FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Moran, LR Almeida, PG Huttner, KM AF Moran, LR Almeida, PG Huttner, KM TI Intrauterine Baclofen exposure: A Multidisciplinary approach SO PEDIATRICS LA English DT Article DE baclofen; pregnancy; neonate withdrawal; multidisciplinary ID INTRATHECAL BACLOFEN; SEVERE SPASTICITY; WITHDRAWAL; CONVULSIONS; PREGNANCY; INFUSION AB Maternal use of the antispasmodic baclofen during pregnancy is an uncommon clinical scenario and leads to uncertainty regarding neonatal risks. We present a team-based, peripartum management plan designed for safe monitoring and minimizing the risk of neonatal withdrawal after unusual drug exposure. Incorporating the expertise of neonatology, nursing, pharmacy, neurology, and the lactation service, as well as parental input, this consensus approach was implemented in a case of maternal oral baclofen use with a successful outcome for the infant and family. C1 Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. MassGen Hosp Children, Dept Pediat, Div Newborn Med, Boston, MA USA. MassGen Hosp Children, Patient Care Serv, Boston, MA USA. RP Moran, LR (reprint author), Massachusetts Gen Hosp, Dept Pharm GB005, 55 fruit St, Boston, MA 02114 USA. EM lrmoran@partners.org NR 17 TC 8 Z9 8 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2004 VL 114 IS 2 BP 267 EP 269 PG 3 WC Pediatrics SC Pediatrics GA 842YG UT WOS:000223040000063 ER PT J AU Wang, ML Dorer, DJ Fleming, MP Catlin, EA AF Wang, ML Dorer, DJ Fleming, MP Catlin, EA TI Clinical outcomes of near-term infants SO PEDIATRICS LA English DT Article DE neonate; outcome; prematurity; near term; costs; newborn ID JAUNDICE; PREMATURITY; MANAGEMENT; PREVENTION; BIRTH; CARE AB Objective. To test the hypothesis that near-term infants have more medical problems after birth than full-term infants and that hospital stays might be prolonged and costs increased. Methods. Electronic medical record database sorting was conducted of 7474 neonatal records and subset analyses of near-term (n = 120) and full-term (n = 125) neonatal records. Cost information was accessed. Length of hospital stay, Apgar scores, clinical diagnoses (temperature instability, jaundice, hypoglycemia, suspicion of sepsis, apnea and bradycardia, respiratory distress), treatment with an intravenous infusion, delay in discharge to home, and hospital costs were assessed. Results. Data from 90 near-term and 95 full-term infants were analyzed. Median length of stay was similar for near-term and full-term infants, but wide variations in hospital stay were documented for near-term infants after both vaginal and cesarean deliveries. Near-term and full-term infants had comparable 1- and 5-minute Apgar scores. Nearly all clinical outcomes analyzed differed significantly between near-term and full-term neonates: temperature instability, hypoglycemia, respiratory distress, and jaundice. Near-term infants were evaluated for possible sepsis more frequently than full-term infants (36.7% vs 12.6%; odds ratio: 3.97) and more often received intravenous infusions. Cost analysis revealed a relative increase in total costs for near-term infants of 2.93 ( mean) and 1.39 ( median), resulting in a cost difference of $2630 (mean) and $429 (median) per near-term infant. Conclusions. Near-term infants had significantly more medical problems and increased hospital costs compared with contemporaneous full-term infants. Near-term infants may represent an unrecognized at-risk neonatal population. C1 MassGen Hosp Children, Serv Pediat, Neonatol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. Partners HealthCare, Serv Line Anal, Boston, MA USA. RP Wang, ML (reprint author), MassGen Hosp Children, Serv Pediat, Neonatol Unit, Founders 442,Fruit St, Boston, MA 02114 USA. EM mwang1@partners.org NR 15 TC 312 Z9 330 U1 1 U2 10 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 2004 VL 114 IS 2 BP 372 EP 376 DI 10.1542/peds.114.2.372 PG 5 WC Pediatrics SC Pediatrics GA 842YG UT WOS:000223040000007 PM 15286219 ER PT J AU Piqueras, L Tache, Y Martinez, V AF Piqueras, L Tache, Y Martinez, V TI Galanin inhibits gastric acid secretion through a somatostatin-independent mechanism in mice SO PEPTIDES LA English DT Article DE galanin; somatostatin; somatostatin receptors; SSTR2; acid secretion; immunoneutralization; pentagastrin ID BOMBESIN-INDUCED INHIBITION; PERFUSED RAT STOMACH; GASTROINTESTINAL-TRACT; MONOCLONAL-ANTIBODY; ANESTHETIZED RATS; HISTAMINE-RELEASE; RECEPTOR SUBTYPE; CONSCIOUS RATS; CELLS; INTESTINE AB The role of somatostatin in galanin-induced inhibition of gastric acid secretion in urethane-anesthetized mice was investigated by using immunoneutralization of endogenous somatostatin and somatostatin receptor type 2 (SSTR2) knockout mice. Intravenous galanin (10 and 20 mug/kg/h) inhibited pentagastrin-stimulated gastric acid secretion by 47 and 33%, respectively. Somatostatin antibody injected i.v. increased acid secretion by 3.5-fold over basal levels but did not modify the antisecretory effects of galanin. Urethane-anesthetized SSTR2 knockout mice had a basal secretion 14-fold higher than wild-type animals, that was inhibited by galanin (10 and 20 mug/kg/h) by 49 and 31% respectively. In mice galanin inhibits gastric acid secretion through a somatostatin-independent mechanism. (C) 2004 Elsevier Inc. All rights reserved. C1 Cardenal Herrera CEU Univ, Dept Physiol Pharmacol & Toxicol, Valencia, Spain. Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Digest Dis Res Ctr, Dept Med & Brain Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womans Hlth, Los Angeles, CA USA. RP Martinez, V (reprint author), AstraZeneca R&D, SE-43183 Molndal, Sweden. EM vicente.martinez@astrazeneca.com RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-41301] NR 38 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD AUG PY 2004 VL 25 IS 8 BP 1287 EP 1295 DI 10.1016/j.peptides.2004.06.003 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 854TQ UT WOS:000223926700008 PM 15350696 ER PT J AU Niccolai, CS Hicks, RW Oertel, L Francis, JL AF Niccolai, CS Hicks, RW Oertel, L Francis, JL CA Heparin Consensus Grp TI Unfractionated heparin: Focus on a high-alert drug SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Meeting on Consensus on Contemporary Issues with Unfractionated Heparin CY OCT 29-30, 2003 CL Pittsburgh, PA DE unfractionated heparin; medication errors; drug-related problems; heparin-induced thrombocytopenia; bleeding events; osteopenia ID MOLECULAR-WEIGHT HEPARINS; DEEP VENOUS THROMBOSIS; INDUCED THROMBOCYTOPENIA; RANDOMIZED-TRIAL; MYOCARDIAL-INFARCTION; METAANALYSIS; THROMBOEMBOLISM; ENOXAPARIN; MANAGEMENT; PREVENTION AB Unfractionated heparin (UFH) is associated with a high rate of drug-related problems due to either its inherent pharmacologic properties or an extension of these properties often caused by medication errors. The drug-related problems associated with UFH can significantly hinder the success of therapy and negatively affect the overall cost of care. Unfractionated heparin has been classified as a high-alert drug by the Institute for Safe Medication Practices. Approximately 2.1% of the total records submitted to the MedMARx national error database were related to UFH; 4.5-5.5% of these errors reported were harmful. With this high potential for error, it is essential that all health care providers adopt a collaborative or systems approach to identify solutions to reduce the occurrence of these medication errors. The joint Commission on Accreditation of Healthcare Organizations has published national patient safety goals for improving the safety of patient care, many of which are applicable to UFH therapy. Unfractionated heparin drug-related problems not necessarily related to medication errors include heparin-induced thrombocytopenia, bleeding events, and osteopenia. Heparin-induced thrombocytopenia is a serious complication of heparin therapy and remains seriously undiagnosed. Bleeding events often occur with therapeutic as well as prophylactic UFH administration even when monitoring indexes are within the therapeutic range. However, due to the variability associated with UFH monitoring methods, definitive guidelines are lacking to assist in avoiding such serious events. Osteopenia has been associated with long-term UFH therapy; one third of patients experience reductions in bone density, potentially leading to fractures. Today, safer alternative anticoagulation therapies are available, such as the low-molecular-weight heparins. When compared with UFH, these alternative therapies provide equivalent or superior efficacy for numerous indications. C1 Univ Pharmacotherapy Associates LLC, Monroeville, PA 15146 USA. US Pharmacopeia, Rockville, MD USA. Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. Florida Hosp, Ctr Thrombosis & Hemostasis, Orlando, FL USA. RP Niccolai, CS (reprint author), Univ Pharmacotherapy Associates LLC, 1405 Monroeville Blvd, Monroeville, PA 15146 USA. EM cniccolai@UPA-LLC.com NR 57 TC 6 Z9 6 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2004 VL 24 IS 8 SU S BP 146 EP 155 PN 2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 843QQ UT WOS:000223099900008 ER PT J AU Oertel, LB AF Oertel, LB CA Heparin Consensus Grp TI Unfractionated heparin: A nursing dilemma SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Meeting on Consensus on Contemporary Issues with Unfractionated Heparin CY OCT 29-30, 2003 CL Pittsburgh, PA DE unfractionated heparin; drug therapy; nursing ID ADVERSE DRUG EVENTS; PATIENT MORTALITY; ERRORS; SAFETY AB Nurses face challenges in all aspects of their practice, especially with administering and monitoring drugs in a safe, effective manner. Key factors known to affect drug administration include general drug knowledge, formal nurse education, continuing education needs, clinical experience, and the nationwide nursing shortage. Other factors are advances in technologic aids and quality improvement initiatives. Emphasis on patient safety is growing, especially as it relates to drug therapy and high-alert drugs such as unfractionated heparin (UFH). Specific interventions related to UFH administration can enhance patient care management. Because nurses are at the site of direct patient care, they are often in an opportune position for identifying medication errors. At the same time, and most important, nurses need to collaborate with other health care professionals to actively develop solutions to minimize these errors. Adopting a systems approach and working collaboratively with an interdisciplinary team can result in improved patient outcomes. C1 Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. RP Oertel, LB (reprint author), Massachusetts Gen Hosp, Anticoagulat Management Serv, Clin 144,55 Fruit St, Boston, MA 02114 USA. EM loertel@partners.org NR 14 TC 0 Z9 0 U1 3 U2 4 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2004 VL 24 IS 8 SU S BP 156 EP 160 PN 2 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 843QQ UT WOS:000223099900009 ER PT J AU Kim, TG Ruprecht, R Langridge, WHR AF Kim, TG Ruprecht, R Langridge, WHR TI SIVmac Gag p27 capsid protein gene expression in potato SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE SIVma Gag; Solanum tuberosum; edible vaccine; immune response; HIV ID TOXIN-B-SUBUNIT; T-LYMPHOCYTE ACTIVITY; VIRUS TYPE-1 INFECTION; NSP4 FUSION PROTEIN; TRANSGENIC POTATO; SURFACE-ANTIGEN; INFLUENZA-VIRUS; HIV TYPE-1; PLANTS; IMMUNOGENICITY AB A cDNA encoding the Simian immunodeficiency virus type (SIVmac) Gag capsid protein was introduced into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated transformation methods. The gag gene was detected in the genomic DNA of transformed leaf tissues by PCR DNA amplification. Immunoblot analysis of transformed potato plant extracts with anti-Gag monoclonal antibody showed that biologically active Gag protein was synthesized in transformed tuber tissues. Based on ELISA results, recombinant Gag protein made up 0.006-0.014% of total soluble tuber protein. The synthesis of SIV Gag in transformed potato tubers opens the way for development of Gag-based edible plant vaccines for protection against SIV and potentially HIV-1 infection. (C) 2004 Elsevier Inc. All rights reserved. C1 Loma Linda Univ, Sch Med, Ctr Mol Biol & Gene Therapy, Dept Biochem & Microbiol, Loma Linda, CA 92350 USA. Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA 02115 USA. RP Langridge, WHR (reprint author), Loma Linda Univ, Sch Med, Ctr Mol Biol & Gene Therapy, Dept Biochem & Microbiol, Loma Linda, CA 92350 USA. EM blangridge@som.llu.edu FU NIDDK NIH HHS [DK-99-013] NR 33 TC 4 Z9 4 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD AUG PY 2004 VL 36 IS 2 BP 312 EP 317 DI 10.1016/j.pep.2004.04.015 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 840MO UT WOS:000222863100020 PM 15249055 ER PT J AU Cocklin, S Zurawski, JA Cocklin, SL Sodroski, JG Chaiken, IM AF Cocklin, S Zurawski, JA Cocklin, SL Sodroski, JG Chaiken, IM TI CCR5 conformation is intimately associated with its lipid environment SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 18th Symposium of the Protein-Society CY AUG 14-18, 2004 CL San Diego, CA SP Protein Soc, Abbott Lab Fund, Amer Peptide Soc, Amgen, Biogen Idec, DARPA, Eli Lilly & Co, Eli Lilly Res Labs, Biotechnol Discovery Res, Genencor Int, Genentech Inc, Merck Res Labs, Natl Sci Fdn, NIH, New England BioLabs, Novartis Inst Biomed Res, Pfizer Inc, Protein Soc Educ Comm, Protein Soc Young Protein Sci Comm, Roche Pharmaceut, Sunesis Pharmaceut Inc ID PROTEIN-COUPLED RECEPTORS; SURFACE-PLASMON RESONANCE; RECONSTITUTION C1 Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 2004 VL 13 SU 1 MA 437 BP 194 EP 194 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 866TL UT WOS:000224796100438 ER PT J AU Banta, SA Casali, M Kelley, Z Mavroidis, C Yarmush, ML AF Banta, SA Casali, M Kelley, Z Mavroidis, C Yarmush, ML TI Site-directed mutagenesis of a peptide from the hemagglutinin protein of the influenza virus: potential application for nanorobotics SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 18th Symposium of the Protein-Society CY AUG 14-18, 2004 CL San Diego, CA SP Protein Soc, Abbott Lab Fund, Amer Peptide Soc, Amgen, Biogen Idec, DARPA, Eli Lilly & Co, Eli Lilly Res Labs, Biotechnol Discovery Res, Genencor Int, Genentech Inc, Merck Res Labs, Natl Sci Fdn, NIH, New England BioLabs, Novartis Inst Biomed Res, Pfizer Inc, Protein Soc Educ Comm, Protein Soc Young Protein Sci Comm, Roche Pharmaceut, Sunesis Pharmaceut Inc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Harvard Univ, Shriners Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 2004 VL 13 SU 1 MA 476 BP 207 EP 207 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 866TL UT WOS:000224796100477 ER PT J AU Kilbourne, AM Haas, GL Mulsant, BH Bauer, MS Pincus, HA AF Kilbourne, AM Haas, GL Mulsant, BH Bauer, MS Pincus, HA TI Concurrent psychiatric diagnoses by age and race among persons with bipolar disorder SO PSYCHIATRIC SERVICES LA English DT Article ID AFRICAN-AMERICAN AB The authors characterized concurrent psychiatric diagnoses among patients with a diagnosis of bipolar disorder who were in routine care by using administrative data from a Department of Veterans Affairs facility. Of 813 patients who had a diagnosis of bipolar disorder in 2000, 21 percent were older (greater than or equal to60 years) whites, and 2 percent were older African Americans. Older African Americans were the most likely to have a diagnosis of schizophrenia documented in the medical record compared with younger African Americans, older whites, and younger whites (67 percent, 34 percent, 38 percent, and 27 percent, respectively). The results suggest that older African-American patients with bipolar disorder are more likely to receive diagnoses of mutually exclusive conditions, such as schizophrenia, and thus appear to have an elevated risk of their illness being underrecognized or misdiagnosed and receiving inappropriate treatment. C1 VA Pittsburgh Ctr Hlth Equity Res & Promot, Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. VA Providence Med Ctr, Providence, RI USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RAND Corp, Univ Pittsburgh, Hlth Inst, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Ctr Hlth Equity Res & Promot, Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Mailstop 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM amy.kilbourne@med.va.gov FU NIMH NIH HHS [MH-30915] NR 8 TC 17 Z9 17 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, 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 2004 VL 55 IS 8 BP 931 EP 933 DI 10.1176/appi.ps.55.8.931 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 843BX UT WOS:000223051500013 PM 15292544 ER PT J AU Kano, Y Ohta, M Nagai, Y Pauls, DL Leckman, JF AF Kano, Y Ohta, M Nagai, Y Pauls, DL Leckman, JF TI Obsessive-compulsive symptoms in parents of Tourette syndrome probands and autism spectrum disorder probands SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE autism spectrum disorders; genetics; obsessive-compulsive symptoms; Tourette syndrome ID FAMILY; CHILDREN; SCALE AB Obsessive-compulsive symptoms (OCS) frequently occur in patients with Tourette syndrome (TS) and autism spectrum disorders (ASD). It has been suggested that genetic factors play a role in the transmission of both TS and ASD and that obsessive-compulsive disorder (OCD) may have some genetic relationship with these disorders. The objective of this study was to explore whether the OCS associated with TS and ASD were found in the parents of TS and ASD probands by comparing them with normal controls. The subjects were parents of 13 TS and 16 ASD probands. All parents underwent an examination for tic symptoms and OCD, and completed the Maudsley Obsessional Compulsive Inventory (MOCI) and State-Trait Anxiety Inventory (STAI). No significant differences were observed in the MOCI and STAI scores among all three groups. However, the MOCI total score was higher in fathers of ASD probands than in male normal controls with a marginal significance. There was a significant tendency for the mean cleaning score of MOCI in fathers of ASD probands to be higher than that in male normal controls, and the mean checking score in fathers of ASD probands was fourfold higher than that in male normal controls, although there was no significant difference. No significant relationship was observed between OCS in TS or ASD probands and OCS of their parents. Further studies on OCD and OCS including a dimensional approach within ASD families are needed. C1 Kitasato Univ, Grad Sch Med Sci, Sagamihara, Kanagawa 2288555, Japan. Tokyo Gakugei Univ, Res Inst Educ Except Children, Tokyo, Japan. Univ Shizuoka, Sch Nursing, Shizuoka, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. RP Kano, Y (reprint author), Kitasato Univ, Grad Sch Med Sci, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan. EM yukiko-k@kitasato-u.ac.jp NR 22 TC 9 Z9 9 U1 1 U2 5 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1323-1316 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PD AUG PY 2004 VL 58 IS 4 BP 348 EP 352 DI 10.1111/j.1440-1819.2004.01266.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 842DE UT WOS:000222982400002 PM 15298645 ER PT J AU Monuteaux, MC Fitzmaurice, G Blacker, D Buka, SL Biederman, J AF Monuteaux, MC Fitzmaurice, G Blacker, D Buka, SL Biederman, J TI Specificity in the familial aggregation of overt and covert conduct disorder symptoms in a referred attention-deficit hyperactivity disorder sample SO PSYCHOLOGICAL MEDICINE LA English DT Article ID MULTIVARIATE LOGISTIC-REGRESSION; EARLY MATERNAL REJECTION; AGE-OF-ONSET; ENVIRONMENTAL-INFLUENCES; REGULATORY POLYMORPHISM; ANTISOCIAL ALCOHOLISM; RELATIONAL AGGRESSION; CHILD PSYCHOPATHOLOGY; OPPOSITIONAL DEFIANT; BIRTH COMPLICATIONS AB Background. To examine the familial associations of overt and covert antisocial behavior within the diagnosis of conduct disorder (CD) in families ascertained by referred children with attention-deficit hyperactivity disorder (ADHD), and to test if these familial associations differed between male and female probands. Method. Subjects were clinically-referred male and female ADHD children (n = 273) and their first-degree biological relatives (n = 807). Scores for overt and covert conduct problems were calculated by summing the DSM-III-R conduct disorder symptoms, as derived from structured diagnostic interviews. Familial aggregation analyses were conducted with multivariate regression modeling methodology. Results. Proband overt scores significantly predicted the overt scores of their relatives, and proband covert scores significantly predicted the covert scores of their relatives. There was no evidence of covert symptom scores predicting overt scores or vice versa. There was some evidence that the aggregation of covert symptoms was stronger in the families of female probands. Conclusions. These results provide preliminary evidence that overt and covert conduct disorder symptoms are independently transmitted through families and may represent distinct familial syndromes. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Monuteaux, MC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM mmonuteaux@partners.org RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 74 TC 18 Z9 18 U1 5 U2 7 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 2004 VL 34 IS 6 BP 1113 EP 1127 DI 10.1017/S0033291703001788 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 857GL UT WOS:000224104300015 PM 15554581 ER PT J AU Cubells, JF Zabetian, CP AF Cubells, JF Zabetian, CP TI Human genetics of plasma dopamine beta-hydroxylase activity: applications to research in psychiatry and neurology SO PSYCHOPHARMACOLOGY LA English DT Review DE catecholamines; norepinephrine; quantitative trait locus; sympathetic nervous system; psychosis; depression; alcoholism; attention deficit hyperactivity disorder; Parkinson's disease; hypotension ID DEFICIT HYPERACTIVITY DISORDER; MULTIPLE SYSTEM ATROPHY; IDIOPATHIC PARKINSONS-DISEASE; PREFRONTAL CORTICAL FUNCTION; GENOTYPE-CONTROLLED ANALYSIS; PLATELET MONOAMINE-OXIDASE; EMOTIONALLY-DISTURBED BOYS; POLYMORPHIC (GT)(N) REPEAT; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE AB Rationale: Norepinephrine (NE) is a key neurotransmitter in the central and peripheral nervous systems. Dopamine beta-hydroxylase (DbetaH) catalyzes the synthesis of NE from dopamine (DA) and occurs in the plasma as a stable heritable trait. Studies of this trait have been useful in psychiatric and neurological research. Objective: To selectively and critically review the literature on plasma DbetaH, and on recent progress understanding the molecular genetic basis for its inheritance. Based on this review, directions for future research in psychiatry and neurology will be suggested. Methods: We selectively review the literature on the biochemical and molecular genetics of plasma DbetaH activity, as well as research on plasma and cerebrospinal fluid (CSF) DbetaH in psychiatric and neurological disorders. Results: Strong evidence implicates DBH, the structural locus encoding DbetaH enzyme, as the major quantitative trait locus influencing plasma DbetaH activity, with one single nucleotide polymorphism (SNP) accounting for up to 50% of the variance. Mutations at DBH appear to be responsible for the rare syndrome of DbetaH deficiency. Some biochemical and genetic studies suggest associations between low plasma or CSF DbetaH and psychotic symptoms in several psychiatric disorders. Studies combining genotyping at DBH with biochemical measurement of plasma DbetaH have proven useful in studies of schizophrenia, cocaine-induced paranoia (CIP), depression, attention deficit hyperactivity disorder, and alcoholism. Such studies may also elucidate the contribution of noradrenergic dysfunction to a variety of symptoms in Parkinson's disease and other degenerative neurological disorders. Conclusions: A model is proposed, in which lower levels of DbetaH protein may lead to elevated ratios of DA to NE. This model may explain associations between lower plasma DbetaH activity and vulnerability to psychotic symptoms. Genotype-controlled analysis of plasma DbetaH holds promise for promoting further progress in research on psychiatric and neurological disorders. C1 Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. VA Connecticut Hlth Care Syst, West Haven, CT 06516 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Cubells, JF (reprint author), Yale Univ, Sch Med, Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM jcubells@genetics.emory.edu FU NIDA NIH HHS [K12 DA 00089, K02 DA 15766, R01 DA 12422]; NINDS NIH HHS [K08 NS 44138] NR 138 TC 109 Z9 124 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2004 VL 174 IS 4 BP 463 EP 476 DI 10.1007/s00213-004-1840-8 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 848NM UT WOS:000223474400004 PM 15088079 ER PT J AU Kalra, MK Maher, MM Toth, TL Kamath, RS Halpern, EF Saini, S AF Kalra, MK Maher, MM Toth, TL Kamath, RS Halpern, EF Saini, S TI Comparison of z-axis automatic tube current modulation technique with fixed tube current CT scanning of abdomen and pelvis SO RADIOLOGY LA English DT Article DE abdomen; CT; computed tomography (CT); radiation exposure; computed tomography (CT); thin section; pelvis; CT ID DOSE REDUCTION; COMPUTED-TOMOGRAPHY; SPIRAL-CT; ONLINE MODULATION; IMAGE QUALITY AB PURPOSE: To compare image quality, diagnostic acceptability, and radiation exposure associated with 16-section multi-detector row computed tomographic (CT) examinations of abdomen and pelvis performed with z-axis modulation technique of automatic tube current modulation and with manual selection of fixed tube current. MATERIALS AND METHODS: Sixty-two consecutive subjects (mean age, 60 years; age range, 19-84 years; male-to-female ratio, 35:27) underwent follow-up CT of abdomen and pelvis with use of a 16-section multi-detector row scanner and z-axis modulation technique (10.5-12.0-HU noise index, 10-380 mA). Scanning parameters included 140 kVp, 0.5-1.0-second gantry rotation time, 0.938:1 beam pitch, and 5-mm reconstructed section thickness. For each subject, images obtained with z-axis modulation were compared with previous images obtained with fixed tube current (200-300 mA) and with other parameters identical. Images were compared for noise and diagnostic acceptability by two subspecialty radiologists using a five-point scale (1, unacceptable; 3, acceptable; 5, excellent) at five levels: upper liver at diaphragm, porta hepatis, right kidney hilum, iliac crest, and upper margin of acetabulum. Tube current and gantry rotation time used for acquisitions at these levels were recorded. Data were analyzed with parametric and nonparametric statistical tests. RESULTS: Although no significant differences were found (P = .34), images acquired with z-axis modulation at the levels of the upper liver (diaphragm) and acetabulum had a higher noise and lower diagnostic quality, compared with images acquired with fixed tube current. Compared with fixed tube current, z-axis modulation resulted in tube current-time product reduction in 54 (87%) of 62 examinations (mean reduction, 71.2 mAs) and increase in eight (13%) (mean increase, 17.0 mAs). CONCLUSION: Compared with manually selected fixed tube current, z-axis automatic tube current modulation resulted in reduced tube current-time product and similar image noise and diagnostic acceptability at CT of abdomen and pelvis. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kalra@yahoo.com NR 13 TC 109 Z9 112 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 2004 VL 232 IS 2 BP 347 EP 353 DI 10.1148/radiol.2322031304 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 840EI UT WOS:000222839500009 PM 15286306 ER PT J AU Alderson, PO Bresolin, LB Becker, GJ Thrall, JH Dunnick, NR Hillman, BJ Lee, JKT Nagy, EC AF Alderson, PO Bresolin, LB Becker, GJ Thrall, JH Dunnick, NR Hillman, BJ Lee, JKT Nagy, EC TI Enhancing research in academic radiology departments: Recommendations of the 2003 consensus conference SO RADIOLOGY LA English DT Article DE radiology and radiologists; departmental management; radiology and radiologists; research; radiology and radiologists; socioeconomic issues; special reports ID AMERICAN-COLLEGE; IMAGING NETWORK AB Opportunities for funded radiologic research are greater than ever, and the amount of federal funding coming to academic radiology departments is increasing. Even so, many medical school-based radiology departments have little or no research funding. Accordingly, a consensus panel was convened to discuss ways to enhance research productivity and broaden the base of research strength in as many academic radiology departments as possible. The consensus panel included radiologists who have leadership roles in some of the best-funded research departments, radiologists who direct other funded research programs, and radiologists with related expertise. The goals of the consensus panel were to identify the attributes associated with successful research programs and to develop an action plan for radiology research based on these characteristics. (C) RSNA, 2004. C1 Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10032 USA. Radiol Soc N Amer, Oak Brook, IL USA. Miami Cardiac & Vasc Inst, Dept Radiol, Miami, FL USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Virginia, Dept Radiol, Charlottesville, VA USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Acad Radiol Res, Washington, DC 20005 USA. RP Alderson, PO (reprint author), Columbia Univ, Med Ctr, Dept Radiol, 622 W 168th St, New York, NY 10032 USA. EM poa1@columbia.edu; Acadrad@aol.com NR 8 TC 18 Z9 19 U1 0 U2 4 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 2004 VL 232 IS 2 BP 405 EP 408 DI 10.1148/radiol.2322040305 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 840EI UT WOS:000222839500016 PM 15286311 ER PT J AU Kalra, MK Maher, MM Toth, TL Kamath, RS Halpern, EF Saini, S AF Kalra, MK Maher, MM Toth, TL Kamath, RS Halpern, EF Saini, S TI Radiation from "extra" images acquired with abdominal and/or pelvic CT: Effect of automatic tube current modulation SO RADIOLOGY LA English DT Article DE abdomen; CT; computed tomography (CT); radiation exposure; computed tomography (CT); thin section; pelvis; CT; special reports ID NOISE-REDUCTION FILTERS; COMPUTED-TOMOGRAPHY; ONLINE MODULATION; DOSE REDUCTION; STRATEGIES AB PURPOSE: To retrospectively determine the number and usefulness of images acquired beyond the intended anatomic area of interest with abdominal and/or pelvic computed tomography (CT) and to assess the effect of automatic tube current modulation (ATCM) on associated radiation. MATERIALS AND METHODS: Superior and inferior levels at routine abdominal and/or pelvic CT were defined as the dome of the diaphragm and the inferior margin of the pubic symphysis, respectively. Records of 106 consecutive examinations (male-to-female ratio, 45:61; age range, 21-86 years) performed from June I to June 30, 2003, were reviewed to determine the number of "extra" images. Sixty-two abdominal and/or pelvic CT examinations performed concurrently with chest or thigh CT or for trauma were not included in the 106. Abdominal and/or pelvic CT was performed with either ATCM (n = 44) or manual selection of tube current (n = 62). CT parameters recorded for each extra image included tube current, peak kilovoltage, and gantry rotation time. Mean and median tube current-time products were calculated for extra images. Extra images were analyzed for pathologic findings. Statistical analysis was performed with the Student t test. RESULTS: Extra images were acquired above the dome of the diaphragm in 103 (97%) of 106 examinations and below the pubic symphysis in 100 (94%) of 106. A total of 1,280 extra images were acquired in 106 examinations (mean, 12 images per examination). Nineteen additional findings were observed on extra images. With ATCM, mean tube current-time product was 74.5 and 120.6 mAs for extra images acquired above the diaphragm and below the pubic symphysis, respectively; with manual selection, mean tube current-time products were 167.5 and 168.3 mAs (P < .05). CONCLUSION: Most extra images acquired at abdominal and/or pelvic CT contributed no additional information. With ATCM, the radiation dose was reduced by a mean of 56% (median, 72%) for extra images above the diaphragm and 29% (median, 36%) for images below the pubic symphysis, compared with dose levels with manual selection. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kalra@yahoo.com NR 12 TC 34 Z9 40 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2004 VL 232 IS 2 BP 409 EP 414 DI 10.1148/radiol.2322031151 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 840EI UT WOS:000222839500017 PM 15286312 ER PT J AU Wright, DL Eroglu, A Toner, M Toth, TL AF Wright, DL Eroglu, A Toner, M Toth, TL TI Use of sugars in cryopreserving human oocytes SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article; Proceedings Paper CT Symposium on Current Concepts, Treatment and Ovulation Induction CY SEP, 2003 CL Antalya, TURKEY DE birth; human; oocyte cryopreservation; slow freezing; sugar vitrification ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION; INTRACELLULAR TREHALOSE IMPROVES; EMBRYO TRANSFER PROGRAM; MOUSE OOCYTES; DESICCATION TOLERANCE; MEIOTIC SPINDLE; MICROINJECTED TREHALOSE; MAMMALIAN-CELLS; FREEZING MEDIUM AB In the last 20 years, a worldwide effort to cryopreserve oocytes has resulted in 40 infants and approximately 50 ongoing pregnancies being reported. While the ability to freeze human embryos has become a standard of practice in assisted reproductive technologies, obtaining reliable techniques for oocyte cryopreservation has been more difficult. The unique properties of the mature oocyte, such as the meiotic stage with sensitive spindle structure as well as the large cell volume are responsible for the limited success obtained to date. There have been two approaches to cryopreserving the oocyte: (i) slow freeze-rapid thaw, and (ii) vitrification protocols with rapid cooling-rapid warming. Both methods have incorporated sugars (sucrose) as a beneficial non-permeating extracellular cryoprotectant. Studies of organisms that survive extreme conditions of freezing/dehydration have demonstrated the ability to accumulate intracellular sugars to afford protection and survival. A novel technique using microinjection of sugars into the oocyte for cryopreservation has been developed as an alternative approach to external addition of sugars. Freezing the human oocyte has been a challenging goal: however, developing research and efforts will, in the near future, provide women with an important option for their reproductive health. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA 02189 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Burn Hosp,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Wright, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, 55 Fruit St,VBK 220, Boston, MA 02189 USA. EM dwright4@partners.org NR 66 TC 38 Z9 40 U1 1 U2 5 PU REPRODUCTIVE HEALTHCARE LTD PI CAMBRIDGE PA DUCK END FARM, DRY DRAYTON, CAMBRIDGE, CB3 8DB, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD AUG PY 2004 VL 9 IS 2 BP 179 EP 186 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 888QA UT WOS:000226388100011 PM 15333248 ER PT J AU Reusch, JEB Watson, PA AF Reusch, JEB Watson, PA TI Loss of CREB regulation of vascular smooth muscle cell quiescence in diabetes SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article ID CAMP-RESPONSE ELEMENT; FACTOR-ALPHA-RECEPTOR; BINDING PROTEIN-DELTA; ARTERIAL-WALL THICKNESS; GROWTH-FACTOR; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; IN-VIVO; ADIPOCYTE DIFFERENTIATION; PROMOTER ACTIVITY C1 Univ Colorado, Boulder, CO 80309 USA. Amer Federat Med Res, Denver VA Med Ctr, Denver, CO USA. RP Reusch, JEB (reprint author), Univ Colorado, Boulder, CO 80309 USA. EM Jane.Reusch@uchsc.edu FU NHLBI NIH HHS [HL56481]; NIDDK NIH HHS [DK57516] NR 69 TC 11 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC PUBL 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 2004 VL 5 IS 3 BP 209 EP 219 DI 10.1023/B:REMD.0000032409.13963.bc PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 840SS UT WOS:000222880500004 PM 15211092 ER PT J AU Wong, AL Harker, JO Mittman, BS Levy, GD Bulpitt, KJ Colburn, KK Liu, HH Kahn, KL Hahn, BH Paulus, HE Rubenstein, LZ AF Wong, AL Harker, JO Mittman, BS Levy, GD Bulpitt, KJ Colburn, KK Liu, HH Kahn, KL Hahn, BH Paulus, HE Rubenstein, LZ TI Development and evaluation of a patient self-report case-finding method for rheumatoid arthritis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE rheumatoid arthritis; case finding; self-report; survey ID CYCLIC CITRULLINATED PEPTIDE; DISEASE-ACTIVITY SCORE; JOINT TENDERNESS; ARTICULAR INDEX; VALIDITY; QUESTIONNAIRE; INFORMATION; PREVALENCE; ANTIBODIES; CRITERIA AB Objective: To describe the development and evaluation of a patient self-report case-finding method for rheumatoid arthritis (RA) not dependent on direct contact with the treating physicians. Methods: The American College of Rheumatology criteria for RA diagnosis were adapted for patient self-report using a questionnaire, and alternative scoring algorithms were evaluated to balance case-finding sensitivity and specificity. Positive rheumatoid factor tests were used to identify 1053 individuals in 2 large healthcare organizations; 440 agreed to receive study materials. Case-finding results were validated by medical record review (MRR) for a random sample of 90 patients. Three scoring algorithms were compared with MRR for likelihood of RA diagnosis. Cases not classifiable by algorithm were flagged and reviewed by 2 expert physicians for likelihood of RA diagnosis. Results: Pilot testing demonstrated that patients comprehended the questionnaire and were willing to answer the questions. Completed questionnaires were returned by 265 (60%) of the 440 patients contacted. Following expert physician review of 16 flagged cases in the 90-patient MRR subsample, the most accurate scoring algorithm demonstrated 80% sensitivity, 67% specificity, 74% accuracy, and 77% positive predictive value for detecting early RA. Conclusion: The case-finding method represents a promising tool for identifying RA patients, with potential application in research and quality-assurance activities. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Kaiser Permanente, Bellflower, CA USA. Jerry L Pettis Mem Vet Adm Med Ctr, Loma Linda, CA USA. Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Wong, AL (reprint author), Olive View UCLA Med Ctr, 14445 Olive View Dr, Sylmar, CA 91342 USA. EM alunwong@ucla.edu FU NIAMS NIH HHS [P60 AR36834] NR 36 TC 7 Z9 7 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 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD AUG PY 2004 VL 34 IS 1 BP 484 EP 499 DI 10.1016/j.semarthrit.2003.12.002 PG 16 WC Rheumatology SC Rheumatology GA 852DK UT WOS:000223735200005 PM 15305246 ER PT J AU Schneyer, A AF Schneyer, A TI Inhibins: A historical perspective SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE inhibin; hormone; endocrine; gonadotropin; follicle-stimulating hormone ID BOVINE FOLLICULAR-FLUID; HUMAN MENSTRUAL-CYCLE; IMMUNOREACTIVE ALPHA-INHIBIN; LINKED-IMMUNOSORBENT-ASSAY; STIMULATING-HORMONE LEVELS; DIMERIC INHIBIN; LUTEINIZING-HORMONE; PRECURSOR PROTEINS; SERUM; SUBUNIT AB Inhibin research began in 1923 with the concept of gonadal feedback regulation of pituitary function. A nonsteroidal substance, capable of inhibiting pituitary cell activity was identified in aqueous testicular extracts and named inhibin in 1932. Another 50 years of research was required before inhibin was purified and cloned in 1985, and inhibin's physiology was not revealed until advances in assay technology allowed analysis of circulating levels in animals and humans. Thus, after 80 years of research, a historical retrospective reveals that many advances were required to achieve our present understanding, and yet there is still a long way to go to reach the original objectives of using inhibin, or compounds based on its structure, to regulate fertility pharmaceutically. Nevertheless, this perspective points out important lessons learned during this journey that are applicable to other areas of endocrinology or are opportunities for future research. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, Boston, MA 02114 USA. FU NICHD NIH HHS [R01 HD39777]; NIDDK NIH HHS [R01 DK55838] NR 37 TC 2 Z9 2 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD AUG PY 2004 VL 22 IS 3 BP 161 EP 164 DI 10.1055/s-2004-831891 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 849VR UT WOS:000223569900003 PM 15319818 ER PT J AU Welt, CK AF Welt, CK TI Regulation and function of inhibins in the normal menstrual cycle SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE menstrual cycle; follicle-stimulating hormone; feedback; activin; follicle; inhibin ID FOLLICLE-STIMULATING-HORMONE; POLYCYSTIC-OVARY-SYNDROME; GRANULOSA-LUTEAL CELLS; MESSENGER RIBONUCLEIC-ACIDS; 2-SITE ENZYME-IMMUNOASSAY; TOTAL ACTIVIN-A; DIMERIC INHIBIN; LUTEINIZING-HORMONE; RAT INHIBIN; DIFFERENTIAL REGULATION AB The development of assays specific for dimeric inhibin A and inhibin B defined the distinct physiology of these two hormones in the normal menstrual cycle. Inhibin A and inhibin B expression and secretion along with their differential regulation by gonado-tropins explain their unique serum patterns and their potential endocrine and ovarian autocrine-paracrine functions. There is evidence that inhibin A and inhibin B play an endocrine role in the negative regulation of follicle-stimulating hormone (FSH) in nonhuman primates and humans. However, some studies suggest that estradiol is a more important, if not the only, negative feedback regulator of FSH in women. There is also evidence from animal models that inhibins and activins play a critical role in follicle development. Future work will be necessary to define further the relative role of the inhibins, estradiol, and other autocrine-paracrine factors in these important reproductive functions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, BHX 511,55 Fruit St, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01 RR01066]; NICHD NIH HHS [U54 HD29164] NR 55 TC 28 Z9 28 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD AUG PY 2004 VL 22 IS 3 BP 187 EP 193 DI 10.1055/s-2004-831894 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 849VR UT WOS:000223569900006 PM 15319821 ER PT J AU Schulze, H Shivdasani, RA AF Schulze, H Shivdasani, RA TI Molecular mechanisms of megakaryocyte differentiation SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE platelet; megakaryocyte; proplatelet; transcription factors; thrombopoiesis ID TRANSCRIPTION FACTOR NF-E2; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; PRIMARY MURINE MEGAKARYOCYTES; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC STEM-CELLS; PLATELET ALPHA-GRANULES; ZINC-FINGER PROTEIN; MPL-DEFICIENT MICE; C-MPL; DOWN-SYNDROME AB Each bone marrow megakaryocyte (MK) releases thousands of platelets into the circulation, and the underlying molecular and cellular mechanisms recently have received intense scrutiny. Genetic studies are beginning to clarify the mechanisms by which transcription factors help distinguish MK progenitors from other blood cell lineages and subsequently confer unique cellular properties. Other investigations demonstrate that platelets are assembled de novo during a terminal phase of MK differentiation in which the cell extends cytoplasmic projections known as proplatelets. This review focuses on the roles of selected transcription factors with key roles in MK differentiation, and on human and murine models of thrombocytopenia that result from impaired MK differentiation. The findings we review help construct a framework to appreciate thrombopoictic mechanisms in the context of underlying lineage and morphologic transitions. Many of these mechanisms are unique to MKs but appear to rely both on genes that are expressed only in that lineage and others that are expressed widely. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NHLBI NIH HHS [R01 HL63143] NR 100 TC 23 Z9 23 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD AUG PY 2004 VL 30 IS 4 BP 389 EP 398 DI 10.1055/s-2004-833474 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 851GN UT WOS:000223673700002 PM 15354260 ER PT J AU Reed, GL AF Reed, GL TI Platelet secretory mechanisms SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Review DE granules; secretion; exocytosis; genetic disorders ID PROTEIN-KINASE-C; GRANULE MEMBRANE-PROTEIN; STORAGE POOL DEFICIENCY; HUMAN-BLOOD-PLATELETS; PERMEABILIZED HUMAN-PLATELETS; ACTIVATED HUMAN PLATELETS; HERMANSKY-PUDLAK-SYNDROME; GUINEA-PIG MEGAKARYOCYTE; WEIBEL-PALADE BODIES; SOLUBLE P-SELECTIN AB Platelet granule secretion or exocytosis is required for normal platelet function and plays an important role in the pathogenesis of cardiovascular diseases. Platelets secrete molecules that amplify thrombosis, induce vascular remodeling, recruit and activate cells. The platelet secretory process begins in megakaryocytes where molecules are targeted to developing granules through specific vesicle trafficking and transporter mechanisms. Secretory granules may continue to mature in the circulation after the platelet has been released from the megakaryocyte. The platelet secretory process culminates when ligands interact with specific platelet receptors to trigger exocytosis. A convergence of new insights from several different organisms has begun to illuminate the molecular mechanisms responsible for the platelet secretory process, from granule development through membrane fusion and exocytosis. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM reed@cvlab.harvard.edu FU NHLBI NIH HHS [HL64057] NR 137 TC 66 Z9 68 U1 0 U2 12 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD AUG PY 2004 VL 30 IS 4 BP 441 EP 450 DI 10.1055/s-2004-833479 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 851GN UT WOS:000223673700007 PM 15354265 ER PT J AU Pittman, SD Ayas, NT MacDonald, MM Malhotra, A Fogel, RB White, DP AF Pittman, SD Ayas, NT MacDonald, MM Malhotra, A Fogel, RB White, DP TI Using a wrist-worn device based on peripheral arterial tonometry to diagnose obstructive sleep apnea: In-laboratory and ambulatory validation SO SLEEP LA English DT Article ID PRACTICE PARAMETERS; POLYSOMNOGRAPHY; HOME; ADULTS; ASSOCIATION; AGREEMENT; HYPERTENSION; DISTURBANCES; ACCIDENTS; HYPOPNEA AB Study Objectives: To assess the accuracy of a wrist-worn device (Watch-PAT 100) to diagnose obstructive sleep apnea in the home. Design: Participants completed 2 overnight diagnostic studies with the test device: I night in the laboratory with concurrent polysomnography and I night in the home with only the Watch-PAT. The order of the laboratory and home study nights was random. The frequency of respiratory events on the PSG was quantified using indexes based on 2 definitions of hypopnea: the respiratory disturbance index (RDI) using American Academy of Sleep Medicine Task Force criteria for clinical research, also referred to as the Chicago criteria (RDI.C), and the Medicare guidelines (RDI.M). The Watch-PAT RIDI (PAT RDI) and oxygen desaturation index (PAT ODI) were then evaluated against the polysomnography RDI.C and RDI.M, respectively, for both Watch-PAT diagnostic nights, yielding INLAB and HOME-LAB comparisons. Setting: Sleep laboratory affiliated with a tertiary-care academic medical center. Patients: 30 patients referred with suspected OSA. Interventions: N/A. Measurements and Results: The polysomnography and PAT measures were compared using the mean [2 SD] of the differences and the intraclass correlation coefficient (ICC). The receiver-operator characteristic curve was used to assess optimum sensitivity and specificity and calculate likelihood ratios. For the IN-LAB comparison, there was high concordance between RDI.C and PAT RDI (ICC = 0.88, mean difference 2.5 [18.9] events per hour); RDI.M and PAT ODI (ICC 0.95, mean difference 1.4 [12.9] events per hour; and sleep time (ICC 0.70, mean difference 7.0 [93.1] minutes) between the test device and PSG. For the HOME-LAB comparison, there was good concordance between RDI.C and PAT RDI (ICC = 0.72, mean difference 1.4 [30.1] events per hour) and RDI.M and PAT ODI (ICC = 0.80, mean difference 1.6 [26.4] events per hour) for the test device and PSG. Home studies were performed with no technical failures. Conclusions: In a population of patients suspected of having obstructive sleep apnea, the Watch-PAT can quantify an ODI that compares very well with Medicare criteria for defining respiratory events and an RDI that compares favorably with Chicago criteria for defining respiratory events. The device can be used with a low failure rate for single use in the lab and home for self-administered testing. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, Div Sleep Med, BIDMC,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vancouver Gen Hosp, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada. RP White, DP (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, Div Sleep Med, BIDMC,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dpwhite@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL073146-02, R01 HL073146]; NIA NIH HHS [K23 AG024837, K23 AG024837-02] NR 43 TC 63 Z9 64 U1 0 U2 5 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD AUG 1 PY 2004 VL 27 IS 5 BP 923 EP 933 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 848EX UT WOS:000223451400015 PM 15453551 ER PT J AU Burns, SP Weaver, FM Parada, JP Evans, CT Chang, H Hampton, RY Kapur, V AF Burns, SP Weaver, FM Parada, JP Evans, CT Chang, H Hampton, RY Kapur, V TI Management of community-acquired pneumonia in persons with spinal cord injury SO SPINAL CORD LA English DT Article DE community-acquired pneumonia; spinal cord injuries; disease management; antibiotics ID PSEUDOMONAS-AERUGINOSA; HOSPITAL STAY; PROGNOSIS; OUTCOMES; CARE; SEVERITY; LENGTH; ADULTS; RISK; GUIDELINES AB Study design: Retrospective case series. Objectives: Respiratory disorders are the leading cause of death in persons with spinal cord injury (SCI), but the epidemiology and medical management of pneumonia in persons with chronic SCI is not well characterized. We describe the clinical presentation of persons with SCI with community-acquired pneumonia ( CAP), characterize its management and compare practice to recommendations for CAP in the general population. Setting: Three United States Veterans A. airs Medical Centers with specialized SCI services. Methods: Chart abstraction was performed for all persons with chronic SCI seen at participating centers for treatment of CAP during a 2-year period. Collected data included presenting signs and symptoms, laboratory and imaging results, initial antibiotic therapy, secretion mobilization techniques, in-patient vs outpatient management, length of stay, and mortality. Results: In all, 41 persons with SCI received treatment for CAP during the study period. A total of 32 (78.0%) patients were admitted for treatment; two (4.8%) required intubation and mechanical ventilation. Initial antibiotic coverage met guideline recommendations for only half of inpatients and infrequently provided adequate antipseudomonal coverage. Microbiologic testing was performed on 26 cases (63.4%) and demonstrated a specific pathogen in only five cases (12.2% of total). Three cases (7.3%) died during treatment for CAP, and 16 (42.1%) of 38 CAP survivors died within a median follow-up of 3 years. Conclusion: The majority of chronic SCI patients who present to specialized SCI centers with CAP are admitted for treatment. Short-term mortality is comparable to CAP in the general population. Sponsorship: This research was supported by the United States Department of Veterans Affairs. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. US Dept Vet Affairs, VA Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv, Chicago, IL 60611 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Div Infect Dis, Maywood, IL 60153 USA. Loyola Med Ctr, Maywood, IL USA. Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, SCI 128,1660 S Columbian Way, Seattle, WA 98108 USA. RI Kapur, Vishesh/K-1054-2014 OI Kapur, Vishesh/0000-0002-5417-1097 NR 28 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD AUG PY 2004 VL 42 IS 8 BP 450 EP 458 DI 10.1038/sj.sc.3101600 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 843GP UT WOS:000223066900005 PM 15037861 ER PT J AU Mandal, AK Drew, N Lapidus, AA AF Mandal, AK Drew, N Lapidus, AA TI The effect of center volume on pancreas transplant outcomes SO SURGERY LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-of-University-Surgeons CY FEB 11-14, 2004 CL St Louis, MO SP Soc Univ Surg ID OPERATIVE MORTALITY; KIDNEY-TRANSPLANTS; SURGICAL VOLUME; HOSPITAL VOLUME; SURGEON VOLUME; UNITED-STATES; QUALITY; PROGRAM; CANCER; CARE AB Background. Caseload often correlates with improved outcomes for several surgical procedures, including, solid organ transplantation. Given the unique nature of pancreas transplantation and large variation in transplant center volumes, this study aims to determine whether center volume affects Patient and graft survival after pancreas transplantation. Methods. Registry data on all forms of whole organ pancreas transplants performed between 1995 and 2000 were obtained from the United Network for Organ Sharing. Patient and graft survival rates were followed until 2002. Center volume then was categorized as: low (< 10/year), medium (10-20/year), high (21-50/year), and very high (< 50/year). Cox proportional hazard regression models were developed to evaluate factors affecting pancreas transplant outcomes. Results. Very-high-volume centers were more likely to do pancreas after kidney transplant, pancreas transplant alone, pancreas with kidney transplant, and repeat transplants, while other centers more frequently performed simultaneous pancreas-kidney transplants (P <. 001). Very-high-volume centers were more likely to transplant older recipients and less likely to transplant minority or Medicaid patients. Low-volume centers tended to accept pancreatic allografts from younger donors and had the longest waiting times. In models adjusting for differences in patient population, there were no differences in Patient survival. However, low-volume centers had a slightly increased risk of graft loss compared to other centers. Early graft loss was similar among all centers, but medium-volume centers were at increased risk for late graft loss. Conclusions. Low center volume is not associated with increased mortality after pancreas transPlantation. Other factors appear to be more important than center volume in determining pancreas transplant outcomes. C1 Portland VA Med Ctr, Dept Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Portland VA Res Fdn, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Liver & Pancreat Transplantat, Portland, OR 97201 USA. RP Mandal, AK (reprint author), Portland VA Med Ctr, Dept Surg, Mail Code R&D66,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. OI Mandal, Aloke/0000-0002-2245-0999 NR 21 TC 10 Z9 10 U1 0 U2 1 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 2004 VL 136 IS 2 BP 225 EP 231 DI 10.1016/j.surg.2004.04.023 PG 7 WC Surgery SC Surgery GA 846LV UT WOS:000223318000017 PM 15300184 ER PT J AU Austen, WG Zhang, M Chan, R Friend, D Hechtman, HB Carroll, MC Moore, FD AF Austen, WG Zhang, M Chan, R Friend, D Hechtman, HB Carroll, MC Moore, FD TI Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM SO SURGERY LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-of-University-Surgeons CY FEB 11-14, 2004 CL St Louis, MO SP Soc Univ Surg ID INTESTINAL ISCHEMIA-REPERFUSION; COMPLEMENT RECEPTOR TYPE-1; NATURAL ANTIBODY; HUMAN C1Q; B-1; ACTIVATION; ORIGIN; MICE; IDENTIFICATION; REPERTOIRE AB Background. Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2(-/-)) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2(-/-) and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R. Methods. IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in marine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2(-/-) mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT Results. Muscle injury in Cr2(-/-) mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and CT2(-/-) mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2(-/-) mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition as found only on injured muscle of WT mice or Cr2(-/-) mice reconstituted with CM22 or WT serum. Conclusion. A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Nat Antibodies Inc, Boston, MA USA. Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moore, FD (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM52585] NR 21 TC 41 Z9 42 U1 0 U2 1 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 2004 VL 136 IS 2 BP 401 EP 406 DI 10.1016/j.surg.2004.05.016 PG 6 WC Surgery SC Surgery GA 846LV UT WOS:000223318000040 PM 15300207 ER PT J AU Dzik, W AF Dzik, W TI Platelet transfusion and cardiac surgery: a cautionary tale SO TRANSFUSION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, W (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 0 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2004 VL 44 IS 8 BP 1132 EP 1134 DI 10.1111/j.1537-2995.2004.44802.x PG 3 WC Hematology SC Hematology GA 841CU UT WOS:000222907700003 PM 15265115 ER PT J AU Halabi, S Small, EJ Vogelzang, NJ Barrier, RC George, SL Gilligan, TD AF Halabi, S Small, EJ Vogelzang, NJ Barrier, RC George, SL Gilligan, TD TI Impact of race on survival in men with metastatic hormone-refractory prostate cancer SO UROLOGY LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; RADICAL PROSTATECTOMY; PROGNOSTIC FACTOR; BLACK; WHITE; CARE; RECURRENCE; MEMBERSHIP; SYSTEM AB Objectives. To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease. Methods. Data from eight multicenter trials (four Phase II and four randomized Phase III studies) conducted by the Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer after androgen deprivation therapy (with documented castration levels of testosterone), an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic function. The proportional hazards model was used to assess the prognostic importance of race, adjusting for important factors. All statistical tests were two-sided. Results. Of the 1 183 patients, 15% were blacks, 45% of patients had a Gleason sum of 8 or greater, and the median age was 7 1 years. Of the 1183 patients, 35% had measurable disease and 89% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Blacks were younger, had a shorter interval between diagnosis and study entry, and had greater prostate-specific antigen levels, lower hemoglobin levels, and a lower likelihood of prior prostatectomy than whites. The median survival was 15 months (95% confidence interval 12 to 18) for blacks compared with 14 months (95% confidence interval 13 to 15) for whites. In a multivariate analysis, adjusting for age, performance status, presence of visceral disease, hemoglobin, Gleason sum, prostate-specific antigen level, alkaline phosphatase, lactate dehydrogenase, and years since diagnosis, the hazard ratio was 0.85 (95% confidence interval 0.71 to 1.02, P = 0.08) for blacks compared with whites. Conclusions. No statistically significant difference was found in overall survival between blacks and whites with metastatic hormone-refractory prostate cancer. (C) 2004 Elsevier Inc. C1 Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Nevada Canc Inst, Las Vegas, NV USA. Univ Calif San Francisco, Urol Oncol Program, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Halabi, S (reprint author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Box 3958, Durham, NC 27710 USA. OI Gilligan, Timothy/0000-0003-2308-9303 FU NCI NIH HHS [CA33601] NR 15 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2004 VL 64 IS 2 BP 212 EP 217 DI 10.1016/j.urology.2004.04.014 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 848UH UT WOS:000223492800004 PM 15302462 ER PT J AU Randolph, GW Kobler, JB Wilkins, J AF Randolph, GW Kobler, JB Wilkins, J TI Recurrent laryngeal nerve identification and assessment during thyroid surgery: Laryngeal palpation SO WORLD JOURNAL OF SURGERY LA English DT Article ID GLAND SURGERY; ELECTROMYOGRAPHY; PALSY; COMPLICATIONS; PRESERVATION; STIMULATION; OPERATIONS; CARCINOMA; DISEASE; RISK AB Electrical identification and monitoring of the recurrent laryngeal nerve (RLN) has been proposed as an adjunct to standard visual identification of the nerve during thyroid and parathyroid surgery. This study was undertaken to assess laryngeal palpation as an intraoperative technique for identifying and assessing the RLN during surgery and to investigate the relation between laryngeal palpation and associated laryngeal electromyographic (EMG) activity. The postericoid region of the larynx during surgery was palpated through the posterior hypopharyngeal wall to sense posterior cricoarytenoid muscle contraction in response to ipsilateral RLN stimulation (i.e., the "laryngeal twitch response.") Laryngeal palpation was performed in a series of 449 consecutive thyroid and parathyroid surgeries with 586 RLNs at risk. All patients underwent preoperative and postoperative laryngoscopy to assess vocal cord mobility. In a subset of patients, laryngeal palpation and simultaneous laryngeal EMG recordings were compared during intraoperative RLN stimulation. In this series, there was no permanent RLN paralysis. There was one case of temporary RLN paralysis secondary to neural stretch that resolved 6 weeks postoperatively (temporary paralysis rate: 0.2% of patients, 0.2% of nerves at risk). Intraoperative laryngeal palpation of the laryngeal twitch response reliably correlated with normal postoperative vocal cord function. Loss of the laryngeal twitch response occurred in the single case of temporary paralysis in the setting of an anatomically intact nerve. Laryngeal palpation correlated well with simultaneous laryngeal EMG activity. There were no palpation-induced laryngeal injuries or laryngeal edema. There were also no RLN injuries due to repetitive neural stimulation. Intraoperative laryngeal palpation during RLN stimulation is a safe, reliable method for neural monitoring that can assist in RLN identification and assessment during thyroid and parathyroid surgery. Most importantly, it provides important prognostic information regarding ipsilateral vocal cord function at the completion of the initial side of the thyroid or parathyroid surgery. Intraoperative laryngeal palpation allows the surgeon to stage contralateral surgery if RLN damage is diagnosed, thereby avoiding the potential for bilateral vocal cord paralysis. We believe that laryngeal palpation is useful as an adjunct to formal EMG monitoring during thyroid and parathyroid surgery. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, HP Mosher Laryngol Res Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Massachusetts Eye & Ear Infirm, Thyroid Surg Serv,Gen Otolaryngol Serv, 243 Charles St, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu NR 35 TC 86 Z9 94 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2004 VL 28 IS 8 BP 755 EP 760 DI 10.1007/s00268-004-7348-x PG 6 WC Surgery SC Surgery GA 859GD UT WOS:000224250500006 PM 15457354 ER PT J AU Wang, YQ Theriault, JR He, HY Gong, JL Calderwood, SK AF Wang, YQ Theriault, JR He, HY Gong, JL Calderwood, SK TI Expression of a dominant negative heat shock factor-1 construct inhibits aneuploidy in prostate carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-1; MOLECULAR CHAPERONES; SPINDLE CHECKPOINT; PROTEIN EXPRESSION; GENE-TRANSCRIPTION; DNA REREPLICATION; MAMMALIAN-CELLS; BREAST-CANCER; C-FOS; ACTIVATION AB Recent studies have implicated heat shock proteins (HSP) and heat shock transcription factor 1 (HSF1) in tumor progression. We have examined the role of HSF1 in the malignant phenotype of PC-3 prostate carcinoma cells. We have developed a dominant negative construct of HSF1 that antagonizes transcription from HSP promoters and results in the depletion of intracellular HSP 70. Our studies indicate that expression of DN-HSF1 dramatically alters the DNA content of PC-3 cells ( derived from p53 null prostatic carcinoma) and inhibits aneuploidy in these cells. This effect is due to prolonged expression of DN-HSF1, and transient expression of the dominant negative factor from an inducible promoter failed to cause the effect. Inhibition of aneuploidy in p53 null PC-3 cells by DN-HSF1 expression was recapitulated by expression within the cells of wild type p53. Furthermore, cells expressing DN-HSF1 showed a profound inhibition in the development of aneuploidy when exposed to chemical agents that disrupt the mitotic spindle and prevent progression through metaphase. Inhibition of aneuploidy in PC-3 cells expressing DN-HSF1 was associated with delayed breakdown of cyclin B1 compared with controls, consistent with a role for wild type HSF1 in the regulation of cyclin B1 degradation, a key step in the control of mitosis. Our experiments therefore demonstrate that HSF1 plays a functional role in cancer cells under nonstress conditions and influences cell cycle behavior and progression through mitosis and promotes the development of the aneuploid state. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol,Div Mol & Cellular Biol, 21-27 Burlington Ave,Rm 553B, Boston, MA 02215 USA. FU NCI NIH HHS [CA50642, CA47407, CA31303] NR 63 TC 36 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 30 PY 2004 VL 279 IS 31 BP 32651 EP 32659 DI 10.1074/jbc.M401475200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 840HW UT WOS:000222849700083 PM 15152009 ER PT J AU Brambilla, P Soloff, PH Sala, M Nicoletti, MA Keshavan, MS Soares, JC AF Brambilla, P Soloff, PH Sala, M Nicoletti, MA Keshavan, MS Soares, JC TI Anatomical MRI study of borderline personality disorder patients SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2002 CL PHILADELPHIA, PA SP Soc Biol Psychiat DE neuroimaging; personality disorder; basal ganglia; hippocampus; amygdala; frontal cortex; temporal cortex; brain; magnetic resonance imaging ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; HIPPOCAMPAL VOLUME; ORBITOFRONTAL CORTEX; SUICIDAL-BEHAVIOR; MAJOR DEPRESSION; BIPOLAR PATIENTS; CHILDHOOD ABUSE; BASAL GANGLIA AB Hippocampal volume reduction has been reported in patients with borderline personality disorder (BPD), and is hypothesized to be associated with traumatic childhood experiences. We extended this investigation to explore additional brain regions and other potential clinical correlates of structural brain changes in BPD. Ten unmedicated BPD subjects and 20 healthy controls were assessed for current and past Axis I and II comorbidities and histories of childhood abuse. All had magnetic resonance imaging (MRI) studies with a 1.5 T GE Signa Imaging System, performing three-dimensional-gradient echo imaging (SPGR) with the following parameters: TR=25 ms, TE=5 ms, and slice-thickness=1.5 mm. Compared with healthy controls, BPD subjects had significantly smaller right and left hippocampal volumes, most marked in subjects with childhood abuse, and significantly increased right and left putamen volumes, especially in subjects with substance use disorders. No significant differences between groups were found for caudate, amygdala, temporal lobes, dorsolateral prefrontal cortex and total brain volumes. This study replicated prior findings of diminished hippocampal volumes in subjects with BPD. Also, increased putamen volumes were found in BPD, a finding that has not been previously reported. Early traumatic experiences may play a role in hippocampal atrophy, whereas substance use disorders may contribute to putamen enlargement. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. Univ Pavia, Sch Med, IRCCS S Matteo, Dept Psychiat, I-27100 Pavia, Italy. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [M01RR0056]; NIMH NIH HHS [MH48463, MH 01736, MH 30915] NR 59 TC 97 Z9 100 U1 2 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 30 PY 2004 VL 131 IS 2 BP 125 EP 133 DI 10.1016/j.pscychresns.2004.04.003 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 852BK UT WOS:000223730000004 PM 15313519 ER PT J AU Lyoo, IK Streeter, CC Ahn, KH Lee, HK Pollack, MH Silveri, MM Nassar, L Levin, JM Sarid-Segal, O Ciraulo, DA Renshaw, PF Kaufman, MJ AF Lyoo, IK Streeter, CC Ahn, KH Lee, HK Pollack, MH Silveri, MM Nassar, L Levin, JM Sarid-Segal, O Ciraulo, DA Renshaw, PF Kaufman, MJ TI White matter hyperintensities in subjects with cocaine and opiate dependence and healthy comparison subjects SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE cocaine-related disorders; opiate-related disorders; white matter hyperintensities; brain magnetic resonance imaging ID BIPOLAR AFFECTIVE-DISORDER; CEREBRAL-BLOOD-FLOW; OBSESSIVE-COMPULSIVE DISORDER; MAGNETIC-RESONANCE; SIGNAL ABNORMALITIES; NEUROVASCULAR COMPLICATIONS; TECHNETIUM-99M-HMPAO SPECT; SYMPTOM PROVOCATION; ELDERLY SUBJECTS; RISK-FACTORS AB The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n = 32) and opiate dependence (n = 32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n = 32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios = 2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio > 3.25 for deep WMH; odds ratio > 4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. Boston Univ, Med Ctr, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Ulsan, Coll Med, Dept Radiol, Seoul, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. Habit Management Inst Inc, Boston, MA USA. RP Lyoo, IK (reprint author), Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM inkylyoo@yahoo.com OI Ciraulo, Domenic/0000-0001-7706-8765 FU NIAAA NIH HHS [K32AA13149]; NIDA NIH HHS [DA50038, DA09448, DA14178, DA00329, DA11231, DA14674]; NIMH NIH HHS [MH58681] NR 74 TC 63 Z9 65 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 30 PY 2004 VL 131 IS 2 BP 135 EP 145 DI 10.1016/j.pscychresns.2004.04.001 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 852BK UT WOS:000223730000005 PM 15313520 ER PT J AU Chung, RT Andersen, J Volberding, P Robbins, GK Liu, T Sherman, KE Peters, MG Koziel, MJ Bhan, AK Alston, B Colquhoun, D Nevin, T Harb, G van der Horst, C AF Chung, RT Andersen, J Volberding, P Robbins, GK Liu, T Sherman, KE Peters, MG Koziel, MJ Bhan, AK Alston, B Colquhoun, D Nevin, T Harb, G van der Horst, C CA AIDS Clinical Trials Grp A5071 Stu TI Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER-DISEASE; COMBINATION THERAPY; INFECTION; REPLICATION; ANTAGONIZES; MORTALITY; EFFICACY; SAFETY; TRIAL AB BACKGROUND: Chronic hepatitis C virus (HCV) infection is a cause of major complications in persons who are also infected with the human immunodeficiency virus (HIV). However, the treatment of HCV infection in such persons has been associated with a high rate of intolerance and a low rate of response. We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV. METHODS: A total of 66 subjects were randomly assigned to receive 180 microg of peginterferon alfa-2a weekly for 48 weeks, and 67 subjects were assigned to receive 6 million IU of interferon alfa-2a three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both groups received ribavirin according to a dose-escalation schedule. At week 24, subjects who did not have a virologic response (those who had an HCV RNA level greater than or equal to 60 IU per milliliter) underwent liver biopsy, and medications were continued in subjects with either a virologic response or histologic improvement. RESULTS: Treatment with peginterferon and ribavirin was associated with a significantly higher rate of sustained virologic response (an HCV RNA level of less than 60 IU per milliliter 24 weeks after completion of therapy) than was treatment with interferon and ribavirin (27 percent vs. 12 percent, P=0.03). In the group given peginterferon and ribavirin, only 14 percent of subjects with HCV genotype 1 infection had a sustained virologic response (7 of 51), as compared with 73 percent of subjects with an HCV genotype other than 1 (11 of 15, P<0.001). Histologic responses were observed in 35 percent of subjects with no virologic response who underwent liver biopsy. CONCLUSIONS: In persons infected with HIV, the combination of peginterferon and ribavirin is superior to the combination of interferon and ribavirin in the treatment of chronic hepatitis C. These regimens may provide clinical benefit even in the absence of virologic clearance. The marked discrepancy in the rates of sustained virologic response between HCV genotypes indicates that strategies are needed to improve the outcome in persons infected with HCV genotype 1. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Cincinnati, Cincinnati, OH USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIAID, Bethesda, MD 20892 USA. Frontier Sci Technol & Res Fdn, Amherst, NY USA. Social & Sci Syst, Rockville, MD USA. Roche Labs, Nutley, NJ USA. Univ N Carolina, Chapel Hill, NC USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org RI Robbins, Gregory/F-7988-2011 FU NCRR NIH HHS [M01 RR000096, M01 RR000044, RR00044, RR00046, RR00096, M01 RR000046]; NIAID NIH HHS [AI046376, AI25868, AI25897, AI27659, AI27661, AI27670, AI27675, AI46370, AI50410, P30 AI027763, P30 AI050410, P30-AI27763D, U01 AI025868, U01 AI025897, U01 AI027659, U01 AI027661, U01 AI027670, U01 AI027675, U01 AI046370, U01 AI046376, U01 AI069502, UM1 AI068636] NR 15 TC 632 Z9 665 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 29 PY 2004 VL 351 IS 5 BP 451 EP 459 DI 10.1056/NEJMoa032653 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 841OJ UT WOS:000222939700008 PM 15282352 ER PT J AU Keroack, MD Peralta, R Abramson, SD Misdraji, J Harris, NL AF Keroack, MD Peralta, R Abramson, SD Misdraji, J Harris, NL TI A man with recurrent gastrointestinal bleeding - Inverted Meckel's diverticulum with ulceration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CAPSULE ENDOSCOPY; DIAGNOSIS; HEMORRHAGE; THERAPY; TRIAL C1 Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, 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 Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, 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 Keroack, MD (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 29 PY 2004 VL 351 IS 5 BP 488 EP 495 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 841OJ UT WOS:000222939700014 PM 15282357 ER PT J AU Roberts, TG Chabner, BA AF Roberts, TG Chabner, BA TI Sounding board: Beyond fast track for drug approvals SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CELL LUNG-CANCER; GEFITINIB; MUTATIONS; THERAPY; TRIAL C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Program Pharmaceut Ind, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Roberts, TG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM troberts@partners.org FU NCI NIH HHS [R25T CA 92203, R25 CA092203] NR 14 TC 32 Z9 36 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 29 PY 2004 VL 351 IS 5 BP 501 EP 505 DI 10.1056/NEJMsb040064 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 841OJ UT WOS:000222939700016 PM 15282359 ER PT J AU Eng, C Iglehart, D AF Eng, C Iglehart, D TI Decision aids from genetics to treatment of breast cancer - Long-term clinical utility or temporary solution? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RISK-ASSESSMENT; WOMEN; SUSCEPTIBILITY; MASTECTOMY; LUMPECTOMY C1 Ohio State Univ, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Human Canc Genet Program,Clin Canc Genet Program, Columbus, OH 43210 USA. Univ Cambridge, Canc Res UK Human Canc Genet Res Grp, Cambridge, England. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Eng, C (reprint author), Ohio State Univ, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Human Canc Genet Program,Clin Canc Genet Program, 420 W 12th Ave,Suite 690 TMRF, Columbus, OH 43210 USA. EM eng.25@osu.edu OI Eng, Charis/0000-0002-3693-5145 NR 18 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 2004 VL 292 IS 4 BP 496 EP 498 DI 10.1001/jama.292.4.496 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 841AA UT WOS:000222900500027 PM 15280348 ER PT J AU Penagos, H Melcher, JR Oxenham, AJ AF Penagos, H Melcher, JR Oxenham, AJ TI A neural representation of pitch salience in nonprimary human auditory cortex revealed with functional magnetic resonance imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pitch; perception; auditory; functional imaging; cortex; hearing ID HUMAN BRAIN; TEMPORAL REGULARITY; ACOUSTIC NOISE; MECHANISMS; SOUND; DISCRIMINATION; HARMONICS; SYSTEM AB Pitch, one of the primary auditory percepts, is related to the temporal regularity or periodicity of a sound. Previous functional brain imaging work in humans has shown that the level of population neural activity in centers throughout the auditory system is related to the temporal regularity of a sound, suggesting a possible relationship to pitch. In the current study, functional magnetic resonance imaging was used to measure activation in response to harmonic tone complexes whose temporal regularity was identical, but whose pitch salience ( or perceptual pitch strength) differed, across conditions. Cochlear nucleus, inferior colliculus, and primary auditory cortex did not show significant differences in activation level between conditions. Instead, a correlate of pitch salience was found in the neural activity levels of a small, spatially localized region of nonprimary auditory cortex, overlapping the anterolateral end of Heschl's gyrus. The present data contribute to converging evidence that anterior areas of nonprimary auditory cortex play an important role in processing pitch. C1 MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Penagos, H (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, 77 Massachusetts Ave,Room E18-310, Cambridge, MA 02139 USA. EM penagos@mit.edu OI Oxenham, Andrew/0000-0002-9365-1157 FU NIDCD NIH HHS [P01 DC 00119, P01 DC000119, P01 DC000119-260023, R01 DC 05216, R01 DC005216] NR 20 TC 148 Z9 149 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 28 PY 2004 VL 24 IS 30 BP 6810 EP 6815 DI 10.1523/JNEUROSCI.0383-04.2004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 841RZ UT WOS:000222950400023 PM 15282286 ER PT J AU Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PWF AF Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PWF TI C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study SO CIRCULATION LA English DT Article DE C-reactive protein; cardiovascular diseases; insulin; prognosis; risk factors ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE ATHEROSCLEROSIS; DIABETES-MELLITUS; SUBCLINICAL INFLAMMATION; ADIPOSE-TISSUE; RISK-FACTORS; POPULATION; MEN; ASSOCIATION; CYTOKINES AB Background-Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results-We assessed the cross-sectional relations of CRP to the MetS ( National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects ( 1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n = 189) over 7 years. MetS (greater than or equal to3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (P trend < 0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P < 0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions-Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events. C1 Countess Chester Hosp, Chester, Cheshire, England. Univ Manchester, Dept Med, Manchester M13 9PL, Lancs, England. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Mass Heart Study, Boston, MA USA. RP Rutter, MK (reprint author), Countess Chester Hosp NHS Trust, Directorate Med, Liverpool Rd, Chester CH2 1UL, Cheshire, England. EM Martin.Rutter@coch.nhs.uk OI Rutter, Martin/0000-0001-6380-539X; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195, R01-HL-073272-01] NR 34 TC 413 Z9 428 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 27 PY 2004 VL 110 IS 4 BP 380 EP 385 DI 10.1161/01.CIR.0000136581.59584.0E PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 841CW UT WOS:000222907900004 PM 15262834 ER PT J AU Singh, J Mela, T Ruskin, J AF Singh, J Mela, T Ruskin, J TI Sleep (vagal)-induced atrial fibrillation SO CIRCULATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 27 PY 2004 VL 110 IS 4 BP E32 EP E33 DI 10.1161/01.CIR.0000136810.16068.10 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 841CW UT WOS:000222907900019 PM 15277334 ER PT J AU De Georgia, MA Krieger, DW Abou-Chebl, A Devlin, TG Jauss, M Davis, SM Koroshetz, WJ Rordorf, G Warach, S AF De Georgia, MA Krieger, DW Abou-Chebl, A Devlin, TG Jauss, M Davis, SM Koroshetz, WJ Rordorf, G Warach, S TI Cooling for acute ischemic brain damage (COOL AID) - A feasibility trial of endovascular cooling SO NEUROLOGY LA English DT Article ID TRANSIENT FOCAL ISCHEMIA; INDUCED HYPOTHERMIA; MILD HYPOTHERMIA; CARDIAC-ARREST; INDUCTION; INJURY; STROKE; RAT AB Objective: To report results of a randomized pilot clinical feasibility trial of endovascular cooling in patients with ischemic stroke. Methods: Forty patients with ischemic stroke presenting within 12 hours of symptom onset were enrolled in the study. An endovascular cooling device was inserted into the inferior vena cava of those randomized to hypothermia. A core body temperature of 33 degreesC was targeted for 24 hours. All patients underwent clinical assessment and MRI initially, at days 3 to 5 and days 30 to 37. Results: Eighteen patients were randomized to hypothermia and 22 to receive standard medical management. Thirteen patients reached target temperature in a mean of 77 +/- 44 minutes. Most tolerated hypothermia well. Clinical outcomes were similar in both groups. Mean diffusion-weighted imaging (DWI) lesion growth in the hypothermia group ( n = 12) was 90.0 +/- 83.5% compared with 108.4 +/- 142.4% in the control group ( n = 11) (NS). Mean DWI lesion growth in patients who cooled well ( n = 8) was 72.9 +/- 95.2% (NS). Conclusions: Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke. Further studies are needed to determine if hypothermia improves outcome. C1 Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Erlanger Med Ctr, Chattanooga, TN USA. Univ Giessen, Giessen, Germany. Royal Melbourne Hosp, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. RP De Georgia, MA (reprint author), Cleveland Clin Fdn, Dept Neurol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM degeorm@ccf.org RI Davis, Stephen/L-5260-2013 OI Davis, Stephen/0000-0003-0962-2300 NR 16 TC 192 Z9 196 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 27 PY 2004 VL 63 IS 2 BP 312 EP 317 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 841CX UT WOS:000222908000021 PM 15277626 ER PT J AU Chin, PS Miller, JW AF Chin, PS Miller, JW TI Ictal head version in generalized epilepsy SO NEUROLOGY LA English DT Article ID LATERALIZING SIGNIFICANCE; SEIZURES AB Focal physical signs may occur with generalized seizures. The authors retrospectively reviewed video-EEG studies of 20 patients with apparent primary generalized epilepsy to assess the frequency of head version during generalized tonic-clonic seizures. Five patients (25%) demonstrated forced head version, including two with turning to the right and left on consecutive seizures. Forced head turning can occur in generalized epilepsy and may not necessarily indicate focal seizure origin. C1 Univ Washington, Reg Epilepsy Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Reg Epilepsy Ctr, Dept Neurol Surg, Seattle, WA 98104 USA. Univ Calif Los Angeles, Robert Wood Johnson VA Clin Scholars Program, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Robert Wood Johnson VA Clin Scholars Program, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Miller, JW (reprint author), Univ Washington, Reg Epilepsy Ctr, Dept Neurol, 325 9th Ave,Box 359745, Seattle, WA 98104 USA. EM millerjw@u.washington.edu NR 8 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 27 PY 2004 VL 63 IS 2 BP 370 EP 372 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 841CX UT WOS:000222908000037 PM 15277642 ER PT J AU Kim, DH Liberati, NT Mizuno, T Inoue, H Hisamoto, N Matsumoto, K Ausubel, FM AF Kim, DH Liberati, NT Mizuno, T Inoue, H Hisamoto, N Matsumoto, K Ausubel, FM TI Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; EMBRYONIC STEM-CELLS; SYNERGISTIC ACTIVATION; ASYMMETRIC DEVELOPMENT; PROTEIN-KINASES; INNATE IMMUNITY; MKK7; ISOFORMS; SAPK/JNK; CASCADE AB The p38 and JNK classes of mitogen-activated protein kinases (MAPKs) have evolutionarily conserved roles in the control of cellular responses to microbial and abiotic stresses. The mechanisms by which crosstalk between distinct p38 and c-Jun N-terminal kinase (JNK) MAPK pathways occurs with resultant integration of signaling information have been difficult to establish, particularly in the context of whole organism physiology. In Caenorhabditis elegans a PMK-1 p38 MAPK pathway is required for resistance to bacterial infection, and a KGB-1 JNK-like MAPK pathway has recently been shown to mediate resistance to heavy metal stress. Here, we show that two components of the KGB-1 pathway, MEK-1 MAPK kinase (MAPKK), a homolog of mammalian MKK7, and VHP-1 MAPK phosphatase (MKP), a homolog of mammalian MKP7, also regulate pathogen resistance through the modulation of PMK-1 activity. The regulation of p38 and JNK-like MAPK pathways mediating immunity and heavy metal stress by common MAPKK and MKP signaling components suggests pivotal roles for MEK-1 and VHP-1 in the integration of diverse stress signals contributing to pathogen resistance in C elegans. In addition, these data point to mechanisms in multicellular organisms by which signals transduced by distinct MAPK pathways may be subject to physiological integration at the level of regulation of MAPK activity by MAPKKs and MKPs. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA. Nagoya Univ, Inst Adv Res, Grad Sch Sci, Dept Mol Biol, Nagoya, Aichi 4648602, Japan. Japan Sci & Technol Corp, Core Res & Evolut Sci & Technol, Chikusa Ku, Nagoya, Aichi 4648602, Japan. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM ausubel@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 41 TC 88 Z9 102 U1 0 U2 11 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 27 PY 2004 VL 101 IS 30 BP 10990 EP 10994 DI 10.1073/pnas.0403546101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 842JM UT WOS:000223000200028 PM 15256594 ER PT J AU Santra, S Barouch, DH Korioth-Schmitz, B Lord, CI Krivulka, GR Yu, F Beddall, MH Gorgone, DA Lifton, MA Miura, A Philippon, V Manson, K Markham, PD Parrish, J Kuroda, MJ Schmitz, JE Gelman, RS Shiver, JW Montefiori, DC Panicali, D Letvin, NL AF Santra, S Barouch, DH Korioth-Schmitz, B Lord, CI Krivulka, GR Yu, F Beddall, MH Gorgone, DA Lifton, MA Miura, A Philippon, V Manson, K Markham, PD Parrish, J Kuroda, MJ Schmitz, JE Gelman, RS Shiver, JW Montefiori, DC Panicali, D Letvin, NL TI Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VACCINIA VIRUS ANKARA; MAJOR HISTOCOMPATIBILITY COMPLEX; VIRAL REPLICATION; PERIPHERAL-BLOOD; PATHOGENIC SIV; FOWLPOX VIRUS; AIDS; INDUCTION; ENV; DIFFERENTIATION AB Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus-boosted monkeys was substantially greater than that seen in the monkeys immunized with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys by the time of viral challenge. Consistent with these comparable memory T cell responses, the clinical protection seen in all groups of experimentally vaccinated monkeys was similar. This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Therion Biol, Cambridge, MA 02142 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Merck Res Labs, W Point, PA 19486 USA. Duke Univ, Ctr Med, Durham, NC 27710 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. EM nletvin@bidmc.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU NIAID NIH HHS [AI-26507, AI-15430, N01AI15430, U01 AI026507, P01 AI026507, N01AI30033] NR 30 TC 57 Z9 57 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 27 PY 2004 VL 101 IS 30 BP 11088 EP 11093 DI 10.1073/pnas.0401954101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 842JM UT WOS:000223000200045 PM 15258286 ER PT J AU Dor, FJMF Doucette, KE Mueller, NJ Wilkinson, RA Bajwa, JA McMorrow, IM Tseng, YL Kuwaki, K Houser, SL Fishman, JA Cooper, DKC Huang, CA AF Dor, FJMF Doucette, KE Mueller, NJ Wilkinson, RA Bajwa, JA McMorrow, IM Tseng, YL Kuwaki, K Houser, SL Fishman, JA Cooper, DKC Huang, CA TI Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine SO TRANSPLANTATION LA English DT Article DE immunosuppression; pig; porcine lymphotropic herpesvirus-1; posttransplant lymphoproliferative disease; spleen transplantation ID LARGE-ANIMAL-MODEL; MIXED CHIMERISM; TOLERANCE; PIGS; XENOTRANSPLANTATION; CYTOMEGALOVIRUS; LYMPHOCYTES; ACTIVATION; DISORDER; THERAPY AB Spleen transplantation (SpTx) was performed in miniature swine across full major histocompatibility complex barriers to study the tolerogenic effect of the spleen. This study describes the development of posttransplant lymphoproliferative disease (PTLD) after allogeneic SpTx. Recipient pigs underwent whole body irradiation (100 cGy), thymic irradiation (700 cGy), and native splenectomy (day 0), and received a 45-day course of intravenous cyclosporine (trough level 400-800 ng/ml). After SpTx, two of seven pigs developed PTLD (1 donor-type, 1 host-type). These two pigs had greater T cell depletion and higher trough levels of cyclosporine. Early changes that occurred prior to the development of clinical features of PTLD were increased porcine lymphotropic herpesvirus-1 viral loads in blood and tissues, and increased numbers of leukocytes, B cells, and total serum IgM. PTLD can occur after allogeneic SpTx in swine. This model may be useful in studies of the pathogenesis of PTLD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Erasmus MC, Dept Surg, Rotterdam, Netherlands. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH East,Bldg 149,13th St, Boston, MA 02129 USA. EM david.cooper@tbrc.mgh.harvard.edu RI Dor, Frank/E-1032-2013; Mueller, Nicolas/B-6864-2013; OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191; Doucette, Karen/0000-0002-1660-9166 FU NIAID NIH HHS [P01 AI 45897, 1P01 AI 45897, 5T32 AI 07529-04] NR 21 TC 9 Z9 9 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 27 PY 2004 VL 78 IS 2 BP 286 EP 291 DI 10.1097/01.TP.0000128342.64240.CF PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 840MV UT WOS:000222863800021 PM 15280692 ER PT J AU Lieberman, J AF Lieberman, J TI Tracking the killers: how should we measure CD8 T cells in HIV infection? SO AIDS LA English DT Editorial Material DE CD8 T lymphocyte; interferon-gamma; cytotoxicity; assay ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; FUNCTIONAL IMPAIRMENT; VIRAL-INFECTION; ELISPOT ASSAY; IN-VITRO; LYMPHOCYTES; VIREMIA; PERFORIN; ANTIGEN C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI42519, AI45406] NR 42 TC 23 Z9 23 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 23 PY 2004 VL 18 IS 11 BP 1489 EP 1493 DI 10.1097/01.aids.0000131320.75396.4d PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 841MN UT WOS:000222934500002 PM 15238766 ER PT J AU Hagendoorn, J Padera, TP Kashiwagi, S Isaka, N Noda, F Lin, MI Huang, PL Sessa, WC Fukumura, D Jain, RK AF Hagendoorn, J Padera, TP Kashiwagi, S Isaka, N Noda, F Lin, MI Huang, PL Sessa, WC Fukumura, D Jain, RK TI Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics SO CIRCULATION RESEARCH LA English DT Article DE microlymphatics; eNOS; lymphatic function; edema; lymphangiography ID IN-VIVO; MESENTERIC LYMPHATICS; RAT MESENTERY; CELLS; PUMP; PERMEABILITY; INHIBITION; MICE AB Functional interactions between the initial and collecting lymphatics, as well as the molecular players involved, remain elusive. In this study, we assessed the influence of nitric oxide ( NO) on lymphatic fluid velocity and flow, using a mouse tail model that permits intravital microscopy and microlymphangiography. We found that NO synthase ( NOS) inhibition decreased lymphatic fluid velocity in the initial lymphatics, without any effect on their morphology. Using the same model, we found a similar effect in eNOS(-/-) mice and in mice treated with a selective endothelial NOS ( eNOS) inhibitor. Next, we uncoupled the superficial initial lymphatics from the deeper collecting lymphatics by ligating the latter and found that lymphatic fluid velocity in NOS-inhibited mice became equal to that in control animals. Surprisingly, lymphatic fluid velocity was significantly increased after ligating the collecting lymphatics, and there was a concomitant increase in injection rate and mean lymphatic vessel diameter. Our results provide the first in vivo evidence that eNOS affects function of the whole microlymphatic system and that it is regulated via the collecting lymphatics. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Pharmacol, New Haven, CT USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Sessa, William/B-6844-2011; OI Padera, Timothy/0000-0002-3453-9384 FU NCI NIH HHS [R24-CA85140] NR 28 TC 51 Z9 52 U1 1 U2 2 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 23 PY 2004 VL 95 IS 2 BP 204 EP 209 DI 10.1161/01.RES.0000135549.72828.24 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 840CW UT WOS:000222835600013 PM 15192027 ER PT J AU Fabbro, M Savage, K Hobson, K Deans, AJ Powell, SN McArthur, GA Khanna, KK AF Fabbro, M Savage, K Hobson, K Deans, AJ Powell, SN McArthur, GA Khanna, KK TI BRCA1-BARD1 complexes are required for p53(Ser-15) phosphorylation and a G(1)/S arrest following ionizing radiation-induced DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAKS; TELANGIECTASIA-MUTATED ATM; S-PHASE CHECKPOINT; HISTONE H2AX; CELL-CYCLE; DEPENDENT PHOSPHORYLATION; BRCA1; CHK1; KINASE; CANCER AB BRCA1 is a major player in the DNA damage response. This is evident from its loss, which causes cells to become sensitive to a wide variety of DNA damaging agents. The major BRCA1 binding partner, BARD1, is also implicated in the DNA damage response, and recent reports indicate that BRCA1 and BARD1 co-operate in this pathway. In this report, we utilized small interfering RNA to deplete BRCA1 and BARD1 to demonstrate that the BRCA1-BARD1 complex is required for ATM/ ATR (ataxia-telangiectasia-mutated/ATM and Rad3-related)mediated phosphorylation of p53(Ser-15) following IR- and UV radiation-induced DNA damage. In contrast, phosphorylation of a number of other ATM/ ATR targets including H2AX, Chk2, Chk1, and c-jun does not depend on the presence of BRCA1-BARD1 complexes. Moreover, prior ATM/ ATR-dependent phosphorylation of BRCA1 at Ser-1423 or Ser-1524 regulates the ability of ATM/ ATR to phosphorylate p53(Ser-15) efficiently. Phosphorylation of p53(Ser-15) is necessary for an IR-induced G(1)/S arrest via transcriptional induction of the cyclin-dependent kinase inhibitor p21. Consistent with these data, repressing p53(Ser-15) phosphorylation by BRCA1-BARD1 depletion compromises p21 induction and the G(1)/S checkpoint arrest in response to IR but not UV radiation. These findings suggest that BRCA1-BARD1 complexes act as an adaptor to mediate ATM/ ATR-directed phosphorylation of p53, influencing G(1)/S cell cycle progression after DNA damage. C1 PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Univ Queensland, Sch Med, Cent Clin Div, Brisbane, Qld 4072, Australia. Peter MacCallum Canc Inst, Oncol Mol Lab, Melbourne 3002, Australia. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Khanna, KK (reprint author), PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. EM kumkumK@qimr.edu.au RI Deans, Andrew/E-5817-2011 OI Deans, Andrew/0000-0002-5271-4422 NR 62 TC 83 Z9 85 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 2004 VL 279 IS 30 BP 31251 EP 31258 DI 10.1074/jbc.M405372200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 838QA UT WOS:000222726800044 PM 15159397 ER PT J AU Bluher, M Patti, ME Gesta, S Kahn, BB Kahn, CR AF Bluher, M Patti, ME Gesta, S Kahn, BB Kahn, CR TI Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; NECROSIS-FACTOR-ALPHA; SKELETAL-MUSCLE; DIABETIC MICE; TNF-ALPHA; OBESITY; METABOLISM; ADIPOGENESIS; RAT; DIFFERENTIATION AB Mice with a fat-specific insulin receptor knock-out (FIRKO) have reduced adipose tissue mass, are protected against obesity, and have an extended life span. White adipose tissue of FIRKO mice is also characterized by a polarization into two major populations of adipocytes, one small (< 50 μm) and one large (> 100 mum), which differ with regard to basal triglyceride synthesis and lipolysis, as well as in the expression of fatty acid synthase, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding protein alpha (C/EBP-alpha). Gene expression analysis using RNA isolated from large and small adipocytes of FIRKO and control (IR lox/lox) mice was performed on oligonucleotide microarrays. Of the 12,488 genes/expressed sequence tags represented, 111 genes were expressed differentially in the four populations of adipocytes at the p < 0.001 level. These alterations exhibited 10 defined patterns and occurred in response to two distinct regulatory effects. 63 genes were identified as changed in expression depending primarily upon adipocyte size, including C/EBP-α, C/EBP-δ, superoxide dismutase 3, and the platelet-derived growth factor receptor. 48 genes were regulated primarily by impairment of insulin signaling, including transforming growth factor β, interferon γ, insulin-like growth factor I receptor, activating transcription factor 3, aldehyde dehydrogenase 2, and protein kinase Cδ. These data suggest an intrinsic heterogeneity of adipocytes with differences in gene expression related to adipocyte size and insulin signaling. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrine, Diabet Unit, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK30136, DK 60837]; PHS HHS [45935] NR 31 TC 54 Z9 57 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 2004 VL 279 IS 30 BP 31891 EP 31901 DI 10.1074/jbc.M404569200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 838QA UT WOS:000222726800116 PM 15131119 ER PT J AU Bluher, M Wilson-Fritch, L Leszyk, J Laustsen, PG Corvera, S Kahn, CR AF Bluher, M Wilson-Fritch, L Leszyk, J Laustsen, PG Corvera, S Kahn, CR TI Role of insulin action and cell size on protein expression patterns in adipocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADIPOSE-TISSUE; MICE LACKING; GLUCOSE; RECEPTOR; OBESITY; CLATHRIN; DISRUPTION; METABOLISM; MEMBRANES; STRESS AB Mice with a fat-specific insulin receptor knock-out (FIRKO) exhibit a polarization of white adipose tissue into two populations of cells, one small ( diameter < 50 μm) and one large ( diameter > 100 mum), accompanied by changes in insulin-stimulated glucose uptake, triglyceride synthesis, and lipolysis. To characterize these subclasses of adipocytes, we have used a proteomics approach in which isolated adipocytes from FIRKO and control (IR lox/lox) mice were separated by size, fractionated into cytosolic and membrane subfractions, and analyzed by sucrose gradient, SDS-PAGE, and mass spectrometry. A total of 27 alterations in protein expression at key steps in lipid and energy metabolism could be defined, which were coordinately regulated by adipocyte cell size, impaired insulin signaling, or both. Nine proteins, including vimentin, EH-domain-containing protein 2, elongation factor 2, glucose-regulated protein 78, transketolase, and succinyl-CoA transferase were primarily affected by presence or absence of insulin signaling, whereas 21 proteins, including myosin non-muscle form A, annexin 2, annexin A6, and Hsp47 were regulated in relation to adipocyte size. Of these 27 alterations in protein expression, 14 changes correlated with altered levels of mRNA, whereas the remaining 13 were the result of changes in protein translation or turnover. These data suggest an intrinsic heterogeneity in adipocytes with differences in protein expression patterns caused by transcriptional and post-transcriptional alterations related to insulin action and cellular lipid accumulation. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK 30136] NR 30 TC 71 Z9 80 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 2004 VL 279 IS 30 BP 31902 EP 31909 DI 10.1074/jbc.M404570200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 838QA UT WOS:000222726800117 PM 15131120 ER PT J AU Keil, DE Dudley, C EuDaly, JG Dempsey, J Butterworth, L Gilkeson, GS Peden-Adams, MM AF Keil, DE Dudley, C EuDaly, JG Dempsey, J Butterworth, L Gilkeson, GS Peden-Adams, MM TI Immunological and hematological effects observed in B6C3F1 mice exposed to Jp-8 jet fuel for 14 days SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID HUMORAL IMMUNE-RESPONSE; LYMPHOCYTE-T ACTIVATION; CELL-MEDIATED-IMMUNITY; ANTIBODY-RESPONSE; INDUCED IMMUNOTOXICITY; DERMAL APPLICATION; HOST-RESISTANCE; RATS; VAPOR; VOLUME AB JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be widespread and to include both military and aviation industry personnel as well as residents living near fuel contaminated sites. This study examines the effects of JP-8 on humoral and cell-mediated and hematological parameters. A suite of immunotoxicological endpoints was evaluated in adult female B6C3F1 mice gavaged with JP-8 (in an olive oil carrier) ranging from 250-2500 mg/kg/d for 14 d. One day following the last exposure, significant increases in liver mass were detected beginning at exposure levels of 1000mg/kg/d, while thymic mass was decreased at exposure levels of 1500 mg/kg/d and above. Decreases in thymic cellularity, however, were only observed at exposure levels of 2000 mg/kg/d and above. Mean corpuscular volume was increased (1500-2500mg/kg/d), while the hematocrit, hemoglobin concentration, and red blood cell count were decreased only at the 2500 mg/kg/d exposure level. Natural killer cell (NK) activity and T- and B-cell proliferation were not altered. Decreases in the plaque forming cell (PFC) response were dose responsive at levels of 500 mg/kg/d and greater while unexpectedly, serum levels of anti-SRBC immunoglobulin M (IgM) were not altered. Alterations were detected in thymic and splenic CD4/8 subpopulations, and proliferative responses of bone marrow progenitor cells were enhanced in mice exposed to 2000 mg/kg/d of JP-8. This study establishes that humoral immune function is impaired with lower exposure levels of JP-8 than are required to affect primary and secondary immune organ weights and cellularities, CD4/8 suhpopulations, and hematological endpoints. C1 NIOSH, OD, AIG, Morgantown, WV 26505 USA. Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. Med Univ S Carolina, Marine Biomed Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Rheumatol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Marine Biomed & Environm Sci Ctr, Charleston, SC 29425 USA. Ralph Johnson VAMC, Med Res Serv, Charleston, SC USA. RP Keil, DE (reprint author), NIOSH, OD, AIG, M-S L1119,1095 Wollowdale Dr, Morgantown, WV 26505 USA. EM dkeil@cdc.gov NR 63 TC 11 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD JUL 23 PY 2004 VL 67 IS 14 BP 1109 EP 1129 DI 10.1080/152839049452335 PG 21 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 834WP UT WOS:000222441900004 PM 15205027 ER PT J AU Aguiar, PD Sweadner, KJ Penniston, JT Zaremba, J Liu, L Caton, M Linazasoro, G Borg, M Tijssen, MAJ Bressman, SB Dobyns, WB Brashear, A Ozelius, LJ AF Aguiar, PD Sweadner, KJ Penniston, JT Zaremba, J Liu, L Caton, M Linazasoro, G Borg, M Tijssen, MAJ Bressman, SB Dobyns, WB Brashear, A Ozelius, LJ TI Mutations in the Na+/K+-ATPase alpha 3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism SO NEURON LA English DT Article ID FAMILIAL HEMIPLEGIC MIGRAINE; SARCOPLASMIC-RETICULUM; SCANNING MUTAGENESIS; CALCIUM-PUMP; NA,K-ATPASE; SUBUNIT; DOMAIN; CA2+-ATPASE; RESOLUTION; SYSTEM AB Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability. We report the finding of six missense mutations in the gene for the Na+/K+-ATPase alpha3 subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and structural analysis of the protein suggest that these mutations impair enzyme activity or stability. This finding implicates the Na+/K+ pump, a crucial protein responsible for the electrochemical gradient across the cell membrane, in dystonia and parkinsonism. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Psychiat & Neurol, Dept Genet, PL-02957 Warsaw, Poland. Clin Quiron, Ctr Neurol & Neurocirugia, San Sebastian 20012, Spain. CHU Nice, Neurol Serv, F-06002 Nice, France. Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1100 DD Amsterdam, Netherlands. Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA. Univ Chicago, Dept Human Genet Neurol & Pediat, Chicago, IL 60637 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. RP Ozelius, LJ (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM ozelius@aecom.yu.edu RI de Carvalho Aguiar, Patricia/B-2350-2013; de Carvalho Aguiar, Patricia/E-8520-2010; Brashear, Allison/G-3853-2015 OI de Carvalho Aguiar, Patricia/0000-0003-2957-9573; de Carvalho Aguiar, Patricia/0000-0003-2957-9573; FU NHLBI NIH HHS [HL36251]; NIA NIH HHS [AG10133]; NIGMS NIH HHS [GM28835]; NINDS NIH HHS [NS26636] NR 34 TC 171 Z9 174 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 22 PY 2004 VL 43 IS 2 BP 169 EP 175 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 841BX UT WOS:000222905400006 PM 15260953 ER PT J AU Loftis, JM Socherman, RE Howell, CD Whitehead, AJ Hill, JA Dominitz, JA Hauser, P AF Loftis, JM Socherman, RE Howell, CD Whitehead, AJ Hill, JA Dominitz, JA Hauser, P TI Association of interferon-alpha-induced depression and improved treatment response in patients with hepatitis C SO NEUROSCIENCE LETTERS LA English DT Article DE antidepressants; selective serotonin reuptake inhibitors; hepatitis C; depression; antiviral therapy ID THERAPY; ILLNESS AB Thirty-nine patients with hepatitis C viral infection on interferon-alpha (IFN-alpha) therapy were monitored weekly using the Beck Depression Inventory (BDI). Thirteen of thirty-nine patients (33%) developed IFN-alpha-induced major depressive disorder (MDD). During the course of IFN-alpha therapy, patients who became depressed were treated with citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant. Results indicated that: (1) IFN-alpha response rates were significantly higher in those patients who developed IFN-alpha-induced MDD than in those who did not (end-of-treatment response (ETR) rates: 61.5% versus 26.9% and sustained viral response (SVR) rates: 38.5% versus 11.5%), (2) male patients with ETR to IFN-alpha therapy were, on average, similar to33 pounds lighter in body weight than male patients who did not respond, and (3) gender, race, past history of MDD, and past history of substance abuse were not significantly associated with ETR. In conclusion, our findings suggest that IFN-alpha-induced MDD may be a predictor of a positive response to IFN-alpha therapy, or an indication of optimal dosing. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. NW Hepatitis C Resource Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. Univ Maryland, Sch Med, VA Med Ctr, Baltimore, MD 21201 USA. Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR USA. Portland VA Med Ctr, P3MHAdm, JENS Lab, Portland, OR 97239 USA. RP Hauser, P (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. EM peter.hauser2@med.va.gov NR 20 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 22 PY 2004 VL 365 IS 2 BP 87 EP 91 DI 10.1016/j.neulet.2004.04.058 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 840OR UT WOS:000222869300003 PM 15245784 ER PT J AU Brower, RG Lanken, PN MacIntyre, N Matthay, MA Morris, A Ancukiewicz, M Schoenfeld, D Thompson, BT AF Brower, RG Lanken, PN MacIntyre, N Matthay, MA Morris, A Ancukiewicz, M Schoenfeld, D Thompson, BT CA Natl Heart Lung Blood Inst ARDS Cl TI Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 98th International Conference of the American-Thoracic-Society CY MAY 17-23, 2002 CL ATLANTA, GA SP Amer Thorac Soc ID ACUTE LUNG INJURY; PEAK AIRWAY PRESSURES; MECHANICAL VENTILATION; TIDAL VOLUME; CONTROLLED-TRIAL; PULMONARY-EDEMA; ADULTS; SURFACTANT; MORTALITY; SEPSIS AB Background: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. Methods: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. Results: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). Conclusions: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure-limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. Univ Penn, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, ARDS, Clin Trials Network, Bethesda, MD 20892 USA. RP Brower, RG (reprint author), Johns Hopkins Univ, 1830 E Monument St,Rm 549, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [N01-HR 46062, N01-HR 46054, N01-HR 46055, N01-HR 46056, N01-HR 46057, N01-HR 46058, N01-HR 46059, N01-HR 46060, N01-HR 46061, N01-HR 46063, N01-HR 46064] NR 37 TC 912 Z9 985 U1 2 U2 34 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 2004 VL 351 IS 4 BP 327 EP 336 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 839RC UT WOS:000222801200006 PM 15269312 ER PT J AU Pallais, JC Kifor, O Chen, YB Slovik, D Brown, EM AF Pallais, JC Kifor, O Chen, YB Slovik, D Brown, EM TI Brief report - Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PRIMARY HYPERPARATHYROIDISM; AUTOIMMUNE HYPOPARATHYROIDISM; CA2+-SENSING RECEPTOR; PARATHYROID-HORMONE; ANTIBODIES; DISORDERS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. RP Pallais, JC (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM jpallais@partners.org FU NIDDK NIH HHS [DK48330, DK52005] NR 23 TC 56 Z9 61 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 2004 VL 351 IS 4 BP 362 EP 369 DI 10.1056/NEJMoa040008 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 839RC UT WOS:000222801200010 PM 15269316 ER PT J AU Hurford, WE Kratz, A Harris, NL Medoff, BD AF Hurford, WE Kratz, A Harris, NL Medoff, BD TI A 50-year-old woman with low oxygen saturation - Methemoglobinemia due to congenital deficiency of erythrocytic cytochrome-b(5) reductase. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PULSE OXIMETRY; HEMOGLOBIN KOLN; B5 REDUCTASE; TASK-FORCE; PATIENT; DESATURATION; MUTATIONS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hurford, WE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 25 TC 15 Z9 15 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 2004 VL 351 IS 4 BP 380 EP 387 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 839RC UT WOS:000222801200014 PM 15269319 ER PT J AU Mega, JL Morrow, DA deLamos, JA Sabatine, MS Murphy, SA Rifai, N Gibson, CM Antman, EM Braunwald, E AF Mega, JL Morrow, DA deLamos, JA Sabatine, MS Murphy, SA Rifai, N Gibson, CM Antman, EM Braunwald, E TI B-Type natriuretic peptide at presentation and prognosis in patients with ST-Segment elevation myocardial infarction - An ENTIRE-TIMI-23 substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR FUNCTION; ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; RISK STRATIFICATION; HEART-FAILURE; TROPONIN-T; THROMBOLYSIS; INDICATOR; PREDICTOR; SURVIVAL AB OBJECTIVES We sought to evaluate B-type natriuretic peptide (BNP), alone and in comparison to cardiac troponin I (cTnI) and high-sensitivity C-reactive protein (hs-CRP), for risk assessment at initial presentation with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Elevated levels of BNP drawn two to four days after acute myocardial infarction are associated with higher mortality. Sparse data are available on its use at first presentation with STEMI. METHODS We obtained samples from 438 patients presenting within 6 h of STEMI enrolled in the Enoxaparin Tenecteplase-Tissue-Type Plasminogen Activator With or Without Glycoprotein IIb/IIIa Inhibitor as Reperfusion Strategy in ST-Segment Elevation Myocardial Infarction (ENTIRE)-Thrombolysis In Myocardial Infarction (TIMI)-23 trial. Outcomes were assessed through 30 days. RESULTS Median BNP was higher in patients who died (89 pg/ml, 25th to 75th percentile: 40 to 192), compared with survivors (15 pg/ml, 25th to 75th percentile: 8.8 to 32, p < 0.0001). Patients with BNP >80 pg/ml were at significantly higher risk of death (17.4% vs. 1.8%, p < 0.0001). Cardiac troponin established a gradient of mortality between the highest and lowest quartile (7.9% vs. 0%, p = 0.007). C-reactive protein was not associated with outcome. After adjustment for cTnI, hs-CRP, and major clinical predictors, including age, heart failure, anterior myocardial infarction location, heart rate, and blood pressure, a BNP level >80 pg/ml was associated with a seven-fold higher mortality risk (odds ratio 7.2, 95% confidence interval 2.1 to 24.5, p = 0.001). Patients with BNP >80 pg/ml were also more likely to have impaired coronary flow (p = 0.049) and incomplete resolution of ST-segment elevation (p = 0.05). CONCLUSIONS Increased concentrations of BNP at initial presentation of patients with STEMI are associated with impaired reperfusion after fibrinolysis and higher short-term risk of mortality. These data support the value of combining markers of hemodynamic stress with traditional approaches to risk assessment in acute myocardial infarction. (C) 2004 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Childrens Hosp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 18 TC 133 Z9 145 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 21 PY 2004 VL 44 IS 2 BP 335 EP 339 DI 10.1016/j.jacc.2004.04.033 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 839LH UT WOS:000222786100020 PM 15261928 ER PT J AU Jernstrom, H Lubinski, J Lynch, HT Ghadirian, P Neuhausen, S Isaacs, C Weber, BL Horsman, D Rosen, B Foulkes, WD Friedman, E Gershoni-Baruch, R Ainsworth, P Daly, M Garber, J Olsson, H Sun, P Narod, SA AF Jernstrom, H Lubinski, J Lynch, HT Ghadirian, P Neuhausen, S Isaacs, C Weber, BL Horsman, D Rosen, B Foulkes, WD Friedman, E Gershoni-Baruch, R Ainsworth, P Daly, M Garber, J Olsson, H Sun, P Narod, SA TI Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CANCER; LACTATION; PREGNANCY; HISTORY; PATTERN; CELLS AB Background: Several studies have reported that the risk of breast cancer decreases with increasing duration of breast-feeding. Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown. Methods: We conducted a case-control study of women with deleterious mutations in either the BRCA1 or the BRCA2 gene. Study participants, drawn from an international cohort, were matched on the basis of BRCA mutation (BRCA1 [n = 685] or BRCA2 [n = 2801), year of birth ( 2 years), and country of residence. The study involved 965 case subjects diagnosed with breast cancer and 965 control subjects who had no history of breast or ovarian cancer. Information on pregnancies and breast-feeding practices was derived from a questionnaire administered to the women during the course of genetic counseling. Conditional logistic regression analyses were used to estimate odds ratios (ORs) for the risk of breast cancer. All statistical tests were two-sided. Results: Among women with BRCA1 mutations, the mean total duration of breast-feeding was statistically significantly shorter for case subjects than for control subjects (6.0 versus 8.7 months, respectively; mean difference = 2.7 months, 95% confidence interval [CI] = 1.4 to 4.0; P<.001). The total duration of breast-feeding was associated with a reduced risk of breast cancer (for each month of breast-feeding, OR = 0.98, 95% CI = 0.97 to 0.99; P-trend <.001)- Women with BRCA1 mutations who breast-fed for more than 1year were less likely to have breast cancer than those who never breast-fed (OR = 0.55, 95% CI = 0.38 to 0.80; P =.001), although no such association was seen for BRCA2 (OR = 0.95, 95% CI = 0.56 to 1.59; P =.83). Conclusions: Women with deleterious BRCA1mutations who breast-fed for a cumulative total of more than 1year had a statistically significantly reduced risk of breast cancer. C1 Univ Lund Hosp, Dept Oncol, Jubileum Inst, Lund, Sweden. Pomeranian Med Univ, Hereditary Canc Ctr, Szczecin, Poland. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Ctr Hosp Univ Montreal, Hotel Dieu, Dept Nutr, Fac Med,Epidemiol Res Unit,Res Ctr, Montreal, PQ, Canada. Univ Calif Irvine, Coll Med, Div Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Princess Margaret Hosp, Familial Ovarian Canc Clin, Toronto, ON M4X 1K9, Canada. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. Chaim Sheba Med Ctr, Suzanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. Rambam Med Ctr, Genet Inst, Haifa, Israel. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Fox Chase Canc Ctr, Div Basic Sci & Populat Sci, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON, Canada. RP Narod, SA (reprint author), Ctr Res Womens Hlth, 790 Bay St,7th Floor, Toronto, ON M5G 1N8, Canada. EM steven.narod@sw.ca OI foulkes, william/0000-0001-7427-4651 FU NCI NIH HHS [CA61231, CA55914, CA63678, CA74415, R01 CA63682] NR 24 TC 106 Z9 112 U1 0 U2 9 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 21 PY 2004 VL 96 IS 14 BP 1094 EP 1098 DI 10.1093/jnci/djh211 PG 5 WC Oncology SC Oncology GA 839RM UT WOS:000222802600013 PM 15265971 ER PT J AU Donta, ST Engel, CC Collins, JF Baseman, JB Dever, LL Taylor, T Boardman, KD Kazis, LE Martin, SE Horney, RA Wiseman, AL Kernodle, DS Smith, RP Baltch, AL Handanos, C Catto, B Montalvo, L Everson, M Blackburn, W Thakore, M Brown, ST Lutwick, L Norwood, D Bernstein, J Bacheller, C Ribner, B Church, LWP Wilson, KH Guduru, P Cooper, R Lentino, J Hamill, RJ Gorin, AB Gordan, V Wagner, D Robinson, C DeJace, P Greenfield, R Beck, L Bittner, M Schumacher, HR Silverblatt, F Schmitt, J Wong, E Ryan, MAK Figueroa, J Nice, C Feussner, JR AF Donta, ST Engel, CC Collins, JF Baseman, JB Dever, LL Taylor, T Boardman, KD Kazis, LE Martin, SE Horney, RA Wiseman, AL Kernodle, DS Smith, RP Baltch, AL Handanos, C Catto, B Montalvo, L Everson, M Blackburn, W Thakore, M Brown, ST Lutwick, L Norwood, D Bernstein, J Bacheller, C Ribner, B Church, LWP Wilson, KH Guduru, P Cooper, R Lentino, J Hamill, RJ Gorin, AB Gordan, V Wagner, D Robinson, C DeJace, P Greenfield, R Beck, L Bittner, M Schumacher, HR Silverblatt, F Schmitt, J Wong, E Ryan, MAK Figueroa, J Nice, C Feussner, JR CA VA Cooperative 475 Grp TI Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; CHRONIC-FATIGUE-SYNDROME; HEALTH-STATUS; MYCOPLASMA-FERMENTANS; DESERT-STORM; DISEASE; QUESTIONNAIRE; GENITALIUM; POPULATION; EXPOSURE AB Background: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. Objective: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. Design: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. Setting: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. Participants: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. Intervention: Doxycycline, 200 mg, or matching placebo daily for 12 months. Measurements: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. Results: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. Limitations: Adherence to treatment after 6 months was poor. Conclusion: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year. C1 Vet Affairs Med Ctr, Boston, MA USA. Vet Affairs Med Ctr, Milwaukee, WI USA. Vet Affairs Med Ctr, Montgomery, AL USA. Vet Affairs Med Ctr, Perry Point, MD USA. Vet Affairs Med Ctr, E Orange, NJ USA. Vet Affairs Med Ctr, White River Jct, VT USA. Vet Affairs Med Ctr, Albuquerque, NM USA. Vet Affairs Med Ctr, Bedford, MA USA. Vet Affairs Med Ctr, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Albany, NY USA. Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Med Ctr, Birmingham, AL USA. Vet Affairs Med Ctr, Bronx, NY USA. Vet Affairs Med Ctr, Brooklyn, NY USA. Vet Affairs Med Ctr, Dayton, OH USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Vet Affairs Med Ctr, Durham, NC USA. Vet Affairs Med Ctr, Fargo, ND USA. Vet Affairs Med Ctr, Hines, IL USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Vet Affairs Med Ctr, Manchester, NH USA. Vet Affairs Med Ctr, New Orleans, LA USA. Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. Vet Affairs Med Ctr, Omaha, NE USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Providence, RI USA. Vet Affairs Med Ctr, Richmond, VA USA. Vet Affairs Med Ctr, San Juan, PR USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. Natl Cent Off, Dept Vet Affairs, Washington, DC USA. RP Collins, JF (reprint author), Vet Affairs Maryland Healthcare Syst, Cooperat Studies Program, Coordinating Ctr 151E, POB 1010, Perry Point, MD 21902 USA. NR 39 TC 17 Z9 17 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 20 PY 2004 VL 141 IS 2 BP 85 EP 94 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 839BL UT WOS:000222758200001 PM 15262663 ER PT J AU Krivacic, RT Ladanyi, A Curry, DN Hsieh, HB Kuhn, P Bergsrud, DE Kepros, JF Barbera, T Ho, MY Chen, LB Lerner, RA Bruce, RH AF Krivacic, RT Ladanyi, A Curry, DN Hsieh, HB Kuhn, P Bergsrud, DE Kepros, JF Barbera, T Ho, MY Chen, LB Lerner, RA Bruce, RH TI A rare-cell detector for cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DISSEMINATED TUMOR-CELLS; EVENT IMAGING-SYSTEM; PERIPHERAL-BLOOD; BONE-MARROW; IMMUNOMAGNETIC ENRICHMENT; SCANNING CYTOMETER; ADHESION MOLECULE; COLORECTAL-CANCER; CARCINOMA-CELLS; BREAST AB Although a reliable method for detection of cancer cells in blood would be an important tool for diagnosis and monitoring of solid tumors in early stages, current technologies cannot reliably detect the extremely low concentrations of these rare cells. The preferred method of detection, automated digital microscopy (ADM), is too slow to scan the large substrate areas. Here we report an approach that uses fiber-optic array scanning technology (FAST), which applies laser-printing techniques to the rare-cell detection problem. With FAST cytometry, laser-printing optics are used to excite 300,000 cells per sec, and emission is collected in an extremely wide field of view, enabling a 500-fold speed-up over ADM with comparable sensitivity and superior specificity. The combination of FAST enrichment and ADM imaging has the performance required for reliable detection of early-stage cancer in blood. C1 Palo Alto Res Ctr, Scripps PARC Inst Adv Biomed Sci, Palo Alto, CA 94304 USA. Synta Pharmaceut Corp, Lexington, MA 02421 USA. Scripps Res Inst, Scripps PARC Inst Adv Biomed Sci, La Jolla, CA 92037 USA. Cima Potenica Ltd, Marblehead, MA 01945 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bruce, RH (reprint author), Palo Alto Res Ctr, Scripps PARC Inst Adv Biomed Sci, 3333 Coyote Hill Rd, Palo Alto, CA 94304 USA. EM richard.bruce@parc.com NR 27 TC 201 Z9 206 U1 2 U2 32 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 20 PY 2004 VL 101 IS 29 BP 10501 EP 10504 DI 10.1073/pnas.0404036101 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 840FN UT WOS:000222842700004 PM 15249663 ER PT J AU Latchman, YE Liang, SC Wu, Y Chernova, T Sobel, RA Klemm, M Kuchroo, VK Freeman, GJ Sharpe, AH AF Latchman, YE Liang, SC Wu, Y Chernova, T Sobel, RA Klemm, M Kuchroo, VK Freeman, GJ Sharpe, AH TI PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; B7 FAMILY; EXPRESSION; ACTIVATION; PATHWAY; B7-H1; RESPONSES; RECEPTOR; LIGANDS; BLOCKADE AB Both positive and negative regulatory roles have been suggested for the B7 family member PD-L1(B7-H1). PD-L1 is expressed on antigen-presenting cells (APCs), activated T cells, and a variety of tissues, but the functional significance of PD-L1 on each cell type is not yet clear. To dissect the functions of PD-L1 in vivo, we generated PD-L1-deficient (PD-L1(-/-)) mice. CD4(+) and CD8(+) T cell responses were markedly enhanced in PD-L1(-/-) mice compared with wild-type mice in vitro and in vivo. PD-L1(-/-) dendritic cells stimulated greater wild-type CD4(+) T cell responses than wild-type dendritic cells, and PD-L1 (-/-) CD4(+) T cells produced more cytokines than wild-type CD4(+) T cells in vitro, demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8(+) T cell responses also were significantly enhanced, indicating that PD-L1 has a role in limiting the expansion or survival of CD8(+) T cells. Studies using the myelin oligodendrocyte model of experimental autoimmune encephalomyelitis showed that PD-L1 on T cells and in host tissues limits responses of self-reactive CD4(+) T cells in vivo. PD-L1 deficiency converted the 129S4/SvJae strain from a resistant to experimental autoimmune encephalomyelitis-susceptible strain. Transfer of encephalitogenic T cells from wild-type mice into PD-L1(- /-) recipients led to exacerbated disease. Disease was even more severe in PD-L1(-/-) recipients of PD-L1(-/-) T cells. These results demonstrate that PD-L1 on T cells, APCs, and host tissue inhibits naive and effector T cell responses and plays a critical role in T cell tolerance. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Vet Affairs Med Ctr, Pathol & Lab Serv, Palo Alto, CA 94304 USA. ProteoSys AG, D-55129 Mainz, Germany. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM asharpe@rics.bwh.harvard.edu NR 26 TC 287 Z9 303 U1 1 U2 9 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 20 PY 2004 VL 101 IS 29 BP 10691 EP 10696 DI 10.1073/pnas.0307252101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 840FN UT WOS:000222842700038 PM 15249675 ER PT J AU Xavier, R Rabizadeh, S Ishiguro, K Andre, N Ortiz, JB Wachtel, H Morris, DG Lopez-Ilasaca, M Shaw, AC Swat, W Seed, B AF Xavier, R Rabizadeh, S Ishiguro, K Andre, N Ortiz, JB Wachtel, H Morris, DG Lopez-Ilasaca, M Shaw, AC Swat, W Seed, B TI Discs large (DIg1) complexes in lymphocyte activation SO JOURNAL OF CELL BIOLOGY LA English DT Article DE discs large; scaffold protein; PDZ domains; lymphocyte activation ID TUMOR-SUPPRESSOR BINDS; IMMUNOLOGICAL SYNAPSE; PLASMA-MEMBRANE; HUMAN HOMOLOG; DISTINCT; CELLS; SAP97; EXPRESSION; RECEPTORS; CHANNEL AB T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (DIg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of DIg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of DIg1 expression by RNA interference enhances both CD3- and superantigen-mediated NEAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM seed@molbio.mgh.harvard.edu FU NIAID NIH HHS [AI46731, AI27849, R01 AI046731, R37 AI027849] NR 22 TC 72 Z9 75 U1 0 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 19 PY 2004 VL 166 IS 2 BP 173 EP 178 DI 10.1083/jcb.200309044 PG 6 WC Cell Biology SC Cell Biology GA 841JT UT WOS:000222926800004 PM 15263016 ER PT J AU Tartar, JL Sheehan, CM Nash, AJ Starratt, C Puga, A Widmayer, S AF Tartar, JL Sheehan, CM Nash, AJ Starratt, C Puga, A Widmayer, S TI ERPs differ from neurometric tests in assessing HIV-associated cognitive deficit SO NEUROREPORT LA English DT Article DE cognitive; ERP; HIV; neurometric; clinical; P3; P300 ID HUMAN-IMMUNODEFICIENCY-VIRUS; EVENT-RELATED POTENTIALS; INFECTION; ABNORMALITIES; DEMENTIA; AIDS AB The onset and time-course of HIV-associated cognitive deficits are not well established. The present experiment compared physiological and neurometric assessments of cognitive decline in HIV-asymptomatic, HIV-symptomatic, and HIV-negative control adult women. The P3 component of standard auditory, event-related electrical potentials of the brain (ERP) and standard nerurometric (pencil and paper) test scores were recorded. The P3 ERP measures differentiated both of the clinical HIV groups from the control group. In contrast, the neurometric measures were more sensitive to the difference in cognitive decline between the two clinical groups. It is concluded that both P3 ERP measures and standard neurometric tests are individually useful and complementary for tracking cognitive decline in the diagnosis and treatment of opportunistic HIV-associated central nervous system impairments. C1 Harvard Univ, Sch Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. Florida Atlantic Univ, Dept Psychol, Boca Raton, FL 33431 USA. Barry Univ, Dept Psychol, Miami Shores, FL 33161 USA. Childrens Diagnost & Treatment Ctr, N Broward Hosp Dist, Ft Lauderdale, FL 33316 USA. RP Tartar, JL (reprint author), Harvard Univ, Sch Med, Res 151-C 940 Belmont St, Brockton, MA 02301 USA. EM jaime_tartar@hms.harvard.edu OI Tartar, Jaime/0000-0002-3452-0579 NR 24 TC 9 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 19 PY 2004 VL 15 IS 10 BP 1675 EP 1678 DI 10.1097/01.wnr.0000134992.74181.4b PG 4 WC Neurosciences SC Neurosciences & Neurology GA 871NP UT WOS:000225140700028 PM 15232305 ER PT J AU Nathan, DG AF Nathan, DG TI Determination can win the battle SO LANCET LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_nathan@dfci.havard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 17 PY 2004 VL 364 IS 9430 BP 301 EP 301 DI 10.1016/S0140-6736(04)16682-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 839KV UT WOS:000222784900035 PM 15262110 ER PT J AU Ogawa, H Yu, RT Haraguchi, T Hiraoka, Y Nakatani, Y Morohashi, K Umesono, K AF Ogawa, H Yu, RT Haraguchi, T Hiraoka, Y Nakatani, Y Morohashi, K Umesono, K TI Nuclear structure-associated TIF2 recruits glucocorticoid receptor and its target DNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE TIF-2; GRIP1; transcription complex; nuclear matrix; nuclear hormone receptor; steroid receptor; nuclear compartment; coactivator; cofactor ID STEROID-HORMONE RECEPTORS; GREEN FLUORESCENT PROTEIN; RNA-POLYMERASE-II; LIVING CELLS; TRANSCRIPTIONAL ACTIVATION; HISTONE ACETYLTRANSFERASE; COACTIVATOR COMPLEXES; NATURAL PROMOTER; GENE-EXPRESSION; LOCALIZATION AB Assembly of multi-protein complexes on promoter and enhancer elements is a prerequisite for onset of gene transcription. At the beginning of this process, transcription factors are thought to act as nucleating centers for complex formation through the binding of their target DNA sequences, and thereafter recruit coactivators. Here, we investigated this process of assembly by determining the distribution of the glucocorticoid receptor (GR) and its coactivator, TIF2. Both endogenously and ectopically expressed TIF2 were shown to form foci in the nucleus, and GR could be recruited to the TIF2 foci upon GR agonist but not antagonist treatment. Moreover, we show that the coactivators, p300 and PCAF, are also recruited to the TIF2 foci. The TIF2 foci could recruit GR carrying a microinjected GR responsive element. We propose that TIF2 provides a nuclear compartment that allows the assembly of multi-protein complexes required for GR-mediated gene activation. (C) 2004 Elsevier Inc. All rights reserved. C1 Kyoto Univ, Inst Virus Res, Dept Biochem, Kyoto, Japan. Nara Inst Sci & Technol, Grad Sch Biol Sci, Ikoma, Japan. Kyoto Univ, Grad Sch Biostudies, Kyoto, Japan. Natl Inst Informat & Commun Technol, Cell Biol Grp, Kobe, Hyogo, Japan. Natl Inst Informat & Commun Technol, Kansai Adv Res Ctr, CREST Res Project, Kobe, Hyogo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Inst Basic Biol, Okazaki, Aichi 444, Japan. RP Ogawa, H (reprint author), Kyoto Univ, Inst Virus Res, Dept Biochem, Kyoto, Japan. EM hidesato@nibb.ac.jp RI Hiraoka, Yasushi/B-5111-2009 OI Hiraoka, Yasushi/0000-0001-9407-8228 NR 52 TC 12 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 16 PY 2004 VL 320 IS 1 BP 218 EP 225 DI 10.1016/j.bbrc.2004.05.161 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 835PA UT WOS:000222494500032 PM 15207724 ER PT J AU Colvin, RA Campanella, GSV Sun, JT Luster, AD AF Colvin, RA Campanella, GSV Sun, JT Luster, AD TI Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ALPHA CHEMOATTRACTANT; CHEMOKINE RECEPTOR CXCR3; ACUTE ALLOGRAFT-REJECTION; HIGH-AFFINITY BINDING; IFN-GAMMA; T-CELLS; BETA-ARRESTIN; DIFFERENTIAL EXPRESSION; SIGNALING PATHWAYS; CARBOXYL-TERMINUS AB The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follows: CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-TAC). Previously, we have found that of the three ligands, CXCL11 is the most potent inducer of CXCR3 internalization and is the physiologic inducer of CXCR3 internalization after T cell contact with activated endothelial cells. We have therefore hypothesized that these three ligands transduce different signals to CXCR3. In light of this hypothesis, we sought to determine whether regions of CXCR3 are differentially required for CXCL9, CXCL10, and CXCL11 function. Here we identified two distinct domains that contributed to CXCR3 internalization. The carboxyl-terminal domain and beta-arrestin1 were predominantly required by CXCL9 and CXCL10, and the third intracellular loop was predominantly required by CXCL11. Chemotaxis and calcium mobilization induced by all three CXCR3 ligands were dependent on the CXCR3 carboxyl terminus and the DRY sequence in the third trans-membrane domain. Our findings demonstrate that distinct domains of CXCR3 mediate its functions and suggest that the differential requirement of these domains contributes to the complexity of the chemokine system. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02129 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Rm 8031, Charlestown, MA 02129 USA. EM aluster@partners.org FU NCI NIH HHS [R01 CA69212]; NIAID NIH HHS [K08 AI50147]; NIDDK NIH HHS [P01 DK50305] NR 52 TC 117 Z9 123 U1 1 U2 9 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 16 PY 2004 VL 279 IS 29 BP 30219 EP 30227 DI 10.1074/jbc.M403595200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836CD UT WOS:000222531900045 PM 15150261 ER PT J AU Schulze, PC Yoshioka, J Takahashi, T He, ZH King, GL Lee, RT AF Schulze, PC Yoshioka, J Takahashi, T He, ZH King, GL Lee, RT TI Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UP-REGULATED PROTEIN-1; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; MAMMALIAN THIOREDOXIN; DEPENDENT ACTIVATION; ENDOTHELIAL-CELLS; NAD(P)H OXIDASE; GENE-EXPRESSION; KINASE-C; SUPEROXIDE AB Increased intracellular reactive oxygen species (ROS) contribute to vascular disease and pro-atherosclerotic effects of diabetes mellitus may be mediated by oxidative stress. Several ROS-scavenging systems tightly control cellular redox balance; however, their role in hyperglycemia-induced oxidative stress is unclear. A ubiquitous antioxidative mechanism for regulating cellular redox balance is thioredoxin, a highly conserved thiol reductase that interacts with an endogenous inhibitor, thioredoxin-interacting protein (Txnip). Here we show that hyperglycemia inhibits thioredoxin ROS-scavenging function through p38 MAPK-mediated induction of Txnip. Overexpression of Txnip increased oxidative stress, while Txnip gene silencing restored thioredoxin activity in hyperglycemia. Diabetic animals exhibited increased vascular expression of Txnip and reduced thioredoxin activity, which normalized with insulin treatment. These results provide evidence for the impairment of a major ROS-scavenging system in hyperglycemia. These studies implicate reduced thioredoxin activity through interaction with Txnip as an important mechanism for vascular oxidative stress in diabetes mellitus. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Cambridge, MA 02139 USA. Joslin Diabet Ctr, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Lee, RT (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, 65 Landsdowne St, Cambridge, MA 02139 USA. EM rlee@rics.bwh.harvard.edu NR 39 TC 193 Z9 208 U1 2 U2 15 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 16 PY 2004 VL 279 IS 29 BP 30369 EP 30374 DI 10.1074/jbc.M400549200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836CD UT WOS:000222531900062 PM 15128745 ER PT J AU Das, I Craig, C Funahashi, Y Jung, KM Kim, TW Byers, R Weng, AP Kutok, JL Aster, JC Kitajewski, J AF Das, I Craig, C Funahashi, Y Jung, KM Kim, TW Byers, R Weng, AP Kutok, JL Aster, JC Kitajewski, J TI Notch Oncoproteins depend on gamma-secretase/presenilin activity for processing and function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR DOMAIN; ENDOTHELIAL-CELLS; SIGNAL-TRANSDUCTION; MAMMALIAN NOTCH; NEOPLASTIC TRANSFORMATION; INTRAMEMBRANE PROTEOLYSIS; NUCLEAR TRANSLOCATION; SECRETASE INHIBITORS; ACTIVATED NOTCH4; PLASMA-MEMBRANE AB During normal development Notch receptor signaling is important in regulating numerous cell fate decisions. Mutations that truncate the extracellular domain of Notch receptors can cause aberrant signaling and promote unregulated cell growth. We have examined two types of truncated Notch oncoproteins that arise from proviral insertion into the Notch4 gene (Notch4/int-3) or a chromosomal translocation involving the Notch1 gene (TAN-1). Both Notch4/int-3 and TAN-1 oncoproteins lack most or all of their ectodomain. Normal Notch signaling requires gamma-secretase/presenilin-mediated proteolytic processing, but whether Notch oncoproteins are also dependent on gamma-secretase/presenilin activity is not known. We demonstrate that Notch4/int-3-induced activation of the downstream transcription factor, CSL, is abrogated in cells deficient in presenilins or treated with a pharmacological inhibitor of gamma-secretase/presenilins. Furthermore, we find that both Notch4/int-3 and TAN-1 accumulate at the cell surface, where presenilin-dependent cleavage occurs, when gamma-secretase/presenilin activity is inhibited. gamma-Secretase/presenilin inhibition effectively blocks cellular responses to Notch4/int-3, but not TAN-1, apparently because some TAN-1 polypeptides lack transmembrane domains and do not require gamma-secretase/presenilin activity for nuclear access. These studies highlight potential uses and limitations of gamma-secretase/presenilin inhibitors in targeted therapy of Notch-related neoplasms. C1 Columbia Univ Coll Phys & Surg, Dept Pathol & Obstet Gynecol, New York, NY 10032 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kitajewski, J (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol & Obstet Gynecol, 630 W 168th St, New York, NY 10032 USA. EM jkk9@columbia.edu RI Weng, Andrew/I-5015-2014; OI Byers, Richard/0000-0003-0796-0365 FU NHLBI NIH HHS [HL-32454] NR 67 TC 50 Z9 52 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 16 PY 2004 VL 279 IS 29 BP 30771 EP 30780 DI 10.1074/jbc.M309252200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836CD UT WOS:000222531900108 PM 15123653 ER PT J AU Gardner, GS Frisch, DR Murphy, SA Kirtane, AJ Giugliano, RP Antman, EM Braunwald, E Gibson, CM AF Gardner, GS Frisch, DR Murphy, SA Kirtane, AJ Giugliano, RP Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI Effect of rescue or adjunctive percutaneous coronary intervention of the culprit artery after fibrinolytic administration on epicardial flow in nonculprit arteries SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TIMI FRAME COUNT; BLOOD-FLOW; PERFUSION; THROMBOLYSIS; IMPAIRMENT; OUTCOMES AB We hypothesized that blood flow in noninfarct arteries would improve after percutaneous coronary intervention of the culprit artery in the setting of ST-elevation myocardial infarction (STEMI). The corrected Thrombolysis In Myocardial Infarction (TIMI) frame count was measured in 94 patients (102 arteries) enrolled in the INTEGRITI, ENTIRE, and FASTER trials of reduced dose fibrinolytic and glycoprotein IIb/IIIa inhibition. The corrected TIMI frame count in nonculprit arteries improved by 3.4 +/- 13.4 frames after percutaneous coronary intervention but remained significantly slower than flow in normal arteries. (C) 2004 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@TIMI.org NR 18 TC 9 Z9 11 U1 0 U2 1 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 2004 VL 94 IS 2 BP 178 EP 181 DI 10.1016/j.amjcard.2004.03.057 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 838LJ UT WOS:000222714500007 PM 15246895 ER PT J AU Legner, VJ Doerner, D Reilly, DF McCormick, WC AF Legner, VJ Doerner, D Reilly, DF McCormick, WC TI Risk factors for nursing home placement following major nonemergent surgery SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID AFFAIRS SURGICAL RISK; NONCARDIAC SURGERY; PERIOPERATIVE COMPLICATIONS; ANESTHESIA; MORBIDITY; MORTALITY; CARE; INDICATORS; ADJUSTMENT; OUTCOMES AB PURPOSE: To determine the association between self-reported exercise tolerance and the risk of unanticipated postoperative nursing home placement in adults undergoing major surgery. METHODS: Consecutive community-dwelling adults (N 586) referred to a medical clinic for evaluation before undergoing major nonemergent surgery at a tertiary care academic medical center were prospectively followed between 1995 and 1997. The main outcome measure was unanticipated postoperative nursing home placement. RESULTS: Overall, 12% (40/324) of patients with poor preoperative exercise tolerance (inability to walk four blocks and climb two flights of stairs without symptomatic limitation) had unanticipated nursing home placement compared with 4% (10/262) of patients with good exercise tolerance. Patient and surgical characteristics associated with nursing home placement in univariate analyses included poor preoperative exercise tolerance, increasing age, living alone, history of heart failure, taking five or more preoperative medications, longer anesthesia duration, and orthopedic surgery. Patients who were married were at lower risk. After adjusting for all other patient and surgical factors, poor preoperative exercise tolerance (odds ratio [OR] 2.8; 95% confidence interval [CI]: 1.3 to 6.2). and serious postoperative complications (OR = 4.7; 95% CI: 2.1 to 10.5) remained associated with postoperative nursing home placement. CONCLUSION: Poor preoperative exercise tolerance was an independent predictor of unanticipated nursing home placement following major nonemergent Surgery. (C) 2004 by Elsevier Inc. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Legner, VJ (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,S-182 GRECC, Seattle, WA 98108 USA. EM legner@u.washington.edu NR 25 TC 11 Z9 11 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL 15 PY 2004 VL 117 IS 2 BP 82 EP 86 DI 10.1016/j.amjmed.2004.02.027 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 837GC UT WOS:000222615700002 PM 15234642 ER PT J AU Kelly, KA Reynolds, F Weissleder, R Josephson, L AF Kelly, KA Reynolds, F Weissleder, R Josephson, L TI Fluorescein isothiocyanate-hapten immunoassay for determination of peptide-cell interactions SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID HIGH-AFFINITY RECEPTORS; BOMBESIN; CANCER AB We have developed a fluorescein isothiocyanate (FITC)-hapten immunoassay, where a FITC-labeled peptide binding to a cell is assayed as the amount of immunoreactive fluorescein present in a cell lysate. An antifluorescein-horseradish peroxidase conjugate binds to either a fluoresceinated peptide in the lysate or a fluorescein attached to the wells of a microtiter plate in a competitive fashion. After washing, solid-phase peroxidase activity is measured and inversely related to the amount of FITC-labeled peptide present. To demonstrate the assay, the interaction of a FITC-labeled bombesin-like peptide with the gastrin-releasing peptide receptor on PC-3 and HT-29 cells was investigated. Using PC-3 cells, we obtained similar displacement curves and numbers of binding sites per cell by both the FITC-hapten immunoassay and a reference radioreceptor assay. The FITC-hapten immunoassay is a sensitive and versatile method, since the same commercially available reagents can be used to assess interactions between any peptide and any receptor. In addition, the FITC-labeled peptide can be used to visualize receptors in fluorescent-activated cell sorting or fluorescent microscopy. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU NIBIB NIH HHS [R01 EB 0062-01] NR 10 TC 18 Z9 19 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 15 PY 2004 VL 330 IS 2 BP 181 EP 185 DI 10.1016/j.ab.2004.02.035 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 834QE UT WOS:000222424800001 PM 15203322 ER PT J AU Thompson, DM King, KR Wieder, KJ Toner, M Yarmush, ML Jayaraman, A AF Thompson, DM King, KR Wieder, KJ Toner, M Yarmush, ML Jayaraman, A TI Dynamic gene expression profiling using a microfabricated living cell array SO ANALYTICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; MICROFLUIDIC SYSTEMS; FLUORESCENT PROTEIN; DNA MICROARRAYS; FABRICATION AB We describe the development of a microfluidic platform for continuous monitoring of gene expression in live cells. This optically transparent microfluidic device integrates high-throughput molecular stimulation with nondestructive monitoring of expression events in individual living cells, hence, a living cell array (LCA). Several concentrations of a soluble molecular stimulus are generated in an upstream microfluidic network and used to stimulate downstream reporter cells, each containing a green fluorescence reporter plasmid for a gene of interest. Cellular fluorescence is continuously monitored and quantified to infer the expression dynamics of the gene being studied. We demonstrate this approach by profiling the activation of the transcription factor NF-kappaB in HeLa S3 cells in response to varying doses of the inflammatory cytokine TNF-alpha. The LCA platform offers a unique opportunity to simultaneously control dynamic inputs and measure dynamic outputs from adherent mammalian cells in a high-throughput fashion. This approach to profiling expression dynamics, in conjunction with complementary techniques such as DNA microarrays, will help provide a more complete picture of the dynamic cellular response to diverse soluble stimuli. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Jayaraman, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. EM jayarama@helix.mgh.harvard.edu FU NIBIB NIH HHS [P41 EB002503] NR 25 TC 127 Z9 133 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 15 PY 2004 VL 76 IS 14 BP 4098 EP 4103 DI 10.1021/ac0354241 PG 6 WC Chemistry, Analytical SC Chemistry GA 838IH UT WOS:000222706400030 PM 15253648 ER PT J AU Praskova, M Khoklatchev, A Ortiz-Vega, S Avruch, J AF Praskova, M Khoklatchev, A Ortiz-Vega, S Avruch, J TI Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras SO BIOCHEMICAL JOURNAL LA English DT Article DE MST1; MST2; NORE1; Ras; RASSF1; tumour suppressor ID TUMOR-SUPPRESSOR GENE; CELL-CYCLE EXIT; PROMOTES APOPTOSIS; EPIGENETIC INACTIVATION; CASPASE CLEAVAGE; FAMILY PROTEIN; ACTIVATION; DROSOPHILA; PHOSPHORYLATION; EFFECTOR AB MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells. In the present study, we show that recombinant MST1/2 undergo a robust auto-activation in vitro, mediated by an intramolecular autophosphorylation of a single site [MST1(Thr(183))/MST2(Thr(180))] on the activation loop of an MST dinner. Endogenous full-length MST1 is activated by a variety of stressful stimuli, accompanied by the secondary appearance of a 36 kDa Thr(183)-phosphorylatect, caspase-cleaved catalytic fragment. Recombinant MST1 exhibits only 2-5 % activation during transient expression; endogenous MST1 in the cycling HeLa or KB cells has a similar low fractional activation, but 2 h incubation with okadaic acid (1 muM) results in 100 % activation. Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein). Co-expression of RASSF1A, RASSF1C, NORE1A and NORE1B with MST1 markedly suppresses MST1(Thr(183)) phosphorylation in vivo and abolishes the ability of MST1 to undergo Mg-ATP-mediated autoactivation in vitro; direct addition of purified NORE1A in vitro also inhibits MST1 activation. In contrast, cotransfection of MST1 with NORE1A modified by the addition of a C-terminal CAAX motif results in a substantial increase in MST1(Thr(183)) phosphorylation, as does fusion of a myristoylation motif directly on to the MST1 N-terminus. Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly(12) --> Val), exhibit higher Thr(183) phosphorylation compared with MST1 bound to NORE1A alone. Nevertheless, serum stimulation of KB cells does not detectably increase the activation state of endogenous MST1 or MST2 despite promoting the recruitment of the endogenous NORE1-MST1 complex to endogenous Ras. We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA073818, R01 CA073818]; NIDDK NIH HHS [DK17776, R37 DK017776] NR 43 TC 178 Z9 189 U1 1 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 2004 VL 381 BP 453 EP 462 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 840SA UT WOS:000222878600016 PM 15109305 ER PT J AU Lichterfeld, M Yu, XG Waring, MT Mui, SK Johnston, MN Cohen, D Addo, MM Zaunders, J Alter, G Pae, E Strick, D Allen, TM Rosenberg, ES Walker, BD Altfeld, M AF Lichterfeld, M Yu, XG Waring, MT Mui, SK Johnston, MN Cohen, D Addo, MM Zaunders, J Alter, G Pae, E Strick, D Allen, TM Rosenberg, ES Walker, BD Altfeld, M TI HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8(+) T cells producing both interferon-gamma and tumor necrosis factor-alpha SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMPAIRED FUNCTION; HIV-1 INFECTION; VIRAL LOAD; LYMPHOCYTES; RESPONSES; EXPRESSION; PERFORIN; ANTIGEN; PROLIFERATION AB CD8(+) T cells play a crucial role in the control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. Recent data suggest that HIV-1-specific CD8(+) T cell subsets may differ in their ability to exert these effector functions. Here, we directly compared the cytokine secretion Patterns and cytotoxic capacity of HIV-1-specific CD8(+) T cells, using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells. These experiments revealed consider- able intraindividual and interindividual differences among epitope-specific T-cell effector functions: while the frequency of HIV-1-specific CD8(+) T cells secreting interferon-gamma but no tumor necrosis factor-alpha (TNF-alpha) following antigenic stimulation was only weakly correlated to their cytotoxic activity (R = 0.05, P = .57), a subset of CD8(+) T cells secreting both interferon-gamma and TNF-a was substantially more strongly associated with cytotoxicity (R = 0.67, P < .001). This subset of CD8(+) T cells also exhibited stronger intracellular perforin expression and more pronounced direct ex vivo HIV-1-specific cytoxicity than CD8(+) T cells secreting solely interferon-gamma following sorting of these subpopulations according to their cytokine profile. These results suggest that HIV-1-specific cytotoxicity of CD8(+) T cells is preferentially mediated by a subset of CD8(+) T cells secreting both interferon-gamma and TNF-alpha. (C) 2004 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Fenway Community Hlth Care Ctr, Boston, MA USA. St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 6613, Boston, MA 02129 USA. EM maltfeld@partners.org RI Zaunders, John/J-6553-2012; Allen, Todd/F-5473-2011 OI Zaunders, John/0000-0002-5912-5989; NR 35 TC 89 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 2004 VL 104 IS 2 BP 487 EP 494 DI 10.1182/blood-2003-12-4341 PG 8 WC Hematology SC Hematology GA 836QU UT WOS:000222571400034 PM 15059848 ER PT J AU Paietta, E Ferrando, AA Neuberg, D Bennett, JM Racevskis, J Lazarus, H Dewald, G Rowe, JM Wiernik, PH Tallman, MS Look, AT AF Paietta, E Ferrando, AA Neuberg, D Bennett, JM Racevskis, J Lazarus, H Dewald, G Rowe, JM Wiernik, PH Tallman, MS Look, AT TI Activating FLT3 mutations in CD117/KIT+ T-cell acute lymphoblastic leukemias SO BLOOD LA English DT Article ID GENE-EXPRESSION SIGNATURES; MINIMAL-RESIDUAL-DISEASE; C-KIT CD117; TANDEM DUPLICATION; HEMATOPOIESIS; DIFFERENTIATION; TRANSCRIPTS; LINEAGE; ALPHA; MLL AB Activating FLT3 mutations are the most common genetic aberrations in acute myeloid leukemia (AML), resulting in the constitutive activation of this receptor tyrosine kinase (RTK), but such mutations are rarely found in acute lymphoblastic leukemia (ALL). Here we describe a unique subset of de novo adult T-cell ALL (T-ALL) cases that coexpress CD117/ KIT and cytoplasmic CD3 (CD117/KIT+ ALL). Activating mutations in the FLT3 RTK gene were found in each of 3 CD117/ KIT+ cases that were analyzed, but not in 52 other adult T-ALL samples from the same series that lacked CD117/KIT expression. Our results indicate the need for clinical trials to test the efficacy of drugs that inhibit the FLT3 RTK in this subset of patients with T-ALL. (C) 2004 by The American Society of Hematology. C1 New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, Bronx, NY 10466 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Stat, ECOG, Boston, MA 02115 USA. Univ Rochester, Rochester, NY USA. Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Mayo Clin, Rochester, MN USA. Rambam Med Ctr, Haifa, Israel. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Paietta, E (reprint author), New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, 600 E 233rd St, Bronx, NY 10466 USA. EM epaietta@earthlink.net FU NCI NIH HHS [CA23318, CA11083, CA21115, CA56771, CA68484] NR 21 TC 63 Z9 66 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2004 VL 104 IS 2 BP 558 EP 560 DI 10.1182/blood-2004-01-0168 PG 3 WC Hematology SC Hematology GA 836QU UT WOS:000222571400043 PM 15044257 ER PT J AU Bagley, J Cortes, ML Breakefield, XO Iacomini, J AF Bagley, J Cortes, ML Breakefield, XO Iacomini, J TI Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice SO BLOOD LA English DT Article ID T-CELL DEPLETION; ATAXIA-TELANGIECTASIA; V(D)J RECOMBINATION; THYMIC LYMPHOMA; LYMPHOCYTES; TOLERANCE; LEUKEMIA; CHIMERAS; INTERLEUKIN-7; TUMORIGENESIS AB Ataxia-telangiectasia (A-T) is a human autosomal recessive disease caused by mutations in the gene encoding ataxia-telangiectasia mutated (ATM). A-T is characterized by progressive cerebellar degeneration, variable immunodeficiency, and a high incidence of leukemia and lymphoma. Recurrent sino-pulmonary infections secondary to immunodeficiency and hematopoietic malignancies are major causes of morbidity and mortality in A-T patients. In mice, an introduced mutation in Atm leads to a phenotype that recapitulates many of the symptoms of A-T, including immune system abnormalities and susceptibility to malignancy. Here we show that the replacement of the bone marrow compartment in Atm knockout mice (Atm(-/-)) using a clinically relevant, nonmyeloablative host-conditioning regimen can be used to overcome the immune deficiencies and prevent the malignancies observed in these mice. Therefore, bone marrow transplantation may prove to be of therapeutic benefit in A-T patients. (C) 2004 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East, 149-5210 13th St, Boston, MA 02129 USA. EM john.iacomini@tbrc.mgh.harvard.edu FU NIAID NIH HHS [R01 AI43619-05, T32 AI07529] NR 38 TC 22 Z9 22 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 JUL 15 PY 2004 VL 104 IS 2 BP 572 EP 578 DI 10.1182/blood-2003-12-4226 PG 7 WC Hematology SC Hematology GA 836QU UT WOS:000222571400046 PM 15044255 ER PT J AU Cutler, CS Lee, SJ Greenberg, P Deeg, HJ Perez, WS Anasetti, C Bolwell, BJ Cairo, MS Gale, RP Klein, JP Lazarus, HM Liesveld, JL McCarthy, PL Milone, GA Rizzo, JD Schultz, KR Trigg, ME Keating, A Weisdorf, DJ Antin, JH Horowitz, MM AF Cutler, CS Lee, SJ Greenberg, P Deeg, HJ Perez, WS Anasetti, C Bolwell, BJ Cairo, MS Gale, RP Klein, JP Lazarus, HM Liesveld, JL McCarthy, PL Milone, GA Rizzo, JD Schultz, KR Trigg, ME Keating, A Weisdorf, DJ Antin, JH Horowitz, MM TI A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; QUALITY-OF-LIFE; WORLD-HEALTH-ORGANIZATION; HLA-IDENTICAL SIBLINGS; LEUKEMIA GROUP-B; PROGNOSTIC FACTORS; SCORING SYSTEM; HODGKINS-DISEASE; PREPARATIVE REGIMENS; TREATMENT STRATEGIES AB Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and non transplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy. (C) 2004 by The American Society of Hematology. C1 Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Hlth Policy Inst, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Columbia Univ, New York, NY USA. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Univ Rochester, Ctr Med, Rochester, NY USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Fundaleu, Buenos Aires, DF, Argentina. British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. Alfred I Dupont Hosp Children, Wilmington, DE USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Minnesota, Minneapolis, MN USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Hlth Policy Inst, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM marymh@mcw.edu FU NCI NIH HHS [U24-CA76518] NR 41 TC 320 Z9 343 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2004 VL 104 IS 2 BP 579 EP 585 DI 10.1182/blood-2004-01-0338 PG 7 WC Hematology SC Hematology GA 836QU UT WOS:000222571400047 PM 15039286 ER PT J AU Kwabi-Addo, B Wang, JH Erdem, H Vaid, A Castro, P Ayala, G Ittmann, M AF Kwabi-Addo, B Wang, JH Erdem, H Vaid, A Castro, P Ayala, G Ittmann, M TI The expression of sprouty1, an inhibitor of fibroblast growth factor signal transduction, is decreased in human prostate cancer SO CANCER RESEARCH LA English DT Article ID FGF RECEPTORS; INTRAEPITHELIAL NEOPLASIA; DROSOPHILA-SPROUTY; OVER-EXPRESSION; PROTEINS; CELLS; ACTIVATION; PATHWAY; GENES; ADENOCARCINOMA AB A considerable body of evidence indicates that alterations of fibroblast growth factors (FGFs) and their receptors contribute to prostate cancer progression. Recently, a new family of regulators of FGF activity has been identified. The Sprouty gene family negatively regulates FGF signaling in a variety of systems and could potentially limit the biological activity of FGFs in prostate cancer. Immunohistochemical analysis of normal and neoplastic prostate tissues using tissue microarrays revealed that Sprouty1 protein is down-regulated in approximately 40% of prostate cancers when compared with matched normal prostate. By quantitative real-time PCR analysis, we found that Sprouty1 mRNA levels were significantly decreased in prostate cancers in vivo in comparison with normal prostate. In prostate cancer cell lines, there is loss of the normal upregulation of Sprouty1 mRNA and protein in response to FGFs. The decrease in Sprouty1 expression in the human prostate cancer, despite elevated levels of FGF ligands and FGF receptors, implies a loss of an important growth regulatory mechanism in prostate cancers that may potentiate the effects of increased FGF and FGF receptor expression in prostate cancer. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Houston Vet Affairs Med Ctr, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350 FU NCI NIH HHS [P50 CA 058204] NR 45 TC 88 Z9 92 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2004 VL 64 IS 14 BP 4728 EP 4735 DI 10.1158/0008-5472.CAN-03-3759 PG 8 WC Oncology SC Oncology GA 837XM UT WOS:000222674700009 PM 15256439 ER PT J AU Brennan, C Zhang, YY Leo, C Feng, B Cauwels, C Aguirre, AJ Kim, MJ Protopopov, A Chin, L AF Brennan, C Zhang, YY Leo, C Feng, B Cauwels, C Aguirre, AJ Kim, MJ Protopopov, A Chin, L TI High-resolution global profiling of genomic alterations with long oligonucleotide microarray SO CANCER RESEARCH LA English DT Article ID COPY NUMBER VARIATION; GENE AMPLIFICATION; CDNA MICROARRAYS; ARRAY CGH; DNA; HYBRIDIZATION; TUMORS; BAC AB Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a full range of biological properties required for tumorigenesis. Among the hallmark features of the cancer genome are recurrent regional gains and losses that, upon detailed characterization, have provided highly productive discovery paths for new oncogenes and tumor suppressor genes. In this study, we describe the use of an oligonucleotide-based microarray platform and development of requisite assay conditions and bioinformatic mining tools that permits high-resolution genome-wide array-comparative genome hybridization profiling of human and mouse tumors. Using a commercially available 60-mer oligonucleotide microarray, we demonstrate that this platform provides sufficient sensitivity to detect single-copy difference in gene dosage of full complexity genomic DNA while offering high resolution. The commercial availability of the microarrays and associated reagents, along with the technical protocols and analytical tools described in this report, should provide investigators with the immediate capacity to perform DNA analysis of normal and diseased genomes in a global and detailed manner. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Lynda_Chin@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [P50 CA 93683, R01 CA 99041, T32 CA 09382, U01 CA 84313] NR 22 TC 98 Z9 108 U1 1 U2 4 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 2004 VL 64 IS 14 BP 4744 EP 4748 DI 10.1158/0008-5472.CAN-04-1241 PG 5 WC Oncology SC Oncology GA 837XM UT WOS:000222674700011 PM 15256441 ER PT J AU Staudt, MR Kanan, Y Jeong, JH Papin, JF Hines-Boykin, R Dittmer, DP AF Staudt, MR Kanan, Y Jeong, JH Papin, JF Hines-Boykin, R Dittmer, DP TI The tumor microenvironment controls primary effusion lymphoma growth in vivo SO CANCER RESEARCH LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; MULTICENTRIC CASTLEMANS-DISEASE; NARROW SUBSTRATE-SPECIFICITY; PROTEIN-COUPLED RECEPTOR; TYPE-1 THYMIDINE KINASE; KAPOSIS-SARCOMA; CELL-LINE; ENDOTHELIAL-CELLS; GENE-EXPRESSION AB Certain lymphomas in AIDS patients, such as primary effusion lymphoma (PEL), are closely associated with the lymphotropic gamma herpes virus Kaposi's sarcoma-associated herpes virus (KSHV), also called human herpesvirus 8. The virus is thought to be essential for tumorigenesis, yet systems to investigate PEL in vivo are rare. Here we describe PEL tumorigenesis in a new xenograft model. Embedded in Matrigel, PEL cells formed rapid, well-organized, and angiogenic tumors after s.c. implantation of C.B.17 SCID mice. Without Matrigel we did not observe comparable tumors, which implies that extracellular support and/or signaling aids PEL. All of the tumors maintained the KSHV genome, and the KSHV latent protein LANA/orf73 was uniformly expressed. However, the expression profile for key lytic mRNAs, as well as LANA-2/vIRF3, differed between tissue culture and sites of implantation. We did not observe a net effect of ganciclovir on PEL growth in culture or as xenograft. These findings underscore the importance of the microenvironment for PEL tumorigenesis and simplify the preclinical evaluation of potential anticancer agents. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ Oklahoma, Hlth Sci Ctr, Grad Program Microbiol & Immunol, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA. RP Dittmer, DP (reprint author), Univ N Carolina, Dept Microbiol & Immunol, CB 7290,804 Mary Ellen Jones, Chapel Hill, NC 27599 USA. EM dirkdittmer@mac.com FU NCI NIH HHS [CA 109232, CA 03017, CA 700580]; NIAID NIH HHS [T32 AI 07364, T32 AI 007633] NR 93 TC 47 Z9 51 U1 1 U2 6 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 2004 VL 64 IS 14 BP 4790 EP 4799 DI 10.1158/0008-5472.CAN-03-3835 PG 10 WC Oncology SC Oncology GA 837XM UT WOS:000222674700018 PM 15256448 ER PT J AU Haddad, RI Weinstein, LJ Wieczorek, TJ Bhattacharya, N Raftopoulos, H Oster, MW Zhang, XX Latham, VM Costello, R Faucher, J DeRosa, C Yule, M Miller, LP Loda, M Posner, MR Shapiro, GI AF Haddad, RI Weinstein, LJ Wieczorek, TJ Bhattacharya, N Raftopoulos, H Oster, MW Zhang, XX Latham, VM Costello, R Faucher, J DeRosa, C Yule, M Miller, LP Loda, M Posner, MR Shapiro, GI TI A phase II clinical and pharmacodynamic study of e7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: Modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle inhibitor SO CLINICAL CANCER RESEARCH 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 DEPENDENT KINASE MODULATORS; ANTICANCER AGENT E7070; SOLID TUMORS; CANCER; PROGRESSION; APOPTOSIS; KI-67; GENE; CHEMOTHERAPY; EXPRESSION AB Purpose: E7070 is a synthetic sulfonamide cell cycle inhibitor that induces hypophosphorylation of the retinoblastoma (Rb) protein and G(1) arrest in vitro. This Phase II study was conducted to explore the efficacy, safety, and pharmacodynamics of E7070 in squamous cell carcinoma of the head and neck (SCCHN). Experimental Design: Patients with metastatic, recurrent, or refractory SCCHN, treated with no more than one prior therapy for recurrent disease, received E7070 at 700 mg/m(2) over 1 h every 3 weeks. Pre- and posttreatment tumor fine needle aspirates were subjected to inummohistochemistry with a panel of phospho-specific anti-Rb antibodies. End points included progression-free survival, response rate and duration, overall survival, toxicity profile, and inhibition of Rb phosphorylation. Results: Because none of the first 15 patients achieved progression-free survival > 4 months, the early stopping rule was invoked. Eleven patients had oropharyngeal cancer and 12 were male. Median age was 59 years (range, 49-73 years). Thirty-nine cycles of E7070 were delivered (median, 2.6 cycles/patient; range, 1-5 cycles). Six patients had stable disease after 2 cycles and 2 patients each subsequently received 1, 2, and 3 additional cycles, respectively, before experiencing progression. Immunohistochemistry of tumor cell aspirates from 3 patients demonstrated reduced Rb phosphorylation posttreatment. Conclusions: At this dose and schedule, E7070 is unlikely to be superior over single-agent chemotherapy in SCCHN. However, the data suggest that cdk activity can be inhibited in tumor cells, resulting in posttreatment modulation of Rb phosphorylation. In the absence of cytotoxicity, more frequent administration of E7070 may be required to sustain Rb hypophosphorylation and cytostatic growth arrest. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Columbia Univ, Dept Med, Div Med Oncol, New York Presbyterian Hosp, New York, NY USA. Eisai Med Res Inc, Teaneck, NJ USA. Eisai Med Res Inc, London, England. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu NR 45 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4680 EP 4687 DI 10.1158/1078-0432.CCR-04-0229 PG 8 WC Oncology SC Oncology GA 840ET UT WOS:000222840700011 PM 15269140 ER PT J AU Avigan, D Vasir, B Gong, JL Borges, V Wu, ZK Uhl, L Atkins, M Mier, J McDermott, D Smith, T Giallambardo, N Stone, C Schadt, K Dolgoff, J Tetreault, JC Villarroel, M Kufe, D AF Avigan, D Vasir, B Gong, JL Borges, V Wu, ZK Uhl, L Atkins, M Mier, J McDermott, D Smith, T Giallambardo, N Stone, C Schadt, K Dolgoff, J Tetreault, JC Villarroel, M Kufe, D TI Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PULSED DENDRITIC CELLS; THERAPEUTIC ANTITUMOR IMMUNITY; COLONY-STIMULATING FACTOR; IN-VITRO; BONE-MARROW; MELANOMA PATIENTS; MULTIPLE-MYELOMA; CARCINOMA-CELLS; TUMOR AB Purpose: Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing tumor-specific immune responses. We have conducted a Phase I trial in which patients with metastatic breast and renal cancer were treated with a vaccine prepared by fusing autologous tumor and DCs. Experimental Design: Accessible tumor tissue was disrupted into single cell suspensions. Autologous DCs were prepared from adherent peripheral blood mononuclear cells that were obtained by leukapheresis and cultured in granulocyte macrophage colony-stimulating factor, interleukin 4, and autologous plasma. Tumor cells and DCs were cocultured in the presence of polyethylene glycol to generate the fusions. Fusion cells were quantified by determining the percentage of cells that coexpress tumor and DC markers. Patients were vaccinated with fusion cells at 3-week intervals and assessed weekly for toxicity, and tumor response was assessed at 1, 3, and 6 months after completion of vaccination. Results: The vaccine was generated for 32 patients. Twenty-three patients were vaccinated with 1 x 10(5) to 4 x 10(6) fusion cells. Fusion cells coexpressed tumor and DC antigens and stimulated allogeneic T-cell proliferation. There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. In a subset of patients, vaccination resulted in an increased percentage of CD4 and CD8+ T cells expressing intracellular IFN-gamma in response to in vitro exposure to tumor lysate. Two patients with breast cancer exhibited disease regressions, including a near complete response of a large chest wall mass. Five patients with renal carcinoma and one patient with breast cancer had disease stabilization. Conclusions: Our findings demonstrate that fusion cell vaccination of patients with metastatic breast and renal cancer is a feasible, nontoxic approach associated with the induction of immunological and clinical antitumor responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu NR 46 TC 158 Z9 168 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4699 EP 4708 DI 10.1158/1078-0432.CCR-04-0347 PG 10 WC Oncology SC Oncology GA 840ET UT WOS:000222840700013 PM 15269142 ER PT J AU Katsivas, T Sokolov, R Miller, M Hever, A Hu, B AF Katsivas, T Sokolov, R Miller, M Hever, A Hu, B TI Primary herpetic peritonitis causing intestinal perforation: Case report and review of the literature SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID DIALYSIS AB Peritonitis of viral etiology is rarely reported in the literature; a prior report described a patient undergoing continuous ambulatory peritoneal dialysis who had the disease. We report a case of primary herpetic peritonitis ( the agent of which was typed by polymerase chain reaction as herpes simplex virus biotype 1), which caused intestinal perforation, and we review the current literature and provide possible pathophysiologic mechanisms. C1 Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Div Infect Dis, Los Angeles, CA 90048 USA. Greater Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Clin Labs, Los Angeles, CA 90024 USA. RP Katsivas, T (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, 111-F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM tkats@prodigy.net NR 13 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2004 VL 39 IS 2 BP E13 EP E16 DI 10.1086/421998 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 835HV UT WOS:000222474300030 PM 15307046 ER PT J AU Mango, SE Smith, P Ao, WY Gaudet, J Muttumu, S Armstrong, C Vidal, M Kent, J AF Mango, SE Smith, P Ao, WY Gaudet, J Muttumu, S Armstrong, C Vidal, M Kent, J TI Genome-wide analysis of foregut development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Calif Santa Cruz, Genome Bioinformat Grp, Santa Cruz, CA 95064 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 2004 VL 271 IS 2 MA 39 BP 555 EP 556 PG 2 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200061 ER PT J AU Albertson, RC Yelick, PC AF Albertson, RC Yelick, PC TI FGF8 deficiency results in left-right craniofacial asymmetry in zebrafish. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Forsyth 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 2004 VL 271 IS 2 MA 288 BP 609 EP 609 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200304 ER PT J AU Gamer, L Nove, J Rosen, V AF Gamer, L Nove, J Rosen, V TI BMP-3 is an antagonist of BMP and activin signaling in Xenopus embryos. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 HSDM, Boston, MA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 1 Z9 1 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 2004 VL 271 IS 2 MA 307 BP 613 EP 613 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200323 ER PT J AU Childs, S Torres-Vasquez, J Lamont, RE Fishman, MC Chen, JN Weinstein, BM Fraser, SD AF Childs, S Torres-Vasquez, J Lamont, RE Fishman, MC Chen, JN Weinstein, BM Fraser, SD TI Loss of plexinDl sends vascular pattern out of bounds. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Univ Calgary, Calgary, AB T2N 1N4, Canada. NICHD, Mol Genet Lab, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA 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 2004 VL 271 IS 2 MA 318 BP 615 EP 615 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200334 ER PT J AU Carey, KB Roberts, LJ Kivlahan, DR Carey, MP Neal, DJ AF Carey, KB Roberts, LJ Kivlahan, DR Carey, MP Neal, DJ TI Problems assessment for substance using psychiatric patients: development and initial psychometric evaluation SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE substance use; problems; psychiatric disorders; psychometrics ID SEVERE MENTAL-ILLNESS; ADDICTION SEVERITY INDEX; ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; ABUSE SCREENING-TEST; DRUG-USE DISORDERS; QUALITY-OF-LIFE; HARM REDUCTION; HEALTH SURVEY; VALIDITY AB Background: Persons with co-occurring Axis I mental disorders and substance use disorders often experience multiple negative consequences as a result of their substance use. Because no existing measure adequately assesses these population-specific problems, we developed the Problems Assessment for Substance Using Psychiatric Patients (PASUPP). This paper describes the scale development and factor structure, and provides initial reliability and validity evidence for the PASUPP. Methods: An initial pool of 54 items was assembled by reviewing existing measures for relevant items and generating new items. Then, 239 patients (90% male, 61% White) with documented Axis I psychiatric and current substance use disorders rated the lifetime and last 3-month occurrence of each problem, and completed additional measures of substance use and related functioning. Results: Lifetime endorsements ranged from 31 to 95%, whereas 3-month endorsements ranged from 24 to 78%. Item analyses reduced the set to 50 items. The PASUPP is internally consistent (alpha = 0.97) and unidimensional. Scale validity was suggested by moderate correlation with other measures of substance problem severity. Conclusions: Promising psychometric properties are reported for a population-specific measure of substance use problems. Such a measure could be useful for initial assessments and outcome evaluations with substance using psychiatric patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Syracuse Univ, Ctr Hlth & Behav, Syracuse, NY 13244 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Carey, KB (reprint author), Syracuse Univ, Ctr Hlth & Behav, 430 Huntington Hall, Syracuse, NY 13244 USA. EM kbcarey@psych.syr.edu FU NIDA NIH HHS [K02 DA000426-05, K02-DA00426, K02 DA000426]; NIMH NIH HHS [K02-MH01582, K02 MH001582, K02 MH001582-05] NR 54 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 15 PY 2004 VL 75 IS 1 BP 67 EP 77 DI 10.1016/j.drugalcdep.2004.01.010 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 842TK UT WOS:000223026900007 PM 15225890 ER PT J AU Choo, YS Johnson, GVW MacDonald, M Detloff, PJ Lesort, M AF Choo, YS Johnson, GVW MacDonald, M Detloff, PJ Lesort, M TI Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release SO HUMAN MOLECULAR GENETICS LA English DT Article ID KNOCK-IN MICE; OUTER-MEMBRANE; CELL-DEATH; EMBRYONIC LETHALITY; INCREASED APOPTOSIS; OXIDATIVE STRESS; MOUSE MODEL; DISEASE; PORE; PROTEIN AB Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine stretch in the huntingtin protein, conferring a novel property on the protein that leads to the loss of striatal neurons. Defects in mitochondrial function have been implicated in the pathogenesis of HD. Here, we have examined the hypothesis that the mutant huntingtin protein may directly interact with the mitochondrion and affect its function. In human neuroblastoma cells and clonal striatal cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant) homozygote mouse knock-in embryos, huntingtin was present in a purified mitochondrial fraction. Subfractionation of the mitochondria and limited trypsin digestion of the organelle demonstrated that huntingtin was associated with the outer mitochondrial membrane. We further demonstrated that a recombinant truncated mutant huntingtin protein, but not a wild-type, directly induced mitochondrial permeability transition (MPT) pore opening in isolated mouse liver mitochondria, an effect that was prevented completely by cyclosporin A (CSA) and ATP. Importantly, the mutant huntingtin protein significantly decreased the Ca2+ threshold necessary to trigger MPT pore opening. We found a similar increased susceptibility to the calcium-induced MPT in liver mitochondria isolated from a knock-in HD mouse model. The mutant huntingtin protein-induced MPT pore opening was accompanied by a significant release of cytochrome c, an effect completely inhibited by CSA. These findings suggest that the development of specific MPT inhibitors may be an interesting therapeutic avenue to delay the onset of HD. C1 Univ Alabama, Dept Psychiat, Birmingham, AL 35294 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Lesort, M (reprint author), Univ Alabama, Dept Psychiat & Behav Neurobiol, 1720,7th Ave S,SC1079, Birmingham, AL 35294 USA. EM mlesort@uab.edu RI Johnson, Gail/K-4723-2012 OI Johnson, Gail/0000-0003-3464-0404 FU NINDS NIH HHS [NS41552, NS32765, NS41744, R01 NS041552, R01 NS041552-04] NR 53 TC 250 Z9 254 U1 0 U2 10 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 JUL 15 PY 2004 VL 13 IS 14 BP 1407 EP 1420 DI 10.1093/hmg/ddh162 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 834GU UT WOS:000222400400001 PM 15163634 ER PT J AU Mueller, A Wallner, K Merrick, G Ford, E Sutlief, S Cavanagh, W Butler, W AF Mueller, A Wallner, K Merrick, G Ford, E Sutlief, S Cavanagh, W Butler, W TI Perirectal seeds as a risk factor for prostate brachytherapy-related rectal bleeding SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostatic carcinoma; brachytherapy; rectum; morbidity ID I-125; MORBIDITY; CANCER AB Purpose: To correlate rectal wall doses and perirectal seed numbers with late rectal bleeding after prostate brachytherapy. Methods and Materials: We studied 148 patients randomized to implantation with I-125 vs. Pd-103 at the VA Puget Sound HCS from 1998 through 2001 and for whom postimplant dosimetry was available. Implants were performed by standard techniques, using a modified peripheral loading pattern. A postimplant computed tomography (CT) scan (3 mm slice thickness) was obtained 1-4 h after implantation. Rectal doses were expressed as the R100, R200, and R300, defined as the rectal volume (cc) that received more than 100%, 200%, or 300% of the prescription dose, respectively. The rectum was considered to be a solid structure defined by the outer wall, without attempting to differentiate the inner wall or contents. In addition to conventional dose parameters, each patient's postimplant CT scan was reviewed for the number of seeds within 0, 0.1-2, and 2.1-4 mm of the outer rectal wall. The proximal edge of the seed was used for distance determinations from the outer rectal wall. Patients who reported Grade 1 or higher Radiation Therapy Oncology Group morbidity were contacted by telephone to obtain more details regarding their rectal bleeding. Those who reported persistent bleeding lasting for more than 1 month were categorized as Grade 2. Results: Patients had a wide range of rectal wall doses, with R100 values ranging from 0.0 to 10.4 cc (median, 0.95 cc). Similarly, the number of perirectal seeds within 0.0 to 2.0 mm of the rectum varied widely, ranging from 0 to 12 seeds (median: 1 seed). Seven patients (7 of 144 = 5%) developed persistent rectal bleeding, one of whom required a colostomy. Both rectal radiation doses and the number of perirectal seeds were higher in patients with persistent rectal bleeding. The number of perirectal seeds less than or equal to2.0 mm of the rectal wall was higher in patients with rectal bleeding (p = 0.037), but the number of seeds 2-4 mm from the wall were not related (p = 0.72). In multivariate regression analysis including prostatic D90 (the dose that covers 90% of the postimplant prostate), preimplant transrectal ultrasound volume, R300, and the number of seeds less than or equal to2 mm from the rectal wall as independent variables, only the R300 was statistically significantly associated with the likelihood of persistent rectal bleeding (p = 0.025). Conclusion: A limited number of errant perirectal sources in itself does not appear to place patients at increased risk of rectal bleeding, providing that the overall rectal wall doses are within acceptable values. (C) 2004 Elsevier Inc. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Schiffler Canc Ctr, Wheeling, WV USA. RP Wallner, K (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 174,1660 S Columbian Way, Seattle, WA 98108 USA. EM kent.wallner@med.va.gov NR 17 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2004 VL 59 IS 4 BP 1047 EP 1052 DI 10.1016/j.ijrobp.2003.12.016 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 836FO UT WOS:000222541300015 PM 15234038 ER PT J AU Zelefsky, MJ Moughan, J Owen, J Zietman, AL Roach, M Hanks, GE AF Zelefsky, MJ Moughan, J Owen, J Zietman, AL Roach, M Hanks, GE TI Changing trends in national practice for external beam radiotherapy for clinically localized prostate cancer: 1999 patterns of care survey for prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiotherapy; androgen deprivation; dose escalation; patterns of care ID THERAPY ONCOLOGY GROUP; RADIATION-THERAPY; ADENOCARCINOMA; GOSERELIN; CARCINOMA; TRIAL; GY AB Purpose: To report changing trends in external beam radiotherapy (EBRT) delivery practice for clinically localized prostate cancer as determined from the 1999 survey from the American College of Radiology National Patterns of Care Study. Methods and Materials: The 1999 survey included a weighted sample of 36,496 patient records obtained from a stratified two-stage sample of 554 patient records. Patients were surveyed from 58 institutions and were treated between January 1999 and December 1999. Of these, 36% (weighted sample size, 13,293; unweighted sample size, 162) were treated with brachytherapy with or without EBRT and 64% (weighted sample size, 23,203; unweighted sample size, 392) were treated with EBRT only. The latter group is the subject of this report. The following trends in clinical practice were analyzed according to prognostic risk groups and other variables and compared with the results of the prior surveys: use of androgen deprivation therapy (ADT) in combination with EBRT, higher prescription dose levels, and administration of elective whole pelvic RT (WPRT). Results: The incidence of ADT use for favorable, intermediate, and unfavorable-risk groups was 31%, 54%, and 79%, respectively. A multivariate logistic regression analysis revealed a statistically significantly increased likelihood of intermediate (p = 0.001) and unfavorable (p 0.0001) risk groups treated with ADT in conjunction with EBRT compared with favorable-risk patients. ADT use was more prevalent among treated patients in the 1999 survey than in the 1994 survey (51% vs. 8%, p <0.0001). Compared with the prior survey, a greater percentage of patients were treated with higher radiation doses in the 1999 survey (greater than or equal to72 Gy, 45% in 1999 vs. 3% in 1994, p <0.0001). In the 1999 survey, the proportion of patients with favorable, intermediate, and unfavorable tumors treated to doses greater than or equal to72 Gy was 43%, 38%, and 60%, respectively, compared with 4%, 3%, and 1%, respectively, in the 1994 survey. Compared with the 1994 survey, a large increase in the number of patients treated with brachytherapy (36 % vs. 3 %, p <0.0001). The frequency of WPRT use decreased from 92% in 1989 to 52% in 1994 to 23% in 1999. For the 1999 survey, a multivariate analysis indicated that unfavorable-risk patients (p = 0.016) and intermediate-risk patients (P = 0.018) were more likely to be treated with WPRT compared with favorable-risk patients. Nevertheless, even among unfavorable-risk patients, a substantial decline had occurred in the use of WPRT for the 1999 survey (70% for the 1994 survey compared with the 31 % for the current survey; p = 0.003). Conclusion: The significantly increased use of ADT for high-risk patients and higher radiation doses, especially for intermediate- and high-risk patients, reflects the penetration and growing acceptance of clinical trial results that have demonstrated the efficacy of these treatment approaches. The relatively high proportion of favorable-risk patients treated with high radiation dose levels was greater than expected. A large increase in brachytherapy was observed compared with prior surveys. Most treated patients with high-risk disease did not undergo elective WPRT, which likely reflects the influences of prior trials, stage migration, and the commonly held belief that WPRT provides minimal benefit in the setting of higher radiation doses. (C) 2004 Elsevier Inc. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Amer Coll Radiol, Philadelphia, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Univ Calif San Francisco, Sch Med, Dept Radiat Oncol, San Francisco, CA 94143 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. RP Zelefsky, MJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave,Box 22, New York, NY 10021 USA. EM zelefskm@mskcc.org FU NCI NIH HHS [CA 65435] NR 12 TC 53 Z9 53 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 2004 VL 59 IS 4 BP 1053 EP 1061 DI 10.1016/j.ijrobp.2003.12.011 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 836FO UT WOS:000222541300016 PM 15234039 ER PT J AU Petrylak, DP Tangen, C Hussain, M Lara, PN Jones, J Talpin, ME Burch, P Greene, G Small, E Crawford, ED AF Petrylak, DP Tangen, C Hussain, M Lara, PN Jones, J Talpin, ME Burch, P Greene, G Small, E Crawford, ED TI SWOG 99-16: Randomized phase III trial of docetaxel (D)/estramustine (E) versus mitoxantrone(M)/prednisone(p) in men with androgen-independent prostate cancer (AIPCA) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 New York Presbyterian Hosp, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. Dana Farber Canc Ctr, Boston, MA USA. Mayo Clin, Rochester, MN USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 2 Z9 2 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 3 BP 2S EP 2S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400005 ER PT J AU Sloan, JA McLeod, H Sargent, D Zhao, X Fuchs, C Ramanathan, R Williamson, S Findlay, B Morton, R Goldberg, RM AF Sloan, JA McLeod, H Sargent, D Zhao, X Fuchs, C Ramanathan, R Williamson, S Findlay, B Morton, R Goldberg, RM TI Preliminary evidence of relationship between genetic markers and oncology patient quality of life (QOL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Natl Canc Inst Canada, St Catharines, ON, Canada. Iowa Oncol Res Associate CCOP, Des Moines, IA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RI Goldberg , Richard/M-1311-2013 NR 0 TC 3 Z9 3 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 15 PY 2004 VL 22 IS 14 SU S MA 5 BP 2S EP 2S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400006 PM 28014162 ER PT J AU Seidman, AD Berry, D Cirrincione, C Harris, L Dressler, L Muss, H Norton, L Winer, E Hudis, C AF Seidman, AD Berry, D Cirrincione, C Harris, L Dressler, L Muss, H Norton, L Winer, E Hudis, C TI CALGB 9840: Phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Vermont, Burlington, VT 05405 USA. NR 0 TC 35 Z9 36 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 512 BP 6S EP 6S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400020 ER PT J AU Baselga, J Fumoleau, P Gil, M Colomer, R Roche, H Cortes-Funes, H Burstein, H Kaufman, P Kong, S Moore, L AF Baselga, J Fumoleau, P Gil, M Colomer, R Roche, H Cortes-Funes, H Burstein, H Kaufman, P Kong, S Moore, L TI Phase II, 3-arm study of CCI-779 in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer: Preliminary results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Ctr Rene Gauducheau, St Herblain, France. Hosp Gen Valle Hebron, Barcelona, Spain. Inst Catala Oncol, Barcelona, Spain. Inst Catala Oncol, Girona, Spain. Inst Claudius Regaud, Toulouse, France. Hosp Univ Madrid, Madrid, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Wyeth Ayerst Res, Cambridge, MA USA. RI Roche, Henri/O-9211-2014; Colomer, Ramon/C-5142-2008 OI Roche, Henri/0000-0001-7463-205X; Colomer, Ramon/0000-0002-6393-3444 NR 0 TC 9 Z9 9 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 544 BP 13S EP 13S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400049 PM 28016595 ER PT J AU Burstein, HJ Overmoyer, B Gelman, R Silverman, P Savoie, J Clarke, K Dumadag, L Younger, J Winer, EP AF Burstein, HJ Overmoyer, B Gelman, R Silverman, P Savoie, J Clarke, K Dumadag, L Younger, J Winer, EP TI Rebeccamycin analog for refractory breast cancer: A randomized phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 547 BP 14S EP 14S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400054 ER PT J AU Dressler, LG Broadwater, G Berry, D Cirrincione, C Cowan, D Harris, L Moore, D Muss, H Hayes, D Ellis, M AF Dressler, LG Broadwater, G Berry, D Cirrincione, C Cowan, D Harris, L Moore, D Muss, H Hayes, D Ellis, M TI A comparison of two HER2 FISH methods to measure HER2 amplification and predict clinical outcome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ N Carolina, Chapel Hill, NC USA. Univ Chicago, Chicago, IL 60637 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. Univ Vermont, Burlington, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, St Louis, MO USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 566 BP 18S EP 18S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400071 PM 28016471 ER PT J AU Jones, JL Rhei, E Gadd, MA Howard-Mcnatt, M Hughes, KS Lesnikoski, BA Christian, RL Rabban, JT Kaelin, C Smith, BL AF Jones, JL Rhei, E Gadd, MA Howard-Mcnatt, M Hughes, KS Lesnikoski, BA Christian, RL Rabban, JT Kaelin, C Smith, BL TI Predictive value of sentinel lymph node biopsy prior to neoadjuvant chemotherapy in clinically node negative breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 606 BP 28S EP 28S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400111 PM 28016633 ER PT J AU Cameron, DA Winer, E Campos, S Guastalla, JP AF Cameron, DA Winer, E Campos, S Guastalla, JP TI A comparative study of exemestane versus anastrozole in post-menopausal breast cancer subjects with visceral disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Leon Berard, F-69373 Lyon, France. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 628 BP 34S EP 34S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400134 PM 28016682 ER PT J AU Kirsch, DG Ledezma, CJ Mathews, CS Ancukiewicz, M Bahn, AK Hochberg, FH Loeffler, JS AF Kirsch, DG Ledezma, CJ Mathews, CS Ancukiewicz, M Bahn, AK Hochberg, FH Loeffler, JS TI Brain metastases from breast cancer: Survival by HER2 status in the trastuzumab era. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 779 BP 71S EP 71S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400281 PM 28014192 ER PT J AU Garber, J Digianni, L Rue, M Schneider, K Shannon, K Borstelmann, N Kalkbrenner, K Scheib, R AF Garber, J Digianni, L Rue, M Schneider, K Shannon, K Borstelmann, N Kalkbrenner, K Scheib, R TI A randomized trial of two different genetic counseling interventions for BRCA1/2 genetic testing. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 1002 BP 97S EP 97S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400383 PM 28014638 ER PT J AU Dorval, M Digianni, L Garber, JE Patenaude, AF AF Dorval, M Digianni, L Garber, JE Patenaude, AF TI Communication of BRCA1/2 test results to first-degree relatives (FDRs): Factors predicting who women tell. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Laval, Laval, PQ, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 1010 BP 99S EP 99S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400391 PM 28014623 ER PT J AU Digianni, L Rue, M Emmons, K Garber, J AF Digianni, L Rue, M Emmons, K Garber, J TI Comparison of complementary medicine use at genetic testing program enrollment and one-year following results disclosure. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 1013 BP 100S EP 100S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400396 PM 28014606 ER PT J AU Hartman, AR Mills, MA Kurian, AW Ford, JM Smith, DN Daniel, BL AF Hartman, AR Mills, MA Kurian, AW Ford, JM Smith, DN Daniel, BL TI Identification of ductal atypia with MR galactography. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 1035 BP 105S EP 105S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400415 PM 28014664 ER PT J AU Raizer, JJ Abrey, LE Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M AF Raizer, JJ Abrey, LE Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M TI A phase II trial of erlotinib (OSI-774) in patients (pts) with recurrent malignant gliomas (MG) not on EIAEDs. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. NCI, Neurooncol Branch, NIH, Bethesda, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 24 Z9 24 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 15 PY 2004 VL 22 IS 14 SU S MA 1502 BP 107S EP 107S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400422 PM 28015384 ER PT J AU Manon, RR Oneill, A Mehta, M Knisely, J Werner-Wasik, M Lazarus, H Wagner, H Gilbert, M AF Manon, RR Oneill, A Mehta, M Knisely, J Werner-Wasik, M Lazarus, H Wagner, H Gilbert, M TI Phase II trial of radiosurgery (RS) for 1 to 3 newly diagnosed brain metastases from renal cell, melanoma, and sarcoma: An Eastern Cooperative Oncology Group Study (E6397). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Wisconsin, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Sch Med, New Haven, CT USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Penn State Canc Inst, Hershey, PA USA. MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1507 BP 108S EP 108S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400428 PM 28015381 ER PT J AU Prados, M Yung, W Wen, P Junck, L Fink, K Cloughesy, T Robins, I Chang, S Kuhn, J AF Prados, M Yung, W Wen, P Junck, L Fink, K Cloughesy, T Robins, I Chang, S Kuhn, J TI Phase I study of ZD1839 plus temozolomide in patients with malignant glioma. a study of the North American Brain Tumor Consortium. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas San Antonio, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas San Antonio SW, Dallas, TX USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1504 BP 108S EP 108S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400425 PM 28015386 ER PT J AU Lieberman, FS Cloughesy, T Fine, H Kuhn, J Lamborn, K Malkin, M Robbins, HI Yung, WA Wen, P Prados, M AF Lieberman, FS Cloughesy, T Fine, H Kuhn, J Lamborn, K Malkin, M Robbins, HI Yung, WA Wen, P Prados, M TI NABTC phase I/II trial of ZD-1839 for recurrent malignant gliomas and unresectable meningiomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Wisconsin, Madison, WI 53706 USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1510 BP 109S EP 109S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400430 PM 28015363 ER PT J AU Batchelo, T Grossman, S Carson, K Fisher, J AF Batchelo, T Grossman, S Carson, K Fisher, J TI Updated results from NABTT CNS consortium studies in primary CNS lymphoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1518 BP 111S EP 111S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400440 ER PT J AU Kieren, MW Packer, R Boyett, J Sugrue, M Kun, L AF Kieren, MW Packer, R Boyett, J Sugrue, M Kun, L TI Phase I trial of the oral farnesyl protein transferase inhibitor lonafamib (SCH66336): A Pediatric Brain Tumor Consortium (PBTC) study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 PBTC, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Schering Plough Corp, Warren, NJ USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 1517 BP 111S EP 111S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400439 PM 28015358 ER PT J AU Shah, G Kesari, S Xu, R Henson, J Batchelor, T Hochberg, F Oneill, A Levy, B Bradshaw, J Wen, PY AF Shah, G Kesari, S Xu, R Henson, J Batchelor, T Hochberg, F Oneill, A Levy, B Bradshaw, J Wen, PY TI Comparison of 1D, 2D, 3D and volumetric parameters in measuring tumor response in high-grade gliomas in adults. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 1523 BP 112S EP 112S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400444 PM 28015429 ER PT J AU New, PZ Grossman, S Mikkelsen, T Batchelor, T Phuphanich, S Carson, K Fisher, J Craig, M Cagnoni, P AF New, PZ Grossman, S Mikkelsen, T Batchelor, T Phuphanich, S Carson, K Fisher, J Craig, M Cagnoni, P TI Evaluation of safety and tolerance of escalating doses of RSR13 administered with a fixed dose of BCNU every six weeks in patients with recurrent malignant glioma: Results of the phase INABTT 9806 clinical trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Baylor Coll Med, Houston, TX 77030 USA. Johns Hopkins Canc Ctr, Baltimore, MD USA. Henry Ford Hosp, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Johns Hopkins Canc Ctr, Baltimore, MD USA. Allos Therapeut Inc, Westminster, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1533 BP 115S EP 115S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400455 PM 28015406 ER PT J AU Chakravarti, A Seiferheld, W Robins, HI Guha, A Brachman, D Curran, W Choucair, A Mehta, M AF Chakravarti, A Seiferheld, W Robins, HI Guha, A Brachman, D Curran, W Choucair, A Mehta, M TI An update of phase I data from RTOG 0211: A phase I/II clinical study of gefitinib plus radiation for newly-diagnosed glioblastoma (GBM) patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Coll Radiol, Philadelphia, PA USA. Univ Wisconsin, Madison, WI USA. Univ Toronto, Toronto, ON, Canada. Fdn Canc Res, Phoenix, AZ USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. LDS Hosp, Salt Lake City, UT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1571 BP 124S EP 124S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400492 ER PT J AU Moots, PL O'Neill, A Barger, GR Mehta, MP Gilbert, MR AF Moots, PL O'Neill, A Barger, GR Mehta, MP Gilbert, MR TI Toxicities associated with chemotherapy followed by craniospinal radiation for adults with poor-risk medulloblastoma/PNET and disseminated ependymoma; a preliminary report of ECOG 4397. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Vanderbilt Univ, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Wisconsin, Madison, WI USA. MD Anderson Canc Ctr, Houston, TX USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 1573 BP 125S EP 125S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400495 PM 28015727 ER PT J AU Suk, R Gurubhagavatula, S Park, S Zhou, W Su, L Lynch, TJ Wain, JC Neuberg, D Liu, G Christiani, DC AF Suk, R Gurubhagavatula, S Park, S Zhou, W Su, L Lynch, TJ Wain, JC Neuberg, D Liu, G Christiani, DC TI The ERCC1 C8092A polymorphism and grade III/IV gastrointestinal (GI) toxicity in non-small cell lung cancer (NSCLC) patients treated with chemoradiation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 2014 BP 130S EP 130S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400514 PM 28015601 ER PT J AU Kolesar, JM Breunig, A Miller, J Stephenson, P McLeod, H Marsh, S Keller, S Johnson, D Schiller, JH AF Kolesar, JM Breunig, A Miller, J Stephenson, P McLeod, H Marsh, S Keller, S Johnson, D Schiller, JH TI CYP3A5*3 and CYP3A4*1B polymorphisms are associated and more frequent in NSCLC tumors than in normal volunteers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Wisconsin, Eastern Cooperat Oncol Grp, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 2016 BP 131S EP 131S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400517 PM 28015596 ER PT J AU Letrent, S Callegri, F Wong, T Burris, H Cohen, R Lorusso, P Papadimitrakopoulou, V Shapiro, G Griffin, T Decillis, A AF Letrent, S Callegri, F Wong, T Burris, H Cohen, R Lorusso, P Papadimitrakopoulou, V Shapiro, G Griffin, T Decillis, A TI Evaluation of a novel RNA biomarker of CDK2 inhibition in phase 1 clinical trials with BMS-387032. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Sarah Canon Canc Ctr, Nashville, TN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 2031 BP 134S EP 134S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400532 PM 28015634 ER PT J AU Fischman, A Letrent, S Bonab, A Livni, E Carter, E Rubin, R Mauro, D Tarby, C Galbraith, S Griffin, T AF Fischman, A Letrent, S Bonab, A Livni, E Carter, E Rubin, R Mauro, D Tarby, C Galbraith, S Griffin, T TI PET as a biomarker of the antitumor effects of the CDK2 inhibitor BMS-387032. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2032 BP 135S EP 135S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400533 PM 28015642 ER PT J AU Supko, JG Alderson, L Wen, P Cassidy, K Pace, S Obrocea, M Hochberg, F AF Supko, JG Alderson, L Wen, P Cassidy, K Pace, S Obrocea, M Hochberg, F TI Pharmacokinetics of gimatecan, and orally administered camptothecin analogue, in patients with malignant gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Rhode Isl Hosp, Providence, RI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sigma Tau Res, Gaithersburg, MD USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 2039 BP 136S EP 136S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400540 ER PT J AU Zhu, AX Bukowski, R Lockhart, AC Wang, KK Cooper, W Grover, J Cohen, M Appleman, L Shapiro, M Rothenberg, ML AF Zhu, AX Bukowski, R Lockhart, AC Wang, KK Cooper, W Grover, J Cohen, M Appleman, L Shapiro, M Rothenberg, ML TI Phase 1 trial of oral MAC-321 in subjects with advanced malignant solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Partners Cancercare, Boston, MA USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Wyeth Ayerst Res, Cambridge, MA USA. Taxolog Inc, Fairfield, NJ USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 2040 BP 137S EP 137S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400541 PM 28015621 ER PT J AU Bonate, P Ebbinghaus, S Eder, JP Mita, A Rubin, E Cunningham, CC Rowinsky, EK Hersh, E Craig, AR Hammond, LA AF Bonate, P Ebbinghaus, S Eder, JP Mita, A Rubin, E Cunningham, CC Rowinsky, EK Hersh, E Craig, AR Hammond, LA TI Pharmacokinetics of synthadotin (ILX651), a novel tubulin polymerization inhibitor, in patients with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 ILEX Prod Inc, San Antonio, TX USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CTRC, Inst Drug Dev, San Antonio, TX USA. Canc Inst New Jersey, New Brunswick, NJ USA. US Oncol, Mary Crowley Res Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 2082 BP 147S EP 147S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400582 PM 28015689 ER PT J AU Roberts, TG Goulart, BHL Stallings, SC Squitieri, L Chabner, BA Finkelstein, SN Clark, JW AF Roberts, TG Goulart, BHL Stallings, SC Squitieri, L Chabner, BA Finkelstein, SN Clark, JW TI Analysis of over 2,400 modern phase I cancer trials: Composition, outcomes, and use of surrogate endpoints. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 2084 BP 148S EP 148S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400585 PM 28015680 ER PT J AU Avigan, DE George, DJ Kantoff, PW Figlin, RA Kufe, DW Olencki, TE Vasconcelles, MJ Vasir, BS Xu, Y Bukowski, RM AF Avigan, DE George, DJ Kantoff, PW Figlin, RA Kufe, DW Olencki, TE Vasconcelles, MJ Vasir, BS Xu, Y Bukowski, RM TI Interim safety and efficacy results from a phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Canc Med, Los Angeles, CA 90024 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Genzyme Corp, Cambridge, MA USA. NR 0 TC 1 Z9 1 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 2526 BP 169S EP 169S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400668 PM 28015017 ER PT J AU Hodi, FS Seiden, M Butler, M Haluska, FG Lowy, I Vincent-Brunick, E Lautz, D Mihm, M Dranoff, G AF Hodi, FS Seiden, M Butler, M Haluska, FG Lowy, I Vincent-Brunick, E Lautz, D Mihm, M Dranoff, G TI Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody blockade in patients previously vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GMCSF). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Medarex Inc, Bloomsbury, NJ USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 2536 BP 172S EP 172S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400679 PM 28015244 ER PT J AU Demetri, GD Desai, J Fletcher, JA Morgan, JA Fletcher, CDM Kazanovicz, A Van den Abbeele, A Baum, C Maki, R Heinrich, MC AF Demetri, GD Desai, J Fletcher, JA Morgan, JA Fletcher, CDM Kazanovicz, A Van den Abbeele, A Baum, C Maki, R Heinrich, MC TI SU11248, a multi-targeted tyrosine kinase inhibitor, can overcome imatinib (IM) resistance caused by diverse genomic mechanisms in patients (pts) with metastatic gastrointestinal stromal tumor (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pfizer Inc, La Jolla, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Portland, OR USA. NR 0 TC 12 Z9 14 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 15 PY 2004 VL 22 IS 14 SU S MA 3001 BP 195S EP 195S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400770 ER PT J AU Rothenberg, ML Lafleur, B Washington, MK Levy, DE Morgan-Meadows, SL Ramanathan, RK Berlin, JD Benson, AIB Coffey, RJ AF Rothenberg, ML Lafleur, B Washington, MK Levy, DE Morgan-Meadows, SL Ramanathan, RK Berlin, JD Benson, AIB Coffey, RJ TI Changes in epidermal growth factor receptor signaling in serum and tumor biopsies obtained from patients with progressive metastatic colorectal cancer (MCRC) treated with gefitinib (ZD1839); An Eastern Cooperative Oncology Group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ECOG Stat Ctr, Boston, MA USA. Univ Wisconsin, Madison, WI USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 2 Z9 3 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 15 PY 2004 VL 22 IS 14 SU S MA 3000 BP 195S EP 195S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400768 ER PT J AU Van Oosterom, AT Dumez, H Desai, J Stroobants, S Van den Abbeele, AD Clement, P Shand, N Kovarik, J Tsyrlova, A Demetri, GD AF Van Oosterom, AT Dumez, H Desai, J Stroobants, S Van den Abbeele, AD Clement, P Shand, N Kovarik, J Tsyrlova, A Demetri, GD TI Combination signal transduction inhibition: A phase I/II trial of the oral mTOR-inhibitor everolimus (E, RAD001) and imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 UZ Gasthuisberg, Louvain, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharma, Basel, Switzerland. NR 0 TC 7 Z9 6 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 15 PY 2004 VL 22 IS 14 SU S MA 3002 BP 195S EP 195S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400769 ER PT J AU Desai, J Shankar, S Heinrich, MC Fletcher, JA Fletcher, CDM Tuncali, K Silverman, SG Van den Abbeele, AD Vansonnenberg, E Demetri, GD AF Desai, J Shankar, S Heinrich, MC Fletcher, JA Fletcher, CDM Tuncali, K Silverman, SG Van den Abbeele, AD Vansonnenberg, E Demetri, GD TI Clonal evolution of resistance to imatinib (IM) in patients (pts) with gastrointestinal stromal tumor (GIST): Molecular and radiologic evaluation of new lesions. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. OHSU, Ctr Canc, Portland, OR USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 3010 BP 197S EP 197S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400777 PM 28015168 ER PT J AU Holdsworth, CH Manola, J Badawi, RD Israel, DA Blanke, C Von Mehren, M Joensuu, HT Dimitrijevic, S Demetri, GD Van den Abbeele, AD AF Holdsworth, CH Manola, J Badawi, RD Israel, DA Blanke, C Von Mehren, M Joensuu, HT Dimitrijevic, S Demetri, GD Van den Abbeele, AD TI Use of computerized tomography (CT) as an early prognostic indicator of response to imatinib mesylate (IM) in patients with gastrointestinal stromal tumors (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 3011 BP 197S EP 197S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400779 PM 28015171 ER PT J AU Van den Abbeele, AD Badawi, RD Manola, J Morgan, JA Desai, J Kazanovicz, A St Armand, M Baum, C Demetri, GD AF Van den Abbeele, AD Badawi, RD Manola, J Morgan, JA Desai, J Kazanovicz, A St Armand, M Baum, C Demetri, GD TI Effects of cessation of imatinib mesylate (IM) therapy in patients (pts) with IM-refractory gastrointestinal stromal tumors (GIST) as visualized by FDG-PET scanning. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer, San Diego, CA USA. NR 0 TC 8 Z9 8 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 15 PY 2004 VL 22 IS 14 SU S MA 3012 BP 198S EP 198S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400780 PM 28015172 ER PT J AU Giantonio, BJ Chen, HX Catalano, PJ Meropol, NJ O'Dwyer, PJ Benson, AIB AF Giantonio, BJ Chen, HX Catalano, PJ Meropol, NJ O'Dwyer, PJ Benson, AIB TI Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NCI, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3017 BP 199S EP 199S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400786 PM 28015163 ER PT J AU Ottmann, OG Deangelo, DJ Stone, RM Pfeifer, H Lowenberg, B Atadja, P Peng, B Scott, JW Dugan, M Sonneveld, P AF Ottmann, OG Deangelo, DJ Stone, RM Pfeifer, H Lowenberg, B Atadja, P Peng, B Scott, JW Dugan, M Sonneveld, P TI A phase 1, pharmacokinetic (PK) and pharmacodynamic (PD) study of a novel histone deacetylase inhibitor LAQ824 in patients with hematologic malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Frankfurt, D-6000 Frankfurt, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus MC, Rotterdam, Netherlands. Novartis, E Hanover, NJ USA. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 3 Z9 7 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 15 PY 2004 VL 22 IS 14 SU S MA 3024 BP 201S EP 201S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400792 ER PT J AU Gurubhagavatula, S Zhou, W Park, S Neuberg, DS Lynch, TJ Wain, JC Su, L Liu, G Christiani, DC AF Gurubhagavatula, S Zhou, W Park, S Neuberg, DS Lynch, TJ Wain, JC Su, L Liu, G Christiani, DC TI Nucleotide excision repair (NER) gene haplotypes and advanced non-small cell lung cancer (NSCLC) prognosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 3040 BP 205S EP 205S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400808 PM 28015219 ER PT J AU Heymach, JV Dong, RP Dimery, I Wheeler, C Fidias, P Lu, C Johnson, B Herbst, R AF Heymach, JV Dong, RP Dimery, I Wheeler, C Fidias, P Lu, C Johnson, B Herbst, R TI ZD6474, a novel antiangiogenic agent, in combination with docetaxel in patients with NSCLC: Results of the run-in phase of a two-part, randomized phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. AstraZeneca, Wilmington, DE USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 3 Z9 3 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 3051 BP 207S EP 207S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400819 PM 28015208 ER PT J AU Hammond, LA Ruvuna, F Cunningham, CC Ebbinghaus, S Rubin, E Mita, A Hersh, E Eder, JP Weiss, J Rowinsky, EK AF Hammond, LA Ruvuna, F Cunningham, CC Ebbinghaus, S Rubin, E Mita, A Hersh, E Eder, JP Weiss, J Rowinsky, EK TI Phase (Ph) I evaluation of the dolastatin analogue synthadotin (SYN-D; ILX651): Pooled data analysis of three alternate schedules in patients (pts) with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 ILEX Prod Inc, San Antonio, TX USA. Mary Crowley Med Res Ctr, US Oncol, Dallas, TX USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Canc Inst New Jersey, New Brunswick, NJ USA. Inst Drug Dev Canc Therapy, Res Ctr, San Antonio, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 3068 BP 212S EP 212S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400836 PM 28014771 ER PT J AU Saltz, LB Niedzwiecki, D Hollis, D Goldberg, RM Hantel, A Thomas, JP Fields, ALA Carver, G Mayer, RJ AF Saltz, LB Niedzwiecki, D Hollis, D Goldberg, RM Hantel, A Thomas, JP Fields, ALA Carver, G Mayer, RJ TI Irinotecan plus fluorouracil/leucovorin (IFL) versus fluorouracil/leucovorin alone (FL) in stage III colon cancer (intergroup trial CALGB C89803). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CALGB, Ctr Stat, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Edward Canc Ctr, Naperville, IL USA. Univ Wisconsin, Madison, WI USA. Canc Board, Edmonton, AB, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Goldberg , Richard/M-1311-2013 NR 0 TC 23 Z9 24 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 3500 BP 245S EP 245S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400968 ER PT J AU Bertagnolli, MM Redston, M Miedema, B Dowell, J Niedzwiecki, D Mayer, R Fleshman, J Bem, J Compton, C AF Bertagnolli, MM Redston, M Miedema, B Dowell, J Niedzwiecki, D Mayer, R Fleshman, J Bem, J Compton, C TI Sentinel node staging of resectable colon cancer: Results of CALGB 80001. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Missouri, Columbia, MO USA. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Syracuse VA Med Ctr, Syracuse, NY USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3506 BP 246S EP 246S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400973 PM 28016487 ER PT J AU Lenz, HJ Mayer, RJ Gold, PJ Mirtsching, B Stella, PJ Cohn, AL Pippas, AW Azarnia, N Needle, MN Van Cutsem, E AF Lenz, HJ Mayer, RJ Gold, PJ Mirtsching, B Stella, PJ Cohn, AL Pippas, AW Azarnia, N Needle, MN Van Cutsem, E TI Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 USC, Norris Canc Ctr, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sweedish Canc Inst, Seattle, WA USA. Ctr Oncol Res & Treatment, Dallas, TX USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Rocky Mt Canc Ctr, Denver, CO USA. Lakeland Reg Canc Ctr, Lakeland, FL USA. ImClone Syst, Somerville, NJ USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. NR 0 TC 10 Z9 12 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 3510 BP 247S EP 247S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400977 ER PT J AU Colacchio, TA Niedzwiecki, D Compton, C Warren, R Benson, AIB Goldberg, R Kerr, D Fields, A Hollis, D Mayer, R AF Colacchio, TA Niedzwiecki, D Compton, C Warren, R Benson, AIB Goldberg, R Kerr, D Fields, A Hollis, D Mayer, R TI Phase III trial of adjuvant immunotherapy with MOAb 17-1A following resection for stage II adenocarcinoma of the colon (CALGB 9581). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Duke Univ, Durham, NC USA. McGill Univ, Montreal, PQ, Canada. Univ Calif San Francisco, San Francisco, CA 94143 USA. Northwestern Univ, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Univ Birmingham, Birmingham, W Midlands, England. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. DFCI, Boston, MA USA. NR 0 TC 6 Z9 6 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 3522 BP 250S EP 250S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400989 PM 28016523 ER PT J AU Fuchs, C Pollak, M Sargent, DJ Meyerhardt, JA Ramanathan, RK Williamson, S Findlay, B Green, E Goldberg, RM AF Fuchs, C Pollak, M Sargent, DJ Meyerhardt, JA Ramanathan, RK Williamson, S Findlay, B Green, E Goldberg, RM TI Insulin-like growth factor-I (IGF-1), IGF binding protein-3 (IGFBP-3), and outcome in metastatic colorectal cancer (CRC): Results from Intergroup Trial N9741. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Montreal, PQ, Canada. NCCTG, Rochester, MN USA. ECOG, Pittsburgh, PA USA. SWOG, Kansas City, KS USA. NCIC, St Catharines, ON, Canada. RI Goldberg , Richard/M-1311-2013 NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 3521 BP 250S EP 250S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400990 PM 28016522 ER PT J AU Mitchell, EP Winter, K Mohiuddin, M Hanna, N Yuen, A Nichols, C Share, R Hayostek, C Willett, C AF Mitchell, EP Winter, K Mohiuddin, M Hanna, N Yuen, A Nichols, C Share, R Hayostek, C Willett, C TI Randomized phase II trial of preoperative combined modality chemoradiation for distal rectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RTOG, Philadelphia, PA USA. Univ Kentucky, Lexington, KY USA. Reading Hosp, Reading, PA USA. Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 3535 BP 253S EP 253S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401003 PM 28016500 ER PT J AU Ryan, DP Niedzwiecki, D Hollis, D Miedema, BE Wadler, S Tepper, JE Mayer, RJ AF Ryan, DP Niedzwiecki, D Hollis, D Miedema, BE Wadler, S Tepper, JE Mayer, RJ TI A phase I/II study of preoperative oxaliplatin (0), 5-fluorouracil (5-FU), and external beam radiation therapy (XRT) in locally advanced rectal cancer: CALGB 89901. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 MGH Canc Ctr, CALGB, Boston, MA USA. Duke Univ, Ctr Med, Durham, NC USA. CALGB, Ctr Stat, Durham, NC USA. Univ Missouri, Columbia, MO USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ N Carolina, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S BP 260S EP 260S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401028 ER PT J AU Meyerhardt, JA Xhu, A Enzinger, PC Ryan, DP Clark, JW Kulke, MH Michelini, A Vincitore, M Thomas, A Fuchs, CS AF Meyerhardt, JA Xhu, A Enzinger, PC Ryan, DP Clark, JW Kulke, MH Michelini, A Vincitore, M Thomas, A Fuchs, CS TI Phase II study of capecitabine, oxaliplatin and erlotinib in previously treated patients with metastatic colorectal cancer (MCRC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 3580 BP 265S EP 265S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401048 ER PT J AU Willett, CG Chung, D Sahani, D Mino, M Clark, J Ryan, D Zhu, A Blaszkowski, L Lauwers, G Jain, R AF Willett, CG Chung, D Sahani, D Mino, M Clark, J Ryan, D Zhu, A Blaszkowski, L Lauwers, G Jain, R TI Phase I study of neoadjuvant bevacizumab, 5-fluorouracil, and radiation therapy followed by surgery for patients with primary rectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 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 15 PY 2004 VL 22 IS 14 SU S MA 3589 BP 267S EP 267S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401058 PM 28016318 ER PT J AU Goldberg, RM Sargent, DJ Morton, RF Fuchs, C Ramanathan, RK Williamson, SK Findlay, BP Pitot, HR Alberts, SR AF Goldberg, RM Sargent, DJ Morton, RF Fuchs, C Ramanathan, RK Williamson, SK Findlay, BP Pitot, HR Alberts, SR TI N9741: FOLFOX (oxaliplatin(Oxal)/5-fluorouracil (5-FUV leucovorin (LV) or reduced dose R-IFL (CPT-11+5-FUAV) in advanced colorectal cancer (CRC): Final efficacy data from an intergroup study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ N Carolina, Chapel Hill, NC USA. Mayo Clin, Rochester, MN USA. Iowa Oncol Res Assoc CCOP, Des Moines, IA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, OR USA. Univ Kansas, Kansas City, KS 66103 USA. St Catharines Hosp, St Catharines, ON, Canada. RI Goldberg , Richard/M-1311-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3621 BP 275S EP 275S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401088 ER PT J AU McCollum, AD Wu, B Clark, J Kulke, M Enzinger, P Ryan, D Earle, C Michelini, A Fuchs, C AF McCollum, AD Wu, B Clark, J Kulke, M Enzinger, P Ryan, D Earle, C Michelini, A Fuchs, C TI Capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Baylor Sammons Canc Ctr, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 3657 BP 283S EP 283S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401123 PM 28014585 ER PT J AU Kulke, MH Niedzwiecki, D Tempero, MA Hollis, DR Mayer, RJ AF Kulke, MH Niedzwiecki, D Tempero, MA Hollis, DR Mayer, RJ TI A randomized phase II study of gemcitabine/cisplatin, gemcitabine fixed dose rate infusion, gemcitabine/docetaxel, or gemcitabinefirinotecan in patients with metastatic pancreatic cancer (CALGB 89904). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 1 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 4011 BP 316S EP 316S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401250 ER PT J AU Enzinger, PC Clark, J Ryan, D Meyerhardt, J Kulke, M Fidias, P Earle, C Vincitore, M Michelini, A Fuchs, C AF Enzinger, PC Clark, J Ryan, D Meyerhardt, J Kulke, M Fidias, P Earle, C Vincitore, M Michelini, A Fuchs, C TI Phase II study of docetaxel, cisplatin, and irinotecan in advanced esophageal and gastric cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Partners Canc Care, Boston, MA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4040 BP 323S EP 323S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401279 PM 28014372 ER PT J AU Roof, KS Coen, J Lynch, TJ Wright, CD Fidias, P Willett, CG Choi, NC AF Roof, KS Coen, J Lynch, TJ Wright, CD Fidias, P Willett, CG Choi, NC TI Neo-adjuvant radiation, cisplatin, 5-FU +/- paclitaxel in locally advanced esophageal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4042 BP 324S EP 324S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401281 PM 28014362 ER PT J AU Motzer, RJ Rini, BI Michaelson, MD Redman, BG Hudes, GR Wilding, G Figlin, RA Zhu, J Kim, ST Baum, C AF Motzer, RJ Rini, BI Michaelson, MD Redman, BG Hudes, GR Wilding, G Figlin, RA Zhu, J Kim, ST Baum, C TI SUO11248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: Results of a phase 2 trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Wisconsin, Madison, WI USA. Univ Calif Los Angeles, Los Angeles, CA USA. Pfizer Inc, La Jolla, CA USA. NR 0 TC 5 Z9 6 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 15 PY 2004 VL 22 IS 14 SU S MA 4500 BP 382S EP 382S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401513 ER PT J AU Crawford, ED Pauler, DK Tangen, CM Hussain, MHA Small, EJ Taplin, ME Burch, PA Greene, GF Lara, P Petrylak, DP AF Crawford, ED Pauler, DK Tangen, CM Hussain, MHA Small, EJ Taplin, ME Burch, PA Greene, GF Lara, P Petrylak, DP TI Three-month change in PSA as a surrogate endpoint for mortality in advanced hormone-refractory prostate cancer (HRPC): Data from Southwest Oncology Group Study S9916 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Colorado, Ctr Hlth Sci, Aurora, CO USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Arkansas, Sch Med, Little Rock, AR 72204 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 4505 BP 383S EP 383S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401518 PM 28016018 ER PT J AU Smith, MR Lee, WC Krupsi, T Brandman, J Wang, Q Botteman, M Pashos, C Litwin, M AF Smith, MR Lee, WC Krupsi, T Brandman, J Wang, Q Botteman, M Pashos, C Litwin, M TI Association between androgen deprivation therapy and fracture risk: A population-based cohort study in men with non-metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. ABT Associates Inc, Bethesda, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Nova Pharmaceut Corp, Florham Pk, NJ USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4507 BP 383S EP 383S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401520 PM 28016016 ER PT J AU Kelly, WK Galsky, MD Small, EJ Oh, W Chen, I Smith, D Martone, L Curley, T Delacruz, A Scher, HI AF Kelly, WK Galsky, MD Small, EJ Oh, W Chen, I Smith, D Martone, L Curley, T Delacruz, A Scher, HI TI Multi-institutional trial of the epothilone B analogue BMS-247550 with or without estramustine phosphate (EMP) in patients with progressive castratemetastatic prostate cancer (PCMPC): Updated results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4509 BP 384S EP 384S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401522 PM 28016010 ER PT J AU Atkins, M McDermott, D Regan, M Stanbridge, E Upton, M Youmans, A Febbo, P Lechpammer, M Signoretti, S AF Atkins, M McDermott, D Regan, M Stanbridge, E Upton, M Youmans, A Febbo, P Lechpammer, M Signoretti, S TI Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 4512 BP 385S EP 385S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401525 ER PT J AU Gordon, MS Manola, J Fairclough, D Cella, D Richardson, R Sosman, J Kasimis, B Dutcher, JP Wilding, G AF Gordon, MS Manola, J Fairclough, D Cella, D Richardson, R Sosman, J Kasimis, B Dutcher, JP Wilding, G TI Low dose interferon-alpha 2b (IFN) + thalidomide (T) in patients (pts) with previously untreated renal cell cancer (RCC). Improvement in progression-free survival (PFS) but not quality of life (QoL) or overall survival (OS). A phase III study of the Eastern Cooperative Oncology Group (E2898). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Arizona Canc Ctr, Scottsdale, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. AMC, Canc Res Ctr, Denver, CO USA. Evanston NW Healthcare, Evanston, IL USA. Mayo Clin, Rochester, MN USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. VA New Jersey Hlth Care Syst, E Orange, NJ USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Univ Wisconsin, Hosp & Clin, Madison, WI 53792 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4516 BP 386S EP 386S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401529 ER PT J AU Carloss, E Regan, M Upton, M Youmans, A McDermott, D Polivy, A Atkins, M AF Carloss, E Regan, M Upton, M Youmans, A McDermott, D Polivy, A Atkins, M TI Concordance of local pathology interpretation (LR) with central pathology review (CR) in primary tumor specimens from patients with renal cancer (RCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Harvard Univ, Dana Farber Canc Ctr, Renal Cell Canc Program Dev, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4548 BP 393S EP 393S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401560 PM 28016044 ER PT J AU Ryan, CH Halabi, S Kaplan, E Vogelzang, N Kantoff, P Small, EJ AF Ryan, CH Halabi, S Kaplan, E Vogelzang, N Kantoff, P Small, EJ TI Use of adrenal androgen levels to predict response to ketoconazole in patients with androgen independent prostate cancer: Results from CALGB 9583. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Durham, NC USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 4558 BP 396S EP 396S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401570 PM 28015948 ER PT J AU Taplin, ME George, DJ Halabi, S Sellers, WR Sanford, B Hennessy, KT Mihos, GG Small, EJ Kantoff, PW AF Taplin, ME George, DJ Halabi, S Sellers, WR Sanford, B Hennessy, KT Mihos, GG Small, EJ Kantoff, PW TI Prognostic significance of plasma chromogranin A levels in hormone-refractory prostate cancer patients treated an Cancer and Leukemia Group B (CALGB) 9480. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4557 BP 396S EP 396S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401569 PM 28015949 ER PT J AU Chen, RC Clark, JA Mitchell, SP Talcott, JA AF Chen, RC Clark, JA Mitchell, SP Talcott, JA TI Treatment "mismatch" in early prostate cancer: An empirical measure of patient-physician communication SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4566 BP 398S EP 398S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401578 PM 28015941 ER PT J AU Messing, EM Manola, J Sarosdy, M Wilding, G Crawford, D Kiernan, M Trump, D AF Messing, EM Manola, J Sarosdy, M Wilding, G Crawford, D Kiernan, M Trump, D TI Immediate hormonal therapy versus observation after radical prostatectomy and pelvic lymphadenectomy for node positive prostate cancer: At 10 years results of EST3886. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Rochester, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. S Texas Urol, San Antonio, NY USA. Univ Wisconsin, Madison, WI USA. Univ Colorado, Denver, CO 80202 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4570 BP 399S EP 399S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401582 PM 28015974 ER PT J AU Halabi, S Small, EJ Gilligian, T Barrier, R George, S Vogelzang, NJ AF Halabi, S Small, EJ Gilligian, T Barrier, R George, S Vogelzang, NJ TI The effect of race on progression-free survival in patients with metastatic hormone-refractory prostate cancer (HRPC): A pooled analysis of CALGB studies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4573 BP 400S EP 400S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401585 PM 28015978 ER PT J AU Berry, DL Moinpour, CM Jiang, C Vinson, V Lara, PN Lanier, S Taplin, ME Burch, PA Petrylak, DP Crawford, ED AF Berry, DL Moinpour, CM Jiang, C Vinson, V Lara, PN Lanier, S Taplin, ME Burch, PA Petrylak, DP Crawford, ED TI Quality of life (QOL) and pain in advanced stage prostate cancer: Impact of missing data on evaluating palliation in SWOG 9916. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Washington, Seattle, WA 98195 USA. SW Oncol Grp, Ctr Stat, FHCRC, Seattle, WA 98195 USA. Columbia Presbyterian Med Ctr, Little Rock, AR USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. SW Med Onc Ctr, Goldsboro, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. NR 0 TC 1 Z9 1 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 4579 BP 401S EP 401S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401591 PM 28015969 ER PT J AU Garzotto, M Mongoue-Tchokote, S Bledsoe, J Parra, RO Peters, L Park, Y Beer, TM Mori, M AF Garzotto, M Mongoue-Tchokote, S Bledsoe, J Parra, RO Peters, L Park, Y Beer, TM Mori, M TI Predictors of prostate cancer in men undergoing serial prostate biopsies: Results from 371 patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4589 BP 404S EP 404S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401601 PM 28015959 ER PT J AU Dipaola, RS Manola, J Li, S Vaughn, D Roth, B Wilding, G AF Dipaola, RS Manola, J Li, S Vaughn, D Roth, B Wilding, G TI A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic hormone refractory prostate cancer: Results of ECOG 3899. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Canc Inst New Jersey, New Brunswick, NJ USA. Dana Farber Canc Inst, Ctr Stat, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Vanderbilt Univ, Nashville, TN USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4594 BP 405S EP 405S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401606 PM 28015980 ER PT J AU Janoff, D Mongoue-Tchokote, S Peterson, C Parra, RO Peters, L Park, Y Beer, TM Mori, M Garzotto, M AF Janoff, D Mongoue-Tchokote, S Peterson, C Parra, RO Peters, L Park, Y Beer, TM Mori, M Garzotto, M TI Outcomes of androgen deprivation as sole therapy for localized prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4627 BP 413S EP 413S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401639 PM 28015746 ER PT J AU Oh, WK Hagmann, E Manola, J George, DJ Gilligan, TD Smith, MR Kaufman, DS Kantoff, PW AF Oh, WK Hagmann, E Manola, J George, DJ Gilligan, TD Smith, MR Kaufman, DS Kantoff, PW TI A phase I study of estramustine, weekly docetaxel and carboplatin (EDC) chemotherapy in patients with hormone refractory prostate cancer (HRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 4656 BP 420S EP 420S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401667 PM 28015800 ER PT J AU Tay, MH George, DJ Gilligan, TD Kelly, SM Appleby, L Taplin, ME Febbo, PG Kantoff, PW Oh, WK AF Tay, MH George, DJ Gilligan, TD Kelly, SM Appleby, L Taplin, ME Febbo, PG Kantoff, PW Oh, WK TI Docetaxel plus carboplatin (DC) may have significant activity in hormone refractory prostate cancer (HRPC) patients who have progressed after prior docetaxel-based chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 4679 BP 426S EP 426S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401690 PM 28015597 ER PT J AU George, D Oh, W Gilligan, T Masson, E Souppart, C Wang, Y Ho, Y Lebwohl, D Laurent, D Kantoff, P AF George, D Oh, W Gilligan, T Masson, E Souppart, C Wang, Y Ho, Y Lebwohl, D Laurent, D Kantoff, P TI Phase I study of the novel, oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK): Evaluating the pharmacokinetic effect of a high-fat meal in patients with hormone-refractory prostate cancer (HRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Duke Univ, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Nova Pharmaceut Corp, E Hanover, NJ USA. Schering AG, D-1000 Berlin, Germany. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 4689 BP 428S EP 428S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401700 PM 28015578 ER PT J AU Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, Y Prchal, JT AF Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, Y Prchal, JT TI Role of African American genetic polymorphisms in prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4710 BP 433S EP 433S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401720 PM 28016992 ER PT J AU Spurgeon, S Riavadeneira, A Peters, LM Yi-Ching, H Beer, TM Mori, M Garzotto, M AF Spurgeon, S Riavadeneira, A Peters, LM Yi-Ching, H Beer, TM Mori, M Garzotto, M TI Prediction of aggressive prostate cancer on biopsy using classification and regression tree analysis (CART). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 4720 BP 436S EP 436S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401730 PM 28016972 ER PT J AU Lubiniecki, GM Chen, Z Thompson, S Algazy, KM AF Lubiniecki, GM Chen, Z Thompson, S Algazy, KM TI Mortality from prostate cancer (PC) in Pennsylvania(PA) in civilian versus Veterans Administration (VA) populations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. UPA, Dept Biostat & Epidemiol, Philadelphia, PA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 4768 BP 448S EP 448S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401778 PM 28017052 ER PT J AU Seiden, MV Benigno, BB AF Seiden, MV Benigno, BB CA SMART Study Investigator Grp TI A pivotal phase III trial to evaluate the efficacy and safety of adjuvant treatment with R1549 (yttrium-90-labeled HMFG1 murine monoclonal antibody) in epithelial ovarian cancer (EOC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, SMART Study Investigator Grp, Boston, MA 02114 USA. SE Gynecol Oncol, Atlanta, GA USA. NR 0 TC 3 Z9 3 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5008 BP 451S EP 451S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401787 PM 28015490 ER PT J AU Krasner, CN McMeekin, S Chan, S Braly, P Kaye, S Provencher, D Klecz, J Michiels, B Van de Velde, HV Gore, M AF Krasner, CN McMeekin, S Chan, S Braly, P Kaye, S Provencher, D Klecz, J Michiels, B Van de Velde, HV Gore, M TI A phase II study of weekly trabectedin (ET-743) in second/third line ovarian carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. City Hosp Nottingham, Nottingham, England. Hematol Oncol Specialists, New Orleans, LA USA. Royal Marsden Hosp, London SW3 6JJ, England. CHUM, Hop Notre Dame, Montreal, PQ, Canada. J&J PRD, Beerse, Belgium. J&J PRD, Titusville, NJ USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5045 BP 460S EP 460S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401825 PM 28015535 ER PT J AU Campos, SM Seiden, MV Oza, A Plante, M Potkul, R Hamid, O Lenehan, P Kaldjian, E Jordan, C Hirte, H AF Campos, SM Seiden, MV Oza, A Plante, M Potkul, R Hamid, O Lenehan, P Kaldjian, E Jordan, C Hirte, H TI A phase 2, single agent study of Cl-1033 administered at two doses in ovarian cancer patients who failed platinum therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pavill Hotel Dieu, Quebec City, PQ, Canada. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Pfizer Inc, Ann Arbor, MI USA. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5054 BP 462S EP 462S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401832 ER PT J AU Matulonis, U Krasner, C Atkinson, T Penson, R AF Matulonis, U Krasner, C Atkinson, T Penson, R TI Long-acting octreotide for the treatment of symptoms of bowel obstruction and intermittent obstruction in advanced ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 5148 BP 486S EP 486S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401927 ER PT J AU Penson, RT Seiden, MV Campos, SM Krasner, CN Fuller, AF Goodman, A Roche, M Willman, A Muzikansky, A Matulonis, UA AF Penson, RT Seiden, MV Campos, SM Krasner, CN Fuller, AF Goodman, A Roche, M Willman, A Muzikansky, A Matulonis, UA TI A phase II study of fixed dose-rate gemcitabine in patients with relapsed Mullerian tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5151 BP 486S EP 486S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401930 PM 28016790 ER PT J AU Argiris, A Li, Y Forastiere, A AF Argiris, A Li, Y Forastiere, A TI Prognostic factors and long-term survivorship in patients with recurrent or metastatic head and neck cancer (HNC): An analysis of two Eastern Cooperative Oncology Group (ECOG) randomized trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Northwestern Univ, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5514 BP 491S EP 491S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401947 ER PT J AU Wirth, LJ Haddad, RI Wieczorek, TJ Faucher, JL Clark, JR Norris, CM Posner, MR AF Wirth, LJ Haddad, RI Wieczorek, TJ Faucher, JL Clark, JR Norris, CM Posner, MR TI Phase I study of gefitinib plus celecoxib in patients with metastatic and/or locally recurrent squamous cell carcinoma of the head and neck (SCCHN). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 5540 BP 498S EP 498S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401974 PM 28013989 ER PT J AU Tishler, RB Haddad, RI Norris, CM Sullivan, C Mahadevan, A Wirth, L Goguen, L Nixon, A Stowell, S Posner, MR AF Tishler, RB Haddad, RI Norris, CM Sullivan, C Mahadevan, A Wirth, L Goguen, L Nixon, A Stowell, S Posner, MR TI A phase I/II study of docetaxel (D) and concomitant boost radiation (CBR) for patients with squamous cell cancer of the head and neck (SCCHN) following induction chemotherapy (IC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Elliot Reg Canc Ctr, Manchester, NH USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 5548 BP 500S EP 500S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401982 PM 28013978 ER PT J AU Chan, AW Liebsch, LJ Deschler, DG Adams, JA Vrishali, LV McIntyre, JF Pommier, P Fabian, RL Busse, PM AF Chan, AW Liebsch, LJ Deschler, DG Adams, JA Vrishali, LV McIntyre, JF Pommier, P Fabian, RL Busse, PM TI Proton radiotherapy for T4 nasopharyngeal carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 5574 BP 506S EP 506S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402007 PM 28014017 ER PT J AU Guadagnolo, BA Tishler, RB Posner, MR Weeks, L Wirth, LJ Norris, CM Sullivan, CA Goguen, L Busse, PM Haddad, RI AF Guadagnolo, BA Tishler, RB Posner, MR Weeks, L Wirth, LJ Norris, CM Sullivan, CA Goguen, L Busse, PM Haddad, RI TI Organ preservation for patients treated with induction chemotherapy OC) followed by radiation therapy (RT) or chemoradiation (CRT) for advanced stage squamous cell carcinoma of the larynx (SCCL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 5600 BP 513S EP 513S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402034 PM 28015295 ER PT J AU Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, L Weeks, JC AF Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, L Weeks, JC TI Fulfillment of the uncertainty principle in cancer clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. NIH, Bethesda, MD 20892 USA. Lesley Coll, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6003 BP 519S EP 519S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402058 PM 28015062 ER PT J AU Goulart, BHL Roberts, TG Clark, JW AF Goulart, BHL Roberts, TG Clark, JW TI Utility and costs of surrogate endpoints (SEs) and biomarkers in phase I oncology trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6012 BP 522S EP 522S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402067 PM 28015126 ER PT J AU Lathan, CS Neville, BA Earle, CC AF Lathan, CS Neville, BA Earle, CC TI The effect of race on recommendation and acceptance of surgical resection for non-metastatic non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Partners Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6018 BP 523S EP 523S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402072 PM 28015111 ER PT J AU Romanus, D Neumann, P Earle, C Weinstein, M Tsai, J Neville, B Weeks, J AF Romanus, D Neumann, P Earle, C Weinstein, M Tsai, J Neville, B Weeks, J TI Out-of-pocket costs (OPC) and time costs (TC) for patients with stage IV non-small cell lung cancer (NSCLC) and their caregivers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 6021 BP 524S EP 524S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402077 PM 28015101 ER PT J AU Earle, CC Schrag, D Neville, BA Yabroff, R Topor, M Fahey, A Warren, J AF Earle, CC Schrag, D Neville, BA Yabroff, R Topor, M Fahey, A Warren, J TI Effect of surgeon specialty an outcomes for ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Informat Management Serv Inc, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6027 BP 525S EP 525S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402082 PM 28015097 ER PT J AU Loberiza, FR Zhang, M Rizzo, JD Lee, SJ Klein, JP Logan, BR Eapen, M Serna, DS Lemaistre, CF Horowitz, MM AF Loberiza, FR Zhang, M Rizzo, JD Lee, SJ Klein, JP Logan, BR Eapen, M Serna, DS Lemaistre, CF Horowitz, MM TI Patient and transplant center factors associated with 1000 mortality after receiving allogeneic hematopoietic stem cell transplantation (HSCT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Texas Transplant Inst, San Antonio, TX USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6026 BP 525S EP 525S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402080 PM 28015094 ER PT J AU Adloff, KO Partridge, A Blood, E Dees, C Kaelin, C Weeks, J Emmons, K Winer, E AF Adloff, KO Partridge, A Blood, E Dees, C Kaelin, C Weeks, J Emmons, K Winer, E TI Accuracy of risk perceptions of women with ductal carcinoma in situ. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6034 BP 527S EP 527S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402088 PM 28015159 ER PT J AU Punglia, RS Hughes, ME Edge, SB Theriault, RL Bookman, MA Burak, WE Ottesen, R Niland, JC Weeks, JC AF Punglia, RS Hughes, ME Edge, SB Theriault, RL Bookman, MA Burak, WE Ottesen, R Niland, JC Weeks, JC TI Factors associated with appropriate use of radiation therapy after mastectomy in women with Stage I-II breast cancer treated within the National Comprehensive Cancer Network (NCCN) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. A James Canc Hosp & R Solove Res Inst, Columbus, OH USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6032 BP 527S EP 527S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402087 PM 28015156 ER PT J AU Miksad, RA Roberts, TG Gonen, M Lynch, TJ AF Miksad, RA Roberts, TG Gonen, M Lynch, TJ TI Bayesian analysis of the International Adjuvant Lung Trial (IALT): Should it change practice? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. RI Miksad, Rebecca/B-8066-2009; Gonen, Mithat/E-4826-2012 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6038 BP 528S EP 528S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402092 PM 28015153 ER PT J AU Godley, PA Clark, JA Gellatly, DD Jackson, ST Talcott, JA AF Godley, PA Clark, JA Gellatly, DD Jackson, ST Talcott, JA TI Race and prostate cancer: Attitudes toward diagnosis and treatment among newly diagnosed patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6056 BP 533S EP 533S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402111 PM 28014975 ER PT J AU Krzyzanowska, MK Treacy, JT Maloney, BA Lavino, A Jacobson, JO AF Krzyzanowska, MK Treacy, JT Maloney, BA Lavino, A Jacobson, JO TI Development of a registry to evaluate hospital admissions related to chemotherapy toxicity in a community cancer center. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. N Shore Canc Ctr, Peabody, MA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6062 BP 534S EP 534S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402116 PM 28014967 ER PT J AU Partridge, AH Gelber, S Peppercorn, J Sampson, E Laufer, M Rosenberg, R Przypyszny, M Rein, A Winer, EP AF Partridge, AH Gelber, S Peppercorn, J Sampson, E Laufer, M Rosenberg, R Przypyszny, M Rein, A Winer, EP TI Fertility outcomes in young women with breast cancer: A Web-based survey. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Young Survival Coalit, New York, NY USA. NR 0 TC 7 Z9 7 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 15 PY 2004 VL 22 IS 14 SU S MA 6085 BP 540S EP 540S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402141 PM 28014990 ER PT J AU Hochster, HS Weller, E Ryan, T Haberman, TM Gascoyne, R Frankel, SR Horning, SJ AF Hochster, HS Weller, E Ryan, T Haberman, TM Gascoyne, R Frankel, SR Horning, SJ TI Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NYU, Sch Med, New York, NY USA. DFCI, Boston, MA USA. Mayo Clin, Rochester, MN USA. British Canc Control Agcy, Vancouver, BC, Canada. Univ Maryland, Baltimore, MD 21201 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 4 Z9 4 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 15 PY 2004 VL 22 IS 14 SU S MA 6502 BP 558S EP 558S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402211 ER PT J AU Rajkumar, SV Blood, E Vesole, DH Shepard, R Greipp, PR AF Rajkumar, SV Blood, E Vesole, DH Shepard, R Greipp, PR TI A randomised phase III trial of thalidomide plus dexamethasone versus dexamethasone in newly diagnosed multiple myeloma (E1AOO): Atrial coordinated by the Eastern Cooperative Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 6 Z9 6 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 15 PY 2004 VL 22 IS 14 SU S MA 6508 BP 560S EP 560S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402218 PM 28016887 ER PT J AU Richardson, P Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Dalton, WS Harousseau, JL San Miguel, JF Anderson, KC AF Richardson, P Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Dalton, WS Harousseau, JL San Miguel, JF Anderson, KC TI Bortezomib vs. dexamethasone in relapsed multiple myeloma: A phase 3 randomized study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. New York Presbyterian Hosp, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Penn Canc Ctr, Philadelphia, PA USA. Hosp Claude Huriez, Lille, France. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Hop Hotel Dieu, Nantes, France. Hosp Univ Salamanca, Salamanca, Spain. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 3 Z9 3 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 15 PY 2004 VL 22 IS 14 SU S MA 6511 BP 560S EP 560S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402221 PM 28016924 ER PT J AU Farag, SS Ruppert, A Mrozek, K Kolitz, JE Mayer, RJ Carroll, AJ Powell, BL Moore, JO Larson, RA Bloomfield, CD AF Farag, SS Ruppert, A Mrozek, K Kolitz, JE Mayer, RJ Carroll, AJ Powell, BL Moore, JO Larson, RA Bloomfield, CD TI Post-remission therapy with 4 cycles of intermediate (I) or high-dose (HD) cytarabine (AC) or autologous hematopoietic stem cell transplantation (ASCT) for acute myeloid leukemia (AML) patients < 60 years with normal cytogenetics: A Cancer and Leukemia Group B (CALGB) Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. N Shore Univ, Manhasset, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Duke Univ, Durham, NC 27706 USA. Univ Chicago, Chicago, IL 60637 USA. RI Mrozek, Krzysztof/A-3142-2008 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6542 BP 568S EP 568S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402249 PM 28016930 ER PT J AU Stock, W Levitsky, HI Borrello, IM Sher, D Deangelo, DJ Alyea, EP Damon, LE Linker, CA Hege, K AF Stock, W Levitsky, HI Borrello, IM Sher, D Deangelo, DJ Alyea, EP Damon, LE Linker, CA Hege, K TI Posttransplant immunotherapy with a GM-CSF-based tumor vaccine following autologous stem cell transplant (ASCT) for acute myeloid leukemia (AML). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cell Genesys, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6545 BP 568S EP 568S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402252 PM 28016933 ER PT J AU Tournilhac, O Santos, DD Branagan, A Hunter, Z Manning, R Tai, YT Kutok, JL Munshi, N Anderson, KC Treon, SP AF Tournilhac, O Santos, DD Branagan, A Hunter, Z Manning, R Tai, YT Kutok, JL Munshi, N Anderson, KC Treon, SP TI Excess bone marrow mast cells constitutively express CD154 (CD40 ligand) in Waldenstrom's macroglobulinemia and may support tumor cell growth through CD154/CD40 pathway SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 6555 BP 571S EP 571S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402263 PM 28016960 ER PT J AU Treon, SP Hansen, M Branagan, A Emmanouilides, C Kimby, E Frankel, S Touroutoglou, N Maloney, D Anderson, KC Fox, EA AF Treon, SP Hansen, M Branagan, A Emmanouilides, C Kimby, E Frankel, S Touroutoglou, N Maloney, D Anderson, KC Fox, EA TI Polymorphisms in Fc gamma RIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom's macroglobulinemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Karolinska Inst, Stockholm, Sweden. Univ Maryland, Baltimore, MD 21201 USA. Nevada Canc Ctr, Las Vegas, NV USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 6556 BP 571S EP 571S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402262 PM 28016961 ER PT J AU Manning, R Branagan, AR Hunter, Z Tournilhac, O Santos, DD Treon, SP AF Manning, R Branagan, AR Hunter, Z Tournilhac, O Santos, DD Treon, SP TI Characterization of familial Waldenstrom's macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 6558 BP 572S EP 572S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402265 PM 28016956 ER PT J AU Cafarella, T Manning, R Hunter, Z Branagan, AR Tournilhac, O Santos, DD Dorfman, DM Treon, SP AF Cafarella, T Manning, R Hunter, Z Branagan, AR Tournilhac, O Santos, DD Dorfman, DM Treon, SP TI Heterogeneous expression of CD5, C010, and CD23 in Waldenstrom's macroglabulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 15 PY 2004 VL 22 IS 14 SU S MA 6730 BP 614S EP 614S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402436 PM 28014496 ER PT J AU Herbst, RS Prager, D Hermann, R Miller, V Fehrenbacher, L Hoffman, P Johnson, B Sandler, AB Mass, R Johnson, DH AF Herbst, RS Prager, D Hermann, R Miller, V Fehrenbacher, L Hoffman, P Johnson, B Sandler, AB Mass, R Johnson, DH TI TRIBUTE - A phase III trial of erlotinib HCI (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NW Georgia Oncol Ctr, Marietta, GA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Kaiser Permanente Med Ctr, Vallejo, CA USA. Univ Chicago Hosp, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Genentech Inc, San Francisco, CA 94080 USA. RI Johnson, David/A-7437-2009 NR 0 TC 9 Z9 9 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 7011 BP 619S EP 619S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402456 ER PT J AU Masters, GA Xu, R Langer, C Dowlati, A Madajewicz, S Johnson, DH AF Masters, GA Xu, R Langer, C Dowlati, A Madajewicz, S Johnson, DH TI A phase II trial of carboplatin and gemcitabine with exisulind (IND # 65,056) in patients with advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Trial 1501. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Helen Graham Canc Ctr, Newark, DE USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Hosp Cleveland, Cleveland, OH USA. Vanderbilt Univ, Nashville, TN USA. Univ Hosp, Stony Brook, NY USA. RI Johnson, David/A-7437-2009 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 7037 BP 626S EP 626S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402481 PM 28016066 ER PT J AU Janne, PA Obasaju, C Simon, G Taub, R Kelly, K Fidias, P Bloss, LP Kindler, HL AF Janne, PA Obasaju, C Simon, G Taub, R Kelly, K Fidias, P Bloss, LP Kindler, HL TI A phase 2 clinical trial of pemetrexed plus gemcitabine as front-line chemotherapy for patients with malignant pleural mesothelioma (MPM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Lilly Oncol, Indianapolis, IN USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Univ Nacl Colombia, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Chicago, Ctr Med, Chicago, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7053 BP 629S EP 629S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402496 PM 28016122 ER PT J AU Loehrer, PJ Wang, W Aisner, S Bonomi, P Einhorn, LH Langer, CJ Green, MR Livingston, RB Johnson, DH Schiller, J AF Loehrer, PJ Wang, W Aisner, S Bonomi, P Einhorn, LH Langer, CJ Green, MR Livingston, RB Johnson, DH Schiller, J TI Long-term follow-up of patients with locally advanced or metastatic thymic malignancies: The Eastern Cooperative Oncology Group (ECOG) experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Indiana Univ, Ctr Canc, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Rush Univ, Chicago, IL 60612 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ S Carolina, Charleston, SC USA. Univ Washington, Seattle, WA 98195 USA. Vanderbilt Univ, Nashville, TN USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 7050 BP 629S EP 629S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402493 PM 28016123 ER PT J AU Johnson, BE Lucca, J Rabin, MS Lynch, TJ Ostler, P Skarin, AT Temel, J Liu, G Janne, PA AF Johnson, BE Lucca, J Rabin, MS Lynch, TJ Ostler, P Skarin, AT Temel, J Liu, G Janne, PA TI Preliminary results from a phase II study of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in patients > 70 years of age with previously untreated advanced non-small cell lung carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA USA. Massachuetts Gen Hosp, Boston, MA USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 7080 BP 636S EP 636S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402523 PM 28016134 ER PT J AU Lynch, TJ Lilenbaum, R Bonomi, P Ansari, R Govindan, R Janne, PA Hanna, N AF Lynch, TJ Lilenbaum, R Bonomi, P Ansari, R Govindan, R Janne, PA Hanna, N TI A phase II trial of cetuximab as therapy for recurrent non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. Rush Univ, Chicago, IL 60612 USA. Michigan Hematol Oncol PC, South Bend, IN USA. Univ Washington, Sch Med, St Louis, MO USA. Indiana Univ, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 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 15 PY 2004 VL 22 IS 14 SU S MA 7084 BP 637S EP 637S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402527 PM 28016130 ER PT J AU Fanucchi, MP Belt, RJ Fossella, FV Natale, RB Robert, F Fidias, P Kelly, K Kashala, O Shenkein, DP Schiller, JH AF Fanucchi, MP Belt, RJ Fossella, FV Natale, RB Robert, F Fidias, P Kelly, K Kashala, O Shenkein, DP Schiller, JH TI Phase (ph) 2 study of bortezomib +/- docetaxel in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC): Preliminary results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Emory Univ, Whipship Canc Inst, Atlanta, GA 30322 USA. Kansa City Canc Ctr, Kansas City, MO USA. Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Millennium Pharmaceut, Cambridge, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Univ Wisconsin, Hosp & Clin, Madison, WI USA. NR 0 TC 8 Z9 8 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 15 PY 2004 VL 22 IS 14 SU S MA 7107 BP 643S EP 643S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402549 ER PT J AU Mamon, HJ Yeap, B Reblando, J Shrager, S Jaklitsch, MT Lukanich, JM Sugarbaker, DJ Baldini, E Janne, P Bueno, R AF Mamon, HJ Yeap, B Reblando, J Shrager, S Jaklitsch, MT Lukanich, JM Sugarbaker, DJ Baldini, E Janne, P Bueno, R TI High risk of brain metastases in surgically staged IIIA NSCLC patients treated with surgery, chemotherapy and radiation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Brigham & Womens Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 7173 BP 659S EP 659S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402615 PM 28014275 ER PT J AU Orlando, M Wozniak, A Janne, P Belani, CP Keohan, ML Ross, H Polikoff, J Mintzer, D Bloss, L Obasaju, C AF Orlando, M Wozniak, A Janne, P Belani, CP Keohan, ML Ross, H Polikoff, J Mintzer, D Bloss, L Obasaju, C TI Pemetrexed alone or in combination with cisplatin in previously treated patients with malignant pleural mesothelioma (MPM): Outcomes of an expanded access program (EAP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Lilly Res Labs, Indianapolis, IN USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Kaiser Hosp San Diego, San Diego, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 7195 BP 664S EP 664S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402636 PM 28014307 ER PT J AU Wozniak, AJ Janne, P Belani, CP Keohan, ML Ross, H Polikoff, J Mintzer, D Obasaju, C AF Wozniak, AJ Janne, P Belani, CP Keohan, ML Ross, H Polikoff, J Mintzer, D Obasaju, C TI Pemetrexed in combination with cisplatin in the treatment of chemonaive patients with malignant pleural mesothelioma (MPM): Outcomes on Expanded Access Program (EAP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Wayne State Univ, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Kaiser Hosp San Diego, San Diego, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. Lilly Oncol, Indianapolis, IN USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 7192 BP 664S EP 664S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402633 PM 28014312 ER PT J AU Bloss, J Wozniak, A Janne, P Belani, C Keohan, M Ross, H Polikoff, J Mintzer, D Bloss, L Obasaju, C AF Bloss, J Wozniak, A Janne, P Belani, C Keohan, M Ross, H Polikoff, J Mintzer, D Bloss, L Obasaju, C TI Pemetrexed alone or in combination with cisplatin in the treatment of patients with peritoneal mesothelioma (PM): Outcomes of an expanded access program (EAP) in patients with malignant mesothelioma (MM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Lilly Oncol, Indianapolis, IN USA. Wayne State Univ, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Kaiser Hosp San Diego, San Diego, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 7198 BP 665S EP 665S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402638 PM 28014304 ER PT J AU Krupski, TL Smith, MR Lew, WC Pashos, CL Brandman, J Wang, Q Botteman, M Litwin, MS AF Krupski, TL Smith, MR Lew, WC Pashos, CL Brandman, J Wang, Q Botteman, M Litwin, MS TI Profile of men with prostate cancer on androgen deprivation therapy at greatest risk of bone complications. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. ABT Associates Inc, Clin Trials, Bethesda, MD USA. Novartis Pharmaceut Corp, Florham Pk, NJ USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8000 BP 729S EP 729S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402890 PM 28015820 ER PT J AU Kimmick, G Kornblith, A Mandelblatt, J Peterson, B Johnson, J Wheeler, J Cohen, H Muss, H AF Kimmick, G Kornblith, A Mandelblatt, J Peterson, B Johnson, J Wheeler, J Cohen, H Muss, H CA CALGB TI A randomized controlled trial of an educational program to improve accrual of older persons to cancer treatment protocols: CALGB 360001. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. CALBG Stat Off, Durham, NC USA. Duke Univ, Durham, NC USA. VA Med Ctr, Durham, NC USA. Univ Vermont, Burlington, VT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8040 BP 739S EP 739S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402930 PM 28015858 ER PT J AU Brouns, MC Beer, TM Ganzini, LK AF Brouns, MC Beer, TM Ganzini, LK TI Interest in physician-assisted suicide (PAS) among Oregon cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NW Canc Specialists, Vancouver, BC, Canada. OHSU, Inst Canc, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8070 BP 746S EP 746S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402959 PM 28015869 ER PT J AU Talcott, JA Yeap, B Godley, PA Lu, C Siegel, RD Clark, JA AF Talcott, JA Yeap, B Godley, PA Lu, C Siegel, RD Clark, JA TI Does home antibiotic therapy increase medical risk for patients with low-risk febrile neutropenia? A multi-institutional randomized trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Helen & Harry Gray Canc Ctr, Hartford, CT USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8113 BP 757S EP 757S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403002 PM 28015352 ER PT J AU Vielhaber, A Homel, P Malamud, S Chang, VT Hwang, SS Cogswell, J Portenoy, RK Kornblith, AB AF Vielhaber, A Homel, P Malamud, S Chang, VT Hwang, SS Cogswell, J Portenoy, RK Kornblith, AB TI Influence of response shift on the perception of fatigue in patients with advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Beth Israel Med Ctr, New York, NY 10003 USA. VA New Jersey Care Syst, E Orange, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8116 BP 757S EP 757S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403005 PM 28015341 ER PT J AU Hurria, A Gupta, S Zauderer, M Zuckerman, E Rodin, M Holland, J Muss, H Cohen, HJ Kornblith, AB AF Hurria, A Gupta, S Zauderer, M Zuckerman, E Rodin, M Holland, J Muss, H Cohen, HJ Kornblith, AB TI Development of a comprehensive geriatric assessment (CGA) measure for older patients (Pts) with cancer: A feasibility study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CALGB, Canc Elderly Comm, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Vermont, Burlington, VT 05405 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8162 BP 769S EP 769S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403052 PM 28015417 ER PT J AU Lipshultz, SE Rifai, N Dalton, VM Levy, DE Silverman, LB Lipsitz, SR Colan, SD Gelber, RD Sallan, SE AF Lipshultz, SE Rifai, N Dalton, VM Levy, DE Silverman, LB Lipsitz, SR Colan, SD Gelber, RD Sallan, SE CA DFCI Childhood ALL Consort TI Echocardiographic (Echo) monitoring of myocardial injury during doxorubicin (DOX) therapy for childhood acute lymphablastic leukemia (ALL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Miami, Miami, FL 33152 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8505 BP 800S EP 800S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403175 PM 28014534 ER PT J AU Frantz, CN London, WB Diller, L Seeger, R Sawyer, K AF Frantz, CN London, WB Diller, L Seeger, R Sawyer, K TI Recurrent neuroblastoma: Randomized treatment with topotecan plus cyclophosphamide (T plus C) vs. topotecan alone(T). A POG/CCG Intergroup Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dupont Hosp, Wilmington, DE USA. COG Stat Dept, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 8512 BP 802S EP 802S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403181 ER PT J AU Mack, JW Hilden, JM Watterson, J Grier, HE Weeks, JC Wolfe, J AF Mack, JW Hilden, JM Watterson, J Grier, HE Weeks, JC Wolfe, J TI Factors associated with the quality of care at the end of life in children with cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. Cleveland Clin, Childrens Hosp, Cleveland, OH USA. Childrens Hosp & Clin, St Paul, MN USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 8529 BP 806S EP 806S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403199 PM 28013755 ER PT J AU Diller, L Mauch, P Nancarrow, CM Byrnes, L Stevenson, MA Ng, A Garber, J AF Diller, L Mauch, P Nancarrow, CM Byrnes, L Stevenson, MA Ng, A Garber, J TI A feasibility study of tamoxifen chemoprevention in Hodgkin's disease (HD) survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8551 BP 811S EP 811S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403220 ER PT J AU Samuels, BL Rushing, D Chawla, SP Schuetze, SM Von Mehren, M Keohan, ML O'Donovan, M Wei, X Sternas, LA Demetri, GD AF Samuels, BL Rushing, D Chawla, SP Schuetze, SM Von Mehren, M Keohan, ML O'Donovan, M Wei, X Sternas, LA Demetri, GD TI Randomized phase II study of trabectedin (ET-743) given by two different dosing schedules in patients (pts) with leiomyosarcomas (LMS) or liposarcomas (LPS) refractory to conventional doxorubicin and ifosfamide chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Oncol Specialists, SC, Park Ridge, IL USA. Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. SP Chawla MD Inc, Los Angeles, CA USA. Seattle Canc Ctr Care Alliance, Seattle, WA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Columbia Univ, Med Ctr, New York, NY USA. Johnson&Johnson Pharmaceut R&D, Raritan, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9000 BP 818S EP 818S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403244 PM 28013625 ER PT J AU Rankin, C Von Mehren, M Blanke, C Benjamin, R Fletcher, CDM Bramwell, V Crowley, J Borden, E Demetri, GD AF Rankin, C Von Mehren, M Blanke, C Benjamin, R Fletcher, CDM Bramwell, V Crowley, J Borden, E Demetri, GD TI Dose effect of imatinib (IM) in patients (pts) with metastatic GIST - phase III Sarcoma Group Study S0033. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Sarcoma Grp, Seattle, WA USA. SWOG Stat Ctr, Seattle, WA USA. Fox Chase Canc Ctr, ECOG, Philadelphia, PA 19111 USA. Sarcoma Grp, Philadelphia, PA USA. SWOG, OHSU, Portland, OR USA. Sarcoma Grp, Portland, OR USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Sarcoma Grp, Houston, TX USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Sarcoma Grp, Boston, MA USA. NCI Canada, Calgary, SK, Canada. Sarcoma Grp, Calgary, SK, Canada. Cleveland Clin, Cleveland, OH 44106 USA. SWOG, Cleveland, OH USA. Sarcoma Grp, Cleveland, OH USA. Dana Farber Canc Inst, CALGB, Sarcoma Grp, Boston, MA 02115 USA. NR 0 TC 16 Z9 18 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 9005 BP 819S EP 819S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403250 ER PT J AU Morgan, JA George, S Desai, J Amand, MS Horton, D Wilkins, E Manola, J Demetri, GD AF Morgan, JA George, S Desai, J Amand, MS Horton, D Wilkins, E Manola, J Demetri, GD TI Phase II study of gemcitabine/vinorelbine (GV) as first or second line chemotherapy in patients with metastatic soft tissue sarcoma (STS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9009 BP 820S EP 820S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403254 PM 28013692 ER PT J AU Borden, EC Jacobs, B Demetri, G Fletcher, J AF Borden, EC Jacobs, B Demetri, G Fletcher, J TI Induction of TRAIL and XAF-1 and inhibition of p-Akt and c-Kit expression by interferons (IFNs) is associated with apoptosis in GIST cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9027 BP 824S EP 824S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403271 PM 28013748 ER PT J AU Dileo, P Randhawa, R Vansonnenberg, E Shankar, S Desai, J Morgan, JA Tuncali, K Van den Abbeele, A Silverman, SG Demetri, GD AF Dileo, P Randhawa, R Vansonnenberg, E Shankar, S Desai, J Morgan, JA Tuncali, K Van den Abbeele, A Silverman, SG Demetri, GD TI Safety and efficacy of percutaneous radio-frequency ablation (RFA) in patients (pts) with metastatic gastrointestinal stromal tumor (GIST) with clonal evolution of lesions refractory to imatinib mesylate (IM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 5 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 JUL 15 PY 2004 VL 22 IS 14 SU S MA 9024 BP 824S EP 824S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403268 PM 28013747 ER PT J AU Harris, L Dressler, L Cowan, D Berry, D Cirrincione, C Broadwater, G Muss, H Hayes, D Ellis, M AF Harris, L Dressler, L Cowan, D Berry, D Cirrincione, C Broadwater, G Muss, H Hayes, D Ellis, M TI The role of HER-2+Topo II alpha amplification in predicting benefit from CAF dose escalation-CALGB 8541. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. CALGB, Chicago, IL USA. Duke Univ, Ctr Canc, Durham, NC USA. NR 0 TC 2 Z9 2 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 15 PY 2004 VL 22 IS 14 SU S MA 9505 BP 836S EP 836S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403317 PM 28016795 ER PT J AU Kurian, AW Mills, MA Nowels, KW Plevritis, SK Sigal, BM Chun, NM Kingham, KE Ford, JM Hartman, AR AF Kurian, AW Mills, MA Nowels, KW Plevritis, SK Sigal, BM Chun, NM Kingham, KE Ford, JM Hartman, AR TI Ductal lavage of non-fluid yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high genetic risk for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9535 BP 843S EP 843S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403346 ER PT J AU Liu, G Zhou, W Park, S Gurubhagavatula, S Yeap, B Nishioka, NS Su, L Wain, JC Lynch, TJ Christiani, DC AF Liu, G Zhou, W Park, S Gurubhagavatula, S Yeap, B Nishioka, NS Su, L Wain, JC Lynch, TJ Christiani, DC TI Polymorphisms of DNA repair and glutathione s-transferase genes and progression-free survival (PFS) in treated advanced esophageal cancer (EC) patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9564 BP 850S EP 850S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403374 PM 28016672 ER PT J AU Dubey, S Miller, J Stephenson, P Keller, SM Johnson, DH Schiller, JH Kolesar, JM AF Dubey, S Miller, J Stephenson, P Keller, SM Johnson, DH Schiller, JH Kolesar, JM TI EGFr dinucleotide repeat polymorphism in non-small cell lung cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Wisconsin, Eastern Cooperat Oncol Grp, Madison, WI USA. Univ Wisconsin, Sch Pharm, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Vanderbilt Univ, Nashville, TN USA. RI Johnson, David/A-7437-2009 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9585 BP 856S EP 856S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403395 PM 28016729 ER PT J AU Isaacs, C Skates, SJ Lehman, C Marcom, K Bowen, DJ Domchek, S Tomlinson, G Armstrong, DK Schnall, M AF Isaacs, C Skates, SJ Lehman, C Marcom, K Bowen, DJ Domchek, S Tomlinson, G Armstrong, DK Schnall, M TI Mammographic, MRI, and ultrasound characteristics of BRCA1, BRCA2, and other genetically high-risk women enrolled in a prospective multi-institution breast cancer screening trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Georgetown Univ, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Durham, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. RI Schnall, Mitchell/D-1149-2009 NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9588 BP 856S EP 856S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403398 PM 28016731 ER PT J AU Lawenda, BD Smith, DEH Niemierko, A Xu, L Silverstein, JR Held, KD Loeffler, JS Jain, RK Blumberg, JB AF Lawenda, BD Smith, DEH Niemierko, A Xu, L Silverstein, JR Held, KD Loeffler, JS Jain, RK Blumberg, JB TI Radiomodifying responses of vitamin E and epigallocatechin gallate supplementation during irradiation of implanted tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, USDA, HNRCA, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9601 BP 860S EP 860S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403411 PM 28016194 ER PT J AU Andre, F Sabourin, JC Assi, H Miran, I Podolsky, D Spielmann, M Zitvogel, L AF Andre, F Sabourin, JC Assi, H Miran, I Podolsky, D Spielmann, M Zitvogel, L TI Targeting toll like receptor 3 by double stranded RNA in breast cancer: Results from in vitro studies and randomized trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Inst Gustave Roussy, Villejuif, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 5 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 15 PY 2004 VL 22 IS 14 SU S MA 9619 BP 864S EP 864S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403429 ER PT J AU Aisner, SC Hameed, MR Wang, W Schiller, JH Johnson, DH Ettinger, DS Loehrer, PJ AF Aisner, SC Hameed, MR Wang, W Schiller, JH Johnson, DH Ettinger, DS Loehrer, PJ TI EGFR and C-kit immunostaining in advanced or recurrent thymic epithelial neoplasms staged according to the WHO: An eastern cooperative oncology group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Med & Dent New Jersey, Newark, NJ USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Wisconsin, Madison, WI USA. Vanderbilt Univ, Nashville, TN USA. Johns Hopkins, Baltimore, MD USA. Indiana Univ, Indianapolis, IN USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9637 BP 869S EP 869S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403447 PM 28016206 ER PT J AU Haddad, RI Gokhale, AS Wirth, L Weeks, L Faucher, J Hallar, M Cavacini, LA Posner, MR AF Haddad, RI Gokhale, AS Wirth, L Weeks, L Faucher, J Hallar, M Cavacini, LA Posner, MR TI Interleukin-8 (IL-8) serum levels and squamous cell cancer of the head and neck (SCCHN). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 15 PY 2004 VL 22 IS 14 SU S MA 9716 BP 888S EP 888S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403526 PM 28016407 ER PT J AU Miser, JS Krailo, MD Tarbell, NJ Link, MP Fryer, CJH Pritchard, DJ Gebhardt, MC Dickman, PS Perlman, EJ Meyers, PA Donaldson, SS Moore, S Rausen, AR Vietti, TJ Grier, HE AF Miser, JS Krailo, MD Tarbell, NJ Link, MP Fryer, CJH Pritchard, DJ Gebhardt, MC Dickman, PS Perlman, EJ Meyers, PA Donaldson, SS Moore, S Rausen, AR Vietti, TJ Grier, HE TI Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: Evaluation of combination ifosfamide and etoposide - A children's cancer group and pediatric oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOTAL-BODY IRRADIATION; SURVIVAL ANALYSIS; RISK AB Purpose One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. Methods Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. Results Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. Conclusion Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis. (C) 2004 by American Society of Clinical Oncology. C1 City Hope Natl Med Ctr, Div Pediat, Dept Pediat Hematol Oncol, Duarte, CA 91010 USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Dept Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Dept Orthoped Surg, Cambridge, MA 02138 USA. Mayo Clin, Rochester, MN USA. Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. NYU, Ctr Med, Dept Pediat, New York, NY USA. Univ Washington, Div Pediat Hematol Oncol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pediat, St Louis, MO USA. King Khalid Natl Gen Hosp, Dept Paediat, Jeddah, Saudi Arabia. RP Miser, JS (reprint author), City Hope Natl Med Ctr, Div Pediat, Dept Pediat Hematol Oncol, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jmiser@coh.org NR 10 TC 85 Z9 93 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 JUL 15 PY 2004 VL 22 IS 14 BP 2873 EP 2876 DI 10.1200/JCO.2004.01.041 PG 4 WC Oncology SC Oncology GA 838QV UT WOS:000222729000017 PM 15254055 ER PT J AU Sansal, I Sellers, WR AF Sansal, I Sellers, WR TI The biology and clinical relevance of the PTEN tumor suppressor pathway SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; FORKHEAD TRANSCRIPTION FACTOR; LIPID PHOSPHATASE-ACTIVITY; PRIMARY PROSTATE-CANCER; HUMAN PANCREATIC-CANCER; MELANOMA-CELL LINES; PTEN/MMAC1 GENE; COWDEN-DISEASE; GLIOBLASTOMA-MULTIFORME; GERMLINE MUTATIONS AB Genetic alterations targeting the PTEN tumor suppressor gene are among the most frequently noted somatic mutations in human cancers. Such lesions have been noted in cancers of the prostate and endometrium and in glioblastoma multiforme, among many others. Moreover, germline mutation of PTEN leads to the development of the related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan-Zonana syndrome, wherein breast and thyroid cancer incidence is elevated. The protein product, PTEN, is a lipid phosphatase, the enzymatic activity of which primarily serves to remove phosphate groups from key intracellular phosphoinositide signaling molecules. This activity normally serves to restrict growth and survival signals by limiting activity of the phosphoinositide-3 kinase (PI3K) pathway. Multiple lines of evidence support the notion that this function is critical to the ability of PTEN to maintain cell homeostasis. Indeed, the absence of functional PTEN in cancer cells leads to constitutive activation of downstream components of the PI3K pathway including the Akt and mTOR kinases. In model organisms, inactivation of these kinases can reverse the effects of PTEN loss. These data raise the possibility that drugs targeting these kinases, or PI3K itself, might have significant therapeutic activity in PTEN-null cancers. Akt kinase inhibitors are still in development; however, as a first test of this hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin and rapamycin analogs are underway. (C) 2004 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM william_sellers@dfci.harvard.edu FU NCI NIH HHS [P01 CA 89021, P50 CA 09038, R01 CA 85912, U01 CA 84995] NR 100 TC 594 Z9 631 U1 6 U2 35 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 15 PY 2004 VL 22 IS 14 BP 2954 EP 2963 DI 10.1200/jco.2004.02.141 PG 10 WC Oncology SC Oncology GA 838QV UT WOS:000222729000026 PM 15254063 ER PT J AU Havari, E Lennon-Dumenil, AM Klein, L Neely, D Taylor, JA McInerney, MF Wucherpfennig, KW Lipes, MA AF Havari, E Lennon-Dumenil, AM Klein, L Neely, D Taylor, JA McInerney, MF Wucherpfennig, KW Lipes, MA TI Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID II-DEFICIENT MICE; DENDRITIC CELLS; NOD MICE; TRANSGENIC MICE; B-LYMPHOCYTES; COXSACKIE-VIRUS; LYMPH-NODES; B7-1; ANTIGEN; AUTOIMMUNITY AB Although HLA-DQ8 has been implicated as a key determinant of genetic susceptibility to human type 1 diabetes, spontaneous diabetes has been observed in HLA-DQ8 transgenic mice that lack expression of murine MHC class II molecules (mII(-/-)) only when the potent costimulatory molecule, B7.1, is transgenically expressed on pancreatic 13 cells. To study the contribution of HLA-DQ8 to the development of diabetes in this model, we crossed RIP-B7.1mII(-/-) mice with a set of transgenic mouse lines that differed in their HLA-DQ8 expression patterns on APC subpopulations, in particular dendritic cells and cortical thymic epithelial cells. Surprisingly, we found that even in the absence of HLA-DQ8 and CD4 T cells, a substantial fraction of the RIP-B7.1mII(-/-) mice developed diabetes. This disease process was remarkable for not only showing insulitis, but also inflammatory destruction of the exocrine pancreas with diffusely up-regulated expression of MHC class I and ICAM-1 molecules. Expression of HLA-DQ8 markedly increased the kinetics and frequency of diabetes, with the most severe disease in the lines with the highest levels of HLA-DQ8 on cortical thymic epithelial cells and the largest numbers of CD4 T cells. However, the adoptive transfer of diabetes was not HLA-DQ8-dependent and disease could be rapidly induced with purified CD8 T cells alone. Expression of B7.1 in the target tissue can thus dramatically alter the cellular and molecular requirements for the development of autoimmunity. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Lipes, MA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM myra.lipes@joshn.harvard.edu RI Klein, Ludger/G-8785-2011; Lennon-Dumenil, Ana-Maria/I-6716-2016 FU NIAID NIH HHS [P01 AI39619] NR 57 TC 11 Z9 11 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 2004 VL 173 IS 2 BP 787 EP 796 PG 10 WC Immunology SC Immunology GA 837IA UT WOS:000222621000011 PM 15240665 ER PT J AU Wysocki, CA Burkett, SB Panoskaltsis-Mortari, A Kirby, SL Luster, AD McKinnon, K Blazar, BR Serody, JS AF Wysocki, CA Burkett, SB Panoskaltsis-Mortari, A Kirby, SL Luster, AD McKinnon, K Blazar, BR Serody, JS TI Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; ACUTE ALLOGRAFT-REJECTION; CHEMOKINE RECEPTOR CXCR3; FAS-LIGAND; HETEROLOGOUS DESENSITIZATION; DENDRITIC CELLS; IMMUNE-RESPONSE; ACUTE GVHD; IFN-GAMMA AB The coordinated expression of chemokines and receptors may be important in the directed migration of alloreactive T cells during graft-vs-host disease (GVHD). Recent work demonstrated in a murine model that transfer of CCR5-deficient (CCR5(-/-)) donor cells to nonconditioned haploidentical recipients resulted in reduced donor cell infiltration in liver and lymphoid tissues compared with transfer of CCR5(+/+) cells. To investigate the function of CCR5 during. GVHD in conditioned transplant recipients, we transferred CCR5(-/-) or wild-type C57BL/6 (136) T cells to lethally irradiated B6D2 recipients. Unexpectedly, we found an earlier time to onset and a worsening of GVHD using CCR5-/- T cells, which was associated with significant increases in the accumulation of alloreactive CD4(+) and CD8(+) T cells in liver and lung. Conversely, the transfer of CCR5(-/-) donor cells to nonirradiated recipients led to reduced infiltration of target organs, confirming previous studies and demonstrating that the role of CCR5 on donor T cells is dependent on conditioning of recipients. Expression of proinflammatory chemokines in target tissues was dependent on conditioning of recipients, such that CXCL10 and CXCL11 were most highly expressed in tissues of irradiated recipients during the first week post-transplant. CCR5(-/-) T cells were shown to have enhanced migration to CXCL10, and blocking this ligand in vivo improved survival in irradiated recipients receiving CCR5-/- T cells. Our data indicate that the effects of inhibiting CCR5/ligand interaction on donor T cells during GVHD differ depending on conditioning of recipients, a finding with potentially important clinical significance. C1 Univ N Carolina, Lineberger Canc Res Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Div Pediat Bone Marrow Transplantat, Dept Pediat, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Serody, JS (reprint author), Univ N Carolina, Lineberger Canc Res Ctr, Campus Box 7295, Chapel Hill, NC 27599 USA. EM jonathan_serody@med.unc.edu OI Serody, Jonathan/0000-0003-4568-1092 FU NCI NIH HHS [CA58223]; NHLBI NIH HHS [HL55209, HL66308]; NIAID NIH HHS [AI34495]; PHS HHS [102052] NR 56 TC 82 Z9 85 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 2004 VL 173 IS 2 BP 845 EP 854 PG 10 WC Immunology SC Immunology GA 837IA UT WOS:000222621000017 PM 15240671 ER PT J AU Fridkis-Hareli, M Reche, PA Reinherz, EL AF Fridkis-Hareli, M Reche, PA Reinherz, EL TI Peptide variants of viral CTL epitopes mediate positive selection and emigration of Ag-specific thymocytes in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; THYMIC SELECTION; NEGATIVE SELECTION; TRANSGENIC MICE; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; MHC MOLECULES; TCR; ANTIGEN; COMPLEX AB During development, thymocytes carrying TCRs mediating low-affinity interactions with MHC-bound self-peptides are positively selected for export into the mature peripheral T lymphocyte pool. Thus, exogenous administration of certain altered peptide ligands (APL) with reduced TCR affinity relative to cognate Ags may provide a tool to elicit maturation of desired TCR specificities. To test this "thymic vaccination" concept, we designed APL of the viral CTL epitopes gp33-41 and vesicular stomatitis virus nucleoprotein octapeptide N52-59 relevant for the lymphocytic choriomeningitis virus-specific P14- and vesicular stomatitis virus-specific N15-TCRs, respectively, and examined their effects on thymocytes in vivo using irradiation chimeras. Injection of APL into irradiated congenic (Ly-5.1) mice, reconstituted with T cell progenitors from the bone marrow of P14 RAG2(-/-) (Ly-5.2) or N15 RAG2(-/-) (Ly-5.2) transgenic mice, resulted in positive selection of T cells expressing the relevant specificity. Moreover, the variants led to export of virus-specific T cells to lymph nodes, but without inducing T cell proliferation. These findings show that the mature T cell repertoire can be altered by in vivo peptide administration through manipulation of thymic selection. C1 Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900] NR 50 TC 3 Z9 4 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 2004 VL 173 IS 2 BP 1140 EP 1150 PG 11 WC Immunology SC Immunology GA 837IA UT WOS:000222621000049 PM 15240703 ER PT J AU Greco, KM McDonough, MA Butterton, JR AF Greco, KM McDonough, MA Butterton, JR TI Variation in the Shiga toxin region of 20th-century epidemic and endemic Shigella dysenteriae 1 strains SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Gordon Research Conference on Microbial Toxins and Pathogenicity CY JUL 16-21, 2000 CL Univ Vermont Coll Med, Andover, NH SP Natl Inst Hlth HO Univ Vermont Coll Med ID DYSENTERIAE TYPE-1 STRAINS; HEMOLYTIC-UREMIC SYNDROME; ESCHERICHIA-COLI O157-H7; ENCODING BACTERIOPHAGES; LYSOGENS; PRODUCE; PHAGE AB The Shiga toxin (Stx) region of Shigella dysenteriae 1 lies on a defective prophage homologous to lambdoid bacteriophages in Stx-producing Escherichia coli. S. dysenteriae 1 strains obtained in locations throughout the world over the course of the past 60 years were assessed for variations in the Stx region by use of polymerase chain reaction and sequence analysis. The defective prophage was present in all strains examined, suggesting that all S. dysenteriae 1 isolates derive from a clone that resulted from a single phage-integration event. All western-hemisphere strains have an additional iso-IS1 insertion element upstream of stxAB, implying that there has been minimal exchange of strains between hemispheres in recent decades. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Butterton, JR (reprint author), Bacterial Pathogenesis, Partners Res Bldg,65 Landsdowne St,Rm 421, Cambridge, MA 02139 USA. EM jbutterton@partners.org FU NIDDK NIH HHS [DK-59010] NR 18 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2004 VL 190 IS 2 BP 330 EP 334 DI 10.1086/421706 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 832GH UT WOS:000222254800017 PM 15216469 ER PT J AU Nardell, EA Fan, D Shepard, JO Harris, NL Medoff, B Mark, EJ AF Nardell, EA Fan, D Shepard, JO Harris, NL Medoff, B Mark, EJ TI A woman with a pericardial effusion - Tuberculosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CARDIAC-TAMPONADE; DIAGNOSIS; ECHOCARDIOGRAPHY; COMPRESSION; ETIOLOGY; DISEASE C1 Cambridge Hosp, Div Pulm Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Cardiol, 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 Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Cardiol, 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 Nardell, EA (reprint author), Cambridge Hosp, Div Pulm Med, Cambridge, MA 02139 USA. NR 23 TC 5 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 15 PY 2004 VL 351 IS 3 BP 279 EP 287 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 837KA UT WOS:000222627200014 PM 15254287 ER PT J AU Hillman, EMC Boas, DA Dale, AM Dunn, AK AF Hillman, EMC Boas, DA Dale, AM Dunn, AK TI Laminar optical tomography: demonstration of millimeter-scale depth-resolved imaging in turbid media SO OPTICS LETTERS LA English DT Article ID LASER-DOPPLER FLOWMETRY; BARREL CORTEX; BLOOD-FLOW; IN-VIVO; BRAIN; RAT AB Laminar optical tomography (LOT) is a new technique that combines the advantages of diffuse optical tomography image reconstruction and a microscopy-based setup to allow noncontact imaging with 100-200-mum resolution effective over depths of 0-2.5 mm. LOT is being developed primarily for multispectral imaging of rat cortex, for which resolving functional dynamics in various layers of the brain's cortex (to depths of 1500 mum) is of increasing interest to neurophysiologists. System design and image reconstruction techniques are described, along with simulation and phantom results that demonstrate the characteristics and limitations of system accuracy and resolution. (C) 2004 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Hillman, EMC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ehillman@nmr.mgh.harvard.edu RI Hillman, Elizabeth/B-9854-2009; Dale, Anders/A-5180-2010; Dunn, Andrew/I-9527-2014; OI Hillman, Elizabeth M. C./0000-0001-5511-1451 FU NIBIB NIH HHS [EB000790-01A2, R01 EB000790]; NINDS NIH HHS [NS41291-01] NR 11 TC 83 Z9 83 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 15 PY 2004 VL 29 IS 14 BP 1650 EP 1652 DI 10.1364/OL.29.001650 PG 3 WC Optics SC Optics GA 835KE UT WOS:000222480800024 PM 15309848 ER PT J AU Counter, SA Buchanan, LH AF Counter, SA Buchanan, LH TI Mercury exposure in children: a review SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE Hg vapors; mercury; fetal exposure ID IN-UTERO EXPOSURE; SKIN-LIGHTENING CREAMS; MATERNAL FISH DIET; THIMEROSAL-CONTAINING VACCINES; DENTAL AMALGAM RESTORATIONS; METALLOTHIONEIN-NULL MICE; STATE-OF-PARA; INORGANIC MERCURY; METHYLMERCURY EXPOSURE; METHYL-MERCURY AB Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage. Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children. Reports of elemental Fig vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Fig for magico-religious purposes in urban communities are also discussed. Studies of inorganic Fig exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Fig exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Labs,Dept Neurol, Cambridge, MA 02138 USA. Univ Massachusetts, Sch Med, Harvard Univ Hlth Serv, Shriver Ctr, Waltham, MA 02452 USA. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_Counter@harvard.edu NR 177 TC 243 Z9 255 U1 6 U2 61 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 15 PY 2004 VL 198 IS 2 BP 209 EP 230 DI 10.1016/j.taap.2003.11.032 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 838LD UT WOS:000222713900009 PM 15236954 ER PT J AU Dor, FJMF Tseng, YL Cheng, J Moran, K Sanderson, TM Lancos, CJ Shimizu, A Yamada, K Awwad, M Sachs, D Hawley, RJ Schuurman, HJ Cooper, DKC AF Dor, FJMF Tseng, YL Cheng, J Moran, K Sanderson, TM Lancos, CJ Shimizu, A Yamada, K Awwad, M Sachs, D Hawley, RJ Schuurman, HJ Cooper, DKC TI alpha 1,3-galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-gal antibodies SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFTS; REJECTION; PIGS AB Background. The expression of galactosealpha1,3galactose (Gal) in pigs has proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal(-/-) pigs) have been produced by nuclear transfer/embryo transfer. Methods. The tissues of five Gal(-/-) pigs of SLA dd haplotype (SLA(dd)) were tested for the presence of Gal epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (Gal(+/+)) SLA-matched pigs; serum cytotoxicity was also assessed. The cellular responses of PBMC from Gal(-/-) swine toward Gal(+/+) SLA-matched PBMC were tested by mixed leukocyte reaction and cell-mediated lympholysis assays. Results. None of the tissues tested showed Gal expression. Sera from all five Gal(-/-) pigs manifested IgM binding to Gal(+/+) pig PBMC, and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal(+/+) cells could be demonstrated, which was lost after treatment of the sera with dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal(-/-) swine had no proliferative or cytolytic T-cell response toward Gal(+/+) SLA-matched PBMC. Conclusions. Gal(-/-) pigs do not express Gal epitopes and develop anti-Gal antibodies that are cytotoxic to Gal(+/+) pig cells. The absence of an in vitro cellular immune response between Gal(-/-) and Gal+/+ pigs is related to their identical SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell responses. The model of Gal(+/+) organ transplantation into a Gal(-/-) SLA-matched recipient would be a valuable large animal model in the study of accommodation or B-cell tolerance. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge BioTherapeut, Cambridge, MA USA. RP Cooper, DKC (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. EM David.Cooper@tbrc.mgh.harvard.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1P01 AI45897] NR 12 TC 48 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2004 VL 78 IS 1 BP 15 EP 20 DI 10.1097/01.TP.0000130487.68051.EB PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 839FB UT WOS:000222767800004 PM 15257033 ER PT J AU Koutkia, P Canavan, B Breu, J Torriani, M Kissko, J Grinspoon, S AF Koutkia, P Canavan, B Breu, J Torriani, M Kissko, J Grinspoon, S TI Growth hormone-releasing hormone in HIV-infected men with lipodystrophy - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID REGIONAL BODY-COMPOSITION; PROTEASE INHIBITORS; REPLACEMENT THERAPY; INSULIN-RESISTANCE; FAT REDISTRIBUTION; PULSE DETECTION; GH SECRETION; ADULTS; METABOLISM; GLUCOSE AB Context Reduced growth hormone (GH) concentrations are observed in men with human immunodeficiency virus (HIV) lipodystrophy. Objective To investigate the effects of growth hormone-releasing hormone (GHRH), a GH secretagogue, in treatment of HIV lipodystrophy. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted at a research center in the United States between October 2002 and June 2003 and enrolling 31 HIV-infected men aged 18 to 60 years with evidence of lipodystrophy. Interventions Participants were assigned to receive GHRH (1 mg subcutaneously twice daily) or placebo for 12 weeks. Main Outcome Measures The primary outcome was change in concentrations of insulin-like growth factor 1 (IGF-1) to detect overall change in GH levels in response to GHRH. Secondary end points included body composition by dual-energy x-ray absorptiometry and computed tomography, lipodystrophy ratings, and levels of glucose, insulin, and lipids. Results Mean (SD) IGF-1 concentrations increased significantly in the GHRH group vs the placebo group (104 [110] ng/mL vs 6 [44] ng/mL, P=.004). Lean body mass significantly increased in the GHRH group vs the placebo group (0.9 [1.3] kg vs -0.3 [1.7] kg, P=.04), trunk fat significantly decreased (-0.4 [0.7] kg vs 0.2 [0.6] kg, P=.03), and the ratio of trunk to lower extremity fat improved significantly (-0.22 [0.32] vs 0.14 [0.29], P=.005). Abdominal visceral fat was reduced (-19.2 [36.6] cm(2) vs 2.3 [24.3] cm(2), P=.07) and the ratio of abdominal visceral fat to abdominal subcutaneous fat improved significantly more in the GHRH group (-0.19 [0.28] vs 0.07 [0.27], P=.02). Both physician and patient rating of lipodystrophy in the arms, legs, and abdomen also improved significantly. Levels of glucose, insulin, and lipids did not change significantly. Conclusions GHRH was well tolerated and effectively increased levels of IGF-1 in HIV-infected men with lipodystrophy. Total and regional body composition improved in response to GHRH, with increased lean mass and reduced truncal and visceral fat. Use of GHRH may potentially be a beneficial treatment strategy for this population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01 DK063639] NR 58 TC 71 Z9 73 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 14 PY 2004 VL 292 IS 2 BP 210 EP 218 DI 10.1001/jama.292.2.210 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 836TS UT WOS:000222579300026 PM 15249570 ER PT J AU Yeni, PG Hammer, SM Hirsch, MS Saag, MS Schechter, M Carpenter, CCJ Fischl, MA Gatell, JM Gazzard, BG Jacobsen, DM Katzenstein, DA Montaner, JSG Richman, DD Schooley, RT Thompson, MA Vella, S Volberding, PA AF Yeni, PG Hammer, SM Hirsch, MS Saag, MS Schechter, M Carpenter, CCJ Fischl, MA Gatell, JM Gazzard, BG Jacobsen, DM Katzenstein, DA Montaner, JSG Richman, DD Schooley, RT Thompson, MA Vella, S Volberding, PA TI Treatment for adult HIV infection - 2004 recommendations of the International AIDS Society-USA panel SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; STRUCTURED TREATMENT INTERRUPTION; SEQUENTIAL 3-DRUG REGIMENS; CD4(+) CELL COUNT; HIV-1-INFECTED PATIENTS; PROGNOSTIC IMPORTANCE; LOPINAVIR-RITONAVIR; COMBINATION THERAPY; PROTEASE-INHIBITOR AB Context Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. Objective To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. DataSources Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. Study Selection Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. DataExtraction Data were reviewed to identify any information that might change previous guidelines. Based on panel; discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. Data Synthesis Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). Conclusion Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management. C1 Hop Bichat Claude Bernard, X Bichat Med Sch, Dept Infect Dis, F-75877 Paris 18, France. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Fed Rio de Janeiro, Dept Prevent Med, Rio De Janeiro, Brazil. Brown Univ, Sch Med, Dept Biomed, Providence, RI 02912 USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Univ Barcelona, Dept Med, Barcelona, Spain. Chelsea & Westminster Hosp, Dept HIV Med, London, England. Int AIDS Soc USA, San Francisco, CA USA. Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. San Diego VA Healthcare Syst, San Diego, CA USA. Univ Colorado, Sch Med, Dept Med, Denver, CO USA. AIDS Res Consortium Atlanta, Atlanta, GA USA. Ist Super Sanita, I-00161 Rome, Italy. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Yeni, PG (reprint author), Hop Bichat Claude Bernard, X Bichat Med Sch, Dept Infect Dis, 46 Rue Henri Huchard, F-75877 Paris 18, France. EM Patrick.Yeni@Bch.Ap-Hop-Paris.Fr RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 88 TC 413 Z9 440 U1 0 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 14 PY 2004 VL 292 IS 2 BP 251 EP 265 DI 10.1001/jama.292.2.251 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 836TS UT WOS:000222579300031 PM 15249575 ER PT J AU Sazani, PL Larralde, R Szostak, JW AF Sazani, PL Larralde, R Szostak, JW TI A small aptamer with strong and specific recognition of the triphosphate of ATP SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR DISCRIMINATION; ADENINE-NUCLEOTIDES; BINDING RNA; ANALOGS; MOTIFS; ION; PH C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM53936] NR 15 TC 92 Z9 93 U1 4 U2 59 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 14 PY 2004 VL 126 IS 27 BP 8370 EP 8371 DI 10.1021/ja049171k PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 837EZ UT WOS:000222612600010 PM 15237981 ER PT J AU Jaffer, FA Tung, CH Wykrzykowska, JJ Ho, NH Houng, AK Reed, GL Weissleder, R AF Jaffer, FA Tung, CH Wykrzykowska, JJ Ho, NH Houng, AK Reed, GL Weissleder, R TI Molecular imaging of factor XIIIa activity in thrombosis using a novel, near-infrared fluorescent contrast agent that covalently links to thrombi SO CIRCULATION LA English DT Article DE blood factors; thrombosis; fluorescence; imaging; contrast media ID COAGULATION FACTOR-XIII; ACTIVATED FACTOR-XIII; FIBRINOLYTIC RESISTANCE; PLASMINOGEN-ACTIVATOR; THROMBOLYSIS; MODEL AB Background-Activated factor XIII (FXIIIa) mediates fibrinolytic resistance and is a hallmark of newly formed thrombi. In vivo imaging of FXIIIa activity could further elucidate the role of this molecule in thrombosis and other biological processes and aid in the clinical detection of acute thrombi. Methods and Results-An FXIIIa-sensitive near-infrared fluorescence imaging agent (A15) was engineered by conjugating a near-infrared fluorochrome to a peptide ligand derived from the amino terminus of alpha(2)-antiplasmin. To evaluate the molecular specificity of A15 for FXIIIa, a control agent (C15) was also synthesized by modifying a single key glutamine residue in A15. Fluorescence imaging experiments with A15 demonstrated stronger thrombosis enhancement in human plasma clots in vitro (P<0.001 versus C15 clots and other controls). A15 was found to be highly specific for the active site of FXIIIa and was covalently bound to fibrin. In vivo murine experiments with A15 demonstrated significant signal enhancement in acute intravascular thrombi (P<0.05 versus C15 group). Minimal A15 enhancement was seen in older aged thrombi (>24 hours), consistent with an expected decline of FXIIIa activity over time. Imaging results were confirmed on correlative histopathology and fluorescence microscopy. Conclusions-A15 is a novel optical imaging agent that is specifically crosslinked to fibrin by FXIIIa, permitting detection of FXIIIa activity in experimental thrombi in vivo. This agent should permit assessment of FXIIIa activity in a broad range of biological processes and could aid in the clinical diagnosis of acute thrombi. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Cardiol Div, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Cardiovasc Biol, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM fjaffer@partners.org; weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385, R24-CA92782]; NHLBI NIH HHS [HL-64057] NR 20 TC 71 Z9 73 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 13 PY 2004 VL 110 IS 2 BP 170 EP 176 DI 10.1161/01.CIR.0000134484.11052.44 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 837BR UT WOS:000222601900013 PM 15210587 ER PT J AU Masland, RH AF Masland, RH TI Neuronal cell types SO CURRENT BIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. EM masland@helix.mgh.harvard.edu NR 5 TC 96 Z9 98 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 13 PY 2004 VL 14 IS 13 BP R497 EP R500 DI 10.1016/j.cub.2004.06.035 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 837XD UT WOS:000222673700006 PM 15242626 ER PT J AU Rosand, J AF Rosand, J TI Hypertension and the brain - Stroke is just the tip of the iceberg SO NEUROLOGY LA English DT Editorial Material ID BLOOD-PRESSURE; HEMORRHAGE; RISK C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurocrit Care Unit, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, WACC 836,15 Parkman St, Boston, MA 02114 USA. EM jrosand@partners.org FU NINDS NIH HHS [1 K23 NS42695-01] NR 10 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 13 PY 2004 VL 63 IS 1 BP 6 EP 7 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 839VJ UT WOS:000222812700002 PM 15249601 ER PT J AU Zhang, L Gjoerup, O Roberts, TM AF Zhang, L Gjoerup, O Roberts, TM TI The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED PROTEIN-KINASE; CLATHRIN-MEDIATED ENDOCYTOSIS; EGF RECEPTOR; CELL-PROLIFERATION; TYROSINE KINASES; COATED VESICLES; PHOSPHORYLATION; PATHWAY; RAF-1; IDENTIFICATION AB Cyclin G-associated kinase (GAK) is a serine/threonine kinase that features high homology outside its kinase domain with auxilin. Like auxilin, GAK has been shown to be a cofactor for uncoating clathrin vesicles in vitro. We investigated epidermal growth factor (EGF) receptor-mediated signaling in cells, in which GAK is down-regulated by small hairpin RNAs. Here, we report that downregulation of GAK by small hairpin RNA has two pronounced effects on EGF receptor signaling: (i) the levels of receptor expression and tyrosine kinase activity go up by >50-fold; and (h) the spectrum of downstream signaling is significantly changed. One very obvious result is a large increase in the levels of activated extracellular signal-regulated kinase 5 and Akt. These two effects of GAK down-regulation result from, at least in part, alterations in receptor trafficking, the most striking of which is the persistence of EGF receptor in altered cellular compartment along with activated extracellular signal-regulated kinase 5. The alterations resulting from GAK down-regulation can have distinctive biological consequences: In CV1P cells, down-regulation of GAK results in outgrowth of cells in soft agar, raising the possibility that loss of GAK function may promote tumorigenesis. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM thomas-roberts@dfci.harvard.edu FU NCI NIH HHS [P01 CA050661, CA50661]; NICHD NIH HHS [P30 HD018655, P30 HD18655] NR 41 TC 43 Z9 43 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 13 PY 2004 VL 101 IS 28 BP 10296 EP 10301 DI 10.1073/pnas.0403175101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200011 PM 15240878 ER PT J AU Paust, S Lu, LR McCarty, N Cantor, H AF Paust, S Lu, LR McCarty, N Cantor, H TI Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; TRYPTOPHAN CATABOLISM; ANTIGEN; INDUCTION; COLITIS; CTLA-4; FOXP3; MICE AB Although there is considerable evidence that a subpopulation of regulatory CD4(+)CD25(+) T cells can suppress the response of autoreactive T cells, the underlying molecular mechanism is not understood. We find that transmission of a suppressive signal by CD4CD25(+) regulatory cells requires engagement of the B7 molecule expressed on target T cells. The response of T cells from B7-deficient mice is resistant to suppression in vitro, and these cells provoke a lethal wasting disease in lymphopenic mice despite the presence of regulatory T cells. Susceptibility of B7-cleficient cells to suppression is restored by lentiviral-based expression of full-length, but not truncated, B7 lacking a transmembrane/ cytoplasmic domain. Because expression of these B7 truncation mutants restores CD28-dependent costimulatory activity, these findings that indicate B7-based transmission of suppressive activity suggest new approaches to modifying autoimmune responses. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol, 44 Binney St,SM 722, Boston, MA 02115 USA. EM harvey.cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013; OI Lu, Linrong/0000-0002-0171-4115 NR 32 TC 208 Z9 226 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 13 PY 2004 VL 101 IS 28 BP 10398 EP 10403 DI 10.1073/pnas.0403342101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200029 PM 15235129 ER PT J AU Ueki, K Kondo, T Tseng, YH Kahn, CR AF Ueki, K Kondo, T Tseng, YH Kahn, CR TI Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE KINASE-ACTIVITY; NECROSIS-FACTOR-ALPHA; DIABETES-MELLITUS; ADIPOSE-TISSUE; MICE; OBESITY; SOCS-3; LIVER; GENE; INHIBITION AB Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism is poorly understood. Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Univ Tokyo, Dept Metab Dis, Grad Sch Med, Tokyo 113, Japan. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK055545, DK33201, DK34834, DK55545, R01 DK033201] NR 39 TC 233 Z9 247 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 13 PY 2004 VL 101 IS 28 BP 10422 EP 10427 DI 10.1073/pnas.0402511101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200033 PM 15240880 ER PT J AU Vergnes, L Peterfy, M Bergo, MO Young, SG Reue, K AF Vergnes, L Peterfy, M Bergo, MO Young, SG Reue, K TI Lamin B1 is required for mouse development and nuclear integrity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nuclear envelope; lamins; knockout mice; gene trapping ID HUTCHINSON-GILFORD-PROGERIA; A-TYPE; INSERTIONAL MUTATIONS; ENVELOPE PROTEINS; BUILDING-BLOCKS; MAMMALIAN-CELLS; DEFICIENT MICE; HUMAN-DISEASE; STEM-CELLS; A/C AB Lamins are key structural components of the nuclear lamina, an intermediate filament meshwork that lies beneath the inner nuclear membrane. Lamins play a role in nuclear architecture, DNA replication, and gene expression. Mutations affecting A-type lamins have been associated with a variety of human diseases, including muscular dystrophy, cardiomyopathy, lipodystrophy, and progeria, but mutations in B-type lamins have never been identified in humans or in experimental animals. To investigate the in vivo function of lamin B1, the major B-type lamin, we generated mice with an insertional mutation in Lmnb1. The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the CAAX motif (the carboxyl-terminal signal for farnesylation). Homozygous Lmnb1 mutant mice survived embryonic development but died at birth with defects in lung and bone. Fibroblasts from mutant embryos grew under standard cell-culture conditions but displayed grossly misshapen nuclei, impaired differentiation, increased polyploidy, and premature senescence. Thus, the lamin B1 mutant mice provide evidence for a broad and nonredundant function of lamin B1 in mammalian development. These mutant mice and cell lines derived from them will be useful models for studying the role of the nuclear lamina in various cellular processes. C1 Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90073 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA. RP Reue, K (reprint author), 11301 Wilshire Blvd,Bldg 113,Room 312, Los Angeles, CA 90073 USA. EM reuek@ucla.edu FU NHLBI NIH HHS [U01 HL066621, U01 HL66621] NR 41 TC 206 Z9 212 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 13 PY 2004 VL 101 IS 28 BP 10428 EP 10433 DI 10.1073/pnas.0401424101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200034 PM 15232008 ER PT J AU Kong, TQ Eltzschig, HK Karhausen, J Colgan, SP Shelley, CS AF Kong, TQ Eltzschig, HK Karhausen, J Colgan, SP Shelley, CS TI Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction Of beta 2 integrin gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL BARRIER FUNCTION; ISCHEMIA-REPERFUSION INJURY; TUMOR-SUPPRESSOR PROTEIN; CELL-LINE U937; TRANSCRIPTION FACTOR; STRUCTURAL BASIS; CD11B PROMOTER; MYELOID CELLS; NEUTROPHIL; HIF-1 AB Inflammatory responses are associated with significant changes in tissue metabolism. In particular, metabolic shifts during inflammation can result in significant tissue hypoxia, with resultant induction of hypoxia-responsive genes. Given this association, we hypothesized that leukocyte functional responses are influenced by hypoxia. Initial experiments revealed that exposure of the promonocytic cell line U937 to hypoxia resulted in increased adhesion to activated endothelia. Such increases were transcription-dependent and were blocked by antibodies directed against beta(2), but not beta(1), integrins. Analysis Of 92 integrin mRNA and protein in U937 cells revealed a 5 to 6-fold increase with hypoxia. Extension of this analysis to hypoxic human whole blood revealed prominent induction Of 92 integrin mRNA and protein ex vivo. Furthermore, murine O-2 integrin mRNA was found to be significantly induced during hypoxia in vivo. Subsequent studies identified a binding site for hypoxia-inclucible factor 1 (HIF-1) in the CD18 gene. This gene encodes the subunit common to all four known types of beta(2). integrin heterodimer. HIF-1 binding was demonstrated in vivo, and mutational analysis of the HIF-11 site within the CD18 promoter resulted in a loss of hypoxia inducibility. Taken together, these results demonstrate that hypoxia induces leukocyte beta(2) integrin expression and function by transcriptional mechanisms dependent upon HIF-1. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Tubingen, Dept Anesthesiol & Intens Care Med, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02129 USA. RP Shelley, CS (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Thorn Bldg 704,20 Shattuck St, Boston, MA 02115 USA. EM shelley@receptor.mgh.harvard.edu RI Colgan, Sean/B-4573-2009 FU NHLBI NIH HHS [HL60569, R01 HL060569]; NIDDK NIH HHS [DK50189, DK50305, P01 DK050305, R01 DK050189, R29 DK050189, R37 DK050189] NR 58 TC 135 Z9 145 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 13 PY 2004 VL 101 IS 28 BP 10440 EP 10445 DI 10.1073/pnas.0401339101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200036 PM 15235127 ER PT J AU Magee, CC Pascual, M AF Magee, CC Pascual, M TI Update in renal transplantation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; LAPAROSCOPIC DONOR NEPHRECTOMY; SOLID-ORGAN TRANSPLANTATION; QUALITY-OF-LIFE; KIDNEY-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; CARDIOVASCULAR-DISEASE; RACIAL-DIFFERENCES; DIABETES-MELLITUS; BLOOD-PRESSURE AB R enal transplantation is the treatment of choice for most patients with end-stage renal disease. The shortage of donor organs, however, remains a major obstacle to successful, early transplantation. This shortage has actually worsened despite an increase in living family-related and unrelated donors. On the other hand, over the last 10 years, allograft and recipient survival have significantly improved. This encouraging outcome reflects many factors, particularly a favorable shift in the balance between the efficacy and toxicity of immunosuppressive regimens. As acute rejection and early graft loss have become less common, the focus is increasingly directed toward the prevention and treatment of the long-term complications of renal transplantation. These include suboptimal allograft function, premature death, cardiovascular disease, and bone disease. Thus, a multidisciplinary approach-rather than management of immunological issues alone-is now required to optimize long-term outcomes of renal transplant recipients. C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. RP Magee, CC (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St,MRB-4, Boston, MA 02115 USA. EM cmagee@partners.org NR 128 TC 67 Z9 67 U1 2 U2 3 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 12 PY 2004 VL 164 IS 13 BP 1373 EP 1388 DI 10.1001/archinte.164.13.1373 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 836VM UT WOS:000222583900004 PM 15249346 ER PT J AU Wilt, TJ Bloomfield, HE MacDonald, R Nelson, D Rutks, I Ho, M Larsen, G McCall, A Pineros, S Sales, A AF Wilt, TJ Bloomfield, HE MacDonald, R Nelson, D Rutks, I Ho, M Larsen, G McCall, A Pineros, S Sales, A TI Effectiveness of statin therapy in adults with coronary heart disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED TRIAL; SCANDINAVIAN SIMVASTATIN SURVIVAL; PLACEBO-CONTROLLED TRIAL; ARTERY-DISEASE; ANGIOGRAPHIC RESTENOSIS; BALLOON ANGIOPLASTY; CARDIAC EVENTS; USUAL CARE; PRAVASTATIN AB Background: We conducted a meta-analysis of patients with coronary. heart disease (CHD) to determine the effectiveness of statin therapy; whether effectiveness varied according to patient characteristics, outcomes, or pretreatment low-density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and the level at which to initiate statin therapy. Methods: Randomized trials or systematic reviews for secondary prevention of CHD with statin therapy published between January 1966 and December 2002 were identified through MEDLINE and the Cochrane Library. Studies were included if they randomly assigned adults with CHD to statin therapy or control, enrolled at least 100 individuals per arm, reported clinical outcomes and LDL-C levels, and were published as full studies in English. Two reviewers abstracted data using a prospectively designed protocol. Results: Twenty-five studies enrolling 69 511 individuals were included. Participants in 19 placebo-controlled trials had a mean age of 63 years and a mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin therapy reduced CHD mortality or non-fatal myocardial infarction 25% (relative risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality 16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71-0.83). Beneficial effects were seen in women and the elderly. There were no data to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59 mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L) Meta-regression analyses revealed risk reductions for CHD mortality or non-fatal myocardial infarction and major vascular events across available pretreatment LDL-C levels. Conclusion: Statin therapy reduces mortality and morbidity in adults with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L). C1 Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. Denver VA Med Ctr, Denver, CO USA. Portland VA Med Ctr, Dept Cardiol, Portland, OR USA. Univ Virginia, Hlth Syst, Dept Internal Med, Charlottesville, VA USA. VA Puget Sound Hlth Care Syst, Ischem Heart Dis Qual Enhancement Res Initiat, Seattle, WA USA. RP Wilt, TJ (reprint author), Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, 1 Vet Dr,111-0, Minneapolis, MN 55417 USA. EM tim.wilt@med.va.gov RI Sales, Anne/D-9678-2012; OI bloomfield, hanna/0000-0002-0756-7064; Sales, Anne/0000-0001-9360-3334 NR 37 TC 149 Z9 158 U1 0 U2 12 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 12 PY 2004 VL 164 IS 13 BP 1427 EP 1436 DI 10.1001/archinte.164.13.1427 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 836VM UT WOS:000222583900010 PM 15249352 ER PT J AU Gauthier, LR Charrin, BC Borrell-Pages, M Dompierre, JP Rangone, H Cordelieres, FP De Mey, J MacDonald, ME Lessmann, V Humbert, S Saudou, F AF Gauthier, LR Charrin, BC Borrell-Pages, M Dompierre, JP Rangone, H Cordelieres, FP De Mey, J MacDonald, ME Lessmann, V Humbert, S Saudou, F TI Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules SO CELL LA English DT Article ID AXONAL-TRANSPORT; PROTEIN-1 HAP1; MOTOR-NEURONS; DISEASE; DYNACTIN; BRAIN; MICE; DROSOPHILA; LOCALIZATION; DEGENERATION AB Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington's disease (HD). Although wild-type huntingtin possesses antiapoptotic properties, the relationship between the neuroprotective functions of huntingtin and pathogenesis of HD remains unclear. Here, we show that huntingtin specifically enhances vesicular transport of brain-derived neurotrophic factor (BDNF) along microtubules. Huntingtin-mediated transport involves huntingtin-associated protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component of molecular motors. BDNF transport is attenuated both in the disease context and by reducing the levels of wild-type huntingtin. The alteration of the huntingtin/HAP1/p150(Glued) complex correlates with reduced association of motor proteins with microtubules. Finally, we find that the polyQ-huntingtin-induced transport deficit results in the loss of neurotrophic support and neuronal toxicity. Our findings indicate that a key role of huntingtin is to promote BDNF transport and suggest that loss of this function might contribute to pathogenesis. C1 Ctr Univ, Inst Curie, CNRS, Unite Mixte Rech 146, F-91405 Orsay, France. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Mainz, Inst Physiol & Pathophysiol, D-55128 Mainz, Germany. RP Saudou, F (reprint author), Ctr Univ, Inst Curie, CNRS, Unite Mixte Rech 146, Bldg 110, F-91405 Orsay, France. EM sandrine.humbert@curie.u-psud.fr; frederic.saudou@curie.u-psud.fr RI Lessmann, Volkmar/E-8125-2013; SAUDOU, Frederic/L-3454-2014; Humbert, Sandrine/S-2981-2016 OI Lessmann, Volkmar/0000-0002-6863-323X; SAUDOU, Frederic/0000-0001-6107-1046; FU NIMH NIH HHS [MH/NS 31862] NR 45 TC 576 Z9 602 U1 0 U2 35 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 9 PY 2004 VL 118 IS 1 BP 127 EP 138 DI 10.1016/j.cell.2004.06.018 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 837JW UT WOS:000222626800013 PM 15242649 ER PT J AU Rabizadeh, S Xavier, RJ Ishiguro, K Bernabeortiz, J Lopez-Ilasaca, M Khokhlatchev, A Mollahan, P Pfeifer, GP Avruch, J Seed, B AF Rabizadeh, S Xavier, RJ Ishiguro, K Bernabeortiz, J Lopez-Ilasaca, M Khokhlatchev, A Mollahan, P Pfeifer, GP Avruch, J Seed, B TI The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIGENETIC INACTIVATION; PROMOTES APOPTOSIS; KINASE ACTIVATION; RAS-EFFECTOR; FAMILY PROTEIN; HUMAN CANCERS; CYCLE EXIT; DROSOPHILA; GENE; PROLIFERATION AB The connector enhancer of KSR (CNK) is a multidomain scaffold protein discovered in Drosophila, where it is necessary for Ras activation of the Raf kinase. Recent studies have shown that CNK1 also interacts with RalA and Rho and participates in some aspects of signaling by these GTPases. Herein we demonstrate a novel aspect of CNK1 function, i.e. reexpression of CNK1 suppresses tumor cell growth and promotes apoptosis. As shown previously for apoptosis induced by Ki-Ras(G12V), CNK1-induced apoptosis is suppressed by a dominant inhibitor of the mammalian sterile 20 kinases 1 and (MST1/MST2). Immunoprecipitates of MST1 endogenous to LoVo colon cancer cells contain endogenous CNK1; however, no association of these two polypeptides can be detected in a yeast two-hybrid assay. CNK1 does, however, bind directly to the RASSF1A and RASSF1C polypeptides, constitutive binding partners of the MST1/2 kinases. Deletion of the MST1 carboxyl-terminal segment that mediates its binding to RASSF1A/C eliminates the association of MST1 with CNK1. Coexpression of CNK1 with the tumor suppressive isoform, RASSF1A, greatly augments CNK1-induced apoptosis, whereas the nonsuppressive RASSF1C isoform is without effect on CNK1-induced apoptosis. Overexpression of CNK1-(1-282), a fragment that binds RASSF1A but is not proapoptotic, blocks the apoptosis induced by CNK1 and by Ki-Ras( G12V). Thus, in addition to its positive role in the proliferative outputs of active Ras, the CNK1 scaffold protein, through its binding of a RASSF1A.MST complex, also participates in the proapoptotic signaling initiated by active Ras. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. Buck Inst Age Res, Discovery Translat Unit, Novato, CA 94945 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. City Hope Natl Med Ctr, Dept Biol, Duarte, CA 91010 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM seed@molbio.mgh.harvard.edu OI Ishiguro, Kazuhiro/0000-0003-1776-2805 NR 43 TC 66 Z9 71 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29247 EP 29254 DI 10.1074/jbc.M401699200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300053 PM 15075335 ER PT J AU Wang, JC Walker, A Blackwell, TK Yamamoto, KR AF Wang, JC Walker, A Blackwell, TK Yamamoto, KR TI The Caenorhabditis elegans ortholog of TRAP240, CeTRAP240/let-19, selectively modulates gene expression and is essential for embryogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTIONAL ACTIVATION; C-ELEGANS; MEDIATOR COMPLEXES; DEPENDENT TRANSCRIPTION; EMBRYONIC-DEVELOPMENT; COACTIVATOR COMPLEX; NUCLEAR RECEPTORS; PROTEIN; YEAST AB Mediator complexes are large multiprotein assemblies that function in the regulation of eukaryotic gene transcription. In yeast, certain mediator subunits appear to comprise a subcomplex that acts in the regulation of a specific subset of genes. We investigated in a metazoan, Caenorhabditis elegans, the roles and interactions of two of those subunits, CeTRAP240/let-19 and CeTRAP230/dpy-22. We found that CeTRAP240/let-19 contains four domains that are conserved in the human TRAP240 protein and that one of those domains displays intrinsic transcriptional repression activity. Using RNA interference, we found that reduced expression of CeTRAP240/let-19 displayed a high penetrance of embryonic lethality in F1 progeny; animals that escaped embryonic arrest showed mutant phenotypes such as burst vulva and molting defects. CeTRAP240/let-19 appeared to affect specific genes, as CeTRAP240/let-19(RNAi) led to selectively reduced expression of a subset of reporter genes examined. Genetic experiments supported the view that CeTRAP240/let-19 and CeTRAP230/dpy-22, like their Drosophila and yeast counterparts, can operate on common pathways. Thus, a male tail phenotype caused by the pal-1(e2091) mutation was suppressed not only by CeTRAP230/dpy-22 mutants, as reported previously, but also by reduced expression of CeTRAP240/let-19. Additionally, CeTRAP240/let-19(RNAi) in a CeTRAP230/dpy-22 mutant background produced a strong synthetic lethal phenotype. Overall, our results establish specific roles of CeTRAP240/let-19 in C. elegans embryonic development and a functional interaction between CeTRAP240/let-19 and CeTRAP230/dpy-22. Interestingly, whereas this interaction has been conserved from yeast to mammals, the subcomplex modulates metazoan-specific genetic pathways, likely in addition to those also controlled in yeast. C1 Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94107 USA. Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. RP Yamamoto, KR (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, S572D,Genentech Hall,600 16th St, San Francisco, CA 94107 USA. EM yamamoto@cmp.ucsf.edu OI Wang, Jen-Chywan/0000-0001-6030-6886 FU NIGMS NIH HHS [R01 GM062891] NR 52 TC 25 Z9 37 U1 3 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29270 EP 29277 DI 10.1074/jbc.M401242200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300056 PM 15073178 ER PT J AU da Silva, FA Santa-Marta, M Freitas-Vieira, A Mascarenhas, P Barahona, I Moniz-Pereira, J Gabuzda, D Goncalves, J AF da Silva, FA Santa-Marta, M Freitas-Vieira, A Mascarenhas, P Barahona, I Moniz-Pereira, J Gabuzda, D Goncalves, J TI Camelized rabbit-derived VH single-domain Intrabodies Against vif strongly neutralize HIV-1 infectivity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE intracellular antibodies; VH single-domains; camelization; Vif neutralization; HIV infectivity ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIBODY FRAGMENTS; INTRACELLULAR ANTIBODIES; SOR GENE; IN-VIVO; ESCHERICHIA-COLI; HIGH-AFFINITY; SWISS-MODEL; H DOMAINS; PROTEIN AB We recently developed a specific single-chain antibody from immunized rabbits to HIV-1 Vif protein that was expressed intracellularly and inhibited reverse transcription and viral replication. The Vif of HIV-1 overcomes the innate antiviral activity of a cytidine deaminase Apobec3G (CEM15) that induces G to A hypermutation in the viral genome, resulting in enhancement of viral replication infectivity. Here, we have developed a minimal scaffold VH fragment with intrabody properties derived from anti-Vif single-chain antibody that was engineered to mimic camelid antibody domains. Non-specific binding of VH by its interface for the light chain variable domain (VL) was prevented through amino acid mutations in framework 2 and 4 (Val37F, G44E, L45R, W47G and W103R). Our results demonstrate that all constructed anti-Vif VH single-domains preserve the antigen-binding activity and specificity in the absence of the parent VL domain. However, only the most highly camelized domains had high levels of intracellular expression. The expression in eukaryotic cells showed that VH single-domains could correctly fold as soluble proteins in the reducing environment. The results demonstrated an excellent correlation between improvements in protein solubility with gradually increasing camelization. Camelized single-domains efficiently bound Vif protein and neutralized its infectivity enhancing function, by reducing late reverse transcripts and proviral integration. The activity of the anti-Vif single-domains was shown to be cell-specific, with inhibitory effects only in cells non-permissive that require Vif for HIV-1 replication. Moreover, cell specificity of anti-Vif intrabodies was correlated with an increase of Apobec3G, which potentiates viral inhibition. The present study strongly suggests that camelization of rabbit VH domains is a potentially useful approach for engineering intrabodies for gene therapy. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Lisbon, URIA, Ctr Patogenese Mol, Fac Farm, P-1649019 Lisbon, Portugal. Inst Super Ciencias Saude Sul, P-2829511 Caparica, Portugal. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Goncalves, J (reprint author), Univ Lisbon, URIA, Ctr Patogenese Mol, Fac Farm, P-1649019 Lisbon, Portugal. EM joao.goncalves@ff.ul.pt RI barahona, isabel/J-6877-2012; Santa-Marta, Mariana/L-2407-2013; Goncalves, Joao/B-2013-2008; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, M2B /B-5277-2014; OI barahona, isabel/0000-0002-2654-0983; Santa-Marta, Mariana/0000-0002-0243-4158; Goncalves, Joao/0000-0002-1245-3715; mascarenhas, paulo/0000-0002-6584-1199; Moniz-Pereira, Jose/0000-0002-8779-2017; Aires da Silva, Frederico/0000-0002-3821-419X NR 58 TC 43 Z9 45 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 9 PY 2004 VL 340 IS 3 BP 525 EP 542 DI 10.1016/j.jmb.2004.04.062 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836MN UT WOS:000222560000011 ER PT J AU Pasinelli, P Belford, ME Lennon, N Bacskai, BJ Hyman, BT Trotti, D Brown, RH AF Pasinelli, P Belford, ME Lennon, N Bacskai, BJ Hyman, BT Trotti, D Brown, RH TI Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria SO NEURON LA English DT Article ID TRANSGENIC MOUSE MODEL; SUPEROXIDE-DISMUTASE GENE; PROGRAMMED CELL-DEATH; MOTOR-NEURON DEATH; ALS-LINKED SOD1; OXIDATIVE DAMAGE; APOPTOTIC DEATH; DEGENERATION; MUTATIONS; MICE AB Familial amyotrophic lateral sclerosis (ALS)-linked mutations in the copper-zinc superoxide dismutase (SOD1) gene cause motor neuron death in about 3% of ALS cases. While the wild-type (wt) protein is anti-apoptotic, mutant SOD1 promotes apoptosis. We now demonstrate that both wt and mutant SOD1 bind the anti-apoptotic protein Bcl-2, providing evidence of a direct link between SOD1 and an apoptotic pathway. This interaction is evident in vitro and in vivo in mouse and human spinal cord. We also demonstrate that in mice and humans, Bcl-2 binds to high molecular weight SIDS-resistant mutant SOD1 containing aggregates that are present in mitochondria from spinal cord but not liver. These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein. C1 Harvard Univ, Sch Med, Mass Gen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Day Lab Neuromusc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Mass Gen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Dept Neurol, Charlestown, MA 02129 USA. RP Pasinelli, P (reprint author), Harvard Univ, Sch Med, Mass Gen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Day Lab Neuromusc Res, Charlestown, MA 02129 USA. EM ppasinelli@partners.org; rhbrown@partners.org FU NIA NIH HHS [P01 AG12992-9, R03-AG022252, R37 AG12406]; NIBIB NIH HHS [EB00768]; NINDS NIH HHS [R01-NS44292] NR 43 TC 287 Z9 303 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 8 PY 2004 VL 43 IS 1 BP 19 EP 30 DI 10.1016/j.neuron.2004.06.021 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 836IT UT WOS:000222549800004 PM 15233914 ER PT J AU D'Amico, AV Chen, MH Roehl, KA Catalona, WJ AF D'Amico, AV Chen, MH Roehl, KA Catalona, WJ TI Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DOUBLING TIME AB Background: We evaluated whether men at risk for death from prostate cancer after radical prostatectomy can be identified using information available at diagnosis. Methods: We studied 1095 men with localized prostate cancer to assess whether the rate of rise in the prostate-specific antigen (PSA) level-the PSA velocity-during the year before diagnosis, the PSA level at diagnosis, the Gleason score, and the clinical tumor stage could predict the time to death from prostate cancer and death from any cause after radical prostatectomy. Results: As compared with an annual PSA velocity of 2.0 ng per milliliter or less, an annual PSA velocity of more than 2.0 ng per milliliter was associated with a significantly shorter time to death from prostate cancer (P<0.001) and death from any cause (P=0.01). An increasing PSA level at diagnosis (P=0.01), a Gleason score of 8, 9, or 10 (P=0.02), and a clinical tumor stage of T2 (P<0.001) also predicted the time to death from prostate cancer. For men with an annual PSA velocity of more than 2.0 ng per milliliter, estimates of the risk of death from prostate cancer and death from any cause seven years after radical prostatectomy were also influenced by the PSA level, tumor stage, and Gleason score at diagnosis. Conclusions: Men whose PSA level increases by more than 2.0 ng per milliliter during the year before the diagnosis of prostate cancer may have a relatively high risk of death from prostate cancer despite undergoing radical prostatectomy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Northwestern Feinberg Sch Med, Dept Urol, Chicago, IL USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L-2 Level,75 Francis St, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu NR 15 TC 487 Z9 502 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 8 PY 2004 VL 351 IS 2 BP 125 EP 135 DI 10.1056/NEJMoa032975 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 835GM UT WOS:000222470700005 PM 15247353 ER PT J AU Lipshultz, SE Rifai, N Dalton, VM Levy, DE Silverman, LB Lipsitz, SR Colan, SD Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Gelber, RD Sallan, SE AF Lipshultz, SE Rifai, N Dalton, VM Levy, DE Silverman, LB Lipsitz, SR Colan, SD Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Gelber, RD Sallan, SE TI The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CARDIAC TROPONIN-T; CHILDHOOD-CANCER; ANTHRACYCLINE CARDIOTOXICITY; CONTINUOUS-INFUSION; 5-YEAR SURVIVORS; LATE MORTALITY; HEART-FAILURE; SERUM-LEVELS; PHASE-I; ICRF-187 AB Background: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. Methods: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter) -- the primary end point -- or extremely elevated (>0.025 ng per milliliter). Results: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). Conclusions: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival. C1 Univ Miami, Sch Med, Holtz Childrens Hosp,Dept Pediat, Jackson Mem Med Ctr, Miami, FL 33101 USA. Sylvester Comprehens Canc Ctr, Miami, FL USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. McMaster Univ, Dept Pediat, Hamilton, ON, Canada. San Jorge Childrens Hosp, Santurce, PR USA. Barbara Bush Childrens Hosp Maine, Med Ctr, Maine Children Canc Program, Portland, ME USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. Alton Ochsner Med Fdn & Ochsner Clin, Dept Pediat, New Orleans, LA 70121 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Lipsitz, SR (reprint author), Univ Miami, Sch Med, Dept Pediat, D820,POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu FU NCI NIH HHS [CA 06516, CA 55576, CA 68484, CA 79060]; NHLBI NIH HHS [HL 53392, HL 59837, HL 72705, HR96041] NR 53 TC 271 Z9 289 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 8 PY 2004 VL 351 IS 2 BP 145 EP 153 DI 10.1056/NEJMoa035153 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 835GM UT WOS:000222470700007 PM 15247354 ER PT J AU Kaufman, DS McDougal, WS Zietman, AL Harisinghani, MG Young, RH Shipley, WU Gomery, P Harisinghani, MG Smith, MR Michaelson, D Althausen, AF Talcott, J AF Kaufman, DS McDougal, WS Zietman, AL Harisinghani, MG Young, RH Shipley, WU Gomery, P Harisinghani, MG Smith, MR Michaelson, D Althausen, AF Talcott, J TI A man with metastatic prostate carcinoma refractory to hormone therapy - Adenocarcinoma of the prostate with metastases SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; SEXUAL FUNCTION; CANCER; RADIOTHERAPY; TRIAL; ESTRAMUSTINE; MITOXANTRONE; SYMPTOMS; SURVIVAL C1 Massachusetts Gen Hosp, Dept Med, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, 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 Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Urol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, 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 Kaufman, DS (reprint author), Massachusetts Gen Hosp, Dept Med, Div Med Oncol, Boston, MA 02114 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 8 PY 2004 VL 351 IS 2 BP 171 EP 178 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 835GM UT WOS:000222470700012 PM 15247358 ER PT J AU Bachand, F Silver, PA AF Bachand, F Silver, PA TI PRMT3 is a ribosomal protein methyltransferase that affects the cellular levels of ribosomal subunits SO EMBO JOURNAL LA English DT Article DE arginine methylation; PRMT3; 40S ribosomal protein S2; ribosome biosynthesis ID ARGININE N-METHYLTRANSFERASE; MASS-SPECTROMETRIC ANALYSIS; SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; NUCLEAR EXPORT; SCHIZOSACCHAROMYCES-POMBE; TRANSLATIONAL CONTROL; BINDING PROTEIN; 40-S SUBUNITS; METHYLATION AB The mammalian protein arginine methyltransferase 3 (PRMT3) catalyzes the formation of asymmetric (type 1) dimethylarginine in vitro. As yet, natural substrates and cellular pathways modulated by PRMT3 remain unknown. Here, we have identified an ortholog of PRMT3 in fission yeast. Tandem affinity purification of fission yeast PRMT3 coupled with mass spectrometric protein identification revealed that PRMT3 associates with components of the translational machinery. We identified the 40S ribosomal protein S2 as the first physiological substrate of PRMT3. In addition, a fraction of yeast and human PRMT3 cosedimented with free 40S ribosomal subunits, as determined by sucrose gradient velocity centrifugation. The activity of PRMT3 is not essential since prmt3-disrupted cells are viable. Interestingly, cells lacking PRMT3 showed an accumulation of free 60S ribosomal subunits resulting in an imbalance in the 40S:60S free subunits ratio; yet pre-rRNA processing appeared to occur normally. Our results identify PRMT3 as the first type I ribosomal protein arginine methyltransferase and suggest that it regulates ribosome biosynthesis at a stage beyond pre-rRNA processing. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu NR 56 TC 100 Z9 102 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 7 PY 2004 VL 23 IS 13 BP 2641 EP 2650 DI 10.1038/sj.emboj.7600265 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 845MT UT WOS:000223249300018 PM 15175657 ER PT J AU Olshevskaya, EV Calvert, PD Woodruff, ML Peshenko, IV Savchenko, AB Makino, CL Ho, YS Fain, GL Dizhoor, AM AF Olshevskaya, EV Calvert, PD Woodruff, ML Peshenko, IV Savchenko, AB Makino, CL Ho, YS Fain, GL Dizhoor, AM TI The Y99C mutation in guanylyl cyclase-activating protein 1 increases intracellular Ca2+ and causes photoreceptor degeneration in transgenic mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retina; guanylyl cyclase; calcium; retinal dystrophy; transgenic mice; cone; retinal degeneration; photoreceptors ID CONE-ROD DYSTROPHY; RETINAL DEGENERATION; OUTER SEGMENTS; VERTEBRATE PHOTORECEPTORS; CALCIUM-CONCENTRATION; CGMP SYNTHESIS; BETA-SUBUNIT; MOUSE; MEMBRANE; LIGHT AB Guanylyl cyclase-activating proteins (GCAPs) are Ca2+-binding proteins that activate guanylyl cyclase when free Ca2+ concentrations in retinal rods and cones fall after illumination and inhibit the cyclase when free Ca2+ reaches its resting level in the dark. Several forms of retinal dystrophy are caused by mutations in GUCA1A, the gene coding for GCAP1. To investigate the cellular mechanisms affected by the diseased state, we created transgenic mice that express GCAP1 with a Tyr99Cys substitution (Y99C GCAP1) found in human patients with a late-onset retinal dystrophy (Payne et al., 1998). Y99C GCAP1 shifted the Ca2+ sensitivity of the guanylyl cyclase in photoreceptors, keeping it partially active at 250 nM free Ca2+, the normal resting Ca2+ concentration in darkness. The enhanced activity of the cyclase in the dark increased cyclic nucleotide-gated channel activity and elevated the rod outer segment Ca2+ concentration in darkness, measured by using fluo-5F and laser spot microscopy. In different lines of transgenic mice the magnitude of this effect rose with the Y99C GCAP1 expression. Surprisingly, there was little change in the rod photoresponse, indicating that dynamic Ca2+-dependent regulation of cGMP synthesis was preserved. However, the photoreceptors in these mice degenerated, and the rate of the cell loss increased with the level of the transgene expression, unlike in transgenic mice that overexpressed normal GCAP1. These results provide the first direct evidence that a mutation linked to congenital blindness increases Ca2+ in the outer segment, which may trigger the apoptotic process. C1 Penn Coll Optometry, Hafter Res Labs, Elkins Pk, PA 19027 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA. RP Dizhoor, AM (reprint author), Penn Coll Optometry, Hafter Res Labs, 8360 Old York Rd, Elkins Pk, PA 19027 USA. EM adizhoor@pco.edu OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [EY11522, EY01844, EY12944]; NIEHS NIH HHS [P30 ES06639] NR 53 TC 71 Z9 74 U1 0 U2 0 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 7 PY 2004 VL 24 IS 27 BP 6078 EP 6085 DI 10.1523/JNEUROSCI.0963-04.2004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 835NR UT WOS:000222491000005 PM 15240799 ER PT J AU Cao, GD Xiao, M Sun, FY Xiao, X Pei, W Li, J Graham, SH Simon, RP Chen, J AF Cao, GD Xiao, M Sun, FY Xiao, X Pei, W Li, J Graham, SH Simon, RP Chen, J TI Cloning of a novel Apaf-1-interacting protein: A potent suppressor of apoptosis and ischemic neuronal cell death SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebral ischemia; mitochondria; AAV; Apaf-1; apoptosome; caspase-9 ID FOCAL CEREBRAL-ISCHEMIA; ADENOASSOCIATED VIRUS VECTORS; HIPPOCAMPAL CA1 NEURONS; CENTRAL-NERVOUS-SYSTEM; CYTOCHROME-C RELEASE; CASPASE ACTIVATION; SUPEROXIDE-DISMUTASE; DNA FRAGMENTATION; ENDOGENOUS INHIBITOR; BRAIN-DEVELOPMENT AB Cytochrome c-initiated activation of apoptotic protease activating factor-1 (Apaf-1) is a key step in the mitochondrial-signaling pathway for the activation of death-executing caspases in apoptosis. This signaling pathway has been implicated in the pathophysiology of various neurological disorders, including ischemic brain injury. In this study, we have cloned a novel rat gene product, designated as Apaf-1-interacting protein (AIP), which functions as a dominant-negative inhibitor of the Apaf-1-caspase-9 pathway. AIP is constitutively expressed in the brain, but at substantially lower levels than Apaf-1 and caspase-9. AIP can directly bind to Apaf-1 in vitro through its N-terminal caspase-recruiting domain, and this protein interaction was increased in cells undergoing apoptosis. Cytosolic extracts from cells overexpressing AIP were highly resistant to cytochrome c-dATP-induced activation of caspase-9 and caspase-3. Gene transfection of AIP into cell lines, including the neuronal-differentiated PC12 cells, potently suppressed apoptosis induced by various pro-apoptotic stimuli. To further investigate the functional role of AIP in primary neurons and in the brain, an adeno-associated virus (AAV) vector carrying the AIP cDNA was constructed. AAV-mediated overexpression of AIP in primary cortical-hippocampal neurons markedly reduced cell death and caspase-3 activation triggered by protein kinase C inhibition, DNA damage, or oxygen-glucose deprivation. Moreover, intracerebral infusion of the AAV vector resulted in robust AIP expression in the hippocampus and significantly promoted CA1 neuronal survival after transient global cerebral ischemia. These results suggest that molecular targeting of the Apaf-1-caspase-9 signaling pathway may be a feasible neuroprotective strategy to enhance the endogenous threshold for caspase activation and prevent neuronal loss in stroke and related disorders. C1 Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Fudan Univ, Sch Med, Natl Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97232 USA. Oregon Hlth Sci Univ, Dept Physiol, Portland, OR 97232 USA. Oregon Hlth Sci Univ, Dept Pharmacol, Portland, OR 97232 USA. Oregon Hlth Sci Univ, RS Dow Neurobiol Labs, Portland, OR 97232 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [NS36736, NS35965, NS43802, NS45048] NR 57 TC 40 Z9 43 U1 0 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 7 PY 2004 VL 24 IS 27 BP 6189 EP 6201 DI 10.1523/JNEUROSCI.1426-04.2004 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 835NR UT WOS:000222491000017 PM 15240811 ER PT J AU Stadius, ML AF Stadius, ML TI Diminishing returns... and too many choices... the saga of pharmacologic therapy to reduce the complications of percutaneous coronary intervention SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID GLYCOPROTEIN-IIB/IIIA BLOCKADE; RANDOMIZED CONTROLLED TRIAL; PLATELET-AGGREGATION; ARTERY STENTS; CLOPIDOGREL; ANGIOPLASTY; ASPIRIN; TICLOPIDINE; PRETREATMENT; HEPARIN C1 Vet Adm Med Ctr, VA Puget Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Stadius, ML (reprint author), Vet Adm Med Ctr, VA Puget Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM michael.stadius@med.va.gov NR 33 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 7 PY 2004 VL 44 IS 1 BP 25 EP 27 DI 10.1016/j.jacc.2004.04.010 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834OX UT WOS:000222421500005 PM 15234400 ER PT J AU Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C AF Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C TI Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SEPTIC SHOCK; DOUBLE-BLIND; ANTIINFLAMMATORY AGENTS; HYDROCORTISONE; METHYLPREDNISOLONE; THERAPIES; MORTALITY; EFFICACY; EPIDEMIOLOGY; STRATEGIES AB Background: Previous meta-analyses demonstrated that highdose glucocorticoids were not beneficial in sepsis. Recently, lowerdose glucocorticolds have been studied. Purpose: To compare recent trials of glucocorticoids for sepsis with previous glucocorticoid trials. Data Sources: Systematic MEDLINE search for studies published between 1988 and 2003. Study Selection: Randomized, controlled trials of sepsis that examined the effects of glucocorticoids on survival or vasopressor requirements. Data Extraction: Two investigators independently collected data on patient and study characteristics, treatment interventions, and outcomes. Data Synthesis: The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival (l(2) = 0%; relative benefit, 1.23, [95% Cl, 1.01 to 1.50]; P= 0.036) and shock reversal (l(2) = 0%; relative benefit, 1.71 [Cl, 1.29 to 2.26]; P < 0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment (l(2) = 14%; relative benefit, 0.89 [Cl, 0.82 to 0.97]; P = 0.008). In comparison with the earlier trials, the more recent trials administered steroids later after patients met enrollment criteria (median, 23 hours vs. <2 hours; P = 0.02), for longer courses (6 days vs. 1 day; P = 0.01), and in lower total dosages (hydrocortisone equivalents, 1209 mg vs. 23 975 mg; P = 0.01) to patients with higher control group mortality rates (mean, 57% vs. 34%; P = 0.06) who were more likely to be vasopressor-dependent (100% vs. 65%; P = 0.03). The relationship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses (P = 0.02). Limitations: We could not analyze time-related improvements in medical care and potential bias secondary to nonreporting of negative study results. Conclusions: Although short courses of high-dose glucocorticolds decreased survival during sepsis, a 5- to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases survival rate and shock reversal in patients with vasopressor-dependent septic shock. C1 NHLBI, Ctr Clin, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 42 TC 205 Z9 223 U1 2 U2 11 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 6 PY 2004 VL 141 IS 1 BP 47 EP 56 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 834RF UT WOS:000222427600007 PM 15238370 ER PT J AU Snow, V Barry, P Fihn, SD Gibbons, RJ Owens, DK Williams, SV Weiss, KB Mottur-Pilson, C AF Snow, V Barry, P Fihn, SD Gibbons, RJ Owens, DK Williams, SV Weiss, KB Mottur-Pilson, C CA ACP ACC Chronic Stable Angina TI Evaluation of primary care patients with chronic stable angina: Guidelines from the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BUNDLE-BRANCH BLOCK; CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; DIPYRIDAMOLE TL-201 SCINTIGRAPHY; INCREMENTAL PROGNOSTIC VALUE; ASSOCIATION TASK-FORCE; TREADMILL SCORE; EXERCISE STRESS; RISK AB In 1999, the American College of Physicians (ACP) then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which the ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the first of 2 that will provide guidance on the management of patients with chronic stable angina. This document will cover diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on history or on electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A future guideline will cover pharmacologic therapy and follow-up. C1 Amer Coll Physicians, Philadelphia, PA 19106 USA. Univ Penn, Philadelphia, PA 19104 USA. Merck Inst Aging & Hlth, Washington, DC USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Edward Hines Jr Vet Adm Hosp, Chicago, IL USA. Northwestern Univ, Chicago, IL 60611 USA. RP Snow, V (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM vincenza@acponline.org NR 36 TC 29 Z9 30 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 6 PY 2004 VL 141 IS 1 BP 57 EP 64 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 834RF UT WOS:000222427600008 PM 15238371 ER PT J AU He, ZH King, GL AF He, ZH King, GL TI Protein kinase C beta isoform inhibitors - A new treatment for diabetic cardiovascular diseases SO CIRCULATION LA English DT Editorial Material ID ENDOTHELIAL-CELLS; GROWTH-FACTOR; ATHEROSCLEROSIS; EXPRESSION; INSULIN; HYPERGLYCEMIA; MELLITUS; TISSUE; ARTERY; RATS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu NR 20 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 6 PY 2004 VL 110 IS 1 BP 7 EP 9 DI 10.1161/01.CIR.0000133428.02295.6C PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 835DZ UT WOS:000222461800004 PM 15238466 ER PT J AU Biswas, DK Shi, Q Baily, S Strickland, I Ghosh, S Pardee, AB Iglehart, JD AF Biswas, DK Shi, Q Baily, S Strickland, I Ghosh, S Pardee, AB Iglehart, JD TI NF-KB activation in human breast cancer specimens and its role in cell proliferation and apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-KAPPA-B; PROTEIN-KINASE CK2; THERAPEUTIC TARGET; ESTROGEN; RECEPTORS; SURVIVAL; OVEREXPRESSION; INHIBITION; RECURRENCE; CARCINOMA AB Lack of molecular targets in estrogen receptor-negative (ER-negative) breast cancer is a major therapeutic hurdle. We studied NF-kappaB activation in human breast tumors and in carcinoma cell lines. Activated NF-kappaB was detected predominantly in ER-negative vs. ER-positive breast tumors and mostly in ER-negative and ErbB2-positive tumors (86%). These in vivo results demonstrate association of activated NF-kappaB with a subgroup of human breast tumors and are consistent with previously reported in vitro observations using similar classes of human breast cancer cell lines. Finding such an association suggested functional and biological significance. Immunofluorescence demonstrated increased nuclear p65, a component of the active NF-kappaB complex, in cytokeratin 19 (CK19)-positive epithelial cells of ER-negative/ErbB2-positive tumor samples. In contrast, nuclear NF-kappaB was detected mostly in stroma of ER-negative and ErbB2-negative tumors, suggesting a role of activated NF-kappaB in intercellular signaling between epithelial and stromal cells in this type of breast cancers. To elucidate roles of activated NF-kappaB, we used an ER-negative and ErbB2-positive human breast tumor cell line (SKBr3). The polypeptide heregulin beta1 stimulated, and herceptin, the anti-ErbB2 antibody, inhibited, NF-kappaB activation in SKBr3 cells. The NF-kappaB essential modulator (NEMO)-binding domain (NBD) peptide, an established selective inhibitor of IkappaB-kinase (IKK), blocked heregulin-mediated activation of NF-kappaB and cell proliferation, and simultaneously induced apoptosis only in proliferating and not resting cells. These results substantiate the hypothesis that certain breast cancer cells rely on NF-kappaB for aberrant cell proliferation and simultaneously avoid apoptosis, thus implicating activated NF-kappaB as a therapeutic target for distinctive subclasses of ER-negative breast cancers. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Room 822 Smith Bldg,44 Binney St, Boston, MA 02115 USA. EM debajit_biswas@dfci.harvard.edu RI Bremner, James/B-1632-2013; Bailey, Shannon/B-8045-2014 NR 42 TC 251 Z9 278 U1 4 U2 26 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 6 PY 2004 VL 101 IS 27 BP 10137 EP 10142 DI 10.1073/pnas.0403621101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 836CZ UT WOS:000222534200036 PM 15220474 ER PT J AU Ledergerber, B Lundgren, JD Walker, AS Sabin, C Justice, A Reiss, P Mussini, C Wit, F Monforte, AD Weber, R Fusco, G Staszewski, S Law, M Hogg, R Lampe, F Gill, MJ Castelli, F Phillips, AN Castelli, F Fusco, GP Gill, MJ Hogg, R Lampe, F Law, M Ledergerber, B Lundgren, JD Monforte, AD Mussini, C Phillips, AN Reiss, P Staszewski, S Walker, AS Rooney, P Taylor, S Couldwell, D Austin, D Block, M Clemons, J Finlayson, R Law, M Petoumenos, K Quan, D Smith, D O'Connor, C Gorton, C Allen, D Mulhall, B Mutimer, K Smith, D Keeffe, N Cooper, D Carr, A Miller, J Pell, C Ellis, D Baker, D Kidd, J McFarlane, R Liang, MT Brown, K Huffam, S Savage, J Morgan, S Knibbs, P Sowden, D Walker, A Orth, D Lister, G Chuah, J Fankhauser, W Dickson, B Bradford, D Wilson, C Ree, H Magon, H Anderson, J Moore, R Russell, D McGovern, G McNair, R Bal, J Fairley, K Roth, N Eu, B Strecker, S Russell, D Wood, H Mijch, A Hoy, J Pierce, A McCormack, C Watson, K Medland, N Daye, J Mallal, S French, M Skett, J Maxwel, D Cain, A Montroni, M Scalise, G Costantini, A Giacometti, A Tirelli, U Nasti, G Pastore, G Ladisa, N Perulli, ML Suter, F Arici, C Chiodo, F Gritti, FM Colangeli, V Fiorini, C Guerra, L Carosi, G Cadeo, GP Castelli, F Minardi, C Vangi, D Rizzardini, G Migliorino, G Manconi, PE Piano, P Ferraro, T Scerbo, A Pizzigallo, E Ricci, F Santoro, D Pusterla, L Carnevale, G Galloni, D Vigano, P Mena, M Ghinelli, F Sighinolfi, L Leoncini, F Mazzotta, F Pozzi, M Lo Caputo, S Angarano, G Grisorio, B Ferrara, S Grima, P Tundo, P Pagano, G Piersantelli, N Alessandrini, A Piscopo, R Toti, M Chigiotti, S Soscia, F Taccooni, L Orani, A Perini, P Scasso, A Vincenti, A Scalzini, A Fibbia, G Moroni, M Lazzarin, A Cargnel, A Vigevani, GM Caggese, L Monforte, AD Tordato, F Novati, R Galli, A Merli, S Pastecchia, C Moioli, C Esposito, R Mussini, C Abrescia, N Chirianni, A Izzo, C Piazza, M De Marco, M Montesarchio, V Manzillo, E Nappa, S Colomba, A Abbadessa, V Prestileo, T Mancuso, S Ferrari, C Pzzaferri, P Filice, G Minoli, L Bruno, R Maserati, R Pauluzzi, S Baldelli, F Petrelli, E Cioppi, A Alberici, F Ruggieri, A Menichetti, F Martinelli, C De Stefano, C La Gala, A Zauli, T Ballardini, G Magnani, G Ursitti, MA Arlotti, M Ortolani, P Ortona, L Dianzani, F Ippolito, G Antinori, A Antonucci, G D'Elia, S Narciso, P Petrosillo, N Vullo, V De Luca, A Del Forno, L Zaccarelli, M De Longis, P Ciardi, M D'Offizi, G Noto, P Lichtner, M Capobianchi, MR Girardi, E Pezzotti, P Rezza, G Mura, MS Mannazzu, M Caramello, P Sinicco, A Soranzo, ML Gennero, L Sciandra, M Salassa, B Grossi, PA Basilico, C Poggio, A Bottari, G Raise, E Pasquinucci, S De Lalla, F Tositti, G Resta, F Chimienti, A Lepri, AC Bachmann, S Battegay, M Bernasconi, E Bucher, H Burgisser, P Cattacin, S Egger, M Erb, P Fierz, W Fischer, M Flepp, M Fontana, A Francioli, P Furrer, HJ Gorgievski, M Hirschel, B Kaiser, L Kind, C Klimkait, T Ledergerber, B Lauper, U Opravil, M Paccaud, F Pantaleo, G Perrin, L Piffaretti, JC Rickenbach, M Rudin, C Schupbach, J Speck, R Tarr, P Telenti, A Trkola, A Vernazza, P Weber, R Yerly, S de Wolf, F van Sighem, AI van Valkengoed, I Gras, L Bronsveld, W Prins, JM Bos, JC Schattenkerk, JKME Godfried, MH Lange, JMA Lowe, SH van der Meer, JTM Nellen, FJB Pogany, K van der Poll, T Reiss, P Ruys, TA Sankatsing, S van der Valk, M van Vonderen, MGA Wit, FWMN van Eeden, A ten Veen, JH van Dam, PS Hillebrand-Haverkort, ME Brinkman, K Frissen, PHJ Weigel, HM Mulder, JW van Gorp, ECM Meenhorst, PL Mairuhu, ATA Veenstra, J Danner, SA Van Agtmael, MA Claessen, FAP Geerlings, SE Perenboom, RM Richter, C van der Berg, J van Leusen, R Vriesendorp, R Jeurissen, FJF Kauffmann, RH Koger, ELW Bravenboer, B ten Napel, CHH Mudrikova, T Sprenger, HG Miesen, WMAJ ten Kate, RW van Houte, DPF Leemhuis, MP Pole, M Kroon, FP Schippers, EF Schreij, G van de Geest, S Verbon, A Koopmans, PP Telgt, M van der Ven, AJAM van der Ende, ME Gyssens, IC de Marie, S Nouwen, JL Juttmann, JR Schneider, MME Bonten, MJM Borleffs, JCC Hoepelman, IM Jaspers, CAJJ Schouten, I Schurink, CAM Blok, WL Groenveld, PHP Jurriaans, S Back, NKT Cuijpers, T Rietra, PJGM Roozendaal, KJ Pauw, W van Zanten, AP Smits, PHM von Blomberg, BME Savelkoul, P Zaaijer, H Swanink, C Franck, PFH Lampe, AS Jansen, CL Hendriks, R Schirm, J Benne, D Veenendaal, D Storm, H van Zeijl, JH Kroes, ACM Claas, HCJ Bruggeman, CAMVA Goossens, VJ Galama, JMD Poort, YAGM Niesters, MG Osterhaus, ADME Schutten, M Buiting, AGM Swaans, CAM Boucher, CAB Schuurman, R Boel, E Jansz, AF Veldkamp, A Beijnen, JH Crommentuyn, KML Huitema, ADR Kappelhoff, B de Maat, MMR Burger, DM Hugen, PWH Dabis, F Thiebaut, R Chene, G Lawson-Ayayi, S Meyer, L Boufassa, F Hamouda, O Pezzotti, P Rezza, G Touloumi, G Hatzakis, A Karafoulidou, A Katsarou, O Brettle, R Del Amo, J del Romero, J van Asten, L van Benthem, B Prins, M Coutinho, R Kirk, O Pedersen, C Aguado, IH Perez-Hoyos, S Eskild, A Bruun, JN Sannes, M Sabin, C Lee, C Johnson, AM Phillips, AN Babiker, A Darbyshire, J Gill, N Porter, K Francioli, P Vanhems, P Egger, M Rickenbach, M Cooper, D Kaldor, J Ashton, L Cooper, D Kaldor, J Ashton, L Cooper, D Vizzard, J Muga, R Vanhems, P Gill, J Cayla, J de Olalla, PG Day, NE De Angelis, D Porter, K Babiker, A Walker, S Darbyshire, J Tyrer, F Beral, V Coutinho, R Darbyshire, J Del Amo, J Gill, N Lee, C Meyer, L Rezza, G Raffanti, S Becker, S Scarsella, A Braun, J Justice, A Fusco, G Most, B Balu, R Gilbert, L Fleenor, R Ising, T Dieterich, D Fusco, J Losso, M Duran, A Vetter, N Clumeck, N De Wit, S Kabeya, K Poll, B Colebunders, R Machala, L Rozsypal, H Nielsen, J Lundgren, J Kirk, O Olsen, CH Gerstoft, J Katzenstein, T Hansen, ABE Skinhoj, P Pedersen, C Zilmer, K Rauka, M Katlama, C De Sa, M Viard, JP Saint-Marc, T Vanhems, P Pradier, C Dietrich, M Manegold, C van Lunzen, J Stellbrink, HJ Miller, V Staszewski, S Goebel, FD Salzberger, B Rockstroh, J Kosmidis, J Gargalianos, P Sambatakou, H Perdios, J Panos, G Filandras, A Banhegyi, D Mulcahy, F Yust, I Burke, M Pollack, S Hassoun, J Sthoeger, Z Maayan, S Vella, S Chiesi, A Arici, C Pristera, R Mazzotta, F Gabbuti, A Esposito, R Bedini, A Chirianni, A Montesarchio, E Vullo, V Santopadre, P Narciso, P Antinori, A Franci, P Zaccarelli, M Lazzarin, A Castagna, A Monforte, AD Viksna, L Rozentale, B Chaplinskas, S Hemmer, R Staub, T Reiss, P Bruun, J Maeland, A Ormaasen, V Knysz, B Gasiorowski, J Horban, A Prokopowicz, D Wiercinska-Drapalo, A Boron-Kaczmarska, A Pynka, M Beniowski, M Trocha, H Smiatacz, T Antunes, F Mansinho, K Maltez, F Duiculescu, D Streinu-Cercel, A Mokras, M Stanekova, D Gonzalez-Lahoz, J Diaz, B Garcia-Benayas, T Martin-Carbonero, L Soriano, V Clotet, B Jou, A Conejero, J Tural, C Gatell, JM Miro, JM Zamora, L Blaxhult, A Karlsson, A Pehrson, P Ledergerber, B Weber, R Francioli, P Hirschel, B Schiffer, V Furrer, H Chentsova, N Barton, S Johnson, AM Mercey, D Phillips, A Youle, M Johnson, MA Mocroft, A Murphy, M Weber, J Scullard, G Fisher, M Brettle, R Loveday, C Clotet, B Ruiz, L Staszewski, S Helm, EB Carlebach, A Mosch, M Muller, A Haberl, A Korn, S Stephan, C Bickel, M Gute, P Locher, L Lutz, T Klauke, S Doerr, HW Sturmer, M Sabin, C Dauer, B Jennings, B Alexander, C Braitstein, P Chan, K Cote, H Gataric, N Harrigan, PR Harris, M Bonner, S Hogg, R Montaner, J O'Shaughnessy, M Wood, E Yip, B Lampe, F Chaloner, C Gumley, H Ransom, D Sabin, CA Mocroft, A Lipman, M Phillips, AN Youle, M Johnson, M Gill, J Read, R Carosi, G Castelli, F Paraninfo, G Casari, S Pan, A Patroni, A Torti, C Quiros-Roldan, E Tomasoni, L Moretti, F Nasta, P Uccelli, MC Cadeo, GP Bertelli, D Orani, A Perini, P Nigro, M Rizzardini, G Migliorino, M Abeli, C Mazzotta, F Suter, F Maggiolo, F Arici, C Ghinelli, F Sighinolfi, L Minoli, L Maserati, R Novati, S Tinelli, C Pastore, G Ladisa, N Carnevale, G Poggio, A Riccio, G Mussini, C Borghi, V Bedini, A Esposito, R AF Ledergerber, B Lundgren, JD Walker, AS Sabin, C Justice, A Reiss, P Mussini, C Wit, F Monforte, AD Weber, R Fusco, G Staszewski, S Law, M Hogg, R Lampe, F Gill, MJ Castelli, F Phillips, AN Castelli, F Fusco, GP Gill, MJ Hogg, R Lampe, F Law, M Ledergerber, B Lundgren, JD Monforte, AD Mussini, C Phillips, AN Reiss, P Staszewski, S Walker, AS Rooney, P Taylor, S Couldwell, D Austin, D Block, M Clemons, J Finlayson, R Law, M Petoumenos, K Quan, D Smith, D O'Connor, C Gorton, C Allen, D Mulhall, B Mutimer, K Smith, D Keeffe, N Cooper, D Carr, A Miller, J Pell, C Ellis, D Baker, D Kidd, J McFarlane, R Liang, MT Brown, K Huffam, S Savage, J Morgan, S Knibbs, P Sowden, D Walker, A Orth, D Lister, G Chuah, J Fankhauser, W Dickson, B Bradford, D Wilson, C Ree, H Magon, H Anderson, J Moore, R Russell, D McGovern, G McNair, R Bal, J Fairley, K Roth, N Eu, B Strecker, S Russell, D Wood, H Mijch, A Hoy, J Pierce, A McCormack, C Watson, K Medland, N Daye, J Mallal, S French, M Skett, J Maxwel, D Cain, A Montroni, M Scalise, G Costantini, A Giacometti, A Tirelli, U Nasti, G Pastore, G Ladisa, N Perulli, ML Suter, F Arici, C Chiodo, F Gritti, FM Colangeli, V Fiorini, C Guerra, L Carosi, G Cadeo, GP Castelli, F Minardi, C Vangi, D Rizzardini, G Migliorino, G Manconi, PE Piano, P Ferraro, T Scerbo, A Pizzigallo, E Ricci, F Santoro, D Pusterla, L Carnevale, G Galloni, D Vigano, P Mena, M Ghinelli, F Sighinolfi, L Leoncini, F Mazzotta, F Pozzi, M Lo Caputo, S Angarano, G Grisorio, B Ferrara, S Grima, P Tundo, P Pagano, G Piersantelli, N Alessandrini, A Piscopo, R Toti, M Chigiotti, S Soscia, F Taccooni, L Orani, A Perini, P Scasso, A Vincenti, A Scalzini, A Fibbia, G Moroni, M Lazzarin, A Cargnel, A Vigevani, GM Caggese, L Monforte, AD Tordato, F Novati, R Galli, A Merli, S Pastecchia, C Moioli, C Esposito, R Mussini, C Abrescia, N Chirianni, A Izzo, C Piazza, M De Marco, M Montesarchio, V Manzillo, E Nappa, S Colomba, A Abbadessa, V Prestileo, T Mancuso, S Ferrari, C Pzzaferri, P Filice, G Minoli, L Bruno, R Maserati, R Pauluzzi, S Baldelli, F Petrelli, E Cioppi, A Alberici, F Ruggieri, A Menichetti, F Martinelli, C De Stefano, C La Gala, A Zauli, T Ballardini, G Magnani, G Ursitti, MA Arlotti, M Ortolani, P Ortona, L Dianzani, F Ippolito, G Antinori, A Antonucci, G D'Elia, S Narciso, P Petrosillo, N Vullo, V De Luca, A Del Forno, L Zaccarelli, M De Longis, P Ciardi, M D'Offizi, G Noto, P Lichtner, M Capobianchi, MR Girardi, E Pezzotti, P Rezza, G Mura, MS Mannazzu, M Caramello, P Sinicco, A Soranzo, ML Gennero, L Sciandra, M Salassa, B Grossi, PA Basilico, C Poggio, A Bottari, G Raise, E Pasquinucci, S De Lalla, F Tositti, G Resta, F Chimienti, A Lepri, AC Bachmann, S Battegay, M Bernasconi, E Bucher, H Burgisser, P Cattacin, S Egger, M Erb, P Fierz, W Fischer, M Flepp, M Fontana, A Francioli, P Furrer, HJ Gorgievski, M Hirschel, B Kaiser, L Kind, C Klimkait, T Ledergerber, B Lauper, U Opravil, M Paccaud, F Pantaleo, G Perrin, L Piffaretti, JC Rickenbach, M Rudin, C Schupbach, J Speck, R Tarr, P Telenti, A Trkola, A Vernazza, P Weber, R Yerly, S de Wolf, F van Sighem, AI van Valkengoed, I Gras, L Bronsveld, W Prins, JM Bos, JC Schattenkerk, JKME Godfried, MH Lange, JMA Lowe, SH van der Meer, JTM Nellen, FJB Pogany, K van der Poll, T Reiss, P Ruys, TA Sankatsing, S van der Valk, M van Vonderen, MGA Wit, FWMN van Eeden, A ten Veen, JH van Dam, PS Hillebrand-Haverkort, ME Brinkman, K Frissen, PHJ Weigel, HM Mulder, JW van Gorp, ECM Meenhorst, PL Mairuhu, ATA Veenstra, J Danner, SA Van Agtmael, MA Claessen, FAP Geerlings, SE Perenboom, RM Richter, C van der Berg, J van Leusen, R Vriesendorp, R Jeurissen, FJF Kauffmann, RH Koger, ELW Bravenboer, B ten Napel, CHH Mudrikova, T Sprenger, HG Miesen, WMAJ ten Kate, RW van Houte, DPF Leemhuis, MP Pole, M Kroon, FP Schippers, EF Schreij, G van de Geest, S Verbon, A Koopmans, PP Telgt, M van der Ven, AJAM van der Ende, ME Gyssens, IC de Marie, S Nouwen, JL Juttmann, JR Schneider, MME Bonten, MJM Borleffs, JCC Hoepelman, IM Jaspers, CAJJ Schouten, I Schurink, CAM Blok, WL Groenveld, PHP Jurriaans, S Back, NKT Cuijpers, T Rietra, PJGM Roozendaal, KJ Pauw, W van Zanten, AP Smits, PHM von Blomberg, BME Savelkoul, P Zaaijer, H Swanink, C Franck, PFH Lampe, AS Jansen, CL Hendriks, R Schirm, J Benne, D Veenendaal, D Storm, H van Zeijl, JH Kroes, ACM Claas, HCJ Bruggeman, CAMVA Goossens, VJ Galama, JMD Poort, YAGM Niesters, MG Osterhaus, ADME Schutten, M Buiting, AGM Swaans, CAM Boucher, CAB Schuurman, R Boel, E Jansz, AF Veldkamp, A Beijnen, JH Crommentuyn, KML Huitema, ADR Kappelhoff, B de Maat, MMR Burger, DM Hugen, PWH Dabis, F Thiebaut, R Chene, G Lawson-Ayayi, S Meyer, L Boufassa, F Hamouda, O Pezzotti, P Rezza, G Touloumi, G Hatzakis, A Karafoulidou, A Katsarou, O Brettle, R Del Amo, J del Romero, J van Asten, L van Benthem, B Prins, M Coutinho, R Kirk, O Pedersen, C Aguado, IH Perez-Hoyos, S Eskild, A Bruun, JN Sannes, M Sabin, C Lee, C Johnson, AM Phillips, AN Babiker, A Darbyshire, J Gill, N Porter, K Francioli, P Vanhems, P Egger, M Rickenbach, M Cooper, D Kaldor, J Ashton, L Cooper, D Kaldor, J Ashton, L Cooper, D Vizzard, J Muga, R Vanhems, P Gill, J Cayla, J de Olalla, PG Day, NE De Angelis, D Porter, K Babiker, A Walker, S Darbyshire, J Tyrer, F Beral, V Coutinho, R Darbyshire, J Del Amo, J Gill, N Lee, C Meyer, L Rezza, G Raffanti, S Becker, S Scarsella, A Braun, J Justice, A Fusco, G Most, B Balu, R Gilbert, L Fleenor, R Ising, T Dieterich, D Fusco, J Losso, M Duran, A Vetter, N Clumeck, N De Wit, S Kabeya, K Poll, B Colebunders, R Machala, L Rozsypal, H Nielsen, J Lundgren, J Kirk, O Olsen, CH Gerstoft, J Katzenstein, T Hansen, ABE Skinhoj, P Pedersen, C Zilmer, K Rauka, M Katlama, C De Sa, M Viard, JP Saint-Marc, T Vanhems, P Pradier, C Dietrich, M Manegold, C van Lunzen, J Stellbrink, HJ Miller, V Staszewski, S Goebel, FD Salzberger, B Rockstroh, J Kosmidis, J Gargalianos, P Sambatakou, H Perdios, J Panos, G Filandras, A Banhegyi, D Mulcahy, F Yust, I Burke, M Pollack, S Hassoun, J Sthoeger, Z Maayan, S Vella, S Chiesi, A Arici, C Pristera, R Mazzotta, F Gabbuti, A Esposito, R Bedini, A Chirianni, A Montesarchio, E Vullo, V Santopadre, P Narciso, P Antinori, A Franci, P Zaccarelli, M Lazzarin, A Castagna, A Monforte, AD Viksna, L Rozentale, B Chaplinskas, S Hemmer, R Staub, T Reiss, P Bruun, J Maeland, A Ormaasen, V Knysz, B Gasiorowski, J Horban, A Prokopowicz, D Wiercinska-Drapalo, A Boron-Kaczmarska, A Pynka, M Beniowski, M Trocha, H Smiatacz, T Antunes, F Mansinho, K Maltez, F Duiculescu, D Streinu-Cercel, A Mokras, M Stanekova, D Gonzalez-Lahoz, J Diaz, B Garcia-Benayas, T Martin-Carbonero, L Soriano, V Clotet, B Jou, A Conejero, J Tural, C Gatell, JM Miro, JM Zamora, L Blaxhult, A Karlsson, A Pehrson, P Ledergerber, B Weber, R Francioli, P Hirschel, B Schiffer, V Furrer, H Chentsova, N Barton, S Johnson, AM Mercey, D Phillips, A Youle, M Johnson, MA Mocroft, A Murphy, M Weber, J Scullard, G Fisher, M Brettle, R Loveday, C Clotet, B Ruiz, L Staszewski, S Helm, EB Carlebach, A Mosch, M Muller, A Haberl, A Korn, S Stephan, C Bickel, M Gute, P Locher, L Lutz, T Klauke, S Doerr, HW Sturmer, M Sabin, C Dauer, B Jennings, B Alexander, C Braitstein, P Chan, K Cote, H Gataric, N Harrigan, PR Harris, M Bonner, S Hogg, R Montaner, J O'Shaughnessy, M Wood, E Yip, B Lampe, F Chaloner, C Gumley, H Ransom, D Sabin, CA Mocroft, A Lipman, M Phillips, AN Youle, M Johnson, M Gill, J Read, R Carosi, G Castelli, F Paraninfo, G Casari, S Pan, A Patroni, A Torti, C Quiros-Roldan, E Tomasoni, L Moretti, F Nasta, P Uccelli, MC Cadeo, GP Bertelli, D Orani, A Perini, P Nigro, M Rizzardini, G Migliorino, M Abeli, C Mazzotta, F Suter, F Maggiolo, F Arici, C Ghinelli, F Sighinolfi, L Minoli, L Maserati, R Novati, S Tinelli, C Pastore, G Ladisa, N Carnevale, G Poggio, A Riccio, G Mussini, C Borghi, V Bedini, A Esposito, R CA PLATO Collaboration TI Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED INDIVIDUALS; BLIND CONTROLLED-TRIAL; CLINICAL PROGRESSION; DISEASE PROGRESSION; HAART REGIMEN; VIRAL LOAD; THERAPY; COHORT; INHIBITOR AB Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline. C1 Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland. Hvidovre Univ Hosp, Copenhagen HIV Programme, DK-2650 Hvidovre, Denmark. MRC, Clin Trials Unit, London, England. UCL Royal Free & Univ Coll Med Sch, London, England. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Natl AIDS Therapy Evaluat Ctr, Amsterdam, Netherlands. Univ Modena, Clin Infect Dis, I-41100 Modena, Italy. Int Antiviral Therapy Evaluat Ctr, Amsterdam, Netherlands. Univ Milan, Inst Infect Dis, Milan, Italy. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Goethe Univ Frankfurt, D-6000 Frankfurt, Germany. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW, Australia. Univ British Columbia, BC Ctr Excellence HIV AIDS, Vancouver, BC V5Z 1M9, Canada. So Alberta Clin, Calgary, AB, Canada. Univ Brescia, Inst Infect & Trop Dis, Brescia, Italy. RP Ledergerber, B (reprint author), Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Ramistr 100, CH-8091 Zurich, Switzerland. EM infled@usz.unizh.ch RI Ledergerber, Bruno/B-5656-2009; DEL AMO VALERO, JULIA/M-7020-2015; SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; chene, genevieve/H-8665-2014; Weber, Rainer/D-5175-2012; Furrer, Hansjakob/G-6768-2013; Perez-Hoyos, Santiago/E-2370-2012; Ven, A.J.A.M./H-8102-2014; Gyssens, I.C.J./L-4343-2015; REZZA, GIOVANNI/D-4393-2016; Vella, Stefano/D-4912-2015; Gill, John/G-7083-2016; Pantaleo, Giuseppe/K-6163-2016; Rizzardini, Giuliano/K-9458-2016; Klimkait, Thomas/A-1057-2008; Sabin, Caroline/C-2464-2008; Castelli, Francesco/E-7045-2010; Phillips, Andrew/B-4427-2008; Mocroft, Amanda/G-8748-2011; Panos, George/H-3944-2011; Hogg, Robert/B-2783-2012; van Valkengoed, Irene/B-2974-2013; Beral, Valerie/B-2979-2013; Kaldor, John /D-4545-2011; Back, Nicole/K-3884-2013; Burger, David/C-9929-2013; Stephan, Christoph/D-1305-2014; Infektiologie, USZ/A-6921-2011 OI Ledergerber, Bruno/0000-0002-6881-4401; DEL AMO VALERO, JULIA/0000-0002-3104-540X; Anderson, Jane/0000-0001-5294-8707; Tyrer, Freya/0000-0003-2877-4342; Antunes, Francisco/0000-0001-7932-1154; Lundgren, Jens/0000-0001-8901-7850; Bruno, Raffaele/0000-0002-0235-9207; petrosillo, nicola/0000-0002-2585-7567; ANGARANO, Gioacchino/0000-0003-3207-7523; Hogg, Robert/0000-0003-3463-5488; Capobianchi, Maria Rosaria/0000-0003-3465-0071; Diaz-Pollan, Beatriz/0000-0002-7241-4208; Streinu-Cercel, Adrian/0000-0001-6382-5067; Furrer, Hansjakob/0000-0002-1375-3146; Perez-Hoyos, Santiago/0000-0001-9797-4917; REZZA, GIOVANNI/0000-0003-0268-6790; Vella, Stefano/0000-0003-2347-5984; Gill, John/0000-0002-8546-8790; Rizzardini, Giuliano/0000-0002-5183-7818; Phillips, Andrew/0000-0003-2384-4807; Stephan, Christoph/0000-0003-3777-9006; FU Medical Research Council [MC_U122886351] NR 47 TC 211 Z9 216 U1 4 U2 39 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 3 PY 2004 VL 364 IS 9428 BP 51 EP 62 DI 10.1016/S0140-6736(04)16589-6 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 834DX UT WOS:000222392900031 PM 15234856 ER PT J AU Lichterfeld, M Yu, XG Cohen, D Addo, MM Malenfant, J Perkins, B Pae, E Johnston, MN Strick, D Allen, TM Rosenberg, ES Korber, B Walker, BD Altfeld, M AF Lichterfeld, M Yu, XG Cohen, D Addo, MM Malenfant, J Perkins, B Pae, E Johnston, MN Strick, D Allen, TM Rosenberg, ES Korber, B Walker, BD Altfeld, M TI HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversity SO AIDS LA English DT Article DE acute HIV-1 infection; HIV-specific CD8 T cells; cellular immune responses; HIV-1 Nef; clade B consensus sequence; viral entropy; HLA ID VIRUS TYPE-1 INFECTION; CELLULAR IMMUNE-RESPONSES; CLASS-I ALLELES; ANTIRETROVIRAL THERAPY; LYMPHOCYTE ESCAPE; VIRAL DIVERSITY; VIREMIA; EXPRESSION; LOAD; HLA AB Objective: To compare the magnitude, breadth and protein specificity of HIV-1-specific CD8 T-cell responses against the clade B consensus sequence during primary and chronic HIV-1 infection and to analyze the impact of viral diversity on the localization of detected responses. Methods: HIV-1-specific CD8 T-cell responses against the clade B consensus sequence in individuals with acute (n = 10), early (n = 19) and chronic (n = 10) infection were longitudinally assessed using an interferon-gamma EliSpot assay. Results: CD8 T-cell responses against clade B consensus sequences were preferentially directed against central regions of Nef during primary HIV-1 infection, despite a relatively higher degree of genetic diversity compared with other subsequently targeted regions. In subjects with acute and early infection, Nef-specific CD8 T-cell responses against the consensus Nef sequence represented 94 and 46% of the total magnitude of HIV-1-specific CD8 T-cell responses, respectively. Subjects with untreated chronic infection exhibited broadly diversified CD8 T-cell responses against more conserved viral regions, with only 17% of virus-specific T-cell responses targeting Nef. The initial immunodominance of Nef persisted in individuals with treated,acute infection, but shifted rapidly to Gag, Env and Pol in subjects with continuous antigen exposure. Conclusion: These data show that despite relatively high sequence variability, viral regions within the clade B consensus sequence of Nef are preferentially recognized during primary HIV-1 infection. Later diversification of responses to other proteins during prolonged antigen exposure provides evidence of the initial preferential immunogenicity of Nef epitopes compared to similarly conserved regions within other viral proteins. (C) 2004 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Fenway Community Hlth Care Ctr, Boston, MA USA. Los Almos Natl Lab, HIV Immunol Database, Los Alamos, NM USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 6613, Boston, MA 02129 USA. RI Allen, Todd/F-5473-2011; OI Korber, Bette/0000-0002-2026-5757 NR 33 TC 90 Z9 91 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 2 PY 2004 VL 18 IS 10 BP 1383 EP 1392 DI 10.1097/01.aids.0000131329.51633.a3 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 837NF UT WOS:000222641500004 PM 15199314 ER PT J AU Zhang, L Keane, MP Zhu, LX Sharma, S Rozengurt, E Strieter, RM Dubinett, SM Huang, M AF Zhang, L Keane, MP Zhu, LX Sharma, S Rozengurt, E Strieter, RM Dubinett, SM Huang, M TI Interleukin-7 and transforming growth factor-beta play counter-regulatory roles in protein kinase C-delta-dependent control of fibroblast collagen synthesis in pulmonary fibrosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; GENE-EXPRESSION; MESSENGER-RNA; ACTIVATION; PATHWAY; SMAD3; CELLS; CD40; IL-2 AB Transforming growth factor-beta (TGF-beta) is a potent fibrogenic factor responsible for promoting synthesis of extracellular matrix. Interleukin-7 (IL-7) inhibits TGF-beta signaling by up-regulating Smad7, a major inhibitor of the Smad family. In a variety of cells, TGF-beta-mediated activation of target genes requires active protein kinase C-delta (PKC-delta) in addition to Smads (1). We determined the role of PKC-delta in the regulation of pulmonary fibroblast collagen synthesis in response to TGF-beta and IL-7 stimulation. Here we show that TGF-beta and IL-7 have opposing effects on PKC-delta; TGF-beta stimulates, while IL-7 inhibits, PKC-delta activity. IL-7 inhibits TGF-beta-induced PKC-delta phosphorylation at Ser-645 and Thr-505. Inhibition of PKC-delta with specific small inhibitory RNA restores TGF-beta-mediated induction of Smad7 and in parallel significantly reduces TGF-beta-mediated collagen synthesis. Thus, PKC-delta may play a critical role in the pathogenesis of pulmonary fibrosis and may serve as a molecular target for therapeutic intervention to suppress fibrosis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Huang, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. EM minhuang@mednet.ucla.edu FU NCI NIH HHS [P50 CA 90388, R01 CA 085686]; NHLBI NIH HHS [P50 HL 67665, P01 HL 03906] NR 21 TC 36 Z9 44 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 28315 EP 28319 DI 10.1074/jbc.C400115200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400063 PM 15133032 ER PT J AU Feng, ZH Kachnic, L Zhang, JR Powell, SN Xia, F AF Feng, ZH Kachnic, L Zhang, JR Powell, SN Xia, F TI DNA damage induces p53-dependent BRCA1 nuclear export SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAKS; CELL-CYCLE REGULATION; OVARIAN-CANCER CELLS; SUBCELLULAR-LOCALIZATION; INDUCED PHOSPHORYLATION; IONIZING IRRADIATION; GENOTOXIC STRESS; EPITHELIAL-CELLS; GROWTH ARREST; MEIOTIC CELLS AB The tumor suppressor gene BRCA1 plays an important role in the response to DNA damage. BRCA1 function is regulated by a variety of mechanisms including transcriptional control, phosphorylation, and protein-protein interactions. Recent studies have shown that BRCA1 is a nuclear-cytoplasmic shuttle protein. Its subcellular localization is controlled by a nuclear localization signal-mediated nuclear import via the importin receptor pathway and a nuclear export signal-facilitated nuclear export through a CRM1-dependent pathway. Using the human breast cancer cell line, MCF7, the subcellular distribution of BRCA1 was assessed by immunohistochemical staining and Western blotting analyses of fractionated subcellullar extracts. Ionizing radiation stimulated BRCA1 nuclear export in a dose-dependent manner. This DNA damage-induced BRCA1 nuclear export utilized a CRM1-dependent mechanism and also required wild-type p53, whose function was abrogated by the E6 protein in MCF7 cells. In addition, the dependence on p53 was confirmed using a second cell type operating a tetracycline-inducible system. The effect of ionizing radiation on BRCA1 export was observed in every phase of the cell cycle, although BRCA1 localization did vary between the G(1), S, and G(2)/M phases. These results imply that, in addition to ATM-, ATR-, and Chk2-dependent phosphorylations, cytoplasmic relocalization of BRCA1 protein is a mechanism whereby BRCA1 function is regulated in response to DNA damage. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. RP Xia, F (reprint author), Vanderbilt Univ, Sch Med, Dept Radiat Oncol, 1301 22nd Ave, Nashville, TN 37232 USA. EM fen.xia@vanderbilt.edu RI Xia, Fen/G-3708-2013 NR 65 TC 39 Z9 44 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 2 PY 2004 VL 279 IS 27 BP 28574 EP 28584 DI 10.1074/jbc.M404137200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400093 PM 15087457 ER PT J AU Hoh, BL Rabinov, JD Pryor, JC Ogilvy, CS AF Hoh, BL Rabinov, JD Pryor, JC Ogilvy, CS TI A modified technique for using elastase to create saccular aneurysms in animals that histologically and hemodynamically resemble aneurysms in human SO ACTA NEUROCHIRURGICA LA English DT Article DE aneurysm; animal model; endovascular; elastase; experimental; rabbit ID CAROTID-ARTERY; FLOW DYNAMICS; ENDOVASCULAR TREATMENT; BIFURCATION ANEURYSM; RABBIT MODEL; COILS; EMBOLIZATION; DEVICES; SWINE; DOGS AB Background. Treatment of intracranial aneurysms is evolving with the development of novel therapies. It is important to have an animal model which simulates human aneurysms. We describe a new modified technique to the elastase aneurysm model which creates aneurysms that histologically and hemodynamically resemble human aneurysms. Methods. Twelve New Zealand white rabbits underwent the aneurysm creation procedure, and 2 underwent a control procedure. In the aneurysm creation procedure, the right common carotid artery (RCCA) origin is surgically exposed and temporarily occluded with a temporary aneurysm clip. The RCCA is ligated distally, and the trapped segment is infused with elastase for 20 minutes, afterwhich the clip is removed. In the control procedure, the RCCA is ligated distally with no elastase. Animals were assessed neurologically using a previously described rabbit neurologic grading scale and food intake scale. Intravenous digital subtraction angiography (IVDSA) was performed 21 days after the procedure. Aneurysms were harvested and stained with H&E and Verhoeff's stain. Findings. All 14 rabbits had normal neurologic and food intake assessments. All 12 rabbits that underwent aneurysm creation procedures demonstrated saccular aneurysms on IVDSA. Mean aneurysm size was 5.9+/-1.9 mm; range 4.3-10.8 mm. The close proximity of the LCCA to the origin of the RCCA on the aortic arch of the New Zealand white rabbit closely resembles a bifurcation aneurysm. Both rabbits that underwent control procedures showed no aneurysm and retrograde thrombosis of the RCCA. Histologic analysis showed the aneurysms had histology characteristic of true human aneurysms. Conclusion. We have developed a new modified technique to the elastase aneurysm model which creates aneurysms that hemodynamically and histologically resemble human aneurysms. There have been previous elastase models described, however we find our model is easier to perform and highly reproducible. The aneurysms can be accessed transfemorally making the model ideal for testing endovascular therapies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Hoh, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Gray 289,55 Fruit St, Boston, MA 02114 USA. EM bhoh@partners.org NR 28 TC 30 Z9 35 U1 0 U2 0 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PD JUL PY 2004 VL 146 IS 7 BP 705 EP 711 DI 10.1007/s00701-004-0276-6 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 829DM UT WOS:000222024100017 PM 15197614 ER PT J AU Stewart, SE Geller, DA Jenike, M Pauls, D Shaw, D Mullin, B Faraone, SV AF Stewart, SE Geller, DA Jenike, M Pauls, D Shaw, D Mullin, B Faraone, SV TI Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE obsessive-compulsive disorder; meta-analysis; prognosis; child; adolescent; pediatrics outcome assessment ID PROSPECTIVE FOLLOW-UP; COMMUNITY SAMPLE; YOUNG ADOLESCENTS; CHILDHOOD; CHILDREN; PREVALENCE; TRIAL; RELIABILITY; PREDICTORS; ADULTS AB Objective: To review the extant literature on the long-term outcome of child/adolescent-onset obsessive-compulsive disorder (OCD). Method: Medline and Psychlit databases were systematically searched for articles regarding long-term outcomes of child/adolescent-onset OCD. Meta-analysis regression was applied to evaluate predictors and persistence of OCD. Results: Sixteen study samples (n = 6-132; total = 521 participants) in 22 studies had follow-up periods ranging between 1 and 15.6 years. Pooled mean persistence rates were 41% for full OCD and 60% for full or subthreshold OCD. Earlier age of OCD onset (z = -3.26, P = 0.001), increased OCD duration (z = 2.22, P = 0.027) and in-patient vs. out-patient status (z = 2.94, P = 0.003) predicted greater persistence. Comorbid psychiatric illness and poor initial treatment response were poor prognostic factors. Although psychosocial function was frequently compromised, most studies lacked comprehensive outcome measures. Conclusion: Long-term persistence of pediatric OCD may be lower than believed. Future studies should include broader measures of outcome including symptomatic persistence and functional impairment in multiple domains. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Cambridge, MA 02138 USA. McLean Hosp, Pediat Obsess Compuls Disorder Clin Res Program, Belmont, MA 02178 USA. McLean Hosp, OCD Inst, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Obsess Compuls Disorder Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM dageller@partners.org RI Stewart, Evelyn/K-6961-2014; OI Faraone, Stephen/0000-0002-9217-3982; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [K08 MH01481] NR 47 TC 155 Z9 156 U1 10 U2 24 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 2004 VL 110 IS 1 BP 4 EP 13 DI 10.1111/j.1600-0447.2004.00302.x PG 10 WC Psychiatry SC Psychiatry GA 825FJ UT WOS:000221741100002 PM 15180774 ER PT J AU Freudenreich, O Deckersbach, T Goff, DC AF Freudenreich, O Deckersbach, T Goff, DC TI Insight into current symptoms of schizophrenia. Association with frontal cortical function and affect SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE schizophrenia; lack of insight; symptom unawareness; dysphoria; frontal lobe dysfunction ID QUALITY-OF-LIFE; CARD SORTING TEST; SCHIZOAFFECTIVE DISORDER; NEUROCOGNITIVE FUNCTION; MOOD DISORDERS; PSYCHOSIS; ILLNESS; PERFORMANCE; DEPRESSION; AWARENESS AB Objective: Examine whether frontal lobe dysfunction or affective experiences correlates with lack of symptom awareness in schizophrenia. Method: A total of 122 consecutive adult schizophrenia outpatients were assessed cross-sectionally with standard rating scales of psychopathology and of insight, and underwent neuropsychological assessment with a battery of tests sensitive to frontal lobe dysfunction. Correlational analyses were used to determine relationships between variables. Results: About 62% of patients had at least partial awareness of symptoms. Anxiety correlated modestly with insight into the abnormal nature of positive and negative symptoms. No cognitive variable was significantly correlated with symptom awareness. Conclusion: The pathological nature of symptoms is better recognized by patients who experience dysphoric affect. Neither severity of psychotic symptoms nor frontal lobe cognitive deficits correlates to symptom awareness. Lack of insight, which can be partial for symptoms of the illness, might be a non-reducible symptom of schizophrenia. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Schizophrenia Program, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreud@massmed.org NR 47 TC 38 Z9 42 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 2004 VL 110 IS 1 BP 14 EP 20 DI 10.1111/j.1600-0447.2004.00319.x PG 7 WC Psychiatry SC Psychiatry GA 825FJ UT WOS:000221741100003 PM 15180775 ER PT J AU Satre, DD Knight, BG Dickson-Fuhrmann, E Jarvik, LF AF Satre, DD Knight, BG Dickson-Fuhrmann, E Jarvik, LF TI Substance abuse treatment initiation among older adults in the GET SMART program: effects of depression and cognitive status SO AGING & MENTAL HEALTH LA English DT Article ID MINI-MENTAL-STATE; PROBLEM DRINKERS; ALCOHOLISM-TREATMENT; BEHAVIORAL TREATMENT; CAGE QUESTIONNAIRE; EARLY-ONSET; DRINKING; SEEKING; POPULATION; VETERANS AB This study examines how individual patient characteristics predict substance abuse treatment initiation among older adults, in an investigation based on the behavioral health service use model. Analyses tested the impact of demographic factors, substance abuse symptoms, depression and cognitive status on subsequent treatment initiation. The sample included 250 older male veterans screened for substance abuse problems during inpatient medical treatment, who also participated in a clinical evaluation for substance abuse treatment. Measures included demographics and CAGE alcohol screening score. A subset of patients also completed the Michigan Alcohol Screening Test-Geriatric Version (MAST-G), Hamilton Depression Scale (HAM-D), and Folstein Mini Mental State Exam (MMSE). Patients who initiated treatment following evaluation had more years of education, better cognitive status, and more symptoms of substance abuse and depression, compared with patients who did not initiate treatment. In logistic regression analysis, CAGE and MMSE scores independently predicted treatment initiation. Findings contribute to the understanding of how clinical characteristics of older adults affect substance abuse treatment initiation. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Kaiser Permanente Div Res, Oakland, CA USA. Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Satre, DD (reprint author), Univ Calif San Francisco, 401 Parnassus Ave,Box 0984-OVS, San Francisco, CA 94143 USA. EM dereks@lppi.ucsf.edu FU NIA NIH HHS [2-T32-AG00037]; NIDA NIH HHS [P50 DA09253, T32 DA07250] NR 37 TC 11 Z9 11 U1 1 U2 2 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD JUL PY 2004 VL 8 IS 4 BP 346 EP 354 DI 10.1080/13607860410001709692 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 839KO UT WOS:000222784200006 PM 15370050 ER PT J AU Kim, SG Kim, CM Kang, DH Kim, YJ Byun, WT Kim, SY Park, JM Kim, MJ Oslin, DW AF Kim, SG Kim, CM Kang, DH Kim, YJ Byun, WT Kim, SY Park, JM Kim, MJ Oslin, DW TI Association of functional opioid receptor genotypes with alcohol dependence in Koreans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; mu-opioid receptor; polymorphism ID GENE POLYMORPHISMS; SUBSTANCE DEPENDENCE; BETA-ENDORPHIN; NALTREXONE; OPRM1; RISK; ETHANOL; SENSITIVITY; RESPONSES; BLOCKADE AB Background: The functional polymorphism (A118G) of the mu-opioid receptor gene (OPRM1) is thought to have clinical significance in the treatment of alcohol dependence. This study compared Koreans with one or two copies of the A118G polymorphism seeking treatment for alcohol dependence with a group of non-alcohol-dependent controls. Methods: Patients hospitalized for alcohol dependence (n = 112) and a group of non-alcohol-dependent controls (n = 140) were interviewed on aspects of drinking history and psychiatric history. Patients and controls were excluded if they met criteria for any other major psychiatric disorder. Participants were genotyped at the OPRM1 locus. Results: The allele frequency of the Asp40 allele was 0.397 in the alcohol-dependent group, which is consistent with other literature demonstrating this polymorphism to be common in Asian populations. Within the alcohol-dependent subjects, being homozygous for the Asp40 allele was associated with more days drinking than those heterozygous or homozygous for the Asn40 allele. Differences in the allele frequencies between alcohol-dependent and non-alcohol-dependent controls were not significant. Conclusions: These results suggest that having one or two copies of the A118G allele is common among Koreans and may be an important genetic factor in the etiology of alcohol dependence and the frequency of alcohol consumption. C1 Pusan Natl Univ, Sch Med, Dept Psychiat, Pusan 602739, South Korea. Pusan Natl Univ, Sch Med, Dept Biochem, Pusan 602739, South Korea. Pusan Natl Univ, Sch Med, Dept Family Med, Pusan 602739, South Korea. Haeundae Ja Myung Hosp, Pusan, South Korea. Yang San Hosp, Kyungsang Nambo, South Korea. Dong A Univ, Div Management Informat Sci, Pusan, South Korea. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. VISN 4 MIRECC, Philadelphia, PA USA. RP Kim, SG (reprint author), Pusan Natl Univ, Sch Med, Dept Psychiat, 1 Ga 10,Ami Dong, Pusan 602739, South Korea. EM sungkim@pusan.ac.kr RI KIM, SEONG YEON/E-4164-2012 NR 32 TC 51 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2004 VL 28 IS 7 BP 986 EP 990 DI 10.1097/01.ALC.0000130803.62768.AB PG 5 WC Substance Abuse SC Substance Abuse GA 840AQ UT WOS:000222829800002 PM 15252283 ER PT J AU Kliethermes, CL Cronise, K Crabbe, JC AF Kliethermes, CL Cronise, K Crabbe, JC TI Anxiety-like behavior in mice in two apparatuses during withdrawal from chronic ethanol vapor inhalation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ELEVATED PLUS-MAZE; ALCOHOL-WITHDRAWAL; ANIMAL-MODEL; PHARMACOLOGICAL CHARACTERIZATION; DAILY EXPOSURE; ZERO-MAZE; RATS; MOUSE; TRIAL; BENZODIAZEPINES AB Background: Anxiety during ethanol withdrawal may be a factor in relapse to alcohol abuse and dependence. Animal models of ethanol withdrawal have typically used forced consumption of an ethanol-containing liquid diet to induce dependence. Ethanol vapor inhalation offers an advantage over liquid diet consumption in that the onset of withdrawal can be temporally controlled more precisely, allowing studies of the development of withdrawal symptoms. Methods: The purpose of the current study was to induce ethanol dependence in mice using an inhalation procedure and to assess withdrawal anxiety symptoms behaviorally in the elevated zero maze and in the light/dark box. Male and female mice were exposed to 3 days of ethanol vapors. Anxiety-like behavior was measured on the elevated zero maze and light/dark box at multiple time points during withdrawal. Results: Mice experiencing ethanol withdrawal demonstrated increased anxiety-like behaviors relative to control animals in both apparatuses. However, this finding was specific to the procedure used with the elevated zero maze and was strongly influenced by sex in the light/dark box. Conclusions: Ethanol vapor inhalation appears to be a valid tool for the study of withdrawal-induced anxiety. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland VA Med Ctr, Portland, OR 97239 USA. VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA. RP Kliethermes, CL (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland VA Med Ctr, R&D 12,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kliether@ohsu.edu FU NIAAA NIH HHS [AA12714, P60 AA010760, AA10760, T32AA07468] NR 49 TC 40 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2004 VL 28 IS 7 BP 1012 EP 1019 DI 10.1097/01.ALC.0000131976.40428.8F PG 8 WC Substance Abuse SC Substance Abuse GA 840AQ UT WOS:000222829800006 PM 15252287 ER PT J AU Schwartz, GG Bolognese, MA Tremblay, BP Caplan, R Hutchinson, H Raza, A Cressman, M AF Schwartz, GG Bolognese, MA Tremblay, BP Caplan, R Hutchinson, H Raza, A Cressman, M TI Efficacy and safety of, rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: A randomized, controlled trial SO AMERICAN HEART JOURNAL LA English DT Article ID DENSITY-LIPOPROTEIN-CHOLESTEROL; PREVENTION; EVENTS; GOALS; PRAVASTATIN; AVERAGE AB Background This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease. Methods After a 6-week dietary lead-in period, patients with LDL-C levels greater than or equal to 160 and <250 mg/dL and triglyceride levels :5400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128). Results At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P < .001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P < .01], 47% [P < .001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P < .01], 59% [P < .001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-1, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P < .01). Effects of the 2 agents on triglycerides were similar. Conclusions Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk. C1 Univ Colorado, Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Bethesda Hlth Res, Bethesda, MD USA. Ctr Hosp Univ, Hotel Dieu, Quebec City, PQ, Canada. AstraZeneca LP, Wilmington, DE USA. RP Univ Colorado, Denver VA Med Ctr, Cardiol Sect, 1055 Clermont St,1118, Denver, CO 80220 USA. EM Gregory.Schwartz@med.va.gov NR 21 TC 12 Z9 12 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUL PY 2004 VL 148 IS 1 BP 105 EP + DI 10.1016/j.ahj.2004.01.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833RX UT WOS:000222357700019 ER PT J AU Kenchaiah, S Pfeffer, MA Sutton, MS Plappert, T Rouleau, JL Lamas, GA Parker, JO Geltman, EW Solomon, SD AF Kenchaiah, S Pfeffer, MA Sutton, MS Plappert, T Rouleau, JL Lamas, GA Parker, JO Geltman, EW Solomon, SD TI Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the survival and ventricular enlargement trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERIAL-HYPERTENSION; HEART-FAILURE; EXPANSION; HYPERTROPHY; RECOVERY; DETERMINANTS; DYSFUNCTION; DILATATION; CAPTOPRIL; PROGNOSIS AB Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SID I I +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure greater than or equal to140 or baseline diastolic blood pressure greater than or equal to90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p less than or equal to0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8%.vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction. (C) 2004 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Partners Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Kingston Gen Hosp, Kingston, ON K7L 2V7, Canada. Washington Univ, Sch Med, Barnes Hosp, St Louis, MO USA. RP Solomon, SD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013; Kenchaiah, Satish/A-1519-2016 NR 30 TC 21 Z9 28 U1 0 U2 1 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 1 PY 2004 VL 94 IS 1 BP 1 EP 8 DI 10.1016/j.amjcard.2004.03.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832QO UT WOS:000222282200001 PM 15219499 ER PT J AU Gurm, HS Lincoff, AM Kleiman, NS Kereiakes, DJ Tcheng, JE Aronow, HD Askari, AT Brennan, DM Topol, EJ AF Gurm, HS Lincoff, AM Kleiman, NS Kereiakes, DJ Tcheng, JE Aronow, HD Askari, AT Brennan, DM Topol, EJ TI Double jeopardy of renal insufficiency and anemia in patients undergoing percutaneous coronary interventions SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLYCOPROTEIN IIB/IIIA RECEPTOR; KIDNEY-FUNCTION; HEART-FAILURE; MORTALITY; REVASCULARIZATION; HEMODIALYSIS; ANGIOPLASTY; BLOCKADE AB Anemia and renal insufficiency impart an increased risk of mortality in patients with congestive heart failure. There is a paucity of data on the mortality hazard associated with anemia and renal insufficiency in patients undergoing percutoneous coronary intervention in the setting of contemporary practice. We analyzed the short- and long-term outcomes among patients enrolled in EPIC, EPILOG and EPISTENT trials according to degree of kidney dysfunction (glomerular filtration rate [GFR] <60, 60 to 75, and >75 mi/min/1.73 m(2)) and by hematocrit (<35, 35 to 39 and 40). GFR was calculated as GFR = 186 x (serum creatinine(-1.154)) X (age (-0.203)) x 1.212 (if black) or x0.742 (if female). There were 20 deaths (3.2%) among 638 patients with a hematocrit of <35, 41 deaths among 2,066 patients (2.0%) with a hematocrit of 35 to 39, and 43 deaths in 3,618 patients (1.2%) with a hematocrit >40 at 6 months (p <0.001). Similarly, a significant increase in mortality was seen with lower GFR [33 of 1,168 (2.9%) at GFR 60, 33 of 1,766 (1.9%) at GFR 60 to 75 and 37 of 3,317 (1.1%) at GFR >75, p <0.001)]. Further, GFR and anemia independently and in combination predicted mortality at 3 years. Thus, renal insufficiency and anemia are significant independent and additive predictors of short- and long-term complications in patients undergoing percutaneous coronary intervention. (C) 2004 by Excerpta Medica, Inc. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Methodist DeBakey Heart Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Duke Clin Res Inst, Durham, NC USA. Lindner Ctr, Cincinnati, OH USA. Ohio Heart Hlth Ctr, Cincinnati, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Lincoff, AM (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,Desk F25, Cleveland, OH 44195 USA. EM lincofa@ccf.org OI Gurm, Hitinder/0000-0002-1646-0218; Topol, Eric/0000-0002-1478-4729 NR 18 TC 33 Z9 33 U1 0 U2 1 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 1 PY 2004 VL 94 IS 1 BP 30 EP 34 DI 10.1016/j.amjcard.2004.03.025 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832QO UT WOS:000222282200006 PM 15219504 ER PT J AU Ruo, B Rumsfeld, JS Pipkin, S Whooley, MA AF Ruo, B Rumsfeld, JS Pipkin, S Whooley, MA TI Relation between depressive symptoms and treadmill exercise capacity in the heart and soul study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; HEALTH-STATUS; MORTALITY; SERTRALINE; DISEASE; ANGINA AB To examine the association between depressive symptoms and exercise capacity, we performed a cross-sectional study of 944 outpatients with stable coronary artery disease and found that the presence of depressive symptoms was independently associated with poor exercise capacity (<5 MET tasks achieved; adjusted odds ratio 1.8, 95% confidence interval 1.1 to 2.7, p = 0.01). Depressive symptoms should be considered in the differential diagnosis of poor exercise capacity. (C) 2004 by Excerpta Medica, Inc. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Calif San Francisco, Sect Gen Int Med, VA Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Denver Vet Affairs Med Ctr, Cardiol & Hlth Serv Res, Denver, CO USA. RP Ruo, B (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, 680 N St Clair, Chicago, IL 60611 USA. EM berniceruo@post.harvard.edu FU NHLBI NIH HHS [R01 HL079235-01A1, R01 HL079235] NR 20 TC 27 Z9 27 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 1 PY 2004 VL 94 IS 1 BP 96 EP 99 DI 10.1016/j.amjcard.2004.03.035 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832QO UT WOS:000222282200017 PM 15219515 ER PT J AU Gibson, CM Bigelow, B James, D Tepper, MR Murphy, SA Kirtane, AJ Giugliano, RP Cannon, CP Antman, EM AF Gibson, CM Bigelow, B James, D Tepper, MR Murphy, SA Kirtane, AJ Giugliano, RP Cannon, CP Antman, EM CA TIMI Study Grp TI Association of lesion complexity following fibrinolytic administration with mortality in ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AMERICAN-HEART-ASSOCIATION; STENOSIS MORPHOLOGY CLASSIFICATION; CORONARY INTERVENTIONS; COLLEGE; TRIAL; ANGIOPLASTY; THROMBOLYSIS; REGISTRY; THERAPY AB Greater lesion complexity, according to the American College of Cardiology and American Heart Association, has been associated with decreased success rates of percutaneous coronary intervention. We hypothesized that greater lesion complexity after fibrinolytic administration for ST-segment elevation myocardial infarction would similarly be associated with increased mortality and other adverse events at 30 days. We studies 2,605 patients from the Thrombolysis In Myocardial Infarction I OB and 14, Integrilin and Tenecteplase in Acute Myocardial Infarction, ENTIRE, and FASTER studies. For all studies, angiographic outcomes were assessed immediately after fibrinolytic administration and clinical outcomes were assessed at 30 days. Greater lesion complexity was associated with poorer epicardial flow and decreased myocardial perfusion at 60 minutes and after percutaneous coronary intervention and with a higher risk of shock and mortality within 30 days. In a multivariate model, type C lesion complexity remained associated with an increased 30-day mortality rate. (C) 2004 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 20 TC 1 Z9 1 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 1 PY 2004 VL 94 IS 1 BP 108 EP 111 DI 10.1016/j.amjcard.2004.03.038 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832QO UT WOS:000222282200020 PM 15219518 ER PT J AU Weisskopf, MG McCullough, ML Calle, EE Thun, MJ Cudkowicz, M Ascherio, A AF Weisskopf, MG McCullough, ML Calle, EE Thun, MJ Cudkowicz, M Ascherio, A TI Prospective study of cigarette smoking and amyotrophic lateral sclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE amyotrophic lateral sclerosis; mortality; motor neuron disease; prospective studies ID MOTOR-NEURON DISEASE; WESTERN WASHINGTON-STATE; ANTECEDENT EVENTS; RISK-FACTORS; MORTALITY; DEATH; ASSOCIATION; SURVIVAL; PROGRESSION; ENGLAND AB Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but because of the low incidence of ALS this association has been examined only with case-control methods. The authors prospectively assessed the relation between cigarette smoking and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort of over 1 million people enrolled in 1982 who completed a lifestyle questionnaire including a detailed smoking history at baseline. Causes of deaths were ascertained through death certificates; ALS was not identified separately until 1989. From January 1, 1989, through 1998, 291 women and 330 men died from ALS. The relative risk of ALS among current smokers compared with never smokers was 1.67 (95% confidence interval: 1.24, 2.24; p = 0.002) in women and 0.69 (95% confidence interval: 0.49, 0.99; p = 0.04) in men. The difference in the relative risk estimates between the sexes was statistically significant (p < 0.0003). This large prospective study provides limited evidence that current cigarette smoking may be associated with increased death rates from ALS in women but not in men. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Landmark Ctr,3rd Floor,POB 15697, Boston, MA 02215 USA. EM mweissko@hsph.harvard.edu NR 42 TC 70 Z9 70 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 2004 VL 160 IS 1 BP 26 EP 33 DI 10.1093/aje/kwh179 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834HV UT WOS:000222403100005 PM 15229114 ER PT J AU Targownik, LE Spiegel, BMR Dulai, GS Karsan, HA Gralnek, IM AF Targownik, LE Spiegel, BMR Dulai, GS Karsan, HA Gralnek, IM TI The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/103rd Annual Meeting of the American-Gastroenterological-Association CY MAY 19-23, 2002 CL SAN FRANCISCO, CA SP Amer Gastroenterol Assoc ID PROSPECTIVE RANDOMIZED-TRIAL; BLEEDING ESOPHAGEAL-VARICES; INTRAHEPATIC PORTOSYSTEMIC SHUNT; PROPRANOLOL PLUS ISOSORBIDE-5-MONONITRATE; ENDOSCOPIC SCLEROTHERAPY; ISOSORBIDE MONONITRATE; PORTAL-HYPERTENSION; INJECTION SCLEROTHERAPY; PRIMARY PROPHYLAXIS; BANDING LIGATION AB OBJECTIVE: Recurrent variceal hemorrhage is common following an initial bleed in patients with cirrhosis. The current standard of care for secondary prophylaxis is endoscopic band ligation (EBL). Combination of beta-blocker and nitrate therapy, guided by hepatic venous pressure gradient (HVPG) monitoring, is a novel alternative strategy. We sought to determine the cost-effectiveness of these competing strategies. METHODS: Decision analysis with Markov modeling was used to calculate the cost-effectiveness of three competing strategies: (1) EBL; (2) beta-blocker and nitrate therapy without HVPG monitoring (HVPG-); and (3) beta-blocker and nitrate therapy with HVPG monitoring (HVPG+). Patients in the HVPG+ strategy who failed to achieve an HVPG decline from medical therapy were offered EBL. Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per recurrent variceal hemorrhage prevented. RESULTS: Under base-case conditions, the HVPG+ strategy was the most effective yet most expensive approach, followed by EBL and HVPG-. Compared to the EBL strategy, the HVPG+ strategy cost an incremental $5,974 per recurrent bleed prevented. In a population with 100% compliance with all therapies, the incremental cost of HVPG- versus EBL fell to $5,270 per recurrent bleed prevented. The model results were sensitive to the cost of EBL, the cost of HVPG monitoring, and the probability of medical therapy producing an adequate HVPG decline. CONCLUSIONS: Compared to EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring is more effective and only marginally more expensive. C1 Univ Calif Los Angeles, David Geffen Sch Med,Div Digest Dis, VA Greater Los Angeles Healthcare Syst,Div Gastro, CURE Digest Dis Res Ctr,Ctr Study Digest Healthca, Los Angeles, CA 90073 USA. Univ Manitoba, Gastroenterol Sect, Winnipeg, MB, Canada. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med,Div Digest Dis, VA Greater Los Angeles Healthcare Syst,Div Gastro, CURE Digest Dis Res Ctr,Ctr Study Digest Healthca, 11301 Wilshire Blvd,Bldg 115 Room 215B, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-07180]; PHS HHS [K23 1618801] NR 51 TC 18 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2004 VL 99 IS 7 BP 1306 EP 1315 DI 10.1111/j.1572-0241.2004.30754.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 837NI UT WOS:000222641800020 PM 15233670 ER PT J AU Walker, AM Bohn, RL Cali, C Cook, SF Ajene, AN Sands, BE AF Walker, AM Bohn, RL Cali, C Cook, SF Ajene, AN Sands, BE TI Risk factors for colon ischemia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLITIS; SPECTRUM AB BACKGROUND: To identify predictors of colon ischemia, we examined demographic and clinical characteristics of patients, as well as their prior health care utilization. METHODS: Using insurance data, we identified 700 persons at least 20-yr old with presumed colon ischemia between 1995 and 1999, and 6,440 controls. Case identification was based on diagnosis and procedure codes in insurance claims for which we used a previously reported, validated algorithm. We ascertained preceding medical diagnoses and the use of drugs and health services from the insurance claims files. RESULTS: Patients with colon ischemia were nearly three times as likely to have IBS than controls. A history of nonspecific colitis, lower gastrointestinal tract hemorrhage, systemic rheumatologic disorders, and ischemic heart disease in the preceding 6 months, and abdominal surgery in the past month were also much more common in colon ischemia cases than controls. Use of a drug to treat diarrhea was strongly associated with risk. The most prevalent risk factor for colon ischemia was the use of drugs with a side effect of constipation, found in one-third of cases and one in nine controls. Cases had seen physicians, particularly gastroenterologists, much more commonly in the preceding 6 months than had controls. CONCLUSIONS: Clinically evident colon ischemia arises preferentially in persons with prior abdominal complaints, many of whom carry a diagnosis of IBS. Drugs that reduce bowel motility may constitute a widespread and potentially avoidable risk factor. The frequency of preceding doctor visits, without a specific diagnosis, suggests that colon ischemia may have a prolonged subacute presentation. C1 Ingenix Epidemiol, Auburndale, MA 02466 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Walker, AM (reprint author), Ingenix Epidemiol, Suite 3-120,275 Grove St, Auburndale, MA 02466 USA. NR 9 TC 44 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2004 VL 99 IS 7 BP 1333 EP 1337 DI 10.1111/j.1572-0241.2004.21436.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 837NI UT WOS:000222641800024 PM 15233674 ER PT J AU Young, RC Gyulai, L Mulsant, BH Flint, A Beyer, JL Shulman, KI Reynolds, CF AF Young, RC Gyulai, L Mulsant, BH Flint, A Beyer, JL Shulman, KI Reynolds, CF TI Pharmacotherapy of bipolar disorder in old age - Review and recommendations\ SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Unmet Needs in Diagnosis and Treatment of Mood Disorders in Life CY OCT 09-10, 2001 CL Washington, DC SP Depress & Bipolar Support Alliance, Abbott Lab, AstraZeneca, Forest Lab Inc, GlaxSmithKline, Janssen Pharmaceut Ment Hlth, Organon Inc, Pfizer INC, Wyeth Ayerst Lab ID MANIC-DEPRESSIVE ILLNESS; ELDERLY PSYCHIATRIC-PATIENTS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; LITHIUM-CARBONATE; LATE-LIFE; GERIATRIC-PATIENTS; DIVALPROEX SODIUM; VALPROIC ACID; TARDIVE-DYSKINESIA AB The authors reviewed the evidence-base for pharmacological treatment of mania and bipolar (BP) depression in late life. Treatment benefits and side effects maybe modified by age-associated factors, such as neurocognitive impairments. Lithium and dival-proex have most often been studied in elderly patients, and both may be efficacious in acute treatment of mania, but there are no controlled efficacy or effectiveness trials. The role of atypical antipsychotic agents remains to be clarified. Similarly, there are no systematic studies of the treatment of BP depression in elderly patients. The authors make suggestions for management and delineate priorities for research. C1 Cornell Univ, Weill Med Coll, Inst Geriatr Psychiat, Dept Psychiat, White Plains, NY 10605 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Western Psychiat Inst, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Western Psychiat Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Sst, Geriatr Res Educ & Clin CCtr, Pittsburgh, PA USA. Univ Toronto, Fac Med, Dept Psychiat, Toronto, ON M5S 1A1, Canada. Duke Univ, Dept Psychiat, Med Ctr, Durham, NC 27706 USA. RP Young, RC (reprint author), Cornell Univ, Weill Med Coll, Inst Geriatr Psychiat, Dept Psychiat, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM ryoung@med.cornell.edu FU NIMH NIH HHS [K01 MH01613, MH43832, MH37869, K02 MH067028, P30 MH52247, MH57027, MH-98-DS-001, P30 MH49762, K02 MH01192, R01 MH52763] NR 131 TC 47 Z9 49 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, 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-AUG PY 2004 VL 12 IS 4 BP 342 EP 357 DI 10.1176/appi.ajgp.12.4.342 PG 16 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 835OT UT WOS:000222493800002 PM 15249272 ER PT J AU Butters, MA Bhalla, RK Mulsant, BH Mazumdar, S Houck, PR Begley, AE Dew, MA Pollock, BG Nebes, RD Becker, JT Reynolds, CF AF Butters, MA Bhalla, RK Mulsant, BH Mazumdar, S Houck, PR Begley, AE Dew, MA Pollock, BG Nebes, RD Becker, JT Reynolds, CF TI Executive functioning, illness course, and relapse/recurrence in continuation and maintenance treatment of late-life depression - Is there a relationship? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID MINI-MENTAL-STATE; GERIATRIC DEPRESSION; COGNITIVE IMPAIRMENT; ELDERLY PATIENTS; RATING-SCALE; ANTIDEPRESSANT TREATMENT; TREATMENT RESPONSE; DOUBLE-BLIND; NORTRIPTYLINE; PAROXETINE AB Objective: The authors tested the hypothesis that impaired executive functioning leads to high rates of relapse and recurrence in late-life depression, Methods: They analyzed data from subjects participating in two independent intervention trials. Study I included 53 elderly depressed patients who participated in an open trial comparing the efficacy of paroxetine and nortriptyline and recurrence prevention over 18 months. Study II focused on 146 elderly depressed patients who received open treatment with paroxetine in a relapse-prevention study over 4 months of continuation treatment. They examined the effect of cognitive functioning, in general, and executive functioning, in particular, on time-to-relapse/recurrence, using baseline and post-treatment measures of neuropsychological functioning. Results: The associations between cognitive measures and both probability of, and time-to-relapse/recurrence were small and statistically nonsignificant. Conclusion: Data failed to support the hypothesis that cognitive impairment, in general, or executive dysfunction, in particular predicts relapse or recurrence of major depression in late life. Authors recommend future testing of the hypothesis with detailed, comprehensive measures over longer periods of observation during maintenance trials. C1 Univ Pittsburgh, Med Ctr, Intervent Res Ctr Late Life Mood Disorders, Western Psychiat Inst,Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Intervent Res Ctr Late Life Mood Disorders, Western Psychiat Clin,Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, GRECC, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Butters, MA (reprint author), WPIC E-464,3811 OHara St, Pittsburgh, PA 15213 USA. EM buttersma@upmc.edu FU NIA NIH HHS [AG05133]; NIMH NIH HHS [MH43832, MH01613, MH37869, MH52247, MH65416, MH01684] NR 28 TC 45 Z9 46 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, 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-AUG PY 2004 VL 12 IS 4 BP 387 EP 394 DI 10.1176/appi.ajgp.12.4.387 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 835OT UT WOS:000222493800006 PM 15249276 ER PT J AU Pergola, PE Habiba, NM Johnson, JM AF Pergola, PE Habiba, NM Johnson, JM TI Body temperature regulation during hemodialysis in long-term patients: Is it time to change dialysate temperature prescription? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE dialysate temperature; hemodialysis (HD); body temperature; blood temperature monitor ID ACTIVE CUTANEOUS VASODILATION; SKIN TEMPERATURE; CARDIOVASCULAR ADJUSTMENTS; VASCULAR STABILITY; ENERGY-TRANSFER; COOL DIALYSATE; HUMANS; EXERCISE; WUNDERLICH,CARL,REINHOLD,AUGUST; VASOCONSTRICTION AB During hemodialysis procedures, changes in the dialysate temperature can raise or lower body temperature because the blood Is returned to the patient in thermal equilibrium with the dialysate. Even a dialysate temperature equal to the patient's body temperature as measured from the tympanic membrane, oral cavity, or axilla can result In an increase in the patient's body temperature, leading to cutaneous vasodilation and the potential for cardiovascular instability and hypotension. This deleterious cycle of events can be prevented by suitably adjusting the dialysate temperature. Lowering the dialysate temperature from 37degreesC to 34-35.5C has Improved the cardiovascular stability of many hemodialysis patients. Continuous monitoring of blood temperature allows the practitioner to make preemptive changes in dialysate temperature because a small change in body temperature can have enormous cardiovascular implications. For example, only 0.3degreesC to 0.8degreesC separates the thresholds for skin vasodilation from that for shivering. A suggested improvement in the hemodialysis procedure is to use devices that allow continuous monitoring of arterial and venous blood temperatures and adjust the dialysate temperature automatically, keeping the patient, not the dialysate, isothermic. Less optimal solutions appear to be (1) to monitor arterial and venous temperatures while manually adjusting the dialysate temperature to maintain arterial (and hence body) temperature stability; (2) to monitor peripheral temperatures (oral, tympanic) at regular intervals and adjust dialysate temperature to maintain the body temperature constant; (3) routinely use a dialysate temperature <37.0&DEG;C in all patients unless contraindicated. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Pergola, PE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Pergola@UTHSCSA.edu FU NHLBI NIH HHS [HL59166] NR 44 TC 19 Z9 19 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2004 VL 44 IS 1 BP 155 EP 165 DI 10.1053/j.ajkd.2004.03.036 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 839RK UT WOS:000222802400017 PM 15211448 ER PT J AU Volpp, KGM Buckley, E AF Volpp, KGM Buckley, E TI The effect. of increases in HMO penetration and changes in payer mix on in-hospital mortality and treatment patterns for acute myocardial infarction SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CARE PLAN PERFORMANCE; MANAGED CARE; COMORBIDITY MEASURES; MARKET SHARE; EXPENDITURES; COMPETITION; MEDICARE; JOB AB Objective: To determine whether changes in health maintenance organization (HMO) penetration or payer mix affected in-hospital mortality and treatment patterns of patients with acute myocardial infarction (AMI). Study Design: Observational study using patient-level logistic regression analysis and hospital and year fixed effects of data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Inpatient Sample, a geographically diverse sample of 20% of the hospitalized patients in the United States. Patients and Methods: Discharges of patients (n = 340 064) with a primary diagnosis of acute myocardial infarction who were treated in general medical or surgical hospitals that contributed at least 2 years of data to the HealthCare Cost and Utilization Project Nationwide Inpatient Sample from 1989 to 1996. In-hospital mortality and rates of cardiac catheterization, angioplasty, or coronary artery bypass grafting for Medicare patients or non-Medicare patients were the main outcome measures. Results: Among Medicare patients, increases in HMO penetration were associated with reduced odds of receiving cardiac catheterization, angioplasty, or coronary artery bypass grafting of 3% to 16%, but were not associated with any change in mortality risk. Increases in the number of HMOs within a metropolitan statistical area, our measure of HMO competition, were associated with small but significant increases in the odds of cardiac catheterization and angioplasty of about 2%. There was no pattern of changes in cardiac procedure rates or in-hospitality mortality among non-Medicare patients. Conclusion: Increases in HMO penetration reduced cardiac procedure rates by statistically significant but small amounts among Medicare patients with AMI, without affecting mortality rates. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Hosp, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Volpp, KGM (reprint author), Univ Penn, Sch Med, Dept Med, 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@mail.med.upenn.edu NR 21 TC 17 Z9 17 U1 0 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2004 VL 10 IS 7 BP 505 EP 512 PN 2 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 839UC UT WOS:000222809400007 PM 15298238 ER PT J AU Glatt, SJ Faraone, SV Tsuang, MT AF Glatt, SJ Faraone, SV Tsuang, MT TI DRD2-141C insertion/deletion polymorphism is not associated with schizophrenia: Results of a meta-analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE gene; allele; association; metaanalysis; schizophrenia ID D2 RECEPTOR GENE; FUNCTIONAL POLYMORPHISM; PROMOTER POLYMORPHISM; -141C INS/DEL; VARIANT; REGION; DISEQUILIBRIUM; POPULATION; PSYCHOSIS AB The gene DRD2, which codes for dopamine receptor D2, has been considered a prime candidate for allelic association testing with schizophrenia based on the strong evidence for involvement of this protein in disease pathophysiology. Recent meta-analyses confirmed a small but reliable association between schizophrenia and the cysteine-coding allele of the Cys311Ser polymorphism of DRD2. In the present study, we sought to determine if another polymorphism (the -141C insertion/deletion) in the same gene, which has been reported to be associated with schizophrenia in several individual studies, would show a similar pattern of association with the disease in a pooled dataset. The pooled odds ratio for the insertion allele obtained from 10 case-control studies was 1.1, which was not significant (P = 0.580); however, there was marked heterogeneity among the findings of individual studies, suggesting that some underlying factor influenced the size of their observed effects. Yet, neither ethnicity, the age of the control group, nor the gender composition of the samples reliably influenced effect size. Because linkage disequilibrium. patterns between various DRD2 polymorphisms are not yet known, it remains possible that divergent meta-analytic findings at both commonly examined mutation sites within DRD2 are accurate. Haplotype analysis within this gene would be useful for definitively specifying the role of this gene in the etiology of schizophrenia. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Psychiat Serv, Brockton, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 NR 21 TC 19 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 1 PY 2004 VL 128B IS 1 BP 21 EP 23 DI 10.1002/ajmg.b.30007 PG 3 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 834PT UT WOS:000222423700005 PM 15211624 ER PT J AU Matthysse, S Holzman, PS Gusella, JF Levy, DL Harte, CB Jorgensen, A Moller, L Parnas, J AF Matthysse, S Holzman, PS Gusella, JF Levy, DL Harte, CB Jorgensen, A Moller, L Parnas, J TI Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: Additional evidence SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE eye tracking; schizophrenia; latent trait model; chromosome 6p; linkage ID TRACKING DYSFUNCTION; SUSCEPTIBILITY LOCUS; SMOOTH-PURSUIT; MOTION PERCEPTION; CANDIDATE REGIONS; ABNORMAL-PURSUIT; RELATIVES; FAMILIES; PERFORMANCE; DISEQUILIBRIUM AB Establishing the genetics of physiological traits associated with schizophrenia may be an important first step in building a neurobiological bridge between the disease phenotype and its genetic underpinnings. One of the best known of the traits associated with schizophrenia is a disorder of smooth pursuit eye tracking (ETD), which is present in 50-80% of schizophrenia patients. ETD is more than three times more prevalent in the families of a schizophrenia patient than is schizophrenia itself. Arolt et al. [1999] estimated LOD scores for ETD of 2.85 for D6S282 and 3.70 for D6S271, two markers on 6p21.1, as well as obtaining an indication of possible linkage for schizophrenia. Our sample comprised two large families in Denmark. Markers in the region that was implicated by the study of Arolt et al. [1996, 1999] were analyzed as part of a genome scan using the "latent trait (L.T.) model" for the co-transmission of schizophrenia and ETD that we had previously fitted to segregation analysis data from Norway. We obtained a LOD score of 2.05 for D6S1017, a marker within 3 cM of the positive markers obtained by Arolt et al. [1996, 1999]. We regard our results as independent evidence supporting the findings of Arolt et al. [1996, 1999] and also as support for the L.T. model as a way of combining the traits ETD and schizophrenia. (C) 2004 Wiley-Liss, Inc. C1 McLean Hosp, Mailman Res Ctr, Psychol Res Lab, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, DK-2650 Hvidovre, Denmark. Kommune Hosp Copenhagen, Dept Psychiat, Copenhagen, Denmark. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, Copenhagen, Denmark. Univ Copenhagen, Ctr Subject Res, Danish Natl Res Fdn, Copenhagen, Denmark. RP Matthysse, S (reprint author), McLean Hosp, Mailman Res Ctr, Psychol Res Lab, 115 Mill St, Belmont, MA 02478 USA. EM steven_matthysse@harvard.edu OI Harte, Christopher/0000-0002-8097-7369 FU NIGMS NIH HHS [R01 GM 57453]; NIMH NIH HHS [R01 MH049487, R01 MH 59513, R37 MH 44876, P01 MH 31154, R01 MH031340, R01 MH 31340, K05 MH 01021, R01 MH 49487, P01 MH031154]; NINDS NIH HHS [NS 036711, NS 16367] NR 44 TC 44 Z9 45 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 1 PY 2004 VL 128B IS 1 BP 30 EP 36 DI 10.1002/ajmg.b.30030 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 834PT UT WOS:000222423700008 PM 15211627 ER PT J AU Qian, Q Wang, YF Zhou, R Yang, L Faraone, SV AF Qian, Q Wang, YF Zhou, R Yang, L Faraone, SV TI Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention deficit hyperactivity disorder (ADHD); dopamine D4 receptor; dopamine transporter; association; genetics ID DOPAMINE TRANSPORTER GENE; RECEPTOR GENE; 7-REPEAT ALLELE; NO ASSOCIATION; POPULATION; CHILDREN; LINKAGE; ADHD; TRANSMISSION; SAMPLE AB Molecular genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated the variable number of tandem repeat (VNTR) polymorphisms of two candidate genes, the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1.). We sought to determine if these genes were relevant to the etiology of ADHD in China by using both family-based (N = 202 nuclear ADHD families) and case-control (N = 340 ADHD cases, and 226 controls) association study designs. Diagnoses and subtypes were ascertained according to Clinical Diagnostic Interview Scales (CDIS) using DSM-IV criteria. The repeat numbers at the DRD4 VNTR ranged from 2 to 6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1 VNTR, the repeat numbers ranged from 6 to 7 repeats and 9 to 11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1. (ranging from 11 to 12 repeats), were present more frequently in ADHD probands than controls (P < 0.05), although there was no significant allelic association when the alleles were analyzed separately from each other and there findings were not supported by within family tests of association. An exploratory stratification by gender suggests that long-repeat alleles of DRD4 and DAT1 may increase the risk for ADHD in Han Chinese children. (C) 2004 Wiley-Liss, Inc. C1 Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Wang, YF (reprint author), Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. EM wangyufengbmu@hotmail.com OI Faraone, Stephen/0000-0002-9217-3982 NR 30 TC 37 Z9 41 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 1 PY 2004 VL 128B IS 1 BP 84 EP 89 DI 10.1002/ajmg.b.30079 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 834PT UT WOS:000222423700019 PM 15211638 ER PT J AU Anaya, HD Yano, EM Asch, SM AF Anaya, HD Yano, EM Asch, SM TI Early adoption of human immunodeficiency virus quality improvement in veterans affairs medical centers: Use of organizational surveys to measure readiness to change and adapt interventions to local priorities SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE clinical reminders; group-based quality improvement; organizations; preinterventional surveys; provider attitudes; Veterans Administration ID PHYSICIAN PERFORMANCE; HEALTH-CARE; FEEDBACK; REMINDERS; EDUCATION AB Potential delivery system responsiveness to quality improvement (QI) interventions is rarely assessed before implementation, although it might aid in interventional design. Preparing for a national initiative, we assessed Veterans Affairs (VA) human immunodeficiency virus (HIV) clinic organizational characteristics and attitudes toward QI interventions. Current QI activities and attitudes toward potential effectiveness of several techniques to improve antiretroviral and opportunistic infection prophylaxis therapy were assessed. These included computerized clinical reminders (CRs), group-based QI, expert advice, and facility and provider-level audit/feedback. Organizational characteristics were also examined. Respondents rated CRs and group-based QI (GBQI) interventions most highly. Western and complex facilities viewed CR and GBQI interventions more positively than less complex facilities or those in other regions, even controlling for organizational characteristics and perceived barriers to change. VA clinicians favored CR and GBQI over facility/ provider feedback. The persistence of regional variation should be further explored. Organizational surveys of attitudes toward potential QI interventions can assist in choosing interventions and targeting specific facilities. C1 VA Greater Los Angeles, HSR&D, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Anaya, HD (reprint author), 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM henry.anaya@med.va.gov NR 25 TC 10 Z9 10 U1 0 U2 3 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 2004 VL 19 IS 4 BP 137 EP 144 DI 10.1177/106286060401900402 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 844EU UT WOS:000223141100002 PM 15368778 ER PT J AU Ambriz, EH Woodard, LD Kressin, NR Petersen, LA AF Ambriz, EH Woodard, LD Kressin, NR Petersen, LA TI Use of smoking cessation interventions and aspirin for secondary prevention: Are there racial disparities? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE aspirin; coronary artery disease; racial differences; secondary prevention; smoking ID CORONARY-REVASCULARIZATION PROCEDURES; ACUTE MYOCARDIAL-INFARCTION; MEDICARE PATIENTS; DISEASE AB We examined whether racial differences exist in the use of aspirin and smoking cessation interventions for secondary prevention in veterans with coronary artery disease (CAD). We enrolled a total of 1045 African-American and white patients with CAD at 5 Veterans Administration hospitals between 1999 and 2001. Data were obtained by chart review. Among current smokers, African-American and white patients were equally likely to receive smoking cessation interventions (55.8% versus 56.1%; P = .97). Similarly, among ideal candidates for aspirin therapy, there was no difference in overall treatment rates between the 2 groups (74.1% versus 73.4%; P = .85). However, in the subsets of ideal candidates with hypercholesterolemia and previous stroke, African-Americans were less likely than whites to receive aspirin (P < .05). In contrast, African-Americans with hypertension were more likely than whites to receive aspirin (P = .05). Our findings highlight the need for improvement in use of smoking cessation interventions and aspirin among all patients with CAD and indicate an area where future quality improvement efforts may be warranted. C1 Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hypertens Clin Pharmacol, Houston, TX 77030 USA. Bedford VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Bedford, MA USA. RP Petersen, LA (reprint author), Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM laurap@bcm.tmc.edu FU BHP HRSA HHS [1 T32 PE 10031-01] NR 20 TC 8 Z9 8 U1 0 U2 0 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 2004 VL 19 IS 4 BP 166 EP 171 DI 10.1177/106286060401900405 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 844EU UT WOS:000223141100005 PM 15368781 ER PT J AU Dahlin, C AF Dahlin, C TI Oral complications at the end of life SO AMERICAN JOURNAL OF NURSING LA English DT Article ID DYSPHAGIA C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, ELNEC Project, Boston, MA USA. RP Dahlin, C (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. EM cdahlin@partners.org NR 23 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUL PY 2004 VL 104 IS 7 BP 40 EP 47 PG 8 WC Nursing SC Nursing GA 835NI UT WOS:000222490000022 PM 15243256 ER PT J AU Gordon, L AF Gordon, L TI Fuch's heterochromic cyclitis: New clues regarding pathogenesis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID AQUEOUS-HUMOR; T-CELLS; UVEITIS C1 Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Gordon, L (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu NR 10 TC 3 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2004 VL 138 IS 1 BP 133 EP 134 DI 10.1016/j.ajo.2004.03.031 PG 2 WC Ophthalmology SC Ophthalmology GA 836PO UT WOS:000222568200017 PM 15234292 ER PT J AU Boulos, PR Bernardino, CR Rubin, PAD AF Boulos, PR Bernardino, CR Rubin, PAD TI Pneumocele - A rare cause of air in the orbit SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MAXILLARY SINUS; DILATANS AB PURPOSE: To report a case of unilateral proptosis and chronic pansinusitis in which the diagnosis of pneumocele was made. DESIGN: Observational case report. METHODS: A retrospective chart review was made. RESULTS: A 52-year-old man with chronic pansinusitis presented with a 5-mm proptosis and a larger palpebral fissure in the left eye. Computed tomography imaging demonstrated an air-filled mass originating from the frontal sinus and protruding into the orbit. After endoscopic sinusotomy and excision of the mucosal sac through anterior orbitotomy, proptosis improved to 3 mm and palpebral fissures became symmetric. CONCLUSIONS: A pneumocele is a rare lesion of the paranasal sinuses that may expand into the orbit and may present with proptosis or motility deficit to the ophthalmologist. Through proper diagnosis and surgical management, the orbital symptoms will resolve. (C) 2004 by Elsevier Inc. All rights reserved. C1 Emory Eye Ctr, Atlanta, GA 30322 USA. Univ Montreal, Hop Maison Neuve Rosemont, Sch Med, Dept Ophthalmol, Montreal, PQ, Canada. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Bernardino, CR (reprint author), Emory Eye Ctr, 1365B Clifton Rd,NE,Room 4514, Atlanta, GA 30322 USA. EM crbernardino@mac.com NR 5 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2004 VL 138 IS 1 BP 168 EP 169 DI 10.1016/j.ajo.2004.02.054 PG 2 WC Ophthalmology SC Ophthalmology GA 836PO UT WOS:000222568200035 PM 15234310 ER PT J AU Fujii, N Boppart, MD Dufresne, SD Crowley, PF Jozsi, AC Sakamoto, K Yu, HY Aschenbach, WG Kim, S Miyazaki, H Rui, LY White, MF Hirshman, MF Goodyear, LJ AF Fujii, N Boppart, MD Dufresne, SD Crowley, PF Jozsi, AC Sakamoto, K Yu, HY Aschenbach, WG Kim, S Miyazaki, H Rui, LY White, MF Hirshman, MF Goodyear, LJ TI Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activity SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE electroporation; gene delivery; muscle contraction; exercise ID JUN NH2-TERMINAL KINASE; INSULIN-RECEPTOR SUBSTRATE-1; SIGNAL-REGULATED KINASE; IN-VIVO; GENE-TRANSFER; CONTRACTILE ACTIVITY; GLUCOSE-TRANSPORT; TERMINAL KINASE; GROWTH-FACTOR; EXERCISE AB c-Jun NH2-terminal kinase (JNK) is highly expressed in skeletal muscle and is robustly activated in response to muscle contraction. Little is known about the biological functions of JNK signaling in terminally differentiated muscle cells, although this protein has been proposed to regulate insulin-stimulated glycogen synthase activity in mouse skeletal muscle. To determine whether JNK signaling regulates contraction-stimulated glycogen synthase activation, we applied an electroporation technique to induce JNK overexpression (O/E) in mouse skeletal muscle. Ten days after electroporation, in situ muscle contraction increased JNK activity 2.6-fold in control muscles and 15-fold in the JNK O/E muscles. Despite the enormous activation of JNK activity in JNK O/E muscles, contraction resulted in similar increases in glycogen synthase activity in control and JNK O/E muscles. Consistent with these findings, basal and contraction-induced glycogen synthase activity was normal in muscles of both JNK1- and JNK2-deficient mice. JNK overexpression in muscle resulted in significant alterations in the basal phosphorylation state of several signaling proteins, such as extracellular signal-regulated kinase 1/2, p90 S6 kinase, glycogen synthase kinase 3, protein kinase B/Akt, and p70 S6 kinase, in the absence of changes in the expression of these proteins. These data suggest that JNK signaling regulates the phosphorylation state of several kinases in skeletal muscle. JNK activation is unlikely to be the major mechanism by which contractile activity increases glycogen synthase activity in skeletal muscle. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Osaka City Univ, Sch Med, Dept Pharmacol, Osaka 5458585, Japan. Univ Tsukuba, Inst Appl Biochem, Gene Expt Ctr, Tsukuba, Ibaraki 3058572, Japan. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR-45670, AR-42338]; NIDDK NIH HHS [5 T32 DK-07260-25] NR 52 TC 29 Z9 31 U1 0 U2 0 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 JUL PY 2004 VL 287 IS 1 BP C200 EP C208 DI 10.1152/ajpcell.00415.2003 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 827UG UT WOS:000221926100023 PM 15013949 ER PT J AU Paunescu, TG Da Silva, N Marshansky, V McKee, M Breton, S Brown, D AF Paunescu, TG Da Silva, N Marshansky, V McKee, M Breton, S Brown, D TI Expression of the 56-kDa B2 subunit isoform of the vacuolar H+-ATPase in proton-secreting cells of the kidney and epididymis SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE vacuolar H+-ATPase B subunit; intercalated cells; clear cells; urogenital tract; immunofluorescence ID MALE REPRODUCTIVE-TRACT; RENAL TUBULAR-ACIDOSIS; LUMINAL ACIDIFICATION; INTERCALATED CELLS; B1 SUBUNIT; CARBONIC-ANHYDRASE; MAMMALIAN KIDNEY; BINDING PROTEIN; COLLECTING DUCT; DEFICIENT MICE AB B1 and B2 are two highly homologous isoforms of the vacuolar H+-ATPase (V-ATPase) 56-kDa B subunit. We investigated whether the B2 subunit is expressed alongside B1 in proton-secreting cells of the rodent kidney collecting duct (intercalated cells, IC) and epididymis (clear cells) by using antibodies against distinct COOH-terminal peptides from the two B isoforms. B2 was detected not only in the kidney proximal tubule, thick ascending limb, distal convoluted tubule, and connecting segment but also in A- and B-type IC of collecting ducts ( CD) in both rat and mouse. B2 had a predominant cytoplasmic localization in most IC but was clearly located in a tighter apical band together with the V-ATPase 31-kDa E subunit in some A- IC, especially in the medulla. Apical membrane staining was confirmed by immunogold electron microscopy. B2 was very weakly expressed on the basolateral membranes of B-IC in control kidney CD, but some connecting segment B-IC had more distinct basolateral staining. In response to chronic carbonic anhydrase inhibition by acetazolamide, many A- IC showed a strong apical membrane localization of B2, where it colocalized with E and B1. In rat and mouse epididymis, B2 isoform expression was detected in clear cells, where it was concentrated in subapical vesicles. Unlike B1, B2 did not colocalize with the E subunit in the apical microvilli. These findings indicate that in addition to its role in the acidification of intracellular organelles, the B2 isoform could also contribute to transepithelial proton secretion and the maintenance of acid-base homeostasis. C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Paunescu, TG (reprint author), Massachusetts Gen Hosp E, Program Membrane Biol, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM paunescu@receptor.mgh.harvard.edu FU NICHD NIH HHS [HD-40793]; NIDDK NIH HHS [T32 DK-07540, DK-57521, DK-43351, DK-42956, DK-38452] NR 37 TC 56 Z9 57 U1 0 U2 1 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 JUL PY 2004 VL 287 IS 1 BP C149 EP C162 DI 10.1152/ajpcell.00464.2003 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 827UG UT WOS:000221926100018 PM 15013950 ER PT J AU Blevins, JE Schwartz, MW Baskin, DG AF Blevins, JE Schwartz, MW Baskin, DG TI Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE brain stem; adiposity; satiety; food intake ID CENTRAL-NERVOUS-SYSTEM; C-FOS EXPRESSION; REDUCES FOOD-INTAKE; SPINAL-CORD; RAT-BRAIN; GASTRIC DISTENSION; SOLITARY TRACT; BODY-WEIGHT; CHOLECYSTOKININ; VASOPRESSIN AB Hindbrain projections of oxytocin neurons in the parvocellular paraventricular nucleus (pPVN) are hypothesized to transmit leptin signaling from the hypothalamus to the nucleus of the solitary tract (NTS), where satiety signals from the gastrointestinal tract are received. Using immunocytochemistry, we found that an anorectic dose of leptin administered into the third ventricle (3V) increased twofold the number of pPVN oxytocin neurons that expressed Fos. Injections of fluorescent cholera toxin B into the NTS labeled a subset of pPVN oxytocin neurons that expressed Fos in response to 3V leptin. Moreover, 3V administration of an oxytocin receptor antagonist, [D-(CH2)5, Tyr(Me)2, Orn8]-vasotocin (OVT), attenuated the effect of leptin on food intake over a 0.5- to 4-h period (P<0.05). Furthermore, to determine whether oxytocin contributes to leptin's potentiation of Fos activation within NTS neurons in response to CCK, we counted the number of Fos-positive neurons in the medial NTS (mNTS) after 3V administration of OVT before 3V leptin and intraperitoneal CCK-8 administration. OVT resulted in a significant 37% decrease (P<0.05) in the potentiating effect of leptin on CCK activation of mNTS neuronal Fos expression. Furthermore, 4V OVT stimulated 2-h food intake by 43% (P<0.01), whereas 3V OVT at the same dose was ineffective. These findings suggest that release of oxytocin from a descending pPVN-to-NTS pathway contributes to leptin's attenuation of food intake by a mechanism that involves the activation of pPVN oxytocin neurons by leptin, resulting in increased sensitivity of NTS neurons to satiety signals. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. RP Blevins, JE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Serv 151, 1660 S Columbian Wy, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-17047, DK-12829, DK-52989]; NINDS NIH HHS [NS-32273] NR 52 TC 186 Z9 191 U1 1 U2 7 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 2004 VL 287 IS 1 BP R87 EP R96 DI 10.1152/ajpregu.00604.2003 PG 10 WC Physiology SC Physiology GA 828AE UT WOS:000221944000015 PM 15044184 ER PT J AU Wolden-Hanson, T Marck, BT Matsumoto, AM AF Wolden-Hanson, T Marck, BT Matsumoto, AM TI Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE energy balance; food intake; proopiomelanocortin; cocaine-amphetamine-regulated transcript ID AGOUTI-RELATED PROTEIN; AMPHETAMINE-REGULATED TRANSCRIPT; THYROTROPIN-RELEASING-HORMONE; LEPTIN SIGNAL-TRANSDUCTION; NPY MESSENGER-RNA; ARCUATE NUCLEUS; FOOD-INTAKE; BODY-WEIGHT; PARAVENTRICULAR NUCLEUS; AGED RATS AB Aging mammals lose the ability to maintain energy balance, exhibiting decreased appetite ( anorexia) and impaired ability to maintain body weight. To determine the contribution of hypothalamic neuropeptides, two experiments were performed in male Brown Norway rats. To assess the hypothalamic neuropeptide response to food deprivation, young (Y; 4 mo old), middle-aged ( M; 13 mo), and old (O; 25 mo) rats were either ad libitum fed or fasted for 72 h (n = 10/group) and killed. Hypothalamic levels of agouti-related peptide ( AgRP), proopiomelanocortin ( POMC), and cocaine-amphetamine-regulated transcript ( CART) mRNA were assessed by in situ hybridization. With aging, arcuate AgRP gene expression decreased and CART mRNA increased, but POMC mRNA did not change. Fasting-induced changes in gene expression of all neuropeptides studied were attenuated with aging. To test the food intake response to appetite-stimulating neuropeptides, Y, M, O, and very old (VO; 33 mo) rats (n = 4-8/group) received one intracerebroventricular injection of each of three treatments: 0.1 nmol AgRP, 2.34 nmol NPY, and saline control. AgRP increased food intake of all groups by 10-20%, compared with saline, and this effect persisted up to 7 days after injection. VO animals were more sensitive to the effects of AgRP than younger animals. In contrast, NPY increased food intake more in Y than in older animals and its effects did not last >24 h. We conclude that the mechanisms by which arcuate nucleus neurons influence appetite are differentially affected by age and speculate that the melanocortin system may be a useful target for treatment of the anorexia of aging. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. RP Wolden-Hanson, T (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM twh@u.washington.edu FU NICHD NIH HHS [P50-HD-12629] NR 57 TC 27 Z9 28 U1 1 U2 1 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 2004 VL 287 IS 1 BP R138 EP R146 DI 10.1152/ajpregu.00465.2003 PG 9 WC Physiology SC Physiology GA 828AE UT WOS:000221944000021 PM 15001433 ER PT J AU Tian, W Salanova, M Xu, HS Lindsley, JN Oyama, TT Anderson, S Bachmann, S Cohen, DM AF Tian, W Salanova, M Xu, HS Lindsley, JN Oyama, TT Anderson, S Bachmann, S Cohen, DM TI Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE water permeability; transient receptor potential ID HEAT-EVOKED ACTIVATION; PROTEIN; KIDNEY; MOUSE; RAT; PATHWAYS; LOCALIZATION; DERIVATIVES; CELLS; MICE AB TRPV4, a nonselective cation channel of the transient receptor potential (TRP) family, is gated by hypotonicity. Expression of TRPV4 mRNA has been detected in the circumventricular organs of the brain responsible for sensing systemic tonicity and in the kidney distal convoluted tubule (DCT), among other sites. No analysis of TRPV4 expression at the protein level has been undertaken and no systematic analysis of expression of this channel has been reported in the kidney. Via RNAse protection assay and immunoblotting, abundant expression of TRPV4 was detected in the cortex, medulla, and papilla. The expression pattern of TRPV4 was characterized in both rat and mouse kidney, which revealed similar patterns of immunoreactivity. TRPV4 expression was absent from the proximal tubule (PT) and descending thin limb (DTL), whereas the strongest expression was observed in the ascending thin limb (ATL). The thick ascending limb ( TAL) was strongly positive as was the DCT and connecting tubule. Importantly, the water-permeant cells of the macula densa were unstained. Moderate TRPV4 expression was noted in all collecting duct portions and in papillary epithelium; intercalated cells ( type A) exhibited a particularly strong signal. In all positive segments, TRPV4 expression was concentrated at the basolateral membrane. Therefore, TRPV4 is expressed in only those nephron segments that are constitutively (i.e., ATL, TAL, and DCT) or conditionally (i.e., collecting duct) water impermeant and where generation of a substantial transcellular osmotic gradient could be expected. TRPV4 expression is absent from nephron segments exhibiting constitutive water permeability and unregulated apical aquaporin expression (i.e., PT and DTL). These data, although circumstantial, are consistent with a role for TRPV4 in the response to anisotonicity in the mammalian kidney. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Charite Sch Med, Dept Anat, D-10115 Berlin, Germany. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu FU NIDDK NIH HHS [DK-52494] NR 27 TC 78 Z9 87 U1 1 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 2004 VL 287 IS 1 BP F17 EP F24 DI 10.1152/ajprenal.00397.2003 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 827FB UT WOS:000221883500003 PM 15026302 ER PT J AU Conroy, MB Delichatsios, KH Hafler, JP Rigotti, NA AF Conroy, MB Delichatsios, KH Hafler, JP Rigotti, NA TI Impact of a preventive medicine and nutrition curriculum for medical students SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PRIMARY-CARE; PHYSICIANS HEALTH; EDUCATION; SCHOOLS; DISEASE; HABITS; TOOL AB Background: United States public health goals call for increased physican counselling about diet and excercise, but many medical schools lack adequate curriculum on these topics. At Havard Medical School, second-year students take a preventive medicine and nutrition (PMN) course. This study evaluated the impact of this innovative cirruiculum on students' confidence about addressing patients' diet and excercise patterns and on their own health habits. Methods: Students enrolled in the 2003 PMN course (N = 137) completed 43-item written survey before and after the course. Surveys were completed by 134 students (98%) and 118 students (86%), respectively. The survey assessed students' diets and excercise habits and students' confidence in their ability to address diet and excercise with patients and family members. Results: Students' confidence in their ability to assess and counsel about diet and excercise significantly improved after the course (all p <0.001). The course was also was also associated with a decrease in students' self-reported consumption of saturated fat (p = 0.002) and trans fatty acids (p < 0.001). Following the course, 72% of students perceived an improvement in their diet but only 18% perceived an improvement in excercise habits. Conclusions: An innovative PMN course improved medical students' confidence in diet and excercise counseling and perceived dietary habits. Improving these mediators of physican counseling in medical students may translate into changes in their practicr patterns. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Off Educ Dev, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org NR 23 TC 26 Z9 26 U1 0 U2 5 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 JUL PY 2004 VL 27 IS 1 BP 77 EP 80 DI 10.1016/j.amepre.2004.03.009 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 831SK UT WOS:000222216200012 PM 15212779 ER PT J AU Brody, AL Olmstead, RE London, ED Farahi, J Meyer, JH Grossman, P Lee, GS Huang, J Hahn, EL Mandelkern, MA AF Brody, AL Olmstead, RE London, ED Farahi, J Meyer, JH Grossman, P Lee, GS Huang, J Hahn, EL Mandelkern, MA TI Smoking-induced ventral striatum dopamine release SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS; C-11 RACLOPRIDE; HUMAN-BRAIN; CONTINUOUS-INFUSION; IN-VIVO; PARKINSONS-DISEASE; CIGARETTE SMOKERS AB Objective: Substantial evidence from animal models demonstrates that dopamine release in the ventral striatum underlies the reinforcing properties of nicotine. The authors used [C-11]raclopride bolus-plus-continuous-infusion positron emission tomography (PET) to determine smoking-induced ventral striatum dopamine release in humans. Method: Twenty nicotine-dependent smokers (who smoked greater than or equal to15 cigarettes/day) underwent a [C-11]raclopride bolus-plus-continuous-infusion PET session. During the session, subjects had a 10-minute break outside the PET apparatus during which 10 subjects smoked a cigarette and 10 did not smoke (as a control condition). Results: The group that smoked had greater reductions in [C-11]raclopride binding potential in ventral striatum regions of interest than the group that did not smoke, particularly in the left ventral caudate/nucleus accumbens and left ventral putamen (range for smoking group-25.9% to -36.6% reduction). Significant correlations were found between change from before to after the smoking break in craving ratings and change from before to after the break in binding potential for these two regions. Conclusions: Nicotine-dependent subjects who smoked during a break in PET scanning had greater reductions in [C-11]raclopride binding potential (an indirect measure of dopamine release) than nicotine-dependent subjects who did not smoke. The magnitude of binding potential changes was comparable to that found in studies that used similar methods to examine the effects of other addictive drugs. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA 15059] NR 69 TC 168 Z9 174 U1 1 U2 6 PU AMER PSYCHIATRIC PRESS, 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 2004 VL 161 IS 7 BP 1211 EP 1218 DI 10.1176/appi.ajp.161.7.1211 PG 8 WC Psychiatry SC Psychiatry GA 835EG UT WOS:000222462700011 PM 15229053 ER PT J AU Kim, DH Millett, PJ Warner, JJP Jobe, FW AF Kim, DH Millett, PJ Warner, JJP Jobe, FW TI Shoulder injuries in golf SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE golf; shoulder; sports injuries; golf rehabilitation ID ARTHROSCOPIC BANKART REPAIR; OPERATIVE TECHNIQUES; SPORTS MEDICINE; ROTATOR CUFF; ELECTROTHERMAL CAPSULORRHAPHY; ELECTROMYOGRAPHIC ANALYSIS; SCAPULAR MUSCLES; INSTABILITY; ATHLETE; TEARS AB Although often perceived as a leisurely activity, golf can be a demanding sport, which can result in injury, usually from overuse and sometimes from poor technique. The shoulder is a commonly affected site, with the lead shoulder, or the left shoulder in the right-handed golfer, particularly vulnerable to injury. A thorough understanding of the biomechanics of the golf swing is helpful in diagnosing and managing these injuries. Common shoulder problems affecting golfers include subacromial impingement, acromioclavicular arthrosis, rotator cuff tear, glenohumeral instability, and glenohumeral arthrosis. Although the majority of patients with these disorders will respond to nonsurgical treatment, including rest and a structured program of physical therapy, further benefits can be obtained with subtle modifications of the golf swing. Those golfers who fail to respond to nonsurgical management can often return to competitive play with appropriate surgical treatment. C1 Kerian Jobe Orthopaed Clin, Los Angeles, CA 90045 USA. Harvard Univ, Shoulder Serv, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA USA. RP Kim, DH (reprint author), Kerian Jobe Orthopaed Clin, 6801 Pk Terrace Dr, Los Angeles, CA 90045 USA. NR 40 TC 16 Z9 16 U1 0 U2 13 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUL-AUG PY 2004 VL 32 IS 5 BP 1324 EP 1330 DI 10.1177/0363546504267346 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 839TR UT WOS:000222808300032 PM 15262661 ER PT J AU Patten, LC Awad, SS Berger, DH Fagan, SP AF Patten, LC Awad, SS Berger, DH Fagan, SP TI A novel technique for the repair of lumbar hernias after iliac crest bone harvest SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE iliac crest bone harvest; abdominal wall hernia; lumbar hernia; corkscrew suture anchor device AB Background: Lumbar hernia is a clinical entity that has been increasingly more common since the advent of iliac bone harvest for bone grafting procedures. These can be very technically difficult to repair and have a high recurrence rate. Methods: Using a corkscrew anchor suture device, we have developed a novel and simple way to repair these hernias with no recurrence. Here we present our experience with the corkscrew Suture anchor device. Results: This technique has been performed in 2 patients at our institution, and in both cases, the hernia was successfully repaired. Our I-year follow-up on this technique demonstrates intact repairs with no sign of recurrence. Conclusions: The placement of corkscrew suture anchors along the iliac crest remnant is a simple technique requiring minimal bony exposure. The anchors facilitate the long-term fixation of mesh despite the lack of fascia in this area. We conclude that this is a simple and effective approach for repair of these challenging hernias. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Surg Serv VA 112, Houston, TX 77030 USA. RP Fagan, SP (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Surg Serv VA 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM ShawnP.Fagan@med.va.gov NR 4 TC 9 Z9 10 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2004 VL 188 IS 1 BP 85 EP 88 DI 10.1016/j.amjsurg.2003.10.026 PG 4 WC Surgery SC Surgery GA 832NY UT WOS:000222275400016 PM 15219491 ER PT J AU Medeiros, F Corless, CL Duensing, A Hornick, JL Oliveira, AM Heinrich, MC Fletcher, JA Fletcher, CDM AF Medeiros, F Corless, CL Duensing, A Hornick, JL Oliveira, AM Heinrich, MC Fletcher, JA Fletcher, CDM TI KIT-negative gastrointestinal stromal tumors - Proof of concept and therapeutic implications SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; KIT; PDGFRA ID IMATINIB MESYLATE; MUTATIONS; ACTIVATION; DIAGNOSIS; CD117; GENE AB The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration of KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic features of GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 tumors with clinical and histologic features typical of GIST, but with negative KIT immunohistochemistry, for KIT and PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most tumors originated in the stomach (N = 14) or omentum/mesentery (N = 5). The neoplasms were composed of epithelioid cells (13 cases), admixed epithelioid and spindle cells (8 cases), or spindle cells (4 cases). Absence of KIT expression was confirmed by immunoblotting in 5 cases. Tumor karyotypes performed in 4 cases were noncomplex with monosomy 14 or 14q deletion, typical of GIST. Mutational analysis revealed PDGFRA and KIT mutations in 18 and 4 tumors, respectively, whereas 3 tumors did not have apparent KIT or PDGFRA mutations. The PDGFRA mutations primarily involved exon 18 (N = 15) and included 1 1 tumors with missense mutation in codon 842 (PDGFRA D842V or D842Y). In conclusion, a small subset of GISTs with otherwise typical clinicopathologic and cytogenetic features do not express detectable KIT protein. When compared with KIT-positive GISTs, these KIT-negative GISTs are more likely to have epithelioid cell morphology, contain PDGFRA oncogenic mutations, and arise in the omentum/peritoneal surface. Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fletcher, CDM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM cfletcher@partners.org OI Duensing, Anette/0000-0002-0168-4067 NR 22 TC 269 Z9 293 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 JUL PY 2004 VL 28 IS 7 BP 889 EP 894 DI 10.1097/00000478-200407000-00007 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 833LS UT WOS:000222339400007 PM 15223958 ER PT J AU Cubilla, AL Velazquez, EF Young, RH AF Cubilla, AL Velazquez, EF Young, RH TI Pseudo hyperplastic squamous cell carcinoma of the penis associated with lichen sclerosus. An extremely well-differentiated, nonverruciform neoplasm that preferentially affects the foreskin and is frequently misdiagnosed - A report of 10 cases of a distinctive clinicopathologic entity SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE penis; squamous cell carcinoma; well differentiated; foreskin mucosa; lichen sclerosus ID HUMAN-PAPILLOMAVIRUS DNA; ET-ATROPHICUS; VERRUCOUS CARCINOMA; VARIANTS; GRADE; FEATURES; INVASION; PREPUCE; LESION; CANCER AB We present 10 cases of well-differentiated, squamous cell carcinoma of the penis with pseudohyperplastic features. At presentation, the median age was 69 years. Seven of the tumors were multicentric, and the majority preferentially involved the foreskin inner mucosal surface. Grossly the tumors were typically flat or slightly elevated, white and granular, and measured approximately 2 cm. Characteristic histologic features included keratinizing nests of squamous cells with minimal atypia surrounded by a reactive fibrous stroma. In biopsies or individual areas of resected specimens, the differential diagnosis with pseudoepitheliomatous hyperplasia was difficult but when samples of adequate size were available, obvious evidence of infiltration was present. The adjacent squamous epithelium typically showed changes that are known to be associated with squamous cell carcinoma ranging from squamous hyperplasia to low-grade, and in a few cases high-grade, squamous intraepithelial lesions. Well-developed lichen sclerosus was seen in all cases. Patients were treated by circumcision or partial penectomy. With the exception of 1 patient who developed a glans recurrence 2 years after initial circumcision, follow-up after the initial surgical procedure has been uneventful. The majority of penile carcinomas with the high degree of differentiation seen in these cases are in the category of the verruciform tumors, either the verrucous or papillary carcinoma, not otherwise-specified subtypes. Experience with the cases reported in this series indicates that a subset of nonverruciform, often multicentric, tumors with a high degree of differentiation and pseudohyperplastic features occur and preferentially involve the foreskin. Because it was present in all cases, lichen sclerosus may play a precancerous role. C1 NYU, Ctr Med, Dept Pathol, New York, NY 10016 USA. Inst Patol & Invest, Asuncion, Paraguay. Fac Ciencias Med, Asuncion, Paraguay. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Velazquez, EF (reprint author), NYU, Ctr Med, Dept Pathol, Tisch 461, New York, NY 10016 USA. EM elsa.velazquez@med.nyu.edu NR 31 TC 38 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2004 VL 28 IS 7 BP 895 EP 900 DI 10.1097/00000478-200407000-00008 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 833LS UT WOS:000222339400008 PM 15223959 ER PT J AU Nakatani, Y Miyagi, Y Takemura, T Oka, T Yokoi, T Takagi, M Yokoyama, S Kashima, K Hara, K Yamada, T Nozawa, A Inayama, Y Sakamoto, K Ogawa, N Kitamura, H Resl, M Cho, SH Koss, MN Mark, EJ AF Nakatani, Y Miyagi, Y Takemura, T Oka, T Yokoi, T Takagi, M Yokoyama, S Kashima, K Hara, K Yamada, T Nozawa, A Inayama, Y Sakamoto, K Ogawa, N Kitamura, H Resl, M Cho, SH Koss, MN Mark, EJ TI Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma - beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pulmonary blastoma; adenocarcinoma of the fetal lung type; well-differentiated fetal adenocarcinoma; carcinosarcoma; beta-catenin ID WNT SIGNALING PATHWAY; RESEMBLING FETAL LUNG; UP-REGULATION; LOW-GRADE; ACTIVATION; ADENOCARCINOMA; TUMORS; P53 AB It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with h-FLAG/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adeno-carcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchytnal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA. Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. Charles Univ, Sch Med, Dept Pathol, Hradec Kralove, Czech Republic. Gifu Municipal Hosp, Dept Pathol, Gifu, Japan. Aichi Med Univ, Dept Pathol, Aichi, Japan. Nagoya Univ, Sch Hlth Sci, Dept Med Technol, Nagoya, Aichi, Japan. Oita Med Univ, Dept Pathol, Oita, Japan. St Marianna Univ, Dept Pathol, Kawasaki, Kanagawa, Japan. Kanto Cent Hosp, Dept Pathol, Tokyo, Japan. Kanagawa Prefectural Cardiovasc & Resp Ctr, Dept Surg, Yokohama, Kanagawa, Japan. Kanagawa Prefectural Canc Ctr, Clin Res Lab, Kanagawa, Japan. Yokohama City Univ, Grad Sch Med, Dept Pathol, Yokohama, Kanagawa 232, Japan. Yokohama City Univ, Grad Sch Med, Dept Surg, Yokohama, Kanagawa 232, Japan. Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan. Yokohama City Univ Med, Div Anat & Surg Pathol, Yokohama, Kanagawa, Japan. Yokohama City Univ, Med Ctr, Dept Pathol, Yokohama, Kanagawa, Japan. RP Nakatani, Y (reprint author), Chiba Univ Hosp, Dept Pathol, Chuo Ku, 1-8-1 Inohana, Chiba 2608677, Japan. EM nakatani@faculty.chiba-u.jp NR 33 TC 33 Z9 37 U1 0 U2 3 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 2004 VL 28 IS 7 BP 921 EP 927 DI 10.1097/00000478-200407000-00012 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 833LS UT WOS:000222339400012 PM 15223963 ER PT J AU Santiago-Palma, J Hord, ED Vallejo, R Trella, J Ahmed, SU AF Santiago-Palma, J Hord, ED Vallejo, R Trella, J Ahmed, SU TI Respiratory distress after intrathecal baclofen withdrawal SO ANESTHESIA AND ANALGESIA LA English DT Article ID SEVERE SPASTICITY; DRUG-THERAPY; DELIVERY; FAILURE; PUMP AB We present the case of a 19-yr-old woman with a history of generalized dystonia who developed sudden onset of adductor spasms of the vocal cords and increased dystonia after the interruption or intrathecal baclofen therapy. Her symptoms resolved after intrathecal baclofen was restored. In patients with dystonia receiving intrathecal baclofen therapy, the onset of dyspnea associated with increased muscle tone should prompt the investigation of baclofen withdrawal. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Massachusetts Gen Hosp Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Santiago-Palma, J (reprint author), 1362 Carlton Dr, Glendale, CA 91205 USA. EM jsantiagopalma@hotmail.com NR 13 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2004 VL 99 IS 1 BP 227 EP 229 DI 10.1213/01.ane.00000121347.11127.99 PG 3 WC Anesthesiology SC Anesthesiology GA 832GW UT WOS:000222256400043 PM 15281534 ER PT J AU Kaazempur-Mofrad, MR Isasi, AG Younis, HF Chan, RC Hinton, DP Sukhova, G LaMuraglia, GM Lee, RT Kamm, RD AF Kaazempur-Mofrad, MR Isasi, AG Younis, HF Chan, RC Hinton, DP Sukhova, G LaMuraglia, GM Lee, RT Kamm, RD TI Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE atherosclerosis; MRI; FEM; carotid 3D geometry; low/oscillatory shear stress; excised plaque composition ID SHEAR-STRESS; ENDOTHELIAL ADHESIVENESS; PULSATILE FLOW; MASS-TRANSPORT; NITRIC-OXIDE; BLOOD-FLOW; ARTERY; CELLS; PLAQUES; HEMODYNAMICS AB Atherogenesis is known to be associated with the stresses that act on or within the arterial wall. Still, the uneven distribution of atherosclerotic lesions and the impact of vessel remodeling on disease progression are poorly understood. A methodology is proposed to study the correlations between fluid dynamic parameters and histological markers of atherosclerosis. Trends suggested by preliminary data from four patients with advanced carotid bifurcation arterial disease are examined and compared to hypotheses in the literature. Four patients were scanned using MRI and ultrasound, and subsequently underwent carotid endarterectomy. For each patient, a geometric model and a numerical mesh were constructed from MR data, and velocity boundary conditions established. Computations yield values for average wall shear stress (WSS), maximum wall shear stress temporal gradient (WSSTG), and Oscillatory Shear Index (OSI). Following surgery, the excised plaques were sectioned, stained for smooth muscle cells (SMC), macrophages (MO), lipid (LIP), and collagen (COL), and analyzed quantitatively. Correlations attempted between the various fluid dynamic variables and the biological markers were interesting but inconclusive. Tendencies of WSSTG and WSS to correlate negatively with Mphi and LIP, and positively with COL and SMC, as well as tendencies of OSI to correlate positively with Mphi and LIP and negatively with COL and SMC, were observed. These trends agree with hypotheses in the literature, which are based on ex vivo and in vitro experimental studies. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiovasc Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Kamm, RD (reprint author), 77 Massachusetts Ave,Room NE47-321, Cambridge, MA 02139 USA. EM rdkamm@mit.edu OI /0000-0002-7232-304X FU NHLBI NIH HHS [HL 61794] NR 41 TC 79 Z9 85 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUL PY 2004 VL 32 IS 7 BP 932 EP 946 DI 10.1023/B:ABME.0000032456.16097.e0 PG 15 WC Engineering, Biomedical SC Engineering GA 840YV UT WOS:000222897400003 PM 15298431 ER PT J AU Dickerson, BC Salat, DH Bates, JF Atiya, M Killiany, RJ Greve, DN Dale, AM Stern, CE Blacker, D Albert, MS Sperling, RA AF Dickerson, BC Salat, DH Bates, JF Atiya, M Killiany, RJ Greve, DN Dale, AM Stern, CE Blacker, D Albert, MS Sperling, RA TI Medial temporal lobe function and structure in mild cognitive impairment SO ANNALS OF NEUROLOGY LA English DT Article ID ENTORHINAL CORTEX NEURONS; PROTEIN TRANSGENIC MICE; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; PRECLINICAL PREDICTION; FRONTAL-CORTEX; VOLUMETRIC MRI; BRAIN ACTIVITY; FMRI RESPONSE; WORK GROUP AB Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Max Planck Inst Psychiat, D-80804 Munich, Germany. Boston Univ Med, Dept Anat, Boston, MA USA. Boston Univ Med, Dept Neurobiol, Boston, MA USA. Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Div Cognit Neurosci, Baltimore, MD 21205 USA. RP Dickerson, BC (reprint author), MGH E, Gerontol Res Unit, 149-2691,149 13th St, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41 RR 14075, P41 RR014075]; NIA NIH HHS [P01 AG 04953, K23 AG 22509, K23 AG022509, P01 AG004953]; NINDS NIH HHS [K23 NS 02189, K23 NS002189] NR 59 TC 308 Z9 318 U1 1 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2004 VL 56 IS 1 BP 27 EP 35 DI 10.1002/ana.20163 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834QM UT WOS:000222425600006 PM 15236399 ER PT J AU McNaught, KSP Perl, DP Brownell, AL Olanow, CW AF McNaught, KSP Perl, DP Brownell, AL Olanow, CW TI Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID MUTANT ALPHA-SYNUCLEIN; CELL-DEATH; IN-VIVO; MESENCEPHALIC CULTURES; DOPAMINERGIC-NEURONS; LEWY BODIES; APOPTOSIS; DEGENERATION; LACTACYSTIN; EXPRESSION AB Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin-proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD-inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z-Ile-Glu(OtBu)-Ala-Leu-al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon-11-labeled 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, alpha-synuclein/ubiquitin-containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness. C1 CUNY Mt Sinai Sch Med, Dept Neurol, Div Neuropathol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Pathol, Div Neuropathol, New York, NY 10029 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP McNaught, KSP (reprint author), CUNY Mt Sinai Sch Med, Dept Neurol, Div Neuropathol, Annenberg 14-73,1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM kevin.mcnaught@mssm.edu FU NINDS NIH HHS [1 R01 NS045999-01] NR 51 TC 328 Z9 360 U1 1 U2 18 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 JUL PY 2004 VL 56 IS 1 BP 149 EP 162 DI 10.1002/ana.20186 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834QM UT WOS:000222425600022 PM 15236415 ER PT J AU Singh, JP Larson, MG Levy, D Evans, JC Tsuji, H Benjamin, EJ AF Singh, JP Larson, MG Levy, D Evans, JC Tsuji, H Benjamin, EJ TI Is baseline autonomic tone associated with new onset atrial fibrillation?: Insights from the framingham Heart Study SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE autonomic tone; heart rate variability; atrial fibrillation; cohort study ID RATE-VARIABILITY; INTERVAL DYNAMICS; NERVOUS-SYSTEM; TACHYCARDIA; RISK AB Background: Recent reports have indicated that autonomic tone fluctuations measured by heart rate variability (HRV) precede episodes of paroxysmal atrial fibrillation (AF). Little is known about the impact of baseline autonomic tone and the development of new onset AF in a population-based cohort. The purpose of this study was to assess the role of HRV as a predictor of new onset AF. Method: Ambulatory ECG recordings obtained from the Framingham Heart Study subjects attending a routine examination were processed for HRV. The HRV variables analyzed included standard deviation of normal R-R intervals (SDNN), low frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434 women and 1142 men (54 +/- 14.1 years) eligible for the study. Results: In 12 years of follow-up, 65 women and 67 men had new onset AF. The Study had 80% power to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in HRV. A one SD decrement in log LF/HF was associated with increased risk of developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06-1.44) in age- and sex-adjusted models; the association was no longer significant (HR = 1.15; 95% CI = 0.98-1.35) after adjusting for potential confounders. Conclusion: Autonomic dysregulation at baseline, as reflected by an altered HRV is associated with risk of AF; however, this association does not persist after adjusting for potential confounders. Much of the apparent association between HRV and AF is mediated by traditional risk factors. C1 Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Cardiol, Beth Israel Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Clin Epidemiol, Beth Israel Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950] NR 25 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JUL PY 2004 VL 9 IS 3 BP 215 EP 220 DI 10.1111/j.1542-474X.2004.93550.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 836OP UT WOS:000222565600004 PM 15245336 ER PT J AU Yoon, SS Coit, DG Portlock, CS Karpeh, MS AF Yoon, SS Coit, DG Portlock, CS Karpeh, MS TI The diminishing role of surgery in the treatment of gastric lymphoma SO ANNALS OF SURGERY LA English DT Review ID NON-HODGKINS-LYMPHOMA; HELICOBACTER-PYLORI INFECTION; B-CELL LYMPHOMA; TERM FOLLOW-UP; LOW-GRADE; MALT-LYMPHOMA; GASTROINTESTINAL-TRACT; TISSUE LYMPHOMA; ENDOSCOPIC ULTRASONOGRAPHY; CONSERVATIVE MANAGEMENT AB Objective: This article reviews the pathogenesis, diagnosis, and treatment of patients with primary gastric lymphoma, with special attention to the changing role of surgery. Summary Background Data: Primary gastric lymphomas are non-Hodgkin lymphomas that originate in the stomach and are divided into low-grade (or indolent) and high-grade (or aggressive) types. Low-grade lesions nearly always arise from mucosa-associated lymphoid tissue (MALT) secondary to chronic Helicobacter pylori (H. pylori) infection and disseminate slowly. High-grade lesions may arise from a low grade-MALT component or arise de novo and can spread to lymph nodes, adjacent organs and tissues, or distant sites. Methods: A review of the relevant English-language articles was performed on the basis of a MEDLINE search from January 1984 to August 2003. Results: About 40% of gastric lymphomas are low-grade, and nearly all these low-grade lesions are classified as MALT lymphomas. For low-grade MALT lymphomas confined to the gastric wall and without certain negative prognostic factors, H. pylori eradication is highly successful in causing lymphoma regression. More advanced low-grade lymphomas or those that do not regress with antibiotic therapy can be treated with combinations of I-I. pylori eradication, radiation therapy, and chemotherapy. Nearly 60% of gastric lymphomas are high-grade lesions with or without a low-grade MALT component. These lymphomas can be treated with chemotherapy and radiation therapy according to the extent of disease. Surgery for gastric lymphoma is now often reserved for patients with localized, residual disease after nonsurgical therapy or for rare patients with complications. Conclusion: The treatment of gastric lymphoma continues to evolve, and surgical resection is now uncommonly a part of the initial management strategy. C1 SUNY Stony Brook, Hlth Sci Ctr, Dept Surg, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Karpeh, MS (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Surg, T-18 Stony Brook, Stony Brook, NY 11794 USA. EM mkarpeh@notes.cc.sunysb.edu NR 75 TC 57 Z9 67 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 2004 VL 240 IS 1 BP 28 EP 37 DI 10.1097/01.sla.0000129356.81281.0c PG 10 WC Surgery SC Surgery GA 832PS UT WOS:000222280000006 PM 15213615 ER PT J AU Mathis, D AF Mathis, D TI The end stage of arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 30 EP 30 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500092 ER PT J AU Lee, DM Brenner, MB Mathis, DJ Benoist, C Gerard, CJ Nigrovic, P AF Lee, DM Brenner, MB Mathis, DJ Benoist, C Gerard, CJ Nigrovic, P TI Synovial mast cells require C5A receptor (CD88) and IGG FC receptors for arthritis induction SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 39 EP 39 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500123 ER PT J AU Tzioufas, AG Moutsopoulos, HM AF Tzioufas, AG Moutsopoulos, HM TI Lymphoma in Sjogren's syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY ID MORTALITY C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 39 EP 40 PG 2 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500125 ER PT J AU Scott, TE Mendez, MV LaMorte, WW Cupples, LA Vokonas, PS Garcia, RI Menzoian, JO AF Scott, TE Mendez, MV LaMorte, WW Cupples, LA Vokonas, PS Garcia, RI Menzoian, JO TI Are varicose veins a marker for susceptibility to coronary heart disease in men? Results from the normative aging study SO ANNALS OF VASCULAR SURGERY LA English DT Article ID EPIDEMIOLOGY AB Clinical observations suggest that varicose veins (VV) are less frequent in patients undergoing infrainguinal bypass surgery for femoral artery occlusive disease. While some previous studies support this relationship, others report that VV are more prevalent in coronary heart disease patients (CHD). This study used the Normative Aging Study (NAS) population to examine the association between VV and symptomatic CHD. The incidence of CHD over 35 years of follow-up was determined in the 2280 initially healthy male volunteers enrolled in the NAS. The incidence of CHD in the VV population and the subjects without VV were compared using Kaplan-Meier survival curves and the log-rank test. A time-dependent proportional hazards regression method was used to further explore the relationship between VV disease and subsequent development of CHD after adjusting for other cardiovascular risk factors. A total of 569 subjects (24.9%) were diagnosed with VV prior to the development of symptomatic CHD, and 1708 (75.1%) were not. Over 35 years of follow-up, 98 subjects with VV developed symptomatic CH D (17.2%), while 363 of those without VV subsequently developed symptomatic CHD (21.2%). Kaplan-Meier survival curves suggested a reduced risk of symptomatic CHD for subjects with VV (p=0.0001). Further exploration of this relationship in a proportional hazards multivariate model showed VV to be associated with a 36% decreased risk of symptomatic CHD after adjusting for other recognized cardiovascular risk factors. In the NAS population, men with VV were less likely to develop symptomatic CHD over the 35+ years of follow-up than were subjects without VV. C1 Boston Med Ctr, Dept Surg, Vasc Surg Sect, Boston, MA 02118 USA. Boston Med Ctr, Surg Res Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. RP Menzoian, JO (reprint author), Boston Med Ctr, Dept Surg, Vasc Surg Sect, 88 E Newton St, Boston, MA 02118 USA. EM james.menzoian@bmc.org OI Scott, Thayer/0000-0003-3900-3244; Garcia, Raul/0000-0003-2153-4629; Cupples, L. Adrienne/0000-0003-0273-7965 FU NIDCR NIH HHS [K24 DE-00419] NR 10 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 2004 VL 18 IS 4 BP 459 EP 464 DI 10.1007/s10016-004-0056-z PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 838ZD UT WOS:000222752200012 PM 15156364 ER PT J AU Pardo, FS Aronen, HJ Fitzek, M Kennedy, DN Efird, J Rosen, BR Fischman, AJ AF Pardo, FS Aronen, HJ Fitzek, M Kennedy, DN Efird, J Rosen, BR Fischman, AJ TI Correlation of FDG-PET interpretation with survival in a cohort of glioma patients SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 6th International Congress of Radiation Oncology CY 2001 CL MELBOURNE, AUSTRALIA DE glioma; central nervous system; tumor progression; brain imaging ID HUMAN-BRAIN-TUMORS; GLUCOSE-UPTAKE; BLOOD-VOLUME; RADIOTHERAPY; PREDICTION; MODELS AB Adult supratentorial gliomas continue to be one of the most challenging diagnostic and therapeutic problems for the neuro-oncologist. Despite a variety of therapeutic approaches, local control and survival rates remain disappointingly low, largely due to a relative inability to localize diffusely infiltrating glial tumor cells. FDG PET provides a relatively noninvasive method for studying glucose metabolism in normal and pathologic brain tissues. In order to assess the usefulness of FDG PET in a prospective cohort of patients, a group of 31 glial tumor patients underwent serial FDG PET scans at specified evaluation time points: initial or perioperative scan; scan following completion of radiation or chemotherapy; scan(s) at 3-month follow-up intervals until last follow-up exam or death. FDG PET score categories were established to provide a visual and clinically useful means for assessing tumor progression and response to treatment. Both progression-free and overall actuarial survival were determined. There were a total of 137 scans interpreted, on a semi-quantitative basis, by two board-certified radiologists. Patients with high FDG PET scores were more likely to progress clinically and demonstrated lower overall actuarial survival times and revealed statistically significant correlations with other determinants of survival (p<0.05, Kaplan Meier). Further prospective studies on an expanded patient population are necessary in order to define the role of FDG PET, compared with conventional magnetic resonance imaging (MRI) and computed tomography (CT), in the evaluation and care of patients with malignant gliomas. C1 Univ Calif San Diego, Div Radiat Oncol, Dept Radiol, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Turku Univ Hosp, Dept Radiol, Helsinki, Finland. Stanford Univ, Div Stat, Med Ctr, Palo Alto, CA 94304 USA. Humboldt Univ, Dept Radiat Oncol, Charite, Berlin, Germany. RP Pardo, FS (reprint author), Univ Calif San Diego, Div Radiat Oncol, Dept Radiol, San Diego, CA 92103 USA. RI Kennedy, David/H-3627-2012 FU NCI NIH HHS [1 K08 CA1761] NR 24 TC 17 Z9 18 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2004 VL 24 IS 4 BP 2359 EP 2365 PG 7 WC Oncology SC Oncology GA 852BY UT WOS:000223731400034 PM 15330185 ER PT J AU Sund, M Xie, L Kalluri, R AF Sund, M Xie, L Kalluri, R TI The contribution of vascular basement membranes and extracellular matrix to the mechanics of tumor angiogenesis SO APMIS LA English DT Review DE basement membrane; angiogenesis; collagen; integrins; MMP; proteases; cancer; extracellular matrix ID DISTINCT ANTITUMOR PROPERTIES; HUMAN ALPHA-1(XV) COLLAGEN; IV COLLAGEN; XV COLLAGEN; ENDOTHELIAL-CELLS; ALPORT SYNDROME; HUMAN ENDOSTATIN; BLOOD-VESSELS; ALPHA(V)BETA(3) INTEGRIN; NONCOLLAGENOUS DOMAINS AB The goal of this review is to highlight the contribution of extracellular matrix and vascular basement membranes to the regulation of angiogenesis and tumor progression. Here we present a new concept that vascular basement membrane influences endothelial cells and possibly other cell types in a solid state assembled form, and also in a degraded solution state form. Depending on the structural integrity, composition and exposure of cryptic sites, the vascular basement membrane proteome exerts functional influences on proliferating and resting endothelial cells. This review provides the reader with an appreciation of this newly evolved concept in the area of vascular biology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Matrix Biol, Boston, MA 02125 USA. RP Sund, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Matrix Biol, 330 Brookline Ave, Boston, MA 02125 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015 OI Sund, Malin/0000-0002-7516-9543; Kalluri, Raghu/0000-0002-2190-547X FU NIDDK NIH HHS [DK55001, DK62987] NR 105 TC 40 Z9 42 U1 0 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD JUL-AUG PY 2004 VL 112 IS 7-8 BP 450 EP 462 DI 10.1111/j.1600-0463.2004.t01-1-apm11207-0806.x PG 13 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 878JL UT WOS:000225643000006 PM 15563309 ER PT J AU Renno, RZ Terada, Y Haddadin, MJ Michaud, NA Gragoudas, ES Miller, JW AF Renno, RZ Terada, Y Haddadin, MJ Michaud, NA Gragoudas, ES Miller, JW TI Selective photodynamic therapy by targeted verteporfin delivery to experimental choroidal neovascularization mediated by a homing peptide to vascular endothelial growth factor receptor-2 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID VIVO PROTEIN TRANSDUCTION; IN-VIVO; MACULAR DEGENERATION; FACTOR ANTIBODY; NORMAL RETINA; MODEL; VEGF; BENZOPORPHYRIN; ANGIOGENESIS; MOUSE AB Objective: To evaluate the feasibility, efficacy, and selectivity of photodynamic therapy (PDT) using targeted delivery of verteporfin to choroidal neovascularization (CNV) in the rat laser-injury model of CNV. Methods: We performed PDT in rat eyes on experimental CNV and normal retina and choroid using verteporfin conjugates. A targeted verteporfin conjugate was made by conjugating verteporfin (after isolation from its liposomal formulation) to a modified polyvinyl alcohol (PVA) polymer (verteporfin-PVA) followed by linkage to the peptide ATWLPPR known to bind the receptor for vascular endothelial growth factor, VEGFR2. The verteporfin-PVA conjugate served as a control. We performed fluorescent fundus angiography to determine the optimal timing of light application for PDT using the conjugates. Closure of CNV was assessed angiographically and graded in a masked standardized fashion. We used standardized histological grading to compare the effects on normal retina and choroid. Results: The verteporfin-PVA conjugation ratio was on average 28:1. The conjugate retained typical emission/excitation spectra and photosensitizing activity and was as efficient as an equivalent amount of verteporfin. Peak intensity of targeted verteporfin in CNV was detected angiographically at 1 hour after intravenous injection. Photodynamic therapy using targeted verteporfin (3 or 4.5 mg/m(2)) with light application I hour after drug injection showed angiographic closure of all treated CNV (17/17) 1. day after treatment. Photodynamic therapy using verteporfin-PVA at the same drug dose achieved closure in 18 of 20 CNV. Histological examination after PDT of normal retina and choroid using targeted verteporfin and irradiation at I hour showed minimal effect on retinal pigment epithelium and no injury to photoreceptors, whereas PDT using verteporfin-PVA resulted in retinal pigment epithelium necrosis and mild damage to photoreceptors. Conclusions: Verteporfin bound to the targeting peptide, ATWLPPR, retained its spectral and photosensitizing properties. Angiography demonstrated localization of the targeted verteporfin I hour after injection. Photodynamic therapy using targeted verteporfin and the control conjugate were more effective in causing CNV closure than standard liposomal verteporfin. The targeted verteporfin resulted in more selective treatment than the control conjugate or standard verteporfin. These results suggest that targeted PDT strategies based on selective expression of receptors on CNV vasculature may improve current therapy. Clinical Relevance: Targeted PDT for CNV is feasible and may offer a qualitative improvement in current treatments for patients with age-related macular degeneration. This study provides the basis for further preclinical studies of targeted PDT strategies and subsequent clinical trials. C1 Harvard Univ, Retina Serv, Angiogenesis & Laser Res Lab,Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02114 USA. Amer Univ Beirut, Dept Chem, Beirut, Lebanon. RP Miller, JW (reprint author), Harvard Univ, Retina Serv, Angiogenesis & Laser Res Lab,Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu NR 38 TC 48 Z9 51 U1 1 U2 9 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 2004 VL 122 IS 7 BP 1002 EP 1011 DI 10.1001/archopht.122.7.1002 PG 10 WC Ophthalmology SC Ophthalmology GA 838HF UT WOS:000222703400008 PM 15249365 ER PT J AU Chiu, CS Dryja, TP Lessell, S AF Chiu, CS Dryja, TP Lessell, S TI A "negative" temporal artery biopsy, positive for arteritis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID VASCULITIS C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Lessell, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St,9th Floor, Boston, MA 02114 USA. EM simmons_lessell@meei.harvard.edu NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2004 VL 122 IS 7 BP 1074 EP 1075 DI 10.1001/archopht.122.7.1074 PG 2 WC Ophthalmology SC Ophthalmology GA 838HF UT WOS:000222703400025 PM 15249381 ER PT J AU Mehta, RP Faquin, WC Franco, RA AF Mehta, RP Faquin, WC Franco, RA TI Pathology quiz case 2 SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID ANGIOMYOMA VASCULAR LEIOMYOMA; ANGIOLEIOMYOMA; LARYNX; TUMOR C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Mehta, RP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2004 VL 130 IS 7 BP 889 EP + DI 10.1001/archotol.130.7.889-a PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 838GN UT WOS:000222701600014 PM 15262769 ER PT J AU Lee, KC Finkelstein, JA Miroshnik, IL Rusinak, D Santoli, JM Lett, SM Lieu, TA AF Lee, KC Finkelstein, JA Miroshnik, IL Rusinak, D Santoli, JM Lett, SM Lieu, TA TI Pediatricians' self-reported clinical practices and adherence to national immunization guidelines after the introduction of pneumococcal conjugate vaccine SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ ID HEPATITIS-B-VACCINE; MULTIPLE INJECTIONS; FEBRILE CHILDREN; OFFICE SETTINGS; UNITED-STATES; RECOMMENDATIONS; IMPACT; ADOLESCENTS; MANAGEMENT; INFECTION AB Background: Little is known about whether pneumococcal conjugate vaccine (PCV) has altered pediatricians' practices regarding well-child and acute care. Objectives: To (1) describe whether PCV caused pediatricians to move other routine infant vaccines and/or add routine visits; (2) characterize adherence to national immunization recommendations; and (3) determine whether PCV altered pediatricians' planned clinical approach to well-appearing febrile infants. Design and Methods: One year after PCV was added to the pediatric immunization schedule, we mailed a 23-item survey to 691 randomly selected pediatricians in Massachusetts. The adjusted response rate was 77%. Results: After PCV introduction, 39% of pediatricians moved other routine infant vaccines to different visits and 15% added routine visits to the infant schedule. The self-reported immunization schedules of 36% were nonadherent to national immunization guidelines for at least 1 vaccine. Nonadherence rates were significantly higher among pediatricians who had been in practice longer, moved another vaccine because of PCV introduction, and/or offered to give shots later when multiple injections were due. For a hypothetical febrile 8-month-old girl who had received 3 doses of PCV, pediatricians reported they were significantly less likely to (1) perform both blood and urine testing and (2) prescribe antibiotics than in the pre-PCV era. Conclusions: The introduction of PCV may have had unintended effects on pediatric primary care, including decreased adherence to national recommendations for the timing of immunizations and decreased urine testing for well-appearing febrile infants. Special efforts may be warranted to ensure that pediatricians remain current with changing recommendations. C1 Harvard Univ, Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Ctr Child Hlth Care Studies, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Pediat Hlth Serv Res Fellowship, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Massachusetts Dept Publ Hlth, Div Epidemiol & Immunizat, Boston, MA USA. RP Lieu, TA (reprint author), Harvard Univ, Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Ctr Child Hlth Care Studies, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM tracy_lieu@harvardpilgrim.org NR 30 TC 20 Z9 20 U1 2 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 JUL PY 2004 VL 158 IS 7 BP 695 EP 701 DI 10.1001/archpedi.158.7.695 PG 7 WC Pediatrics SC Pediatrics GA 836PY UT WOS:000222569200014 PM 15237070 ER PT J AU Zhang, L Plotkin, RC Wang, G Sandel, ME Lee, S AF Zhang, L Plotkin, RC Wang, G Sandel, ME Lee, S TI Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE acetylcholine; brain injuries; cognition disorders; rehabilitation ID PLACEBO-CONTROLLED TRIAL; DIFFUSE AXONAL INJURY; ALZHEIMERS-DISEASE; HEAD-INJURY; DOUBLE-BLIND; REHABILITATION; SYSTEMS; ACETYLCHOLINE; SCALE; RAT AB Objective: To examine effects of donepezil on short-term memory and sustained attention in postacute patients with traumatic brain injury (TBI). Design: A 24-week, randomized, placebo-controlled, double-blind crossover trial. Setting: Outpatient clinics in 2 teaching hospitals. Participants: Eighteen postacute TBI patients with cognitive impairment. Intervention: Patients were randomly assigned to group A or group B. Patients in group A received donepezil for the first 10 weeks and then a placebo for another 10 weeks. The 2 treatment phases were separated by a washout period of 4 weeks. Patients in group B received the preparations in the opposite order. Main Outcome Measures: Short-term memory and sustained attention were assessed by 2 indexes (Auditory Immediate Index [All], Visual Immediate Index [VII]) of the Wechsler Memory Scale-III and the Paced Auditory Serial Addition Test (PASAT), at baseline, week 10, and week 24 of the trial. Results: Intragroup comparison of different phases of the trial in both groups showed that donepezil significantly increased the testing scores of the All and VII, as well as PASAT scores, compared with baseline. There was no significant change in the testing scores between assessment at baseline and the end of the placebo phase in group B. Intergroup comparison at the 10-week assessment showed significantly improved testing scores in group A with donepezil over group B with the placebo. The improved testing scores with donepezil in group A were sustained after the washout period and placebo phase, suggesting a carry-over effect of the medication. Conclusions: Donepezil increased neuropsychologic testing scores in short-term memory and sustained attention in post-acute TBI patients. Cholinergic augmentation may be a viable approach to restore memory and attention after TBI. (C) 2004 by the American Congress of Rehabilitation Medici. ne and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78285 USA. Dept Vet Affairs Med Ctr, San Antonio, TX USA. Univ Penn, Ctr Med, Philadelphia, PA 19104 USA. SUNY Syracuse, Upstate Med Univ, Syracuse, NY 13210 USA. Kaiser Fdn Rehabil Ctr, Vallejo, CA USA. RP Zhang, L (reprint author), San Antonio Brain & Spine Consultants, 19114 La Verita, San Antonio, TX 78258 USA. EM neurorehab@yahoo.com NR 38 TC 87 Z9 90 U1 0 U2 7 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 2004 VL 85 IS 7 BP 1050 EP 1055 DI 10.1016/j.apmr2003.10.014 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 835XU UT WOS:000222519600002 PM 15241749 ER PT J AU Bodenheimer, CF Roig, RL Worsowicz, GM Cifu, DX AF Bodenheimer, CF Roig, RL Worsowicz, GM Cifu, DX TI Geriatric rehabilitation. 5. The societal aspects of disability in the older adult SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE automobile driving; ethics; geriatrics; rehabilitation; sexuality; vocations ID ELDER ABUSE; DEMENTIA; STROKE; RESTRICTIONS; DYSFUNCTION; WOMEN; RISK AB This self-directed learning module highlights the societal aspects of disability and the older adult. It is part of the study guide on geriatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and geriatric medicine. This article specifically focuses on ethical issues, including capacity, psychodynamics, sexuality, community integration, work, leisure skills, and the issue of driving a motor vehicle. Overall Article Objective: To summarize the societal aspects of disability and the older adult. C1 Philadelphia VA Med Ctr, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. Northlake Rehabil Profess, Hammond, LA USA. Univ Missouri, Dept Phys Med & Rehabil, Columbia, MO USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Phys Med & Rehabil, Richmond, VA 23298 USA. RP Bodenheimer, CF (reprint author), Philadelphia VA Med Ctr, Dept Phys Med & Rehabil, RMS 117,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Carol.Bodenheimer2@med.va.gov NR 35 TC 2 Z9 2 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2004 VL 85 IS 7 SU 3 BP S23 EP S26 DI 10.1016/j.apmr.2004.03.009 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 837ZG UT WOS:000222679600006 PM 15221719 ER PT J AU Phillips, EM Bodenheimer, CF Roig, RL Cifu, DX AF Phillips, EM Bodenheimer, CF Roig, RL Cifu, DX TI Geriatric rehabilitation. 4. Physical medicine and rehabilitation interventions for common age-related disorders and geriatric syndromes SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE activities of daily living; behavior; bladder; bowel; cognition; disability; exercise; geriatrics; osteoporosis; rehabilitation ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED TRIAL; ESTROGEN PLUS PROGESTIN; BONE-MINERAL DENSITY; URINARY-INCONTINENCE; HIP FRACTURE; FECAL INCONTINENCE; OSTEOPOROSIS; RISK; CONSTIPATION AB This self-directed learning module highlights physical medicine and rehabilitation (PM&R) interventions for age-related physiologic changes. It is part of the study guide on geriatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in PM&R and geriatric medicine. This article specifically focuses on PM&R interventions (including exercise) for mobility alterations, activities of daily living alterations, osteoporosis, cognitive and behavioral changes, bladder changes, and bowel changes. Overall Article Objective: To summarize the physical medicine and rehabilitation interventions for age-related physiologic changes. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Philadelphia VA Med Ctr, Dept Phys Med & Rehabil, Philadelphia, PA USA. Northlake Rehabil Profess, Dept Phys Med & Rehabil, Hammond, LA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Phys Med & Rehabil, Richmond, VA 23298 USA. RP Phillips, EM (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM ephillips1@partners.org NR 42 TC 3 Z9 3 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2004 VL 85 IS 7 SU 3 BP S18 EP S22 DI 10.1016/j.apmr.2004.03.008 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 837ZG UT WOS:000222679600005 PM 15221718 ER PT J AU Stewart, DG Phillips, EM Bodenheimer, CF Cifu, DX AF Stewart, DG Phillips, EM Bodenheimer, CF Cifu, DX TI Geriatric rehabilitation. 2. Physiatric approach to the older adult SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE falls; geriatrics; pain; pharmacology; prevention; rehabilitation ID EVIDENCE-BASED MEDICINE; PAIN MANAGEMENT; VULNERABLE ELDERS/; QUALITY INDICATORS; PATIENT SAFETY; IMPROVE; COMMUNITY; FALLS; CARE; RELIABILITY AB This self-directed learning module highlights the physiatric approach to the older adult. It is part of the study guide on geriatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation (PM&R) and geriatric medicine. This article specifically focuses' on the advantages of the physiatric approach, PM&R training in geriatric rehabilitation, metrics in geriatric assessment, prevention, symptom management, medical management, falls, pain, and pharmacology. Overall Article Objective: To summarize the physiatric approach to the older adult. C1 Brooks Hlth Syst Adm, Jacksonville, FL USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. Philadelphia VA Med Ctr, Dept Phys Med & Rehabil, Philadelphia, PA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Phys Med & Rehabil, Richmond, VA 23298 USA. RP Stewart, DG (reprint author), Brooks Rehabil Hosp, 3599 Univ Blvd, Jacksonville, FL 32216 USA. EM deborah.stewart@brookshealth.org NR 41 TC 2 Z9 2 U1 3 U2 4 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 2004 VL 85 IS 7 SU 3 BP S7 EP S11 DI 10.1016/j.apmr.2004.03.006 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 837ZG UT WOS:000222679600003 PM 15221716 ER PT J AU Kim, DH Gill, TJ Millett, PJ AF Kim, DH Gill, TJ Millett, PJ TI Arthroscopic treatment of the arthrofibrotic knee SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE knee; arthrofibrosis; arthroscopy; stiffness; motion loss; lysis of adhesions ID ANTERIOR CRUCIATE LIGAMENT; FOLLOW-UP; CONTRACTURE SYNDROME; OPERATIVE TREATMENT; PATELLA-INFERA; CYCLOPS LESION; RECONSTRUCTION; MOTION; MANAGEMENT; DISLOCATION AB The management of motion loss of the knee is challenging. A clear understanding of the pathoanatomic causes of motion loss is necessary to establish a careful and rational approach to treatment. Early recognition and physical therapy are effective for the majority of patients, but when these conservative measures fail, operative intervention is indicated. The purpose of this article is to outline a comprehensive approach to the arthroscopic evaluation and treatment of the arthrofibrotic knee. This technique is designed to allow the surgeon to systematically address the numerous causes of motion loss of the knee. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Millett, PJ (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. EM pmillett@partners.org NR 46 TC 18 Z9 20 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD JUL-AUG PY 2004 VL 20 IS 6 SU 1 BP 187 EP 194 DI 10.1016/j.arthro.2004.04.036 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 839HJ UT WOS:000222774300045 PM 15243457 ER PT J AU Fehr, T Kahlert, C Fierz, W Joller-Jemelka, HI Riesen, WF Rickli, H Wuthrich, RP Ammann, P AF Fehr, T Kahlert, C Fierz, W Joller-Jemelka, HI Riesen, WF Rickli, H Wuthrich, RP Ammann, P TI Statin-induced immunomodulatory effects on human T cells in vivo SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; inflammation; HMG-CoA reductase inhibitors; T cells; MHC class II; immunomodulation; transplant rejection ID C-REACTIVE PROTEIN; COA REDUCTASE INHIBITOR; UNSTABLE ANGINA; FLOW-CYTOMETRY; INFLAMMATION; PRAVASTATIN; SIMVASTATIN; DISEASE; TRANSPLANTATION; ATORVASTATIN AB Statins are widely used for treatment of hypercholesterolemia. Recent experimental studies revealed that these drugs also exert anti-inflammatory effects. The aim of this study was to assess immunomodulatory effects of statins in humans in vivo. Twenty-seven healthy volunteers were analyzed for serum Cytokines and acute phase proteins, HLA-DR and CD38 expression on T cells and superantigen-mediated T cell activation ex vivo before and after 14 days of statin treatment. First, simvastatin 40 ring was compared to atorvastatin 20 mg. Second, two different doses of simvastatin (20 and 40 mg) were tested. Atorvastatin treatment led to a significant down-regulation of HLA-DR and the CD38 activation marker on peripheral T cells, whereas simvastatin up-regulated both of these molecules. In contrast, superantigen-mediated T cell activation was inhibited by simvastatin and enhanced by atorvastatin. No significant effect of statin treatment on inflammatory serum markers was detected. Thus. immunomodulatory effects of statins on human T cells are first demonstrated in vivo and are differentially induced by two different statins: atorvastatin led to a major histocompatibility class II (MHC II) antigens down-regulation and may therefore be investigated for treatment of chronic transplant rejection; simvastatin inhibited superantigen-mediated T cell activation, which might explain reduced mortality of sirrivastatin-treated patients with staphylococcal bacteremia. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Kantonsspital, Div Nephrol, St Gallen, Switzerland. Kantonsspital, Inst Clin Microbiol & Immunol, St Gallen, Switzerland. Univ Zurich Hosp, Div Clin Immunol, CH-8091 Zurich, Switzerland. Kantonsspital, Inst Clin Chem & Hematol, St Gallen, Switzerland. Kantonsspital, Div Cardiol, St Gallen, Switzerland. RP Fehr, T (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E Bldg 149,13th St, Boston, MA 02129 USA. EM thomas.fehr@tbrc.mgh.harvard.edu OI Kahlert, Christian R./0000-0002-0784-3276 NR 34 TC 72 Z9 83 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL PY 2004 VL 175 IS 1 BP 83 EP 90 DI 10.1016/j.atherosclerosis.2004.02.016 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 832QS UT WOS:000222282600011 PM 15186950 ER PT J AU Gorin, Y Ricono, JM Wagner, B Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Wagner, B Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Angiotensin II-induced ERK1/ERK2 activation and protein synthesis are redox-dependent in glomerular mesangial cells SO BIOCHEMICAL JOURNAL LA English DT Article DE angiotensin II; arachidonic acid; extracellular-signal-regulated kinase 1 and 2 (ERK1/ERK2); hypertrophy; Nox4 NADPH oxidase; reactive oxygen species ID SMOOTH-MUSCLE-CELLS; TUBULAR EPITHELIAL-CELLS; ARACHIDONIC-ACID; NAD(P)H OXIDASE; GROWTH-FACTOR; CELLULAR MECHANISMS; SIGNALING PATHWAYS; PHOSPHOLIPASE A(2); KINASE; HYPERTROPHY AB Angiotensin II (Ang II) stimulates hypertrophy of glomerular mesangial cells. The signalling mechanism by which Ang II exerts this effect is not precisely known. Downstream potential targets of Ang II are the extracellular-signal-regulated kinases 1 and 2 (ERK1/ERK2). We demonstrate that Ang II activates ERK1/ERK2 via the AT, receptor. Arachidonic acid (AA) mimics the action of Ang II on ERK1/ERK2 and phospholipase A(2) inhibitors blocked Ang II-induced ERK1/ERK2 activation. The antioxidant N-acetylcysteine as well as the NAD(P)H oxidase inhibitors diphenylene iodonium and phenylarsine oxide abolished both Ang II- and AA-induced ERK1/ERK2 activation. Moreover, dominant-negative Rac1 (N17Rac1) blocks activation of ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity. Antisense oligonucleotides for Nox4 NAD(P)H oxidase significantly reduce activation of ERK1/ERK2 by Ang II and AA. We also show that protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor. These results demonstrate that Ang II stimulates ERK1/ ERK2 by AA and Nox4-derived reactive oxygen species, suggesting that these molecules act as downstream signal transducers of Ang II in the signalling pathway linking the Ang II receptor AT, to ERK1/ERK2 activation. This pathway involving AA, Rac1, Nox4, reactive oxygen species and ERK1/ERK2 may play an important role in Ang II-induced mesangial cell hypertrophy. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Gorin, Y (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gorin@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925; Wagner, Brent/0000-0002-7063-0142 FU NIDDK NIH HHS [R01 DK055815, DK 55815, R01 DK033665, DK 33665, DK 43988, R37 DK033665] NR 43 TC 91 Z9 99 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 2004 VL 381 BP 231 EP 239 DI 10.1042/BJ20031614 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 838PB UT WOS:000222724200027 PM 15027896 ER PT J AU Huber, W Gentleman, R AF Huber, W Gentleman, R TI matchprobes: a Bioconductor package for the sequence-matching of microarray probe elements SO BIOINFORMATICS LA English DT Article AB The nucleotide sequences of the probes on a microarray can be used for a variety of purposes in the analysis of microarray experiments. We describe software and a paradigm for the creation of data packages for curating, distributing and working with probe sequence data in a uniform, across-types-of-microarrays manner. While the implementation is specific to the Bioconductor project, the ideas and general strategies are more general and could be easily adopted by other projects. C1 German Canc Res Ctr, Dept Mol Genome Anal, D-69120 Heidelberg, Germany. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Huber, W (reprint author), German Canc Res Ctr, Dept Mol Genome Anal, INF 580, D-69120 Heidelberg, Germany. EM w.huber@dkfz.de OI Huber, Wolfgang/0000-0002-0474-2218 NR 6 TC 25 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2004 VL 20 IS 10 BP 1651 EP 1652 DI 10.1093/bioinformatics/bth133 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 834HO UT WOS:000222402400029 PM 14988118 ER PT J AU Csutoras, C Zhang, A Zhang, KH Kula, NS Baldessarini, RJ Neumeyer, JL AF Csutoras, C Zhang, A Zhang, KH Kula, NS Baldessarini, RJ Neumeyer, JL TI Synthesis and neuropharmacological evaluation of R(-)-N-alkyl-11-hydroxynoraporphines and their esters SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE apomorphine.; 11-hydroxyaporphine; Parkinson's disease; dopamine receptor; motor activity; bioavailablity ID RECEPTOR INTERACTIONS; DOPAMINE-RECEPTORS; RAT-BRAIN; APORPHINES; DERIVATIVES; BINDING; PHARMACOLOGY; AFFINITY; TISSUE; ACID AB We synthesized several N-substituted-11-hydroxynoraporphines and their esters of varying chain length, evaluated their binding affinity at dopamine (DA) receptor sites in rat caudate-putamen membranes, and quantified their effects on motor activity in normal adult male rats. The 11-hydroxyaporphines showed similar neuropharmacological properties to the corresponding 10,11-catecholaporphines. At moderate doses, their esters proved to have more prolonged behavioral actions and superior oral bioavailability. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, McLean Div, Massachusetts Gen Hosp,Alcohol & Drug Abuse Res C, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Mailman Res Ctr, Belmont, MA 02478 USA. RP Neumeyer, JL (reprint author), Harvard Univ, Sch Med, McLean Div, Massachusetts Gen Hosp,Alcohol & Drug Abuse Res C, 115 Mill St, Belmont, MA 02478 USA. EM neumeyer@mclean.harvard.edu RI zhang, ao/B-8365-2008 NR 20 TC 25 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL 1 PY 2004 VL 12 IS 13 BP 3553 EP 3559 DI 10.1016/j.bmc.2004.04.029 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 831LM UT WOS:000222195900013 PM 15186839 ER PT J AU Bonetti, M Gelber, RD AF Bonetti, M Gelber, RD TI Patterns of treatment effects in subsets of patients in clinical trials SO BIOSTATISTICS LA English DT Article DE breast cancer; STEPP; subset analysis; survival data; treatment-covariate interaction ID POSITIVE BREAST-CANCER; RANDOMIZED-TRIALS; ADJUVANT THERAPY; SURVIVAL-DATA; CHEMOTHERAPY; STATISTICS; TAMOXIFEN; MODEL AB We discuss the practice of examining patterns of treatment effects across overlapping patient subpopulations. In particular, we focus on the case in which patient subgroups are defined to contain patients having increasingly larger (or smaller) values of one particular covariate of interest, with the intent of exploring the possible interaction between treatment effect and that covariate. We formalize these subgroup approaches (STEPP: subpopulation treatment effect pattern plots) and implement them when treatment effect is defined as the difference in survival at a fixed time point between two treatment arms. The joint asymptotic distribution of the treatment effect estimates is derived, and used to construct simultaneous confidence bands around the estimates and to test the null hypothesis of no interaction. These methods are illustrated using data from a clinical trial conducted by the International Breast Cancer Study Group, which demonstrates the critical role of estrogen receptor content of the primary breast cancer for selecting appropriate adjuvant therapy. The considerations are also relevant for general subset analysis, since information from the same patients is typically used in the estimation of treatment effects within two or more subgroups of patients defined with respect to different covariates. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bonetti, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM bonetti@jimmy.harvard.edu OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA-06516, CA-75362] NR 25 TC 79 Z9 79 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2004 VL 5 IS 3 BP 465 EP 481 DI 10.1093/biostatistics/kxh002 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 838OV UT WOS:000222723600009 PM 15208206 ER PT J AU Cunningham, MJ Macklin, EA Neufeld, EJ Cohen, AR AF Cunningham, MJ Macklin, EA Neufeld, EJ Cohen, AR CA Thalassemia Clinical Res Network TI Complications of beta-thalassemia major in north America SO BLOOD LA English DT Article ID IRON-CHELATING THERAPY; HEPATITIS-C VIREMIA; COOLEYS-ANEMIA; VIRUS; DISEASE; DEFEROXAMINE; MANAGEMENT; DISORDERS; CLEARANCE; SURVIVAL AB Treatment of patients with beta-thalassemia major has improved dramatically during the past 40 years; however, the current clinical status of these patients remains poorly characterized. We performed a cross-sectional study of 342 patients in the Registry of the National Institutes of Health-sponsored Thalassemia Clinical Research Network. Evidence of hepatitis C exposure was present in 35% of tested patients, was associated with age, and had a rate of spontaneous viral clearance of 33%. Ferritin levels ranged from 147 to 11010 ng/mL (median, 1696 ng/mL). Median hepatic iron content was 7.8 mg/g dry weight and 23% of patients had values of 15 mg/g dry weight or higher. No patients 15 years or younger and 5% of patients aged 16 to 24 years had heart disease requiring medication. Ten percent had cirrhosis on biopsy. Endocrinologic complications were common among adults. Seventy-four (22%) patients had recent implantable central venous access devices (CVADs) placed. Among 80 episodes of bacteremia in 38 patients, 90% were attributable to the CVAD. Among 330 patients who had received deferoxamine chelation therapy, 224 (68%) reported no complications. We conclude that hepatitis C, iron-related organ dysfunction, and complications of iron chelation therapy are strongly age-dependent in North American patients with beta-thalassemia. (C) 2004 by The American Society of Hematology. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol, 300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 32 TC 213 Z9 216 U1 1 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 1 PY 2004 VL 104 IS 1 BP 34 EP 39 DI 10.1182/blood-2003-09-3167 PG 6 WC Hematology SC Hematology GA 832ZZ UT WOS:000222307500013 PM 14988152 ER PT J AU Van Cott, EM Laposata, M Hartnett, ME AF Van Cott, EM Laposata, M Hartnett, ME TI Prothrombin gene mutation G20210A, homocysteine, antiphospholipid antibodies and other hypercoagulable states in ocular thrombosis SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE antiphospholipid antibodies; antithrombin; factor V Leiden; hypercoagulable state; homocysteine; ocular thrombosis; protein C; protein S; prothrombin G2021 0A; lupus anticoagulant; anticardiolipin antibodies ID RETINAL VEIN OCCLUSION; PROTEIN-C RESISTANCE; FACTOR-V; VENOUS THROMBOSIS; YOUNG-ADULTS; RISK-FACTORS; HYPERHOMOCYSTEINEMIA; ANTICOAGULANT; DEFICIENCIES; SYMPTOMS AB The purpose of the present study was to determine whether using an extended panel of laboratory tests increases the detection of a hypercoagulable state in patients with ocular thromboses. Twenty consecutive patients with ocular thromboses (vein, artery, or choriocapillaris occlusions) underwent testing for activated protein C resistance/factor V Leiden, prothrombin G20210A, lupus anticoagulant, anticardiolipin antibodies, hyperhomocysteinemia, and deficiencies of protein C, protein S, and antithrombin. For each patient, we selected two age-matched and gender-matched individuals without ocular thromboses as controls. Sixteen of the 20 patients (80%) had one or more laboratory tests that supported a hypercoagulable condition. Prothrombin G20210A (P < 0.02) and hyperhomocysteinernia (P < 0.0006) were significantly more frequent in ocular thrombosis patients compared with controls. The most common condition was antiphospholipid antibody syndrome, present in 40% of patients (confirmed by repeat testing at least 6 weeks later), but this did not reach statistical significance compared with the controls. No patients with ocular thromboses had hereditary abnormalities of protein S, protein C, or antithrombin. In conclusion, an extended panel of laboratory tests improved the detection of a hypercoagulable state in ocular thromboses. Testing for homocysteine, antiphospholipid antibodies, and the prothrombin G20210A mutation should be considered in patients with ocular thromboses. (C) 2004 Lippincott Williams Wilkins. C1 Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hartnett, ME (reprint author), Univ N Carolina, Dept Ophthalmol, 5109D Bioinformat Bldg,130 Mason Farm Rd,CB 7040, Chapel Hill, NC 27599 USA. EM hartnet@med.unc.edu NR 33 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD JUL PY 2004 VL 15 IS 5 BP 393 EP 397 DI 10.1097/01.mbc.0000114442.59147.8d PG 5 WC Hematology SC Hematology GA 839HE UT WOS:000222773700004 PM 15205587 ER PT J AU Alyea, EP Canning, C Neuberg, D Daley, H Houde, H Giralt, S Champlin, R Atkinson, K Soiffer, RJ AF Alyea, EP Canning, C Neuberg, D Daley, H Houde, H Giralt, S Champlin, R Atkinson, K Soiffer, RJ TI CD8+cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study SO BONE MARROW TRANSPLANTATION LA English DT Article DE donor lymphocyte infusion; CD8; allogeneic ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; HOST-DISEASE; LEUKOCYTE TRANSFUSIONS; HEMATOLOGIC RELAPSE; IMPROVED SURVIVAL; MULTIPLE-MYELOMA; REMISSION AB A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8 + T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4 + T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8 + cells was 99.3% (97.8- >499.5%). CD8 depletion was highly specific, with a median recovery of CD4 + cells of 75%. A median of 2.9 x 10(7) CD4 + cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8 + T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD. C1 Dana Farber Canc Inst, Dept Adult Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Biotransplant Inc, Charlestown, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM edwin_alyea@DFCI.Harvard.edu FU NIAID NIH HHS [AI29530] NR 36 TC 34 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2004 VL 34 IS 2 BP 123 EP 128 DI 10.1038/sj.bmt.1704536 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 834CF UT WOS:000222388500005 PM 15133487 ER PT J AU Gertz, MA Blood, E Vesole, DH Abonour, R Lazarus, HM Greipp, PR AF Gertz, MA Blood, E Vesole, DH Abonour, R Lazarus, HM Greipp, PR TI A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study SO BONE MARROW TRANSPLANTATION LA English DT Article DE amyloidosis; myeloma; transplantation ID PRIMARY SYSTEMIC AMYLOIDOSIS; HIGH-DOSE CHEMOTHERAPY; AL AMYLOIDOSIS; MULTIPLE-MYELOMA; RANDOMIZED-TRIAL; INTRAVENOUS MELPHALAN; NEPHROTIC SYNDROME; PROGNOSTIC-FACTOR; VINCRISTINE; PREDNISONE AB Stem cell transplantation was introduced as a new therapeutic modality for amyloidosis. The purpose of the current study was to determine the feasibility and toxicity of stem cell transplantation for amyloidosis in a cooperative group setting in which most participating institutions would have limited experience in managing the disorder. A total of 30 patients with biopsy-proven amyloidosis shown to be immunoglobulin light-chain type were enrolled on this trial. The protocol required mobilization of a minimum of 6 x 10(8) mononuclear cells/kg or 5 x 10(6) CD34(+) cells/kg ideal body weight. These targets had to be achieved within seven collections. Patients with advanced hepatic, renal, or cardiac failure were excluded. End points included objective response rate and overall survival. The secondary end point of the protocol was nonhematologic toxicity. Accrual to the study was faster than expected. The overall response rate (hematologic and organ) was 64%, with three treatment-related deaths. Another patient died before day 30 of sudden cardiac death not treatment related. The median follow-up of surviving patients is 30.3 months. Median survival has not been reached. Stem cell transplantation for selected patients with amyloidosis is feasible in a cooperative group setting. A multicenter phase 3 trial of high-dose therapy is indicated. C1 Mayo Clin, Div Hematol & Internal Med, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Gertz, MA (reprint author), Mayo Clin, Div Hematol & Internal Med, 200 1st St SW, Rochester, MN 55905 USA. EM gertz.morie@mayo.edu FU NCI NIH HHS [CA23318, CA13650, CA6636, CA21115, CA49883] NR 38 TC 32 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 2004 VL 34 IS 2 BP 149 EP 154 DI 10.1038/sj.bmt.1704539 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 834CF UT WOS:000222388500009 PM 15156165 ER PT J AU Shao, C Held, KD Folkard, M Michael, BD Prise, KM AF Shao, C Held, KD Folkard, M Michael, BD Prise, KM TI Oestrogen modulation of a radiation-induced bystander effect in targeted breast cells SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract CT British Cancer Research Meeting 2004 CY JUN 27-30, 2004 CL Manchester, ENGLAND C1 Mt Vernon Hosp, Gray Canc Inst, Northwood HA6 2JR, Middx, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 NR 0 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 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 2004 VL 91 SU 1 BP S47 EP S47 PG 1 WC Oncology SC Oncology GA 841YN UT WOS:000222968700175 ER PT J AU Hettiaratchy, S Randolph, MA Petit, F Lee, WPA Butler, PEM AF Hettiaratchy, S Randolph, MA Petit, F Lee, WPA Butler, PEM TI Composite tissue allotransplantation - a new era in plastic surgery? SO BRITISH JOURNAL OF PLASTIC SURGERY LA English DT Article DE composite tissue transplantation; immunosuppression; tolerance ID RENAL-ALLOGRAFT RECIPIENTS; HAND TRANSPLANTATION; MINIATURE SWINE; FOLLOW-UP; TOLERANCE; CHIMERISM; EXTREMITY; INDUCTION AB Composite tissue allotransplantation (CTA) holds great potential for reconstructive surgery. The recent hand transplants have made this a clinical reality. However, concerns about CTA have divided the medical community. The current transplants require life-long immunosuppression, which could place the recipients at risk of serious complications. In addition despite potent immunosuppression, chronic rejection may still negate any early favourable results. This article will outline the clinical experience of CTA, the major problems of the technique and the potential solutions to these problems. (C) 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02115 USA. CHU Henri Mondor, Dept Plast Reconstruct & Aesthet Surg, Paris, France. Univ Pittsburgh, Sch Med, Div Plast Surg, Pittsburgh, PA USA. Royal Free Hosp, Dept Plast & Reconstruct Surg, London NW3 2QG, England. RP Hettiaratchy, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg,Transplantat Biol Res Ctr, WACC-453, Boston, MA 02114 USA. EM shehan_h@hotmail.com OI Butler, Peter/0000-0001-7419-1493 NR 34 TC 55 Z9 61 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 0007-1226 J9 BRIT J PLAST SURG JI Br. J. Plast. Surg. PD JUL PY 2004 VL 57 IS 5 BP 381 EP 391 DI 10.1016/j.bjps.2004.02.012 PG 11 WC Surgery SC Surgery GA 832ZW UT WOS:000222307200002 PM 15191817 ER PT J AU Hur, C Simon, LS Gazelle, GS AF Hur, C Simon, LS Gazelle, GS TI The cost-effectiveness of aspirin versus cyclooxygenase-2-selective inhibitors for colorectal carcinoma chemoprevention in healthy individuals SO CANCER LA English DT Article DE cancer chemoprevention; colorectal carcinoma; cost-effectiveness; cyclooxygenase-2 selective inhibitors; aspirin ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CORONARY HEART-DISEASE; PRIMARY PREVENTION; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; RHEUMATOID-ARTHRITIS; TASK-FORCE; CANCER; RISK AB BACKGROUND. Aspirin therapy is accepted widely for secondary prevention in patients with documented cardiovascular disease, but there is a growing trend among healthy individuals to use aspirin as primary chemoprevention for both cardiovascular and oncologic diseases. Accruing evidence suggests that cyclooxygenase-2-selective inhibitors (coxibs) may be effective for colorectal carcinoma (CRC) chemoprevention but would not provide the primary cardiac benefit of aspirin. METHODS. A computer-based Markov model simulated hypothetical cohorts of healthy men age 50 years who took either 325 mg of enteric-coated aspirin daily or celecoxib at a dose of 400 mg twice a day. Patients in both cohorts could develop drug-related complications that would lead to its discontinuation. The aspirin group also was modeled to have a decreased rate of coronary ischemic events; however, decreased CRC mortality was not modeled in either group based on the assumption that the two treatments were effective equally in this regard. Data sources included published literature and the Centers for Medicare and Medicaid Services. Endpoints used to compare the two strategies included quality-adjusted life years (QALYs), mortality and complication rates, and cost. The analysis was from a societal perspective with a time horizon of 10 years from age 50 years. Extensive sensitivity analyses were performed. RESULTS. Aspirin therapy resulted in 0.03 more QALYs and cost $23,000 less than coxib therapy over a 10-year period. Compared with the aspirin group, the coxib group had 3.877% more complications and 0.17% more deaths. Alternatively stated, coxib therapy resulted in 1 patient complication or death for every 26 or 588 patients treated with coxibs, respectively. CONCLUSIONS. Assuming equal efficacy in CRC prevention over a 10-year period, aspirin was both more effective and less costly than coxib therapy when used for primary chemoprevention of CRC. (C) 2004 American Cancer Society. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 42 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2004 VL 101 IS 1 BP 189 EP 197 DI 10.1002/cncr.20329 PG 9 WC Oncology SC Oncology GA 830PF UT WOS:000222134200023 PM 15222006 ER PT J AU Brugarolas, J Kaelin, WG AF Brugarolas, J Kaelin, WG TI Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes SO CANCER CELL LA English DT Review ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE CASCADE; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; MAMMALIAN TARGET; TUBEROUS SCLEROSIS; SIGNALING PATHWAY; CANCER; TSC2 AB The LKB1 tumor suppressor protein controls the activity of the TSC1/TSC2 tumor suppressor complex. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), and mutations in either TSC1 or TSC2 cause tuberous sclerosis complex-two syndromes characterized by the development of hamartomas. LKB1 activation by energy deprivation activates AMPK, which in turn phosphorylates and activates TSC2. TSC2 activation results in the inactivation of mTOR, a critical regulator of protein translation. How mTOR dysregulation after inactivation of LKB1 or TSC1/2 contributes to hamartoma development is not known. However, hypoxia-inducible factor (HIF) and VEGF are regulated by mTOR and are likely to play a contributory role. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 47 TC 113 Z9 118 U1 3 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2004 VL 6 IS 1 BP 7 EP 10 DI 10.1016/j.ccr.2004.06.020 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 842FE UT WOS:000222987900004 PM 15261137 ER PT J AU Allinen, M Beroukhim, R Cai, L Brennan, C Lahti-Domenici, J Huang, HY Porter, D Hu, M Chin, L Richardson, A Schnitt, S Sellers, WR Polyak, K AF Allinen, M Beroukhim, R Cai, L Brennan, C Lahti-Domenici, J Huang, HY Porter, D Hu, M Chin, L Richardson, A Schnitt, S Sellers, WR Polyak, K TI Molecular characterization of the tumor microenvironment in breast cancer SO CANCER CELL LA English DT Article ID HUMAN MYOEPITHELIAL CELL; COMPARATIVE GENOMIC HYBRIDIZATION; CONTRIBUTE ONCOGENIC SIGNALS; GENE-EXPRESSION PATTERNS; IN-VITRO; EPITHELIAL-CELLS; MICROARRAY ANALYSIS; MAMMARY-CARCINOMA; PHYLLODES TUMORS; MALIGNANT BREAST AB Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Res Comp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, MIT, Cambridge, MA 02142 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [5F32CA94788-02, P50 CA89393-01, T32 CA009172] NR 91 TC 739 Z9 768 U1 11 U2 69 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2004 VL 6 IS 1 BP 17 EP 32 DI 10.1016/j.ccr.2004.06.010 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 842FE UT WOS:000222987900006 PM 15261139 ER PT J AU Kung, AL Zabludoff, SD France, DS Freedman, SJ Tanner, EA Vieira, A Cornell-Kennon, S Lee, J Wang, BQ Wang, JM Memmert, K Naegeli, HU Petersen, F Eck, MJ Bair, KW Wood, AW Livingston, DM AF Kung, AL Zabludoff, SD France, DS Freedman, SJ Tanner, EA Vieira, A Cornell-Kennon, S Lee, J Wang, BQ Wang, JM Memmert, K Naegeli, HU Petersen, F Eck, MJ Bair, KW Wood, AW Livingston, DM TI Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway SO CANCER CELL LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; PROTEIN-PROTEIN INTERACTIONS; ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; FACTOR 1-ALPHA; STRUCTURAL BASIS; BINDING-PROTEIN; HIF-ALPHA; FACTOR-1-ALPHA; ANGIOGENESIS AB Homeostasis under hypoxic conditions is maintained through a coordinated transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway and requires coactivation by the CBP and p300 transcriptional coactivators. Through a target-based high-throughput screen, we identified chetomin as a disrupter of HIF binding to p300. At a molecular level, chetomin disrupts the structure of the CH1 domain of p300 and precludes its interaction with HIF, thereby attenuating hypoxia-inducible transcription. Systemic administration of chetomin inhibited hypoxia-inducible transcription within tumors and inhibited tumor growth. These results demonstrate a therapeutic window for pharmacological attenuation of HIF activity and further establish the feasibility of disrupting a signal transduction pathway by targeting the function of a transcriptional coactivator with a small molecule. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Novartis Pharmaceut Corp, Dept Oncol, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. Novartis Pharma AG Nat Prod Unit, Discovery Technol, CH-4002 Basel, Switzerland. RP Kung, AL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM andrew-kung@dfci.harvard.edu; david_livingston@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X NR 53 TC 311 Z9 329 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2004 VL 6 IS 1 BP 33 EP 43 DI 10.1016/j.ccr.2004.06.009 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 842FE UT WOS:000222987900007 PM 15261140 ER PT J AU Senoo, M Manis, JP Alt, FW McKeon, F AF Senoo, M Manis, JP Alt, FW McKeon, F TI P63 and p73 are not required for the development and p53-dependent apoptosis of T cells SO CANCER CELL LA English DT Article ID KINASE C-ABL; DNA-DAMAGE; INDUCE APOPTOSIS; P53 HOMOLOG; DEATH; ACTIVATION; LYMPHOCYTES; MICE AB The recent discoveries of p63 and p73, homologs of the tumor suppressor p53, raised the possibility of a network of these family members governing cell cycle arrest and apoptosis in response to stress. However, mice lacking p73 show no tendency for spontaneous tumors, and mutations in p63 or p73 are rare in human tumors, rendering any obligate role of these genes in cell death and tumor suppression unclear. In an effort to reconcile these incongruent data, we examined the genetic interactions between p53, p63, and p73 in well-established paradigms of p53-dependent and -independent T cell death using primary, genetically defined lymphocytes. Our findings challenge the generality of the notion that p63 and p73 are required for p53 function or for apoptosis in T cells. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP McKeon, F (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM fmckeon@hms.harvard.edu NR 31 TC 72 Z9 72 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2004 VL 6 IS 1 BP 85 EP 89 DI 10.1016/j.ccr.2004.06.005 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 842FE UT WOS:000222987900011 PM 15261144 ER PT J AU Shaw, RJ Bardeesy, N Manning, BD Lopez, L Kasmatka, M DePinho, RA Cantley, LC AF Shaw, RJ Bardeesy, N Manning, BD Lopez, L Kasmatka, M DePinho, RA Cantley, LC TI The LKB1 tumor suppressor negatively regulates mTOR signaling SO CANCER CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; CELL-CYCLE PROGRESSION; TUBEROUS SCLEROSIS; MAMMALIAN TARGET; GROWTH-FACTOR; ENHANCED SENSITIVITY; CATALYTIC SUBUNIT; MOUSE MODEL AB Germline mutations in LKB1, TSC2, or PTEN tumor suppressor genes result in hamartomatous syndromes with shared tumor biological features. The recent observations of LKB1-mediated activation of AMP-activated protein kinase (AMPK) and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical and biological relationship between LKB1 and mTOR regulation. Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR. These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP 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 NIGMS NIH HHS [R01 GM056203] NR 61 TC 612 Z9 635 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2004 VL 6 IS 1 BP 91 EP 99 DI 10.1016/j.ccr.2004.06.007 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 842FE UT WOS:000222987900012 PM 15261145 ER PT J AU Oh, K Willett, WC Fuchs, CS Giovannucci, EL AF Oh, K Willett, WC Fuchs, CS Giovannucci, EL TI Glycemic index, glycemic load, and carbohydrate intake in relation to risk of distal colorectal adenoma in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; DENSITY-LIPOPROTEIN CHOLESTEROL; DEPENDENT DIABETES-MELLITUS; COLON-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; POSTMENOPAUSAL WOMEN; SERUM TRIGLYCERIDES; NUTRITIONAL FACTORS; INSULIN-RESISTANCE AB Case-control studies and a cohort study have shown inconsistent associations between a high glycemic index or a high glycemic load and risk of colorectal cancer. These dietary variables have not been examined in relation to risk of colorectal adenoma. We thus examined the associations between dietary glycemic index, glycemic load, and carbohydrate intake with risk of adenoma of the distal colon or rectum among 34,428 US women who were initially free of cancer or polyps, who completed a semi-quantitative food-frequency questionnaire in 1980, and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704 large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal adenomas) were documented during 18 years of follow-up. Dietary glycemic index, glycemic load, and carbohydrate intake were not related to risk of total colorectal adenoma after adjustment for age and established risk factors [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95% confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load = 0.92, 95% Cl 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90, 95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations were found for large or small adenoma, distal colon or rectal adenoma, or across strata of body mass index. Our findings do not support the hypothesis that a high glycemic index diet, a high glycemic load diet, or high carbohydrate intake overall are associated with risk of colorectal adenoma. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.harvard.edu FU NCI NIH HHS [CA 87969, CA 55075] NR 53 TC 27 Z9 27 U1 0 U2 0 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 JUL PY 2004 VL 13 IS 7 BP 1192 EP + PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 836EW UT WOS:000222539400014 PM 15247130 ER PT J AU Isaka, N Padera, TP Hagendoorn, J Fukumura, D Jain, RK AF Isaka, N Padera, TP Hagendoorn, J Fukumura, D Jain, RK TI Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function SO CANCER RESEARCH LA English DT Article ID TUMOR LYMPHANGIOGENESIS; FACTOR (VEGF)-C; IN-VIVO; METASTASIS; EXPRESSION; VESSELS; CANCER; ANGIOGENESIS; MICROSCOPY; MECHANISMS AB Vascular endothelial growth factor (VEGF)-C is known to induce hyperplasia in normal murine lymphatics and in peritumor lymphatics. Here, we examine the function of these hyperplastic peritumor lymphatics. Microlymphangiograpby of B16F10 melanomas growing in the murine dorsal skinfold chamber showed that the number of functional, draining lymphatics in the peritumor tissue of VEGF-C-overexpressing tumors was significantly greater than that in mock-transduced tumors (9.5 +/- 1.0 versus 6.3 +/- 0.4; n = 6; P < 0.05). Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 734, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R24-CA85140] NR 21 TC 84 Z9 91 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4400 EP 4404 DI 10.1158/0008-5472.CAN-04-0752 PG 5 WC Oncology SC Oncology GA 834JL UT WOS:000222407300004 PM 15231646 ER PT J AU Tassone, P Gozzini, A Goldmacher, V Shammas, MA Whiteman, KR Carrasco, DR Li, C Allam, CK Venuta, S Anderson, KC Munshi, NC AF Tassone, P Gozzini, A Goldmacher, V Shammas, MA Whiteman, KR Carrasco, DR Li, C Allam, CK Venuta, S Anderson, KC Munshi, NC TI In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N-2 '-deacetyl-N-2 '-(3-mercapto-1-oxopropyl)-maytansine against CD56(+) multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY THERAPY; ADHESION MOLECULE NCAM; NATURAL-KILLER-CELLS; PLASMA-CELLS; PHASE-I; GEMTUZUMAB OZOGAMICIN; EXPRESSION; ANTIGEN; LEUKEMIA; CANCER AB HuN901 is a humanized monoclonal antibody that binds with high affinity to CD56, the neuronal cell adhesion molecule. HuN901 conjugated with the maytansinoid N-2'-deacetyl-N-2'-(3-mereapto-1-oxopropyl)-maytansine (DM1), a potent antimicrotubular cytotoxic agent, may provide targeted delivery of the drug to CD56 expressing tumors. Based on gene expression profiles of primary multiple myeloma (MM) cells showing expression of CD56 in 10 out of 15 patients (66.6%) and flow cytometric profiles of MM (CD38(bright)CD45(lo)) cells showing CD56 expression in 22 out of 28 patients (79%), we assessed the efficacy of huN901-DM1 for the treatment of MM. We first examined the in vitro cytotoxicity and specificity of huN901-DM1 on a panel of CD56(+) and CD56(-) MM cell lines, as well as a CD56(-) Waldenstrom's macroglobulinemia cell line. HuN901DM1 treatment selectively decreased survival of CD56(+) MM cell lines and depleted CD56(+) MM cells from mixed cultures with a CD56(-) cell line or adherent bone marrow stromal cells. In vivo antitumor activity of huN901-DM1 was then studied in a tumor xenograft model using a CD56(+) OPM2 human MM cell line in SCID mice. We observed inhibition of serum paraprotein secretion, inhibition of tumor growth, and increase in survival of mice treated with huN901-DM1. Our data therefore demonstrate that huN901-DM1 has significant in vitro and in vivo antimyeloma activity at doses that are well tolerated in a murine model. Taken together, these data provide the framework for clinical trials of this agent to improve patient outcome in MM. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. ImmunoGen Inc, Cambridge, MA USA. Univ Magna Graecia, Catanzaro, Italy. 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 FU PHS HHS [P01-78378, P50-100707, R01-50947] NR 48 TC 109 Z9 114 U1 3 U2 14 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 1 PY 2004 VL 64 IS 13 BP 4629 EP 4636 DI 10.1158/0008-5472.CAN-04-0142 PG 8 WC Oncology SC Oncology GA 834JL UT WOS:000222407300033 PM 15231675 ER PT J AU Sang, CN Ramadan, NM Wallihan, RG Chappell, AS Freitag, FG Smith, TR Silberstein, SD Johnson, KW Phebus, LA Bleakman, D Ornstein, PL Arnold, B Tepper, SJ Vandenhende, F AF Sang, CN Ramadan, NM Wallihan, RG Chappell, AS Freitag, FG Smith, TR Silberstein, SD Johnson, KW Phebus, LA Bleakman, D Ornstein, PL Arnold, B Tepper, SJ Vandenhende, F TI LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine SO CEPHALALGIA LA English DT Article DE migraine; randomized controlled trial; glutamate receptors; LY293558 ID TRIGEMINAL NUCLEUS CAUDALIS; AMINO-ACID RECEPTORS; C-FOS EXPRESSION; GLUTAMATE RECEPTORS; RAT; PAIN; FORMALIN; GLUR5 AB Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis. C1 Finch Univ Hlth Sci Chicago Med Sch, N Chicago, IL 60064 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Diamond Headache Clin Ltd, Chicago, IL USA. Mercy Hlth Res, St Louis, MO USA. Jefferson Headache Ctr, Philadelphia, PA USA. New England Ctr Headache, Stamford, CT USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Ramadan, NM (reprint author), Finch Univ Hlth Sci Chicago Med Sch, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM ramadan@finchcms.edu RI Ornstein, Paul/E-4212-2016 OI Ornstein, Paul/0000-0002-4335-1877 NR 18 TC 95 Z9 97 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JUL PY 2004 VL 24 IS 7 BP 596 EP 602 DI 10.1111/j.1468-2982.2004.00723.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 829LR UT WOS:000222050400012 PM 15196302 ER PT J AU Salat, DH Buckner, RL Snyder, AZ Greve, DN Desikan, RSR Busa, E Morris, JC Dale, AM Fischl, B AF Salat, DH Buckner, RL Snyder, AZ Greve, DN Desikan, RSR Busa, E Morris, JC Dale, AM Fischl, B TI Thinning of the cerebral cortex in aging SO CEREBRAL CORTEX LA English DT Article DE aging; atrophy; calcarine cortex; cortical thickness; dementia; executive function; magnetic resonance imaging; MRI; prefrontal cortex ID SURFACE-BASED ANALYSIS; AGE-RELATED-CHANGES; CORTICAL SURFACE; COORDINATE SYSTEM; GRAY-MATTER; IN-VIVO; BRAIN; THICKNESS; RECONSTRUCTION; LOCALIZATION AB The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T(1)-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Dept Radiol, Charlestown, MA 02129 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63130 USA. Washington Univ, Dept Radiol, St Louis, MO USA. Washington Univ, Dept Neurol, St Louis, MO USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Salat, DH (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM salat@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Morris, John/A-1686-2012 FU NCRR NIH HHS [P41RR14075, RR14075]; NIA NIH HHS [AG03991, AG05681, AG05886]; NINDS NIH HHS [NS39581] NR 37 TC 737 Z9 746 U1 2 U2 46 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2004 VL 14 IS 7 BP 721 EP 730 DI 10.1093/cercor/bhh032 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 830LQ UT WOS:000222124000003 PM 15054051 ER PT J AU Atwood, CW McCrory, D Garcia, JGN Abman, SH Ahearn, GS AF Atwood, CW McCrory, D Garcia, JGN Abman, SH Ahearn, GS TI Pulmonary artery hypertension and sleep-disordered breathing - ACCP evidence-based clinical practice guidelines SO CHEST LA English DT Article DE clinical guideline; continuous positive airway pressure therapy; evidenced-based review; hypoxemia; pulmonary arterial hypertension; sleep-disordered breathing ID POSITIVE AIRWAY PRESSURE; APNEA SYNDROME; PARALLEL TRIAL; LUNG-DISEASE; HEMODYNAMICS; HYPOXEMIA; OXYGEN AB The objective of this article is to review the available data on the relationship between sleep-disordered breathing (SDB) and pulmonary arterial hypertension (PAH), with a focus on the prevalence of SDB in patients with idiopathic PAH (IPAH); the prevalence of PAH in patients with SDB; and the effects of SDB treatment on PAH. The evidence to date suggests that PAH may occur in the setting of SDB, although the prevalence is low. However, pulmonary hypertension (PH) in SDB is most strongly associated with other risk factors, such as left-sided heart disease, parenchymal lung disease, nocturnal desaturation, and obesity. The limited data available also suggest that SDB is uncommon in patients with IPAH. Treatment of SDB with continuous positive airway pressure may lower pulmonary artery pressures when the degree of PH is mild. C1 Univ Pittsburgh, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Duke Univ, Med Ctr, Duke Ctr Clin Hlth Res, Dept Med, Durham, NC USA. Johns Hopkins Univ Hosp, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA. Univ Colorado, Childrens Hosp, Hlth Sci Ctr, Denver, CO 80202 USA. RP Atwood, CW (reprint author), UPMC, Montefiore PACCM, MUH, NW 628, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu RI Garcia, Joe/E-8862-2010 NR 27 TC 67 Z9 71 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2004 VL 126 IS 1 SU S BP 72S EP 77S DI 10.1378/chest.126.1_suppl.72S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 843EB UT WOS:000223057600007 PM 15249496 ER PT J AU Park, JY Kob, M Prodeus, AP Rosen, FS Shcherbina, A Remold-O'Donnell, E AF Park, JY Kob, M Prodeus, AP Rosen, FS Shcherbina, A Remold-O'Donnell, E TI Early deficit of lymphocytes in Wiskott-Aldrich syndrome: possible role of WASP in human lymphocyte maturation (vol 136, pg 104, 2004) SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Correction C1 Ctr Blood Res, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2004 VL 137 IS 1 BP 223 EP 223 DI 10.1111/j.1365-2249.2004.02486.x PG 1 WC Immunology SC Immunology GA 829LO UT WOS:000222050100031 ER PT J AU Megyesi, JF Kachur, E Lee, DH Zlatescu, MC Betensky, RA Forsyth, PA Okada, Y Sasaki, H Mizoguchi, M Louis, DN Cairncross, JG AF Megyesi, JF Kachur, E Lee, DH Zlatescu, MC Betensky, RA Forsyth, PA Okada, Y Sasaki, H Mizoguchi, M Louis, DN Cairncross, JG TI Imaging correlates of molecular signatures in oligodendrogliomas SO CLINICAL CANCER RESEARCH LA English DT Article ID CHROMOSOME ARMS 1P; SUCCESSFUL CHEMOTHERAPY; ALLELIC LOSS; TUMORS; HETEROZYGOSITY; PREDICTORS; DIAGNOSIS; SURVIVAL; 19Q AB Molecular subsets of oligodendroglioma behave in biologically distinct ways. Their locations in the brain, rates of growth, and responses to therapy differ with their genotypes. Retrospectively, we inquired whether allelic loss of chromosomal arms 1p and 19q, an early molecular event and favorable prognostic marker in oligodendrogliomas, were reflected in their appearance on magnetic resonance imaging. Loss of 1p and 19q was associated with an indistinct border on T-1 images and mixed intensity signal on T-1 and T-2. Loss of 1p and 19q was also associated with paramagnetic susceptibility effect and with calcification, a common histopathological finding in oligodendrogliomas. These data encourage prospective evaluation of molecular alterations and magnetic resonance imaging characteristics of glial neoplasms. C1 Univ Western Ontario, Dept Clin Neurosci, London, ON, Canada. Univ Western Ontario, Dept Radiol, London, ON, Canada. Univ Western Ontario, Dept Oncol, London, ON, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Oncol, Calgary, AB, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cairncross, JG (reprint author), Foothills Med Ctr, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM jgcairnx@ucalgary.ca RI Lee, Donald/B-7859-2015 FU NCI NIH HHS [CA57683] NR 20 TC 84 Z9 86 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2004 VL 10 IS 13 BP 4303 EP 4306 DI 10.1158/1078-0432.CCR-04-0209 PG 4 WC Oncology SC Oncology GA 835CK UT WOS:000222457300003 PM 15240515 ER PT J AU Koutsilieris, M Mitsiades, CS Bogdanos, J Dimopoulos, T Karamanolakis, D Milathianakis, C Tsintavis, A AF Koutsilieris, M Mitsiades, CS Bogdanos, J Dimopoulos, T Karamanolakis, D Milathianakis, C Tsintavis, A TI Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID GLUCOCORTICOID RECEPTOR FUNCTION; OSTEOBLASTIC METASTASES; ADENOCARCINOMA CELLS; GROWTH-FACTORS; PHASE-I; DISEASE; BUSERELIN; ORCHIECTOMY; EXPRESSION; MEDIATION AB Purpose: Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy). Experimental Design: Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days). Results: Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, greater than or equal to50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse. Conclusion: The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients. C1 Univ Athens, Sch Med, Dept Expt Physiol, Athens 11527, Greece. 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. Anticanc Hosp, METAXA Anticanc Hosp, Urol Clin, Piraeus, Greece. PANAGIA Gen Hosp, Urol Clin, Thessaloniki, Greece. RP Koutsilieris, M (reprint author), Univ Athens, Sch Med, Dept Expt Physiol, 75 Micras Asias, Athens 11527, Greece. EM mitsiades@dfci.harvard.edu NR 37 TC 32 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2004 VL 10 IS 13 BP 4398 EP 4405 DI 10.1158/1078-0432.CCR-04-0077 PG 8 WC Oncology SC Oncology GA 835CK UT WOS:000222457300016 PM 15240528 ER PT J AU Hecht, DW AF Hecht, DW TI Prevalence of antibiotic resistance in anaerobic bacteria: Worrisome developments SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BACTEROIDES-FRAGILIS GROUP; CARBAPENEMASE GENE CFIA; BETA-LACTAM RESISTANCE; 5-NITROIMIDAZOLE RESISTANCE; ANTIMICROBIAL SUSCEPTIBILITY; FLUOROQUINOLONE RESISTANCE; INTRAABDOMINAL INFECTIONS; SEQUENCE-ANALYSIS; GYRA MUTATIONS; INSERTION AB Antibiotic-resistant anaerobic bacteria have become increasingly recognized as a confounding factor in the selection of therapeutic agents. The use of potent, broad-spectrum antibiotics as empirical therapy, along with appropriate adjunctive measures, has, in some ways, masked the magnitude of the antibiotic resistance problem that parallels that observed for nonanaerobic pathogens. The use of standardized testing methods that recognize resistance and an understanding of resistance mechanisms have become essential for the treatment of patients and the development of new agents. C1 Loyola Univ, Med Ctr, Dept Med, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Hecht, DW (reprint author), Loyola Univ, Med Ctr, Dept Med, Bldg 54,Rm 101,2160 S 1st Ave, Maywood, IL 60153 USA. EM dhecht@lumc.edu FU NIAID NIH HHS [AI050122] NR 47 TC 69 Z9 72 U1 2 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2004 VL 39 IS 1 BP 92 EP 97 DI 10.1086/421558 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 829YJ UT WOS:000222087800016 PM 15206059 ER PT J AU Weems, SA Zaidel, E Berman, S Mandelkern, MA AF Weems, SA Zaidel, E Berman, S Mandelkern, MA TI Asymmetry in alpha power predicts accuracy of hemispheric lexical decision SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE alpha; laterality; electroencephalography; hemispheric specialization ID TERM-MEMORY TASK; BILATERAL PRESENTATIONS; BRAIN ACTIVITY; EEG; GAMMA; HUMANS; PERFORMANCE; SCALES AB Objective: Previous work has shown that individual differences in resting alpha asymmetry are associated with efficacy on a variety of cognitive tasks. Still unresolved is how ongoing alpha asymmetry relates to behavioral asymmetry, explored here using lateralized lexical decision. Methods: Alpha power immediately preceding lexical decision trials was measured to assess cognitive engagement during word recognition. This was compared with behavioral performance for the task, measured by accuracy and latency of the lexical decision response. Results: Greater relative left hemisphere alpha power (i.e. higher asymmetry) immediately before presentation of a word led to reduced likelihood for its successful identification. Greater alpha asymmetry was also associated with reduced performance for identifying stimuli lateralized to the right visual field. Conclusions: Word recognition is facilitated by decreased asymmetry in cognitive engagement in the two cerebral hemispheres, particularly when the stimuli are lateralized to the left hemisphere (right visual field). Significance: Results address the role of cognitive engagement in the two cerebral hemispheres, and its relationship with lexical access. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif Irvine, Irvine, CA USA. RP Weems, SA (reprint author), Univ Maryland, Dept Comp Sci, AV Williams Bldg, College Pk, MD 20742 USA. EM sweems@cs.umd.edu FU NIDCD NIH HHS [F31 DC 04916-01]; NINDS NIH HHS [NS 20187] NR 30 TC 4 Z9 5 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2004 VL 115 IS 7 BP 1575 EP 1582 DI 10.1016/j.clinph.2004.02.020 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839WE UT WOS:000222814800010 PM 15203058 ER PT J AU Chao, LL Lindgren, JA Flenniken, DL Weiner, MW AF Chao, LL Lindgren, JA Flenniken, DL Weiner, MW TI ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE human immunodeficiency virus; P3a; P3b; viral load; antiretroviral therapy ID EVENT-RELATED POTENTIALS; AIDS DEMENTIA COMPLEX; P3 LATENCY; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; TEMPORAL-LOBE; RARE TARGET; INFECTION; DEPRESSION; LESIONS AB Objective: To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. Methods: Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. Results: Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with NI latency in HIV patients and negatively with P3b amplitude in all subjects. Conclusions: These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 San Francisco Vet Affairs Med Ctr, Dept Radiol, Magnet Resonance Unit, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Chao, LL (reprint author), San Francisco Vet Affairs Med Ctr, Dept Radiol, Magnet Resonance Unit, 4150 Clement St,116R, San Francisco, CA 94121 USA. EM llchao@itsa.ucsf.edu FU NIA NIH HHS [P50 AG023501, P50 AG023501-059004]; NIAAA NIH HHS [P01 AA011493, P01 AA11493] NR 59 TC 14 Z9 16 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2004 VL 115 IS 7 BP 1583 EP 1591 DI 10.1016/j.clinph.2004.02.015 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839WE UT WOS:000222814800011 PM 15203059 ER PT J AU George, MS Nahas, Z Bohning, DE Mu, QW Kozel, FA Borckhardt, J Denslow, S AF George, MS Nahas, Z Bohning, DE Mu, QW Kozel, FA Borckhardt, J Denslow, S TI Mechanisms of action of vagus nerve stimulation (VNS) SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT 83rd Conference on Convulsants and AntiConvulsants in Psychiatry and Neurology CY NOV 14-15, 2003 CL New York, NY SP Assoc Res Nervous & Ment Dis DE vagus nerve; VNS; locus ceruleus; anticonvulsant; antidepressant; brain stimulation; fMRI ID TREATMENT-RESISTANT DEPRESSION; PARTIAL SEIZURES; SOLITARY TRACT; NORADRENERGIC FUNCTION; ANTIANXIETY TREATMENT; REFRACTORY EPILEPSY; VAGAL-STIMULATION; BRAIN; NUCLEUS; RAT AB In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve in the neck could stop seizures. Since that time, repeated stimulation of the vagus nerve has been FDA approved as an anticonvulsant. Zabara's work is built on a 50-year-old theme in the literature where scientists had sought to exploit the fact that the vagus nerve is composed of 80% afferent fibers. Thus vagus stimulation might potentially provide a 'window' into the brain. This manuscript reviews the basic science and brain imaging work done to date with VNS, attempting to understand how VNS affects the brain. This research is crucial to perfecting VNS as an anticonvulsant, and for determining other neuropsychiatric conditions that might be helped by VNS. (C) 2004 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC USA. Ralph H Johson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 67 President St,Room 502, Charleston, SC USA. EM georgem@musc.edu RI Kozel, Frank/I-5366-2012 NR 56 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JUL PY 2004 VL 4 IS 1-2 BP 71 EP 79 DI 10.1016/j.cnr.2004.06.006 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 861EU UT WOS:000224399700007 ER PT J AU Ganis, G Thompson, WL Kosslyn, SM AF Ganis, G Thompson, WL Kosslyn, SM TI Brain areas underlying visual mental imagery and visual perception: an fMRI study SO COGNITIVE BRAIN RESEARCH LA English DT Article DE visual cognition; visual imagery; cognitive neuroscience; fMRI; cognitive control processes ID INFERIOR PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; NEURAL SYSTEMS; TRANSIENT ACTIVATION; WORKING-MEMORY; FUNCTIONAL MRI; EYE-MOVEMENTS; BASE-LINE; ATTENTION; FACES AB We used functional magnetic resonance imaging (fMRI) to assess the maximal degree of shared neural processing in visual mental imagery and visual perception. Participants either visualized or saw faint drawings of simple objects, and then judged specific aspects of the drawings (which could only be evaluated properly if they used the correct stimulus). The results document that visual imagery and visual perception draw on most of the same neural machinery. However, although the vast majority of activated voxels were activated during both conditions, the spatial overlap was neither complete nor uniform; the overlap was much more pronounced in frontal and parietal regions than in temporal and occipital regions. This finding may indicate that cognitive control processes function comparably in both imagery and perception, whereas at least some sensory processes may be engaged differently by visual imagery and perception. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Martinos Ctr, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ganis, G (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM ganis@wjh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618 NR 59 TC 264 Z9 274 U1 4 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUL PY 2004 VL 20 IS 2 BP 226 EP 241 DI 10.1016/j.cogbrainres.2004.02.012 PG 16 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 833WH UT WOS:000222370900011 ER PT J AU Sbafizadeh, E Peterson, RT Lin, S AF Sbafizadeh, E Peterson, RT Lin, S TI Induction of reversible hemolytic anemia in living zebrafish using a novel small molecule SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY LA English DT Article; Proceedings Paper CT Conference on Aquatic Animal Models of Human Disease CY SEP 29-OCT 02, 2003 CL Amer Type Culture Collect, Manassas, VA SP Univ Miami HO Amer Type Culture Collect DE zebrafish; small molecules; hemolytic anemia; hematopoiesis; phenylhydrazine; Heinz bodies; GATA1; transgenic zebrafish ID INDUCED OXIDATIVE DENATURATION; RED-BLOOD-CELLS; VERTEBRATE DEVELOPMENT; PHENYLHYDRAZINE; MECHANISM; INVITRO; INVIVO; MODEL; GENE AB We used zebrafish to screen and identify small molecules that affect the process of vertebrate hematopoietic development. Zebrafish embryos were exposed to a library of 5000 synthetic compounds and screened for defects in primitive erythropoiesis. Here, we present the characterization of hemolytic anemia induced in zebrafish by the small molecule 5115318 (3-[5-methyl-furan 2-yl]-propionic acid N' - phenyl-hydrazide). This compound is capable of generating hemoglobin aggregates and Heinz bodies in red cells in vivo only. The induced anemia is reversible and treated fish recover in about 4 days. This study shows the feasibility of using zebrafish to screen for small molecules that can modulate the specific process of erythropoiesis. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. RP Lin, S (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, 621 Charles E Young Dr,S Life Sci Bldg,LS4325, Los Angeles, CA 90095 USA. EM shuolin@ucla.edu NR 18 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1532-0456 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Toxicol. Pharmacol. PD JUL PY 2004 VL 138 IS 3 BP 245 EP 249 DI 10.1016/j.cca.2004.05.003 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 873ZB UT WOS:000225319400003 ER PT J AU Abel, MD Levine, RA AF Abel, MD Levine, RA TI Muscle contractions and auditory perception in tinnitus patients and nonclinical subjects SO CRANIO-THE JOURNAL OF CRANIOMANDIBULAR PRACTICE LA English DT Article ID DORSAL COCHLEAR NUCLEUS; INFERIOR COLLICULUS; PROJECTIONS; NEURONS; RAT; CAT AB Evidence has been accumulating linking subjective tinnitus to the somatosensory system. Most subjective tinnitus patients can change the psychoacoustic attributes of their tinnitus with forceful head and neck contractions. This study assessed the significance of such somatic modulation of tinnitus by testing nonclinical subjects. Like tinnitus patients, about 80% of nonclinical subjects, who had ongoing tinnitus at the time of testing (whether or not they were previously aware of it), could modulate their tinnitus with head and neck contractions. Over half of those with no tinnitus at the time of testing could elicit a tinnitus-like auditory perception with head and neck contractions. The finding that forceful head and neck contractions, as well as loud sound exposure, were significantly more likely to modulate ongoing auditory perception in people with tinnitus than in those without tinnitus supports the concept of a neural threshold for tinnitus. Somatic influences upon auditory perception are not limited to tinnitus sufferers but appear to be a fundamental property of the auditory system. C1 Hosp Univ Penn, Dept Oral & Maxillofacial Surg, Philadelphia, PA 19104 USA. Massachusetts Eye & Ear Infirm, Tinnitus clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abel, MD (reprint author), Hosp Univ Penn, Dept Oral & Maxillofacial Surg, 3400 Spruce St,5th Fl,White Bldg, Philadelphia, PA 19104 USA. EM abelm@mail.med.upenn.edu FU Action on Hearing Loss [G8] NR 25 TC 26 Z9 29 U1 0 U2 2 PU CHROMA INC PI CHATTANOOGA PA PO BOX 8887, CHATTANOOGA, TN 37414 USA SN 0886-9634 J9 CRANIO JI Cranio-J. Craniomandib. Pract. PD JUL PY 2004 VL 22 IS 3 BP 181 EP 191 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 837IR UT WOS:000222622900004 PM 15293775 ER PT J AU Mularski, RA AF Mularski, RA TI Pain management in the intensive care unit SO CRITICAL CARE CLINICS LA English DT Review ID END-OF-LIFE; CRITICALLY-ILL PATIENTS; CLINICAL-PRACTICE GUIDELINES; MECHANICAL VENTILATION; HOSPITALIZED-PATIENTS; EPIDURAL ANALGESIA; NATIONAL-SURVEY; CANCER PAIN; ICU; SEDATIVES AB Pain management is an essential component of quality care delivery for the critically ill patient. Because outcomes are difficult to predict in the intensive care unit (ICU), high-quality pain management and palliative therapy should be a goal for every patient. For those patients actively dying, palliation may be among the main benefits offered by the health care team. Appropriate palliation of pain begins with the use of effective strategies for recognizing, evaluating, and monitoring pain. Skill in pain management requires knowledge of both pharmacologic and nonpharmacologic therapies. This article focuses on expertise in the use of opiates to facilitate confident and appropriate pain therapy To optimize palliative therapy, symptoms are best addressed by interdisciplinary care teams guided by models that acknowledge a continuum of curative therapies and palliative care. C1 Univ Calif Los Angeles, Sch Publ Hlth, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Hlth Sci,Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. RP Mularski, RA (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Hlth Sci,Div Pulm & Crit Care Med, 11301 Wilshire Blvd,Mail Code G111, Los Angeles, CA 90073 USA. EM rmularsk@ucla.edu NR 115 TC 22 Z9 22 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 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD JUL PY 2004 VL 20 IS 3 BP 381 EP + DI 10.1016/j.ccc.2004.03.010 PG 22 WC Critical Care Medicine SC General & Internal Medicine GA 848IK UT WOS:000223460700005 PM 15183209 ER PT J AU Nelson, JE Meier, DE Litke, A Natale, DA Siegel, RE Morrison, RS AF Nelson, JE Meier, DE Litke, A Natale, DA Siegel, RE Morrison, RS TI The symptom burden of chronic critical illness SO CRITICAL CARE MEDICINE LA English DT Article DE ventilator weaning; respiration; artificial; palliative care; critical illness ID PROLONGED MECHANICAL VENTILATION; INTENSIVE-CARE UNIT; CONFUSION ASSESSMENT METHOD; ILL PATIENTS; BONE HYPERRESORPTION; ASSESSMENT SCALE; LUNG-CANCER; EXPERIENCE; SURVIVAL; PAIN AB Objective. To assess self-reported symptom burden of chronic critical illness. Design: Prospective cohort study. Setting. Respiratory care unit for treatment of chronically critically ill patients at an academic, tertiary-care, urban medical center. Patients: Fifty patients who underwent elective tracheotomy and transfer from an adult intensive care unit to the respiratory care unit for weaning from mechanical ventilation. Interventions. Assessment of physical and psychological symptoms through patients' self-reports using a modification of the Condensed Form of the Memorial Symptom Assessment Scale. Measurements and Main Results: We measured self-reported symptom burden, ventilator outcomes, and vital status and functional status at discharge and 3 and 6 months after discharge. Half of the patients were successfully liberated from mechanical ventilation, but most hospital survivors were discharged to skilled nursing facilities and more than half of the cohort was dead at 3 months after discharge. Seventy-two percent (36 of 50) of patients were able to self-report symptoms during the period of respiratory care unit treatment. Among patients responding to symptom assessment, approximately 90% were symptomatic. Forty-four percent of patients reported pain at the highest levels. More than 60% reported psychological symptoms at these levels, and approximately 90% of patients reported severe distress due to difficulty communicating. Conclusions: Physical and psychological symptom distress is common and severe among patients receiving treatment for chronic critical illness. The majority of these patients die soon after hospital discharge. Given the level of distress in our study patients and the high mortality rate that we and others have observed, greater attention should be given to relief of pain and other distressing symptoms and to assessment of burdens and benefits of treatment for the chronically critically ill. C1 Mt Sinai Sch Med, Div Pulm & Crit Care Med, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Dept Geriatr & Adult Dev, New York, NY 10029 USA. Crit Care Ctr, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Nelson, JE (reprint author), Mt Sinai Sch Med, Div Pulm & Crit Care Med, Dept Med, Box 1232,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Judith.nelson@mountsinai.org FU NIA NIH HHS [K07 AG00903-03, K08AG00833-01, AG021172] NR 56 TC 114 Z9 115 U1 6 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2004 VL 32 IS 7 BP 1527 EP 1534 DI 10.1097/01.CCM.0000129485.08835.5A PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 837QZ UT WOS:000222651800010 PM 15241097 ER PT J AU Levin, M AF Levin, M TI The embryonic origins of left-right asymmetry SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE left-right asymmetry; developmental biology; embryo; ion transport; motor proteins; cilia ID POLYCYSTIC KIDNEY-DISEASE; RIGHT AXIS FORMATION; GROWTH FACTOR-ALPHA; SITUS-INVERSUS; CHICK-EMBRYO; CLEFT-LIP; NODAL CILIA; EXPRESSION PATTERNS; SEX DETERMINATION; IMMOTILE CILIA AB The bilaterally symmetric body plan of vertebrates features several consistent asymmetries in the placement, structure, and function of organs such as the heart, intestine, and brain. Deviations from the normal pattern result in situs inversus, isomerisms, or heterotaxia (independent randomization), which have significant clinical implications. The invariance of the left-right (LR) asymmetry of normal morphology, neuronal function, and phenotype of several syndromes raises fascinating and fundamental questions in cell, developmental, evolutionary, and neurobiology. While a pathway of asymmetrically expressed signaling factors has been well-characterized in several model systems, very early steps in the establishment of LR asymmetry remain poorly understood. In particular, the origin of consistently oriented asymmetry is unknown. Recently, a candidate for the origins of asymmetry has been suggested: bulk transport of extracellular morphogens by rotating primary cilia during gastrulation. This model is appealing because it 'bootstraps' morphological asymmetry of the embryo from the intrinsic structural (molecular) chirality of motile cilia. However, conceptual and practical problems remain with this hypothesis. Indeed, the genetic data are also consistent with a different mechanism: cytoplasmic transport roles of motor proteins. This review outlines the progress and remaining questions in the field of left-right asymmetry, and focuses on an alternative model for 'Step 1' of asymmetry. More specifically, based on wide-ranging data on ion fluxes and motor protein function in several species, it is suggested that laterality is driven by pH/voltage gradients across the midline, which are established by chiral movement of motor proteins with respect to the cytoskeleton. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Cytol Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Craniofacial & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Cytol Biol Dept, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NIGMS NIH HHS [1-R01-GM-06227] NR 111 TC 46 Z9 49 U1 3 U2 8 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD JUL PY 2004 VL 15 IS 4 BP 197 EP 206 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 895AO UT WOS:000226833300003 PM 15284185 ER PT J AU Patti, ME AF Patti, ME TI Gene expression in humans with diabetes and prediabetes: what have we learned about diabetes pathophysiology? SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE insulin resistance/genetics; diabetes mellitus; type II/genetics; muscle; skeletal/metabolism; oxidative phosphorylation; gene expression profiling; transcription factors/physiology ID HUMAN SKELETAL-MUSCLE; RECEPTOR-GAMMA COACTIVATOR-1; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; FREE FATTY-ACIDS; INSULIN-RESISTANCE; METABOLIC SYNDROME; ADIPOSE-TISSUE; PIMA-INDIANS; GLUCOSE-TOLERANCE AB Purpose of review Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic beta-cell dysfunction. In high-risk individuals, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, and glycogen synthesis, and the accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and diabetes mellitus has been identified in humans. However, recent analyses of gene expression patterns in muscle tissue from metabolically characterized humans have highlighted new genes and pathways potentially important in the pathogenesis of diabetes mellitus. This review will summarize these data and highlight the potential importance of oxidative metabolism in diabetes pathophysiology. Recent findings Genomic analysis of skeletal muscle samples from patients with diabetes mellitus has revealed the reduced expression of genes encoding key enzymes in oxidative metabolism and mitochondrial function. Moreover, the same pattern of gene expression is also observed in insulin resistant 'prediabetic' individuals with normal glucose tolerance. Many of the genes dysregulated in both diabetes and 'prediabetes' are regulated by the transcription factor nuclear respiratory factor-1 and the peroxisome proliferator-activated receptor gamma co-activator 1. These data suggest a potential role for both genetic and environmental factors to modify the risk of diabetes by modifying the expression or activity of these transcriptional regulators. Summary Nuclear respiratory factor and peroxisome proliferator activated receptor gamma co-activator-1-dependent oxidative metabolic pathways may play a central, and potentially primary, role in the pathogenesis of type 2 diabetes. Additional studies will be required to identify upstream genetic and environmental determinants of this expression phenotype. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [DK060837, R01 DK 62948] NR 59 TC 24 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JUL PY 2004 VL 7 IS 4 BP 383 EP 390 DI 10.1097/01.mco.0000134359.23288.72 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 835KC UT WOS:000222480600004 PM 15192439 ER PT J AU Ingelfinger, JR AF Ingelfinger, JR TI Pathogenesis of perinatal programming SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE perinatal programming; fetal origins; nephrogenesis; in utero; hypertension ID MATERNAL PROTEIN RESTRICTION; LOW-BIRTH-WEIGHT; BLOOD-PRESSURE; PRENATAL DEXAMETHASONE; ADULT HYPERTENSION; CARDIOVASCULAR-DISEASE; RECEPTOR EXPRESSION; KIDNEY DEVELOPMENT; GLUCOSE-TOLERANCE; IRON RESTRICTION AB Purpose of review In recent years, there has been an increase in research designed to delineate the underlying causes of perinatal programming. Starting with epidemiological observations that birth weight was inversely associated with cardiovascular disease, a variety of studies both in humans and in experimental models have begun to demonstrate how the perinatal milieu can subtly alter vasculogenesis and nephrogenesis. Additionally, rates of prenatal and postnatal growth each appear to contribute to future vascular, renal and metabolic function. The purpose of this review is to discuss recent reports that have begun to elucidate factors that initiate perinatal programming as it affects renal disease and cardiovascular disease in later life. Recent findings Nephrogenesis per se is affected by changes in maternal nutrition and health, and recent data more specifically linking these changes with renal function and hypertension are presented. Additionally, renal functional changes in later life may be influenced by changes in renal tubular transporters noted early when maternal nutrition is compromised. Various hormonal systems affected by maternal nutrition in utero may effect subsequent changes in renal function via subtle alterations in renal function and structure initiated during nephrogenesis. Summary Current research is beginning to clarify certain aspects of perinatal programming and indicates that broad educational programmes might ultimately lessen both perinatal risks and long-term outcomes by encouraging therapeutic interventions in at-risk persons. C1 Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 15 Parkman St, Boston, MA 02114 USA. EM Jingelfinger@partners.org FU NHLBI NIH HHS [HL48455] NR 54 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JUL PY 2004 VL 13 IS 4 BP 459 EP 464 DI 10.1097/01.mnh.0000133977.09688.2f PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 836BV UT WOS:000222531000009 PM 15199297 ER PT J AU Chanin, TD Merrick, DT Franklin, WA Hirsch, FR AF Chanin, TD Merrick, DT Franklin, WA Hirsch, FR TI Recent developments in biomarkers for the early detection of lung cancer: perspectives based on publications 2003 to present SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE lung cancer; biomarkers; proteomics; gene analysis ID ATYPICAL ADENOMATOUS HYPERPLASIA; BRONCHIAL PRECANCEROUS LESIONS; ABERRANT PROMOTER METHYLATION; K-RAS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; PROTEOMIC PATTERNS; TISSUE MICROARRAYS; SPUTUM CYTOLOGY; EXPRESSION; MARKERS AB Purpose of review Given the poor prognosis associated with lung cancer, the ability to diagnose lung cancer in its early stages is considered crucial to achieving decreased lung cancer mortality. Herein, we discuss recent advances in biomarker discovery and evaluation of their potential application in the clinical setting. Recent findings Novel potential biomarkers have been identified via new techniques including cDNA microarray analysis, comparative genomic hybridization, and proteomics. These factors have been evaluated in various validation studies including tissue microarrays, RT-PCR, and assays of bioactivity. The characterization of these potential biomarkers through analysis of pathways that have been associated with neo-plastic transformation may help to identify the precursor lesions that are associated with subsequent progression to invasive carcinoma. In addition, the past year has also produced intriguing results regarding the detection of biomarkers in easily accessible screening specimens such as sputa, serum, and exhaled breath. Recent advances in these aspects of biomarker identification for the early detection of lung cancer are reviewed. Summary Identification of new candidate biomarkers and improved applications of previously detected biomarkers show great promise for the ultimate establishment of practical lung cancer screening. While recent studies engender optimism for the creation of clinically applicable screening tests, the biomarkers that have been identified need larger, follow-up validational studies and further characterization as to their biologic importance. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO USA. RP Hirsch, FR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, B216,4200 E 9th Ave, Denver, CO 80262 USA. EM fred.hirsch@uchsc.edu FU NCI NIH HHS [P50-CA58187, U01-CA85070] NR 63 TC 35 Z9 37 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD JUL PY 2004 VL 10 IS 4 BP 242 EP 247 DI 10.1097/01.mcp.0000130321.11513.13 PG 6 WC Respiratory System SC Respiratory System GA 835BS UT WOS:000222455500002 PM 15220746 ER PT J AU Dotto, GP Silke, J AF Dotto, GP Silke, J TI More than cell death: Caspases and caspase inhibitors on the move SO DEVELOPMENTAL CELL LA English DT Editorial Material ID APOPTOSIS; HID; GRIM AB It is becoming clear that "apoptotic" caspases can effect cellular processes other than cell death. A recent paper in Cell points to a novel role of the Drosophila caspase inhibitor DIAP1 as a determinant of cell migration. C1 Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3055, Australia. RP Dotto, GP (reprint author), Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. RI Silke, John/B-7622-2008 OI Silke, John/0000-0002-7611-5774 NR 7 TC 7 Z9 7 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2004 VL 7 IS 1 BP 2 EP 3 DI 10.1016/j.devcel.2004.06.014 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 838EM UT WOS:000222696300002 PM 15239946 ER PT J AU Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JD Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM AF Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JD Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM TI Semaphorin-plexin signaling guides patterning of the developing vasculature SO DEVELOPMENTAL CELL LA English DT Article ID ENDOTHELIAL GROWTH FACTOR-165; ZEBRAFISH EMBRYOS; IN-VIVO; MOLECULAR-CLONING; NEUROPILIN-1; EXPRESSION; RECEPTOR; DIFFERENTIATION; VASCULOGENESIS; INHIBITION AB Major vessels of the vertebrate circulatory system display evolutionarily conserved and reproducible anatomy, but the cues guiding this stereotypic patterning remain obscure. In the nervous system, axonal pathways are shaped by repulsive cues provided by ligands of the semaphorin family that are sensed by migrating neuronal growth cones through plexin receptors. We show that proper blood vessel pathfinding requires the endothelial receptor PlexinD1 and semaphorin signals, and we identify mutations in plexinD1 in the zebrafish vascular patterning mutant out of bounds. These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Univ Calgary, Smooth Muscle Res Grp, Calgary, AB T2N 4N1, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Weinstein, BM (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM bw96w@nih.gov FU NHLBI NIH HHS [R01 HL092263] NR 31 TC 238 Z9 243 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2004 VL 7 IS 1 BP 117 EP 123 DI 10.1016/j.devcel.2004.06.008 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 838EM UT WOS:000222696300015 PM 15239959 ER PT J AU Ogawa, N List, JF Habener, JF Maki, T AF Ogawa, N List, JF Habener, JF Maki, T TI Cure of overt diabetes in NOD mice by transient treatment with anti-lymphocyte serum and exendin-4 SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; BETA-CELLS; 7-36 AMIDE; MELLITUS; ANTIBODY; EXPRESSION; RECEPTOR; RATS; DIFFERENTIATION; STREPTOZOTOCIN AB Treatment of overtly diabetic NOD mice with antilymphocyte serum (ALS), a polyclonal anti-T-cell antibody, abrogates autoimmunity and achieves partial clinical remission. Here we investigated whether the addition of exendin-4, a hormone that stimulates insulin secretion and P-cell replication and differentiation, improves induction of remission by ALS. Transient treatment of overtly diabetic NOD mice with ALS and exendin-4 achieved complete remission in 23 of 26 mice (88%) within 75 days, accompanied by progressive normalization of glucose tolerance, improved islet histology, increased insulin content in the pancreas, and insulin release in response to a glucose challenge. Syngeneic islets transplanted into mice cured by treatment with ALS plus exendin-4 remained intact, and cotransfer of lymphocytes from cured mice delayed diabetes induction by adoptive transfer, suggesting the long-lasting presence of autoimmune regulatory cells. Although ALS alone also achieved reversal of diabetes, the frequency of remission was low (40%). No treatment or exendin-4 alone failed to produce remission. These results show that exendin-4 synergistically augments the remission-inducing effect of ALS. The addition of beta-cell growth factors, such as exendin-4, to immunotherapy protocols with anti-T-cell antibodies presents a potential novel approach to the cure of patients with new-onset type 1 diabetes. C1 Beth Israel Deaconess Med Ctr, Harvard Inst Med, Transplant Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Endocrinol, Boston, MA 02115 USA. RP Maki, T (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Transplant Ctr, Rm 1024,77 Ave Louis Pasteur, Boston, MA 02215 USA. EM tamaki@caregroup.harvard.edu FU NIDDK NIH HHS [DK30834, DK60721] NR 33 TC 114 Z9 117 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1700 EP 1705 DI 10.2337/diabetes.53.7.1700 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000010 PM 15220193 ER PT J AU Bonora, E Kiechl, S Willeit, J Oberhollenzer, F Egger, G Meigs, JB Bonadonna, RC Muggeo, M AF Bonora, E Kiechl, S Willeit, J Oberhollenzer, F Egger, G Meigs, JB Bonadonna, RC Muggeo, M TI Population-based incidence rates and risk factors for a type 2 diabetes in white individuals - The Bruneck study SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; INSULIN SECRETORY DYSFUNCTION; HOMEOSTASIS MODEL ASSESSMENT; FOLLOW-UP; NATURAL-HISTORY; CARDIOVASCULAR-DISEASE; SEX-DIFFERENCES; PIMA-INDIANS; LIFE-STYLE AB Incidence rates and risk factors for type 2 diabetes in low-risk populations are not well documented. We investigated these in white individuals who were aged 40-79 years and from the population of Bruneck, Italy. Of an age- and sex-stratified. random sample of 1,000 individuals who were identified in 1990, 919 underwent an oral glucose tolerance test (OGTT) and an assessment of physiological risk factors for diabetes, including insulin resistance (homeostasis model assessment, HOMA-IR), and postchallenge insulin response (Sluiter's Index). Diabetes at baseline by fasting or 2-h OGIT plasma glucose (World Health Organization criteria, n = 82) was excluded, leaving 837 individuals who were followed for 10 years. Incident cases of diabetes were ascertained by confirmed diabetes treatment or a fasting glucose greater than or equal to7.0 mmol/l. At follow-up, 64 individuals had developed diabetes, corresponding to a population-standardized incidence rate of 7.6 per 1,000 person-years. Sex-and age-adjusted incidence rates were elevated 11-fold in individuals with impaired fasting glucose at baseline, 4-fold in those with impaired glucose tolerance, 3-fold in overweight individuals, 10-fold in obese individuals, and similar to2-fold in individuals with dyslipidemia or hypertension. Incidence rates increased with increasing HOMA-IR and decreasing Sluiter's Index. As compared with normal insulin sensitivity and normal insulin response, individuals with low insulin sensitivity and. low insulin response had a sevenfold higher risk of diabetes. Baseline impaired fasting glucose, BMI, HOMA-IR, and Sluiter's Index were the only independent predictors of incident diabetes in multivariate analyses. We conclude that similar to1% of European white individuals aged 40-79 years develop type 2 diabetes annually and that "subdiabetic" hyperglycemia, obesity, insulin resistance, and impaired insulin response to glucose are independent predictors of diabetes. C1 Univ Verona, Sch Med, Div Endocrinol & Metab Dis, I-37100 Verona, Italy. Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. Hosp Bruneck, Div Internal Med, Brunico, Italy. Massachusetts Gen Hosp, Div Gen Med, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bonora, E (reprint author), Osped Maggiore, Piazzale Stefani 1, I-37126 Verona, Italy. EM enzobonora@virgilio.it NR 57 TC 156 Z9 166 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1782 EP 1789 DI 10.2337/diabetes.53.7.1782 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000019 PM 15220202 ER PT J AU Goldstein, DE Little, RR Lorenz, RA Malone, JI Nathan, D Peterson, CM Sacks, DB AF Goldstein, DE Little, RR Lorenz, RA Malone, JI Nathan, D Peterson, CM Sacks, DB TI Tests of glycemia in diabetes SO DIABETES CARE LA English DT Review ID SERUM FRUCTOSAMINE CONCENTRATION; GLYCOSYLATED HEMOGLOBIN LEVELS; LONG-TERM COMPLICATIONS; BLOOD-GLUCOSE MONITORS; GLYCATED HEMOGLOBIN; CLINICAL-USEFULNESS; URINE GLUCOSE; GLYCOHEMOGLOBIN DETERMINATIONS; PROTEIN-CONCENTRATION; BIOLOGICAL VARIATION C1 Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO 65212 USA. Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO 65212 USA. Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO 65212 USA. Univ Illinois, Coll Med, Dept Pediat, Peoria, IL 61656 USA. Univ S Florida, Coll Med, Tampa, FL USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Little, RR (reprint author), Univ Missouri, Sch Med, Dept Pathol & Anat Sci, M7676,1 Hosp Dr, Columbia, MO 65212 USA. EM littler@health.missouri.edu OI Little, Randie/0000-0001-6450-8012; Sacks, David/0000-0003-3100-0735 NR 183 TC 248 Z9 281 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2004 VL 27 IS 7 BP 1761 EP 1773 DI 10.2337/diacare.27.7.1761 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100042 PM 15220264 ER PT J AU Maciejewski, ML Reiber, GE Smith, DG Wallace, C Hayes, S Boyko, EJ AF Maciejewski, ML Reiber, GE Smith, DG Wallace, C Hayes, S Boyko, EJ TI Effectiveness of diabetic therapeutic footwear in preventing reulceration SO DIABETES CARE LA English DT Review ID ULCERS; SHOES; MANAGEMENT; MEDICARE; PATIENT; TRIALS; COHORT; COSTS; RISK AB OBJECTIVE - To review the evidence for the effectiveness of therapeutic footwear in preventing foot reulceration in individuals with diabetes and foot risk factors. RESEARCH DESIGN AND METHODS - We conducted a structured literature review based on a Medline search for studies of therapeutic footwear that examined prevention of reulceration. Nine published articles were identified. Characteristics of the study population, components of the intervention, and level of adherence were evaluated. U.S. preventive Services Task Force criteria for evaluating research were applied to rate each study on study design and internal validity. RESULTS - Risk ratios in all studies assessing the association between therapeutic footwear and reulceration were below 1.0, suggesting some protective footwear benefit. However, in the most rigorous experimental study, no statistically significant benefit was observed between control patients wearing their own footwear and intervention patients wearing study footwear. Annual reulceration in these studies control groups ranged from 8.4 to 59.3%. In patients with severe foot deformity or prior toe or ray amputation, observational studies suggested a significant protective benefit from therapeutic footwear. CONCLUSIONS - Therapeutic footwear has been used for decades as one of many strategies to prevent reulceration in patients with diabetes and foot risk factors. The findings of several studies reporting statistically significant protective effects from therapeutic footwear may have been influenced by several design issues. When considering the appropriateness of therapeutic footwear recommendations for moderate-risk patients, clinicians and patients should jointly explore individual strategies to decrease events that lead to foot ulcers. C1 VA Puget Sound Hlth Care Syst HSR&D 152, Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped Surg, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Maciejewski, ML (reprint author), VA Puget Sound Hlth Care Syst HSR&D 152, Hlth Serv Res & Dev, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mlmaciej@u.washington.edu NR 36 TC 42 Z9 46 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 JUL PY 2004 VL 27 IS 7 BP 1774 EP 1782 DI 10.2337/diacare.27.7.1774 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100043 PM 15220265 ER PT J AU Mullooly, C AF Mullooly, C TI Physical activity specialty educator SO DIABETES EDUCATOR LA English DT Editorial Material RP Mullooly, C (reprint author), Joslin Clin Exercise Physiol, 1 Joslin Pl, Boston, MA 02215 USA. EM cathy.mullooly@joslin.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JUL-AUG PY 2004 VL 30 IS 4 BP 594 EP + DI 10.1177/014572170403000410 PG 2 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 852EO UT WOS:000223738200004 PM 15669777 ER PT J AU Walsh, SR Ferraro, MJ Durand, ML AF Walsh, SR Ferraro, MJ Durand, ML TI Clindamycin-resistant Streptococcus pyogenes: report of a case SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Editorial Material ID MACROLIDE-RESISTANCE; ERYTHROMYCIN; ANTIBIOTICS; INFECTIONS; PREVALENCE; GROWTH AB A sentinel isolate of clindamycin-resistant Streptococcus pyogenes from a case of mixed aerobic-anaerobic necrotizing fasciitis prompted our clinical laboratory to change its protocol and subsequently perform routine susceptibility testing on all S. pyogenes isolated from blood and soft tissue specimens. Emerging clindamycin resistance may have serious implications in the treatment of severe S. pyogenes infections. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Div Microbiol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Div Infect Dis, Boston, MA 02114 USA. RP Walsh, SR (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM swalsh@partners.org NR 19 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 2004 VL 49 IS 3 BP 223 EP 225 DI 10.1016/j.diagmicrobio.2004.03.005 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 842EG UT WOS:000222985400012 PM 15246514 ER PT J AU Williams, R Ehde, D Smith, D Czerniecki, J Hoffman, A Robinson, L AF Williams, R Ehde, D Smith, D Czerniecki, J Hoffman, A Robinson, L TI A two-year longitudinal study of social support following amputation SO DISABILITY AND REHABILITATION LA English DT Article ID LOWER-LIMB AMPUTATION; CHRONIC PAIN; LIFE SCALE; ADJUSTMENT; REHABILITATION; SATISFACTION; DEPRESSION; STRESS; DISABILITY; MORTALITY AB Purpose : (1) To describe one aspect of social support, social integration, longitudinally for 2 years following lower limb amputation and (2) to explore the impact of social support on depression, pain interference, life satisfaction, mobility, and occupational functioning. Method : Eighty-nine adults recruited from consecutive admissions to an orthopaedic surgery service completed telephone interviews 1, 6, 12 and 24 months following amputation surgery. Dependent variables included the Social Integration (SI) sub-scale of the Craig Handicap Assessment and Reporting Technique (CHART) and the Multidimensional Scale of Perceived Social Support (MSPSS). Results : There was a high level of SI among most persons following lower limb amputations that was relatively unchanged in the 2 years following surgery. However, mean levels of SI were lower in this group compared to a sample without disabilities. MSPSS scores were highly variable, ranging from almost no support to the maximum amount of support. MSPSS was an important concurrent predictor of pain interference, life satisfaction, and mobility, controlling for demographic and amputation-related factors. Baseline MSPSS predicted mobility and occupational functioning 6 months post-amputation, controlling for demographic and amputation-related factors. Conclusions : Findings suggest that interventions aimed at improving the quality of social relationships after amputation may facilitate participation in activities. C1 Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Ctr Amputat Prosthet & Limb Loss Prevent, Seattle, WA USA. RP Ehde, D (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Box 359740,325 9th Ave, Seattle, WA 98104 USA. EM ehde@u.washington.edu RI Robinson , Lawrence/D-8455-2013 FU NICHD NIH HHS [P01 HD/NS33988]; PHS HHS [MM-0127-02/02] NR 52 TC 31 Z9 31 U1 1 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PD JUL-AUG PY 2004 VL 26 IS 14-15 BP 862 EP 874 DI 10.1080/09638280410001708878 PG 13 WC Rehabilitation SC Rehabilitation GA 835ZJ UT WOS:000222524200005 PM 15497915 ER PT J AU Waeber, C Blondeau, N Salomone, S AF Waeber, C Blondeau, N Salomone, S TI Vascular sphingosine-1-phosphate SIP1 and SIP3 receptors SO DRUG NEWS & PERSPECTIVES LA English DT Review ID PROTEIN-COUPLED RECEPTOR; SMOOTH-MUSCLE-CELLS; HUMAN ENDOTHELIAL-CELLS; SPHINGOSINE 1-PHOSPHATE RECEPTOR; FOCAL ADHESION KINASE; STIMULATES TYROSINE PHOSPHORYLATION; MULTIPLE SIGNALING PATHWAYS; FACTOR-INDUCED ACTIVATION; GROWTH-FACTOR RECEPTORS; NITRIC-OXIDE PRODUCTION AB The sphingolipid sphingosine-1-phosphate (S1P) acts on five subtypes of G-protein-coupled receptors, termed S1P(1) (formerly endothelial differentiation gene-1 [Edg-1]), S1P(2) (Edg-5), S1P(3) (Edg-3), S1P(4) (Edg-6) and S1P(5) (Edg-8), and possibly several other "orphan" receptors, such as GPR3, GPR6 and GPR12. These receptors are coupled to different intracellular second messenger systems, including adenylate cyclase, phospholipase C, phosphatidylinositol 3-kinase/protein kinase Akt, mitogen-activated protein kinases, as well as Rho- and Ras-dependent pathways. Consistently with this receptor multiplicity and pleiotropic signaling mechanisms, S1P influences numerous cell functions. S1P(1), S1P(2) and S1P(3) receptors are the major S1P receptor subtypes in the cardiovascular system, where they mediate the effects of S1P released from platelets, and possibly other tissues (such as brain). Thus S1P(1) and S1P(3) receptors enhance endothelial and vascular smooth muscle cell proliferation and migration, playing a key role in developmental and pathological angiogenesis. In contrast, S1P(2) receptors inhibit migration of these cell types, probably because of their unique stimulatory effect on a GTPase-activating protein inhibiting the activity of Rac. S1P receptors can also cause relaxation and constriction of blood vessels. The former effect is mediated by pertussis toxin-sensitive receptors (possibly S1P(1)) located on the endothelium and stimulating phosphaticlylinositol 3-kinase/Akt/endothelial nitric oxide synthase (eNOS). The vasoconstricting effect of S1P is likely to be mediated by S1P(2) and/or S1P(3) receptors, via Rho-Rho-kinase, and is more potent in coronary and cerebral blood vessels. Finally, S1P also protects endothelial cells from apoptosis through activation of phosphaticlylinositol 3-kinase/Akt/eNOS via S1P(1) and S1P(3) receptors. The variety of these effects, taken together with the existence of multiple receptor subtypes, provides an abundance of therapeutic targets that currently still await the development of selective agents. (C) 2004 Prous Science. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Waeber, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, CNY149,Room 6403,149 13th St, Charlestown, MA 02129 USA. EM waeber@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009; Blondeau, Nicolas/M-5002-2016 OI Waeber, Christian/0000-0001-6078-0027; Blondeau, Nicolas/0000-0001-5954-4094 FU NINDS NIH HHS [NS043216] NR 207 TC 93 Z9 102 U1 0 U2 8 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD JUL-AUG PY 2004 VL 17 IS 6 BP 365 EP 382 DI 10.1358/dnp.2004.17.6.829028 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 854LE UT WOS:000223903600002 PM 15334188 ER PT J AU Madison, DL Bliziotes, M AF Madison, DL Bliziotes, M TI Severe dystrophic calcification confounded by secondary hyperparathyroidism in a patient with thyroid lymphoma and CREST syndrome SO ENDOCRINOLOGIST LA English DT Article DE calcinosis; vitamin D; hyperparathyroidism; extraskeletal calcification ID TUMORAL CALCINOSIS; SYSTEMIC-SCLEROSIS; PARATHYROIDECTOMY; DILTIAZEM; HEMODIALYSIS; REGRESSION; PATHOGENESIS; SCLERODERMA AB The extraskeletal calcific disorders represent a wide variety of metabolic, genetic, and autoimmune diseases causing abnormal calcium salt deposition. Sequelae resulting from calcifications can be severe, causing dermal breakdown, superinfection, and restriction of joint mobility with a significant decrease in patient quality of life.. The pathophysiology and extent of extraskeletal calcification is directly dependent on the causative disease process, and therefore the determination of the etiology of extraskeletal calcification can lead to early treatment and significant reduction in comorbidities related to the underlying clinical condition. We discuss a case of extreme subcutaneous extraskeletal calcification resulting from an autoimmune inflammatory process that is confounded by secondary hyperparathyroidism. C1 Oregon Hlth Sci Univ, Div Endocrinol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Endocrinol Diabet & Clin Nutr, Dept Med, Portland, OR 97239 USA. Portland VA Med Ctr, Endocrinol Sect, Portland, OR USA. RP Madison, DL (reprint author), Oregon Hlth Sci Univ, Div Endocrinol, L-607,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM madisond@ohsu.edu NR 27 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL-AUG PY 2004 VL 14 IS 4 BP 195 EP 198 DI 10.1097/01.ten.0000134719.42806.64 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 840YJ UT WOS:000222896200004 ER PT J AU Larsson, T Marsell, R Schipani, E Ohlsson, C Ljunggren, O Tenenhouse, HS Juppner, H Jonsson, KB AF Larsson, T Marsell, R Schipani, E Ohlsson, C Ljunggren, O Tenenhouse, HS Juppner, H Jonsson, KB TI Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha 1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis SO ENDOCRINOLOGY LA English DT Article ID DOMINANT HYPOPHOSPHATEMIC RICKETS; ONCOGENIC OSTEOMALACIA; PROTEOLYTIC CLEAVAGE; COTRANSPORTER GENES; SKELETAL PHENOTYPE; PARATHYROID CELLS; TARGETED ABLATION; FACTOR (FGF)-23; HYP MICE; IN-VIVO AB Mutations in the fibroblast growth factor 23 gene, FGF23, cause autosomal dominant hypophosphatemic rickets (ADHR). The gene product, FGF-23, is produced by tumors from patients with oncogenic osteomalacia (OOM), circulates at increased levels in most patients with X-linked hypophosphatemia (XLH) and is phosphaturic when injected into rats or mice, suggesting involvement in the regulation of phosphate (Pi) homeostasis. To better define the precise role of FGF-23 in maintaining Pi balance and bone mineralization, we generated transgenic mice that express wild-type human FGF-23, under the control of the alpha1(I) collagen promoter, in cells of the osteoblastic lineage. At 8 wk of age, transgenic mice were smaller (body weight = 17.5 +/- 0.57 vs. 24.3 +/- 0.37 g), exhibited decreased serum Pi concentrations (1.91 +/- 0.27 vs. 2.75 +/- 0.22 mmol/liter) and increased urinary Pi excretion when compared with wild-type littermates. The serum concentrations of human FGF-23 (undetectable in wild-type mice) was markedly elevated in transgenic mice (>7800 reference units/ml). Serum PTH levels were increased in transgenic mice (231 +/- 62 vs. 139 +/- 44 pg/ml), whereas differences in calcium and 1,25-dihydroxyvitamin D were not apparent. Expression of Npt2a, the major renal Na+/Pi cotransporter, as well as Npt1 and Npt2c mRNAs, was significantly decreased in the kidneys of transgenic mice. Histology of tibiae displayed a disorganized and widened growth plate and peripheral quantitative computerized tomography analysis revealed reduced bone mineral density in transgenic mice. The data indicate that FGF-23 induces phenotypic changes in mice resembling those of patients with ADHR, OOM, and XLH and that FGF-23 is an important determinant of Pi homeostasis and bone mineralization. C1 Univ Uppsala Hosp, Dept Surg Sci, SE-75185 Uppsala, Sweden. Univ Uppsala Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Sahlgrens Univ Hosp, Dept Internal Med, Div Endocrinol, SE-41345 Gothenburg, Sweden. McGill Univ, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3Z 2Z3, Canada. RP Jonsson, KB (reprint author), Univ Uppsala Hosp, Dept Surg Sci, SE-75185 Uppsala, Sweden. EM Kenneth.Jonsson@surgsci.uu.se NR 55 TC 282 Z9 289 U1 1 U2 5 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 JUL PY 2004 VL 145 IS 7 BP 3087 EP 3094 DI 10.1210/en.2003-1768 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900008 PM 14988389 ER PT J AU Goren, HJ Kulkarni, RN Kahn, CR AF Goren, HJ Kulkarni, RN Kahn, CR TI Glucose homeostasis and tissue transcript content of insulin signaling intermediates in four inbred strains of mice: C57BL/6, C57BLKS/6, DBA/2, and 129X1 SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; BETA-CELL; RECEPTOR GENE; ADIPOSE-TISSUE; KNOCKOUT MICE; MOUSE STRAINS; SECRETION; RESISTANCE; EXPRESSION; LACKING AB Transgenic mice phenotypes generally depend on the background strains used in their creation. To examine the effects of genetic background on insulin signaling, we analyzed glucose homeostasis in four inbred strains of mice [C57BL/6 (B6), C57BLKS/6 (KLS), DBA/2 (DBA), and 129X1] and quantitated mRNA content of insulin receptor (IR) and its substrates in insulin-responsive tissues. At 2 months, the male B6 mouse is the least glucose-tolerant despite exhibiting similar insulin sensitivity and first-phase insulin secretion as the other strains. The 129X1 male mouse islet contains less insulin and exhibits a higher threshold for glucose-stimulated first-phase insulin secretion than the other strains. Female mice generally manifest better glucose tolerance than males, which is likely due to greater insulin sensitivity in liver and adipose tissue, a robust first-phase insulin secretion in B6 and KLS females, and improved insulin sensitivity in muscle in DBA and 129X1 females. At 6 months, although males exhibit improved first-phase insulin secretion, their physiology was relatively unchanged, whereas female B6 and KLS mice became less insulin sensitive. Gene expression of insulin signaling intermediates in insulin-responsive tissues was generally not strain dependent with the cell content of IR mRNA being highest. IR substrate (IRS)-1 and IRS-2 mRNA are ubiquitously expressed and IRS-3 and IRS-4 mRNA were detected in significant amounts in fat and brain tissues, respectively. These data indicate strain-, gender-, and age-dependent tissue sensitivity to insulin that is generally not associated with transcript content of IR or its substrates and should be taken into consideration during phenotypic characterization of transgenic mice. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Goren, HJ (reprint author), Univ Calgary, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM goren@ucalgary.ca; c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [K08 DK 02885-02, R01 DK67536, R03 DK66207] NR 67 TC 93 Z9 94 U1 0 U2 6 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 JUL PY 2004 VL 145 IS 7 BP 3307 EP 3323 DI 10.1210/en.2003-1400 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900036 PM 15044376 ER PT J AU Chattopadhyay, N Yano, S Tfelt-Hansen, J Rooney, P Kanuparthi, D Bandyopadhyay, S Ren, XH Terwilliger, E Brown, EM AF Chattopadhyay, N Yano, S Tfelt-Hansen, J Rooney, P Kanuparthi, D Bandyopadhyay, S Ren, XH Terwilliger, E Brown, EM TI Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; EXTRACELLULAR CA2+-SENSING RECEPTOR; PROTOONCOGENE C-FOS; MESSENGER-RIBONUCLEIC-ACID; BOVINE PARATHYROID CELLS; ACTIVATED PROTEIN-KINASE; HUMAN OSTEOSARCOMA CELLS; CYCLIN D1 EXPRESSION; OUTWARD K+ CHANNEL; SECONDARY HYPERPARATHYROIDISM AB The parathyroid calcium-sensing receptor (CaR) plays a nonredundant role in systemic calcium homeostasis. In bone, Ca-o(2+), a major extracellular factor in the bone microenvironment during bone remodeling, could potentially serve as an extracellular first messenger, acting via the CaR, that stimulates the proliferation of preosteoblasts and their differentiation to osteoblasts ( OBs). Primary digests of rat calvarial OBs express the CaR as assessed by RT-PCR, Northern, and Western blot analysis, and immunocolocalization of the CaR with the OB marker cbfa-1. Real-time PCR revealed a significant increase in CaR mRNA in 5- and 7-d cultures compared with 3-d cultures post harvesting. High Ca-o(2+) did not affect the expression of CaR mRNA during this time but up-regulated cyclin D(D1, D2, and D3) genes, which are involved in transition from the G1 to the S phase of the cell cycle, as well as the early oncogenes, c-fos and early growth response-1; high Ca-o(2+) did not, however, alter IGF-I expression, a mitogenic factor for OBs. The high Ca-o(2+)-dependent increase in the proliferation of OBs was attenuated after transduction with a dominant-negative CaR (R185Q), confirming that the effect of high Ca-o(2+) is CaR mediated. Stimulation of proliferation by the CaR involves the Jun-terminal kinase (JNK) pathway, as high Ca-o(2+) stimulated the phosphorylation of JNK in a CaR-mediated manner, and the JNK inhibitor SP600125 abolished CaR-induced proliferation. Our data, therefore, show that the parathyroid/kidney CaR expressed in rat calvarial OBs exerts a mitogenic effect that involves activation of the JNK pathway and up-regulation of several mitogenic genes. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02115 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. RP Chattopadhyay, N (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM Naibedya@rics.bwh.harvard.edu OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599; Chattopadhyay, Naibedya/0000-0003-2473-0246 FU NIAMS NIH HHS [AR02215]; NIDDK NIH HHS [DK41415, DK48330, DK52005] NR 73 TC 96 Z9 101 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2004 VL 145 IS 7 BP 3451 EP 3462 DI 10.1210/en.2003-1127 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900051 PM 15084499 ER PT J AU Wiren, KM Zhang, XW Toombs, AR Kasparcova, V Gentile, MA Harada, SI Jepsen, KJ AF Wiren, KM Zhang, XW Toombs, AR Kasparcova, V Gentile, MA Harada, SI Jepsen, KJ TI Targeted overexpression of androgen receptor in osteoblasts: Unexpected complex bone phenotype in growing animals SO ENDOCRINOLOGY LA English DT Article ID NORMAL ELDERLY MEN; I COLLAGEN; BIOCHEMICAL MARKERS; OSTEOGENESIS IMPERFECTA; POSTMENOPAUSAL WOMEN; ORCHIECTOMIZED RAT; CANCELLOUS BONE; DEFICIENT MICE; GROWTH-PLATE; ESTROGEN AB The androgen receptor (AR), as a classic steroid receptor, generally mediates biologic responses to androgens. In bone tissue, both AR and the estrogen receptor ( ER) are expressed in a variety of cell types. Because androgens can be converted into estrogen via aromatase activity, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR as a means of elucidating the specific role(s) for AR transactivation in bone homeostasis. Rat AR cDNA was cloned downstream of a 3.6-kb alpha1(I)-collagen promoter fragment and used to create AR-transgenic mice. AR-transgenic males gain less weight and body and femur length is shorter than wild-type controls, whereas females are not different. AR-transgenic males also demonstrate thickened calvaria and increased periosteal but reduced endosteal labeling by fluorescent labeling and reduced osteocalcin levels. High-resolution micro-computed tomography shows normal mineral content in both male and female AR-transgenic mice, but male AR-transgenics reveal a reduction in cortical area and moment of inertia. Male AR-transgenics also demonstrate an altered trabecular morphology with bulging at the metaphysis. Histomorphometric analysis of trabecular bone parameters confirmed the increased bone volume comprised of more trabeculae that are closer together but not thicker. Biomechanical analysis of the skeletal phenotype demonstrate reduced stiffness, maximum load, post-yield deflection, and work-to-failure in male AR-transgenic mice. Steady-state levels of selected osteoblastic and osteoclastic genes are reduced in tibia from both male and female transgenics, with the exception of increased osteoprotegerin expression in male AR-transgenic mice. These results indicate that AR action is important in the development of a sexually dimorphic skeleton and argue for a direct role for androgen transactivation of AR in osteoblasts in modulating skeletal development and homeostasis. C1 Portland Vet Affairs Med Ctr, Bone & Mineral Res Unit, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Merck Res Labs, Dept Mol Endocrinol Bone Biol, W Point, PA 19486 USA. CUNY Mt Sinai Sch Med, Dept Orthopaed, New York, NY 10029 USA. RP Wiren, KM (reprint author), Portland Vet Affairs Med Ctr, Bone & Mineral Res Unit, P3-R&D39,3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 NR 60 TC 53 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2004 VL 145 IS 7 BP 3507 EP 3522 DI 10.1210/en.2003-1016 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900056 PM 15131013 ER PT J AU Jensen, DM Chaves, DM Grund, KE AF Jensen, DM Chaves, DM Grund, KE TI Endoscopic diagnosis and treatment of watermelon stomach SO ENDOSCOPY LA English DT Article ID ANTRAL VASCULAR ECTASIA; ARGON PLASMA COAGULATION; LASER THERAPY; GAVE AB The aim of the Expert Approach section is to contribute to the dissemination and standardization of new endoscopic procedures. Authors from three distinct geographic areas combine forces, sharing their experience to form a consensus of opinion. Readers' comments are welcome and will be published in the Mailbox which appears at the end of each Expert Approach article. C1 Univ Calif Los Angeles, CURE, Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. Univ Sao Paulo, Sch Med, Endoscopy Serv, Sao Paulo, Brazil. Univ Hosp, Dept Gen Surg, Tubingen, Germany. RP Jensen, DM (reprint author), Univ Calif Los Angeles, CURE, Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Bldg 115,Room 318, Los Angeles, CA 90073 USA. EM djensen@mednet.ucla.edu FU NCRR NIH HHS [M01 RR 008658]; NIDDK NIH HHS [DK 02650] NR 19 TC 13 Z9 14 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JUL PY 2004 VL 36 IS 7 BP 640 EP 647 DI 10.1055/s-2004-814525 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 835LG UT WOS:000222484000012 PM 15243889 ER PT J AU Garshick, E Laden, F Hart, JE Dockery, DW Rosner, B Smith, TJ AF Garshick, E Laden, F Hart, JE Dockery, DW Rosner, B Smith, TJ TI The association of lung cancer mortality with job title and work location in unionized trucking employees 1985-2000 SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 VA Boston Healthcare Syst, Boston, MA USA. Channing Labs, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S83 EP S83 DI 10.1097/00001648-200407000-00202 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800203 ER PT J AU Green, R Hauser, R Calafat, A Wueve, J Schettler, T Ringer, S Huttner, K Hu, H AF Green, R Hauser, R Calafat, A Wueve, J Schettler, T Ringer, S Huttner, K Hu, H TI Urinary levels of di-2-ethylhexyl phthalate metabolites in NICU infants SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Sci & Environm Hlth Network, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S86 EP S87 DI 10.1097/00001648-200407000-00214 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800215 ER PT J AU Morrow, DA Antman, EM Murphy, SA Assmann, SF Giugliano, RP Cannon, CP Gibson, CM McCabe, CH Barron, HV de Werf, FV Braunwald, E AF Morrow, DA Antman, EM Murphy, SA Assmann, SF Giugliano, RP Cannon, CP Gibson, CM McCabe, CH Barron, HV de Werf, FV Braunwald, E TI The Risk Score Profile: a novel approach to characterising the risk of populations enrolled in clinical studies SO EUROPEAN HEART JOURNAL LA English DT Article DE clinical trials; prognosis; myocardial infarction; mortality; risk factors ID ACUTE MYOCARDIAL-INFARCTION; NATIONAL REGISTRY; INTRAVENOUS NPA; TRIAL; FIBRINOLYSIS; MANAGEMENT; ALTEPLASE; OUTCOMES; ANGINA; CURVE AB Aims Interpreting the results and practice implications of clinical studies requires accurate characterisation of the baseline risk of the population. We evaluated the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI as a too[ to describe and compare the risk profile of populations enrolled in three clinical trials (InTIME-II, ASSENT-2 and MAGIC) and the National Registry of Myocardial Infarction. Methods and Results The risk score was calculated for each patient (N = 1211 085) and the frequency distribution plotted for each population. The Risk Score Profiles were compared using the Kolmogorov-Smirnov test. The Risk Score Profile demonstrated a striking concordance between the baseline risk of patients in InTIME-II and ASSENT-2 (median scores in each = 3[1,4], P = 0.11). In contrast, the distributions in MAGIC (designed to enroll high risk) and NRMI (registry) were shifted significantly toward higher risk (median scores = 4[3, 5] for MAGIC and 4[2,6] in NRMI, P < 0.0001 for each vs. InTIME-II). A graded relationship between the risk score and mortality was evident in each study (P < 0.0001). Conclusions The frequency distribution of the TIMI Risk Score, or similar tools for risk assessment, may be used to quantify and readily compare the risk profile of populations enrolled in clinical studies. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. New England Res Inst, Watertown, MA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Genentech Inc, Dept Med Affairs, San Francisco, CA USA. UH Gasthuisberg, Dept Cardiol, Louvain, Belgium. RP Morrow, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org OI Van de Werf, Frans/0000-0001-9479-7767 NR 18 TC 15 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2004 VL 25 IS 13 BP 1139 EP 1145 DI 10.1016/j.ehj.2004.04.036 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841DV UT WOS:000222910400009 PM 15231372 ER PT J AU Boll, W Ehrlich, M Collier, RJ Kirchhausen, T AF Boll, W Ehrlich, M Collier, RJ Kirchhausen, T TI Effects of dynamin inactivation on pathways of anthrax toxin uptake SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article ID COATED VESICLE FORMATION; PROTECTIVE ANTIGEN; LETHAL FACTOR; MAMMALIAN-CELLS; MUTANT DYNAMIN; MEMBRANE; RECEPTOR; TRANSLOCATION; ENDOCYTOSIS; INHIBITORS AB Internalization and traffic to acidic endosomes of anthrax lethal factor (LF) and protective antigen (PA), bound to the anthrax toxin receptor (ATR), is required for LF translocation into the cytosol, where it can elicit its toxic effects. Dynamin is required for clathrin-mediated endocytosis, and long-term disruption of dynamin function blocks internalization of PA. We have used LFn-DTA, a surrogate of LF consisting of the N-terminal domain of LF fused to the catalytic subunit of diphtheria toxin, to differentiate the effects of acute and long-term block of dynamin function on LFn-DTA toxicity. Both forms of interference reduce LFn-DTA toxicity only partially, consistent with alternative routes for LFn-DTA endocytosis. In contrast, a long-term block of dynamin activity results in a further interference with LFn-DTA toxicity that is consistent with an altered endosomal environment, probably an increase in endosomal pH. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res,Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol, Boston, MA USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res,Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu OI Collier, R John/0000-0002-2427-4239 FU NIGMS NIH HHS [GM36548] NR 21 TC 19 Z9 22 U1 1 U2 3 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUL PY 2004 VL 83 IS 6 BP 281 EP 288 DI 10.1078/0171-9335-00373 PG 8 WC Cell Biology SC Cell Biology GA 863AE UT WOS:000224531800007 PM 15511085 ER PT J AU Loser, K Mehling, A Apelt, J Stander, S Andres, PG Reinecker, HC Eing, BR Skryabin, BV Varga, G Schwarz, T Beissert, S AF Loser, K Mehling, A Apelt, J Stander, S Andres, PG Reinecker, HC Eing, BR Skryabin, BV Varga, G Schwarz, T Beissert, S TI Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte-targeted overexpression of IL-15 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-15; transgenic mice; vaccination; HSV infection; T lymphocytes ID HERPES-SIMPLEX-VIRUS; CD8(+) T-CELLS; DENDRITIC CELLS; LANGERHANS CELLS; NATURAL-KILLER; MESSENGER-RNA; INTERLEUKIN-15; MICE; DIFFERENTIATION; PROLIFERATION AB IL-15 is involved in lymphocyte homeostasis. To investigate the role of IL-15 in the skin in vivo, mice were generated that overexpress IL-15 in keratinocytes, resulting in increased IL-15 protein levels in the skin but not elevated IL-15 serum concentrations. Keratin 14 (K14)-IL-15 transgenic (tg) mice showed increased contact hypersensitivity (CHS) responses. Transfer of primed wild-type (wt) and tg T cells into naive wt or tg recipients indicated that skin-derived IL-15 enhanced the induction but not the elicitation phase of CHS. Tg mice could be sensitized even by suboptimal hapten concentrations. Accordingly, Langerhans cells (LC) from tg skin were identified as potent allostimulators, suggesting the involvement of IL-15-stimulated LC in the induction of adaptive immunity. Overexpression of IL-15 also strengthened innate immunity since tg mice infected with human HSV type I developed significantly smaller HSV skin lesions. In addition, tg mice resisted re-infection with HSV more effectively than wt mice did, which was associated with an elevated anti-HSV Ab production. Accordingly, injection of serum from re-infected tg mice protected naive recipients significantly from epicutaneous HSV infection, indicating that anti-HSV Ab produced by tg mice play an important role in resistance in vivo. Together, our results show that overexpression of IL-15 in the epidermis enhances both innate and adaptive cutaneous immunity. C1 Univ Munster, Dept Dermatol, D-48149 Munster, Germany. Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. German Res Ctr Biotechnol, GBF, Dept Expt Immunol, Braunschweig, Germany. Univ Munster, Inst Expt Pathol, ZMBE, D-4400 Munster, Germany. Univ Munster, Dept Med Microbiol, D-4400 Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Beissert, S (reprint author), Univ Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany. EM beisser@uni-muenster.de RI Schwarz, Thomas/A-9148-2010 FU NIDDK NIH HHS [DK 43351, DK 33506, DK 51003, DK 54427] NR 24 TC 16 Z9 17 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2004 VL 34 IS 7 BP 2022 EP 2031 DI 10.1002/eji.200324785 PG 10 WC Immunology SC Immunology GA 836NY UT WOS:000222563800026 PM 15214050 ER PT J AU Alam, MN McGinty, D Bashir, T Kumar, S Imeri, L Opp, MR Szymusiak, R AF Alam, MN McGinty, D Bashir, T Kumar, S Imeri, L Opp, MR Szymusiak, R TI Interleukin-1 beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cytokine; extracellular unit recording; interleukin-1 receptor antagonist; microdialysis; rat ID RECEPTOR MESSENGER-RNA; EYE-MOVEMENT SLEEP; NF-KAPPA-B; CEREBRAL-CORTEX; CHOLINERGIC NEURONS; BRAIN TEMPERATURE; GABAERGIC NEURONS; RAT-BRAIN; ACTIVATION; ADENOSINE AB Interleukin-1beta (IL-1) is a pro-inflammatory cytokine that has been implicated in the regulation of nonrapid eye movement (nonREM) sleep. IL-1, IL-1 receptors and the IL-1 receptor antagonist (ra) are present normally in discrete brain regions, including the preoptic area (POA) of the hypothalamus and the adjoining magnocellular basal forebrain (BF). The POA/BF have been implicated in the regulation of sleep-wakefulness. We hypothesized that IL-1 promotes nonREM sleep, in part by altering the state-dependent discharge activity of POA/BF neurons. We recorded the sleep-wake discharge profiles of 83 neurons in the lateral POA/BF and assessed the effects of IL-1, IL-1ra, and IL-ra + IL-1 delivered through a microdialysis probe on state-dependent neuronal discharge activity. IL-1 decreased the discharge rate of POA/BF neurons as a group (n = 55) but wake-related and sleep-related neurons responded differently. IL-1 significantly decreased the discharge rate of wake-related neurons. Of 24 wake-related neurons studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge in the presence of IL-1 during waking. IL-1 suppressed the discharge activity of 18 of 19 responsive neurons. Of 13 sleep-related neurons studied, IL-1 increased the discharge activity of five and suppressed the discharge activity of four neurons. IL-1ra increased the discharge activity of four of nine neurons and significantly attenuated IL-1-induced effects on neuronal activity of POA/BF neurons (n = 19). These results suggest that the sleep-promoting effects of IL-1 may be mediated, in part, via the suppression of wake-related neurons and the activation of a subpopulation of sleep-related neurons in the POA/BF. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, North Hills, CA 91343 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90033 USA. Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. Univ Milan, Inst Human Physiol 2, Milan, Italy. Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Szymusiak, R (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH47480, MH61354, MH63323, MH64843] NR 59 TC 49 Z9 52 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2004 VL 20 IS 1 BP 207 EP 216 DI 10.1111/j.1460-9568.2004.03469.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 835YQ UT WOS:000222522000020 PM 15245493 ER PT J AU Brenner, GJ Ji, RR Shaffer, S Woolf, CJ AF Brenner, GJ Ji, RR Shaffer, S Woolf, CJ TI Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dorsal horn; plasticity; rat; spinal cord ID PROTEIN-KINASE-C; SPINOTHALAMIC TRACT NEURONS; D-ASPARTATE RECEPTORS; RAT MODEL; SECONDARY HYPERALGESIA; GLUTAMATE RECEPTORS; ER RETENTION; TYROSINE PHOSPHORYLATION; MECHANICAL HYPERALGESIA; NEUROGENIC HYPERALGESIA AB The N-methyl-D-aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord and the generation of pain hypersensitivity. NMDAR function is modulated by post-translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity in the spinal cord. We now, show that a noxious heat stimulus applied to the rat hindpaw induces phosphorylation of the NMDAR NR1 subunit at a protein kinase C (PKC)-dependent site, serine-896, in superficial dorsal horn neurons. Phosphorylation of NRII serine-896 is essentially absent in the superficial dorsal horn laminae of naive rats, but, there is rapid (<2 min) induction following a noxious but not in-nocuous heat stimulus. The number of pNR1-immunoreactive neuronal profiles in the superficial dorsal horn peaks 30 min after noxious heat stimulation and persists for up to 1 h. pNR1serine896 induction occurs in the endoplasmic reticulum, suggesting that it contributes to trafficking of the receptor from intracellular stores to the membrane. The phosphorylation of the subunit is attenuated by intrathecal injection of the. NMDAR antagonist, MK801, suggesting that the NMDAR is involved via a feed-forward mechanism in its own phosphorylation. The pNR1serine896-positive neurons are highly co-localized with PKCdelta and only rarely with PKCgamma. These data provide evidence for an activity-dependent NMDAR phosphorylation at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons initiated by peripheral noxious stimuli. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02110 USA. Brigham & Womens Hosp, Dept Anesthesia, Pain Res Ctr, Boston, MA 02115 USA. RP Brenner, GJ (reprint author), 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM gjbrenner@partners.org OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [K08 NS44139, R01 NS039518, K08 NS044139, R01 NS038253, R01 NS040698] NR 69 TC 87 Z9 93 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2004 VL 20 IS 2 BP 375 EP 384 DI 10.1111/j.1460-9568.2004.03506.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 839FZ UT WOS:000222770300007 PM 15233747 ER PT J AU Zhang, P Iwasaki-Arai, J Iwasaki, H Duprez, EA Huettner, CS Geary, K Fenyus, M Shigematsu, H Akashi, K Tenen, DG AF Zhang, P Iwasaki-Arai, J Iwasaki, H Duprez, EA Huettner, CS Geary, K Fenyus, M Shigematsu, H Akashi, K Tenen, DG TI Myeloid transcription factors: Effect on stem cells, hematopoiesis, and leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 59 BP 45 EP 45 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700055 ER PT J AU Colvin, GA Lambert, JF Lum, LG Abedi, M Rathore, R Falvey, M Ballen, KK Novitsky, N Elfenbein, GE Quesenberry, PJ AF Colvin, GA Lambert, JF Lum, LG Abedi, M Rathore, R Falvey, M Ballen, KK Novitsky, N Elfenbein, GE Quesenberry, PJ TI Outpatient HLA-haploidentical transplants for refractory acute myeloid leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Roger Williams Med Ctr, Adele R Decof Canc Ctr, Providence, RI USA. Univ Hosp, Div Hematol, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 91 BP 53 EP 53 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700084 ER PT J AU Colvin, GA Lambert, JF Lum, LG Rathore, R Abedi, M Ballen, KK Novitsky, N Falvey, M Elfenbein, GE Quesenberry, PJ AF Colvin, GA Lambert, JF Lum, LG Rathore, R Abedi, M Ballen, KK Novitsky, N Falvey, M Elfenbein, GE Quesenberry, PJ TI The haploimmunostorm syndrome: A clinical entity observed in mini-haploidentical bone marrow transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Roger Williams Med Ctr Adele R Decof Canc Ctr, Providence, RI USA. Univ Hosp, Div Hematol, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 202 BP 81 EP 81 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700188 ER PT J AU Joussen, AM Poulaki, V Le, ML Koizumi, K Esser, C Janicki, H Schraermeyer, U Kociok, N Fauser, S Kirchhof, B Kern, TS Adamis, AP AF Joussen, AM Poulaki, V Le, ML Koizumi, K Esser, C Janicki, H Schraermeyer, U Kociok, N Fauser, S Kirchhof, B Kern, TS Adamis, AP TI A central role for inflammation in the pathogenesis of diabetic retinopathy SO FASEB JOURNAL LA English DT Article DE adhesion molecules; retina; vascular lesions ID INTERCELLULAR-ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; SELECTIN; RETINA; MODEL; ANGIOPOIETIN-1; LEUKOSTASIS; MOUSE; DEATH; RATS AB Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and CD18. Mice deficient in the genes encoding for the leukocyte adhesion molecules CD18 and ICAM-1 were studied in two models of diabetic retinopathy with respect to the long-term development of retinal vascular lesions. CD18(-/-) and ICAM-1(-/-) mice demonstrate significantly fewer adherent leukocytes in the retinal vasculature at 11 and 15 months after induction of diabetes with STZ. This condition is associated with fewer damaged endothelial cells and lesser vascular leakage. Galactosemia of up to 24 months causes pericyte and endothelial cell loss and formation of acellular capillaries. These changes are significantly reduced in CD18(-/-) and ICAM(-/-) deficient mice. Basement membrane thickening of the retinal vessels is increased in long-term galactosemic animals independent of the genetic strain. Here we show that chronic, low-grade subclinical inflammation is responsible for many of the signature vascular lesions of diabetic retinopathy. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy. C1 Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50924 Cologne, Germany. Univ Cologne, Ctr Ophthalmol, Angiogenesis Lab, D-50924 Cologne, Germany. Univ Cologne, Ctr Mol Med ZMMK, Cologne, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Lab, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Surg Res Lab, Boston, MA USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Ophthalmol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Diabet Res, Cleveland, OH 44106 USA. Eyetech Res Ctr, Woburn, MA USA. RP Joussen, AM (reprint author), Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. EM JoussenA@aol.com; tony.adamis@eyetk.com FU NEI NIH HHS [EY11627, EY12611] NR 26 TC 532 Z9 588 U1 5 U2 40 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 JUL PY 2004 VL 18 IS 10 BP 1450 EP + DI 10.1096/fj.03-1476fje PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 842CB UT WOS:000222979200022 PM 15231732 ER PT J AU del Monte, F Dalal, R Tabchy, A Couget, J Bloch, KD Peterson, R Hajjar, RJ AF del Monte, F Dalal, R Tabchy, A Couget, J Bloch, KD Peterson, R Hajjar, RJ TI Transcriptional changes following restoration of SERCA2a levels in failing rat hearts SO FASEB JOURNAL LA English DT Article DE heart failure; calcium ATPase; transcript profile ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; GLYCOGEN-SYNTHASE KINASE-3-BETA; ADENOVIRAL GENE-TRANSFER; IN-VIVO; VENTRICULAR-FUNCTION; SIGNAL-TRANSDUCTION; AKT ACTIVATION; FAILURE; TENSIN; EXPRESSION AB Heart failure is characterized at the cellular level by impaired contractility and abnormal Ca2+ homeostasis. We have previously shown that restoration of a key enzyme that controls intracellular Ca2+ handling, the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), induces functional improvement in heart failure. We used high-density oligonucleotide arrays to explore the effects of gene transfer of SERCA2a on genetic reprogramming in a model of heart failure. A total of 1,300 transcripts were identified to be unmodified by the effect of virus alone. Of those, 251 transcripts were found to be up- or down-regulated upon failure. A total of 51 transcripts which were either up- ( 27) or down- ( 24) regulated in heart failure were normalized to the nonfailing levels by the restoration of SERCA2a by gene transfer. The microarray analysis identified new genes following SERCA2a restoration in heart failure, which will give us insights into their role in the normalization of multiple pathways within the failing cell. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Bauer Ctr Genom Res, Boston, MA 02115 USA. RP del Monte, F (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, E 149 13th St, Charlestown, MA 02129 USA. EM fdelmonte@partners.org NR 28 TC 9 Z9 9 U1 0 U2 0 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 JUL PY 2004 VL 18 IS 10 BP 1474 EP + DI 10.1096/fj.04-1714fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 842CB UT WOS:000222979200004 PM 15247151 ER PT J AU Pastor, MF Iglesias-Osma, MC Garcia-Barrado, MJ Carretero, J Moratinos, J Burks, D White, M AF Pastor, M. F. Iglesias-Osma, M. C. Garcia-Barrado, M. J. Carretero, J. Moratinos, J. Burks, D. White, M. TI Defects in insulin secretion and lipolysis display gender-differences in the IRS-2 knockout model SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Pastor, M. F.; Iglesias-Osma, M. C.; Garcia-Barrado, M. J.; Carretero, J.; Moratinos, J.; Burks, D.] Fac Med Salamanca, Salamanca, Spain. [White, M.] Joslin Diabet Ctr, EEUU, Boston, MA 02215 USA. RI Garcia Barrado, Maria Jose/L-4852-2014; Iglesias-Osma, Maria Carmen/B-1641-2013 OI Garcia Barrado, Maria Jose/0000-0003-2552-5973; Iglesias-Osma, Maria Carmen/0000-0002-2206-9119 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 87 EP 87 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600482 ER PT J AU Christofi, FL Kim, M Wunderlich, JE Xue, JJ Suntres, Z Cardounel, A Javed, NH Yu, JG Grants, I Cooke, HJ AF Christofi, FL Kim, M Wunderlich, JE Xue, JJ Suntres, Z Cardounel, A Javed, NH Yu, JG Grants, I Cooke, HJ TI Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model SO GASTROENTEROLOGY LA English DT Article ID GUINEA-PIG; 5-HT RELEASE; BON CELLS; RECEPTORS; DESENSITIZATION; SECRETION; NEURONS AB Background & Aims: The aim was to determine whether adenosine receptors modulate CAMP, intracellular free calcium ([Ca2+](i)), and 5-hydroxytrypta mine (5-HT) release in human carcinoid BON cells. Methods: Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca2+](i) imaging, and pharmacologic/ physiologic techniques. Results: A1, A2, and A3Rs were present in BON cells and carcinoid tumors. Baseline 5-HT levels increased with adenosine deaminase, activation of A2Rs, and inhibition of A3Rs, whereas A3R activation decreased 5-HT. A2R antagonists or blockade of adenosine reuptake that elevates extracellular adenosine reduced mechanically evoked 5-HT release. In single BON cells, touch elevated [Ca2+](i) responses were augmented by adenosine deaminase, A1, and A3R antagonists. Conclusions: Tonic or mechanically evoked release of endogenous adenosine is a critical determinant of differential activation of adenosine receptors and may have important implications for gut mechanosensory reflexes. C1 Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Heart & Lung Inst, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Dept Anesthesiol, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Ball State Univ, Dept Physiol & Hlth Sci, Muncie, IN 47306 USA. RP Cooke, HJ (reprint author), Ohio State Univ, Dept Neurosci, 333 W 10th Ave, Columbus, OH 43210 USA. EM cooke.1@osu.edu FU NIDDK NIH HHS [DK37240, DK44179, DK57016] NR 30 TC 34 Z9 35 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2004 VL 127 IS 1 BP 188 EP 202 DI 10.1053/j.gastro.2004.04.070 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836HE UT WOS:000222545700025 PM 15236185 ER PT J AU Sanderson, IR Bustin, SA Dziennis, S Paraszczuk, J Stamm, DS AF Sanderson, IR Bustin, SA Dziennis, S Paraszczuk, J Stamm, DS TI Age and diet act through distinct isoforms of the class II transactivator gene in mouse intestinal epithelium SO GASTROENTEROLOGY LA English DT Article ID BARE LYMPHOCYTE SYNDROME; MESSENGER-RNA; INTERFERON-GAMMA; IFN-GAMMA; T-CELLS; ANTIGEN PRESENTATION; ELEMENTAL DIET; IA-ANTIGEN; MHC; EXPRESSION AB Background & Aims: Normal weaning induces class 11 major histocompatibility complex (Ia) and invariant chain (Ii) expression in the mouse intestinal epithelium. Because the class II transactivator protein (CIITA) induces la and Ii in most cell types, we hypothesized that diet-induced expression of these genes was through CIITA. Methods: Mouse litters were split and weaned onto an elemental diet or a normal (complex) chow diet. On days 24, 31, and 45, epithelial cells were isolated from small intestine with EDTA, and the RNA was extracted from both wild-type and interferon (IFN)-gamma receptor knockout mice. Messenger RNA (mRNA) was measured by Northern blotting, RNase protection assay, and real-time polymerase chain reaction and la localized by immunohistochemistry. Results : By day 31, CIITA mRNA was induced in the intestinal epithelium of normally weaned wild-type mice, and this mirrored the expression of Ii chain mRNA. Mice weaned onto an elemental diet did not exhibit Ii mRNA or increased CIITA mRNA in the intestinal epithelium by day 31, but low levels of Ii mRNA were detectable by day 45. Of the 3 isoforms of CIITA, weaning onto a complex diet induced only CIITA IV by day 31. Mice deficient in the IFN-gamma receptor expressed Ia in the epithelium and they also accumulated Ii mRNA (at low levels) by day 45, irrespective of diet. CIITA III mRNA accumulation mirrored the dietary-independent changes of Ii mRNA. Conclusions: Two mechanisms regulate Ii in the mouse intestinal epithelium: a rapid one, which is diet-induced acting through CIITA IV; and a slower, dietary-independent pathway, acting through CIITA III. C1 Barts & London Queen Mary Univ London, Inst Cell & Mol Sci, Res Ctr Gastroenterol, London, England. Harvard Univ, Massachusetts Gen Hosp, Clin Nutr Res Ctr,Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Barts & London Queen Mary Univ, Inst Cell & Mol Sci, Surg Res Ctr, London, England. RP Sanderson, IR (reprint author), Royal London Hosp, DDRC, Turner St, London E1 2AD, England. EM i.r.sanderson@qmul.ac.uk RI Bustin, Stephen/H-3086-2013; OI Bustin, Stephen/0000-0003-1870-6098; Sanderson, Ian/0000-0002-9814-0161 FU NIAID NIH HHS [AI43472]; NIDDK NIH HHS [DK47753] NR 42 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2004 VL 127 IS 1 BP 203 EP 212 DI 10.1053/j.gastro.2004.04.014 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836HE UT WOS:000222545700026 PM 15236186 ER PT J AU Cario, E Gerken, G Podolsky, DK AF Cario, E Gerken, G Podolsky, DK TI Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; PROINFLAMMATORY GENE-EXPRESSION; INFLAMMATORY-BOWEL-DISEASE; IN-VITRO MODEL; TIGHT JUNCTION; PHORBOL ESTER; SIGNAL-TRANSDUCTION; BACTERIAL LIGANDS; ENDOTHELIAL-CELLS; CUTTING EDGE AB Background & Aims: Protein kinase C (PKC) has been implicated in regulation of intestinal epithelial integrity in response to lumenal bacteria. Intestinal epithelial cells (IECs) constitutively express Toll-like receptor (TLR)2, which contains multiple potential PKC binding sites. The aim of this study was to determine whether TLR2 may activate PKC in response to specific ligands, thus potentially modulating barrier function in IECs. Methods: TLR2 agonist (synthetic bacterial lipopeptide Pam(3)CysSK4, peptidoglycan)-induced activation of PKC-related signaling cascades were assessed by immunoprecipitation, Western blotting, immunofluorescence, and kinase assays-combined with functional transfection studies in the human model IEC lines HT-29 and Caco-2. Transepithelial electrical resistance characterized intestinal epithelial barrier function. Results: Stimulation with TLR2 ligands led to activation (phosphorylation, enzymatic activity, translocation) of specific PKC isoforms (PKCalpha and PKCdelta). Phosphorylation of PKC by TLR2 ligands was blocked specifically by transfection with a TLR2 deletion mutant. Ligand-induced activation of TLR2 greatly enhanced transepithelial resistance in IECs, which was prevented by pretreatment with PKC-selective antagonists. This effect correlated with apical tightening and sealing of tight junction (TJ)-associated ZO-1, which was mediated via PKC in response to TLR2 ligands, whereas morphologic changes of occludin, claudin-1, or actin cytoskeleton were not evident. Downstream the endogenous PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS), but not transcriptional factor activator protein-1 (AP-1), was activated significantly on stimulation. Conclusions: The present study provides evidence that PKC is an essential component of the TLR2 signaling pathway with the physiologic consequence of directly enhancing intestinal epithelial integrity through translocation of ZO-1 on activation. C1 Univ Hosp Essen, Inst Grp 1, Div Gastroenterol & Hepatol, D-45147 Essen, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Ctr Study Inflammat Bower D, Boston, MA USA. RP Cario, E (reprint author), Univ Hosp Essen, Inst Grp 1, Div Gastroenterol & Hepatol, Virchowstr 171, D-45147 Essen, Germany. EM eike.cario@uni-essen.de OI Gerken, Guido/0000-0001-6734-5001 FU NIDDK NIH HHS [DK43351, DK60049, R01 DK060049] NR 71 TC 232 Z9 239 U1 1 U2 18 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2004 VL 127 IS 1 BP 224 EP 238 DI 10.1053/j.gastro.2004.04.015 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836HE UT WOS:000222545700028 PM 15236188 ER PT J AU Gralnek, IM Dulai, GS AF Gralnek, IM Dulai, GS TI Incremental value of upper endoscopy for triage of patients with acute non-variceal upper-GI hemorrhage SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID UPPER-GASTROINTESTINAL HEMORRHAGE; LOW-RISK PATIENTS; RANDOMIZED CONTROLLED-TRIAL; OUTPATIENT MANAGEMENT; TRACT HEMORRHAGE; CARE; DISCHARGE; COMMUNITY AB Background: Risk scores for triage of patients with acute upper-GI hemorrhage that incorporate endoscopic variables (e.g., the complete Rockall Score) may have better test characteristics for identification of "low-risk" bleeding episodes than those (e.g., Blatchford Score, clinical Rockall Score) that rely solely on clinical variables. An endoscopy-based risk score was compared with two clinically based risk scores in a large cohort of patients hospitalized for treatment of acute upper-GI hemorrhage to quantify the incremental value of endoscopy in the identification of low-risk bleeding. Methods: ICD-9-CMcodes for discharge diagnosis were used to identify a cohort of patients(n=175) hospitalized at a university medical center with acute non-variceal upper-GI hemorrhage. Medical record data were abstracted by two data abstractors blinded to the study intent by using a standardized data collection instrument. Blatchford and Rockall Scores were generated for each case. Low risk was defined as a Blatchford Score of 0, a clinical Rockall Score of 0, or complete Rockall Score of 2 or less. Results: The Blatchford Score risk stratified only 14 of 175 (8%) patients with acute, non-variceal upper-GI hemorrhage as "low risk," while the clinical Rockall Score identified 12%. However, the complete Rockall Score identified the greatest number of low-risk cases, 53/175 (30%) (p<0.0001), when compared with either the Blatchford or clinical Rockall Score. Conclusions: The complete Rockall Score identified significantly more low-risk patients with acute upper-GI hemorrhage than either the clinical Rockall Score or the Blatchford Score. Identification of additional low-risk patients via this endoscopy-based score could lead to decreases in the use of hospital-based services, iatrogenic complications, and time lost from work or usual activity, while improving quality of care. Use of the clinical and complete Rockall Scores sequentially, with consideration of outpatient care for patients at identified as low risk, is recommended. C1 Univ Calif Los Angeles, David Geffen Sch Med ,CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst,Dept Med, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol & Hepatol, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med ,CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst,Dept Med, Ctr Study Digest Healthcare Qual & Outcomes, 11301 Wilshire Blvd,Bldg 115,Rm 215, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [K23 RR1618801] NR 22 TC 44 Z9 47 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2004 VL 60 IS 1 BP 9 EP 14 AR PII S0016-5107(04)01524-X DI 10.1016/S0016-5107(04)01524-X PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 835SN UT WOS:000222505900002 PM 15229418 ER PT J AU Abraham, NS Wieczorek, P Huang, J Mayrand, S Fallone, CA Barkun, AN AF Abraham, NS Wieczorek, P Huang, J Mayrand, S Fallone, CA Barkun, AN TI Assessing clinical generalizability in sedation studies of upper GI endoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/104th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-22, 2003 CL ORLANDO, FL SP Amer Gastroenterol Assoc ID UPPER GASTROINTESTINAL ENDOSCOPY; CONSCIOUS SEDATION; RANDOMIZED-TRIAL; TOLERANCE AB Background: Prior endoscopic studies evaluating conscious sedation have recruited only a small proportion of the patients actually approached. The generalizability of such results to an unselected adult ambulatory care population is thus questionable. The objectives of this study were to determine the characteristics of patients who refused inclusion in a randomized controlled trial of sedation and to compare these characteristics to those of patients who agreed to participate. Methods: Patients who refused participation in a randomized controlled trial of sedation completed standardized questionnaires addressing demographic data and possible confounding variables, and they also completed a validated anxiety questionnaire. Characteristics associated with refusal to participate in the randomized controlled trial were assessed by using uni- and multivariate analysis. Exploratory comparisons of outcomes between both groups included self-reported satisfaction with level of comfort and technical adequacy. Results: Of 302 patients screened, 203 refused to participate in the randomized controlled trial. The most common reason for refusal was the request for no sedation (135/203). A total of 163 were enrolled in this synchronous study. Patients who refused to participate exhibited 3 distinguishing characteristics: prior treatment for an anxiety disorder (risk difference 9.4%: 95% CI[3%,17%]), use of analgesic medication (risk difference 10.4%: 95% CI[2%, 19%]), and prior experience with EGD (risk difference 17.9: 95% CI[5%, 30%]). Only upper endoscopy experience was predictive of refusal to participate in the randomized controlled trial. No differences in outcomes existed between patients randomized to sedation and those refusing the randomized controlled trial who chose to receive sedative medication. Patients who refused participation in the randomized controlled trial and who underwent upper endoscopy without sedation were more satisfied than patients randomized to placebo (1.33 vs. 2.58; risk difference -1.25: 95% CI[-0.385 -2.1]). Moreover, the procedure in these patients was more adequate technically (4.86 vs. 4.18; risk difference 0.68: 95% CI[0.21, 1.13]). Conclusions: Characteristics of patients accepting and refusing randomization were highly similar, differing only with regard to upper endoscopy experience. An exploratory analysis of outcomes suggests that randomized controlled trial results may be biased in a direction that may underestimate the benefits of not administering sedative medication in a real-life setting. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. McGill Univ, Ctr Hlth, Div Gastroenterol, Montreal, PQ, Canada. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2004 VL 60 IS 1 BP 28 EP 33 AR PII S0016-5107(04)01307-0 DI 10.1016/S0016-5107(04)01307-0 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 835SN UT WOS:000222505900005 PM 15229421 ER PT J AU Yeung, A Kung, WW Chung, H Rubenstein, G Roffi, P Mischoulon, D Fava, M AF Yeung, A Kung, WW Chung, H Rubenstein, G Roffi, P Mischoulon, D Fava, M TI Integrating psychiatry and primary care improves acceptability to mental health services among Chinese Americans SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE treatment acceptability; mental health services; primary care; Chinese Americans ID DEPRESSION; GUIDELINES; MANAGEMENT; ILLNESS AB The objective of this study was to investigate whether integrating psychiatry and primary healthcare improves referral to and treatment acceptability of mental health services among Chinese Americans. The "Bridge Project," a program to enhance collaboration between primary care and mental health services for low-income Chinese immigrants was implemented at South Cove Community Health Center in Boston. The project consisted of conducting training seminars to primary care physicians to enhance recognition of common mental disorders, using a primary care nurse as the "bridge" to facilitate referrals to the Behavioral Health Department of the same facility, and co-locating a psychiatrist in the primary care clinic to provide onsite evaluation and treatment. The rate of mental health service referrals and successful treatment engagement before and during the project were compared. During the 12-month period of the Bridge Project, primary care physicians referred 64 (1.05% of all clinic patients) patients to mental health services, a 60% increase (chi(2) = 4.97, P < .05) in the percentage of clinic patients referred in the previous 12 months. Eighty-eight percent of patients referred during the project showed up for psychiatric evaluation, compared to 53% (chi(2) = 15.3, P < .001) in the previous 12 months. Integrating psychiatry and primary care is effective in improving access to mental health services and in increasing treatment engagement among low-income immigrant Chinese Americans. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. S Cove Community Hlth Ctr, Boston, MA 02111 USA. Fordham Univ, Grad Sch Social Serv, New York, NY 10023 USA. NYU, Sch Med, New York, NY USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM ayeung@partners.org FU NIMH NIH HHS [5T32MH19126-10] NR 16 TC 25 Z9 26 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2004 VL 26 IS 4 BP 256 EP 260 DI 10.1016/j.genhosppsych.2004.03.008 PG 5 WC Psychiatry SC Psychiatry GA 838WZ UT WOS:000222745400002 PM 15234819 ER PT J AU Flynn, HA Davis, M Marcus, SM Cunningham, R Blow, FC AF Flynn, HA Davis, M Marcus, SM Cunningham, R Blow, FC TI Rates of maternal depression in pediatric emergency department and relationship to child service utilization SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE maternal depression; depression screening; child health outcomes ID HEALTH-CARE USE; PRESCHOOL-CHILDREN; DOMESTIC VIOLENCE; BEHAVIOR PROBLEMS; SUBSTANCE-ABUSE; YOUNG-CHILDREN; MOTHERS; SYMPTOMS; DISORDERS; PARENTS AB This cross-sectional study aimed to (a) identify rates and correlates of untreated elevated depression in mothers of young children in a pediatric emergency department (ED) setting and (b) examine the association of depression and other key variables to child healthcare use. Mothers (n=176) bringing their child (30 missense mutations in the SPM domain of SCM. Genetic rescue assays showed that SCM repressor function in vivo is disrupted by mutations that impair SPM domain interactions in vitro. Furthermore, overexpression of an isolated, wild-type SPM domain produced PcG loss-of-function phenotypes in flies. Coassembly of SCM with a reconstituted PRC1 core complex shows that SCM can partner with PRC1 However, gel filtration chromatography showed that the bulk of SCM is biochemically separable from PH in embryo nuclear extracts. These results suggest that SCM, although not a core component of PRC1, interacts and functions with PRC1 in gene silencing. C1 Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Simon, JA (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, 321 Church St SE, Minneapolis, MN 55455 USA. EM simon@cbs.umn.edu FU NICHD NIH HHS [HD07480]; NIGMS NIH HHS [GM20895] NR 73 TC 40 Z9 43 U1 2 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2004 VL 167 IS 3 BP 1225 EP 1239 DI 10.1534/genetics.104.027474 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 843TL UT WOS:000223109300017 PM 15280237 ER PT J AU Fearing, MK Levy, HL Wilkins-Haug, LE Larson, C Shih, VE AF Fearing, MK Levy, HL Wilkins-Haug, LE Larson, C Shih, VE TI Maternal liver diseases (MLD) in the pregnancies of infants with the spectrum of fatty acid oxidation defects (FAOD) compared to matched population controls. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Amino Acid Lab, Boston, MA 02114 USA. Childrens Hosp Boston, Boston, MA USA. Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. Univ Massachusetts, New England Newborn Screening Program, Boston, MA 02125 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 48 BP 269 EP 269 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200060 ER PT J AU Tan, W Eichler, F Hoda, S Lee, M Grant, P Krishnamoorthy, K Shih, V AF Tan, W Eichler, F Hoda, S Lee, M Grant, P Krishnamoorthy, K Shih, V TI Isolated sulfite oxidase deficiency - report of a case in a newborn and review of the literature. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Combined Med Pediat Program, Boston, MA USA. Massachusetts Gen Hosp, Div Neuroradiol, 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 69 BP 280 EP 280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200081 ER PT J AU Smith, SE Marsden, D Stoler, JM AF Smith, SE Marsden, D Stoler, JM TI Detection of Smith-Magenis in infancy. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 137 BP 310 EP 310 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200146 ER PT J AU Finn, CT Wilcox, MA Korf, BR Blacker, DL Racette, SA Sklar, P Smoller, JW AF Finn, CT Wilcox, MA Korf, BR Blacker, DL Racette, SA Sklar, P Smoller, JW TI A survey of psychiatrists' knowledge, opinions and practice patterns regarding genetics, with implications for patient care. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Alabama, Birmingham, AL USA. Whitehead Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 185 BP 334 EP 334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200194 ER PT J AU Tache, Y AF Tache, Y TI Corticotropin releasing factor receptor antagonists: potential future therapy in gastroenterology? SO GUT LA English DT Editorial Material ID IRRITABLE-BOWEL-SYNDROME; CRF1 RECEPTOR; LOCUS-COERULEUS; GASTROINTESTINAL MOTILITY; INTERFERON-ALPHA; COLONIC MUCOSA; MOTOR FUNCTION; STRESS; HORMONE; RATS AB New corticotropin releasing factor (CRF) antagonists in irritable bowel disease (IBS) warrant testing, and CRF1 receptors may be a promising target for the treatment of IBS. C1 VA Greater Los Angeles Hlth Care Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Hlth Care Syst, CURE, Digest Dis Res Ctr, Bldg 115,Room 117,1130 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yTache@ucla.edu NR 44 TC 27 Z9 31 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUL PY 2004 VL 53 IS 7 BP 919 EP 921 DI 10.1136/gut.2003.036400 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829CS UT WOS:000222021800002 PM 15194633 ER PT J AU Schouten, R Callahan, MV Bryant, S AF Schouten, R Callahan, MV Bryant, S TI Community response to disaster: The role of the Workplace SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE disasters; disaster management; disaster preparedness; occupational mental health; terrorism; trauma; violence; workplace ID NATURAL DISASTER; SOCIAL SUPPORT; TERRORIST ATTACKS; VIOLENT CRIME; VICTIMS; STRESS; TRAUMA; CITY; BIOTERRORISM; STRATEGIES AB Disasters, natural and man-made, have a considerable impact on communities. Most recently, disasters stemming from terrorist attacks have become a leading cause of concern. The importance of work in the lives of employees, coupled with the vulnerability of workplaces as potential targets of terrorist attacks, suggests that workplaces can and should play a role in planning for, and responding to, disasters. This article addresses the role of the workplace in disasters, with an emphasis on the psychological impact of such events, by drawing upon experience and literature related to workplace violence and to other traumatic events in the workplace. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Integrating Med & Innovat Technol, Boston, MA 02114 USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, 60 Staniford St, Boston, MA 02114 USA. EM rschouten@partners.org NR 68 TC 17 Z9 17 U1 4 U2 8 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2004 VL 12 IS 4 BP 229 EP 237 DI 10.1080/10673220490509624 PG 9 WC Psychiatry SC Psychiatry GA 860QH UT WOS:000224357600006 PM 15371065 ER PT J AU Poon, EG Blumenthal, D Jaggi, T Honour, MM Bates, DW Kaushal, R AF Poon, EG Blumenthal, D Jaggi, T Honour, MM Bates, DW Kaushal, R TI Overcoming barriers to adopting and implementing computerized physician order entry systems in US hospitals SO HEALTH AFFAIRS LA English DT Article AB Few U.S. hospitals have implemented computerized physician order entry (CPOE) in spite of its effectiveness at preventing serious medication errors. We interviewed senior management at twenty-six hospitals to identify ways to overcome barriers to adopting and implementing CPOE. Within the hospital, strong leadership and high-quality technology were critical. Hospitals that placed a high priority on patient safety could more easily justify the cost of CPOE. Outside the hospital, financial incentives and public pressures encouraged CPOE adoption. Dissemination of data standards would accelerate the maturation of vendors and lower CPOE costs. These findings highlight several policy levers to speed the adoption of this important patient safety technology. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. RP Poon, EG (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM epoon@partners.org NR 15 TC 170 Z9 171 U1 0 U2 13 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2004 VL 23 IS 4 BP 184 EP 190 DI 10.1377/hlthaff.23.4.184 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 835QC UT WOS:000222499600019 PM 15318579 ER PT J AU Friedman, PL Dubuc, M Green, MS Jackman, WM Keane, DTJ Marinchak, RA Nazari, J Packer, DL Skanes, A Steinberg, JS Stevenson, WG Tchou, PJ Wilber, DJ Worley, SJ AF Friedman, PL Dubuc, M Green, MS Jackman, WM Keane, DTJ Marinchak, RA Nazari, J Packer, DL Skanes, A Steinberg, JS Stevenson, WG Tchou, PJ Wilber, DJ Worley, SJ TI Catheter cryoablation of supraventricular tachycardia: Results of the multicenter prospective "frosty" trial SO HEART RHYTHM LA English DT Article DE catheter ablation; mapping; atrioventricular node; tachycadia; Wolff-Parkinson-White syndrome ID PARKINSON-WHITE-SYNDROME; ACCESSORY ATRIOVENTRICULAR PATHWAYS; NODAL REENTRANT TACHYCARDIA; RADIOFREQUENCY CURRENT; ATRIAL-FIBRILLATION; SLOW-PATHWAY; ABLATION AB OBJECTIVE To study the safety, efficacy, and mapping utility of a new cryoablation catheter. BACKGROUND The CryoCath Technologies Freezor catheter has been used successfully for cryoablation of supraventricular tachycardia (SVT), but has not been evaluated in a large clinical trial. METHODS A multicenter clinical trial to evaluate the safety, efficacy, and cryomapping utility of this cryoablation catheter was conducted in 166 subjects. The target of ablation was the slow pathway in patients with SVT due to AV nodal reentry (AVNRT, n = 103), an accessory pathway in patients with AV reentrant SVT (AVRT, n = 51) and the AV junction in patients with atrial fibrillation (AF, n = 12). RESULTS Acute procedural success (APS) was achieved in 83% of the overall group (95% CI, 76% to 88%). APS in the AVNRT group was 91% (98.3% CI, 82% to 97%), compared to 69% for AVRT (98.3% CI, 51% to 84%) and 67% for AF (98.3% CI, 29% to 93%), a highly significant difference (P < .001 by stepwise logistic regression). In patients with APS, long-term success after 6 months was 91% overall (95% CI, 86% to 96%) and 94% for AVNRT subjects (98.3% CI, 87% to 100%). None of the AVNRT or AVRT subjects required a permanent pacemaker. Cryomapping successfully identified ablation targets in 64% of patients in whom it was attempted. The electrophysiologic effects of cryomapping were completely reversible within minutes in 94% of such attempts. CONCLUSIONS Catheter cryoablation of SVT is a safe alternative to RF ablation and is clinically effective in patients with AVNRT. Cryomapping can reversibly identify targets for ablation and can help minimize the risk of inadvertent AV block during ablation. (C) 2004 Heart Rhythm Society. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cardiol Fdn Lankenau, Wynnewood, PA USA. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. Mayo Clin Fdn, Rochester, MN USA. London Hlth Sci Ctr, London, ON, Canada. St Lukes Roosevelt Hosp, New York, NY USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Chicago, Chicago, IL 60637 USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Lancaster Heart Fdn, Lancaster, PA USA. RP Friedman, PL (reprint author), Cardiovasc Specialists, 25 Main St, Hyannis, MA 02601 USA. NR 14 TC 96 Z9 100 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2004 VL 1 IS 2 BP 129 EP 138 DI 10.1016/j.hrthm.2004.02.022 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 879KB UT WOS:000225715600001 PM 15851143 ER PT J AU Ruskin, JN Singh, JP AF Ruskin, JN Singh, JP TI Atrial fibrillation endpoints: Hospitalization SO HEART RHYTHM LA English DT Article; Proceedings Paper CT Atrial Fibrillation Endpoints Symposium CY NOV 24-25, 2003 CL Minneapolis, MN SP Medtron Inc ID CONGESTIVE-HEART-FAILURE; RISK; PREVALENCE; STROKE; PREVENTION; PROGNOSIS; MORTALITY; TRENDS; DEATH C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 109, Boston, MA 02114 USA. EM jruskin@partners.org NR 18 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2004 VL 1 IS 2 SU S BP B31 EP B34 DI 10.1016/j.hrthm.2004.04.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880BM UT WOS:000225763300009 PM 15851136 ER PT J AU Butt, AA Fultz, SL Kwoh, CK Kelley, D Skanderson, M Justice, AC AF Butt, AA Fultz, SL Kwoh, CK Kelley, D Skanderson, M Justice, AC TI Risk of diabetes in HIV infected veterans pre- and Post-HAART and the role of HCV coinfection SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 10th Conference on Retroviruses and Opportunistic Infections CY FEB 10-14, 2003 CL BOSTON, MA ID HEPATITIS-C VIRUS; UNITED-STATES; MELLITUS; PREVALENCE; ASSOCIATION; COHORT AB We examined the association of hepatitis C virus (HCV) infection with diabetes in veterans infected with human immunodeficiency virus (HIV) before and after the institution of highly active antiretroviral therapy (HAART). The role of age, race, liver disease, alcohol, and drug diagnoses upon the risk of diabetes was also determined. Male veterans with HIV who entered care between 1992 and 2001 were identified from the Veterans Affairs (VA) administrative database. Demographic and disease data were extracted. Kaplan-Meier curves were plotted to determine the incidence of diabetes. Unadjusted and adjusted hazards ratios for diabetes were determined using Cox regression method. A total of 26,988 veterans were studied. In multivariate Cox regression analysis, factors associated with a diagnosis of diabetes included increasing age (HR, 1.44 per 10-year increase in age; 95% CI, 1.39-1.49), minority race (African American: HR, 1.35; 95% Cl, 1.24-1.48; Hispanic: HR, 1.63; 95% Cl, 1.43-1.86), and care in the HAART era (HR, 2.35; 95% CI, 2.01-2.75). There was a significant interaction between care in the HAART era and HCV infection, with HCV infection being associated with a significant risk of diabetes in the HAART era (HR, 1.39; 95% Cl, 1.27-1-53) but not in the pre-HAART era (HR, 1.01; 95% CI, 0.75-1.36). In conclusion, HIV-infected veterans in the HAART era are at a higher risk for diabetes compared with those in the pre-HAART era. HCV coinfection is associated with a significantly higher risk of diabetes in the HAART era, but not in the pre-HAART era. HCV HIV coinfected patients should be aggressively screened for diabetes. C1 Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. Div Rheumatol, Pittsburgh, PA USA. Div Endocrinol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Yale Univ, Sch Med, New Haven, CT USA. VA Connecticut Healthcare Syst, West Haven, CT USA. RP Justice, AC (reprint author), W Haven VA Healthcare Syst, 950 Campbell Ave,11-ACSLG, West Haven, CT 06516 USA. EM amy.justice2@med.va.gov FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [3U01 AA 13566]; NIDA NIH HHS [1 K23 DA016175-01A1] NR 18 TC 66 Z9 66 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2004 VL 40 IS 1 BP 115 EP 119 DI 10.1002/hep.20289 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 835SO UT WOS:000222506000018 PM 15239093 ER PT J AU Talavage, TM Edmister, WB AF Talavage, TM Edmister, WB TI Nonlinearity of fMRI responses in human auditory cortex SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; BOLD response; acoustic noise ID ACOUSTIC NOISE; ORGANIZATION; INTERFERENCE AB An investigation was made into the nature of the nonlinearity observed in auditory functional magnetic resonance imaging (fMRI) experiments associated with increases in total duration of acoustic imaging noise [e.g., Edmister et al., 1999; Shah et al., 1999]. A two-stimulus, four-condition paradigm was used to evaluate four acoustic conditions involving: (1) the presence or absence of a desired broadband music stimulus; and (2) two possible durations of trains of acoustic noise associated with image acquisition. Responses observed while increasing the duration of acoustic imaging noise were consistent with previous work (Talavage et al. [1999]: Hum Brain Mapp7:79-88) but the response to combined stimulation did not exhibit variation as a function of the acoustic imaging noise duration. These results suggest that spectral overlap of the stimuli produced colocalized responses that did not add linearly. This conclusion has implications for conducting both blocked and rapid-presentation event-related auditory fMRl experiments. The cortical activity induced by the stimulus may not reflect the activation, in spatial extent or magnitude of signal change, occurring in the absence of other acoustic noise. (C) 2004 Wiley-Liss, Inc. C1 Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. Purdue Univ, Dept Biomed Engn, W Lafayette, IN 47907 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. Mayo Clin, Dept Radiol, Rochester, MN USA. RP Talavage, TM (reprint author), Purdue Univ, Sch Elect & Comp Engn, 465 Northwestern Ave, W Lafayette, IN 47907 USA. EM tmt@ecn.purdue.edu FU NIDA NIH HHS [P01DA09467-03]; NIDCD NIH HHS [T32DC00038-04, P01DC00119] NR 18 TC 25 Z9 25 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2004 VL 22 IS 3 BP 216 EP 228 DI 10.1002/hbm.20029 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 833ZJ UT WOS:000222380000005 PM 15195288 ER PT J AU Paris, PL Andaya, A Fridlyand, J Jain, AN Weinberg, V Kowbel, D Brebner, JH Simko, J Watson, JEV Volik, S Albertson, DG Pinkel, D Alers, JC van der Kwast, TH Vissers, KJ Schroder, FH Wildhagen, MF Febbo, PG Chinnaiyan, AM Pienta, KJ Carroll, PR Rubin, MA Collins, C van Dekken, H AF Paris, PL Andaya, A Fridlyand, J Jain, AN Weinberg, V Kowbel, D Brebner, JH Simko, J Watson, JEV Volik, S Albertson, DG Pinkel, D Alers, JC van der Kwast, TH Vissers, KJ Schroder, FH Wildhagen, MF Febbo, PG Chinnaiyan, AM Pienta, KJ Carroll, PR Rubin, MA Collins, C van Dekken, H TI Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors SO HUMAN MOLECULAR GENETICS LA English DT Article ID CANCER AGGRESSIVENESS LOCUS; HIGH-RESOLUTION ANALYSIS; HOMEOBOX GENE NKX3.1; DNA COPY NUMBER; RADICAL PROSTATECTOMY; SQUAMOUS-CELL; ALLELIC IMBALANCE; EPITHELIAL-CELLS; HYBRIDIZATION; WIDE AB Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm among American males and is the second leading cause of cancer-related death. Prostate specific antigen screening has resulted in earlier disease detection, yet similar to30% of men will die of metastatic disease. Slow disease progression, an aging population and associated morbidity and mortality underscore the need for improved disease classification and therapies. To address these issues, we analyzed a cohort of patients using array comparative genomic hybridization (aCGH). The cohort comprises 64 patients, half of whom recurred postoperatively. Analysis of the aCGH profiles revealed numerous recurrent genomic copy number aberrations. Specific loss at 8p23.2 was associated with advanced stage disease, and gain at 11q13.1 was found to be predictive of postoperative recurrence independent of stage and grade. Moreover, comparison with an independent set of metastases revealed approximately 40 candidate markers associated with metastatic potential. Copy number aberrations at these loci may define metastatic genotypes. C1 Univ Calif San Francisco, Ctr Comprehens Canc, Dept Urol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Pathol Anat, San Francisco, CA 94115 USA. Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Urol, Rotterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Pathol, Rotterdam, Netherlands. RP Collins, C (reprint author), Univ Calif San Francisco, POB 808, San Francisco, CA 94143 USA. EM collins@cc.ucsf.edu RI Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50CA69568, P50CA89520] NR 66 TC 135 Z9 143 U1 0 U2 5 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 JUL 1 PY 2004 VL 13 IS 13 BP 1303 EP 1313 DI 10.1093/hmg/ddh155 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 830LD UT WOS:000222122700002 PM 15138198 ER PT J AU Tantisira, KG Lake, S Silverman, ES Palmer, LJ Lazarus, R Silverman, EK Liggett, SB Gelfand, EW Rosenwasser, LJ Richter, B Israel, E Wechsler, M Gabriel, S Altshuler, D Lander, E Drazen, J Weiss, ST AF Tantisira, KG Lake, S Silverman, ES Palmer, LJ Lazarus, R Silverman, EK Liggett, SB Gelfand, EW Rosenwasser, LJ Richter, B Israel, E Wechsler, M Gabriel, S Altshuler, D Lander, E Drazen, J Weiss, ST TI Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids SO HUMAN MOLECULAR GENETICS LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; RANDOMIZED CONTROLLED TRIAL; PERSISTENT ASTHMA; FACTOR-RECEPTOR; NEUROENDOCRINE; BUDESONIDE; RESPONSES; CHILDREN; DISEASE; STRESS AB Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Western Australia, Med Res Ctr, Western Australian Inst Med Res, Perth, WA 6000, Australia. Univ Cincinnati, Div Pulm, Cincinnati, OH 45867 USA. Natl Jewish Med & Res Ctr, Dept Pediat & Med, Denver, CO 80206 USA. Eli & Edythe L Borad Inst, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02141 USA. MIT, Dept Biol, Cambridge, MA 02141 USA. RP Weiss, ST (reprint author), Brigham & Womens Hosp, Channing Lab, 102 Longwood Ave, Boston, MA 02115 USA. EM scott.weiss@channing.harvard.edu RI Altshuler, David/A-4476-2009; liggett, stephen/E-7453-2012; Wechsler, Michael /B-3979-2013; Palmer, Lyle/K-3196-2014 OI Altshuler, David/0000-0002-7250-4107; Wechsler, Michael /0000-0003-3505-2946; Palmer, Lyle/0000-0002-1628-3055 FU NCRR NIH HHS [M01 RR00079, M01 RR03186]; NHLBI NIH HHS [HR16046, HR16045, HR16047, HR16048, HR16049, HR16050, HR16051, HR16052, N01 HR16044, P01 HL67664, U01 HL 51843, U01 HL51510, U01 HL51831, U01 HL51834, U01 HL51845] NR 28 TC 194 Z9 208 U1 0 U2 5 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 JUL 1 PY 2004 VL 13 IS 13 BP 1353 EP 1359 DI 10.1093/hmg/ddh149 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 830LD UT WOS:000222122700007 PM 15128701 ER PT J AU Nakatani, Y Masudo, K Nozawa, A Inayama, Y Yamanaka, S Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Resl, M Mark, EJ AF Nakatani, Y Masudo, K Nozawa, A Inayama, Y Yamanaka, S Ito, T Kitamura, H Notohara, K Kashima, K Yokoyama, S Tsujimoto, M Tamai, S Abe, Y Resl, M Mark, EJ TI Biotin-rich, optically clear nuclei express estrogen receptor-beta: Tumors with morules may develop under the influence of estrogen and aberrant beta-catenin expression SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol DE estrogen receptor-beta; beta-catenin; Wnt-signaling pathway; morules ID CONTAINING INTRANUCLEAR INCLUSIONS; FETAL LUNG TYPE; THYROID-CARCINOMA; TRANSCRIPTIONAL ACTIVITY; OVARIAN CARCINOMAS; COLORECTAL-CANCER; LOW-GRADE; ER-ALPHA; LOCALIZATION; MUTATIONS AB Recent studies have indicated that aberrant beta-catenin expression may be a common denominator for the morular formation of tumors from various anatomic sites. The evidence for the influence of female sex hormones in the formation of morules has been circumstantial, most previous studies having failed to demonstrate female sex hormone receptors in the mondar cells. We investigated a possible role of estrogen receptor (ER)-beta in the occurrence of tumors that form morules with biotin-rich optically clear nuclei (BROCN)(BROCN-family tumors) and its possible relationship with aberrant nuclear/cytoplasmic (N/C) beta-catenin expression. We immunostained 14 BROCN-family tumors, including 6 low-grade adenocarcinomas of the fetal lung type, 3 papillary thyroid carcinomas of cribriform-morular variant (CMV), 2 ovarian endometrioid tumors, 2 colonic adenocarcinomas, and 1 gallbladder adenoma, as well as 4 cases of endometrial tissue with BROCN during gestation, for ERbeta, ERalpha, progesterone receptor (PgR), beta-catenin, and, on a subset of cases, c-Fos and MIB-1 as well. BROCN in all 18 cases expressed ERbeta but not ERalpha or PgR. In the BROCN-family tumors, the morular cells and budding glandular cells expressed ERbeta in the cytoplasm and BROCN, which overlapped with the N/C expression pattern of beta-catenin. beta-catenin showed only membranous expression in the endometrial glands during gestation. In CMV and ovarian endometrioid tumors, nuclear expression of ERalpha and PgR were observed in association with N/C beta-catenin expression only in the glandular component. C-Fos was also constantly and strongly expressed in BROCN in all cases examined. The MIB-1 labeling index was low in the morular area, ranging from 1% to 3 %. The present study indicates that N/C co-localization of ERbeta and beta-catenin is a feature common to the morules with BROCN that appear in the BROCN-family tumors from various anatomic sites. Whether the estrogen-signaling pathway and the Wnt-signaling pathway have crosstalk, cooperating in the development of the BROCN-family tumors, awaits further study. (C) 2004 Elsevier Inc. All rights reserved. C1 Yokohama City Univ, Ctr Med, Dept Pathol, Yokohama, Kanagawa 232, Japan. Hosp Yokohama City Univ, Div Anatom & Surg Pathol, Yokohama, Kanagawa 232, Japan. Yokohama City Univ, Sch Med, Dept Pathol, Yokohama, Kanagawa 232, Japan. Ito Hosp, Dept Surg, Tokyo, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Pathol Res, Okayama, Japan. Med Coll Oita, Dept Pathol, Oita 87956, Japan. Osaka Police Hosp, Dept Pathol, Osaka, Japan. Natl Def Med Coll, Dept Lab Med, Tokorozawa, Saitama, Japan. Natl Kanagawa Hosp, Dept Pathol, Hadano, Japan. Charles Univ, Sch Med, Hradec Kralove, Czech Republic. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nakatani, Y (reprint author), Chiba Univ Hosp, Dept Pathol, Chuo Ku, 1-8-1 Inohana, Chiba 2608677, Japan. NR 44 TC 24 Z9 24 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 2004 VL 35 IS 7 BP 869 EP 874 DI 10.1016/j.humpath.2004.03.018 PG 6 WC Pathology SC Pathology GA 843CK UT WOS:000223052900014 PM 15257551 ER PT J AU Shigematsu, H Reizis, B Iwasaki, H Mizuno, S Hu, D Traver, D Leder, P Sakaguchi, N Akashi, K AF Shigematsu, H Reizis, B Iwasaki, H Mizuno, S Hu, D Traver, D Leder, P Sakaguchi, N Akashi, K TI Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin SO IMMUNITY LA English DT Article ID RECEPTOR-ALPHA-GENE; COMMON PRECURSOR POPULATION; HEMATOPOIETIC STEM-CELLS; MOUSE BONE-MARROW; T-CELLS; MYELOID PROGENITOR; FLT3 LIGAND; COMMITTED PROGENITORS; ARTIFICIAL CHROMOSOME; DEFICIENT MICE AB The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTalpha transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTalpha transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Kumamoto Univ, Grad Sch Med Sci, Dept Immunol, Kumamoto 8608556, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Higashi Ku, Fukuoka 8128582, Japan. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM koichi_akashi@dfci.harvard.edu RI Hu, Dan/D-9642-2015 FU NCI NIH HHS [CA072009]; NIDDK NIH HHS [DK050654, DK061320] NR 60 TC 137 Z9 143 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2004 VL 21 IS 1 BP 43 EP 53 DI 10.1016/j.immuni.2004.06.011 PG 11 WC Immunology SC Immunology GA 842AU UT WOS:000222975500007 PM 15345219 ER PT J AU Anzueto, A Norris, S AF Anzueto, A Norris, S TI Clarithromycin in 2003: sustained efficacy and safety in an era of rising antibiotic resistance SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Review DE clarithromycin; antibiotic resistance; respiratory tract infection ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE BACTERIAL EXACERBATIONS; RESPIRATORY-TRACT INFECTIONS; COMPARATIVE INVITRO ACTIVITY; IMMEDIATE-RELEASE FORMULATIONS; BREAKTHROUGH PNEUMOCOCCAL BACTEREMIA; ANTIMICROBIAL SURVEILLANCE PROGRAM; TWICE-DAILY CLARITHROMYCIN; IN-VITRO ACTIVITIES; STREPTOCOCCUS-PNEUMONIAE AB Data from surveillance studies show increasing prevalence of respiratory pathogens resistant to commonly used antibiotics. Thus, a Medline search was conducted to identify studies of clarithromycin, especially those addressing macrolide resistance. Changing trends of in vitro susceptibility have not affected clinical efficacy with clarithromycin. Over the last 12 years, clarithromycin study results have shown consistent rates of clinical cure and bacteriological eradication, which are similar to those observed with comparator agents. The incidence of clarithromycin treatment failure in patients infected with Streptococcus pneumoniae is substantially less than that predicted by macrolide resistance rates from surveillance programmes. In summary, despite widespread use since its introduction, clarithromycin remains active both in vitro and in vivo against clinically relevant respiratory tract pathogens. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Wayne State Univ, Detroit, MI USA. RP Anzueto, A (reprint author), Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM anzueto@uthscsa.edu RI Gough, Ethan/B-8633-2012 NR 160 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUL PY 2004 VL 24 IS 1 BP 1 EP 17 DI 10.1016/j.ijantimicag.2004.03.003 PG 17 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 841SZ UT WOS:000222953200001 PM 15225854 ER PT J AU Sherman, AC Mosier, J Leszcz, M Burlingame, GM Ulman, KH Cleary, T Simonton, S Latif, U Hazelton, L Strauss, B AF Sherman, AC Mosier, J Leszcz, M Burlingame, GM Ulman, KH Cleary, T Simonton, S Latif, U Hazelton, L Strauss, B TI Group interventions for patients with cancer and HIV disease: Part III. Moderating variables and mechanisms of action SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Review ID BEHAVIORAL STRESS-MANAGEMENT; STRUCTURED PSYCHIATRIC INTERVENTION; AFRICAN-AMERICAN ADOLESCENTS; METASTATIC BREAST-CANCER; SEXUALLY-TRANSMITTED-DISEASE; RANDOMIZED CONTROLLED-TRIAL; SUPPORT GROUP INTERVENTION; AIDS-PREVENTION PROGRAM; TERM GROUP-THERAPY; RISK-REDUCTION AB Growing evidence supports the value of group interventions for individuals who are at risk for or have developed cancer or HTV disease. However, information is more limited concerning how these services can be delivered in an optimal manner, and what processes contribute to their benefits. Parts I and II of this review examined the efficacy of different interventions for individuals at different phases of illness, ranging from primary prevention to late-stage disease, in both psychosocial and biological domains. The current paper examines some of the factors other than phase of illness that might influence group treatment effects (e.g., intervention parameters, participant characteristics), and explores mechanisms of action. C1 Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA. Univ Toronto, Dept Psychiat & Head, Grp Psychotherapy, Toronto, ON, Canada. Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Private Practice, Chevy Chase, MD USA. Univ Arkansas, Program Dev Behav Med, Fayetteville, AR 72701 USA. Univ Arkansas, Dept Otolaryngol, Fayetteville, AR 72701 USA. Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 3J5, Canada. RP Sherman, AC (reprint author), Univ Arkansas Med Sci, Dept Otolaryngol, 4301 W Markham St, Little Rock, AR 72205 USA. EM ShermanAllenC@uams.edu RI Burlingame, Gary/L-2449-2014; Leszcz, Molyn/N-9043-2016 NR 127 TC 12 Z9 12 U1 6 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2004 VL 54 IS 3 BP 347 EP 387 DI 10.1521/ijgp.54.3.347.40339 PG 41 WC Psychology, Clinical SC Psychology GA 833FD UT WOS:000222321000004 PM 15253509 ER PT J AU Pantanowitz, L Bauer, K Tefs, K Schuster, V Balogh, K Pilch, BZ Adcock, P Cirovic, C Kocher, O AF Pantanowitz, L Bauer, K Tefs, K Schuster, V Balogh, K Pilch, BZ Adcock, P Cirovic, C Kocher, O TI Ligneous (Pseudomembranous) inflammation involving the female genital tract associated with type-1 plasminogen deficiency SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ligneous inflammation; female genital tract; type-1 plasminogen deficiency ID CONJUNCTIVITIS; CERVIX AB Ligneous (pseudomembranous) inflammation of the female genital tract is a rare and unusual condition characterized by extensive subepithelial fibrin deposition and associated inflammation. Ligneous inflammation in extragenital sites, predominantly the conjunctiva, has been linked to plasminogen deficiency, Individuals with plasminogen deficiency are unable to remove fibrin deposited in injured mucosal tissue. Severe systemic ligneous inflammation involving the female genital tract that is linked to hypoplasminogenemia has not previously been described. We present a patient with ligneous inflammation of her genital. middle ear, and oral mucosa that was associated with type-1 homozygous plasminogen deficiency due to a novel missense mutation in the plasminogen gene. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Univ Leipzig, Sch Med, Dept Pediat, Leipzig, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Univ Colorado, Ctr Hlth Sci, Dept Pathol, Aurora, CO USA. RP Pantanowitz, L (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM lpantano@bidmc.harvard.edu NR 10 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2004 VL 23 IS 3 BP 292 EP 295 DI 10.1097/01.pgp.0000130043.59593.82 PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 833GG UT WOS:000222324200014 PM 15213608 ER PT J AU Arsuaga, J Greulich-Bode, KM Vazquez, M Bruckner, M Hahnfeldt, P Brenner, DJ Sachs, R Hlatky, L AF Arsuaga, J Greulich-Bode, KM Vazquez, M Bruckner, M Hahnfeldt, P Brenner, DJ Sachs, R Hlatky, L TI Chromosome spatial clustering inferred from radiogenic aberrations SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID INDUCED STRUCTURAL-ABERRATIONS; HUMAN-LYMPHOCYTES; MAMMALIAN-CELLS; DNA-CONTENT; RADIATION; NUCLEI; INTERPHASE; MITOSIS; ORDER; MFISH AB Purpose: Analysing chromosome aberrations induced by low linear energy transfer (LET) radiation in order to characterize systematic spatial clustering among the 22 human autosomes in human lymphocytes and to compare their relative participation in interchanges. Materials and methods: A multicolour fluorescence in situ hybridization (mFISH) data set, specifying colour junctions in metaphases of human peripheral blood lymphocytes 72 h after in vitro exposure to low LET radiation, was analysed separately and in combination with previously published results. Monte Carlo computer simulations and mathematical modelling guided data analysis. Results and conclusions: Statistical tests on aberration data confirmed two clusters of chromosomes, {1, 16, 17, 19, 22} and {13, 14, 15, 21, 22}, as having their members being on average closer to each other than randomness would predict. The first set has been reported previously to be near the centre of the interphase nucleus and to be formed mainly by gene-rich chromosomes, while the second set comprises the nucleolus chromosomes. The results suggest a possible interplay between chromosome positioning and transcription. A number of other clusters suggested in the literature were not confirmed and considerable randomness of chromosome-chromosome juxtapositions was present. In addition, and consistent with previous results, it was found that chromosome participation in interchanges is approximately proportional to the two-thirds power of the DNA content. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Tech Univ Munich, Dept Radiat Oncol, D-8000 Munich, Germany. German Canc Res Ctr, Dept Skin Carcinogenesis, Heidelberg, Germany. Harvard Univ, Sch Med, DFCI, Boston, MA 02115 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. RP Sachs, R (reprint author), Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. EM sachs@math.berkeley.edu FU NCI NIH HHS [CA78496]; NIGMS NIH HHS [GM68423] NR 39 TC 21 Z9 22 U1 0 U2 2 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 JUL PY 2004 VL 80 IS 7 BP 507 EP 515 DI 10.1080/09553000410001723857 PG 9 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 836JC UT WOS:000222550800006 PM 15360089 ER PT J AU Wyss, C Moter, A Choi, BK Dewhirst, FE Xue, Y Schupbach, P Gobel, UB Paster, BJ Guggenheim, B AF Wyss, C Moter, A Choi, BK Dewhirst, FE Xue, Y Schupbach, P Gobel, UB Paster, BJ Guggenheim, B TI Treponema putidum sp nov., a medium-sized proteolytic spirochaete isolated from lesions of human periodontitis and acute necrotizing ulcerative gingivitis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID SACCHAROLYTIC SPIROCHETE; ORAL SPIROCHETE; DIVERSITY; DENTICOLA; PALLIDUM; IDENTIFICATION; SOCRANSKII; ACID AB So far, little phenotypic heterogeneity has been detected in cultured oral treponemes with trypsin-like proteolytic activity, and all have been assigned to the species Treponema denticola. However, comparisons of protein patterns and antigen expression in our collection of proteolytic oral treponemes occasionally identified isolates with a unique phenotype; e.g. strain OMZ 830 (=ATCC 700768), which qualified as a 'pathogen-related oral spirochaete' due to the presence of a similar to37 kDa protein reactive with the Treponema pallidum FlaA-specific mAb H9-2. In addition to such single isolates, a homogeneous group of seven independent strains is described that were highly motile, medium-sized, proteolytic but asaccharolytic spirochaetes and were cultured from human gingivitis, periodontitis and acute necrotizing ulcerative gingivitis in medium OMIZ-Pat supplemented with 1% human serum and antibiotics. Growth of these spirochaetes in OMIZ-Pat was not dependent on, but was stimulated by, human or bovine serum. Carbohydrates were neither required nor stimulatory for growth. The protein and antigen patterns of total cell extracts of these organisms separated by SIDS-PAGE were distinct from those of all previously cultured spirochaetes, with highest similarity to T denticola. The novel spirochaete has a 2: 4: 2 arrangement of the periplasmic flagella, similar to T denticola. However, the flagellin pattern as detected by immunostaining or glycan staining of Western blots readily distinguished the novel group from T denticola. Also, distinct from reference strains of T denticola, none of the novel isolates displayed sialidase or dentilisin activities, both of which are expressed by most strains of T denticola. Trypsin-like activity and other enzymes as detected by API ZYM test were similar to those of T denticola. The status of a novel species is supported by the 16S rRNA gene sequence, with 98-5% similarity to its closest cultured relative, T denticola. The name Treponema putidum sp, nov. is proposed (type strain OMZ 758(T) = ATCC 700334(T)=CIP 108088(T)). C1 Univ Zurich, Zentrum Zahn Mund & Kieferheilkunde, Inst Orale Mikrobiol & Allgemeine Immunol, CH-8028 Zurich, Switzerland. Charite Univ Med Berlin, Inst Mikrobiol & Hyg, D-10117 Berlin, Germany. Seoul Natl Univ, Coll Dent, Dept Oromaxillofacial Infect & Immun, Seoul 110749, South Korea. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Wyss, C (reprint author), Univ Zurich, Zentrum Zahn Mund & Kieferheilkunde, Inst Orale Mikrobiol & Allgemeine Immunol, Plattenstr 11, CH-8028 Zurich, Switzerland. EM wyss.c@zzmk.unizh.ch OI Moter, Annette/0000-0003-1318-5780 FU NIDCR NIH HHS [DE-11443, DE-10374] NR 22 TC 31 Z9 35 U1 2 U2 6 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUL PY 2004 VL 54 BP 1117 EP 1122 DI 10.1099/ijs.0.02806-0 PN 4 PG 6 WC Microbiology SC Microbiology GA 844IO UT WOS:000223151800017 PM 15280279 ER PT J AU Proano, CE Mulroy, L Jones, E Azar, DT Redmond, RW Kochevar, IE AF Proano, CE Mulroy, L Jones, E Azar, DT Redmond, RW Kochevar, IE TI Photochemical keratodesmos for bonding corneal incisions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BIOLOGIC TISSUE GLUE; PENETRATING KERATOPLASTY; CATARACT INCISIONS; RADIAL KERATOTOMY; SUTURES; MONOFILAMENT; COLLAGEN; CLOSURE; STRENGTH; EYES AB PURPOSE. To evaluate the immediate and long-term effectiveness of a dye-plus-laser irradiation treatment ( photochemical keratodesmos [PKD]) for sealing corneal incisions. METHODS. Incisions (3.5 mm) in rabbit corneas were treated on the incision walls with rose bengal dye followed by exposure to 514-nm laser radiation. PKD was evaluated in three groups (n = 3-6) using laser fluences of 115, 153, or 192 J/cm(2) (180-, 240-, and 300- second exposures, respectively) compared with an untreated group (n = 8). The intraocular pressure at which leakage occurred (IOPL) during infusion of saline into the anterior chamber was determined. In a long-term study, treated and control corneas were observed weekly for 10 weeks for the appearance of neovascularization, anterior chamber inflammation, iridocorneal adhesion, corneal melting, and scarring. RESULTS. Immediately after treatment, the IOPL increased with increasing laser fluence, producing IOPs of 230 +/- 90, 370 +/- 120, and more than 500 mm Hg at 115, 153, and 192 J/cm2, respectively, compared with 40 +/- 20 mm Hg in control eyes (P < 0.005). No reduction in the IOPL was observed up to 14 days after surgery. Corneal melting in PKD-treated or control eyes was not observed in the 10-week healing study. Neovascularization, which peaked at 4 weeks but resolved by 8 weeks, was detected around the incision in both PKD-treated and control eyes. CONCLUSIONS. Immediate and lasting sealing of corneal incisions was obtained in eyes treated with PKD, using short irradiation times. These results suggest that PKD has potential for improved corneal tissue bonding. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, WEL-224, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu NR 30 TC 25 Z9 27 U1 1 U2 2 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 JUL PY 2004 VL 45 IS 7 BP 2177 EP 2181 DI 10.1167/iovs.03-1066 PG 5 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900017 PM 15223792 ER PT J AU Yamada, K Chan, WM Andrews, C Bosley, TM Sener, EC Zwaan, JT Mullaney, PB Ozturk, BT Akarsu, AN Sabol, LJ Demer, JL Sullivan, TJ Gottlob, I Roggenkaemper, P Mackey, DA de Uzcategui, CE Uzcategui, N Ben-Zeev, B Traboulsi, EI Magli, A de Berardinis, T Gagliardi, V Awasthi-Patney, S Vogel, MC Rizzo, JF Engle, EC AF Yamada, K Chan, WM Andrews, C Bosley, TM Sener, EC Zwaan, JT Mullaney, PB Ozturk, BT Akarsu, AN Sabol, LJ Demer, JL Sullivan, TJ Gottlob, I Roggenkaemper, P Mackey, DA de Uzcategui, CE Uzcategui, N Ben-Zeev, B Traboulsi, EI Magli, A de Berardinis, T Gagliardi, V Awasthi-Patney, S Vogel, MC Rizzo, JF Engle, EC TI Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MAPS; FAMILY; CHROMOSOME-12; REFINEMENT; REGION; PHOX2A; LOCUS; ARIX AB PURPOSE. Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype. C1 Childrens Hosp, Div Genet, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. King Khalid Eye Specialist Hosp, Div Neuroophthalmol, Riyadh 11462, Saudi Arabia. Ankara Guven Hosp, Dept Ophthalmol, Ankara, Turkey. Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. Sligo Gen Hosp, Dept Ophthalmol, Sligo, Ireland. Hacettepe Univ, Fac Med, Dept Pediat, Pediat Hematol Unit,Gene Mapping Lab, TR-06100 Ankara, Turkey. Geisinger Med Inst, Dept Ophthalmol, Danville, PA USA. Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Queensland, Dept Ophthalmol, Royal Childrens Hosp, Brisbane, Qld, Australia. Univ Leicester, Dept Ophthalmol, Leicester, Leics, England. Univ Eye Clin, Bonn, Germany. Univ Melbourne, Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, Melbourne, Vic, Australia. Inst Otorrinolaringol, Caracas, Venezuela. Univ So Calif, Doheny Eye Inst, Childrens Hosp Los Angeles, Los Angeles, CA USA. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Univ Naples Federico II, Fac Med & Chirurg, Dipartimento Sci Oftalmolli, Naples, Italy. JKA Inst Strabismol, Rajkot, Gujarat, India. Dr HL Patney Mem Eye Clin, Rajkot, Gujarat, India. Hosp Ninos Roberto del Rio, Dept Ophthalmol, Santiago, Chile. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Engle, EC (reprint author), Childrens Hosp, Div Genet, Dept Genet, Enders 5,300 Longwood Ave, Boston, MA 02115 USA. EM engle@enders.tch.harvard.edu RI Akarsu, Nurten/E-9758-2013; Mackey, David/H-5340-2014; OI Akarsu, Nurten/0000-0001-5432-0032; Mackey, David/0000-0001-7914-4709; DE BERARDINIS, Teresa/0000-0001-6872-0432; Magli, Adriano/0000-0002-6490-2068 FU NEI NIH HHS [R01-EY12498, R01-EY13583]; NICHD NIH HHS [P30-HD18655] NR 17 TC 48 Z9 53 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2004 VL 45 IS 7 BP 2218 EP 2223 DI 10.1167/iovs.03-1413 PG 6 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900023 PM 15223798 ER PT J AU Yeh, DC Bula, DV Miller, JW Gragoudas, ES Arroyo, JG AF Yeh, DC Bula, DV Miller, JW Gragoudas, ES Arroyo, JG TI Expression of leukocyte adhesion molecules in human subfoveal choroidal neovascular membranes treated with and without photodynamic therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; GRANULOMATOUS INFLAMMATION; BREAST-CANCER; HUMAN RETINA; ANGIOGENESIS; VERTEPORFIN; RAT; MODULATION AB PURPOSE. The purposes of this study were to investigate the immunostaining of the leukocyte adhesion molecules intercellular adhesion molecule (ICAM)-1 and E-selectin in subfoveal choroidal neovascular membranes (CNVMs) surgically excised from patients with age-related macular degeneration (AMD) and to determine whether prior photodynamic therapy (PDT) alters their immunostaining. METHODS. The localization of ICAM-1 and E-selectin in 10 subfoveal CNVMs was determined by immunohistochemistry. Membranes were also immunostained for CD31 to assess vascularity. RESULTS. Significantly higher numbers of CD31-staining vessels per unit membrane area were found in the peripheral regions of the membranes compared with the central regions (P = 0.05). ICAM-1 immunoreactivity in the CNVMs was found predominantly on RPE cells, but also on small vessels in the periphery. ICAM-1 staining was significantly more intense in the peripheral, more cellular areas of the membranes than in the central, more fibrotic regions (P = 0.04). ICAM-1 staining in the periphery of the CNVMs was greater than that in choroidal vessels and the RPE of the normal control eye. ICAM-1 immunostaining grade in peripheral regions of the CNVMs decreased with the increasing number of PDT treatments (P = 0.05). Some of the CNVMs also stained for E-selectin in RPE cells and small vessels in the periphery. CONCLUSIONS. In subfoveal CNVMs from patients with AMD, there is increased immunostaining for leukocyte adhesion molecules, particularly in the peripheral, more cellular regions where angiogenesis may be ongoing. Increasing numbers of PDT treatments may be associated with decreased ICAM-1 immunostaining in the proliferating edges of the CNVMs. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02215 USA. RP Arroyo, JG (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Ophthalmol,Retina Serv, 330 Brookline Ave,Shapiro 5th Floor, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu NR 40 TC 32 Z9 36 U1 0 U2 1 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 JUL PY 2004 VL 45 IS 7 BP 2368 EP 2373 DI 10.1167/iovs.03-0981 PG 6 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900044 PM 15223819 ER PT J AU Stone, VE Jordan, J Tolson, J Miller, R Pilon, T AF Stone, VE Jordan, J Tolson, J Miller, R Pilon, T TI Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy - Self-report of the relative importance of multiple attributes of highly active Antiretroviral therapy (HAART) regimens in predicting adherence SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; HIV/AIDS; regimen attribute; compliance; antiretroviral therapy; HAART; pill burden; dosing complexity; adverse events; once-daily dosing simultaneously; patient survey ID VERBAL REPORTS; PREFERENCES AB Background: Adherence to highly active antiretroviral therapy (HAART) of 95% or greater seems to be required for successful treatment of HIV/AIDS. Efforts to simplify regimens to improve adherence are ongoing, including the advent of once-daily (QD) dosing regimens, which are presumed to be beneficial, although data regarding their overall impact on adherence are not yet available. Objective: To assess patient perceptions of the impact on adherence of 10 attributes of HAART, including QD dosing, and to compare 7 actual regimens based on patients' perceptions of their likelihood to promote adherence. Methods: Two hundred ninety-nine highly treatment-experienced patients with HIV/AIDS completed a questionnaire that evaluated perceptions of the impact on adherence of 10 HAART regimen attributes using a modified adaptive conjoint analysis. Patients' perceptions of the likelihood that they would adhere to 7 actual HAART regimens were scored on Likert scales. Results: Pill count, dosing frequency, and adverse events had the greatest impact on patients' perceived ability to adhere to antiretroviral medication regimens. QD was the preferred dosing frequency, but QD dosing regimens did not score better than other regimens. Among actual regimens, predicted adherence was highest for a twice-daily (BID) regimen with 2 pills daily,no dietary restrictions, and I prescription and copayment and lowest for a BID regimen with 13 pills daily, food requirements, and 3 prescriptions and copayments. Conclusions: All HAART regimen attributes studied were perceived to have an impact on adherence, but pill count, dosing frequency, and adverse events had the greatest perceived impact. These data are of potential importance to clinicians as they seek to structure HAART regimens to which their patients are most likely to adhere. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. GlaxoSmithKline, Global Hlth Outcomes N Amer, Res Triangle Pk, NC USA. Cooper Res, Cincinnati, OH USA. TomPilon Com, Carrollton, TX USA. RP Stone, VE (reprint author), Massachusetts Gen Hosp, Bulfinch 130,55 Fruit St, Boston, MA 02114 USA. EM vstone@parmers.org NR 22 TC 100 Z9 103 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2004 VL 36 IS 3 BP 808 EP 816 DI 10.1097/00126334-200407010-00007 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 835KL UT WOS:000222481700006 PM 15213564 ER PT J AU Wilson, PW Carey, K AF Wilson, PW Carey, K TI Nonparametric analysis of returns to scale in the us hospital industry SO JOURNAL OF APPLIED ECONOMETRICS LA English DT Article ID FLEXIBLE FUNCTIONAL FORMS; COMMERCIAL-BANKS; COST-FUNCTIONS; REGRESSION; DEMAND; EFFICIENCY; ECONOMIES AB This paper presents new estimates of scale economies for US hospitals. We show that the common translog specification of hospital costs is a misspecification, and employ nonparametric, local linear estimation with both continuous and discrete covariates. A bootstrap method is used to provide inferences regarding ray scale economies and expansion path scale economies for a large sample of hospitals covering 1984-1996. We find evidence of changes in the structure of hospital costs over the sample period, as well as evidence of locally optimal hospital sizes. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Texas, Dept Econ, Austin, TX 78712 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. US Dept Vet Affairs, Management Sci Grp, Bedford, MA USA. RP Wilson, PW (reprint author), Univ Texas, Dept Econ, 1 Univ Stn,C3100, Austin, TX 78712 USA. EM wilson@eco.utexas.edu NR 38 TC 23 Z9 23 U1 0 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0883-7252 J9 J APPL ECONOM JI J. Appl. Econom. PD JUL-AUG PY 2004 VL 19 IS 4 BP 505 EP 524 DI 10.1002/jae.801 PG 20 WC Economics; Social Sciences, Mathematical Methods SC Business & Economics; Mathematical Methods In Social Sciences GA 847BH UT WOS:000223363200004 ER PT J AU Ring, D Guss, D Malhotra, L Jupiter, JB AF Ring, D Guss, D Malhotra, L Jupiter, JB TI Idiopathic arm pain SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID UPPER-EXTREMITY DISORDERS; LOW-BACK-PAIN; PSYCHOSOCIAL FACTORS; DIAGNOSTIC-TEST; COMPUTER USERS; RISK-FACTORS; WORK; POPULATION; SOMATIZATION; ARTICLE AB Background: Arm pain with little or no objective abnormality (referred to herein as idiopathic arm pain) is a common and frustrating problem for both patients and physicians. We investigated the relative effect of idiopathic arm pain and arm pain due to a discrete diagnosis on upper-extremity-specific health status. Methods: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was completed by 3888 patients seen over a twelve-month period. Scores for the entire sample, for 496 patients diagnosed with idiopathic arm pain, and for 1379 patients diagnosed with one of twenty-one discrete conditions were compared. Results: Patients with idiopathic pain reported substantial and highly variable upper-limb-specific dysfunction (average DASH score [and standard deviation], 36 24 points). Patients with discrete diagnoses also exhibited substantial variation (average standard deviation, 25; range, 6 to 27) as well as long right tails indicating floor effects, particularly for less severe conditions (Pearson correlation of r = -0.87 between the mean DASH score and skewness). Analysis of variance confirmed the ability of the DASH instrument to discriminate among groups of diagnoses of varying severity, but post hoc Tukey analysis identified ten subgroups with substantial overlap of the DASH scores. Conclusions: Patients with idiopathic arm pain report substantial and highly variable upper-extremity dysfunction. The wide variations observed in the DASH scores of the patients with idiopathic pain and those with discrete diagnoses are greater than would be expected on the basis of the variations in the objective pathological conditions and may reflect the strong influence of psychological and sociological factors on health status measures. C1 Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, ACC 525,15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org NR 27 TC 28 Z9 28 U1 0 U2 0 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 JUL PY 2004 VL 86A IS 7 BP 1387 EP 1391 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 835IK UT WOS:000222475900005 PM 15252084 ER PT J AU Sargent, MC Sotile, W Sotile, MO Rubash, H Barrack, RL AF Sargent, MC Sotile, W Sotile, MO Rubash, H Barrack, RL TI Stress and coping among orthopaedic surgery residents and faculty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MEDICAL RESIDENTS; UNITED-STATES; HEALTH; WORK; COHABITATION; SATISFACTION; ADJUSTMENT; BURNOUT AB Background: Evaluations of physicians and residents have revealed concerning levels of psychosocial dysfunction. The purposes of this study were to determine the quality of life of orthopaedic residents and faculty and to identify the risk factors for decompensation. Methods: Twenty-one orthopaedic residents and twenty-five full-time orthopaedic faculty completed a 102-question voluntary, anonymous survey. The survey consisted of three validated instruments, i.e., the Maslach Burnout Inventory, the General Health Questionnaire-12, and the Revised Dyadic Adjustment Scale; and three novel question sets addressing background and demographic information, stress reaction and management, and the balance between work and home life. Descriptive statistics, pairwise correlations, simple t tests, and Pearson and nonparametric Spearman correlations were calculated. The simple correlation coefficient was used to assess bivariate relationships. Results: The mean overall quality-of-life score, on a scale of 0 to 4 points, was 2.5 points for residents compared with 3.6 points for faculty members. Residents reported considerable burnout, showing a high level of emotional exhaustion and depersonalization and an average level of personal achievement, whereas faculty reported minimal burnout, showing a low level of emotional exhaustion (p < 0.0003), an average level of depersonalization (p < 0.0001), and a high level of personal achievement (p < 0.0001). Only two of twenty-five faculty members (compared with seven of twenty-one residents) scored over 4 points on the General Health Questionnaire-12, indicating significant symptomatology (p < 0.01). The majority of subjects reported that a partner or spouse showed nondistressed levels of marital adjustment and satisfaction. All residents and nine of the twenty-five faculty members had mentors but judged the resource to be minimally beneficial. Resident burnout and psychiatric morbidity correlated with weekly work hours; conflict between the commitments of work and home life; discord with faculty, nursing staff, and senior residents; debt load; and work-related stress. Protective factors included being a parent, spending time with a spouse, having a physician father, and deriving satisfaction from discussing concerns with colleagues, friends, and family. Conclusions: In pursuit of our goal of determining the quality of life of orthopaedic residents and faculty, we identified a large disparity between the two groups. The resident group reported much greater levels of dysfunction particularly with regard to burnout and psychiatric morbidity. Furthermore, with regard to our second goal; our data revealed a number of risk factors for resident decompensation, most notably, increased workload, high debt levels, and discord with superiors. In addition, our research revealed that the current support interventions by the residency program, including mentoring and facilitation of spousal adjustment, are viewed as being of little help. C1 Tulane Univ, Hlth Sci Ctr, Dept Orthopaed Surg, New Orleans, LA 70112 USA. Sotile Psychol Associates, Winston Salem, NC 27103 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Barrack, RL (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Orthopaed Surg, 1430 Tulane Ave,S1-32, New Orleans, LA 70112 USA. EM rbarrack@tulane.edu NR 25 TC 68 Z9 70 U1 0 U2 12 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 JUL PY 2004 VL 86A IS 7 BP 1579 EP 1586 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 835IK UT WOS:000222475900032 PM 15252111 ER PT J AU Akins, CW Hilgenberg, AD Vlahakes, GI Madsen, JC Phil, D MacGillivray, TE AF Akins, CW Hilgenberg, AD Vlahakes, GI Madsen, JC Phil, D MacGillivray, TE TI Aortic valve replacement in patients with previous cardiac surgery SO JOURNAL OF CARDIAC SURGERY LA English DT Article; Proceedings Paper CT 5th International Symposium on Redo Cardiac Surgery in Adults CY MAY 02-03, 2003 CL Boston, MA ID BYPASS GRAFT-SURGERY; STENOSIS; PROGRESSION; MANAGEMENT AB Background. Whether minimally diseased aortic valves should be replaced during other necessary cardiac operations remains controversial. Part of the decision-making process in that issue revolves around the risks of subsequent aortic valve replacement. This study evaluated the results of aortic valve replacement in patients following prior cardiac surgery. Methods: From February, 1984 through December, 2001 first-time aortic valve replacement was performed in 132 consecutive patients who had previous cardiac surgery utilizing cardiopulmonary bypass. Of those patients 89 (67%) had aortic valve replacement at a mean of 8.3 years after prior coronary artery bypass grafting, and 43 (33%) had aortic valve replacement at a mean of 13.0 years after previous procedures other than myocardial revascularization. Hospital records of all patients were retrospectively reviewed. Results: Early complications included operative mortality in six (6.7%) of the patients with prior coronary grafting and no mortality in the group with other prior operations. Patients having prior coronary grafting had more nonfatal complications than those with other previous procedures. Conclusions: Aortic valve replacement in patients following previous cardiac surgery can be accomplished with acceptable mortality and morbidity. Routine replacement of aortic valves that are minimally diseased during coronary artery bypass grafting may not be warranted. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, White 503,55 Fruit St, Boston, MA 02114 USA. EM cakins@partners.org NR 15 TC 10 Z9 11 U1 1 U2 1 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD JUL-AUG PY 2004 VL 19 IS 4 BP 308 EP 312 DI 10.1111/j.0886-0440.2004.4055_11.x PG 5 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 840CE UT WOS:000222833800006 PM 15245459 ER PT J AU Monks, NR Biswas, DK Pardee, AB AF Monks, NR Biswas, DK Pardee, AB TI Blocking anti-apoptosis as a strategy for cancer chemotherapy: NF-kappa B as a target SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE apoptosis; NF-kappa B; inhibitors; Go6976; siRNA ID PROTEIN-KINASE CK2; BREAST-CANCER; CELL-CYCLE; THERAPEUTIC TARGET; ACTIVATION; ALPHA; INHIBITION; RECEPTOR; PATHWAY; PROTEASOME AB Critical processes underlying cancers must be better understood to develop strategies for treatment and prevention. A chemotherapeutic strategy is proposed that is based upon re-establishment, with a drug, of nullified programmed cell death (apoptosis) in cancer cells, which to survive have mutated to block apoptosis. A chemotherapy that is specific against tumors implanted in mice demonstrated the feasibility of this principle. This therapy is specific because it affects a process unique to cancer cells. It also has the advantage of killing these cells, in contrast to reversibly blocking their proliferation. The anti-apoptotic transcription factor NF-kappaB provides a potential therapeutic target in estrogen receptor negative (ER-) breast cancers that over-express the epidermal growth factor family of receptors (EGFR). Further investigations of the pathways utilize dominant negative protein inhibitory peptide, and small inhibitory RNAs (siRNAs) to block the production of relevant enzymes. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Arthur_Pardee@dfci.harvard.edu RI Monks, Noel/B-5886-2013 OI Monks, Noel/0000-0001-6587-9827 NR 38 TC 52 Z9 53 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2004 VL 92 IS 4 BP 646 EP 650 DI 10.1002/jcb.20080 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 834LT UT WOS:000222413300001 PM 15211562 ER PT J AU Bettencourt, R Asha, H Dearolf, C Ip, YT AF Bettencourt, R Asha, H Dearolf, C Ip, YT TI Hemolymph-dependent and -independent responses in Drosophila immune tissue SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE innate immunity; hemolymph; Drosophila; NF-kappaB; dorsal ID NF-KAPPA-B; PEPTIDOGLYCAN RECOGNITION PROTEIN; TOLL-LIKE RECEPTOR-5; REL PROTEINS; SIGNALING PATHWAYS; GENE-EXPRESSION; HOST-DEFENSE; CUTTING EDGE; DIF; ACTIVATION AB Insects possess an antimicrobial defense response that is similar to the mammalian innate immune response. The innate immune system is designed to recognize conserved components of microorganisms called pathogen associated molecular patterns (PAMPs). How host receptors detect PAMPs and transmit the signals to mount the immune response is being elucidated. Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, have both hemolymph-dependent and -independent responses. Microbial preparations such as lipoteichoic acid (LTA) and peptidoglycan (PGN) can stimulate some responses from dissected and rinsed larval fat bodies. Therefore, at least some aspects of recognition can occur on fat body cell surfaces, bypassing the requirement of hemolymph. Our results also show that supernatants from bacterial cultures can stimulate the nuclear translocation of Dorsal in dissected fat bodies, but this stimulation is strictly hemolymph-dependent. Various biochemical assays suggest that the factors from bacterial supernatants that stimulate the hemolymph-dependent nuclear translocation are likely made up of proteins. We further show that Dorsal mutant larvae have much lower phenoloxidase activity, consistent with a more important role of Dorsal in innate immunity than previously shown. (C) 2004 Wiley-Liss, Inc. C1 Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Cell Dynam, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Ip, YT (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, 373 Plantat St,Room 109, Worcester, MA 01605 USA. EM Tony.Ip@umassmed.edu RI Bettencourt, Raul/A-4511-2009 OI Bettencourt, Raul/0000-0001-6866-7029 FU NCRR NIH HHS [RR15061]; NIGMS NIH HHS [GM53269] NR 45 TC 28 Z9 29 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2004 VL 92 IS 4 BP 849 EP 863 DI 10.1002/jcb.20123 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 834LT UT WOS:000222413300019 PM 15211580 ER PT J AU Lee, SR Lo, EH AF Lee, SR Lo, EH TI Induction of caspase-mediated cell death by matrix metalloproteinases in cerebral endothelial cells after hypoxia-reoxygenation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE matrix metalloproteinases; caspase; cerebral ischemia; blood-brain barrier ID APOPTOSIS-INDUCING FACTOR; INTEGRIN-LINKED KINASE; GENE KNOCK-OUT; BRAIN-INJURY; NEURONAL APOPTOSIS; NERVOUS-SYSTEM; MOUSE HIPPOCAMPUS; PROTEIN-KINASE; ISCHEMIA; MATRIX-METALLOPROTEINASE-9 AB Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell-matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia-reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the beta1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia-reoxygenation by disrupting cell-matrix interactions and homeostatic integrin signaling. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NINDS NIH HHS [R01-NS38731, R01-NS40529, P50-NS10828, R01-NS37074] NR 57 TC 83 Z9 90 U1 0 U2 4 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 JUL PY 2004 VL 24 IS 7 BP 720 EP 727 DI 10.1097/01.WCB.0000122747.72175.47 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 835RR UT WOS:000222503700002 PM 15241180 ER PT J AU Ayata, C Dunn, AK Gursoy-Ozdemir, Y Huang, ZH Boas, DA Moskowitz, MA AF Ayata, C Dunn, AK Gursoy-Ozdemir, Y Huang, ZH Boas, DA Moskowitz, MA TI Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood flow; optical imaging; metabolic coupling; hypercapnia; autoregulation; focal cerebral ischemia ID CEREBRAL-BLOOD-FLOW; CORTICAL SPREADING DEPRESSION; RODENT BARREL CORTEX; NITRIC-OXIDE; FUNCTIONAL ACTIVATION; DOPPLER FLOWMETRY; RAT; OXYGENATION; STIMULATION; MICE AB Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [C-14]iodoamphetamine technique, and 1/tau(c) values obtained using LSF, and used 1/tau(c) values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In Summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit, Charlestown, MA USA. RP Ayata, C (reprint author), Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014 FU NIBIB NIH HHS [R01 EB00790-01 A2]; NINDS NIH HHS [K25 NS041291, P01 NS35611, P50 NS10828] NR 36 TC 163 Z9 167 U1 0 U2 8 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 JUL PY 2004 VL 24 IS 7 BP 744 EP 755 DI 10.1097/01.WCB.0000122745.72175.D5 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 835RR UT WOS:000222503700004 PM 15241182 ER PT J AU Meysing, AU Kanasaki, H Bedecarrats, GY Acierno, JS Conn, PM Martin, KA Seminara, SB Hall, JE Crowley, WF Kaiser, UB AF Meysing, AU Kanasaki, H Bedecarrats, GY Acierno, JS Conn, PM Martin, KA Seminara, SB Hall, JE Crowley, WF Kaiser, UB TI GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR GENE; HOMOZYGOUS MUTATION; OVULATION INDUCTION; IN-VITRO; EXPRESSION; SUBUNIT; INFERTILITY; RESISTANCE; SECRETION; DISORDERS AB Mutations in the GnRH receptor gene (GNRHR) are a cause of idiopathic hypogonadotropic hypogonadism. We describe a normosmic female subject with congenital idiopathic hypogonadotropic hypogonadism in whom treatment with pulsatile GnRH resulted in an unusual response. The subject not only required an increased dose of pulsatile GnRH for ovarian follicular development, but LH secretion did not increase appropriately, estradiol levels remained low, and she did not ovulate spontaneously. Sequencing of the GNRHR coding sequence revealed compound heterozygous mutations leading to amino acid substitutions [N10K + Q11K] and P320L. The introduction of the P320L mutation into the GnRH receptor led to failure of detectable ligand binding and failure of stimulation of inositol phosphate production and gonadotropin subunit gene promoter activity in response to GnRH in transiently transfected cells. The [N10K + Q11K] mutation resulted in reduced binding of a GnRH agonist to 25% of the wild-type receptor. In addition, the EC(50) value for GnRH stimulation of inositol phosphate production was significantly increased, and the dose-response curves for stimulation of alpha gonadotropin subunit, LHbeta, and FSHbeta gene transcription by GnRH were similarly shifted to the right. Stimulation of FSHbeta gene transcription was more sensitive to GnRH than LHbeta for both wild-type and [N10K + Q11K] GnRH receptors, resulting in a greater loss of LHbeta stimulation than FSHbeta by the [N10K + Q11K] mutant at any given submaximal GnRH concentration. We propose that the mutations in the GnRH receptor result in a rightward shift of the dose-response curves of gonadotropin responses to pulsatile GnRH in the subject and unmask the differential sensitivities of LH and FSH to GnRH, resulting in low LH and estradiol levels despite appropriate FSH secretion and follicular growth. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Wide Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Beaverton, OR 97006 USA. RP Meysing, AU (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Barlett Hall Extens 5, Boston, MA 02114 USA. EM ameysing@partners.org FU NICHD NIH HHS [U54 HD029164, U564 HD 28138, U54 HD028138, R01 HD043341, HD 19899, R01 HD015788] NR 41 TC 33 Z9 38 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3189 EP 3198 DI 10.1210/jc.2003-031808 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500020 PM 15240592 ER PT J AU Yao, K Singer, FR Roth, SI Sassoon, A Ye, C Giuliano, AE AF Yao, K Singer, FR Roth, SI Sassoon, A Ye, C Giuliano, AE TI Weight of normal parathyroid glands in patients with parathyroid adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NORMOCALCEMIC HYPERPARATHYROIDISM; SURGERY; FAT; DISEASE AB Although the size and weight of a parathyroid gland are frequently the only intraoperative determinants of abnormality, these parameters have not been examined in living patients with primary hyperparathyroidism (PHP). The records of 240 patients who underwent parathyroidectomy according to standard surgical practice by a single surgeon were reviewed to identify those who were euparathyroid after in toto removal of a histologically confirmed normal gland and a histologically confirmed adenoma. The 25 (86%) females and 4 (14%) males who met the study criteria had a mean age of 60 yr (range, 33-82 yr). The mean PTH level was 130.1 pg/ml (range, 58-278) before parathyroidectomy and 32.4 pg/ml (range, 1-68) after parathyroidectomy. The mean calcium level was 11.1 mg/dl (range, 10-14) before and 8.7 mg/dl (range, 8-10) after parathyroidectomy. Thirty-four intact normal glands were removed and available for analysis. Their mean weight was 62.4 +/- 31.6 mg (range, 18-161 mg), and 15 (44%) weighed 60 mg or more. The mean weight of the adenomas was 553.7 +/- 520.5 mg (range, 66-2536). Adenomas were clearly distinguished from normal glands by cellularity, stromal fat, and intracellular fat in chief cells. The weight of normal parathyroid glands removed at surgery in patients with PHP may be greater than that reported in autopsy studies. Therefore, certain histological features are a better measure than weight in determining whether a gland is normal, and intraoperative identification of slightly enlarged glands should not lead to immediate subtotal parathyroidectomy. C1 St Johns Hlth Ctr, John Wayne Canc Inst, Dept Breast & Endocrine Dis, Santa Monica, CA 90404 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Johns Hlth Ctr, Dept Pathol, Santa Monica, CA 90404 USA. RP Giuliano, AE (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, Dept Breast & Endocrine Dis, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. EM giulianoa@jwci.org NR 22 TC 24 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3208 EP 3213 DI 10.1210/jc.2003-031184 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500022 PM 15240594 ER PT J AU Schurgin, S Dolan, S Perlstein, A Sullivan, MP Aliabadi, N Grinspoon, S AF Schurgin, S Dolan, S Perlstein, A Sullivan, MP Aliabadi, N Grinspoon, S TI Effects of testosterone administration on growth hormone pulse dynamics in human immunodeficiency virus-infected women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FACTOR-I AXIS; ESTROGEN REPLACEMENT THERAPY; CLINICAL-RESEARCH-CENTER; POSTMENOPAUSAL WOMEN; GH SECRETION; HYPOGONADOTROPIC HYPOGONADISM; NONAROMATIZABLE ANDROGEN; TRANSDERMAL ESTROGEN; PREMENOPAUSAL WOMEN; SOMATOTROPIC AXIS AB The effects of testosterone administration on the GH axis in androgen-deficient HIV-infected women are unknown. In this study, we determined the effects of transdermal testosterone administration on GH secretory dynamics and pulse characteristics in this population. GH-IGF-I parameters were determined in response to testosterone (4.1 mg/patch, twice a week; estimated delivery rate, 150 mug/d) vs. placebo over 6 months in 31 HIV-infected women. IGF-I increased significantly in the testosterone-treated compared with the placebo-treated patients [37 (-4, 73) vs. -30 (-98, 39) ng/ml, P = 0.01; 4.8 (-0.5, 9.6) vs. -3.9 (-12.8, 5.1) nmol/liter]. GH pulse frequency increased significantly in the testosterone-treated compared with the placebo-treated subjects [1.0 (1.0, 2.0) vs. 0.0 (-0.5, 1.5) peaks per 12 h, respectively; P = 0.02]. Before testosterone administration, overnight GH pulse amplitude was significantly related to IGF-I in univariate (r = 0.41, P = 0.03) and multivariate regression analysis; however, free testosterone, estradiol, and body mass index were not significantly correlated with base-line IGF-I. In contrast, after 6 months of treatment with testosterone, the change in IGF-I was significantly correlated to the change in free testosterone in univariate (r = 0.40, P = 0.04) and multivariate regression analysis. For each 1.0 pg/ml (3.5 pmol/liter) increase in free testosterone, IGF-I increased 19 ng/ml (2.5 nmol/liter), controlling for estradiol, body mass index, and GH pulse parameters (r(2) = 0.64). We demonstrate that IGF-I increases in response to physiologic, transdermal testosterone in HIV-infected women. The mechanism of this effect is unknown, but may involve a direct effect of testosterone on IGF-I, independent of changes in GH pulse dynamics. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Longfellow 207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR 00088]; NIDDK NIH HHS [DK 541667] NR 33 TC 3 Z9 4 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3290 EP 3297 DI 10.1210/jc.2003-032112 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500033 PM 15240605 ER PT J AU Misra, M Miller, KK Almazan, C Ramaswamy, K Aggarwal, A Herzog, DB Neubauer, G Breu, J Klibanski, A AF Misra, M Miller, KK Almazan, C Ramaswamy, K Aggarwal, A Herzog, DB Neubauer, G Breu, J Klibanski, A TI Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE; SERUM LEPTIN; PLASMA-LEVELS; CIRCULATING LEPTIN; BONE METABOLISM; GH DEFICIENCY; HEALTHY-MEN; WEIGHT-LOSS; OBESE GENE; FAT MASS AB Anorexia nervosa ( AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery ( defined as an increase in body mass index of greater than or equal to10%, n = 11), and with resumption of menstrual cycles ( n = 13). Girls with AN had significantly higher levels of sOB-R ( P = 0.0008) and significantly lower levels of leptin and FLI ( P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = - 0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole ( r = 0.61, P < 0.0001) and in girls with AN considered alone ( r = 0.66, P =\ 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat ( r = - 0.44, P = 0.003) and levels of IGF-I ( r = - 0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R ( 24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 mu g/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant increases in FLI (0.19 +/- 0.04 to 0.50 +/- 0.09 mu g/U x 10(-3), P = 0.02). We demonstrate an increase in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and also demonstrate that cortisol is the most important predictor of levels of sOB-R in this condition. Levels of leptin and FLI, conversely, are primarily predicted by body composition. Weight recovery is associated with a decrease in sOB-R and an increase in leptin. Resumption of menses is associated with significant increases in the FLI, suggesting that free leptin may be an important determinant of menstrual recovery. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Core Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. MIT, Core Lab, Cambridge, MA 02139 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01 RR 01066]; NIDDK NIH HHS [DK 062249, DK 52625-05] NR 66 TC 78 Z9 81 U1 0 U2 2 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 JUL PY 2004 VL 89 IS 7 BP 3486 EP 3495 DI 10.1210/jc.2003-032251 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500064 PM 15240636 ER PT J AU Bastepe, M Raas-Rothschild, A Silver, J Weissman, I Wientroub, S Juppner, H Gillis, D AF Bastepe, M Raas-Rothschild, A Silver, J Weissman, I Wientroub, S Juppner, H Gillis, D TI A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and skeletal abnormalities is caused by a novel activating parathyroid hormone (PTH)/PTH-related peptide receptor mutation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE; GENE; PTHRP AB A novel heterozygous PTH/PTHrP receptor missense mutation (T410R) was identified in a male and his two sons who are all affected by a less severe form of Jansen's metaphyseal chondrodysplasia (JMC). JMC is a rare disorder that is typically characterized by severe growth plate abnormalities that lead to short-limbed dwarfism. Furthermore, affected individuals usually show significant hypercalcemia, despite normal or undetectable levels of PTH and PTHrP. In contrast, the three affected members of this new family showed only mild skeletal dysplasia, comparatively normal stature, and blood calcium concentrations either within or at the upper end of the normal range. However, PTH levels were suppressed, and urinary calcium excretion was elevated, which led to nephrolithiasis in both children. When expressed in COS-7 cells, the PTH/PTHrP receptor with the T410R mutation led to agonist-independent cAMP formation, which was less pronounced than that observed with the previously identified T410P mutant. Our findings indicate that a mild form of JMC has been identified that is characterized by less pronounced skeletal and laboratory abnormalities. C1 Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hadassah Hebrew Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Nephrol, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. Western Galilee Hosp, Dept Pediat Nephrol, IL-22100 Naharyia, Israel. Tel Aviv Univ, Sackler Sch Med, Tel Aviv Med Ctr, Dana Childrens Hosp,Dept Pediat Orthoped, IL-64239 Tel Aviv, Israel. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 062973, DK 50708] NR 20 TC 27 Z9 28 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3595 EP 3600 DI 10.1210/jc.2004-0036 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500079 PM 15240651 ER PT J AU Rowan, PJ Tabasi, S Abdul-Latif, M Kunik, ME El-Serag, HB AF Rowan, PJ Tabasi, S Abdul-Latif, M Kunik, ME El-Serag, HB TI Psychosocial factors are the most common contraindications for antiviral therapy at initial evaluation in veterans with chronic hepatitis C SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE depression; interferon; HCV; risk factors; epidemiology; outcomes; anxiety ID QUALITY-OF-LIFE; VIRUS-INFECTION; UNITED-STATES; DEPRESSION AB Goals: To understand the degree to which psychosocial factors were preventing veterans with chronic hepatitis C virus from being eligible for antiviral treatment. Background: Nearly 2% of the US population is infected with hepatitis C. Antiviral treatment requires substantial adherence despite challenging side effects. Psychosocial factors, including depression and substance abuse, are clinically recognized contraindications for antiviral treatment. Study: At the Houston Veterans Affairs Medical Center HCV Clinic, we prospectively gathered medical and psychosocial data, as well as treatment disposition data, for consecutively referred patients who had screened positive for hepatitis C by enzyme-linked immunosorbent assay serology. Results: Of the 697 patients referred from September 2000 to May 2001, 580 had chronic hepatitis C. The mean age was 51 years, and 99% were men. Psychosocial contraindications prevented hepatitis C antiviral treatment from being started for 406 (70.0%) patients. These contraindications included alcohol abuse (124, 21.4%), substance abuse (21, 3.6%), and depression (93, 16.0%). Among the medical contraindications were end-stage liver disease (34, 5.9%) and poorly controlled diabetes mellitus (20, 3.4%). Conclusion: Overall, our experience was that a significant portion of hepatitis C patients could not initially be started on antiviral treatment due to psychosocial factors. To make these patients eligible for treatment, future studies of multidisciplinary interventions are required. C1 Houston Vet Affairs Med Ctr 152, Houston, TX 77030 USA. Univ St Thomas, Houston, TX 77006 USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holocombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 21 TC 43 Z9 46 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 JUL PY 2004 VL 38 IS 6 BP 530 EP 534 DI 10.1097/01.mcg.0000123203.36471.70 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 831IG UT WOS:000222187500011 PM 15220690 ER PT J AU Shivdasani, RA AF Shivdasani, RA TI Lonely in Paris: when one gene copy isn't enough SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID DNA-BINDING; EXPRESSION; FLI-1; MEGAKARYOCYTES; PLATELETS; THROMBOCYTOPENIA; SPECIFICITIES; ALLELES AB Circulating platelets are continually replenished by fragmentation of terminally differentiated megakaryocytes. Processes disrupted in inherited thrombocytopenias frequently shed fight on normal thrombopoietic mechanisms. An especially rare condition called Paris-Trousseau syndrome (PTS) seems to occur by virtue of hemizygous loss of the FLI1 transcription factor gene. Provocative new data suggest that FLI1 shows monoallelic expression during a brief window in megakaryocyte differentiation, which thus explains the dominant inheritance pattern of PTS despite the presence of one normal FLI1 allele. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2004 VL 114 IS 1 BP 17 EP 19 DI 10.1172/JC1200422292 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 834EG UT WOS:000222393800004 PM 15232606 ER PT J AU Ghannoum, MA Chaturvedi, V Espinel-Ingroff, A Pfaller, MA Rinaldi, MG Lee-Yang, W Warnock, DW AF Ghannoum, MA Chaturvedi, V Espinel-Ingroff, A Pfaller, MA Rinaldi, MG Lee-Yang, W Warnock, DW TI Intra- and interlaboratory study of a method for testing the antifungal susceptibilities of dermatophytes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRICHOPHYTON-RUBRUM; COLLABORATIVE EVALUATION; MICRODILUTION METHOD; FILAMENTOUS FUNGI; TERBINAFINE; RESISTANCE; GROWTH AB The National Committee for Clinical Laboratory Standards (NCCLS) M38-A standard for the susceptibility testing of conidium-forming filamentous fungi does not explicitly address the testing of dermatophytes. This multicenter study, involving six laboratories, investigated the MIC reproducibility of seven antifungal agents tested against 25 dermatophyte isolates (5 blinded pairs of five dermatophyte species per site for a total of 300 tests), using the method of dermatophyte testing developed at the Center for Medical Mycology, Cleveland, Ohio. The dermatophytes tested included Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis. Seven antifungals with activity against dermatophytes were tested, including ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinaline, and voriconazole. Interlaboratory MICs for all isolates were in 92 to 100% agreement at a visual endpoint reading of 50% inhibition as compared to the growth control and 88 to 99% agreement at a visual endpoint reading of 80% inhibition as compared to the growth control. Intralaboratory MICs between blinded pairs were in 97% agreement at a visual endpoint reading of 50% inhibition as compared to the growth control and 96% agreement at a visual endpoint reading of 80% inhibition as compared to the growth control. Data from this study support consideration of this method as an amendment to the NCCLS M38-A standard for the testing of dermatophytes. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Ctr Med Mycol, Cleveland, OH 44106 USA. State New York, Dept Hlth, Albany, NY USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Univ Texas, Hlth Sci Ctr, Lab Serv, Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. RP Ghannoum, MA (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Ctr Med Mycol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM mag3@cwru.edu NR 13 TC 56 Z9 62 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2004 VL 42 IS 7 BP 2977 EP 2979 DI 10.1128/JCM.42.7.2977-2979.2004 PG 3 WC Microbiology SC Microbiology GA 837WN UT WOS:000222672100016 PM 15243047 ER PT J AU Smith, MR Goode, M Zietman, AL McGovern, FJ Lee, H Finkelstein, JS AF Smith, MR Goode, M Zietman, AL McGovern, FJ Lee, H Finkelstein, JS TI Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: Effects on bone mineral density and body composition SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX ID ANDROGEN-DEPRIVATION THERAPY; OSTEOBLAST-LIKE CELLS; QUALITY-OF-LIFE; HORMONE AGONISTS; ADIPOSE-TISSUE; MUSCLE SIZE; NORMAL MEN; TESTOSTERONE; CARCINOMA; ESTROGEN AB Purpose Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. Patients and Methods In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily), Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. Results Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P < .001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P less than or equal to .003 for each comparison). Fat mass increased by 11.1% +/- 1.3% in the leuprolide group and by 6.4% +/- 1.1% in the bicalutamide group (P = .01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. Conclusion In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist. (C) 2004 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [R21 CA10353-01]; NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [K24 DK02759] NR 44 TC 103 Z9 106 U1 1 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 JUL 1 PY 2004 VL 22 IS 13 BP 2546 EP 2553 DI 10.1200/JCO.2004.01.174 PG 8 WC Oncology SC Oncology GA 834JW UT WOS:000222408400007 PM 15226323 ER PT J AU Gurubhagavatula, S Liu, G Park, S Zhou, W Su, L Wain, JC Lynch, TJ Neuberg, DS Christiani, DC AF Gurubhagavatula, S Liu, G Park, S Zhou, W Su, L Wain, JC Lynch, TJ Neuberg, DS Christiani, DC TI XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy 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 NUCLEOTIDE EXCISION-REPAIR; 18 MAJOR CANCERS; DNA-REPAIR; PROLONG SURVIVAL; CISPLATIN; ADDUCT; DETERMINANT; RESISTANCE; CAPACITY; DAMAGE AB Purpose Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of DNA repair genes are associated with differential DNA repair activity and may explain interindividual differences in overall survival after therapy with platinum agents for non-small-cell lung cancer (NSCLC). Methods We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes in 103 patients with stage III (54%) and IV (46%) NSCLC treated with platinum-based chemotherapy. Results Median age was 58 years (range, 32 to 77 years), 49% were females, and there were 86 deaths. Median follow-up period was 61.9 months. Median survival time (MST) was 14.9 months; by stage, MST was 28.6 months (IIIA), 16.0 months (IIIB), and 9.3 months (IV). Genotypes were not associated with stage. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival (P = .003 and P = .07, respectively, by log-rank test). Similarly, when we compared combinations of variant alleles across both polymorphisms, we found that a greater number of variant alleles was associated with decreasing overall survival (P = .009, log-rank test). These polymorphisms independently predicted overall survival even after taking into account stage, performance status, and chemotherapy regimen. Conclusion Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in platinum-treated patients with advanced NSCLC. (C) 2004 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA092824, 5T32 CA71345-07, CA74386, CA90578] NR 41 TC 231 Z9 264 U1 0 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 JUL 1 PY 2004 VL 22 IS 13 BP 2594 EP 2601 DI 10.1200/JCO.2004.08.067 PG 8 WC Oncology SC Oncology GA 834JW UT WOS:000222408400012 PM 15173214 ER PT J AU Waber, DP Silverman, LB Catania, L Mautz, W Rue, M Gelber, RD Levy, DE Goldwasser, MA Adams, H Dufresne, A Metzger, V Romero, I Tarbell, NJ Dalton, VK Sallan, SE AF Waber, DP Silverman, LB Catania, L Mautz, W Rue, M Gelber, RD Levy, DE Goldwasser, MA Adams, H Dufresne, A Metzger, V Romero, I Tarbell, NJ Dalton, VK Sallan, SE TI Outcomes of a randomized trial of hyperfractionated cranial radiation therapy for treatment of high-risk acute lymphoblastic leukemia: Therapeutic efficacy and neurotoxicity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; DANA-FARBER; COGNITIVE SEQUELAE; CHILDREN; CHILDHOOD; IRRADIATION; CHEMOTHERAPY; PERFORMANCE; SYSTEM; MEMORY AB Purpose We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT. Patients and Methods Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol. Results Eight-year event-free survival (+/-SE) was 80% +/- 3% for children randomly assigned to CFX and 72% +/- 3% for HFX (P = .06). Overall survival was 85% +/- 3% for CFX and 78% +/- 3% for HFX (P = .06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P = .99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P < .05). Conclusion HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia. (C) 2004 by American Society of Clinical Oncology. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Rochester, Med Ctr, Golisano Childrens Hosp Strong, Dept Pediat, Rochester, NY USA. Interamer Univ, San Juan, PR USA. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. Hop St Justine, Div Hematol Oncol, Dept Pediat Hematol, Montreal, PQ H3T 1C5, Canada. RP Waber, DP (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. EM deborah.waber@childrens.harvard.edu RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA 68484, CA06516]; NICHD NIH HHS [P30-HD18655] NR 31 TC 28 Z9 28 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 1 PY 2004 VL 22 IS 13 BP 2701 EP 2707 DI 10.1200/JCO.2004.10.173 PG 7 WC Oncology SC Oncology GA 834JW UT WOS:000222408400024 PM 15226337 ER PT J AU Hounie, AG Pauls, DL Mercadante, MT Rosairio-Campos, MC Shavitt, RG de Mathis, MA de Alvarenga, PG Curi, M Miguel, EC AF Hounie, AG Pauls, DL Mercadante, MT Rosairio-Campos, MC Shavitt, RG de Mathis, MA de Alvarenga, PG Curi, M Miguel, EC TI Obsessive-compulsive spectrum disorders in rheumatic fever with and without Sydenham's chorea SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TOURETTE SYNDROME; SYMPTOMS; FAMILY; DIAGNOSIS; CRITERIA; DISEASE; SCALE; TICS AB Background. Recent findings suggest that acute-phase rheumatic fever (RF) patients present with higher frequencies of obsessive-compulsive disorder (OCD) and tic disorders. Until now, there have been no such studies in RF in non-acute phases. Objective: To verify whether patients with a history of RF with or without Sydenham's chorea (SC) present with higher rates of OCD, tic disorders, and other obsessive-compulsive (OC) spectrum disorders (such as body dysmorphic disorder [BDD]) than controls. Method. Between February 1999 and December 2002, 59 consecutive outpatients with non-acute RF (28 with and 31 without SC) from an RF clinic and 39 controls from an orthopedics clinic were blindly assessed for OC spectrum disorders using structured interviews to assign DSM-IV diagnosis. Data were analyzed with Fisher exact and chi(2) tests to compare frequencies of disorders, and Kaplan-Meier survival analyses were used to obtain age-corrected rates. Results: The age-corrected rates of tic disorders were higher in patients with RF without SC (N = 3; 14.39%) (p = .003) when compared with controls. Age-corrected rates for OC spectrum disorders (OCD, tic disorders, and BDD) combined were higher both in RF without SC (N = 4, 20.65%) and RF with SC (N = 5; 19.55%) groups than in controls (N = 1; 2.56%) (p = .048). Conclusions: RF, even in the non-acute phase, may increase the risk for some OC spectrum disorders, such as OCD, tic disorders, and BDD. These data, although preliminary, reinforce the idea that OC spectrum disorders may share common underlying pathophysiologic mechanisms and vulnerability factors with RF or that RF could trigger central nervous system late manifestations such as OC spectrum disorders. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, BR-01241040 Sao Paulo, SP, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Hounie, AG (reprint author), Univ Sao Paulo, Sch Med, Dept Psychiat, Rua Dr Jose Pereira Queiroz 67, BR-01241040 Sao Paulo, SP, Brazil. EM anah@protoc.com.br RI Miguel, Euripedes/B-2871-2008; de mathis, maria alice/D-7269-2012; Curi, Mariana/E-8468-2011 NR 39 TC 42 Z9 47 U1 1 U2 1 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 JUL PY 2004 VL 65 IS 7 BP 994 EP 999 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 845ZD UT WOS:000223283200017 PM 15291690 ER PT J AU Davidson, L Shahar, G Stayner, DA Chinman, MJ Rakfeldt, J Tebes, JK AF Davidson, L Shahar, G Stayner, DA Chinman, MJ Rakfeldt, J Tebes, JK TI Supported socialization for people with psychiatric disabilities: Lessons from a randomized controlled trial SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID LONG-STAY PATIENTS; SOCIAL NETWORKS; MENTAL-ILLNESS; VOCATIONAL-REHABILITATION; PSYCHOLOGICAL REACTANCE; TAPS PROJECT; INNER-CITY; SCHIZOPHRENIA; COMMUNITY; MODEL AB Two hundred and sixty people with psychiatric disabilities who were socially isolated and withdrawn were randomly assigned to one of three conditions to facilitate their engagement in social and recreational activities: They were (a) not matched with a volunteer partner (N = 70), (b) matched with a volunteer partner who had a personal history of psychiatric disability (N = 95), or (c) matched with a volunteer partner with no history of psychiatric disability (N = 95). Participants and volunteers received a $28 stipend each month to cover the expenses of their activities. Comprehensive assessments of symptoms, functional impairment, self-esteem, and satisfaction were made at baseline, after 4 months, and after 9 months. While all participants appeared to improve in terms Of symptom reduction and increases in functioning and self-esteem, differences between conditions were found only when participants' degree of contact with their partner was considered. Mile participants assigned to the nonconsumer volunteer Partner condition improved in terms of their social functioning and self-esteem when meeting with their partners, those who were assigned to consumer partners only improved when they did not. Findings highlight the important role of participants' expectations and perceptions in designing and evaluating psychosocial interventions for people with psychiatric disabilities. (C) 2004 Wiley Periodicals, Inc. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. RAND Corp, Santa Monica, CA 90406 USA. W Los Angeles Vet Adm, VISN 22 MIRECC, Los Angeles, CA USA. RP Davidson, L (reprint author), Yale Univ, Sch Med, Dept Psychiat, Erector Sq 6W,Suite 1C,319 Peck St, New Haven, CT 06511 USA. EM Larry.Davidson@Yale.edu RI Shahar, Golan/F-1502-2012 NR 88 TC 63 Z9 65 U1 6 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 2004 VL 32 IS 4 BP 453 EP 477 DI 10.1002/jcop.20013 PG 25 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 829JQ UT WOS:000222044700007 ER PT J AU Sahani, DV Krishnamurthy, SK Kalva, S Cusack, J Hahn, PF Santilli, J Saini, S Mueller, PR AF Sahani, DV Krishnamurthy, SK Kalva, S Cusack, J Hahn, PF Santilli, J Saini, S Mueller, PR TI Multidetector-row computed tomography angiography for planning intra-arterial chemotherapy pump placement in patients with colorectal metastases to the liver SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, IL SP Radiol Soc N Amer DE MDCT; angiography; chemotherapy pump; celiac axis; colorectal; hepatic ID HEPATIC ARTERIAL INFUSION; RESECTION; CANCER; CARCINOMA; CT AB Purpose: The purpose of this study was to evaluate the use of multidetector computed tomography (MDCT) in the preoperative arterial evaluation of patients scheduled to undergo intra-arterial chemotherapy pump placement. Methods: Computed tomography scans of 30 patients with hepatic malignancies who were imaged with multiphase MDCT angiography for intra-arterial chemotherapy pump placement were retrospectively analyzed. Dual-phase helical CT was performed, and the arterial phase images were processed to depict the arterial anatomy and to identify pertinent anomalies. All findings were compared and correlated with surgical findings or catheter angiography if surgery was contraindicated. Results: Arterial anomalies identified on CT angiography in 20 of 30 patients included a replaced right hepatic artery (RHA; n = 6) or left hepatic artery (LHA; n = 8), a replaced common hepatic a (n = 1), an accessory RHA (n = 2) or LHA (n = 6), a replaced gastroduodenal artery (GDA; n = 2), an extrahepatic connection between the accessory RHA and the replaced RHA (n = 1), and a common origin composed of the GDA and RHA and LHA (n = 2). There were no additional arteries or anomalies identified by catheter angiography, when available, or during surgery. Only I variant, an accessory hepatic artery, was not located during surgery. In 2 patients, the surgical team decided that pump placement was not feasible because of overly complex anatomy as determined by CT angiography. Computed tomography angiography showed an overall sensitivity of 100% and specificity of 97%. Conclusions: Multidetector computed tomography angiography is accurate for the preoperative evaluation of normal and aberrant hepatic vasculature in patients under consideration for intra-arterial chemotherapy pump placement. Axial images alone permit recognition of vascular anomalies, including complex anatomy. Nevertheless, 3-dimensional rendering is useful to evaluate complex vascular anatomy and does not require catheter angiographic confirmation. In addition to aiding in selecting patients ideal for pump placement, MDCT permits noninvasive planning of their surgical approach. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Radiol & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Vasc Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Dept Radiol, Minneapolis, MN 55455 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Radiol & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 18 TC 19 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2004 VL 28 IS 4 BP 478 EP 484 DI 10.1097/00004728-200407000-00007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 840LZ UT WOS:000222861400007 PM 15232378 ER PT J AU Kalra, MK Maher, MM Rizzo, S Saini, S AF Kalra, MK Maher, MM Rizzo, S Saini, S TI Radiation exposure and projected risks with multidetector-row computed tomography scanning - Clinical strategies and technologic developments for dose reduction SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article; Proceedings Paper CT Conference on Advances in Multi-Detector CT CY SEP 13-14, 2003 CL Washington, DC DE multidetector CT; radiation dose reduction ID CT; FILTERS; CANCER AB A substantial increase in computed tomography (CT) scanning with availability of state-of-the-art multidetector-row CT scanners has generated debate about its safety and considerable interest in formulating clinical and technologic strategies to reduce radiation exposure. This review describes the magnitude of radiation exposure associated with CT scanning and projected radiation risks as well as clinical strategies and major technologic innovations for reducing radiation dose to patients undergoing CT scanning. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 26 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2004 VL 28 SU 1 BP S46 EP S49 DI 10.1097/01.rct.0000120856.80935.f4 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 841YO UT WOS:000222968800009 PM 15258493 ER PT J AU Kalra, MK Maher, MM Toth, TL D'Souza, R Saini, S AF Kalra, MK Maher, MM Toth, TL D'Souza, R Saini, S TI Multidetector computed tomography technology - Current status and emerging developments SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article; Proceedings Paper CT Conference on Advances in Multi-Detector CT CY SEP 13-14, 2003 CL Washington, DC DE CT; radiation; multidetector; technology ID MULTISLICE SPIRAL CT; IMAGE QUALITY; RECONSTRUCTION; REDUCTION; SCANNER AB By virtue of its speed and isotropic resolution of thin slices, multidetector-row computed tomography (MDCT) offers unique advantages over previous single-detector-row CT, with improved temporal and spatial resolution. This review describes the historical perspective and growth trends of MDCT scanners and highlights the current status and emerging developments in multidetector technology based on presentations at the symposium "Advances in Multidetector CT," under the auspices of the Institute for Advanced Medical Education in Washington, DC. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kalra@yahoo.com NR 24 TC 51 Z9 55 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2004 VL 28 SU 1 BP S2 EP S6 DI 10.1097/01.rct.0000120857.80935.bd PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 841YO UT WOS:000222968800002 PM 15258486 ER PT J AU Saini, S AF Saini, S TI Advances in multi-detector CT SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2004 VL 28 SU 1 BP S1 EP S1 DI 10.1097/01.rct.0000138530.60133.60 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 841YO UT WOS:000222968800001 ER PT J AU Klein, WM Rencic, A Munshi, NC Nousari, CH AF Klein, WM Rencic, A Munshi, NC Nousari, CH TI Multicentric plasma cell variant of Castleman's disease with cutaneous involvement SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID LYMPH-NODE HYPERPLASIA AB Background: Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants. Methods: We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities. Results: Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia. Conclusion: Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Dermatol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn Hlth Syst, Dept Dermatol, Philadelphia, PA USA. RP Nousari, CH (reprint author), Univ Penn, Dept Dermatol, 2 Rhoads Pavill,3600 Spruce St, Philadelphia, PA 19104 USA. EM hcnousari@hotmail.com NR 18 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUL PY 2004 VL 31 IS 6 BP 448 EP 452 DI 10.1111/j.0303-6987.2004.00117.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 827NL UT WOS:000221906500005 PM 15186433 ER PT J AU Duailibi, MT Duailibi, SE Young, CS Bartlett, JD Vacanti, JP Yelick, PC AF Duailibi, MT Duailibi, SE Young, CS Bartlett, JD Vacanti, JP Yelick, PC TI Bioengineered teeth from cultured rat tooth bud cells SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE tooth tissue engineering; dental stem cells ID BIODEGRADABLE POLYMER SCAFFOLDS; DENTAL-PULP; STEM-CELLS; IN-VITRO; REPLACEMENT AB The recent bioengineering of complex tooth structures from pig tooth bud tissues suggests the potential for the regeneration of mammalian dental tissues. We have improved tooth bioengineering methods by comparing the utility of cultured rat tooth bud cells obtained from three- to seven-day post-natal (dpn) rats for tooth-tissue-engineering applications. Cell-seeded biodegradable scaffolds were grown in the omenta of adult rat hosts for 12 wks, then harvested. Analyses of 12-week implant tissues demonstrated that dissociated 4-dpn rat tooth bud cells seeded for 1 hr onto PGA or PLGA scaffolds generated bioengineered tooth tissues most reliably. We conclude that tooth-tissue-engineering methods can be used to generate both pig and rat tooth tissues. Furthermore, our ability to bioengineer tooth structures from cultured tooth bud cells suggests that dental epithelial and mesenchymal stem cells can be maintained in vitro for at least 6 days. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Univ Fed Sao Paulo, Dept Otorhinolaryngol & Human Commun Disorders, Sao Paulo, Brazil. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Yelick, PC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org FU NIDCR NIH HHS [P01 DE013237] NR 27 TC 169 Z9 207 U1 5 U2 31 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2004 VL 83 IS 7 BP 523 EP 528 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 891RL UT WOS:000226598200003 PM 15218040 ER PT J AU Brown, DFM Nadel, ES AF Brown, DFM Nadel, ES TI Posterior wall myocardial infarction SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PRIMARY CORONARY ANGIOPLASTY; ACUTE AORTIC DISSECTION; ELECTROCARDIOGRAPHIC MANIFESTATIONS; TRIAL; POPULATION; MORTALITY; DISEASE C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2004 VL 27 IS 1 BP 75 EP 78 DI 10.1016/j.jemermed.2004.03.003 PG 4 WC Emergency Medicine SC Emergency Medicine GA 832PM UT WOS:000222279400013 PM 15219307 ER PT J AU Loftis, JM Wall, JM Linardatos, E Benvenga, S Hauser, F AF Loftis, JM Wall, JM Linardatos, E Benvenga, S Hauser, F TI A quantitative assessment of depression and thyroid dysfunction secondary to interferon-alpha therapy in patients with hepatitis C SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE thyroid dysfunction; interferon; hepatitis C; antidepressants; and depression ID CHRONIC VIRAL-HEPATITIS; IMMUNE INTERACTIONS; DISEASE; CYTOKINES; HYPOTHYROIDISM; COMBINATION; DISORDER; SYMPTOMS; STRESS; GAMMA AB The most effective treatment for hepatitis C virus (HCV) is interferon-alpha (IFN) therapy in combination with ribavirin. Although symptoms of depression are among the most common side effects of IFN therapy in treating patients with HCV, the mechanisms by which IFN produces these neuropsychiatric side effects remain unclear. In the brain, IFNs are involved in a number of regulatory functions, including but not limited to regulation of the endocrine system via the hypothalamic-pituitary-adrenal and -thyroid axes. The purpose of this study was to assess the effect of IFN therapy on thyroid function and to characterize the relationship between thyroid dysfunction and major depressive disorder during IFN therapy in patients with hepatitis C. Thirty-three patients with HCV were administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis 1 Disorders (SCID) and completed the Beck Depression Inventory (BDI). Patients were on IFN for an average of 6 to 12 months depending on their viral genotype. Serum samples were collected at baseline, during and after IFN therapy, and measured for free thryoxine (FT4) and TSH levels. Patients who developed IFN-induced depression were treated with selective serotonin reuptake inhibitor antidepressants. Only one patient developed transient IFN-induced overt hypothyroidism, but he did not develop depression. Analysis of variance showed that there were no significant differences in either FT4 or TSH serum levels between patients who developed major depressive disorder (MDD) (no.= 10) during IFN therapy and those who did not (no.=23). These results illustrate the frequency and severity of depressive symptoms associated with IFN therapy and the apparent absence of a relationship between IFN-induced MDD and changes in thyroid function. (C) 2004, Editrice Kurtis. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Univ Messina, Sch Med, Clin Expt Dept Med & Pharmacol, Endocrinol Sect, I-98100 Messina, Italy. Univ Messina, Policlin Gaetano Martino, Azienda Osped, Mol Clin Endocrinol Program, I-98100 Messina, Italy. RP Hauser, F (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Dr,P3MHAdm, Portland, OR 97239 USA. EM peter.hauser2@med.va.gov NR 29 TC 6 Z9 8 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL-AUG PY 2004 VL 27 IS 7 BP RC16 EP RC20 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 858JA UT WOS:000224186900001 PM 15505982 ER PT J AU Chan, S Mohammed, N Dobeck, JM White, RR Socransky, SS Skobe, Z AF Chan, S Mohammed, N Dobeck, JM White, RR Socransky, SS Skobe, Z TI Evaluation of the whole genome DNA-DNA hybridization technique to identify bacteria in histological sections of periradicular lesions SO JOURNAL OF ENDODONTICS LA English DT Article; Proceedings Paper CT 58th Annual Session of the American-Association-of-Endodontics CY MAR 28-APR 01, 2001 CL new orleans, LA SP Amer Assoc Endodont ID INDUCED PERIAPICAL LESIONS; ENDODONTIC INFECTIONS AB Whole genome DNA-DNA hybridization has been used to identify bacteria in periradicular lesions partly because there is no amplification of the bacteria, therefore, minor contaminants are not detected. There are, however, potential pitfalls with this technique, including inability to distinguish dead bacteria, cross-reactions of species within a genus, and inability to detect species present in low numbers because of loss of DNA during extraction and purification. Alternatively, inadequate extraction and purification of DNA could result in false positives. Therefore, controls are required to monitor DNA loss, DNA cross-reactions, and DNA of pure cultures mixed with bacteria-free tissue to monitor for false positives. We determined that the quality of DNA extracted from histological sections of periradicular lesions is excellent for DNA-DNA hybridization. Although lesions contain large numbers of bacteria, histological sections through lesions barely contain sufficient quantity of bacteria for such analysis. This was confirmed by histological observation of sparsely distributed bacteria within lesions. Furthermore, we found that the bacteria are not distributed evenly throughout periradicular lesions, in numbers or species. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Boston, MA 02115 USA. RP Skobe, Z (reprint author), Forsyth Inst, Dept Periodontol, 140 The Fenway, Boston, MA 02115 USA. EM zskobe@forsyth.org NR 18 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD JUL PY 2004 VL 30 IS 7 BP 518 EP 522 DI 10.1097/00004770-200407000-00014 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 834IK UT WOS:000222404600014 PM 15220650 ER PT J AU Morris, CA Cabral, D Cheng, HL Katz, JN Finkelstein, JS Avorn, J Solomon, DH AF Morris, CA Cabral, D Cheng, HL Katz, JN Finkelstein, JS Avorn, J Solomon, DH TI Patterns of bone mineral density testing - Current guidelines, testing rates, and interventions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE osteoporosis; research methods; diagnosis; clinical reviews ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; CORTICOSTEROID-INDUCED OSTEOPOROSIS; DIAGNOSED VERTEBRAL FRACTURES; UK CONSENSUS GROUP; HIP FRACTURE; POSTMENOPAUSAL WOMEN; CLINICAL-PRACTICE; MANAGEMENT; PREVENTION; DENSITOMETRY AB OBJECTIVES: To identify potential obstacles to bone mineral density (BMD) testing, we performed a structured review of current osteoporosis screening guidelines, studies of BMD testing patterns, and interventions to increase BMD testing. DESIGN: We searched MEDLINE and HealthSTAR from 1992 through 2002 using appropriate search terms. Two authors examined all retrieved articles, and relevant studies were reviewed with a structured data abstraction form. MEASUREMENTS AND MAIN RESULTS: A total of 235 articles were identified, and 51 met criteria for review: 24 practice guidelines, 22 studies of screening patterns, and 5 interventions designed to increase BMD rates. Of the practice guidelines, almost one half (47%) lacked a formal description of how they were developed, and recommendations for populations to screen varied widely. Screening frequencies among at-risk patients were low, ranging from 1% to 47%. Only eight studies assessed factors associated with BMD testing. Female patient gender, glucocorticoid dose, and rheumatologist care were positively associated with BMD testing; female physicians, rheumatologists, and physicians caring for more postmenopausal patients were more likely to test patients. Five articles described interventions to increase BMD testing rates, but only two tested for statistical significance and no firm conclusions can be drawn. CONCLUSIONS: This systematic review identified several possible contributors to suboptimal BMD testing rates. Osteoporosis screening guidelines lack uniformity in their development and content. While some patient and physician characteristics were found to be associated with BMD testing, few articles carefully assessed correlates of testing. Almost no interventions to improve BMD testing to screen for osteoporosis have been rigorously evaluated. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, Boston, MA 02120 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Morris, CA (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM camorris@partners.org FU NIAMS NIH HHS [K23 AR048616, K24 AR002123, P60-AR47782, P60 AR047782, K23-AR48616, K24-AR02123] NR 62 TC 71 Z9 74 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2004 VL 19 IS 7 BP 783 EP 790 DI 10.1111/j.1525-1497.2004.30240.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 828KY UT WOS:000221973400011 PM 15209594 ER PT J AU Gerrity, MS Tierney, WM AF Gerrity, MS Tierney, WM TI Stepping up to the plate SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID JGIM C1 Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Indiana Univ, Sch Med, Regenstrief Inst Inc, Div Gen Med & Geriatr, Indianapolis, IN USA. Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN 46202 USA. RP Gerrity, MS (reprint author), Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Portland, OR 97201 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2004 VL 19 IS 7 BP 805 EP 807 DI 10.1111/j.1525-1497.2004.40404.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 828KY UT WOS:000221973400013 ER PT J AU Luo, J Field, SJ Lee, JY Cantley, LC AF Luo, J Field, SJ Lee, JY Cantley, LC TI Unique spatial localization of phosphatidylinositol 3-kinase in response to insulin-like growth factor signaling SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the Society-of-General-Physiologists CY SEP 08-12, 2004 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2004 VL 124 IS 1 MA 13 BP 6A EP 6A PG 1 WC Physiology SC Physiology GA 836JD UT WOS:000222550900022 ER PT J AU Field, SJ Madson, N Tahiliani, M Cantley, LC AF Field, SJ Madson, N Tahiliani, M Cantley, LC TI PI(4,5)P-2 is required for mitotic cytokinesis SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the Society-of-General-Physiologists CY SEP 08-12, 2004 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Syst Biol,Div Signal Transduct, Boston, MA USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2004 VL 124 IS 1 MA 47 BP 20A EP 20A PG 1 WC Physiology SC Physiology GA 836JD UT WOS:000222550900056 ER PT J AU Xiao, YF Ma, L Wang, SY Wang, GK Morgan, JP Leaf, A AF Xiao, YF Ma, L Wang, SY Wang, GK Morgan, JP Leaf, A TI Inhibition of inactivation-deficient cardiac Na+ channels by n-3 polyunsaturated fatty acids SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the Society-of-General-Physiologists CY SEP 08-12, 2004 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia, Boston, MA USA. SUNY Albany, Dept Biol, Albany, NY 12222 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2004 VL 124 IS 1 MA 55 BP 23A EP 23A PG 1 WC Physiology SC Physiology GA 836JD UT WOS:000222550900064 ER PT J AU Ring, D Tavakolian, J Kloen, P Helfet, D Jupiter, JB AF Ring, D Tavakolian, J Kloen, P Helfet, D Jupiter, JB TI Loss of alignment after surgical treatment of posterior Monteggia fractures: Salvage with dorsal contoured plating SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE elbow; fracture; dislocation; instability; internal fixation; revision ID ELBOW AB Purpose: To review the results of internal fixation with a dorsal contoured plate in patients with malalignment after internal fixation of a posterior Monteggia fracture. Methods: Seventeen patients with malalignment after surgical treatment of a posterior Monteggia fracture were treated with realignment of the ulna and fixation with a contoured dorsal plate. Fifteen patients had loose fixation and 12 patients had subluxation or dislocation of the ulnohumeral joint. Sixteen patients had fracture of the radial head and 9 patients had fracture of the coronoid process. Nine patients had ancillary procedures on the radial head, 4 had ancillary procedures on the coronoid, 5 had hinged external fixation, and one had fascial arthroplasty. Seven patients had another surgery before the final evaluation related to a complication in 6 patients and a to subsequent injury in 1 patient. Results: At the final evaluation at an average of 59 months the fracture was healed and the ulnohumeral joint was reduced concentrically in all 17 patients. The average arc of elbow flexion was 108degrees and the average arc of forearm rotation was 134degrees. The average American Shoulder and Elbow Surgeons Elbow Evaluation Score was 88. According to the system of Broberg and Morrey, the final result was rated excellent for 5 patients, good for 9, fair for 2, and poor for 1. One patient had fascial arthroplasty as part of the index procedure and 9 patients had radiographic signs of ulnohumeral arthrosis. Conclusions: Malalignment after surgical treatment of posterior Monteggia fractures often is associated with unstable fixation. Dorsal contoured plating of the ulna in combination with other procedures can help salvage a malaligned posterior Monteggia fracture with satisfactory function restored in the majority of patients. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Acad Med Ctr, Dept Orthopaed Surg, Orthopaed Traumatol Serv, Amsterdam, Netherlands. Hosp Special Surg, New York, NY 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. NR 16 TC 19 Z9 22 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2004 VL 29A IS 4 BP 694 EP 702 DI 10.1016/j.jhsa.2004.02.015 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 839VD UT WOS:000222812100022 PM 15249096 ER PT J AU Kretschmer, K Stopkowicz, J Scheffer, S Greten, TF Weiss, S AF Kretschmer, K Stopkowicz, J Scheffer, S Greten, TF Weiss, S TI Maintenance of peritoneal B-1a lymphocytes in the absence of the spleen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL SUBSETS; REPERTOIRE; EXPRESSION; ORIGINS; BROMODEOXYURIDINE; SELECTION; HEAVY; MICE AB Positive selection by autoantigens is believed to play an important role in the generation/maintenance of B-1a cells. Recently, it has been described that splenectomy results in the loss of an already established B-1a cell pool. To elucidate whether the spleen influences the peritoneal B-1a repertoire, we have analyzed the consequences of splenectomy in the recently established IgL-transgenic L2 mouse model. L2 mice are characterized by a severe block of B-2 development and predominance of B-1a cells, which exhibit a pronounced IgH oligoclonality, presumably due to positive selection by autoantigens. In this study, we show that, in striking contrast to splenectomized normal mice, L2 mice exhibit unchanged frequencies of peritoneal B-1a cells. The IgH repertoire of these B-1a cells, however, was severely perturbed in that the previously described predominant B-1a H chains were no longer present. The repertoire changes were partial since phosphatidylcholine-specific B-1a cells were present in similar numbers before and after splenectomy. Thus, splenic Ags appear to act as "survival factors" for major subsets of peritoneal B cells. The loss of B-1a cells in the absence of such factors is compensated by repertoire changes among B-1a cells in B cell lymphopenic L2 but not normal mice. C1 German Res Ctr Biotechnol, Braunschweig, Germany. Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. RP Kretschmer, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM Karsten_Kretschmer@dfci.harvard.edu RI Kretschmer, Karsten/E-8174-2010; Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 25 TC 15 Z9 16 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 1 PY 2004 VL 173 IS 1 BP 197 EP 204 PG 8 WC Immunology SC Immunology GA 831CQ UT WOS:000222170900028 PM 15210775 ER PT J AU Zeitels, SM Mauri, M Dailey, SH AF Zeitels, SM Mauri, M Dailey, SH TI Adduction arytenopexy for vocal fold paralysis: indications and technique SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE vocal cord paralysis; surgical procedures; operative ID LARYNGOPLASTIC PHONOSURGERY; MEDIALIZATION LARYNGOPLASTY; CRICOTHYROID SUBLUXATION; CADAVER LARYNGES; VOICE AB Adduction arytenopexy was designed as an innovation to arytenoid adduction, however the pragmatic issues regarding patient selection for these procedures has not been comprehensively assessed. A prospective examination was performed on 100 consecutive patients who had undergone laryngoplastic phonosurgical reconstruction for paralytic dysphonia. Seventy-seven of 100 (77 per cent) were judged pre-operatively to gain potentially significant phonatory enhancement from an arytenoid procedure. Fifty-six of 77 (73 per cent) underwent adduction arytenopexy; 17 of 77 (22 per cent) were judged pre-operatively to have inadequate respiratory abduction of the contralateral arytenoid and two out of 77 (three per cent) had athletic aerodynamic requirements. In another two out of 77 (three per cent), there was a chance of favourable reinnervation and thus it was not the preferred method. The majority of patients were judged pre-operatively to gain potentially substantial phonatory enhancement from an arytenoid procedure. However, in this series, approximately 25 per cent of the patients were considered to be unsuitable candidates for an arytenoid medializing procedure, primarily because it was deemed that the operation could result in an inadequate airway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 1 Bowdoin Sq, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu NR 17 TC 16 Z9 17 U1 0 U2 0 PU HEADLEY BROTHERS LTD PI ASHFORD PA INVICTA PRESS, ASHFORD TN24 8HH, KENT, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD JUL PY 2004 VL 118 IS 7 BP 508 EP 516 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 847VE UT WOS:000223425200005 PM 15318956 ER PT J AU Nieland, TJF Chroni, A Fitzgerald, ML Maliga, Z Zannis, VI Kirchhausen, T Krieger, M AF Nieland, TJF Chroni, A Fitzgerald, ML Maliga, Z Zannis, VI Kirchhausen, T Krieger, M TI Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide SO JOURNAL OF LIPID RESEARCH LA English DT Article DE scavenger receptor class B type 1; ATP binding cassette transporter Al; blockers of lipid transport ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR CLASS-B; BINDING CASSETTE TRANSPORTER; APOLIPOPROTEIN-A-I; SCAVENGER RECEPTOR; TANGIER-DISEASE; SELECTIVE UPTAKE; DEFICIENT MICE; APOA-I; CELLULAR CHOLESTEROL AB Scavenger receptor class B type I (SR-BI) and ABCA1 are structurally dissimilar cell surface proteins that play key roles in HDL metabolism. SR-BI is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterified cholesterol from cells to HDL. ABCA1 mediates the efflux of unesterified cholesterol and phospholipids from cells to lipid-poor apolipoprotein A-I (apoA-I). The activities of ABCA1 and other ATP binding cassette superfamily members are inhibited by the drug glyburide, and SR-BI-mediated lipid transport is blocked by small molecule inhibitors called BLTs. Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC50 similar to55-60 muM). Reciprocally, glyburide blocked SR-BI-mediated selective lipid uptake and efflux at a potency similar to that for its inhibition of ABCA1 (IC50 similar to275-300 muM). As is the case with BLTs, glyburide increased the apparent affinity of HDL binding to SR-BI. The reciprocal inhibition of SR-BI and ABCA1 by BLT-4 and glyburide raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.-Nieland, T.J. F., A. Chroni, M. L. Fitzgerald, Z. Maliga, V. I. Zannis, T. Kirchhausen, and M. Krieger. Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Med & Biochem, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Inst, Chem & Cell Biol, Boston, MA 02115 USA. RP Krieger, M (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM krieger@mit.edu FU NCI NIH HHS [CA-78048]; NHLBI NIH HHS [HL-48739, HL-52212, HL-66105, HL-68216]; NIGMS NIH HHS [GM-62566] NR 69 TC 61 Z9 62 U1 0 U2 3 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 JUL PY 2004 VL 45 IS 7 BP 1256 EP 1265 DI 10.1194/jlr.M300358-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831HV UT WOS:000222186400007 PM 15102890 ER PT J AU Tsoporis, JN Haddad, A Marks, A Huttunen, HJ Parker, TG AF Tsoporis, JN Haddad, A Marks, A Huttunen, HJ Parker, TG TI Expression and functional consequences of RAGE (receptor for advanced glycation end products)/S100B expression in rat myocardium SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000189 ER PT J AU Scholtens, D Miron, A Merchant, FM Miller, A Miron, PL Iglehart, JD Gentleman, R AF Scholtens, D Miron, A Merchant, FM Miller, A Miron, PL Iglehart, JD Gentleman, R TI Analyzing factorial designed microarray experiments SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE estrogen target; gene expression; gene selection; linear model; experimental design ID DIFFERENTIALLY EXPRESSED GENES; FALSE DISCOVERY RATE; ESTROGEN-RECEPTOR; BREAST-CANCER; OLIGONUCLEOTIDE ARRAYS; REGULATED GENES; CDNA MICROARRAY; SACCHAROMYCES-CEREVISIAE; PROTEIN COMPLEXES; CELL-LINE AB High-throughput quantification of gene expression using microarray technology has dramatically changed biological investigation into the roles of genes in normal cell functioning, as well as the mechanisms of disease. We discuss an analytic approach for framing biological questions in terms of statistical parameters to efficiently and confidently answer questions of interest using microarray data from factorial designed experiments. Investigators can extract pertinent and interpretable information from the data about the effects of the factors, their interactions with each other, and the statistical significance of these effects, rather than rely solely on clustering techniques or fold change point estimates in hopes of finding co-expressed genes. By first examining how biological mechanisms are reflected in mRNA transcript abundance, investigators can better design microarray experiments to answer the most interesting questions. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Sch Med, Durham, NC 27708 USA. Univ Auckland, Dept Stat, Auckland 1, New Zealand. RP Scholtens, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM dscholte@hsph.harvard.edu NR 56 TC 15 Z9 15 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 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD JUL PY 2004 VL 90 IS 1 BP 19 EP 43 DI 10.1016/j.jmva.2004.02.004 PG 25 WC Statistics & Probability SC Mathematics GA 828IV UT WOS:000221967900002 ER PT J AU Biederman, J Faraone, SV AF Biederman, J Faraone, SV TI Attention deficit hyperactivity disorder - A worldwide concern SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Editorial Material ID AGE-DEPENDENT DECLINE; DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADULTS C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit WACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit WACC 725, WRN 705,55 Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 22 TC 18 Z9 18 U1 0 U2 4 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 JUL PY 2004 VL 192 IS 7 BP 453 EP 454 DI 10.1097/01.nmd.0000131803.68229.96 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 837MV UT WOS:000222640500001 PM 15232314 ER PT J AU Blais, MA AF Blais, MA TI Development of an inpatient treatment alliance scale SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE inpatient treatment; alliance; quality; outcome ID THERAPEUTIC ALLIANCE; PHASE MODEL; PSYCHOTHERAPY AB Although alliance has been one of the most widely investigated variables in outpatient treatment research, its role in inpatient care has received little attention. One factor likely contributing to the lack of inpatient alliance research is the burdensome quality of most alliance scales. Guided by the existing alliance literature, we developed a brief 10-item scale that is designed to measure patients overall level of alliance to their inpatient care. This new scale was administered to 140 inpatients receiving standard inpatient care early in their hospitalization. Seventy-two patients completed the scale a second time at discharge. The scale demonstrated strong psychometric properties including internal consistency, adjusted item-to-scale correlations, and test-retest reliability. Scores from the inpatient alliance scale were meaningfully related to multiple outcome and treatment variables. Overall, this study demonstrates both the feasibility and potential benefit of exploring the effect of alliance on the process and outcome of inpatient treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Blais, MA (reprint author), MGH, 55 Fruit St Blake 11, Boston, MA 02114 USA. NR 22 TC 20 Z9 20 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 JUL PY 2004 VL 192 IS 7 BP 487 EP 493 DI 10.1097/01.nmd.000013191.53489.af PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 837MV UT WOS:000222640500006 PM 15232319 ER PT J AU Li, HW Liu, H Corrales, CE Mutai, H Heller, S AF Li, HW Liu, H Corrales, CE Mutai, H Heller, S TI Correlation of Pax-2 expression with cell proliferation in the developing chicken inner ear SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE otic vesicle; hair cell; apoptosis; proliferation; paired-box ID SENSORY ORGAN GENERATION; HAIR-CELLS; OTIC PLACODE; STEM-CELLS; EMBRYO; SPECIFICATION; APOPTOSIS; GENES; DEATH AB in vertebrates, the paired-box transcription factor Pax-2 is one of the earliest markers of the developing inner ear and is robustly expressed in the otic placode and the otic vesicle. Mutations in the Pax-2 gene result in developmental defects of the vestibular and auditory apparatus. We set out to investigate whether regions of Pax-2 expression in the developing otic vesicle correlate with areas of cell proliferation or cell death, which would indicate a possible role of Pax-2 in these processes. Regionalized proliferation and local apoptosis are the principal mechanisms that lead to the complex morphogenesis of the highly compartmentalized inner ear starting from a simple vesicle. We found a high correlation of Pax-2 expression with proliferating cells in the walls of the early otic vesicle. Apoptotic cells were mostly localized outside of the Pax-2-expressing regions. At later stages, we found the highest intensity of proliferating and Pax-2-positive cells in areas of the developing sensory epithelia. When hair cells begin to differentiate, they maintain a lower level of Pax-2 expression than neighboring cells for a brief period, before they completely down-regulate expression of this transcription factor. We conclude that a significant proportion of proliferating cells in the developing otocyst express Pax-2, in particular in regions that include developing sensory patches. This implicates Pax-2 as a marker for proliferating hair and supporting cell progenitors. Furthermore, the likelihood that Pax-2-expressing cells in the otocyst die by apoptosis is much lower when compared with cells residing in Pax-2-negative regions. (C) 2004 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Heller, S (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. EM hellers@epl.meei.harvard.edu FU NIDCD NIH HHS [DC04563, DC006167] NR 29 TC 33 Z9 33 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD JUL PY 2004 VL 60 IS 1 BP 61 EP 70 DI 10.1002/neu.20013 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 830DO UT WOS:000222102000007 PM 15188273 ER PT J AU Paintlia, AS Paintlia, MK Singh, AK Stanislaus, R Gilg, AG Barbosa, E Singh, I AF Paintlia, AS Paintlia, MK Singh, AK Stanislaus, R Gilg, AG Barbosa, E Singh, I TI Regulation of gene expression associated with acute experimental autoimmune encephalomyelitis by Lovastatin SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; multiple sclerosis; microarray; Lovastatin; inflammation ID COA REDUCTASE INHIBITOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS; VASCULAR ENDOTHELIAL-CELLS; ACTIVATED RECEPTOR-GAMMA; GLATIRAMER ACETATE; INTERFERON BETA-1B; NERVOUS-SYSTEM; PROGRESSIVE MS; FACTOR-I AB The attenuation of experimental autoimmune encephalomyelitis (EAE) by Lovastatin (LOV) has now been well established. The present study was designed to explore the global effect of LOV treatment on expression of immune-related genes in lumbar spinal cord (LSC) during acute EAE by using Affymetrix DNA microarrays. LOV treatment demonstrated the limited infiltration of inflammatory cells into the LSC, and microarray analysis further validated those interpretations by demonstrating relatively less alteration in expression of immune response genes in LOV-treated EAE rats on peak clinical day and recovery vs. untreated EAE counterparts. There was significant change in expression of about 158 immune-related genes (including 127 genes reported earlier) in LOV-treated vs. untreated EAE (>1.5 or <-1.5 fold change; P less than or equal to .05), of which 140 genes were suppressed and only 18 genes were up-regulated. These altered genes encode for leukocyte-specific markers and receptors, histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, cellular activation, and transcription factors and signal transduction-related molecules. Interestingly, T(H)2 phenotype cytokines such as interleukin-4, interleukin-10, and transforming growth factor-beta1 and transcription factors such as peroxisome proliferator-activated receptor (PPAR)-gamma were upregulated in LSC by LOV treatment as further revealed by real-time PCR and immunoblotting. These findings indicate that PPARs may be mediating the anti inflammatory and immunomodulatory effects of LOV. Together, these findings provide new insight into the molecular events associated with the protection provided by statins during treatment of demyelinating diseases such as multiple sclerosis. (C) 2004 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,CSB-316, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NINDS NIH HHS [NS-40144, NS-22576, NS-34741, NS-37766] NR 43 TC 60 Z9 64 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 2004 VL 77 IS 1 BP 63 EP 81 DI 10.1002/jnr.20130 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 834KW UT WOS:000222411000007 PM 15197739 ER PT J AU Matejuk, A Bakke, AC Hopke, C Dwyer, J Vandenbark, AA Offner, H AF Matejuk, A Bakke, AC Hopke, C Dwyer, J Vandenbark, AA Offner, H TI Estrogen treatment induces a novel population of regulatory cells, which suppresses experimental autoimmune encephalomyelitis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE CD45; EAE; suppression; estrogen ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; T-CELLS; MULTIPLE-SCLEROSIS; GENDER-DIFFERENCES; IMMUNE PATHOLOGY; GENE-EXPRESSION; TNF-ALPHA; MICE; PREGNANCY AB Multiple sclerosis (MS) is a debilitating neurological disease characterized by a progressive loss of motor and sensory function, eventually leading to paralysis and death. The primary cause of neurological impairment is demyelination of the central nervous system (CNS) caused by an inflammatory autoimmune response. Previous studies have shown that the severity of MS is reduced during pregnancy, suggesting that the increased level of sex hormones may reduce the autoimmune response. Recently, we have shown that estrogen treatment confers protection from experimental autoimmune encephalomyelitis (EAE), which is an animal model for MS. However, the cellular basis of estrogen's action remains unknown. In the current study, we demonstrate that estrogen treatment led to the induction of a novel subpopulation of regulatory cells in spleen and CNS, which also occurs naturally in pregnant mice. These previously uncharacterized cells display a low level expression of CD45 (CD45 dim) and no detectable expression of many cell surface markers related to TCR signaling, including CD3 and TCR. However, these cells retained expression of VLA-4, an extracellular protein involved in cellular migration. Several lines of evidence suggest that these novel cells, defined as CD45(dim)VLA-4(+) cells, may play a role in the protective effects of estrogen in EAE. Injection of purified CD45(dim)VLA-4(+) cells conferred protection from spontaneous EAE (Sp-EAE). In contrast, injection of CD45(high)VLA-4(+) cells exacerbated the disease course. CD45(dim)VLA-4(+) cells also suppressed antigen-specific proliferation of primed lymphocytes in coculture. A better understanding of how CD45(dim)VLA-4(+) cells suppress the harmful immune response of EAE may help in explaining the induction of immune tolerance during pregnancy and lead to novel therapeutic approaches to combat MS and other autoimmune diseases. (C) 2004 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Neuroimmunol Res, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Matejuk, A (reprint author), Portland VA Med Ctr, Neuroimmunol Res, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM matejuka@ohsu.edu FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 32 TC 26 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 2004 VL 77 IS 1 BP 119 EP 126 DI 10.1002/jnr.20145 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 834KW UT WOS:000222411000013 PM 15197745 ER PT J AU Valente, SM Bullough, V AF Valente, SM Bullough, V TI Sexual harassment of nurses in the workplace SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE evaluation; legal issues; sexual harassment ID BEHAVIOR AB Nurses who are sexually harassed at work face frustration and emotional and economic consequences. Historically before the 1970s, nurses had little legal recourse and tolerated sexual harassment as a necessary "evil" associated with working. The Civil Rights Act of 1964 created the option for legal remedies for sexual harassment/discrimination cases. Successful court cases established the legal criteria for sexual harassment. This article discusses the history, definition, high profile cases, research, consequences, and prevention of sexual harassment. Although research is scant and little is known of how nurses respond to harassing behavior, prevention requires coordinated activities of employers, individual employees, and the healthcare profession. Sexual harassment at work increases anxiety and undermines the nurse's ability to focus on the delivery of safe and competent care. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Los Angeles, CA USA. RP Valente, SM (reprint author), 346 N Bowling Green Way, Los Angeles, CA 90049 USA. EM Sharon.Valente@med.va.gov NR 27 TC 8 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-3631 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD JUL-SEP PY 2004 VL 19 IS 3 BP 234 EP 241 PG 8 WC Nursing SC Nursing GA 831SD UT WOS:000222215500009 PM 15326993 ER PT J AU Lopez-Garcia, E Schulze, MB Manson, JAE Meigs, JB Albert, CM Rifai, N Willett, WC Hu, FB AF Lopez-Garcia, E Schulze, MB Manson, JAE Meigs, JB Albert, CM Rifai, N Willett, WC Hu, FB TI Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women SO JOURNAL OF NUTRITION LA English DT Article DE (n-3) fatty acids; inflammation; endothelial activation; C-reactive protein; fish ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SELF-ADMINISTERED QUESTIONNAIRE; FOOD FREQUENCY QUESTIONNAIRE; HORMONE REPLACEMENT THERAPY; CARDIOVASCULAR-DISEASE; CELL-ADHESION; DIETARY-INTAKE; E-SELECTIN; FISH OIL AB We evaluated the hypothesis that intake of (n-3) fatty acids is inversely associated with biomarkers of inflammation and endothelial activation. We conducted a cross-sectional study of 727 women from the Nurses' Health Study I cohort, aged 43-69 y, apparently healthy at time of a blood draw in 1990. Dietary intake was assessed by a validated FFQ in 1986 and 1990. C-reactive protein (CRP) levels were 29% lower among those in the highest quintile of total (n-3) fatty acids, compared with the lowest quintile; interleukin-6 (IL-6) levels were 23% lower, E-selectin levels 10% lower, soluble intracellular adhesion molecule (sICAM-1) levels 7% lower, and soluble vascular adhesion molecule (sVCAM-1) levels 8% lower. The intake of a-linolenic acid was inversely related to plasma concentrations of CRP (beta = -0.55, P = 0.02), II-6 (P = -0.36, P = 0.01), and E-selectin (beta = -0.24, P = 0.008) after controlling for age, BMI, physical activity, smoking status, alcohol consumption, and intake of linoleic acid (n-6) and saturated fat. Long-chain (n-3) fatty acids (eicosapentaenoic and docosahexaenoic) were inversely related to sICAM-1 (beta = -0.11, P = 0.03) and sVCAM-1 (beta = -0.17, P = 0.003). Total (n-3) fatty acids had an inverse relation with CRP (beta = -0.44, P = 0.007), IL-6 (beta = -0.26, P = 0.009), E-selectin (beta = -0.17, P = 0.004), sICAM-1 (beta = -0.07, P = 0.02), and sVCAM-1 (beta = -0.10, P = 0.004). These associations were not modified by intake of vitamin E, dietary fiber, trans fatty acids, or by the use of postmenopausal hormone therapy. In conclusion, this study suggests that dietary (n-3) fatty acids are associated with levels of these biomarkers reflecting lower levels of inflammation and endothelial activation, which might explain in part the effect of these fatty acids in preventing cardiovascular disease. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Cambridge, MA USA. Harvard Univ, Sch Med, Div Prevent Med, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Lopez-Garcia, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. EM elopezga@hsph.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK55523, DK58845] NR 43 TC 213 Z9 221 U1 2 U2 19 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 2004 VL 134 IS 7 BP 1806 EP 1811 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 836UP UT WOS:000222581600022 PM 15226473 ER PT J AU Garofalakis, A Zacharakis, G Filippidis, G Sanidas, E Tsiftsis, D Ntziachristos, V Papazoglou, TG Ripoll, J AF Garofalakis, A Zacharakis, G Filippidis, G Sanidas, E Tsiftsis, D Ntziachristos, V Papazoglou, TG Ripoll, J TI Characterization of the reduced scattering coefficient for optically thin samples: theory and experiments SO JOURNAL OF OPTICS A-PURE AND APPLIED OPTICS LA English DT Article DE reduced scattering coefficient; diffusion approximation; time-resolved spectroscopy; small samples; optical characterization ID PHOTON-DENSITY WAVES; TIME-RESOLVED REFLECTANCE; 2-LAYERED TURBID MEDIA; DISCRETE RANDOM-MEDIA; DIFFUSION-COEFFICIENT; MULTIPLE-SCATTERING; BOUNDARY-CONDITIONS; RADIATIVE-TRANSFER; FREQUENCY-DOMAIN; DIFFRACTION TOMOGRAPHY AB Diffusion theory is currently used to characterize highly scattering media from time and/or spatially resolved measurements. However, many of the limits of validity of the diffusion approximation in its standard form have been set through assumptions taken during its derivation, and it is generally believed that the diffusion equation holds only for length scales much larger than the transport mean free path (l(tr)). We here present several modifications to the standard diffusion approximation to provide a simple expression for characterizing optically thin scattering slabs. The improvements concern mainly the correct modelling of the temporal and spatial distribution of the source term and the use of a frequency dependent diffusion coefficient and boundary conditions. This novel expression is put to the test against Monte Carlo simulations and experimental data taken from measurements with phantoms of known optical properties. The reduced scattering coefficient can be retrieved accurately for slab widths of the order of the mean free path. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, GR-71110 Iraklion, Greece. Univ Crete, Gen Hosp, Sch Med, Dept Surg Oncol, GR-71110 Iraklion, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Garofalakis, A (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, GR-71110 Iraklion, Greece. EM agarof@iesi.forth.gr; jripoll@iesl.forth.gr RI Filippidis, George/A-2473-2014; Zacharakis, Giannis/A-2544-2014; Papazoglou, Theodore/B-4794-2015; Ripoll, Jorge/J-8134-2012 OI Filippidis, George/0000-0003-4748-5968; Zacharakis, Giannis/0000-0002-6438-0773; Papazoglou, Theodore/0000-0002-2789-8880; Ripoll, Jorge/0000-0001-8856-7738 NR 79 TC 9 Z9 10 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1464-4258 J9 J OPT A-PURE APPL OP JI J. Opt. A-Pure Appl. Opt. PD JUL PY 2004 VL 6 IS 7 BP 725 EP 735 AR PII S1464-4285(04)73742-3 DI 10.1088/1464-4258/6/7/012 PG 11 WC Optics SC Optics GA 842RM UT WOS:000223021700012 ER PT J AU Woo, VV Chuang, SK Daher, S Muftu, A Dodson, TB AF Woo, VV Chuang, SK Daher, S Muftu, A Dodson, TB TI Dentoalveolar reconstructive procedures as a risk factor for implant failure SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ATROPHIC EDENTULOUS MAXILLA; 3-YEAR PROSPECTIVE MULTICENTER; SEVERELY RESORBED MAXILLA; SINUS FLOOR AUGMENTATION; LONG-TERM EVALUATION; FORT-I OSTEOTOMY; BONE-GRAFTS; ENDOSSEOUS IMPLANTS; FOLLOW-UP; RIDGE AUGMENTATION AB Purpose: Dentoalveolar reconstructive procedures (DRPs) are commonly used to enhance deficient implant recipient sites. It is unclear, however, if these procedures are independent risk factors for implant failure. The specific aim of this study was to assess the use of DRPs as a risk factor for implant failure. Materials and Methods: To address the research aim, we used a retrospective cohort study design and a study sample derived from the population of patients who had one or more implants inserted between May 1992 and July 2000. The main predictor variable was the use of DRPs, such as external or internal sinus lifts, onlay bone grafting, or guided-tissue regeneration with autogenous bone grafts or autogenous bone graft substitutes, to enhance the recipient sites before implant insertion. The major outcome variable was implant failure. Appropriate descriptive, bivariate, and multivariate statistics were computed. Results: The study sample was composed of 677 patients who had 677 implants randomly selected (I implant per patient) for analysis. The overall 1- and 5-year implant survival rates were 95.2% and 90.2%, respectively. Bivariate analyses revealed 4 factors statistically or nearly statistically associated with implant failure: current tobacco use, implant length, implant staging, and type of prosthesis (P < .15). In the multivariate model, patients with DRPs did not have a statistically significant increased risk for implant failure (odds ratio = 1.4, P =.3). Conclusions: The results of this study suggest that the use of DRPs to reconstruct deficient implant recipient sites was not an independent risk factor for implant failure in either the unadjusted or adjusted analyses. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA USA. Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org RI Muftu, Ali/N-1232-2013 OI Muftu, Ali/0000-0002-6702-5945 FU NIDCR NIH HHS [K24 DE00448, K16 DE00275] NR 62 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2004 VL 62 IS 7 BP 773 EP 780 DI 10.1016/j.joms.2003.12.017 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 832RY UT WOS:000222285900002 PM 15218553 ER PT J AU Troulis, MJ Kaban, LB AF Troulis, MJ Kaban, LB TI Endoscopic vertical ramus osteotomy: Early clinical results SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MANAGEMENT; FRACTURES AB Purpose: The benefits of minimally invasive surgery have been well documented. The purpose of this report was to present early results in a series of patients who had endoscopic mandibular orthognathic surgery. Patients and Methods: This is a retrospective evaluation of 14 patients who underwent endoscopic vertical ramus osteotomy and rigid fixation for the treatment of mandibular prognathism (n = 9), malocclusion secondary to trauma (n = 3), or other pathology (n = 2). A 1.5-cm incision was made directly below the mandibular angle. The dissection was continued bluntly to the masseter muscle, which was incised using a needlepoint electrocautery. Then, with endoscopic elevators, an optical cavity was created for insertion of a Hopkins endoscope and visualization of the ramus/condyle unit. Anatomic landmarks were identified and the operation carried out with specially designed endoscopic equipment. Preoperative (TO), postoperative (T1), and follow-up (T2) clinical examinations; lateral cephalograms; and panoramic radiographs were used to evaluate the outcomes. Results: The procedures performed included: vertical ramus osteotomy (n = 13 patients, 23 sides) and condylectomy plus vertical ramus osteotomy (n = 1 patient, 1 side). Mean operating time was 37 minutes per side. One patient had temporary marginal mandibular nerve weakness. The occlusal result was as planned in all cases. Panoramic radiographs documented postoperative ramus/condyle unit position and lateral cephalograms documented mandibular position. Conclusions: The results of this case series indicate that endoscopic vertical ramus osteotomy with rigid fixation is feasible for correction of a variety of mandibular deformities. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [K23-DE 14070-02] NR 23 TC 25 Z9 26 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 JUL PY 2004 VL 62 IS 7 BP 824 EP 828 DI 10.1016/j.joms.2003.012.021 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 832RY UT WOS:000222285900009 PM 15218560 ER PT J AU Li, G DeFrate, LE Zayontz, S Park, SE Gill, TJ AF Li, G DeFrate, LE Zayontz, S Park, SE Gill, TJ TI The effect of tibiofemoral joint kinematics on patellofemoral contact pressures under simulated muscle loads SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE patellofemoral joint; contact pressure; knee kinematics; osteoarthritis ID POSTERIOR CRUCIATE LIGAMENT; TOTAL KNEE ARTHROPLASTY; IN-SITU FORCES; PATELLAR TENDON; Q-ANGLE; RECONSTRUCTION; VITRO; QUADRICEPS; DEFICIENCY; TRACKING AB Altered patellofemoral joint contact pressures are thought to contribute to patellofemoral joint symptoms. However, little is known about the relationship between tibiofemoral joint kinematics and patellofemoral joint contact pressures. The objective of this paper was to investigate the effect of tibiofemoral joint kinematics on patellofemoral joint pressures using an established in vitro robotic testing experimental setup. Eight cadaveric knee specimens were tested at 0degrees, 30degrees, 60degrees, 90degrees, and 120degrees of flexion under an isolated quadriceps load of 400 N and a combined quadriceps/hamstrings load of 400 N/200 N. Tibiofemoral joint kinematics were measured by the robot and contact pressures by a TekScan pressure sensor. The isolated quadriceps loading caused anterior translation and internal rotation of the tibia up to 60degrees of flexion and posterior translation and external rotation of the tibia beyond 60degrees. The co-contraction of the hamstring muscles caused a posterior translation and external rotation of the tibia relative to the motion of the tibia under the quadriceps load. Correspondingly, the contact pressures were elevated significantly at all flexion angles. For example, at 60degrees of flexion, the hamstrings co-contraction increased the posterior tibial translation by approximately 2.8 mm and external tibia] rotation by approximately 3.6degrees. The peak contact pressure increased from 1.4 +/- 0.8 to 1.7 +/- 1.0 MPa, a 15% increase. The elevated contact pressures after hamstrings co-contraction indicates an intrinsic relation between the tibiofemoral joint kinematics and the patellofemoral joint biomechanics. An increase in posterior tibial translation and external rotation is accompanied by an increase in contact pressure in the patellofernoral joint. These results imply that excessive strength conditioning with the hamstring muscles might not be beneficial to the patellofemoral joint. Knee pathology that causes an increase in tibial posterior translation and external rotation might contribute to degeneration of the patellofemoral joint. These results suggest that conservative treatment of posterior cruciate ligament injury should be reconsidered. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med,Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM glil@partners.org NR 34 TC 81 Z9 84 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JUL PY 2004 VL 22 IS 4 BP 801 EP 806 DI 10.1016/j.orthres.2003.11.011 PG 6 WC Orthopedics SC Orthopedics GA 834HK UT WOS:000222402000016 PM 15183437 ER PT J AU Ferrick, MR Birch, JG Albright, M AF Ferrick, MR Birch, JG Albright, M TI Correction of non-Blount's angular knee deformity by permanent hemiepiphyseodesis SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE valgus; varus; hemiepiphyseodesis; lower extremity; alignment; knee ID IDIOPATHIC GENU-VALGUM; PARTIAL EPIPHYSIODESIS; ANKLE VALGUS; EPIPHYSEODESIS; CHILDREN; SCREW AB This retrospective study evaluated the results of permanent hemiepiphyseodesis for the correction of non-Blount's coronal plane angular knee deformity. The medical records and radiographs of 75 patients with 125 angular knee deformities were analyzed for overall rate of success and factors predicting successful correction of deformity. There were 38 patients with idiopathic genu valgum and 37 with various other skeletal disorders. Sixty-nine out of 75 patients had reached skeletal maturity at latest follow-up. One hundred six knees out of 125 were successfully treated by the procedure. Of the 19 remaining knees, 15 were operated on too close to skeletal maturity to expect correction and 4 were technically unsuccessful in achieving closure of the targeted physis. There were no complications other than overcorrection, which occurred in 15 knees (I I patients). This study indicates that permanent hemiepiphyseodesis is a very useful procedure if performed in a timely and technically successful manner. C1 Womens & Childrens Hosp, Dept Orthopaed Surg, Buffalo, NY 14222 USA. Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferrick, MR (reprint author), Womens & Childrens Hosp, Dept Orthopaed Surg, 219 Bryant St, Buffalo, NY 14222 USA. EM mferrick@buffalo.edu NR 13 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD JUL-AUG PY 2004 VL 24 IS 4 BP 397 EP 402 PG 6 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 834MA UT WOS:000222414000010 PM 15205622 ER PT J AU Hosgor, M Karaca, I Ozer, E Erdag, G Ulukus, C Fescekoglu, O Aikawa, M AF Hosgor, M Karaca, I Ozer, E Erdag, G Ulukus, C Fescekoglu, O Aikawa, M TI The role of smooth muscle cell differentiation in the mechanism of obliteration of processus vaginalis SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE myosin heavy chains; smooth muscle; inguinal hernia; hydrocele ID HEAVY-CHAIN ISOFORMS; INGUINAL-HERNIA; UNDESCENDED TESTIS; EXPRESSION; CHILDREN; SAC AB Background/Purpose: Development of indirect inguinal hernia and hydrocele in childhood is readily explained by the persistence of smooth muscle component around the processus vaginalis (PV) after the descent of the testis into the scrotum. The aim of this study was to investigate the expression of smooth muscle myosin heavy chain (SM MHC) isoforms as the markers of smooth muscle cell (SMC) differentiation in childhood inguinal hernia and hydrocele and in age-matched controls. Methods: The authors analyzed sacs from patients with inguinal hernia (male, 10; female, 10) and hydrocele (n = 10) immunohistochemically using monoclonal antibodies against a-smooth muscle actin, SM1, SM2 and SMemb. Peritoneal samples (male, 5; female, 5) obtained from age-matched patients served as controls. Immunostaining was evaluated with semiquantitative scoring and chi(2) test. Results: The expression pattern of SM MHC isoforms did not differ among sacs obtained from female inguinal hernia when compared with that of controls. However, strong expression of SMemb within the sac walls of male inguinal hernia and SM1 in hydrocele groups were observed. Conclusions: Our results indicate that SMC differentiation may play an important role in the obliteration of processus vaginalis in male inguinal hernia and hydrocele after the descent of the testis. (C) 2004 Elsevier Inc. All rights reserved. C1 Dr Behcet Uz Childrens Hosp, Dept Pediat Surg, Izmir, Turkey. Dokuz Eylul Univ, Dept Pathol, Izmir, Turkey. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hosgor, M (reprint author), Koruturk Mh Simsek Sk Yagmur Sitesi K1,D1,68-B, TR-35330 Izmir, Turkey. NR 20 TC 7 Z9 7 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2004 VL 39 IS 7 BP 1018 EP 1023 DI 10.1016/j.jpedsurg.2004.03.056 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 839RN UT WOS:000222802700003 PM 15213890 ER PT J AU Hosgor, M Karaca, I Karkiner, A Ucan, B Temir, G Erdag, G Fescekoglu, O AF Hosgor, M Karaca, I Karkiner, A Ucan, B Temir, G Erdag, G Fescekoglu, O TI Associated malformations in delayed presentation of congenital diaphragmatic hernia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE congenital diaphragmatic hernia; delayed presentation; Bochdalek hernia ID PULMONARY SEQUESTRATION; BOCHDALEK HERNIA; DUPLICATION CYST; DEFECTS; SURVIVAL; CHILDREN AB Background/Purpose: Delayed presentation of congenital diaphragmatic hernia (CDH) has been considered rare, and clinical manifestations differ from the more common newborn entity. Associated malformations in late-appearing CDH have been reported in a few patients. The authors reviewed their clinical experience to catalogue the frequency and clinical importance of associated malformations in patients with late-presenting CDH. Methods: The records of patients greater than 1 month of age with Bochdalek type CDH treated in the authors' clinic, from 1991 to 2001, were retrospectively reviewed. Twenty patients (age range, 1 month to 10 years) were included in the study. Results: Associated malformations were documented in 16 of the patients (80%) and included malrotation in 12 patients, umbilical hernia in 2, pulmonary hypoplasia in 4, pulmonary sequestration in 1, gastroesophageal duplication cyst coexisting with polysplenia in 1, atrial septal defect and ventricular septal defect in 1, hydronephrosis in 1, wandering spleen in 1, talipes equinovarus in 1, and type I diabetes mellitus in 1. Conclusions: The results of this study show a significant incidence and a wide spectrum of associated malformations. These findings suggest that patients with late CDH should be evaluated carefully for additional anomalies that may help to establish correct diagnosis and treatment. (C) 2004 Elsevier Inc. All rights reserved. C1 Dr Behcet Uz Childrens Hosp, Dept Pediat Surg, Izmir, Turkey. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hosgor, M (reprint author), Koruturk Mh,Simsek Sk,Yagmur Sitesi K,1 D 1,68-B, TR-35330 Izmir, Turkey. NR 24 TC 23 Z9 26 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2004 VL 39 IS 7 BP 1073 EP 1076 DI 10.1016/j.jpedsurg.2004.03.050 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 839RN UT WOS:000222802700015 PM 15213902 ER PT J AU Singh, JA Pando, JA Tomaszewski, J Schumacher, HR AF Singh, JA Pando, JA Tomaszewski, J Schumacher, HR TI Quantitative analysis of immunohistologic features of very early rheumatoid synovitis in disease modifying antirheumatic drug- and corticosteroid-naive patients SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; very early synovitis; quantitative immunohistochemistry ID MORPHOMETRIC ANALYSIS; BLOOD-VESSELS; KNEE JOINTS; ARTHRITIS; MEMBRANE; DURATION; TISSUE AB Objective. To describe the immunohistochemical features of very early rheumatoid synovitis in disease modifying antirheumatic drug- and corticosteroid-naive patients. Methods. Eight patients presenting with oligoarthritis or polyarthritis, who later met American Rheumatism Association criteria for rheumatoid arthritis (RA), underwent needle synovial biopsies of a knee joint within the first 6 weeks after onset of disease symptoms. Using antibodies to CD3, CD8, L26, CD68, and von Willebrand factor, a detailed quantitative immunohistochemical analysis was done. Results. CD3+ T lymphocytes, CD8+ T lymphocytes, L26+ B lymphocytes, and CD68+ macrophages were seen in 8/8 (100%), 7/8 (87%), 4/8 (50%), and 6/6 (100%) of synovial biopsies stained with the respective marker. There was a wide variation in number of positive cells between patients. CD3+ and CD8+ T cells were seen predominantly in perivascular areas, less often in a diffuse distribution, and not in aggregates. L26+ B lymphocytes were found in much smaller numbers compared with T lymphocytes. A mean of 67 vessels/mm(2) was noted. No lymphoid aggregates were seen. In all cases, infiltration of macrophages and lymphocytes was limited mainly to relatively superficial parts of synovium, i.e., within 1 to 2 high power fields of the surface. Conclusion. An absence of lymphoid aggregates or dramatic vascularity and a predominantly superficial infiltrate consisting mainly of perivascular T cell's with few B cells characterized our patients with very early RA of < 6 weeks' duration. Thus, there appear to be some potentially important differences from findings reported in well established disease. C1 Univ Minnesota, Div Rheumatol, Minneapolis, MN USA. Beebe Hosp, Lewes, DE USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Arthrit Res 151 K, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Philadelphia VA Med Ctr, Arthrit Res 151 K, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu OI singh, jasvinder/0000-0003-3485-0006 NR 24 TC 11 Z9 11 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2004 VL 31 IS 7 BP 1281 EP 1285 PG 5 WC Rheumatology SC Rheumatology GA 835KK UT WOS:000222481600009 PM 15229944 ER PT J AU Gariti, P Alterman, AI Lynch, KG Kampman, K Whittingham, T AF Gariti, P Alterman, AI Lynch, KG Kampman, K Whittingham, T TI Adding a nicotine blocking agent to cigarette tapering SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT 65th Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14-19, 2003 CL Bal Harbour, FL SP Coll Problems Drug Dependence DE nicotine fading; cigarette tapering; Accu Drop; smoking cessation; motivational interviewing ID SMOKING CESSATION; PATCH THERAPY; RELIABILITY; WITHDRAWAL; ABSTINENCE; DEPENDENCE; VALIDITY AB A non-pharmacologic nicotine-blocking agent (Accu Drop; AD) was preliminarily tested in combination with cigarette tapering and brief counseling (C) in a random assignment, double-blind, placebo controlled, 6-week smoking cessation study (n=60). It was hypothesized that the AD&C group would have higher rates of treatment completion and smoking abstinence than the placebo drop group plus counseling (PD&C). The participants were 37 women and 23 men averaging 24 cigarettes per day along with high Fagerstrom nicotine dependence scores (FTQsimilar to7) and high plasma cotinine levels (>250ng/ml). There were no significant differences between groups for withdrawal scores, treatment completion (55%), or average number of sessions attended. Point prevalence followup evaluations were obtained 1 week, 1 month, and 6 months post projected treatment completion. Biochemically confirmed abstinence rates at followups did not differ between treatment groups (AD&C=10%, 13%, 10% vs. PD&C=3%, 10%, 13%). There is not enough evidence to suggest a Stage II trial. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Gariti, P (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA. EM gariti_p@mail.trc.upenn.edu FU NIDA NIH HHS [DA 11645] NR 26 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL PY 2004 VL 27 IS 1 BP 17 EP 25 DI 10.1016/j.jsat.2004.03.005 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 836AZ UT WOS:000222528400003 PM 15223089 ER PT J AU Willis, DJ Kalish, JA Li, C Deutsch, ER Contreras, MA LoGerfo, FW Quist, WC AF Willis, DJ Kalish, JA Li, C Deutsch, ER Contreras, MA LoGerfo, FW Quist, WC TI Temporal gene expression following prosthetic arterial grafting SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE gene expression; microarray; prosthetic arterial grafting; vascular smooth muscle; intimal hyperplasia; neointima ID SMOOTH-MUSCLE-CELLS; INFLAMMATORY FACTOR-I; RAT CAROTID ARTERIES; OLIGONUCLEOTIDE ARRAYS; INTIMAL HYPERPLASIA; MICROARRAY ANALYSIS; ENDOTHELIAL-CELLS; PROLIFERATION; FAILURE; MECHANISMS AB Background. Following prosthetic arterial grafting, cytokines and growth factors released within the peri-anastomotic tissues stimulate smooth muscle cell proliferation and matrix production. While much in vitro work has characterized this response, little understanding exists regarding the sequential up- and down-regulation of genes following prosthetic arterial grafting. This study evaluates temporal gene expression at the distal anastomosis of prosthetic arterial grafts using microarray analysis. Methods. Expanded polytetrafluoroethylene (ePTFE) carotid interposition grafts (n = 12) were surgically implanted into mongrel dogs. Distal anastomotic segments were harvested at 7, 14, 30, or 60 days. Contralateral. carotid artery served as control. Total RNA was isolated from the anastomotic tissue and paired controls. Samples were probed with oligonucleotide microarrays consisting of approximately 10,000 human genes to analyze differential gene expression at each time point. Results. Forty-nine genes were found to be upregulated and 37 genes were found to be downregulated at various time points. Six genes were found to be consistently up-regulated at all time intervals, including collagen type 1 alpha-1 and alpha-2, 80K-L protein (MARCKS), and osteopontin. Six genes were found to be consistently down-regulated, including smoothelin and tropomyosin 2. RT-PCR and immunohistochemistry confirmed the microarray data. Conclusions. This study uses microarray analysis to identify genes that were temporally up- and downregulated after prosthetic arterial grafting. Genes with similar patterns of expression have been identified, providing insights into related cellular pathways that may result in the formation of anastomotic intimal hyperplasia. (C) 2004 Elsevier Inc. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Willis, DJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, HIM Bldg,4 Blackfan Circle,Room 131, Boston, MA 02115 USA. EM willid01@popmail.med.nyu.edu FU NHLBI NIH HHS [T32-HL07734, R01-HL21796] NR 40 TC 11 Z9 11 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2004 VL 120 IS 1 BP 27 EP 36 DI 10.1016/j.jss.2003.12.014 PG 10 WC Surgery SC Surgery GA 827IR UT WOS:000221893400004 PM 15172187 ER PT J AU Lin, T Guinan, JJ AF Lin, T Guinan, JJ TI Time-frequency analysis of auditory-nerve-fiber and hasilar-membrane click responses reveal glide irregularities and non-characteristic-frequency skirts SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BASILAR-MEMBRANE; IMPULSE RESPONSES; PATTERNS; COCHLEA; PHASE; ORGAN AB Although many properties of click responses can be accounted for by a single, frequency-dispersive traveling wave exciting a single, characteristic-frequency (CF) resonance, some properties, such as waxing and waning cannot. Joint time-frequency distributions (TFDs) were used to help understand click responses of cat single auditory-nerve (AN) fibers (CFs < 4 kHz) and published measurements of chinchilla basilar-membrane (BM) motion. For CFs > 800 Hz, the peak energy of the response decreased in latency and frequency as the level increased, as expected. However, at high levels the trend reversed for AN, but not BM, responses. Normalized TFDs, which show the frequency with the peak energy at each response time, revealed glides, as previously reported. Classical theory predicts smooth, upward glides. Instead, at low CFs there were downward glides, and at other CFs glides had substantial irregularities. Finally, click skirts, defined as the longest-latency part of click responses, sometimes showed deviations from CF for above-threshold sound levels. Most of these phenomena are not explained by a single, frequency-dispersive traveling wave exciting a single CF resonance, but they can be accounted for by the interaction of two (or more) excitation drives with different latencies and frequency contents. (C) 2004 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Lin, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIDCD NIH HHS [P30 DC05209, 5 R01 DC 00235] NR 30 TC 24 Z9 24 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2004 VL 116 IS 1 BP 405 EP 416 DI 10.1121/1.1753294 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 837XN UT WOS:000222674800041 PM 15296001 ER PT J AU Michelson, D Buitelaar, JK Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Faries, DE Zhang, SY Biederman, J AF Michelson, D Buitelaar, JK Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Faries, DE Zhang, SY Biederman, J TI Relapse prevention in pediatric patients with ADHD treated with atomoxetine: A randomized, double-blind, placebo-controlled study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; pediatric patients; relapse prevention ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CHILDREN; ADOLESCENTS; TRIAL; SAMPLE AB Objective: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. Method: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. Results: A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p = .002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p < .001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. Conclusions: In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. Katholieke Univ Leuven, Louvain, Belgium. Barnneuropsykiatriska Kliniken, Gothenburg, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cagliari, Clin Neuropsichiat Infantile, Cagliari, Italy. RP Michelson, D (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 1730, Indianapolis, IN 46285 USA. EM michelson@lilly.com RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 29 TC 84 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2004 VL 43 IS 7 BP 896 EP 904 DI 10.1097/01.chi.0000125089.35109.81 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 832DF UT WOS:000222246700015 PM 15213591 ER EF