment elevation. Results In all, 409 patients aged 18 to 75 years with myocardial infarction were enrolled. The incidence of TIMI grade 3 flow at 60 minutes did not differ significantly among dose groups, ranging from 50% to 68%. The corrected TIMI frame count likewise did not differ substantially (range 34-42). More patients given combined therapy had complete resolution of ST-segment elevation at 60 minutes compared with patients given tenecteplase alone. Major bleeding was infrequent, and no strokes occurred. Based on angiographic results of the first stage, the second planned stage of the study was not performed. Conclusions Although combination therapies were not associated with increased reperfusion compared with full-close tenecteplase alone, similar TIMI flow grades were achieved despite reductions in tenecteplase doses. ST-segment resolution was more rapid and complete with combination therapy versus full-dose tenecteplase, suggesting enhanced microcirculatory perfusion to the infarct zone in this close-ranging trial. C1 Univ N Carolina, Ctr Heart, Div Cardiol, Chapel Hill, NC USA. Univ Louvain, Dept Cardiol, Louvain, Belgium. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Duke Clin Res Inst, Durham, NC USA. Univ Texas SW, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX USA. Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. Merck & Co Inc, Whitehouse Stn, NJ USA. RP Ohman, EM (reprint author), 130 Mason Farm Rd,Bioinformat Bldg,CB 7075, Chapel Hill, NC 27599 USA. EM mohman@med.unc.edu OI Van de Werf, Frans/0000-0001-9479-7767 NR 23 TC 5 Z9 5 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2005 VL 150 IS 1 BP 79 EP 88 DI 10.1016/j.ahj.2005.01.007 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969FS UT WOS:000232219900012 PM 16084152 ER PT J AU Rodriguez, AE Alemparte, MR Pereira, CF Vigo, CF Sampaolesi, A Bernardi, V Marchand, E Tronge, J Palacios, IF AF Rodriguez, AE Alemparte, MR Pereira, CF Vigo, CF Sampaolesi, A Bernardi, V Marchand, E Tronge, J Palacios, IF CA LASMAL II Investigators TI Latin American randomized trial of balloon angioplasty versus coronary stenting in diabetic patients with small vessel reference size (Latin American Small Vessel [LASMAL II] Trial): Immediate and long-term results SO AMERICAN HEART JOURNAL LA English DT Article ID ARTERY DISEASE; ELUTING STENT; RESTENOSIS; PLACEMENT; LESIONS; IMPLANTATION; OCCLUSION; REVASCULARIZATION; DIAMETER; 6-MONTH AB Percutaneous coronary interventions (PCIs) in diabetic patients with small reference diameter vessels remain an important challenge in interventional cardiology because it is associated with increased complications and restenosis rates. Plain old balloon angioplasty (POBA) has limited efficacy in patients with lesions in small vessels. Although coronary stenting (stent) has been demonstrated to improve both immediate and long-term results after coronary intervention, small reference diameter is a strong predictor of restenosis after stent implantation. Thus, the question of how to best treat diabetic patients with lesions in small reference diameter remains unanswered. The purpose of this international and multicenter study was to compare the incidence of angiographic restenosis between percutaneous transluminal coronary angioplasty (PTCA) and stent in diabetic patients undergoing PCI of small reference diameter vessels using a specially designed phosphoryl choline (PC)-coated stent for small vessels. The patient population comprised of 220 diabetic patients with lesions in small reference diameter (<2.9 mm but >2.0 mm) that were randomized into two different PCI strategies: PTCA with provisional stenting (n = 109) versus stent (n = 111). In the PTCA arm, 26 patients (24%) crossed over to stent during the initial procedure; glycoproteins Ilb to IIIa was used in 40.5% of patients in both groups. During initial procedure and at 30 days, both strategies of revoscularitation had similar clinical success and acute complications. During long-term follow-up, even though requirements of target vessel revascularization and incidence of major adverse cardiovascular event were similar with both techniques, angiographic binary restenosis (45% with PTCA and 28% with stents, P =.047), net gain (0.74 mm with POBA and 0.94 mm with stents, P =.008), and freedom from target vessel failure (66% with POBA and 81.2% with stents, P =.013) were significantly improved when diabetic patients were initially treated with stent therapy. In summary, in diabetic patients with small coronary arteries, the use of a coronary PC-coated stent as a primary device during percutaneous interventions was associated with better angiographic and long-term outcome. C1 Otamendi Hosp, Buenos Aires Sch Med, Cardiac Catheterizat Lab, Buenos Aires, DF, Argentina. Inst med Adrogue, Buenos Aires, DF, Argentina. Inst Modelo Cardiol, Cordoba, Argentina. Inst Excelsitas, Buenos Aires, DF, Argentina. Pontificia Univ Catolica Chile, Santiago, Chile. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rodriguez, AE (reprint author), Otamendi Hosp, Buenos Aires Sch Med, Cardiac Catheterizat Lab, Buenos Aires, DF, Argentina. EM centroceci@sion.com NR 31 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2005 VL 150 IS 1 AR 188.e1-188.e7 DI 10.1016/j.ahj.2005.05.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969FS UT WOS:000232219900030 ER PT J AU Fung, TT McCullough, ML Newby, PK Manson, JE Meigs, JB Rifai, N Willett, WC Hu, FB AF Fung, TT McCullough, ML Newby, PK Manson, JE Meigs, JB Rifai, N Willett, WC Hu, FB TI Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; diet quality; inflammation; endothelial dysfunction; women ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; MAJOR CHRONIC DISEASE; ADHESION MOLECULES; FATTY-ACIDS; WOMEN; RISK; INTERLEUKIN-6; QUESTIONNAIRE; POPULATIONS AB Background: Endothelial dysfunction is one of the mechanisms linked to an increased risk of cardiovascular disease. Objective: We assessed the association between several diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. Design: Diet-quality scores on the Healthy Eating Index (HEI), Alternate Healthy Eating Index (AHEI), Diet Quality Index Revised (DQI-R), Recommended Food Score (RFS), and the alternate Mediterranean Diet Index (aMED) were calculated by using a food-frequency questionnaire that was administered in 1990 to 690 women in the Nurses' Health Study (ages 43-69 y, no cardiovascular disease or diabetes). Blood collection was completed in the same year. We used regression analysis to assess the associations between these diet-quality scores and plasma concentrations of C-reactive protein, interleukin 6, E-selectin, soluble intercellular cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1. Results: The various diet-quality scores were significantly correlated with each other; correlation coefficients ranged from 0.56 to 0.80 (all P values < 0.0001). After adjustment for age, body mass index, alcohol intake, physical activity, smoking status, and energy intake, the HEI and DQI-R were not significantly associated with any of the biomarkers, whereas the AHEI and aMED scores were associated with significantly lower concentrations of most biomarkers. The RFS was significantly associated with a lower concentration of E-selectin only. C-reactive protein concentrations were 30% (P < 0.05) and 24% (P < 0.05) lower in the top than in the bottom quintile of the AHEI and of the aMED, respectively Conclusion: Higher AHEI and aMED scores were associated with lower concentrations of biomarkers of inflammation and endothelial dysfunction and therefore may be useful as guidelines for reducing the risk of diseases involving such biological pathways. AmJ Clin Nutr 2005;82:163-73. C1 Simmons Coll, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fung, TT (reprint author), Simmons Coll, Dept Nutr, 300 Fenway, Boston, MA 02115 USA. EM fung@simmons.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845] NR 32 TC 266 Z9 269 U1 1 U2 21 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2005 VL 82 IS 1 BP 163 EP 173 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 945BC UT WOS:000230474400025 PM 16002815 ER PT J AU Scully, RE Young, RH AF Scully, RE Young, RH TI Austin L. Vickery, Jr, MD (1919,2005) SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Scully, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 2005 VL 124 IS 1 BP 152 EP 153 PG 2 WC Pathology SC Pathology GA 938CE UT WOS:000229976700022 ER PT J AU Ho, PM Masoudi, FA Peterson, PN Shroyer, AL McCarthy, M Grover, FL Hammermeister, KE Rumsfeld, JS AF Ho, PM Masoudi, FA Peterson, PN Shroyer, AL McCarthy, M Grover, FL Hammermeister, KE Rumsfeld, JS TI Health-related quality of life predicts mortality in older but not younger patients following cardiac surgery SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Article ID BYPASS GRAFT-SURGERY; SELF-RATED HEALTH; VALVE-REPLACEMENT; OPERATIVE MORTALITY; VETERAN POPULATION; MEDICAL OUTCOMES; RISK; DISEASE; CARE AB The investigators assessed preoperative health-related quality of life as a predictor of 6-month mortality after cardiac surgery in older. (65 years of age and older) vs. younger patients. Multivariable regression, stratified by age groups, was used to compare the association between preoperative Physical Component Summary and Mental Component Summary scores from the Short Form-36 health status survey and mortality. In multivariable analyses of older patients, lower preoperative Physical Component Summary (odds ratio, 1.54; 95% confidence interval, 1.19-2.00; p=0.01) and Mental Component Summary (odds ratio, 1.26; 95% confidence interval, 1.06-1.49; p=0.03) scores were independently associated with mortality. In contrast, neither Physical Component Summary (p=0.82) nor Mental Component Summary (p=0.79) scores were associated with mortality in the younger subgroup. This study demonstrated that preoperative health status is an independent predictor of mortality following cardiac surgery in older but not younger patients. Preoperative patient self-report of health status may be particularly useful in refining risk stratification and informing decision-making before and following cardiac surgery in older patients. C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. Colorado Hlth Outcomes Program, Denver, CO USA. RP Ho, PM (reprint author), 111B,1055 Clermont St, Denver, CO 80220 USA. EM michael.ho@uchsc.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU NIA NIH HHS [K08-AG01011] NR 26 TC 15 Z9 15 U1 0 U2 0 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD JUL-AUG PY 2005 VL 14 IS 4 BP 176 EP 182 DI 10.1111/j.1076-7460.2005.04312.x PG 7 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 009AM UT WOS:000235083500003 PM 16015058 ER PT J AU Chopra, MP Zubritsky, C Knott, K Ten Have, T Hadley, T Coyne, JC Oslin, DW AF Chopra, MP Zubritsky, C Knott, K Ten Have, T Hadley, T Coyne, JC Oslin, DW TI Importance of subsyndromal symptoms of depression in elderly patients SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PRIMARY-CARE PATIENTS; MINOR DEPRESSION; LATE-LIFE; FUNCTIONAL DISABILITY; SERVICE UTILIZATION; OLDER-ADULTS; FOLLOW-UP; PREVALENCE; DISORDERS; COMMUNITY AB Objective: There is a debate about the importance of subsyndromal symptoms of depression (SSD). The current study examined the cross-sectional and longitudinal significance of SSD in geriatric subjects both with and without a past history of major depression. Methods: Elderly primary-care subjects with SSD, both with ( SSD +; N = 54) and without ( SSD -; N = 204) a history of major depression, were compared with subjects with major depression (MDD; N = 111), minor depression ( MinD; N = 74), and symptom-free comparison subjects ( N = 59). Assessment domains included physical and psychological disability, health-care utilization, hopelessness, death and suicidal ideation, and a diagnostic evaluation at a 3-month follow-up. Results: Both subjects with SSD + and SSD - differed from the symptom-free comparison subjects on measures of psychological disability, hopelessness, and death ideation, with SSD + subjects being more severely psychologically disabled than SSD - subjects. There were few differences between SSD + and MinD subjects or those with MDD, except on measures of psychological disability. Finally, more than 24% of SSD + subjects progressed to meet criteria of MDD, MinD, or dysthymia over a 3-month period. Utilization of outpatient services did not differ among any of the depression groups or comparison subjects. Conclusions: SSD (with or without a past history of MDD) is associated with significant disability. Moreover, the risk of developing a diagnosis of MDD, MinD, or dysthymia is substantially elevated in subjects with a past history of MDD. C1 Univ Penn, Hlth Syst, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Ctr Mental Hlth Care Policy & Serv Res, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA 19104 USA. RP Oslin, DW (reprint author), Univ Penn, Hlth Syst, Dept Psychiat, Sect Geriatr Psychiat, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu RI Chopra, Mohit P/F-7250-2013 OI Chopra, Mohit P/0000-0002-9208-7224 FU CMHS SAMHSA HHS [1UD1SM53033]; NIMH NIH HHS [1K08MH01599, 5P30MH52129] NR 43 TC 52 Z9 52 U1 3 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2005 VL 13 IS 7 BP 597 EP 606 DI 10.1176/appi.ajgp.13.7.597 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 944KO UT WOS:000230427100008 PM 16009736 ER PT J AU Charytan, C Coburn, JW Chonchol, M Herman, J Lien, YH Liu, W Klassen, PS McCary, LC Pichette, V AF Charytan, C Coburn, JW Chonchol, M Herman, J Lien, YH Liu, W Klassen, PS McCary, LC Pichette, V TI Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE calcimimetic; chronic kidney disease (CKD); hyperparathyroidism; predialysis ID CHRONIC-RENAL-FAILURE; REDUCES PARATHYROID-HORMONE; CHRONIC KIDNEY-DISEASE; BONE-DISEASE; CALCIMIMETIC COMPOUND; HEMODIALYSIS-PATIENTS; CALCIUM RECEPTOR; MORTALITY RISK; INSUFFICIENCY; PHOSPHORUS AB Background. Secondary hyperparathyroidism develops early in patients with chronic kidney disease (CKD). Clinical guidelines from the National Kidney Foundation-Kidney/Disease Outcomes Quality Initiative emphasize the need to control parathyroid hormone (PTH), calcium, and phosphorus levels in patients with CKD not receiving dialysis to reduce poor outcomes. This phase 2 study evaluated the effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD not on dialysis therapy. Methods: A randomized, double-blind, placebo-controlled, 18-week study enrolled adults with an estimated glomerular filtration rate of 15 to 50 mL/min/1.73 m(2) (0.25 to 0.83 mL/s/1.73 m(2)) and an intact PTH (iPTH) level greater than 130 pg/mL (ng/L). Cinacalcet (or placebo) was titrated from 30 to 180 mg once daily to obtain a 30% or greater reduction in iPTH levels from baseline. Results: Baseline mean iPTH levels were 243 pg/mL (ng/L) in the cinacalcet group (n = 27) and 236 pg/mL (ng/L) in the control group (n = 27). At baseline, 28% of subjects were being administered vitamin D sterols and 43% were being administered phosphate binders or calcium supplements. The addition of cinacalcet significantly decreased iPTH concentrations compared with controls during the efficacy-assessment phase: 56% versus 19% of subjects achieved a 30% or greater reduction in iPTH levels (P = 0.006), and mean iPTH levels decreased by 32% in the cinacalcet group, but increased by 6% in the control group (P < 0.001). Mean serum calcium and phosphorus levels remained within normal range throughout the study. Cinacalcet generally was well tolerated; the most frequent adverse events were gastrointestinal. Conclusion: This preliminary study provides evidence that cinacalcet is efficacious for the treatment of secondary hyperparathyroidism in subjects with CKD not receiving dialysis. (c) 2005 by the National Kidney Foundation, Inc. C1 New York Hosp, Queens Med Ctr, Flushing, NY 11355 USA. Vet Affairs Greater Los Angeles Hlth Care Serv, Los Angeles, CA USA. Univ Colorado, Denver, CO 80202 USA. Palmetto Internal Med, Columbia, SC USA. Univ Arizona, Tucson, AZ USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. RP Charytan, C (reprint author), New York Hosp, Queens Med Ctr, 56-45 Main St, Flushing, NY 11355 USA. EM charytan@pol.net NR 38 TC 74 Z9 77 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2005 VL 46 IS 1 BP 58 EP 67 DI 10.1053/j.ajkd.2005.04.013 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 947CY UT WOS:000230622000008 PM 15983958 ER PT J AU Humphreys, BD Forman, JP Zandi-Nejad, K Bazari, H Seifter, J Magee, CC AF Humphreys, BD Forman, JP Zandi-Nejad, K Bazari, H Seifter, J Magee, CC TI Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (Pyroglutamic aciduria) acquired in hospital SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE metabolic acidosis; anion gap; 5-oxoprolinuria; pyroglutamic aciduria; glutathione; acetaminophen ID GLUTATHIONE SYNTHETASE DEFICIENCY; TRANSIENT 5-OXOPROLINURIA; N-ACETYLCYSTEINE; INBORN ERROR; MUTATIONS; ACIDEMIA; PATIENT; CYCLE AB A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy. The patient subsequently developed fever and neutropenia and was administered 20.8 g of acetaminophen during 10 days. During this time, anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental status developed. After usual causes of high anion gap acidosis were ruled out, a screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold greater than normal values. Predisposing factors in this case included renal dysfunction and sepsis. Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N-acetylcysteine could be beneficial. (c) 2005 by the National Kidney Foundation, Inc. C1 Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02114 USA. RP Humphreys, BD (reprint author), Harvard Univ, Inst Med, Rm 550,4 Blackfan Circle, Boston, MA 02115 USA. EM bhumphreys@partners.org FU NIDDK NIH HHS [F32 DK069037-01] NR 15 TC 31 Z9 31 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2005 VL 46 IS 1 BP 143 EP 146 DI 10.1053/j.ajkd.2005.04.010 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 947CY UT WOS:000230622000018 PM 15983968 ER PT J AU McFarland, LV Reiber, GE Norman, JE AF McFarland, LV Reiber, GE Norman, JE TI Recruitment of medicaid and dual-enrolled medicare beneficiaries with diabetes mellitus into a randomized controlled trial SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SELF-MANAGEMENT; PRIMARY-CARE; CLINICAL-TRIALS; INTERVENTIONS; EXPERIENCE; PROGRAM; DISPARITIES; ETHNICITY AB Objective: To document the recruitment of Medicaid and dual-enrolled Medicare beneficiaries with diabetes mellitus into a randomized clinical trial. Study Design: Randomized controlled trial with 1-year follow-up. Methods: A total of 2242 Medicaid or dual-enrolled Medicare beneficiaries with diabetes residing in King County, Washington, were recruited by direct mail for a clinical trial of diabetes self-care management. Washington State Medicaid program databases were used to identify the target population who received recruitment packets from the program director. Individuals who did not return a participation refusal letter were telephoned to determine study eligibility. Subjects were screened during a study visit, and written informed consent was obtained. Enrolled subjects were randomized to a self-care intervention group or a usual care group. Results: Of 2242 recruitment packets sent, we were unable to contact 40% of the target population, despite the fact that packets were sent to the same mailing addresses used for monthly Medicaid check distributions. The primary recruitment challenges were missing telephone contact information and a lack of interpreters speaking needed dialects. Of the 146 subjects enrolled, 71% were nonwhite, 28% were non-English speaking, 69% were women, and the mean age was 59.8 years. Conclusions: Research in Medicaid and Medicare populations is possible but requires additional time, energy, and resources. The finding that 40% of the Medicaid population could not be contacted suggests that Medicaid may want to revisit their contact information procedures to facilitate case management and other programs. C1 VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Washington State Dept Hlth, Diabet Prevent & Control Program, Olympia, WA USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@med.va.gov NR 24 TC 0 Z9 0 U1 1 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2005 VL 11 IS 7 BP 445 EP 450 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 945AO UT WOS:000230472900004 ER PT J AU Rosen, AK Gardner, J Montez, M Loveland, S Hendricks, A AF Rosen, AK Gardner, J Montez, M Loveland, S Hendricks, A TI Dual-system use: Are there implications for risk adjustment and quality assessment? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE quality assessment; risk adjustment; case-mix; dual eligibility/enrollment; veterans; health status ID OF-VETERANS-AFFAIRS; ACUTE MYOCARDIAL-INFARCTION; LONG-TERM-CARE; DIAGNOSTIC COST GROUPS; HEALTH-CARE; VA FACILITIES; MEDICARE; ENROLLEES; SERVICES; DISTANCE AB The authors examined the implications of dual-system use for risk adjustment and quality assessment. The sample (n = 34 151) included all veterans dually enrolled in the Veterans Health Administration (VA) and the private sector in 1998 with (1) an inpatient discharge from either a VA or Medicare setting for 1 of 6 conditions/procedures and (2) inpatient and/or outpatient use in both the VA and private sector. The authors used the Diagnostic Cost Groups risk-adjustment system to obtain concurrent and prospective health status (relative risk scores) using veterans' Medicare diagnoses only, VA diagnoses only, and diagnoses from both systems. Both concurrent and prospective relative risk scores increased when diagnoses from both systems were used; the population's disease profile also was affected. The authors conclude that it is important to capture the true disease burden of the population by obtaining diagnoses from all health care systems providing care to facilitate meaningful comparisons of performance. C1 Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston VA Healthcare Syst, Boston, MA USA. RP Rosen, AK (reprint author), Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM akrosen@bu.edu NR 50 TC 20 Z9 20 U1 8 U2 9 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JUL-AUG PY 2005 VL 20 IS 4 BP 182 EP 194 DI 10.1177/1062860605275791 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 947QF UT WOS:000230660400003 PM 16020675 ER PT J AU Segreti, J House, HR Siegel, RE AF Segreti, J House, HR Siegel, RE TI Principles of antibiotic treatment of community-acquired pneumonia in the outpatient setting SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE antibiotics; community-acquired pneumonia; fluoroquinolones; short-course therapy ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; OPEN-LABEL; ANTIMICROBIAL RESISTANCE; RANDOMIZED-TRIAL; THERAPY; LEVOFLOXACIN; ADULTS; MULTICENTER; EFFICACY; GATIFLOXACIN AB Community-acquired pneumonia (CAP) is a common illness with high rates of morbidity and mortality. Nearly 80% of the treatment for this condition is provided in the outpatient setting. Among the etiologic agents associated with bacterial CAP, the predominant pathogen is Streptococcus pneumoniae. Treatment of CAP for the most part is empirical; therefore, any antibiotic treatment should cover both typical and atypical pathogens. The beta-lactams have historically been considered standard therapy for the treatment of CAP. However, the impact of rising resistance rates is now a primary concern facing physicians. For patients with comorbidifies or recent antibiotic therapy, current guidelines recommend either combination therapy with a beta-lactam and a macrolide or an antipneumococcal fluoroquinolone alone. Fluoroquinolones are broad-spectrum antibiotics that exhibit high levels of penetration into the lungs and low levels of resistance. Evidence from clinical trials indicates clinical success rates of >90% for moxifloxacin, gatifloxacin, and levofloxacin in the treatment of CAP due to S pneumoniae. Data from comparative clinical trials suggest fluoroquinolone monotherapy is as efficacious as beta-lactam-macrolide combination therapy in the treatment of CAP patients. The respiratory fluoroquinolone levofloxacin has also been shown to be effective in CAP patients for the treatment of macrolide-resistant S pneumoniae. The use of azithromycin, telithromycin, and fluoroquinolones in short-course regimens has been shown to be efficacious, safe, and tolerable in patients with CAP. Based on clinical evidence, high-dose, short-course therapies may represent a significant advance in the management of CAP. (C) 2005 Elsevier Inc. All rights reserved. C1 Rush Univ, Rush Med Coll, Med Ctr, Dept Internal Med,Sect Infect Dis, Chicago, IL 60612 USA. Univ Iowa, Dept Emergency Med, Iowa City, IA USA. Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Crit Care Ctr, New York, NY USA. RP Segreti, J (reprint author), Rush Univ, Rush Med Coll, Med Ctr, Dept Internal Med,Sect Infect Dis, 600 S Paulina,Suite 143, Chicago, IL 60612 USA. EM john_segreti@rush.edu NR 51 TC 19 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2005 VL 118 SU 7A BP 21 EP 28 DI 10.1016/j.amjmed.2005.05.010 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 946JF UT WOS:000230567600004 ER PT J AU Rodriguez, A Alemparte, MR Pereira, CF Sampaolesi, A Bueno, RDL Vigo, F Obregon, A Palacios, IF AF Rodriguez, A Alemparte, MR Pereira, CF Sampaolesi, A Bueno, RDL Vigo, F Obregon, A Palacios, IF CA LASMAL Investigators TI Latin American randomized trial of balloon angioplasty vs coronary stenting for small vessels (LASMAL): Immediate and tong-term results SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE coronary stenting; PTCA; percutaneous coronary intervention ID ARTERY DISEASE; STRUT THICKNESS; RESTENOSIS; PLACEMENT; DIAMETER; REVASCULARIZATION; IMPLANTATION; OCCLUSION; LESIONS AB PURPOSE: To assess the potential role of coronary stent to improved acute success and reduce late restenosis in lesions with reference diameter < 2.9 turn using a bare metal stent specifically designed for small coronary vessels. There is controversy on the results among previous studies comparing bare metal stent implantation with conventional balloon percutaneous transluminal coronary angioplasty (PTCA). Differences in baseline characteristics, inclusion and exclusion criteria, and stent design may account for these discrepancies. METHODS: The population of this multicenter, multinational randomized study (LASMAL) consisted of 246 patients undergoing percutaneous coronary intervention of small vessel reference diameter. They were randomized into 2 strategies of percutancous revascularization: elective primary stent (n = 124) or conventional balloon PTCA with provisional stenting (n = 122) in the presence of acute, threatened closure or flow-limiting dissections. RESULTS: The clinical success rate was significantly better for the stent group (98.3% vs 91.8%; P = 0.038). At 30 days follow-up, requirements of target vessel revascularization (TVR) (6.6% vs 0.8%; P = 0.018) and incidence of major adverse cardiac and cerebrovascular events (MACCE) (9.8% vs 2.4%; P = 0.01) was significantly lower in the stent strategy. Postpercutaneous coronary intervention minimal luminal diameter (MLD) was significantly larger in the stent group (2.3 +/- 0.2 mm vs 2.2 +/- 0.2 mm; P = 0.003). At follow-up, MLD in the stent group was larger than with PTCA (1.7 +/- 0.7 mm vs 1.5 +/- 0.7 mm, respectively; P = 0.035). Net gain was also significantly better with stent strategy (1.1 +/- 0.7 turn vs 0.8 +/- 0.7 mm, respectively; P = 0.002). Stenting resulted in a significant lower angiographic binary restenosis (20% vs 31%; P = 0.02) than PTCA. Furthermore, patients treated with stent were more frequently free from MACCE at 9-month follow-up (death, acute myocardial infarction [AMI], stroke, repeat revascularization procedures) than those treated initially with PTCA (82.2% vs 72% of PTCA, P = 0.046). CONCLUSIONS: The use of a specifically designed bare metal coronary phosphoril choline-coated stent as primary device during percutaneous interventions in small coronary arteries was associated with high procedural success and low in-hospital and 30-day follow-up complications. At long-term follow-up, patients initially treated with stents had lower angiographic restenosis rate and were more frequently free from major adverse cardiac events. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. Otamendi Hosp, Buenos Aires, DF, Argentina. Inst Modelo Cardiol, Cordova, Argentina. Hosp Univ Evangel, Curitiba, Parana, Brazil. Ctr Invest Med Quirurg Havana, Havana, Cuba. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. EM palacios.igor@mgh.harvard.edu NR 29 TC 8 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2005 VL 118 IS 7 BP 743 EP 751 DI 10.1016/j.amjmed.2005.03.030 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 945AL UT WOS:000230472600012 PM 15989908 ER PT J AU Wolf, M Shah, A Lam, C Martinez, A Smirnakis, KV Epstein, FH Taylor, RN Ecker, JL Karumanchi, SA Thadhani, R AF Wolf, M Shah, A Lam, C Martinez, A Smirnakis, KV Epstein, FH Taylor, RN Ecker, JL Karumanchi, SA Thadhani, R TI Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preeclampsia; angiogenesis; nulliparity ID PLACENTAL GROWTH-FACTOR; RISK-FACTORS; HYPERTENSIVE DISORDERS; INSULIN-RESISTANCE; TYROSINE KINASE-1; PREECLAMPSIA; WOMEN; ANGIOGENESIS AB Preeclampsia is far more common in women's first pregnancy but the mechanism of this Preeclampsia association is unknown. Altered angiogenesis, marked by increased levels of circulating soluble Angiogenesis fins-like tyrosine kinase (sFlt-1), an inhibitor of placental growth factor (PIGF) and vascular Nulliparity endothelial growth factor, has been implicated in the pathogenesis of preeclampsia. We tested the hypothesis that nulliparous women demonstrate increased sFlt-1 levels compared with multiparous women, suggesting an overall increase in relative antiangiogenesis during first pregnancies. We measured sFlt-1 and PIGF levels in early pregnancy serum samples from the first 2 completed pregnancies of 97 women who participated in the MOMS cohort study. Repeated measures analyses demonstrated that sFlt-1 levels were significantly increased in first compared with second pregnancies (877 +/- 598 pg/mL vs 728 +/- 399 pg/mL; P =.01) but there was no significant difference in PlGF levels (45.3 +/- 40.7 pg/mL vs 40.1 +/- 31.9 pg/mL; P =.14). After adjusting for age, gestational age, blood pressure, body mass index, smoking, and the interpregnancy time interval, the residual decrease in sFlt-1 levels from the first to the second pregnancy remained significant at 107 pg/mL (P =.04). Significant interaction between ethnicity and pregnancy order on sFlt-1 levels was observed such that Hispanic women demonstrated greater sFlt-1 levels than white women during their first pregnancy but lower levels in their second pregnancies. Increased sFlt-I secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Additional studies are needed to verify these findings and to further examine ethnic differences in angiogenesis factors and their potential impact on the incidence of preeclampsia. (c) 2005 Mosby, Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Renal Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. RP Wolf, M (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Bartlett 911,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org NR 29 TC 73 Z9 76 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2005 VL 193 IS 1 BP 16 EP 22 DI 10.1016/j.ajog.2005.03.016 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 948BR UT WOS:000230691500005 PM 16021053 ER PT J AU Sandberg, MA Gaudio, AR Berson, EL AF Sandberg, MA Gaudio, AR Berson, EL TI Disease course of patients with pericentral retinitis pigmentosa SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID VISUAL-FIELD LOSS; RETINAL DEGENERATION; VITAMIN-A; RETINOPATHY; ULTRASTRUCTURE; DYSTROPHY; RATES; ROD AB PURPOSE: To estimate the mean rates of decline of ocular function in patients with an atypical form of retinitis pigmentosa, termed "pericentral retinitis pigmentosa." DESIGN: Retrospective observational study. METHODS: SETTING: Single,center. PATIENT POPULATION: Eighteen patients (ages 32 to 65 years) with pericentral retinitis pigmentosa followed for 3 to 26 years. OBSERVATIONAL PROCEDURES: Snellen visual acuity, Goldmann visual field area (V-4e white test light), and full,field electroretinogram (ERG) amplitudes (0.5 Hz and 30 Hz white flashes). MAIN OUTCOME MEASURES: Mean annual exponential rates of change quantified by repeated-measures longitudinal regression. RESULTS: Estimated mean annual rates of decline of remaining ocular function were 1.2% for visual acuity, 1.9% for visual field area, 2.5% for ERG amplitude to 0.5 Hz flashes, and 2.9% for ERG amplitude to 30 Hz flashes. CONCLUSIONS: The mean rates of loss of remaining ocular function of patients with pericentral retinitis pigmentosa were generally slower than those previously reported for patients with typical forms of retinitis pigmentosa. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM masandberg@aol.com NR 26 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2005 VL 140 IS 1 BP 100 EP 106 DI 10.1016/j.ajo.2005.02.038 PG 7 WC Ophthalmology SC Ophthalmology GA 949IN UT WOS:000230778700015 PM 15953579 ER PT J AU Matsumoto, N Jo, OD Shih, RNJ Brochmann, EJ Murray, SS Hong, V Yanagawa, J Yanagawa, N AF Matsumoto, N Jo, OD Shih, RNJ Brochmann, EJ Murray, SS Hong, V Yanagawa, J Yanagawa, N TI Increased cathepsin D release by Hyp mouse osteoblast cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hypophosphatemia; rickets; bone; pepstatin ID MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; ABNORMAL PHEX EXPRESSION; DEFECTIVE BONE-FORMATION; X-LINKED RICKETS; PROCATHEPSIN-D; PARATHYROID-HORMONE; CANCER CELLS; NORMAL MICE; MEPE; MINERALIZATION AB The X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, is caused by loss-of-function mutations of PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) leading to rachitic bone disease and hypophosphatemia. Available evidence today indicates that the bone defect in XLH is caused not only by hypophosphatemia and altered vitamin D metabolism but also by factor(s) locally released by osteoblast cells (ObCs). The identity of these ObC-derived pathogenic factors remains unclear. In our present study, we report our finding of a prominent protein in the culture media derived from ObC of the hypophosphatemic (Hyp) mice, a murine homolog of human XLH, which was identified as the murine procathepsin D ( Cat D). By metabolic labeling studies, we further confirmed that Hyp mouse ObCs released greater amount of Cat D into culture media. This increased Cat D release by Hyp mouse ObCs was unlikely to be due to nonspecific cell damage or heterogeneous cell population and was found to be associated with an increased Cat D expression at the protein level, possibly due to a reduced Cat D degradation. However, we were not able to detect a direct effect of PHEX protein on Cat D cleavage. In support of the involvement of Cat D in mediating the inhibitory effect of Hyp mouse ObC-conditioned media on ObC calcification, we found that exposure to Cat D inhibited ObC Ca-45 incorporation and that inhibition of Cat D abolished the inhibitory effect of Hyp mouse-conditioned media on ObC calcification. In conclusion, results from our present study showed that Hyp mouse ObCs release a greater amount of Cat D, which may contribute to the inhibitory effect of Hyp mouse ObC-conditioned media on ObC mineralization. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Med Serv, Sepulveda, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Res Serv, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Yanagawa, N (reprint author), Vet Adm Med Ctr, 111R,16111 Plummer St, Sepulveda, CA 91343 USA. EM nori@ucla.edu FU NIDDK NIH HHS [DK-AR58886] NR 42 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2005 VL 289 IS 1 BP E123 EP E132 DI 10.1152/ajpendo.00562.2004 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 939ZR UT WOS:000230113600018 PM 15958652 ER PT J AU Bradesi, S Schwetz, I Ennes, HS Lamy, CMR Ohning, G Fanselow, M Pothoulakis, C McRoberts, JA Mayer, EA AF Bradesi, S Schwetz, I Ennes, HS Lamy, CMR Ohning, G Fanselow, M Pothoulakis, C McRoberts, JA Mayer, EA TI Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE chronic psychological stress; visceral nociception ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; MAST-CELLS; GASTROINTESTINAL-TRACT; EXPERIMENTAL COLITIS; COLON IRRITATION; FOS EXPRESSION; LEWIS RATS; ADULT RATS; HYPERSENSITIVITY AB Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA ( but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1 beta and IFN-gamma. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Ulcer Res & Educ, Ctr Neurovisceral Sci & Womens Hlth,Brain Res Ins, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Ulcer Res & Educ, Digest Dis Res Ctr,David Geffen Sch Med, Los Angeles, CA 90073 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastroenterol Neuropeptide Ctr, Boston, MA 02115 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Ulcer Res & Educ, Ctr Neurovisceral Sci & Womens Hlth,Brain Res Ins, Bldg 115 Rm 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM emayer@ucla.edu RI Lamy, Christophe/B-6432-2016 OI Lamy, Christophe/0000-0001-6944-9787 FU NIDDK NIH HHS [R21-DK-066065, P50-DK-64539] NR 52 TC 123 Z9 133 U1 1 U2 10 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 JUL PY 2005 VL 289 IS 1 BP G42 EP G53 DI 10.1152/ajpgi.00500.2004 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 936GJ UT WOS:000229843200007 PM 15746211 ER PT J AU Kokkotou, E Jeon, JY Wang, XM Marino, FE Carlson, M Trombly, DJ Maratos-Flier, E AF Kokkotou, E Jeon, JY Wang, XM Marino, FE Carlson, M Trombly, DJ Maratos-Flier, E TI Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE melanin-concentrating hormone; obesity; hypothalamus; diet-induced obesity; 129; C57Bl/6; strains; locomotor activity; energy expenditure ID MELANIN-CONCENTRATING HORMONE; RECEPTOR-DEFICIENT MICE; FOOD-INTAKE; OB/OB MICE; MELANOCORTIN-4 RECEPTOR; INSULIN-RESISTANCE; BODY-COMPOSITION; LEPTIN; C57BL/6J; MOUSE AB Genetics and environment contribute to the development of obesity, in both humans and rodents. However, the potential interaction between genes important in energy balance, strain background, and dietary environment has been only minimally explored. We investigated the effects of genetic ablation of melanin-concentrating hormone (MCH), a neuropeptide with a key role in energy balance, with chow and a high-fat diet (HFD) in two different mouse strains, one obesity-prone (C57BL/6) and the other obesity-resistant (129). Substantial differences were seen in wild-type (WT) animals of different strains. 129 animals had significantly lower levels of spontaneous locomotor activity than C57BL/6; however, 129 mice gained less weight on both chow and HFD. In both strains, deletion of MCH led to attenuated weight gain compared with WT counterparts, an effect secondary to increased energy expenditure. In both strains, feeding a HFD led to further increases in energy expenditure in both WT and MCH-KO mice; however, this increase was more pronounced in 129 mice. In addition, mice lacking MCH have a phenotype of increased locomotor activity, an effect also seen in both strains. The relative increase in activity in MCH-/- mice is modest in animals fed chow but increases substantially when animals are placed on HFD. These studies reinforce the important role of MCH in energy homeostasis and indicate that MCH is a plausible target for antiobesity therapy. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Marino, FE (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM emaratos@bidmc.harvard.edu FU NIDDK NIH HHS [DK-36836-16, DK-56113, DK-53978] NR 38 TC 90 Z9 91 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 2005 VL 289 IS 1 BP R117 EP R124 DI 10.1152/ajpregu.00861.2004 PG 8 WC Physiology SC Physiology GA 935PI UT WOS:000229793800017 PM 15731402 ER PT J AU Breusegem, SY Halaihel, N Inoue, M Zajicek, H Lederer, E Barry, NP Sorribas, V Levi, M AF Breusegem, SY Halaihel, N Inoue, M Zajicek, H Lederer, E Barry, NP Sorribas, V Levi, M TI Acute and chronic changes in cholesterol modulate Na-P-i cotransport activity in OK cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE two-photon fluorescence microscopy; filipin; lipid microdomains; laurdan; opossum kidney cells ID RENAL PHOSPHATE-TRANSPORT; LIPID RAFTS; BRUSH-BORDER; GENERALIZED POLARIZATION; PLASMA-MEMBRANE; MODEL MEMBRANES; RAT; PROTEINS; RECEPTOR; EXPRESSION AB Acute and chronic changes in cholesterol modulate Na-P-i cotransport activity in OK cells. Am J Physiol Renal Physiol 289: F154 - F165, 2005. First published March 15, 2005; doi: 10.1152/ ajprenal. 00331.2004. - We previously showed an inverse correlation between membrane cholesterol content and Na-P-i cotransport activity during the aging process and adaptation to alterations in dietary P-i in the rat (Levi M, Jameson DM, and van der Meer BW. Am J Physiol Renal Fluid Electrolyte Physiol 256: F85 - F94, 1989). The purpose of the present study was to determine whether alterations in cholesterol content per se modulate Na-P-i cotransport activity and apical membrane Na-P-i protein expression in opossum kidney (OK) cells. Acute cholesterol depletion achieved with beta-methyl cyclodextrin (beta-MCD) resulted in a significant increase in Na-P-i cotransport activity accompanied by a moderate increase in apical membrane Na-P-i protein abundance and no alteration of total cellular Na-P-i protein abundance. Conversely, acute cholesterol enrichment achieved with beta-MCD/cholesterol resulted in a significant decrease in Na-P-i cotransport activity with a moderate decrease in apical membrane Na-P-i protein abundance and no change of the total cellular Na-P-i protein abundance. In contrast, chronic cholesterol depletion, achieved by growing cells in lipoprotein-deficient serum (LPDS), resulted in parallel and significant increases in Na-P-i cotransport activity and apical membrane and total cellular Na-P-i protein abundance. Cholesterol depletion also resulted in a significant increase in membrane lipid fluidity and alterations in lipid microdomains as determined by laurdan fluorescence spectroscopy and imaging. Chronic cholesterol enrichment, achieved by growing cells in LPDS followed by loading with low-density lipoprotein, resulted in parallel and significant decreases in Na-P-i cotransport activity and apical membrane and total cellular Na-P-i protein abundance. Our results indicate that in OK cells acute and chronic alterations in cholesterol content per se modulate Na-P-i cotransport activity by diverse mechanisms that also include significant interactions of Na-P-i protein with lipid microdomains. C1 Univ Colorado, Ctr Hlth Sci, Dept Physiol & Biophys, Denver, CO 80262 USA. Univ Colorado, Ctr Hlth Sci, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX USA. Univ Louisville, Dept Internal Med, Louisville, KY USA. Univ Zaragoza, Dept Toxicol, Zaragoza, Spain. RP Levi, M (reprint author), Univ Colorado, Ctr Hlth Sci, Dept Physiol & Biophys, 4200 E 9th Ave, Denver, CO 80262 USA. EM Moshe.Levi@UCHSC.edu RI Halaihel , Nabil/J-2973-2016; OI Levi, Moshe/0000-0002-6225-946X; Sorribas, Victor/0000-0003-3457-323X FU NCRR NIH HHS [RR-03155]; NIA NIH HHS [7R03-AG-20361-2]; NIDDK NIH HHS [K08 DK-62220-01, 1 F32 DK-09689-01, 5R01-DK-062209-02, R01-DK-066029] NR 61 TC 15 Z9 15 U1 0 U2 2 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 JUL PY 2005 VL 289 IS 1 BP F154 EP F165 DI 10.1152/ajprenal.00331.2004 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 934XC UT WOS:000229741900017 PM 15769937 ER PT J AU Mahimainathan, L Ghosh-Choudhury, N Venkatesan, BA Danda, RS Choudhury, GG AF Mahimainathan, L Ghosh-Choudhury, N Venkatesan, BA Danda, RS Choudhury, GG TI EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27(Kip1) SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE epidermal growth factor; signal transduction; DNA synthesis ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; DNA-SYNTHESIS; PHOSPHOINOSITIDE 3-KINASE; GENE-TRANSCRIPTION; INHIBITOR P27(KIP1); SIGNALING PATHWAY; INTERFERON-GAMMA; PDGF AB Mahimainathan, Lenin, Nandini Ghosh-Choudhury, Balachandar A. Venkatesan, Ratna S. Danda, and Goutam Ghosh Choudhury. EGF stimulates mesangial cell mitogenesis via PI 3 kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27(Kip1). Am J Physiol Renal Physiol 289: F72-F82, 2005. First published February 8, 2005; doi: 10.1152/ ajprenal.00277.2004. - Epidermal growth factor ( EGF) is a potent mitogen for mesangial cells. The mechanism by which EGF induces DNA synthesis is not precisely understood. We investigated the role of phosphatidylinositol (PI)3-kinase in regulating mitogenesis. EGF increased PI3-kinase activity resulting in stimulation of PDK-1 and Akt kinase activities. Blocking of PI3-kinase activity using LY-294002 or adenoviral expression of PTEN, which dephosphorylates PI3,4,5-tris-phosphate and thus inactivates PI3-kinase signaling, significantly inhibits EGF-induced DNA synthesis. Expression of dominant-negative Akt kinase, however, had no effect on DNA synthesis. But it inhibited EGF-induced phosphorylation of FoxO3a transcription factor, thus demonstrating its functional consequences. These data indicate that EGF increases the DNA synthesis in a PI3-kinase-dependent but Akt-independent manner. In addition to activating PI3-kinase signaling, EGF increased Erk1/2 MAPK activity, leading to transcriptional activation of its nuclear target Elk-1 and resulting in c-fos expression. Inhibition of MAPK activity by MEK inhibitor U-0126 abolished EGF-induced DNA synthesis. Because EGF activates PI3-kinase, which also regulates DNA synthesis, the effect of PI3-kinase on MAPK activity was also examined. Inhibition of PI3- kinase signaling blocked EGF- induced MAPK activity as well as Elk-1-dependent reporter transcription and c-fos gene transcription. To further determine the mechanism of EGF- induced DNA synthesis, we investigated the effect of EGF on the cyclin-dependent kinase inhibitor p27(Kip1). EFG reduced the expression of p27(Kip1). Inhibition of PI3- kinase action or MAPK activity abolished the reduction in p27(Kip1) expression induced by EGF. These data provide the evidence that a linear signal transduction pathway involving PI3-kinase-dependent MAPK regulates EGF-induced DNA synthesis in mesangial cells by regulating c-fos and p27(Kip1) expression. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU NIDDK NIH HHS [R01-DK-55815, P50-DK-061597] NR 54 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2005 VL 289 IS 1 BP F72 EP F82 DI 10.1152/ajprenal.00277.2004 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 934XC UT WOS:000229741900008 PM 15701816 ER PT J AU Gorton, GE AF Gorton, GE TI Milton Hyland Erickson, 1901-1980 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Biographical-Item C1 Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA 19140 USA. RP Gorton, GE (reprint author), Philadelphia VA Med Ctr, Dept Psychiat, Mailstop 116,Univ & Woodland Ave, Philadelphia, PA 19140 USA. EM gregg.gorton@med.va.gov NR 0 TC 1 Z9 1 U1 1 U2 2 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 JUL PY 2005 VL 162 IS 7 BP 1255 EP 1255 DI 10.1176/appi.ajp.162.7.1255 PG 1 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500005 ER PT J AU Frazier, JA Chiu, SF Breeze, JL Makris, N Lange, N Kennedy, DN Herbert, MR Bent, EK Koneru, VK Dieterich, ME Hodge, SM Rauch, SL Grant, PE Cohen, BM Seidman, LJ Caviness, VS Biederman, J AF Frazier, JA Chiu, SF Breeze, JL Makris, N Lange, N Kennedy, DN Herbert, MR Bent, EK Koneru, VK Dieterich, ME Hodge, SM Rauch, SL Grant, PE Cohen, BM Seidman, LJ Caviness, VS Biederman, J TI Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ADULT HUMAN BRAIN; MOOD DISORDERS; MORPHOMETRIC-ANALYSIS; 1ST-DEGREE RELATIVES; ADOLESCENT PATIENTS; HIPPOCAMPAL VOLUME; EMOTION PERCEPTION; SEXUAL-DIMORPHISM; MAJOR DEPRESSION; HUMAN NEOCORTEX AB Background: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. Method: Forty-three youths 6 - 16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. Results: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. Conclusions: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder. 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 Hosp, Child Psychiat Outpatient Clin, Brain Imaging Ctr,Stat Neuroimaging Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Dev Neurosci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Dev Neurosci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Dev Neurosci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Dev Neurosci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Dev Neurosci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. RP Frazier, JA (reprint author), Cambridge Hlth Alliance, Myst Ctr, 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 [K08 MH 01573-01, K08 MH001573]; NINDS NIH HHS [NS 37483] NR 58 TC 171 Z9 175 U1 2 U2 9 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 JUL PY 2005 VL 162 IS 7 BP 1256 EP 1265 DI 10.1176/appi.ajp.162.7.1256 PG 10 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500006 PM 15994707 ER PT J AU Tohen, M Greil, W Calabrese, JR Sachs, GS Yatham, LN Oerlinghausen, BM Koukopoulos, A Cassano, GB Grunze, H Licht, RW Dell'Osso, L Evans, AR Risser, R Baker, RW Crane, H Dossenbach, MR Bowden, CL AF Tohen, M Greil, W Calabrese, JR Sachs, GS Yatham, LN Oerlinghausen, BM Koukopoulos, A Cassano, GB Grunze, H Licht, RW Dell'Osso, L Evans, AR Risser, R Baker, RW Crane, H Dossenbach, MR Bowden, CL TI Olanzapine versus lithium in the maintenance treatment of bipolar disorder: A 12-month, randomized, double-blind, controlled clinical trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th International Conference on Bipolar Disorder CY JUN 12-14, 2003 CL Pittsburgh, PA ID CONTROLLED 18-MONTH TRIAL; ACUTE MANIA; I DISORDER; PROPHYLACTIC EFFICACY; PLACEBO; DIVALPROEX; LAMOTRIGINE; RECURRENCE; ILLNESS AB Objective: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/ recurrence. Method: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score >= 20 entered the study and received open-label cotreatment with olanzapine and lithium for 6 - 12 weeks. Those meeting symptomatic remission criteria ( Young Mania Rating Scale score <= 12; 21-item Hamilton depression scale score = 8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5 - 20 mg/ day (N = 217), or lithium (target blood level: 0.6-1.2 meq/liter) (N = 214). Results: Symptomatic relapse/ recurrence ( score = 15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium ( primary objective) in preventing relapse/ recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/ recurrence. Depression relapse/ recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label cotreatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg). Conclusions: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/ recurrence in patients acutely stabilized with olanzapine and lithium cotreatment. Both agents were comparable in preventing depression relapse/ recurrence. C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. Univ Pisa, Dept Psychiat, Pisa, Italy. Aarhus Univ Hosp, Mood Disorders Res Unit, DK-8000 Aarhus, Denmark. Lilly Area Med Ctr, Vienna, Austria. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78285 USA. RP Tohen, M (reprint author), Lilly Res Labs, Indianapolis, IN 46285 USA. EM m.tohen@lilly.com NR 22 TC 198 Z9 203 U1 1 U2 8 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 JUL PY 2005 VL 162 IS 7 BP 1281 EP 1290 DI 10.1176/appi.ajp.162.7.1281 PG 10 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500009 PM 15994710 ER PT J AU Saxe, GN Stoddard, F Hall, E Chawla, N Lopez, C Sheridan, R King, D King, L Yehuda, R AF Saxe, GN Stoddard, F Hall, E Chawla, N Lopez, C Sheridan, R King, D King, L Yehuda, R TI Pathways to PTSD, part I: Children with burns SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV 07-10, 2002 CL Baltimore, MD SP Int Soc Traumat Stress Studies ID ACUTE STRESS DISORDER; HEART-RATE-VARIABILITY; POSTTRAUMATIC-STRESS; PREDICTORS; TRAUMA; INJURY; HOSPITALIZATION; DISSOCIATION; SURVIVORS; SYMPTOMS AB Objective: The goal of this study was to develop a model of risk factors for post-traumatic stress disorder (PTSD) in a group of acutely burned children. Method: Seventy-two children between the ages of 7 and 17 who were admitted to the hospital for an acute burn were eligible for study. Members of families who consented completed the Child PTSD Reaction Index, the Multidimensional Anxiety Scale for Children, and other self-report measures of psychopathology and environmental stress both during the hospitalization and 3 months following the burn. A path analytic strategy was used to build a model of risk factors for PTSD. Results: Two pathways to PTSD were discerned: 1) from the size of the burn and level of pain following the burn to the child's level of acute separation anxiety, and then to PTSD, and 2) from the size of the burn to the child's level of acute dissociation following the burn, and then to PTSD. Together these pathways accounted for almost 60% of the variance in PTSD symptoms and constituted a model with excellent fit indices. Conclusions: These findings support a model of complex etiology for childhood PTSD in which two independent pathways may be mediated by different biobehavioral systems. C1 Boston Univ, Sch Med, Dept Child & Adolescent Psychiat, Boston, MA 02118 USA. Shriners Burns Hosp, Dept Psychiat, Boston, MA USA. Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. RP Saxe, GN (reprint author), Boston Univ, Sch Med, Dept Child & Adolescent Psychiat, Dowling 1 N,1 Boston Med Ctr Pl, Boston, MA 02118 USA. EM glenn.saxe@bmc.org OI Saxe, Glenn/0000-0002-4756-1169 FU CMHS SAMHSA HHS [U79 SM 54305]; NIMH NIH HHS [R01 MH 57370] NR 45 TC 71 Z9 72 U1 0 U2 4 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 JUL PY 2005 VL 162 IS 7 BP 1299 EP 1304 PG 6 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500011 PM 15994712 ER PT J AU McFall, M Saxon, AJ Thompson, CE Yoshimoto, D Malte, C Straits-Troster, K Kanter, E Zhou, XHA Dougherty, CM Steele, B AF McFall, M Saxon, AJ Thompson, CE Yoshimoto, D Malte, C Straits-Troster, K Kanter, E Zhou, XHA Dougherty, CM Steele, B TI Improving the rates of quitting smoking for veterans with posttraumatic stress disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY DEC 04-09, 2001 CL NEW ORLEANS, LA SP Int Soc Traumat Stress Studies ID VIETNAM COMBAT VETERANS; MAJOR DEPRESSION; CESSATION INTERVENTIONS; DEPENDENCE TREATMENT; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; MENTAL-DISORDERS; RANDOMIZED TRIAL; UNITED-STATES; SMOKERS AB Objective: Smoking is highly prevalent and refractory among people with post-traumatic stress disorder ( PTSD). This study aimed to improve the rate of quitting smoking for veterans with PTSD by integrating treatment for nicotine dependence into mental health care. Method: Smokers undergoing treatment for PTSD (N = 66) were randomly assigned to 1) tobacco use treatment delivered by mental health providers and integrated with psychiatric care ( integrated care) versus 2) cessation treatment delivered separately from PTSD care by smoking-cessation specialists ( usual standard of care). Seven-day point prevalence abstinence was the primary outcome, measured at 2, 4, 6, and 9 months after random assignment. Data were analyzed by using a generalized estimating equations approach following the intent-to-treat principle. Results: Subjects assigned to integrated care were five times more likely than subjects undergoing the usual standard of care to abstain from smoking across follow-up assessment intervals (odds ratio = 5.23). Subjects in the integrated care condition were significantly more likely than subjects in usual standard of care to receive transdermal nicotine and nicotine gum. They also received a greater number of smoking-cessation counseling sessions. Stopping smoking was not associated with worsening symptoms of PTSD or depression. Conclusions: Smoking-cessation interventions can be safely incorporated into routine mental health care for PTSD and are more effective than treatment delivered separately by a specialized smoking-cessation clinic. Integrating cessation treatment into psychiatric care may have the potential for improving smoking quit rates in other populations of chronically mentally ill smokers. C1 Dept Vet Affairs, NW Network Mental Illness Res Educ & Clin Ctr, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. Dept Vet Affairs, Biostat Unit, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. RP McFall, M (reprint author), VA Puget Sound Hlth Care Syst, PTSD Programs, S-116 MHC,1660 S Columbian Way, Seattle, WA 98108 USA. EM miles.mcfall@med.va.gov NR 72 TC 76 Z9 77 U1 1 U2 3 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 JUL PY 2005 VL 162 IS 7 BP 1311 EP 1319 DI 10.1176/appi.ajp.162.7.1311 PG 9 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500013 PM 15994714 ER PT J AU Emmons, KM Stoddard, AM Fletcher, R Gutheil, C Suarez, EG Lobb, R Weeks, J Bigby, JA AF Emmons, KM Stoddard, AM Fletcher, R Gutheil, C Suarez, EG Lobb, R Weeks, J Bigby, JA TI Cancer prevention among working class, multiethnic adults: Results of the healthy directions - Health centers study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NUTRITION EXAMINATION SURVEY; CHRONIC DISEASE PREVENTION; 3RD NATIONAL-HEALTH; PHYSICAL-ACTIVITY; DIETARY INTERVENTION; VEGETABLE CONSUMPTION; RANDOMIZED-TRIAL; EATING PATTERNS; SOCIAL-CLASS; US ADULTS AB Objectives. We analyzed outcomes from a study that examined social-contextual factors in cancer prevention interventions for working class, multiethnic populations. Methods. Ten community health centers were randomized to intervention or to control. Patients who resided in low-income, multiethnic neighborhoods were eligible; the intervention targeted fruit and vegetable consumption, red meat consumption, multivitamin intake, and physical activity. Outcomes were measured at 8 months. Results. The intervention led to significant increases in fruit and vegetable consumption and multivitamin intake and reductions in red meat consumption; no change was found in physical activity levels. The intervention effect was not changed when contextual variables that may function as confounders or effect modifiers (e.g., gender, education, race/ethnicity, respondent and parents' country of birth, and poverty status) were included in the analyses. Conclusions. The intervention led to significant improvements in health behaviors among a working class, multiethnic population, regardless of race/ ethnicity and socioeconomic status. Interventions that respond to the social context of working class individuals across racial/ethnic categories hold promise for improving cancer-related risk behaviors. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. EM karen_m_emmons@dfci.harvard.edu OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [5 P01 CA75308, P01 CA075308] NR 42 TC 46 Z9 47 U1 4 U2 5 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 JUL PY 2005 VL 95 IS 7 BP 1200 EP 1205 DI 10.2105/AJPH.2004.038695 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 940EN UT WOS:000230126600031 PM 15933240 ER PT J AU Bai, KJ Spicer, AP Mascarenhas, MM Yu, LY Ochoa, CD Garg, HG Quinn, DA AF Bai, KJ Spicer, AP Mascarenhas, MM Yu, LY Ochoa, CD Garg, HG Quinn, DA TI The role of hyaluronan synthase 3 in ventilator-induced lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hyaluronic acid; knockout mice; mechanical ventilation; tidal volume ID RESPIRATORY-DISTRESS-SYNDROME; FACTOR-KAPPA-B; MECHANICAL STRAIN; MURINE MACROPHAGES; RNA EXPRESSION; CELLS; ACTIVATION; FRAGMENTS; ACID; KINASE AB We recently found that low-molecular-weight hyaluronan was induced by cyclic stretch in lung fibroblasts and accumulated in lungs from animals with ventilator-induced lung injury. The low-molecular weight hyaluronan produced by stretch increased interleukin-8 production in epithelial cells, and was accompanied by an upregulation of hyaluronan synthase-3 mRNA. We hypothesized that low molecular-weight hyaluronan induced by high V-T was dependent on hyaluronan synthase 3, and was associated with ventilator-induced lung injury. Effects of high VT ventilation in C57BL/6 wild-type and hyaluronan synthase-3 knockout mice were compared. Significantly increased neutrophil infiltration, macrophage inflammatory protein-2 production, and lung microvascular leak were found in wild-type animals ventilated with high VT. These reactions were significantly reduced in hyaluronan synthase-3 knockout mice, except the capillary leak. Wild-type mice ventilated with high VT were found to have increased low-molecular-weight hyaluronan in lung tissues and concomitant increased expression of hyaluronan synthase-3 mRNA, neither of which was found in hyaluronan synthase-3 knockout mice. We conclude that high VT induced low molecular-weight hyaluronan production is dependent on de novo synthesis through hyaluronan synthase 3, and plays a role in the inflammatory response of ventilator-induced lung injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. Taipei Med Univ, Wan Fang Hosp, Dept Med, Div Pulm & Crit Care Med, Taipei, Taiwan. Texas A&M Univ, Syst Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX USA. RP Quinn, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM dquinn1@partners.org FU NHLBI NIH HHS [2T32 HL 07874, HL 03920] NR 43 TC 61 Z9 67 U1 1 U2 2 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 JUL 1 PY 2005 VL 172 IS 1 BP 92 EP 98 DI 10.1164/rccm.200405-6520C PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 939WD UT WOS:000230102400015 PM 15790861 ER PT J AU Holbrook, EH Brown, CL Lyden, ER Leopold, DA AF Holbrook, EH Brown, CL Lyden, ER Leopold, DA TI Lack of significant correlation between rhinosinusitis symptoms and specific regions of sinus computer tomography scans SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT 49th Annual Fall Meeting of the American-Rhinologic-Society CY SEP 20, 2003 CL Orlando, FL SP Amer Rhinol Soc ID PATIENT SYMPTOMS; FACIAL-PAIN; CT; EOSINOPHILIA; ENDOSCOPY; SEVERITY; VALIDITY AB Background: The sinonasal computer tomography (CT) scan is frequently used to help confirm the diagnosis of rhinosinusitis. However, little data exist correlating patient symptoms with CT findings. Methods: Immediately preceding CT of the sinuses, 94 subjects without evidence of trauma, nasal tumors, or previous sinus surgery completed the Rhinosinusitis Outcome Measure 31 symptom questionnaire and were asked to locate areas of facial pain or pressure. CT scans were graded according to the Lund-MacKay system, and agger nasi and ethmoid bulla cells were measured. Data from CT scans and symptom/pain questionnaire responses were analyzed for significant correlations. Results: No correlation was identified when comparing total Lund-MacKay scores, opacification of individual sinuses, and size of the agger nasi and ethmoid bulla cells with the Rhino-sinusitis Outcome Measure 31 subset scores and areas of facial pain or pressure. Conclusion: The sinus CT scan is a necessary tool for preoperative planning; however, it should not be used to predict symptoms or to localize areas responsible for facial pain or pressure. C1 Univ Nebraska, Med Ctr, Dept Otolaryngol Head & Neck Surg, Omaha, NE 68182 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68182 USA. Royal Victorian Eye & Ear Hosp, Dept Otolaryngol Head & Neck Surg, Melbourne, Vic 3002, Australia. RP Holbrook, EH (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 28 Z9 31 U1 0 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD JUL-AUG PY 2005 VL 19 IS 4 BP 382 EP 387 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 961RR UT WOS:000231680000011 PM 16171173 ER PT J AU Muradin, GSR Bosch, JL Verstijnen, ACM Hunink, MGM AF Muradin, GSR Bosch, JL Verstijnen, ACM Hunink, MGM TI Reporting success rate at 12 months after percutaneous treatment for peripheral arterial disease: The impact of outcome criteria SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID STANDARDS; ANGIOPLASTY; THERAPY AB OBJECTIVE. The objectives of our study were to assess the influence of varying outcome criteria on the success rate at 12 months after percutaneous intervention for peripheral arterial disease and to suggest a reporting method that can be used in studies that report results of interventions as measured by parameters of daily clinical practice. MATERIALS AND METHODS. The outcomes of 1,411 consecutive procedures in 1,583 limbs recorded in a multicenter registry involving six hospitals were analyzed. Six sets of outcome criteria were evaluated: one based on symptomatic change, three based on ankle-brachial index (ABI) measurements, and two based on combining the symptomatic and ABI outcome measures. Agreement among the outcome measures was compared using the kappa statistic. RESULTS. The ABI outcome measures alone showed good agreement (kappa = 0.74-0.94). The symptomatic outcome measures yielded a substantially higher 12-month success rate than the ABI outcome measures (difference, 18-24%) and the agreement was only fair (kappa = 0.52-0.60). The agreement between symptomatic outcome and ABI outcome measures was poor in patients with a pretreatment ABI measurement at rest of more than 0.90 (kappa = 0.20). Combining symptomatic outcome and the ABI outcome measures with the logical operator "OR" showed good agreement with the symptomatic outcome measures alone (kappa = 0.97) and using "AND" showed good agreement with the ABI outcome measures alone (kappa = 0.87). CONCLUSION. In patients with a pretreatment ABI measurement at rest of more than 0.90, classifying procedures using a criterion based on improvement in ABI measurements with more than 0.10 is inaccurate and underestimates the actual success rate at 12 months after percutaneous intervention. Furthermore, combining subjective improvement in symptoms and improvement in ABI measurements does not yield more information than reporting these outcome measures separately. Therefore, we suggest that improvement in symptoms and improvement in ABI measurements should be reported separately to indicate the 12-month success rate of percutaneous interventions for peripheral arterial disease. C1 Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, NL-3015 GE Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Radiol, Assessment Radiol Technol Program, NL-3015 GE Rotterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Bosch, JL (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rm EE21-40B,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM j.l.bosch@erasmusmc.nl NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2005 VL 185 IS 1 BP 46 EP 50 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900008 PM 15972397 ER PT J AU Gervais, DA McGovern, FJ Arellano, RS McDougal, WS Mueller, PR AF Gervais, DA McGovern, FJ Arellano, RS McDougal, WS Mueller, PR TI Radiofrequency ablation of renal cell carcinoma: Part I, indications, results, and role in patient management over a 6-year period and ablation of 100 tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID RADIO-FREQUENCY ABLATION; TISSUE ABLATION; CLINICAL-EXPERIENCE; COAGULATION NECROSIS; MASSES; METASTASES; ELECTRODE; OUTCOMES; SUCCESS; CANCER AB OBJECTIVE. The objectives of our article are to review our experience with radio-frequency ablation of renal cell carcinoma and to assess size and location as predictors of the ability to achieve complete necrosis by imaging criteria. MATERIALS AND METHODS. Over a 6-year period, 100 renal tumors in 85 patients underwent radiofrequency ablation at a single institution. The absence of enhancement on CT or MRI after radiofrequency ablation was interpreted as complete coagulation necrosis. Results were analyzed by tumor size and location using multivariate, analysis. A p value of 0.05 or less was considered significant. RESULTS. All 52 small (3 cm) and all 69 exophytic tumors underwent complete necrosis regardless of size, although many large tumors (> 3 cm) required a second ablation session. Using multivariate analysis, we found that both small size (p < 0.0001) and noncentral location (p = 0.0049) proved to be independent predictors of complete necrosis after a single ablation session. Location was a significant predictor (p = 0.015) of complete necrosis after any number of sessions, whereas size showed a strong trend (p = 0.059) toward predicting success after any number of sessions. Complications were either self-limited or readily treated and included hemorrhage (major, n = 2; minor, n = 3), inflammatory track mass (n = 1), transient lumbar plexus pain (n = 2), ureteral injury (n = 2), and skin bums (n = 1). CONCLUSION. Radiofrequency ablation is a promising minimally invasive therapy for renal cell carcinoma in patients who are not good operative candidates. Small size and noncentral location are favorable tumor characteristics, although large tumors can sometimes be successfully treated with multiple ablation sessions. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 24 TC 324 Z9 342 U1 0 U2 9 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 JUL PY 2005 VL 185 IS 1 BP 64 EP 71 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900011 PM 15972400 ER PT J AU Gervais, DA Arellano, RS McGovern, FJ McDougal, WS Mueller, PR AF Gervais, DA Arellano, RS McGovern, FJ McDougal, WS Mueller, PR TI Radiofrequency ablation of renal cell carcinoma: Part 2, lessons learned with ablation of 100 tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CLINICAL-EXPERIENCE; TISSUE; MASSES; COAGULATION; SUCCESS; MODEL AB OBJECTIVE. The objective of our study was to review radiofrequency ablation of 100 renal tumors and lessons learned with respect to electrode approach, effects on collecting system, bowel proximity, and patterns of residual disease. MATERIALS AND METHODS. Over 6 years, 100 renal tumors in 85 patients underwent radiofrequency ablation. Images were reviewed to determine the following: effect of initial electrode approach at and parallel to the tumor-kidney interface; effect of collecting system proximity to the tumor and to the zone of ablation; bowel proximity to the tumor and strategies to protect bowel; patterns of residual disease; and approaches at subsequent sessions. RESULTS. The initial placement of the electrode at and parallel to the tumor-kidney interface did not result in significantly fewer overlapping ablations (p = 0.91) or a lower rate of residual disease (p = 0.86). Direct contiguity of tumor or zone of ablation to the collecting system did not increase the complication rate. However, obscuration of calyces by a central tumor was a significant predictor of collecting system hemorrhage necessitating treatment (P < 0.001) seen in three of nine tumors obscuring calyces. Clinically significant urine leaks were rare (1/100) and related to downstream obstruction. There were no bowel complications despite the fact that 27 of the tumors were within I cm of bowel. Protective strategies progressed from reliance on electrode positioning to hydrodissection. Residual patterns were predominantly nodules or crescents, and straight electrodes were commonly used to approach residual disease. CONCLUSION. Initial electrode position at and parallel to the tumor-kidney interface does not result in less difficult or more successful ablations. Contiguity of tumor or zone of ablation to the collecting system does not increase the risk of complications, but obscuration of calyces does. Bowel complications are rare, and protection with hydrodissection is becoming more common. Residual tumor presents as nodules or crescents of persistent enhancement. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 16 TC 139 Z9 143 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 JUL PY 2005 VL 185 IS 1 BP 72 EP 80 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900012 PM 15972401 ER PT J AU Morrison, PR Brown, SD vanSonnenberg, E AF Morrison, PR Brown, SD vanSonnenberg, E TI Pediatric return electrodes for radiofrequency ablation in children SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID TUMORS C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Morrison, PR (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pmorrison@partners.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2005 VL 185 IS 1 BP 84 EP 85 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900014 PM 15972403 ER PT J AU Kassarjian, A Torriani, M Ouellette, H Palmer, WE AF Kassarjian, A Torriani, M Ouellette, H Palmer, WE TI Intramuscular rotator cuff cysts: Association with tendon tears on MRI and arthroscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CLINICAL-SIGNIFICANCE; ARTHROGRAPHY AB OBJECTIVE. This study was designed to explore the relationship between intramuscular cysts and rotator cuff tendon tears. CONCLUSION. Intramuscular cysts are strongly associated with rotator cuff tendon tears. Identification of such a cyst should prompt a search for a rotator cuff tear. Findings on MR arthrography and surgery suggest that a delaminating component of the rotator cuff tear may lead to the development of these cysts and may explain the occasional discrepancy between location of tears and location of cysts. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Kassarjian, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 55 Fruit St, Boston, MA 02114 USA. EM akassarjian@partners.org NR 13 TC 21 Z9 21 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2005 VL 185 IS 1 BP 160 EP 165 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900028 PM 15972417 ER PT J AU Kopans, DB AF Kopans, DB TI Bias in the medical journals: A commentary SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material AB Most readers are not aware of the fact that medical journals may have an unspoken bias in the papers that they select for publication. These biases can have far-reaching consequences. The controversy over mammography screening for women ages AM, -49 is a case in point. Several medical journals knowingly have refused to provide women with accurate information. Consequently, women have been led to believe that the age of 50 has some real significance with regard to screening when the fact is that it has none. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Breast Imaging, Boston, MA 02114 USA. Avon Fdn Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Dept Radiol, 15 Parkman St,Ste 240, Boston, MA 02114 USA. NR 0 TC 11 Z9 11 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2005 VL 185 IS 1 BP 176 EP 177 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900031 PM 15972420 ER PT J AU Sahani, DV Kalva, SP Fischman, AJ Kadavigere, R Blake, M Hahn, PF Saini, S AF Sahani, DV Kalva, SP Fischman, AJ Kadavigere, R Blake, M Hahn, PF Saini, S TI Detection of liver metastases from adenocarcinoma of the colon and pancreas: Comparison of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; COLORECTAL-CANCER; ARTERIAL PORTOGRAPHY; PHASE-III; GADOBENATE DIMEGLUMINE; HEPATIC METASTASES; SPIRAL CT; MN-DPDP; LESIONS; RESECTION AB OBJECTIVE. The objective of our study was to assess the relative performance of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET for the detection of liver metastases from adenocarcinoma of the colon and pancreas. MATERIALS AND METHODS. Imaging data of 34 patients (23 men, I I women; age range, 44-78 years) with adenocarcinoma of the colon (n = 27) or adenocarcinoma of the pancreas (n = 7) who had undergone mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET were retrospectively reviewed for the presence and number of liver metastases. Histopathology (n = 25) or follow-up imaging (n = 9) served as the standard of reference. Breath-hold T1-weighted gradient-recalled echo, respiratory-triggered T2-weighted fast spin-echo, and mangafodipir trisodium-enhanced axial fat-saturated high- spatial -resolution (256 x 512) T1 -weighted gradient-recalled echo images were obtained on a 1.5-T scanner. FDG PET was performed after the injection of 15-20 mCi (555-740 MBq) of FDG. The sensitivity, positive predictive value, and accuracy were calculated for each technique. The performances of the two techniques were compared using the Fisher's exact test. RESULTS. Thirty patients had hepatic metastases and four had no hepatic metastases according to the standard of reference. The total number of metastases was 79, including 33 that measured less than I cm. Based on a per-patient analysis, MRI and FDG PET showed sensitivities of 96.6% and 93.3%, positive predictive values of 100% and 90.3%, and accuracies of 97.1% and 85.3%, respectively. According to a per-lesion analysis, MRI and FDG PET showed sensitivities of 81.4% and 67.0%, positive predictive values of 89.8% and 81.3%, and accuracies of 75.5% and 64.1%, respectively. MRI detected more hepatic metastases than FDG PET (p = 0.016). Of the 33 subcentimeter lesions confirmed on the standard of reference, all were identified on MRI, whereas only 12 were detected on FDG PET (p = 0.0001). CONCLUSION. In patients with colon and pancreatic adenocarcinoma, high- spatial -resolution mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET were comparable in the detection of patients with liver metastases. FDG PET provided additional information about extrahepatic disease and was useful in initial staging. However, significantly more and smaller liver metastases were detected on MRI than on FDG PET. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 34 TC 58 Z9 62 U1 0 U2 4 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 JUL PY 2005 VL 185 IS 1 BP 239 EP 246 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937US UT WOS:000229951900042 PM 15972430 ER PT J AU Irving, JA Lerwill, ME Young, RH AF Irving, JA Lerwill, ME Young, RH TI Gastrointestinal stromal tumors metastatic to the ovary - A report of five cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; gastrointestinal stromal tumor; metastasis ID SMOOTH-MUSCLE TUMORS; GRANULOSA-CELL TUMOR; C-KIT EXPRESSION; DIFFERENTIAL-DIAGNOSIS; CLINICOPATHOLOGICAL ANALYSIS; IMMUNOHISTOCHEMICAL ANALYSIS; MESENCHYMAL TUMORS; UTERUS; MELANOMA; FEATURES AB Five cases of gastrointestinal stromal tumor metastatic to the ovary are reported. The average patient age was 59 years (range, 44-81 years). The primary turner was in the small bowel or its mesentery (4 cases) or stomach (I case). The primary and metastatic tumors were discovered synchronously in 3 cases. In the other 2 cases, the ovarian tumors were discovered 18 months before a gastric tumor was identified and 27 years after a small bowel tumor had been resected. The ovarian tumors (three of which were bilateral) were usually solid, tan, and lobulated. Microscopically, three tumors had a pure spindle cell morphology, and two both spindle and epithelioid cell components. The diagnosis in all 5 cases was confirmed with positive c-kit (CD117) and negative desmin immunostaining. Variably positive immunoreactivity for either or both h-caldesmon and smooth muscle actin was seen in all 5 cases, and 3 cases were CD34-positive. Four patients died between 1 and 6.5 years (mean, 2.8 years) from the time of ovarian tumor diagnosis. The main differential diagnostic consideration was leiomyosarcoma; the most important features to help exclude this diagnosis were an absence of tumor in the uterus, low histologic grade, and a desmin-negative, c-kit-positive immunophenotype. Other differential considerations, including endometrial stromal sarcoma and fibrosarcoma, are discussed. Most of the ovarian tumors in this series were initially diagnosed as tumors of other types, a misdiagnosis with significant therapeutic and prognostic implications because of the specific therapy now available for gastrointestinal stromal tumors. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Irving, JA (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 1212 Ave, Vancouver, BC V5Z 1M9, Canada. EM jirving@vanhosp.bc.ca NR 52 TC 41 Z9 46 U1 0 U2 10 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 JUL PY 2005 VL 29 IS 7 BP 920 EP 926 DI 10.1097/01.pas.0000155161.55915.c3 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 939WF UT WOS:000230102600010 PM 15958857 ER PT J AU Shoji, T Wain, JC Houser, SL Benjamin, LC Johnston, DR Hoerbelt, R Hasse, RS Lee, RS Muniappan, A Guenther, DA Bravard, MA Ledgerwood, LG Sachs, DH Sayegh, MH Madsen, JC Allan, JS AF Shoji, T Wain, JC Houser, SL Benjamin, LC Johnston, DR Hoerbelt, R Hasse, RS Lee, RS Muniappan, A Guenther, DA Bravard, MA Ledgerwood, LG Sachs, DH Sayegh, MH Madsen, JC Allan, JS TI Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Indirect allorecognition; Lung; MHC peptides; rejection; swine; transplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; BRONCHIOLITIS OBLITERANS SYNDROME; TRANSPLANT RECIPIENTS; INDIRECT ALLORECOGNITION; WORKING FORMULATION; PEPTIDES; ALLOREACTIVITY; VASCULOPATHY; LYMPHOCYTES; PATHWAYS AB The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively. All four recipients developed T-cell reactivity to donor-derived class I major histocompatibility complex (MHC) peptides. Second, six swine were immunized with synthetic donor-derived class I allopeptides prior to transplantation. Control groups consisted of nonimmunized recipients (n = 6) and recipients immunized with an irrelevant peptide (n = 3). These recipients all received a 12-day course of post-operative CsA. Swine immunized with allopeptides exhibited accelerated graft rejection, as compared to both control groups (p < 0.01 and p = 0.03, respectively). Within the experimental group, the dominant histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was seen in the graft with the longest survival. Both control groups showed a lesser degree of AR, with four out of six nonimmunized swine ultimately developing OB. These studies suggest that indirect allorecognition is operative during lung allograft rejection, and that pre-transplant sensitization to donor-derived MHC allopeptides can accelerate graft rejection. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM jallan@partners.org FU NHLBI NIH HHS [1R01-HL67110-01-A1]; NIAID NIH HHS [1P01-AI50157-01] NR 29 TC 15 Z9 15 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2005 VL 5 IS 7 BP 1626 EP 1634 DI 10.1111/j.1600-6143.2005.00925.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 933MV UT WOS:000229635100008 PM 15943620 ER PT J AU Wilens, TE Kwon, A Tanguay, S Chase, R Moore, H Faraone, SV Biederman, J AF Wilens, TE Kwon, A Tanguay, S Chase, R Moore, H Faraone, SV Biederman, J TI Characteristics of adults with attention deficit hyperactivity disorder plus substance use disorder: The role of psychiatric comorbidity SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SEEKING COCAINE ABUSERS; CONDUCT DISORDER; RISK-FACTORS; DEFICIT/HYPERACTIVITY DISORDER; ALCOHOL-ABUSE; DOUBLE-BLIND; FOLLOW-UP; ADHD; CHILDREN; DRUG AB The objective of the study was to investigate the characteristics of adults with Attention Deficit Hyperactivity Disorder (ADHD) or substance use disorder (SUD), especially in the context of comorbid psychiatric disorders. Subjects were adults (n = 78) participating in a controlled family study of ADHD and SUD. Four groups were identified based on a diagnosis of ADHD or SUD: ADHD, SUD, ADHD + SUD, and neither ADHD nor SUD. All diagnoses were determined by structured clinical interview for DSM IV. Rates of psychiatric comorbidity were lowest in the controls, intermediate in the ADHD and SUD groups, and highest in the ADHD + SUD group. Relative to controls, the ADHD, SUD, and ADHD + SUD groups bad higher rates of major depression (Z = 1.98, p = 0.05), conduct disorder ( Z = 2.0, p = 0.04), antisocial personality disorder (Z = 2.6, p = 0.009), agoraphobia (.Z = 2.5, p = 0.01) and social phobia (Z = 2.7, p = 0.007). Higher rates of psychiatric comorbidity, especially mood and anxiety disorders, exist in subjects with SUD+ADHD relative to subjects with SUD, ADHD, or controls. Clinicians need to be attentive to other psychiatric disorders that may occur in the large group of adults with ADHD + SUR C1 Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Wilens, TE (reprint author), Yawkey Ctr Outpatient Care, YAW-6-6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [DA11929, DA14419, R29 DA11315]; NIMH NIH HHS [MH 57934] NR 54 TC 38 Z9 39 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-SEP PY 2005 VL 14 IS 4 BP 319 EP 327 DI 10.1080/10550490591003639 PG 9 WC Substance Abuse SC Substance Abuse GA 966PI UT WOS:000232032700003 PM 16188712 ER PT J AU Liao, M Sonner, JM Husain, SS Miller, KW Jurd, R Rudolph, U Eger, EI AF Liao, M Sonner, JM Husain, SS Miller, KW Jurd, R Rudolph, U Eger, EI TI R (+) Etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta 3 subunit SO ANESTHESIA AND ANALGESIA LA English DT Article ID GATED ION CHANNELS; SITES AB A photoactivable diazirine derivative of etomidate, azietomidate, shares many actions of etomidate, including a capacity to abolish the righting reflexes in tadpoles and enhance gamma-aminobutyric acid (GABA)induced currents. Azietomidate's usefulness in studies of mechanisms of anesthesia depends on the assumption that it shares a site of action with etomidate. Mice bearing an N265M beta 3 subunit point mutation in GABA, receptors have a markedly decreased sensitivity to loss of righting reflexes induced by etomidate over a range of doses. Accordingly, in the present study we measured the time to recovery of righting reflexes of wild type and mutant mice as a function of dose given as an IV bolus. Analysis of the data for azietomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 10.0 +/- 0.9 min and 3.0 +/- 1.6 min for wild type and mutant mice, respectively (mean +/- SD). A similar analysis for etomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 12.0 +/- 1.3 min and 4.0 +/- 0.7 min for wild type and mutant mice respectively. Thus, at this dose a single mutation, N265M on the 03 subunit of the GABA(A) receptor, approximately halved the time to recovery of righting reflexes for both etomidate and azietomidate (by 7.6 +/- 1.5 min and 7.2 +/- 1.8 min, respectively), emphasizing the contribution of this residue as a determinant of a behavioral response of azietomidate in mice. C1 Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Zurich, Inst Pharmacol & Toxicol, Zurich, Switzerland. RP Eger, EI (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455, San Francisco, CA 94143 USA. EM egere@anesthesia.ucsf.edu FU NIGMS NIH HHS [1 P01 GM58448, 1PO1GM47818] NR 10 TC 24 Z9 24 U1 0 U2 3 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 JUL PY 2005 VL 101 IS 1 BP 131 EP 135 DI 10.1213/01.ANE.0000153011.64764.6F PG 5 WC Anesthesiology SC Anesthesiology GA 936XE UT WOS:000229888000024 PM 15976219 ER PT J AU Magid, DJ Masoudi, FA Vinson, DR van der Vlugt, TM Padgett, TG Tricomi, AJ Lyons, EE Crounse, L Brand, DW Go, AS Ho, PM Rumsfeld, JS AF Magid, DJ Masoudi, FA Vinson, DR van der Vlugt, TM Padgett, TG Tricomi, AJ Lyons, EE Crounse, L Brand, DW Go, AS Ho, PM Rumsfeld, JS TI Older emergency department patients with acute myocardial infarction receive lower quality of care than younger patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 17-18, 2004 CL San Francisco, CA SP Amer Coll Emergency Physicians ID COOPERATIVE CARDIOVASCULAR PROJECT; WORCESTER HEART-ATTACK; BETA-BLOCKER THERAPY; AGE-RELATED TRENDS; THROMBOLYTIC THERAPY; NATIONAL REGISTRY; ELDERLY-PATIENTS; PRIMARY ANGIOPLASTY; MORTALITY; PATTERNS AB Study objective: We assessed the independent relationship between age and the quality of medical care provided to patients presenting to the emergency department (ED) with acute myocardial infarction. Methods: We conducted a 2-year retrospective cohort study of 2,216 acute myocardial infarction patients presenting urgently to 5 EDs in Colorado and California from July 1, 2000, through June 30, 2002. Data on patient characteristics, clinical presentation, and ED processes of care were obtained from the ED record and ECG review. Patients were divided into 6 groups based on their age at the time of their ED visit: younger than 50 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, 80 to 89 years, and 90 years or older. Hierarchic multivariable regression was used to assess the independent association between age and the provision of aspirin, beta-blockers, and reperfusion therapy (fibrinolytic agent or percutaneous coronary intervention) in the ED to eligible acute myocardial infarction patients. Results: Of ideal candidates for treatment in the ED, 1,639 (80.5%) of 2,036 received aspirin, 552 (60.3%) of 916 received beta-blockers, and 358 (77.8%) of 460 received acute reperfusion therapy. After adjustment for demographic, medical history, and clinical factors, older patients were less likely to receive aspirin (odds ratio [OR] 0.85, 95% confidence interval [Cl] 0.77 to 0.93), beta-blockers (OR 0.79, 95% CI 0.71 to 0.88), and reperfusion therapy (OR 0.30, 95% CI 0.18 to 0.52). Conclusion: Older patients presenting to the ED with acute myocardial infarction receive lower-quality medical care than younger patients. Further investigation to identify the reasons for this disparity and to intervene to reduce gaps in care quality will likely lead to improved outcomes for older acute myocardial infarction patients. C1 Kiaser Permanente Colorado, Clin Res Unit, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80202 USA. Denver Hlth Med Ctr, Div Cardiol, Denver, CO USA. Permanente Med Grp Inc, Oakland, CA USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Denver VA Med Ctr, Denver, CO USA. Denver Hlth Med Ctr, Dept Med, Denver, CO USA. RP Magid, DJ (reprint author), Kiaser Permanente Colorado, Clin Res Unit, POB 378066, Denver, CO USA. EM David.J.Magid@kp.org OI Vinson, David/0000-0001-6559-1858 FU NIA NIH HHS [K08-AG01011] NR 48 TC 30 Z9 30 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2005 VL 46 IS 1 BP 14 EP 21 DI 10.1016/j.annemergmed.2004.12.012 PG 8 WC Emergency Medicine SC Emergency Medicine GA 941PP UT WOS:000230227000004 PM 15988420 ER PT J AU Pallin, DJ Chng, YM McKay, MP Ernond, JA Pelletier, AJ Camargo, CA AF Pallin, DJ Chng, YM McKay, MP Ernond, JA Pelletier, AJ Camargo, CA TI Epidemiology of epistaxis in US emergency departments, 1992 to 2001 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SINGLE-BLIND AB Study objective: The epidemiology of emergency department (ED) visits for epistaxis is unknown. We use national data to fill this gap and test hypotheses that epistaxis visits are more common with increasing age and in winter. Methods: We identify ED visit with ePistaxis from 10 years of the National Hospital Ambulatory Medical Care Survey. We calculate visit rates by age and other demographic characteristics and assess mode of arrival and disposition. Results are presented with 95% confidence intervals (Cis). Results: From 1992 to 2001, epistaxis occurred at 4,503,000 ED visits, or 0.46% (95% Cl 0.41% to 0.51%) of all visits. Per 1,000 population, 1.7 (95% Cl 1.5 to 1.9) ED visits for epistaxis occurred annually. The age-related frequency was bimodal, with peaks among those younger than 10 years (4.0 per 1,000 visits) and aged 70 to 79 years (12.0 per 1,000 visits). Most cases (83%; 95% Cl 80% to 86%) were atraumatic. Traumatic cases were younger than atraumatic cases (mean age 31 versus 49 years). From December to February, atraumatic epistaxis occurred in 0.50% (95% Cl 0.40% to 0.60%) of all visits versus 0.34% (95% Cl 0.30% to 0.39%) during nonwinter months. Fifteen percent (95% Cl 12% to 18%) of cases arrived by ambulance, and 6% (95% Cl 5% to 7%) of patients were hospitalized. Conclusion: Epistaxis accounts for about 1 in 200 ED visits in the United States. Although there is an early age peak (age > 10 years), the frequency increases from age 20 years onward, with the highest rates in the elderly. Epistaxis visits are more common in the winter. Future efforts to decrease epistaxis visits might focus on education of the elderly and parents of young children about nasal mucosa care and basic approaches to home management. C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 9 TC 47 Z9 49 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2005 VL 46 IS 1 BP 77 EP 81 DI 10.1016/j.annemergmed.2004.12.014 PG 5 WC Emergency Medicine SC Emergency Medicine GA 941PP UT WOS:000230227000014 PM 15988431 ER PT J AU Halpin, C Owen, G Gutierez-Espeleta, GA Sims, K Rehm, HL AF Halpin, C Owen, G Gutierez-Espeleta, GA Sims, K Rehm, HL TI Audiologic features of Norrie disease SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE audiometry; NDP gene; Norrie disease; speech intelligibility; stria vascularis ID MISSENSE MUTATIONS; ND GENE; CARRIERS; DEAFNESS; MODEL AB Objectives: Norrie disease is an X-linked recessive disorder in which patients are born blind and develop sensory hearing loss in adolescence. The hearing loss associated with Norrie disease has been shown in a genetically altered knockout mouse to involve dysfunction of the stria vascularis; most other structures are preserved until the later stages of the disease. The objective of this study was to characterize the audiologic phenotype of Norrie disease for comparison with the pathophysiologic mechanism. Methods: The design combined two series of clinical audiologic evaluations, with special attention to speech intelligibility. Results: The audiologic results for 12 affected individuals and 10 carriers show that patients with Norrie disease retain high speech intelligibility scores even when the threshold loss is severe. Conclusions: The cochlear mechanism - failure of the stria vascularis - accounts for some of the higher values in the wide distribution of speech scores in cases with similar pure tone audiograms. C1 Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Univ Costa Rica, Escuela Biol, Inst Invest Salud, San Jose, Costa Rica. RP Halpin, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC02281] NR 28 TC 11 Z9 11 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 JUL PY 2005 VL 114 IS 7 BP 533 EP 538 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 946KL UT WOS:000230570900007 PM 16134349 ER PT J AU Silber, JH Rosenbaum, PR Trudeau, ME Chen, W Zhang, XM Lorch, SA Kelz, RR Mosher, RE Even-Shoshan, O AF Silber, JH Rosenbaum, PR Trudeau, ME Chen, W Zhang, XM Lorch, SA Kelz, RR Mosher, RE Even-Shoshan, O TI Preoperative antibiotics and mortality in the elderly SO ANNALS OF SURGERY LA English DT Article ID TOTAL HIP-REPLACEMENT; PROPHYLACTIC ANTIBIOTICS; ANTIMICROBIAL PROPHYLAXIS; PROPENSITY SCORE; BIAS REDUCTION; SURGERY; RISK; GUIDELINES; SEVERITY; OUTCOMES AB Objective and Background: It is generally thought that the use of preoperative antibiotics reduces the risk of postoperative infection, yet few studies have described the association between preoperative antibiotics and the risk of dying. The objective of this study was to determine whether preoperative antibiotics are associated with a reduced risk of death. Methods: We performed a multivariate matched, population-based, case-control study of death following surgery on 1362 Pennsylvania Medicare patients between 65 and 85 years of age undergoing general and orthopedic surgery. Cases (681 deaths within 60 days from hospital admission) were randomly selected throughout Pennsylvania using claims from 1995 and 1996. Models were developed to scan Medicare claims, looking for controls who did not die and who were the closest matches to the previously selected cases based on preoperative characteristics. Cases and their controls were identified, and charts were abstracted to define antibiotic use and obtain baseline severity adjustment data. Results: For general surgery, the odds of dying within 60 days were less than half in those treated with preoperative antibiotics within 2 hours of incision as compared with those without such treatment: (odds ratio = 0.44; 95% confidence interval, 0.32-0.60), P < 0.0001). For orthopedic surgery, no significant mortality reduction was observed (OR = 0.85; 95% confidence interval, 0.54-1.32; P < 0.464). Interpretation: Preoperative antibiotics are associated with a substantially lower 60-day mortality rate in elderly patients undergoing general surgery. In patients who appear to be comparable, the risk of death was half as large among those who received preoperative antibiotics. C1 Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesia, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Hosp Univ Penn, VA Ctr Hlth Equi Res & Promot, Philadelphia, PA 19104 USA. RP Silber, JH (reprint author), Childrens Hosp Philadelphia, Ctr Outcomes Res, 3535 Market St,Suite 1029, Philadelphia, PA 19104 USA. EM silberj@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012 FU AHRQ HHS [HS-R01-9460] NR 35 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 2005 VL 242 IS 1 BP 107 EP 114 DI 10.1097/01.sla.0000167850.49819.ea PG 8 WC Surgery SC Surgery GA 940OB UT WOS:000230152700015 PM 15973108 ER PT J AU Pierie, JPEN Muzikansky, A Tanabe, KK Ott, MJ AF Pierie, JPEN Muzikansky, A Tanabe, KK Ott, MJ TI The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE hepatocellular carcinoma; resection; transplantation; outcome ID CIRRHOTIC-PATIENTS; HEPATIC RESECTION; ETHANOL INJECTION; MALIGNANT DISEASE; UNITED-STATES; SURVIVAL; EXPERIENCE; CANCER AB Background: Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. Methods: Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. Results: A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 5 1 % in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). Conclusions: Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients. C1 Ctr Med, Dept Gastrointestinal Surg, NL-8934 AD Leeuwarden, Netherlands. Massachusetts Gen Hosp, Ctr Canc Stat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Ott, MJ (reprint author), Latter Day St Hosp, Dept Surg, 324 10th Ave,Suite 184, Salt Lake City, UT 84103 USA. EM ldmott@ihc.com NR 37 TC 11 Z9 13 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 JUL PY 2005 VL 12 IS 7 BP 552 EP 560 DI 10.1245/ASO.2004.03.029 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 940YU UT WOS:000230182600009 PM 15889217 ER PT J AU Von Boehmer, H AF Von Boehmer, H TI Origin, lifestyle and function of suppressor T cells SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 15 EP 15 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100050 ER PT J AU Finckh, A Choi, HK Michaud, K Wolfe, F AF Finckh, A Choi, HK Michaud, K Wolfe, F TI Progression of radiographic joint damage in different eras. Has rheumatoid arthritis become a milder disease over the past decades? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Massachusetts Gen Hosp, Dept Med, Arthritis Unit, Boston, MA 02114 USA. Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 91 EP + PG 2 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100282 ER PT J AU Reginato, AM Neer, R Briggs, C Olsen, BR AF Reginato, AM Neer, R Briggs, C Olsen, BR TI Low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms in patients with osteoporosis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. Childrens Hosp, Dept Human Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 363 EP 363 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909101541 ER PT J AU Wright, CD Grillo, HC Hammoud, ZT Wain, JC Gaissert, HA Zaydfudim, V Mathisen, DJ AF Wright, CD Grillo, HC Hammoud, ZT Wain, JC Gaissert, HA Zaydfudim, V Mathisen, DJ TI Tracheoplasty for expiratory collapse of central airways SO ANNALS OF THORACIC SURGERY LA English DT Article ID TRACHEOBRONCHIAL COLLAPSE; TRACHEOMALACIA; COLLAPSIBILITY; EMPHYSEMA AB Background. Severe central airway obstruction due to expiratory collapse occurs with malacia of intrathoracic trachea and main bronchi, often with chronic obstructive pulmonary disease. Bronchoscopically observed, it is confirmed by inspiratory-expiratory computerized tomographic chest scans. Prior attempts at surgical stabilization have not given dependable results. Methods. Posterior tracheobronchial splinting with polypropylene mesh (Marlex) holds cartilages in more normal configuration, and fixes redundant membranous walls. Fourteen consecutive patients were so treated for severe dyspnea. Prior trials of various autologous and exogenous splints failed. Results. All felt subjectively improved early, with decreased dyspnea, cough, and secretion retention, and with increased activities. Mean forced expiratory volume in 1 second rose from 51% predicted to 73% (p = 0.009), and peak expiratory flow rate from 49% to 70% (p < 0.00001). One patient was lost to follow-up (1 year), 1 died of unrelated cause (5 years), 1 died of chronic obstructive pulmonary disease (3 years), and 1 had decreased respiratory function over 5 years. Ten patients were available for long-term follow-up: 6 were judged to have an excellent result, 2 were good, and 2 were poor due to collapse of unsplinted main bronchi. Conclusions. Complete splinting of all malacic central airways with Marlex restores anatomic configuration and permanently prevents expiratory collapse, with relief of extreme dyspnea, cough, and secretion retention. (c) 2005 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Surg Serv, Gen Thorac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Surg Serv, Gen Thorac Surg Div, Blake 1570, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 22 TC 27 Z9 27 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2005 VL 80 IS 1 BP 259 EP 267 DI 10.1016/j.athoracsur.2005.01.032 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 941LG UT WOS:000230215700042 PM 15975378 ER PT J AU Hamblin, MR Viveiros, J Yang, CM Ahmadi, A Ganz, RA Tolkoff, MJ AF Hamblin, MR Viveiros, J Yang, CM Ahmadi, A Ganz, RA Tolkoff, MJ TI Helicobacter pylori accumulates photoactive porphyrins and is killed by visible light SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PROPIONIBACTERIUM-ACNES; PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; ARGON-LASER; BACTERIA; PORPHYROMONAS; IRRADIATION; INFECTION; UPDATE AB Helicobacter pylori colonizes the mucus layer of the human stomach and duodenum, causes chronic gastritis, gastric ulcer, and is a risk factor for gastric adenocarcinoma. There is a 20% failure rate in antibiotic therapy, which is increasingly due to antibiotic resistance and necessitates the search for alternative antimicrobial methods. We have discovered that H. pylori when cultured in liquid medium, accumulates significant quantities of coproporphyrin and protoporphyrin IX, both in the cells and secreted into the medium. These photoactive porphyrins lead to cell death (up to 5 logs) by photodynamic action upon illumination with low doses of visible light, with blue/violet light being most efficient. The degree of killing increases with the age of the culture and is greater than that found with Propionibacterium acnes (another bacterium known to be photosensitive due to porphyrin accumulation). Both virulent and drug-resistant strains are killed. The data suggest that phototherapy might be used to treat H. pylori infection in the human stomach. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Sterilite LLC, Minnetonka, MN USA. Abbott NW Hosp, Dept Gastroenterol, Minneapolis, MN 55407 USA. Seedling Ventures LLC, Boston, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR314B, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2] NR 31 TC 70 Z9 75 U1 1 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2005 VL 49 IS 7 BP 2822 EP 2827 DI 10.1128/AAC.49.7.2822-2827.2005 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 940YM UT WOS:000230181800034 PM 15980355 ER PT J AU Robicsek, A Sahm, DF Strahilevitz, J Jacoby, GA Hooper, DC AF Robicsek, A Sahm, DF Strahilevitz, J Jacoby, GA Hooper, DC TI Broader distribution of plasmid-mediated quinolone resistance in the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; TRANSFERABLE PLASMID; GENE AB The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains in the United States. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Focus Technol, Herndon, VA USA. Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI043312, AI57576, AI43312, R01 AI057576] NR 11 TC 65 Z9 84 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2005 VL 49 IS 7 BP 3001 EP 3003 DI 10.1128/AAC.49.7.3001-3003.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 940YM UT WOS:000230181800063 PM 15980384 ER PT J AU Eliopoulos, GM Ferraro, MJ Wennersten, CB Moellering, RC AF Eliopoulos, GM Ferraro, MJ Wennersten, CB Moellering, RC TI In vitro activity of an oral streptogramin antimicrobial, XRP2868, against gram-positive bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUINUPRISTIN-DALFOPRISTIN; CLINDAMYCIN; VANCOMYCIN; XRP-2868 AB The comparative in vitro potency of XRP2868, a new oral semisynthetic streptogramin antibiotic, was evaluated against gram-positive bacteria. XRP2868 inhibited all staphylococci at <= 1 mu g/ml and all nonpneumococcal streptococci at <= 0.25 mu g/ml and was fourfold more potent than quinupristin-dalfopristin against Staphylococcus aureus and Enterococcus faecium. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Eliopoulos, GM (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM geliopou@bidmc.harvard.edu NR 7 TC 9 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2005 VL 49 IS 7 BP 3034 EP 3039 DI 10.1128/AAC.49.7.3034-3039.2005 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 940YM UT WOS:000230181800073 PM 15980394 ER PT J AU Tran, JH Jacoby, GA Hooper, DC AF Tran, JH Jacoby, GA Hooper, DC TI Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB Purified QnrA blocked ciprofloxacin inhibition of topoisomerase IV, just as QnrA was previously found to prevent quinolone inhibition of DNA gyrase. With a gel displacement assay, tagged QnrA was shown to bind to topoisomerase IV and its subunits in a reaction that did not depend on the presence of DNA, quinolone, or ATP. C1 Lahei Clin, Dept Infect Dis, Burlington, MA 01805 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), Lahei Clin, Dept Infect Dis, 41 Mall Rd, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU NIAID NIH HHS [AI43312, R01 AI057576, AI57576, R01 AI043312] NR 5 TC 93 Z9 116 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2005 VL 49 IS 7 BP 3050 EP 3052 DI 10.1128/AAC.49.7.3050-3052.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 940YM UT WOS:000230181800076 PM 15980397 ER PT J AU Benavides, JM Webb, RH AF Benavides, JM Webb, RH TI Optical characterization of ultrabright LEDs SO APPLIED OPTICS LA English DT Article AB Ultrabright light emitting diodes (LEDs) are a new light source for visual psychophysics and microscopy. The new LEDs are intended primarily for room and exterior illumination, and the manufacturers' specifications are adequate for that. However, we use them as light sources in situations where a more complete characterization may be useful. For one set of LEDs we have measured the radiometric intensity and its distribution in space and wavelength, and we have tested for interactions of these variables and their dependence on driver configuration. We describe techniques for making these measurements and give a link to a simple calculator for converting among radiometric and photometric measures, as well as an evaluation of the safety considerations these very bright sources demand. (c) 2005 Optical Society of America. C1 Eye Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Benavides, JM (reprint author), Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM webb@eri.harvard.edu FU NEI NIH HHS [R01EY14165] NR 5 TC 15 Z9 15 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 2005 VL 44 IS 19 BP 4000 EP 4003 DI 10.1364/AO.44.004000 PG 4 WC Optics SC Optics GA 940OM UT WOS:000230153800017 PM 16004046 ER PT J AU Ang, GC Werth, VP AF Ang, GC Werth, VP TI Combination antimalarials in the treatment of cutaneous dermatomyositis - A retrospective study SO ARCHIVES OF DERMATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; LUPUS-ERYTHEMATOSUS; JUVENILE DERMATOMYOSITIS; TNF-ALPHA-308A ALLELE; QUINACRINE ATABRINE; OCULAR SAFETY; HYDROXYCHLOROQUINE; ASSOCIATION; CHLOROQUINE; RETINOPATHY AB Objective: To observe whether the use of antimalarials in combination resulted in significant improvement in the cutaneous signs and symptoms of patients with dermatomyositis who did not other-wise respond to the use of single-agent antimalarial therapy. Design: Retrospective case series of 17 patients treated between January 1, 199 1, and December 31, 2002. Setting: An ambulatory medical dermatology clinic in an academic center. Patients: Patients had adult-onset dermatomyositis with predominantly cutaneous symptoms and a follow-up period at our clinic of at least 6 months. Cases in which it was not possible to assess the effect of treatment on cutaneous symptoms were not included. Intervention: Treatment regimens varied and included the use of antimalarials, prednisone, methotrexate, and other medications. Main Outcome Measures: Physician-observed and patient-reported improvement based on erythema, pruritus, and extent of affected skin. Results: Seven of 17-patients experienced at least near clearance in cutaneous symptoms with the use of antimalarial therapy alone: 4 of these patients required combination therapy (hydroxychloroquine sulfate-quinacrine hydrochloride or chloroquine phosphatequinacrine), while 3 of them responded well to antimalarial monotherapy. The median time required to reach the response milestones on the final working therapeutic regimen was 3 months (mean, 4.8 months; range, 2-14 months). Six patients did not respond significantly to any type of therapy, including nonantimalarials. Conclusion: Our experience suggests that a significant subgroup of patients whose skin lesions have been unresponsive to a single antimalarial benefit from combination therapy with hydroxychloroquine and quinacrine or chloroquine and quinacrine, but controlled clinical trials are warranted to assess the extent of benefit. C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Jefferson Med Coll, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhoads Pavil,36th & Spruce, Philadelphia, PA 19104 USA. FU NIAMS NIH HHS [1K24 AR02207] NR 21 TC 24 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2005 VL 141 IS 7 BP 855 EP 859 DI 10.1001/archderm.141.7.855 PG 5 WC Dermatology SC Dermatology GA 944PV UT WOS:000230442100006 PM 16027300 ER PT J AU Suhler, EB Smith, JR Wertheim, MS Lauer, AK Kurz, DE Pickard, TD Rosenbaum, JT AF Suhler, EB Smith, JR Wertheim, MS Lauer, AK Kurz, DE Pickard, TD Rosenbaum, JT TI A prospective trial of infliximab therapy for refractory uveitis - Preliminary safety and efficacy outcomes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; JUVENILE IDIOPATHIC ARTHRITIS; RHEUMATOID-ARTHRITIS; FACTOR-ALPHA; POSTERIOR UVEITIS; MONOCLONAL-ANTIBODY; BEHCETS-SYNDROME; CROHNS-DISEASE; CLINICAL-TRIAL; TNF-ALPHA AB Objective: Infliximab, a monoclonal antibody against tumor necrosis factor a, is approved by the US Food and Drug Administration for treatment of numerous autoimmune disorders. We conducted a prospective, open-label phase 2 clinical trial to assess the effectiveness of infliximab in treating refractory autoimmune uveitis. Methods: We prospectively enrolled 23 patients from the uveitis clinic of the Casey Eye Institute, Portland, Ore, into this trial. All patients meeting eligibility criteria received 3 infliximab infusions at weeks 0, 2, and 6. Clinical success was ascertained at week 10. Patients meeting initial criteria for success received an infusion at week 14 and every 8 weeks thereafter, with dose escalation permitted for breakthrough inflammation, and underwent outcome measurements at week 50. Results: All patients underwent outcome assessment at week 10. Eighteen (78%) of these subjects met criteria for clinical success at this time. Success was judged by the composite clinical end point of visual acuity, control of intraocular inflammation, ability to taper concomitant medication therapy, and improvement in inflammatory signs on fluorescein angiography and/or ocular coherence tomography. Successful grading required improvement in at least 1 of 4 subcomponents and worsening in none. Seven of 14 patients enrolled for I year continued infliximab therapy and maintained their successful grading. Five did not complete I year of treatment because of significant adverse events, and 2 terminated treatment early for reasons unrelated to the study. Serious adverse events that were potentially related to infliximab included pulmonary embolus, congestive heart failure, lupus-like reaction in 2, and vitreous hemorrhage in 2 patients. Antinuclear antibodies developed in 15 of 20 enrolled patients receiving 3 or more infusions. Conclusions: Infliximab was an effective short-term immunosuppressive agent in most of the patients, with 18 of 23 meeting criteria for clinical success at week 10. Infliximab was effective in the long term in all patients able to complete 50 weeks of therapy. Although some patients achieved clear benefit, the rate of serious toxic effects was unexpectedly high. Further long-term studies are warranted to determine the safety and efficacy of infliximab in treating intraocular inflammation. C1 Case Eye Inst, Uveitis Div, Portland, OR 97239 USA. Case Eye Inst, Retina Div, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Cell Biol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Dept Ophthalmol, Portland, OR USA. RP Suhler, EB (reprint author), Case Eye Inst, Uveitis Div, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM suhlere@ohsu.edu FU NCRR NIH HHS [5M01 RR 000334] NR 39 TC 169 Z9 176 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2005 VL 123 IS 7 BP 903 EP 912 DI 10.1001/archopht.123.7.903 PG 10 WC Ophthalmology SC Ophthalmology GA 943KR UT WOS:000230352900002 PM 16009830 ER PT J AU Cohen, EG Deschler, DG Walsh, K Hayden, RE AF Cohen, EG Deschler, DG Walsh, K Hayden, RE TI Early use of a mechanical stretching device to improve mandibular mobility after composite resection: A pilot study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE head and neck neoplasms; rehabilitation; surgical flaps; trismus ID TRISMUS AB Objective: To evaluate the use of a mechanical stretching device, the Therabite, for the early postoperative management of trismus in select patients. Design: Prospective series of consecutive head and neck cancer patients. Setting: Academic, tertiary referral center. Participants: Seven patients with oropharyngeal carcinoma who underwent resection and radial forearm flap reconstruction. Five had midline mandibulotomy procedures for exposure. Six had radiation therapy (2 pre, 4 post). Interventions: Patients were given a Therabite mechanical jaw mobilization device, were instructed in its proper use, and began using it within 6 weeks postoperatively. Main Outcome Measures: Maximal interincisor opening (MIO) was measured at the beginning of use and at the most recent postoperative visit. A 5-question self-assessment telephone survey was administered on study completion. Results: The average MIO was 30mm (range, 21-38mm) at the beginning of the study and 40mm (range, 30-57mm) at the last visit. Average gain in MIO was 10mm (range, 1-21mm). Four of 5 assessable patients had minimal or no limitation on overall quality of life relative to jaw opening. No complications were associated with use of the device. Two patients could not be located for follow-up. Conclusions: The Therabite mechanical stretching device is effective and safe for the management of trismus in a select group of head and neck cancer patients after extensive ablation and complex reconstruction. Specifically, there were no adverse effects in the 5 patients who had undergone midline mandibulotomy. (c) 2005 by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Dept Otolaryngol Head & Neck Surg, Newark, NJ 07103 USA. Mayo Clin, Dept Otolaryngol Head & Neck Surg, Scottsdale, AZ USA. RP Deschler, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 38 Z9 38 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2005 VL 86 IS 7 BP 1416 EP 1419 DI 10.1016/j.aprm.2004.10.035 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 944FR UT WOS:000230412500024 PM 16003674 ER PT J AU Burns, SP Spanier, DE AF Burns, SP Spanier, DE TI Break-technique handheld dynamometry: Relation between angular velocity and strength measurements SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE muscle spasticity; rehabilitation; reproducibility of results; spinal cord injuries ID MUSCLE STRENGTH; AGED 20; RELIABILITY; TORQUE; ACTIVATION; EXTREMITY; ADULTS; TESTS; EMG AB Objectives: To determine whether the muscle strength, as measured with break-technique handheld dynamomety (HHD), is dependent on the angular velocity achieved during testing and to compare reliability at different angular velocities. Design: Repeated-measures study. Participants underwent HHD by using make-technique (isometric) and break-technique (eccentric) dynamometry at 3 prespecified angular velocities. Elbow movement was recorded with an electrogoniometer. Setting: Inpatient spinal cord injury unit. Participants: Convenience sample of 20 persons with tetraplegia with weakness of elbow flexors or extensors. Interventions: Not applicable. Main Outcome Measures: Elbow angular velocity and muscle strength recorded during HHD. Results: With the break technique, angular velocities averaging 15 degrees, 33 degrees, and 55 degrees/s produced 16%, 30%, and 51% greater strength measurements, respectively, than velocities recorded by using the make technique (all P <.006 for comparisons between successive techniques). The intraclass correlation coefficient for intrarater reliability was.89 or greater for all testing techniques. Conclusions: Greater strength is recorded with faster angular velocities during HHD. Differences in angular velocity may explain the wide range previously reported for break- versus make-technique strength measurements. Variation in angular velocity is a potential source of variability in serial HHD strength measurements, and for this reason the make technique may be preferable. (c) 2005 by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98109 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, SCI 128,1660 S Columbian Way, Seattle, WA 98109 USA. EM spburns@u.washington.edu NR 26 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2005 VL 86 IS 7 BP 1420 EP 1426 DI 10.1016/j.apmr.2004.12.041 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 944FR UT WOS:000230412500025 PM 16003675 ER PT J AU Wagner, DD AF Wagner, DD TI New links between inflammation and thrombosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE platelets; inflammation; adhesion molecules; Weibel-Palade body ID WEIBEL-PALADE BODIES; SELECTIN-DEFICIENT MICE; HUMAN-ENDOTHELIAL CELLS; PLATELET P-SELECTIN; TISSUE FACTOR; IN-VIVO; ACTIVATED PLATELETS; ADHESION MOLECULES; CYTOPLASMIC DOMAIN; CD40 LIGAND AB This article is a summary of the Sol Sherry Lecture of the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, which was presented at the Scientific Sessions of the American Heart Association in November 2004. It highlights work from our laboratory, focusing mainly on new aspects of P-selectin and CD40L (CD154) biology and on the interplay of platelets and leukocytes in thrombosis and inflammation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R01 HL53756, P01 HL056949, P01 HL56949, R01 HL053756, R37 HL041002, R37 HL41002] NR 41 TC 106 Z9 110 U1 0 U2 4 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 JUL PY 2005 VL 25 IS 7 BP 1321 EP 1324 DI 10.1161/01.ATV.0000166521.90532.44 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 939ZH UT WOS:000230112200005 PM 15831808 ER PT J AU Purcell, S Koenen, KC AF Purcell, S Koenen, KC TI Environmental mediation and the twin design SO BEHAVIOR GENETICS LA English DT Article DE environmental mediation; maximum likelihood; regression; simulation; twins; variance components ID MULTIPLE-REGRESSION ANALYSIS; VIOLENCE; CHILDREN; NURTURE AB Behavior genetic twin designs are increasingly used to study the effects of a measured environment whilst controlling for genetic variation. In this research note, we show that, in the context of the classical twin design, (1) when the environmental variable is necessarily shared between twins, the notion of controlling for genetic influence is logically flawed and (2) when the environmental variable varies between twins in the same family, partial control for genetic influence is possible, but only if appropriate analytic models are used, which is commonly not the case. Based on a simple simulation study, recommendations are given as to which methods should be applied and which should be avoided. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Purcell, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. FU NIMH NIH HHS [1K08MH070627] NR 15 TC 41 Z9 42 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JUL PY 2005 VL 35 IS 4 BP 491 EP 498 DI 10.1007/s10519-004-1484-9 PG 8 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 938AL UT WOS:000229972200011 PM 15971029 ER PT J AU Safren, SA Otto, MW Sprich, S Winett, CL Wilens, TE Biederman, J AF Safren, SA Otto, MW Sprich, S Winett, CL Wilens, TE Biederman, J TI Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE adult attention deficit hyperactivity disorder; cognitive-behavioral therapy; randomized controlled trial ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PSYCHOSOCIAL TREATMENTS; PSYCHIATRIC STATUS; RATING-SCALE; DOUBLE-BLIND; SELF-CONTROL; CHILDREN; ADOLESCENTS; DEPRESSION AB The purpose of the present study was to examine the potential efficacy, patient acceptability, and feasibility of a novel, cognitive-behavioral therapy (CBT) for adults with attention-deficit hyperactivity disorder (ADHD) who have been stabilized on medications but still show clinically significant symptoms. Thirty-one adults with ADHD and stable psychopharmacology for ADHD were randomized to CBT plus continued psychopharmacology or continued psychopharmacology alone. Assessments included ADHD severity and associated anxiety and depression rated by an independent evaluator (IE) and by self-report. At the outcome assessment, those who were randomized to CBT had lower IE-rated ADHD symptoms (p < .01) and global severity (p < .002), as well as self-reported ADHD symptoms (p < .0001) than those randomized to continued psychopharmacology alone. Those in the CBT group also had lower IE-rated and self-report anxiety (p's < .04), lower IE-rated depression (p < .01), and a trend to have lower self-reported depression (p = .06). CBT continued to show superiority over continued psychopharmacology alone when statistically controlling levels of depression in analyses of core ADHD symptoms. There were significantly more treatment responders among patients who received CBT (56%) compared to those who did not (13%) (p < .02). These data support the hypothesis that CBT for adults with ADHD with residual symptoms is a feasible, acceptable, and potentially efficacious next-step treatment approach, worthy of further testing. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, MGH Psychiat, Sch Med, Boston, MA 02114 USA. RP Safren, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Psychiat, Sch Med, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM ssafren@partners.org FU PHS HHS [60940] NR 64 TC 180 Z9 187 U1 11 U2 47 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2005 VL 43 IS 7 BP 831 EP 842 DI 10.1016/j.brat.2004.07.001 PG 12 WC Psychology, Clinical SC Psychology GA 938JB UT WOS:000229994700001 PM 15896281 ER PT J AU Bohne, A Keuthen, NJ Tuschen-Caffier, B Wilhelm, S AF Bohne, A Keuthen, NJ Tuschen-Caffier, B Wilhelm, S TI Cognitive inhibition in trichotillomania and obsessive-compulsive disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE trichotillomania; obsessive-compulsive disorder; information processing; cognitive inhibition ID THOUGHT SUPPRESSION; ANXIETY DISORDERS; ATTENTIONAL BIAS; MEMORY; INDIVIDUALS; SCALE AB Cognitive inhibition was investigated in 21 trichotillomania (TTM), 21 obsessive-compulsive disorder (OCD) and 26 healthy control (HC) participants using a block cued directed forgetting task. After encoding a word list, participants were instructed to intentionally FORGET these words and to REMEMBER another word list. Both lists included TTM-related and neutral (kitchen-related) words in equal proportions, with the TTM-related words generally of negative valence and the kitchen-related words generally of neutral valence for all participants. A superior free recall of REMEMBER versus FORGET words suggests intact cognitive inhibition. The performance of OCD participants indicated a specific deficit in inhibiting the retrieval of information with negative valence, which was not found in TTM. HC participants, in contrast to TTM and OCD participants, were rather inattentive to negative information. In conclusion, although attention was disproportionately directed towards negative information in both disorders, cognitive inhibition deficits appeared specific to OCD. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, OCD Clin, Charlestown, MA 02129 USA. Univ Siegen, Clin Psychol, D-57068 Siegen, Germany. RP Wilhelm, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, OCD Clin, 9th Floor,149 13th St, Charlestown, MA 02129 USA. EM wilhelm@psych.mgh.harvard.edu RI Citations, TLC SAB/C-4006-2011 NR 59 TC 31 Z9 31 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2005 VL 43 IS 7 BP 923 EP 942 DI 10.1016/j.brat.2004.06.014 PG 20 WC Psychology, Clinical SC Psychology GA 938JB UT WOS:000229994700007 PM 15896287 ER PT J AU Bal, HP Cheng, JH Murakami, A Tallarico, AS Wang, W Zhou, DX Vasicek, TJ Marasco, WA AF Bal, HP Cheng, JH Murakami, A Tallarico, AS Wang, W Zhou, DX Vasicek, TJ Marasco, WA TI GITR overexpression on CD4+CD25+HTLV-1 transformed cells: Detection by massively parallel signature sequencing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE regulatory T-cells; adult T-cell leukemia; cancer; gene expression profiling; tax ID LYMPHOTROPIC VIRUS TYPE-1; REGULATORY T-CELLS; BASE-EXCISION-REPAIR; DNA-POLYMERASE-BETA; IMMUNOLOGICAL SELF-TOLERANCE; GENE-EXPRESSION PROFILES; KAPPA-B ACTIVATION; I-INFECTED CELLS; READING FRAME-I; GTP-BOUND RAN AB HTLV-1 is the etiologic agent of adult T-cell leukemia (ATL), a fatal T-cell malignancy that is associated with profound immunosuppression. In this Study, comprehensive gene expression profiling was performed using massively parallel signature sequencing (MPSS) to investigate virus-host interactions in acutely HTLV-1 transformed cells. The analysis revealed the modulation of numerous genes across different functional classes, many of which have not been previously implicated in HTLV-1 transformation or ATL. Differences in the transcriptomes of transformed cell lines were observed that have provided clues on how different clonal populations of cells respond to virus transformation. Quantitation of HTLV-1 transcription was possible, thus making MPSS a useful tool to study emerging pathogens and unknown microbial causes Of human diseases. Importantly, overexpression of GfTR, an activation marker that has not been previously reported to be upregulated by HTLV-1-infection or in transformed/leukemic cells and that is associated with the suppressor phenotype of CD4+CD25+ regulatory T-cells (Tregs), was also observed. The deep and quantitative gene expression profile generated by MPSS should provide additional leads for discovery research that can be applied to better understand the pathobiology of HTLV-1 transformation and ATL as well as to developing new therapies. (C) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Lynx Therapeut Inc, Hayward, CA 94545 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfi.harvard.edu FU NIAID NIH HHS [R21 AI053822] NR 98 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 1 PY 2005 VL 332 IS 2 BP 569 EP 584 DI 10.1016/j.bbrc.2005.04.162 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 932RY UT WOS:000229572300036 PM 15896717 ER PT J AU Banerjee Sr Maresca, KP Stephenson, KA Valliant, JF Babich, JW Graham, WA Barzana, M Dong, Q Fischman, AJ Zubieta, J AF Banerjee, SR Maresca, KP Stephenson, KA Valliant, JF Babich, JW Graham, WA Barzana, M Dong, Q Fischman, AJ Zubieta, J TI N,N-bis(2-mercaptoethyl)methylamine: A new coligand for Tc-99m labeling of hydrazinonicotinamide peptides SO BIOCONJUGATE CHEMISTRY LA English DT Review ID IIB/IIIA-RECEPTOR ANTAGONIST; TC-99M-LABELED CHEMOTACTIC PEPTIDES; INFECTION IMAGING PROPERTIES; POLYCLONAL IMMUNOGLOBULIN-G; WATER-SOLUBLE PHOSPHINES; TERNARY LIGAND COMPLEXES; STRUCTURAL-CHARACTERIZATION; TECHNETIUM RADIOPHARMACEUTICALS; IN-VITRO; MOLECULAR-STRUCTURES AB Hydrazinonicotinamide (HYNIC) forms stable coordination complexes with Tc-99m when reacted with Tc(V)oxo species such as Tc-mannitol or other Tc-polyhydric complexes. However, radio-HPLC of [Tc-For-MLFK-HYNIC] labeled via Tc-polyhydric ligands demonstrated multiple radiochemical species each with unique biodistribution patterns. This is likely due to the fact that Tc can bind to the hydrazino moiety, as well as polyhydric ligands, in a variety of coordination geometries. Tridentate ligands, such as bis(mercaptoethyl)methylamine (NS(2)), may constrain the possible coordination geometries and improve overall stability. To investigate this, we synthesized NS2, converted the [Tc-mannitol-For-MLFK-HYNIC] to the corresponding NS(2)-containing complex [Tc-NS(2)-For-MLFK-HYNIC], and compared its infection imaging and biodistribution properties with [Tc-mannitol-For-MLFK-HYNIC]. Conversion to the NS2 complex was confirmed by HPLC which showed a single unique hydrophobic species with retention time greater than the [Tc-mannitol-For-MLFK-HYNIC.] complex. Imaging experiments with both preparations were performed in rabbits with E. coli infections in the left thigh. Tissue radioactivity measurements demonstrated that compared to Tc-mannitol-peptide, accumulation of Tc-NS(2)-peptide was lower in blood, heart, and normal muscle and higher in spleen, infected muscle, and pus (p < 0.01). These results indicate that the Tc-NS2-peptide complex is chemically more homogeneous and exhibits improved infection localization and biodistribution properties. In an effort to model the interactions of the metal-HYNIC core with NS2 and related ligand types, the reactions of [ReCl(3)(NNC(5)H(4)NH)(NHNC(5)H(4)N)] and [(99)TcCl(3)(NNC(5)H(4)NH)(NHNC(5)H(4)N)], effective structural analogues for the {M(NNC(5)H(4)NH(x))(2)} core, with NS(2), C(5)H(3)N-2,6-(CH(2)SH)(2), O(CH(2)CH(2)SH)(2), and S(CH(2)CH(2)SH)(2) were investigated and the compounds [M{CH(3)N(CH(2)CH(2)S)(2)}(NNC(5)H(4)N)(NHNC(5)H(4)N] (M = 99Tc (5a), Re (5b)), [Re{C(5)H(3)N-2,6-(CH(2)S)(2)}(NNC(5)H(4)N)(NHNC(5)H(4)N)]-CH(2)Cl(2)-0.5MeOH (7), [Re{SCH(2)CH(2))(2)O} (NNC(5)H(4)N)(NHNC(5)H(4)N)] (8), and [Re{(SCH(2)CH(2))(2)S}(NNC(5)H(4)NH)(NHNC(5)H(4)N)]Cl (9) were isolated. Similarly, the reaction of [ReCl(3)(NNC(5)H(4)NH)(NHNC(5)H(4)N)] with the bidentate ligands pyridine-2-methanethiol and 3-(trimethlysilyl)pyridine-2-thiol led to the isolation of [ReCl(C(5)H(4)N-2-CH(2)S) (NNC(5)H(4)N)(NHNC(5)H(4)N)] (10) and [Re(2-SC(5)H(3)N-3-SiMe(3))(2) (NNC(5)H(4)N)(NHNC(5)H(4)N)] (11), respectively, while reaction with N-methylimidazole-2-thiol yielded the binuclear complex [Re(OH)Cl(SC(3)H(2)N(2)CH(3))(2)(NNC(5)H(4)N)(2) (NHNC(5)H(4)N)(2)] (12). The analogous metal-(HYNIC-OH) precursor, [ReC(3){NNC(5)H(3)NH(CO(2)R)} {NHNC(5)H(3)N(CO(2)R)}] (R = H, 13a; R = CH(3), 13b) has been prepared and coupled to lysine to provide [RCl(3){NNC(5)H(3)NH(CONHCH(2)CH(2)CH(2)CH(2)CH(NH(2))CO(2)H)} {NHNC(5)H(3)NH(CONHCH(2)CH(2)CH(2)CH(2)CH(NH(2))CO(2)H)}]-2HCl (14-2HCl), while the reaction of the methyl ester 13b with 2-mercaptopyridine yields [Re(2-SC(5)H(4)N)(2){NNC(5)H(3)N(CO(2)Me)} {NHNC(5)H(3)N(CO(2)Me)}] (15). While the chemical studies confirm the robustness of the M-HYNIC core (M = Tc, Re) and its persistence in ligand substitution reactions at adjacent coordination sites of the metal, the isolation of oligomeric structures and the insolubility of the peptide conjugates of 13, 14, and 15 underscore the difficulty of characterizing these materials on the macroscopic scale, an observation relevant to the persistent concerns with reagent purity and identity on the tracer level. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. McMaster Univ, Dept Chem, Hamilton, ON L8S 4M1, Canada. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA. Mol Insight Pharmaceut, Cambridge, MA USA. RP Zubieta, J (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. EM jazubiet@syr.edu NR 105 TC 15 Z9 15 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 2005 VL 16 IS 4 BP 885 EP 902 DI 10.1021/bc050040y PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 948JU UT WOS:000230712900017 PM 16029030 ER PT J AU Cutler, C Henry, NL Magee, C Li, SL Kim, HT Alyea, E Ho, V Lee, SJ Soiffer, R Antin, YH AF Cutler, C Henry, NL Magee, C Li, SL Kim, HT Alyea, E Ho, V Lee, SJ Soiffer, R Antin, YH TI Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE thrombotic microangiopathy; hematopoictic stem cell transplantation; sirolimus; calcineurin inhibitor ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; HEMOLYTIC-UREMIC SYNDROME; ACUTE-RENAL-FAILURE; THROMBOCYTOPENIC PURPURA; MINIDOSE METHOTREXATE; PROPHYLAXIS REGIMENS; CLINICAL-OUTCOMES; CYCLOSPORINE; TACROLIMUS AB Thrombotic microangiopathy (TMA) may occur after allogeneic hematopoietic stem cell transplantation (HSCT) and is related in part to calcineurin inhibitor toxicity. We observed a higher-than-expected rate of TMA when calcineurin inhibitors were combined with sirolimus. To determine the incidence of and risk factors for TMA after HSCT, we performed a retrospective cohort analysis of myeloalblative allogeneic HSCT recipients between 1997 and 2003. TMA diagnosis required the simultaneous occurrence of (1) creatinine increase > 2 mg/dL or > 50% above baseline, (2) schistocytosis, (3) increased lactate dehydrogenase, and (4) no evidence of disseminated intravascular coagulopathy. A total of 111 sirolimus-exposed subjects were compared with 216 nonexposed subjects after HSCT. TMA occurred in 10.8% of the sirolimus group and 4.2% in the nonsirolimus group (odds ratio, 2.79; P =.03). Sirolimus exposure was associated with TMA earlier than in nonsirolimus patients (25 versus 58 days; P =.04). Only the use of sirolimus (exact odds ratio, 3.49; P =.02) and grade II to IV acute graft-versus-host disease (exact odds ratio, 6.60; P =.0002) were associated with TMA in regression analyses. Treatment of TMA varied among affected individuals. Renal recovery was complete in 92% of sirolimus-treated patients. Overall survival after TMA diagnosis was better for sirolimus subjects than for nonsirolimus subjects (58.3% versus 11.1%; P =.02). Sirolimus seems to potentiate the effects of calcineurin inhibitors on TMA after HSCT. TMA associated with sirolimus seems reversible and has a favorable prognosis when compared with TMA associated with calcineurin inhibitors alone. A careful monitoring strategy for TMA should be used with a sirolimus-containing graft-versus-host disease prophylaxis regimen. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Nephrol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149-01A1] NR 51 TC 80 Z9 80 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2005 VL 11 IS 7 BP 551 EP 557 DI 10.1016/j.bbmt.2005.04.007 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 944KD UT WOS:000230425500008 PM 15983555 ER EF