FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Qiu, DY Cheng, SM Wozniak, L McSweeney, M Perrone, E Levin, M AF Qiu, DY Cheng, SM Wozniak, L McSweeney, M Perrone, E Levin, M TI Localization and loss-of-function implicates ciliary proteins in early, cytoplasmic roles in left-right asymmetry SO DEVELOPMENTAL DYNAMICS LA English DT Review DE left-right asymmetry; cilia; motor protein; lrd; inversin; kif3b; polaris ID LEFT-RIGHT AXIS; POLYCYSTIC KIDNEY-DISEASE; ACETYLATED ALPHA-TUBULIN; CONFOCAL IMMUNOFLUORESCENCE MICROSCOPY; CALCIUM-RELEASE CHANNEL; EARLY STEP; AMPHIBIAN OOGENESIS; EPITHELIAL-CELLS; KUPFFERS VESICLE; XENOPUS-OOCYTES AB Left-right asymmetry is a crucial feature of the vertebrate body plan. While much molecular detail of this patterning pathway has been uncovered, the embryonic mechanisms of the initiation of asymmetry, and their evolutionary conservation among species, are still not understood. A popular recent model based on data from mouse embryos suggests extracellular movement of determinants by ciliary motion at the eastrulating node as the initial step. An alternative model, driven by findings in the frog and chick embryo, focuses instead on cytoplasmic roles of motor proteins. To begin to test the latter hypothesis, we analyzed the very early embryonic localization of ciliary targets implicated in mouse LR asymmetry. Immunohistochemistry was performed on frog and chick embryos using antibodies that have (KIF3B, Polaris, Polycystin-2, acetylated a-tubulin) or have not (LRD, INV, detyrosinated alpha-tubulin) been shown to detect in frog embryos only the target that they detect in mammalian tissue. Immunohistochemistry revealed localization signals for all targets in the cytoplasm of cleavage-stage Xenopus embryos, and in the base of the primitive streak in chick embryos at streak initiation. Importantly, several left-right asymmetries were detected in both species, and the localization signals were dependent on microtubule and actin cytoskeletal organization. Moreover, loss-of-function experiments implicated very early intracellular microtubule-dependent motor protein function as an obligate aspect of oriented LR asymmetry in Xenopus embryos. These data are consistent with cytoplasmic roles for motor proteins in patterning the left-right axis that do not involve ciliary motion. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Harvard Univ, Sch Dent Med, Forsyth Inst, Cytokine Biol Dept, 140 The Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244]; NIGMS NIH HHS [1-R01-GM-06227] NR 103 TC 49 Z9 50 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2005 VL 234 IS 1 BP 176 EP 189 DI 10.1002/dvdy.20509 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 957EY UT WOS:000231353700019 PM 16059906 ER PT J AU Boyko, EJ AF Boyko, EJ TI Progress in the estimation of mortality due to diabetes SO DIABETES CARE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; FOLLOW-UP; POPULATION; DEATHS; ADULTS; RISK C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, S-152E,1660 S Columbian Way, Seattle, WA 98108 USA. EM eboyko@u.washington.edu NR 11 TC 6 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2005 VL 28 IS 9 BP 2320 EP 2321 DI 10.2337/diacare.28.9.2320 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NV UT WOS:000231525700040 PM 16123511 ER PT J AU Polonsky, WH Zee, J Yee, MA Crosson, MA Jackson, RA AF Polonsky, WH Zee, J Yee, MA Crosson, MA Jackson, RA TI A community-based program to encourage patients' attention to their own diabetes care - Pilot development and evaluation SO DIABETES EDUCATOR LA English DT Article ID BLOOD-PRESSURE; MICROVASCULAR COMPLICATIONS; RISK; KNOWLEDGE; NEPHROPATHY; ASSOCIATION; PROGRESSION; RETINOPATHY; AWARENESS; EDUCATION AB Purpose The authors evaluated the ability of a brief educational program to enhance patients' self-care behavior and their familiarity with the meaning and utility of 5 of the major clinical tests in diabetes (A1C, blood pressure, low-density lipoprotein [LDL] cholesterol, microalbumin, and the dilated eye examination). Methods Adults with type 1 or type 2 diabetes were invited to attend a free, 90-minute small-group workshop about diabetes care, which included on-site metabolic testing that provided patients with immediate results and personalized feedback to understand those results. In total, 221 individuals with diabetes participated and completed baseline and 3-month follow-up questionnaires. Results From baseline to 3 months, participants reported significant improvement in following recommendations for meal planning (P < .001), regular exercise (P < .002), and blood glucose monitoring (P < .05) and a significant rise in test awareness for A1C, blood pressure, LDL cholesterol, and microalbumin (in all cases, P < .001). Conclusions A brief educational intervention appeared effective in encouraging patients toward better self-management and more regular metabolic testing and to become more aware of their own test results. Future research should aim to replicate and extend these findings in a randomized controlled trial. C1 Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Hawaii, Honolulu, HI 96822 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Polonsky, WH (reprint author), POB 2148, Del Mar, CA 92014 USA. EM whp@behavioraldiabetes.org NR 19 TC 8 Z9 8 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD SEP-OCT PY 2005 VL 31 IS 5 BP 691 EP 699 DI 10.1177/0145721705280416 PG 9 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 967XS UT WOS:000232125100007 PM 16203853 ER PT J AU Rosengren, DB Baer, JS Hartzler, B Dunn, CW Wells, EA AF Rosengren, DB Baer, JS Hartzler, B Dunn, CW Wells, EA TI The video assessment of simulated encounters (VASE): Development and validation of a group-administered method for evaluating clinician skills in motivational interviewing SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE motivational interviewing; training evaluation; skill assessment AB The authors developed and evaluated a group-administered method for measuring motivational interviewing (MI) skills. The video assessment of simulated encounters (VASE) consists of three videotaped vignettes of actors playing substance abusers. Each vignette is followed by eight questions asking examinees to generate written responses consistent with MI principles. Twenty-two clinicians completed the VASE questionnaire and two other measures of MI skill: a paper-and-pencil measure that elicited responses to written scenarios and an audiotaped interaction with a standardized patient (SP), subsequently scored for MI skill by independent tape raters. Psychometric analyses of this original VASE scale evaluated: (1) scoring reliability of the 24 VASE items; (2) internal reliability of the VASE full-scale score, seven subscale scores and the three vignettes; and (3) concurrent validity with aforementioned indices of MI skill. Analyses informed the removal of two subscales, redesign of a third and revisions to a fourth. The resulting 18-item VASE-R scale retains its three-vignette format, and assesses overall MI skill as well as the following five MI "microskills": reflective listening, responding to resistance, summarizing, eliciting change talk and developing discrepancy. The VASE-R requires further analysis to evaluate these revisions, but shows promise as a cost-effective alternative for use in MI skill assessment in a variety of training and research contexts. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Univ Washington, Sch Social Work, Seattle, WA 98195 USA. RP Rosengren, DB (reprint author), Univ Washington, Inst Alcohol & Drug Abuse, 1107 NE 45th St,Suite 120, Seattle, WA 98195 USA. EM dbr@u.washington.edu NR 25 TC 18 Z9 19 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2005 VL 79 IS 3 BP 321 EP 330 DI 10.1016/j.drugalcdep.2005.02.004 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 960YG UT WOS:000231628500005 PM 16102376 ER PT J AU Hind, JA Nicosia, MA Gangnon, R Robbins, J AF Hind, JA Nicosia, MA Gangnon, R Robbins, J TI The effects of intraoral pressure sensors on normal young and old swallowing patterns SO DYSPHAGIA LA English DT Article DE deglutition; lingual pressure; instrumentation; deglutition disorders ID PENETRATION-ASPIRATION SCALE; VOLUME; AGE AB Lingual pressure generation plays a crucial role in oropharyngeal swallowing. To more discretely study the dynamic oropharyngeal system, a 3-bulb array of pressure sensors was designed with the Kay Elemetrics Corporation (Lincoln Park, NJ). The influence of the device upon normal swallowing mechanics and boluses representative of flow relative to age and bolus condition was the focus of this study. Twelve healthy adults in two age groups (31 +/- 5 years, 2 males and 4 females, and 78 +/- 7 years, 2 males and 4 females) participated. Each subject was instructed to swallow four boluses representative of conditions with and without three pressure sensors affixed to the hard palate. Post-swallow residue at four locations, Penetration/Aspiration Scale scores, and three bolus flow timing measures were assessed videofluoroscopically with respect to age and bolus condition. The only statistically significant influences attributable to the presence of the pressure sensors were slight increases in residue in the oral cavity and upper esophageal sphincter with some bolus consistencies, 8% more frequent trace penetration of the laryngeal vestibule predominantly with effortful swallowing, and variances in oral clearance duration. We conclude that the presence of the pressure sensors does not significantly alter normal swallowing patterns of healthy individuals. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Minnesota, Dept Biomed Engn, Minneapolis, MN USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. RP Hind, JA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, GRECC 11G,2500 Overlook Terrace, Madison, WI 53705 USA. EM jahind@wisc.edu FU NINDS NIH HHS [NS24427] NR 12 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 2005 VL 20 IS 4 BP 249 EP 253 DI 10.1007/s00455-005-0020-2 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 024EV UT WOS:000236179200001 PM 16633867 ER PT J AU Tsai, J Tong, Q Tan, G Chang, AN Orkin, SH Hotamisligil, GS AF Tsai, J Tong, Q Tan, G Chang, AN Orkin, SH Hotamisligil, GS TI The transcription factor GATA2 regulates differentiation of brown adipocytes SO EMBO REPORTS LA English DT Article DE differentiation; transcription; brown adipocyte; obesity; metabolic regulation ID UNCOUPLING PROTEIN GENE; ADIPOSE-TISSUE; PPAR-GAMMA; INSULIN-RESISTANCE/; TRANSGENIC MICE; C/EBP FAMILY; OBESITY; EXPRESSION; CELLS; THERMOGENESIS AB Brown adipose tissue ( BAT) is a specialized mammalian tissue and a site of adaptive thermogenesis. Although the metabolic functions of brown and white adipocytes are distinct, terminal differentiation of both adipocyte lineages is regulated by well-characterized common transcription factors. However, the early stages of adipocyte differentiation and regulation of precursor cells are not well understood. We report here that GATA2 is expressed in brown adipocyte precursors, and its expression is downregulated in a differentiation- dependent manner. Constitutive expression of GATA2 suppressed expression of BAT-specific genes in brown adipocytes, whereas disruption of a GATA2 allele in brown preadipocytes resulted in significantly elevated differentiation and expression of several markers of brown adipogenesis. Collectively, these results show that GATA2 functions to suppress brown adipocyte differentiation, whereas reduction of GATA2 promotes brown adipogenesis. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hotamisligil, GS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM ghotamis@hsph.harvard.edu FU NIDDK NIH HHS [R01 DK056894, DK56894]; NIEHS NIH HHS [T32-ES07155-17, T32 ES007155] NR 32 TC 20 Z9 22 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2005 VL 6 IS 9 BP 879 EP 884 DI 10.1038/sj.embor.7400490 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 965VL UT WOS:000231978400019 PM 16082385 ER PT J AU Antonescu, CN Huang, C Niu, W Liu, Z Eyers, PA Heidenreich, KA Bilan, PJ Klip, A AF Antonescu, CN Huang, C Niu, W Liu, Z Eyers, PA Heidenreich, KA Bilan, PJ Klip, A TI Reduction of insulin-stimulated glucose uptake in L6 myotubes by the protein kinase inhibitor SB203580 is independent of p38MAPK activity SO ENDOCRINOLOGY LA English DT Article ID TYPE-2 DIABETIC-PATIENTS; RAT SKELETAL-MUSCLE; GLUT4 TRANSLOCATION; 3T3-L1 ADIPOCYTES; P38 MAPK; CELLULAR STRESSES; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; ECTOPIC EXPRESSION; MAMMALIAN-CELLS AB Insulin increases glucose uptake through translocation of the glucose transporter GLUT4 to the plasma membrane. We previously showed that insulin activates p38MAPK, and inhibitors of p38MAPK alpha and p38MAPK beta (e. g. SB203580) reduce insulin-stimulated glucose uptake without affecting GLUT4 translocation. This observation suggested that insulin may increase GLUT4 activity via p38 alpha and/or p38 beta. Here we further explore the possible participation of p38MAPK through a combination of molecular strategies. SB203580 reduced insulin stimulation of glucose uptake in L6 myotubes overexpressing an SB203580-resistant p38 alpha (drug-resistant p38 alpha) but barely affected phosphorylation of the p38 substrate MAPK-activated protein kinase-2. Expression of dominant-negative p38 alpha or p38 beta reduced p38MAPK phosphorylation by 70% but had no effect on insulin-stimulated glucose uptake. Gene silencing via isoform-specific small interfering RNAs reduced expression of p38 alpha or p38 beta by 60-70% without diminishing insulin-stimulated glucose uptake. SB203580 reduced photoaffinity labeling of GLUT4 by bio-LC-ATB-BMPA only in the insulin-stimulated state. Unless low levels of p38MAPK suffice to regulate glucose uptake, these results suggest that the inhibition of insulin-stimulated glucose transport by SB203580 is likely not mediated by p38MAPK. Instead, changes experienced by insulin-stimulated GLUT4 make it susceptible to inhibition by SB203580. C1 Hosp Sick Children, Cell Biol Programme, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. Univ Manchester, Sch Life Sci, Manchester M13 9PT, Lancs, England. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Klip, A (reprint author), Hosp Sick Children, Cell Biol Programme, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM amira@sickkids.ca RI Antonescu, Costin/A-2353-2011; Huang, Carol/H-2248-2014 NR 58 TC 41 Z9 45 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2005 VL 146 IS 9 BP 3773 EP 3781 DI 10.1210/en.2005-0404 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955RB UT WOS:000231243600015 PM 15947002 ER PT J AU Cohen, LE AF Cohen, LE TI Endocrine late effects of cancer treatment SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; LONG-TERM SURVIVORS; GROWTH-HORMONE SECRETION; PITUITARY-ADRENAL AXIS; CHILDHOOD BRAIN-TUMORS; CENTRAL PRECOCIOUS PUBERTY; YOUNG-ADULT SURVIVORS; CRANIAL IRRADIATION; MINERAL DENSITY AB Endocrinopathies are significant consequences of the treatment of childhood cancers. The risk of developing these adverse events is related to the underlying disease and its treatment with cytotoxic agents and radiation therapy This article reviews hypothalamic-pituitary, thyroid, and gonadal dysfunction, as well as osteopenia-osteoporosis and obesity. C1 Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, LE (reprint author), Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. EM laurie.cohen@childrens.harvard.edu NR 118 TC 17 Z9 21 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 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2005 VL 34 IS 3 BP 769 EP + DI 10.1016/j.ecl.2005.04.008 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 961QR UT WOS:000231677400016 PM 16085170 ER PT J AU Green, R Hauser, R Calafat, AM Weuve, J Schettler, T Ringer, S Huttner, K Hu, H AF Green, R Hauser, R Calafat, AM Weuve, J Schettler, T Ringer, S Huttner, K Hu, H TI Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE di(2-ethylhexyl) phthalate; hospital equipment and supplies; mono (2-ethylhexyl) phthallate; neonatal intensive care units; newborn infants ID PLASTICIZER; EXPOSURE; CELLS AB OBJECTIVE: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds non-covalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. DESIGN: We used a cross-sectional design for this study. PARTICIPANTS: We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 36 April 2003. MEASUREMENTS: A priori, we classified the infants' exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants' urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/tandem mass spectrometry. RESULTS: Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03). CONCLUSION: Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Sci & Environm Hlth Network, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Neonatol Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neonatol Unit, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. RP Hu, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr E 3-110A,401 Pk Dr, Boston, MA 02215 USA. EM lihu@hsph.harvard.edu FU NIEHS NIH HHS [P30 ES000002, ES00002] NR 19 TC 96 Z9 101 U1 3 U2 17 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2005 VL 113 IS 9 BP 1222 EP 1225 DI 10.1289/chp.7932 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 961QU UT WOS:000231677700043 PM 16140631 ER PT J AU O'Neill, MS Zanobetti, A Gold, DR Sarnat, JA Panayiotis, AE Horton, E Veves, A Schwartz, J AF O'Neill, MS Zanobetti, A Gold, DR Sarnat, JA Panayiotis, AE Horton, E Veves, A Schwartz, J TI Airborne particles and cell adhesion molecules among people with type II diabetes SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. Ctr Endocrinol & Metab, Nicosia, Cyprus. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess 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 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S59 EP S60 DI 10.1097/00001648-200509000-00142 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200141 ER PT J AU Park, SK O'Neill, MS Vokonas, PS Sparrow, D Hu, H Schwartz, J AF Park, SK O'Neill, MS Vokonas, PS Sparrow, D Hu, H Schwartz, J TI Air pollution, lead exposure, and heart rate variability: The VA normative aging study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S127 EP S128 DI 10.1097/00001648-200509000-00322 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200321 ER PT J AU Dworetzky, BA Strahonja-Packard, A Shanahan, CW Paz, J Schauble, B Bromfield, EB AF Dworetzky, BA Strahonja-Packard, A Shanahan, CW Paz, J Schauble, B Bromfield, EB TI Characteristics of male veterans with psychogenic nonepileptic seizures SO EPILEPSIA LA English DT Article DE gender; men; veterans; psychogenic nonepileptic seizures; video-EEG monitoring ID QUALITY-OF-LIFE; PSEUDOSEIZURES; EEG; DIAGNOSIS; EPILEPSY; STRESS; INJURY; TRAUMA AB Purpose: To describe male patients (pts) with psychogenic nonepileptic seizures (PNESs) followed up in a Veteran's Administration (VA) seizure clinic and to compare them with those with epileptic seizures (ESs) by using clinical, and psychosocial variables. Methods: Adult male veterans seen between 1997 and 2000 with ESs were compared with those with PNESs with respect to clinical history (head trauma, antiepileptic drug exposure, depression, anxiety, substance abuse, seizure description), documented chronic pain, posttraumatic stress disorder (PTSD), compensation for diagnosis, neurologic examination, and test results including imaging and EEG data. Results: Men with PNESs were younger and reported more frequent events, and diagnoses of chronic pain, anxiety, and PTSD were significantly greater. Neuroimaging [computed tomography (CT) or magnetic resonance imaging (MRI) of the brain] and neurologic examination were significantly more likely to be normal or nonspecific in pts with PNESs, although history of ictal urinary incontinence or service-connected compensation for diagnosis did not distinguish the groups. Conclusions: Male veterans with PNESs have characteristics similar to those reported in the literature, even though younger women have dominated previously studied populations. Compared with men with ESs, those with PNESs are more likely to have chronic pain, anxiety, and PTSD, as well as normal examinations and brain imaging. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. RP Dworetzky, BA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM bdworetzky@partners.org RI Shanahan, Christopher/H-6592-2015; OI Shanahan, Christopher/0000-0001-9067-5922; Dworetzky, Barbara/0000-0002-3364-2347 NR 39 TC 30 Z9 30 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2005 VL 46 IS 9 BP 1418 EP 1422 DI 10.1111/j.1528-1167.2005.13004.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 959GV UT WOS:000231507100009 PM 16146437 ER PT J AU Lyczkowski, DA Pfeifer, HH Ghosh, S Thiele, EA AF Lyczkowski, DA Pfeifer, HH Ghosh, S Thiele, EA TI Safety and tolerability of the ketogenic diet in pediatric epilepsy: Effects of valproate combination therapy SO EPILEPSIA LA English DT Article DE valproic acid; ketogenic diet; adverse-event profile ID ACID HEPATIC FATALITIES; CHILDHOOD EPILEPSY; CARNITINE LEVELS; 150 CHILDREN; COMPLICATIONS; PANCREATITIS; EFFICACY AB Purpose: To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures. Methods: The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated. Results: Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups. Conclusions: KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control. C1 Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Pediat, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 30 TC 21 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2005 VL 46 IS 9 BP 1533 EP 1538 DI 10.1111/j.1528-1167.2005.22705.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 959GV UT WOS:000231507100022 PM 16146450 ER PT J AU McNabb, DS Reed, R Marciniak, RA AF McNabb, DS Reed, R Marciniak, RA TI Dual luciferase assay system for rapid assessment of gene expression in Saccharomyces cerevisiae SO EUKARYOTIC CELL LA English DT Article ID ESCHERICHIA-COLI; BETA-GALACTOSIDASE; 2-HYBRID SYSTEM; REPORTER ASSAY; CYC1 GENE; YEAST; PROTEIN; TERMINATION; TRANSFORMATION; CONSTRUCTION AB A new reporter system has been developed for quantifying gene expression in the yeast Saccharomyces cerevisiae. The system relies on two different reporter genes, Renilla and firefly luciferase, to evaluate regulated gene expression. The gene encoding Renilla luciferase is fused to a constitutive promoter (PGK1 or SPT15) and integrated into the yeast genome at the CAN1 locus as a control for normalizing the assay. The firefly luciferase gene is fused to the test promoter and integrated into the yeast genome at the ura3 or leu2 locus. The dual luciferase assay is performed by sequentially measuring the firefly and Renilla luciferase activities of the same sample, with the results expressed as the ratio of firefly to Renilla luciferase activity (Fluc/Rluc). The yeast dual luciferase reporter (DLR) was characterized and shown to be very efficient, requiring approximately I minute to complete each assay, and has proven to yield data that accurately and reproducibly reflect promoter activity. A series of integrating plasmids were generated that contain either the firefly or Renilla luciferase gene preceded by a multicloning region in two different orientations and the three reading frames to make possible the generation of translational fusions. Additionally, each set of plasmids contains either the URA3 or LEU2 marker for genetic selection in yeast. A series of S288C-based yeast strains, including a two-hybrid strain, were developed to facilitate the use of the yeast DLR assay. This assay can be readily adapted to a high-throughput platform for studies requiring numerous measurements. C1 Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Univ Arkansas, Dept Biol Sci, SCEN601, Fayetteville, AR 72701 USA. EM dmcnabb@uark.edu FU NIAID NIH HHS [AI51470, R01 AI051470] NR 36 TC 37 Z9 43 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD SEP PY 2005 VL 4 IS 9 BP 1539 EP 1549 DI 10.1128/EC.4.9.1539-1549.2005 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 965HV UT WOS:000231942100004 PM 16151247 ER PT J AU Finsen, AV Ostli, EK Wilcox-Adelman, SA Goetinck, PF Lyberg, T Sjaastad, I Djurovic, S Christensen, G AF Finsen, A. V. Ostli, E. K. Wilcox-Adelman, S. A. Goetinck, P. F. Lyberg, T. Sjaastad, I. Djurovic, S. Christensen, G. TI A role for syndecan-4 during development of heart failure following myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Ullevaal Univ Hosp, Expt Med Res Inst, Oslo, Norway. Ullevaal Univ Hosp, Cent HF Res, Oslo, Norway. Ullevaal Univ Hosp, Dept Med Genet, Oslo, Norway. Ullevaal Univ Hosp, CHFR, Oslo, Norway. Ullevaal Univ Hosp, Clin Res Ctr, Oslo, Norway. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P548 BP 67 EP 67 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987100262 ER PT J AU Janardhanan, R Kenchaiah, S Park, Y McMurray, J Pfeffer, MA Weaver, WD Finn, PV Solomon, SD AF Janardhanan, R. Kenchaiah, S. Park, Y. McMurray, J. Pfeffer, M. A. Weaver, W. D. Finn, P. V. Solomon, S. D. TI Extent of coronary artery disease and cardiovascular outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Brigham & Womens Hosp, Dept Cardiol, Boston, MA USA. Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. Western Infirm & Associated Hosp, Dept Cardiol, Glasgow, Lanark, Scotland. Henry Ford Hosp, Dept Cardiol, Detroit, MI USA. RI Solomon, Scott/I-5789-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA 831 BP 117 EP 117 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987100462 ER PT J AU Pitschner, HF Reddy, V Kuniss, M Neuzil, P Laragy, M Taborsky, M Ruskin, J Hamm, C AF Pitschner, H. F. Reddy, V. Kuniss, M. Neuzil, P. Laragy, M. Taborsky, M. Ruskin, J. Hamm, C. TI Pulmonary vein isolation in patients with atrial fibrillation using a novel balloon cryoablation catheter SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, Dept Cardiol, D-6350 Bad Nauheim, Germany. Homolka Hosp, Prague, Czech Republic. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA 961 BP 131 EP 131 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987100518 ER PT J AU Achenbach, S Ferencik, M Ropers, D Abbara, S Cury, R Nieman, K Hoffmann, U Daniel, WG AF Achenbach, S. Ferencik, M. Ropers, D. Abbara, S. Cury, R. Nieman, K. Hoffmann, U. Daniel, W. G. TI Diagnostic accuracy of image postprocessing methods for the detection of coronary artery stenoses by multi-detector computed tomography SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Univ Erlangen Nurnberg, Med Klin 2, Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P1016 BP 134 EP 134 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987100528 ER PT J AU Januzzi, J Tung, R Chen, A Lloyd-Jones, D Baggish, A Krauser, D Anwaruddin, S Camargo, C AF Januzzi, J. Tung, R. Chen, A. Lloyd-Jones, D. Baggish, A. Krauser, D. Anwaruddin, S. Camargo, C. TI The utility of NT-proBNP testing for the diagnosis of destabilised CHF in patients with obstructive airway disease: a ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) substudy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 178 EP 178 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987101167 ER PT J AU Carroll, DL Hamilton, GA Kenney, B AF Carroll, D. L. Hamilton, G. A. Kenney, B. TI Long-term effects of the implanted cardioverter defibrillator on quality of life SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Hosp Norway, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 268 EP 268 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987101516 ER PT J AU Januzzi, J Anwaruddin, S Krauser, D Tung, R Baggish, A Cameron, R Lloyd-Jones, D AF Januzzi, J. Anwaruddin, S. Krauser, D. Tung, R. Baggish, A. Cameron, R. Lloyd-Jones, D. TI NT-proBNP testing is useful for evaluation of dyspneic patients with impaired renal function: a proBNP investigation of dyspnea in the Emergency Department (PRIDE) substudy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P1759 BP 274 EP 274 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987102002 ER PT J AU Staszewsky, L Masson, S Carretta, E Amigoni, M Wong, M Anand, I Cohn, JN Latini, R AF Staszewsky, L. Masson, S. Carretta, E. Amigoni, M. Wong, M. Anand, I. Cohn, J. N. Latini, R. CA Val-HeFT investigators TI Prognostic value of chronic obstructive pulmonary disease in heart failure patients: data from the Val-HeFT trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Mario Negri Inst Pharmacol Res, Dept Cardiovasc Res, Milan, Italy. VA Greater Healthcare Syst, Los Angeles, CA USA. Univ Minnesota, Sch Med, VA Med Ctr, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P1782 BP 280 EP 280 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987102025 ER PT J AU Thibault, H Gomez, L Bardet, A Chavanis, N Scherrer-Crosbie, M Ovize, M Derumeaux, GA AF Thibault, H. Gomez, L. Bardet, A. Chavanis, N. Scherrer-Crosbie, M. Ovize, M. Derumeaux, G. A. TI Assessment of regional myocardial function after acute myocardial infarction in mice: a strain rate study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Fac Med Lyon, EMIU N 0226, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P1868 BP 301 EP 301 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987102111 ER PT J AU Kirtane, AJ Murphy, SA Morrow, DA McCabe, CH Braunwald, E Gibson, CM AF Kirtane, A. J. Murphy, S. A. Morrow, D. A. McCabe, C. H. Braunwald, E. Gibson, C. M. TI Correlates of bleeding complications among moderate-high risk ACS patients undergoing contemporary PCI with eptifibatide SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P2228 BP 350 EP 350 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987102304 ER PT J AU Rodriguez, A Grindfeld, L Fernandez-Pereira, C Mieres, J Berrocal, D Vigo, CF O'Neill, W Palacios, I AF Rodriguez, A. Grindfeld, L. Fernandez-Pereira, C. Mieres, J. Berrocal, D. Vigo, C. F. O'Neill, W. Palacios, I. CA ERACI III Investigators TI Multiple vessel stenting in drug eluting stent era: one year follow up of the ERACI III study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Otamendi Hosp, Intervent Cardiol Dept, Buenos Aires, DF, Argentina. Italian Hosp, Buenos Aires, DF, Argentina. Otamendi Hosp, Buenos Aires, DF, Argentina. William Beaumont Hosp, Dept Cardiol, Royal Oak, MI 48072 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 410 EP 410 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987103023 ER PT J AU Tricoci, P Pieper, K Newby, LK Giugliano, RP Van de Werf, F Armstrong, PW Harrington, RA Califf, RM AF Tricoci, P. Pieper, K. Newby, L. K. Giugliano, R. P. Van de Werf, F. Armstrong, P. W. Harrington, R. A. Califf, R. M. TI Simplifying risk stratification in non-ST-segment elevation acute coronary syndromes SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Duke Univ, Ctr Med, Duke Clin Res Inst, Durham, NC 27706 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Hosp, Dept Cardiol, Louvain, Belgium. Univ Alberta, Edmonton, AB T6G 2M7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 431 EP 431 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987103108 ER PT J AU Gibson, CM Kirtane, AJ Murphy, SA Morrow, DA McCabe, CH Braunwald, E AF Gibson, C. M. Kirtane, A. J. Murphy, S. A. Morrow, D. A. McCabe, C. H. Braunwald, E. TI Associations of TIMI myocardial perfusion grade with biomarkers, Holter findings, and clinical outcomes among patients with moderate-high risk ACS SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 432 EP 432 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987103111 ER PT J AU Uemura, T Otsuji, Y Nakashiki, K Yu, B Kisanuki, A Minagoe, S Levine, R Tei, C AF Uemura, T. Otsuji, Y. Nakashiki, K. Yu, B. Kisanuki, A. Minagoe, S. Levine, R. Tei, C. TI Preserved papillary muscle function with significant adjacent left ventricular wall remodelling contributes to ischaemic mitral regurgitation in patients with prior inferior myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Kagoshima Univ, Ctr Cardiovasc, Kagoshima 890, Japan. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 540 EP 540 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987104029 ER PT J AU Ray, KK Cannon, CP Rader, DJ Cairns, R McCabe, CH Sacks, FM Braunwald, E AF Ray, K. K. Cannon, C. P. Rader, D. J. Cairns, R. McCabe, C. H. Sacks, F. M. Braunwald, E. TI Baseline ApoB predicts benefit of intensive statin therapy in patients with ACS: an analysis from PROVE IT-TIMI 22 SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 TIMI Study Grp, British Heart Fdn Int Fellow, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Philadelphia, Philadelphia, PA USA. Nottingham Clin Res Inst, Nottingham, England. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 553 EP 553 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987104080 ER PT J AU Goehler, AG Dietz, RD Osterziel, JKO Siebert, US AF Goehler, A. G. Dietz, R. D. Osterziel, J. K. O. Siebert, U. S. TI Systematic review of decision models in heart failure treatment SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Campus Virchow Klinikum, Charite, Div Cardiol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Tech Assessment, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 598 EP 598 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987104263 ER PT J AU Hatsukami, T Zhao, XQ Kraiss, LW Parker, DL Waterton, J Cain, V Raichlen, J Yuan, C AF Hatsukami, T. Zhao, X. Q. Kraiss, L. W. Parker, D. L. Waterton, J. Cain, V. Raichlen, J. Yuan, C. TI Assessment of rosuvastatin treatment on carotid atherosclerosis in moderately hypercholesterolemic subjects using high-resolution magnetic resonance imaging SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Univ Washington, Sch Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Utah, Salt Lake City, UT USA. AstraZeneca, Alderley Pk, Cheshire, England. AstraZeneca, Wilmington, DE USA. RI Waterton, John/A-8565-2008 OI Waterton, John/0000-0002-7734-2290 NR 0 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 626 EP 627 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987104362 ER PT J AU Nakashiki, K Otsuji, Y Uemura, T Yuasa, T Mizukami, N Kisanuki, A Levine, RA Tei, C AF Nakashiki, K. Otsuji, Y. Uemura, T. Yuasa, T. Mizukami, N. Kisanuki, A. Levine, R. A. Tei, C. TI Left atrial dilatation is an incremental factor to worsen mitral stenosis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Kagoshima Univ, Clin Lab, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 690 EP 690 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987105106 ER PT J AU Calderwood, SK Theriault, JR Gong, JL AF Calderwood, SK Theriault, JR Gong, JL TI Message in a bottle: Role of the 70-kDa heat shock protein family in anti-tumor immunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Review DE heat shock protein 70; tumor immunity; APC; internalization; immunogenic peptides ID ANTIGEN-PRESENTING CELLS; CLASS-I MOLECULES; PEPTIDE BINDING SPECIFICITIES; RECEPTOR-MEDIATED ENDOCYTOSIS; TOLL-LIKE RECEPTORS; NF-KAPPA-B; CROSS-PRESENTATION; ENDOTHELIAL-CELLS; COGNATE PROTEIN; DENDRITIC CELLS AB Extracellular heat shock protein 70 (HSP70) is a potent agent for tumor immunotherapy, which can break tolerance to tumor-associated antigens and cause specific tumor cell killing by cytotoxic CD8(+) T cells. The pro-immune effects of extracellular HSP70 are, to some extent, extensions of its molecular properties as an intracellular stress protein. The HSP70 are characterized by massive inducibility after stress, preventing cell death by inhibiting aggregation of cell proteins and directly antagonizing multiple cell death pathways. HSP70 family members possess a domain in the C terminus that chaperones unfolded proteins and peptides, and a N-terminal ATPase domain that controls the opening and closing of the peptide binding domain. These properties not only enable intracellular HSP70 to inhibit tumor apoptosis, but also promote formation of stable complexes with cytoplasmic tumor antigens that can then escape intact from dying cells to interact with antigen-processing cells (APC) and stimulate anti-tumor immunity. HSP70 may be released from tumors undergoing therapy at high local extracellular concentrations, and send a danger signal to the host leading to APC activation. Extracellular HSP70 bind to high-affinity receptors on APC, leading to activation of maturation and re-presentation of the peptide antigen cargo of HSP70 by the APC. The ability of HSP70-peptide complexes (HSP70-PC) to break tolerance and cause tumor regression employs these dual properties as signaling ligand and antigen transporter. HSP70-PC thus coordinately activate innate immune responses and deliver antigens for re-presentation by MHC class I and II molecules on the APC cell surface, leading to specific anti-tumor immunity. C1 Harvard Univ, Sch Med, BIDMC, Div Mol & Cellular Endocrinol, Boston, MA USA. Boston Univ, Sch Med, Ctr Mol Stress Response, Boston, MA 02118 USA. RP Calderwood, SK (reprint author), 21-27 Burlington Ave,Room 553B, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu FU NCI NIH HHS [CA31303, CA47407, CA50642] NR 105 TC 96 Z9 106 U1 0 U2 1 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 SEP PY 2005 VL 35 IS 9 BP 2518 EP 2527 DI 10.1002/eji.200535002 PG 10 WC Immunology SC Immunology GA 967BY UT WOS:000232067700001 PM 16144035 ER PT J AU Benatuil, L Kaye, J Rich, RF Fishman, JA Green, WR Iacomini, J AF Benatuil, L Kaye, J Rich, RF Fishman, JA Green, WR Iacomini, J TI The influence of natural antibody specificity on antigen immunogenicity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE natural antibodies; vaccine; B cells; T cells; immunogenicity ID FOLLICULAR DENDRITIC CELLS; AKR/GROSS VIRAL LEUKEMIAS; RETROVIRAL GENE-THERAPY; LYMPHOCYTE-T RESPONSES; COMPLEMENT RECEPTORS; IMMUNE-RESPONSE; MARGINAL ZONE; HUMAN SERUM; MICE; INDUCTION AB The natural antibody repertoire in humans, apes and Old World primates is distinct from the repertoire of all other placental mammals, and encodes antibodies specific for the carbohydrate epitope Gal alpha 1-3 Gal beta 1-4GlcNAc-R (alpha Gal). Here, we examined whether conjugating antigens to the alpha Gal epitope can augment their immunogenicity in alpha(1,3)galactosyltransferase knockout mice (GT(o) mice) which, like humans, produce alpha Gal-specific antibodies. Immunization of GT(o) mice with BSA conjugated to alpha Gal (alpha GalBSA) led to significant production of anti-BSA IgG antibodies without the need for adjuvant. This response was dependent on the presence of alpha Gal-reactive antibodies. Immunization of wild-type mice with alpha Gal-BSA failed to induce an anti-BSA response. The presence of aGal-reactive antibodies also led to an increase in the T cell response to BSA following immunization with alpha Gal-BSA when compared with mice that received BSA alone, resulting in an increased frequency of IFN-gamma- and IL-4-producing BSA-specific T cells. In addition, the ability to produce alpha Gal-reactive antibodies enhanced the cytotoxic T lymphocyte anti-viral antigen response following vaccination with murine leukemia virus transformed cell lines that express alpha Gal on their cell surface. Natural antibodies that bind alpha Gal therefore play a key role in increasing the efficiency of priming to antigens decorated with alpha Gal epitopes. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, MGH E, Boston, MA USA. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Iacomini, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, 221 Longwood Ave,LM 303, Boston, MA 02115 USA. EM jiacomini@rics.bwh.harvard.edu FU NIAID NIH HHS [R01AI044268, R01AI050602] NR 50 TC 17 Z9 18 U1 0 U2 0 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 SEP PY 2005 VL 35 IS 9 BP 2638 EP 2647 DI 10.1002/eji.200526146 PG 10 WC Immunology SC Immunology GA 967BY UT WOS:000232067700014 PM 16082726 ER PT J AU Fehr, T Takeuchi, Y Kurtz, J Wekerle, T Sykes, M AF Fehr, T Takeuchi, Y Kurtz, J Wekerle, T Sykes, M TI Early regulation of CD8 T cell alloreactivity by CD4(+)CD25(-) T cells in recipients of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral deletion of donor-reactive CD8(+) T cells, precluding a role for sustained regulation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE bone marrow transplantation; CD8 T cell; clonal deletion; regulatory cell; anti-CD154 ID BONE-MARROW-TRANSPLANTATION; TERM ALLOGRAFT SURVIVAL; VERSUS-HOST-DISEASE; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; MIXED CHIMERISM; COSTIMULATORY BLOCKADE; TOLERANCE INDUCTION; ANTIGEN RECEPTOR; IMMUNOREGULATORY CELLS AB While acquisition of regulatory function by CD4(+)CD25(-) T cells has been reported following antigenic stimulation, "naturally occurring" regulatory CD4(+) T cells (Treg) are believed to express CD25. We examined the mechanisms involved in peripheral CD8 T cell tolerance by induction of mixed chimerism using non-myeloablative conditioning with low-dose (3 Gy) total body irradiation and anti-CD154 antibody. Recipient CD4(+) T cells were initially required for the induction of CD8 cell tolerance, but were not needed beyond 2 weeks. Depletion of CD25(+) Treg prior to bone marrow transplantation and blockade of IL-2 with neutralizing antibody did not impede tolerance induction. Tolerance was dependent on CTLA4, but not on IFN-gamma. In C57BL/6 mice containing a fraction of 2C TCR transgenic CD8(+) T cells, which recognize the MHC class I alloantigen L-d, induction of chimerism with L, but not L, bone marrow cells led to deletion of peripheral 2C(+) CD8(+) cells within 1 week in peripheral blood and spleen. Complete deletion required the presence of recipient CD4(+) T cells. Thus, a novel, rapid form of regulation by CD4(+)CD25(-) T cells permits initial CD8 T cell tolerance in this model. Rapid peripheral deletion of donor-specific CD8 T cells precludes an ongoing requirement for CD4 T cell-mediated regulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH East,13th St,Bldg 149-5102, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01HL49915] NR 56 TC 58 Z9 58 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2005 VL 35 IS 9 BP 2679 EP 2690 DI 10.1002/eji.200526190 PG 12 WC Immunology SC Immunology GA 967BY UT WOS:000232067700018 PM 16082727 ER PT J AU Scarmeas, N Hadjigeorgiou, G Papadimitriou, A Dubois, B Sarazin, M Brandt, J Blacker, D Albert, M Devanand, D Honig, L Marder, K Bell, K Stern, Y AF Scarmeas, N. Hadjigeorgiou, G. Papadimitriou, A. Dubois, B. Sarazin, M. Brandt, J. Blacker, D. Albert, M. Devanand, D. Honig, L. Marder, K. Bell, K. Stern, Y. TI Behavioral abnormalities predict poor cognitive and functional outcomes and institutionalization in Alzheimer's disease (AD) SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Columbia Univ, Med Ctr, New York, NY 10027 USA. Johns Hopkins Univ, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Univ Thessaly, Larisa, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2005 VL 12 SU 2 BP 17 EP 18 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GW UT WOS:000202992200051 ER PT J AU Scarmeas, N Honig, L Choi, H Cantero, J Brandt, J Blacker, D Albert, M Marder, K Bell, K Hauser, WA Stern, Y AF Scarmeas, N. Honig, L. Choi, H. Cantero, J. Brandt, J. Blacker, D. Albert, M. Marder, K. Bell, K. Hauser, W. A. Stern, Y. TI Seizures in Alzheimer's disease (AD): and predictors SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 [Scarmeas, N.; Honig, L.; Choi, H.; Cantero, J.; Marder, K.; Bell, K.; Hauser, W. A.; Stern, Y.] Columbia Univ, Med Ctr, New York, NY USA. [Brandt, J.; Albert, M.] Johns Hopkins Univ, Baltimore, MD USA. [Blacker, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2005 VL 12 SU 2 BP 59 EP 59 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GW UT WOS:000202992200175 ER PT J AU Limmroth, V Biondi, D Pfeil, J Schwalen, S AF Limmroth, V. Biondi, D. Pfeil, J. Schwalen, S. TI Exploring the potential for topiramate to reduce the risk of developing a chronic migraine condition SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Dept Neurol, Essen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Estimate Med Stat BV, Doesburg, Netherlands. Janssen Cilag EMEA, Neuss, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2005 VL 12 SU 2 BP 202 EP 203 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GW UT WOS:000202992200618 ER PT J AU Bonab, AA Alpert, NM Liu, B Fischman, AJ AF Bonab, A. A. Alpert, N. M. Liu, B. Fischman, A. J. TI Low Dose CT Attenuation Correction for Brain imaging with PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Bonab, A. A.; Alpert, N. M.; Liu, B.; Fischman, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S258 EP S258 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745101582 ER PT J AU Gong, MN Zhou, W Williams, PL Thompson, BT Pothier, L Boyce, P Christiani, DC AF Gong, MN Zhou, W Williams, PL Thompson, BT Pothier, L Boyce, P Christiani, DC TI -308GA and TNFB polymorphisms in acute respiratory distress syndrome SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE acute respiratory distress syndrome; genetic susceptibility; tumour necrosis factor ID TUMOR-NECROSIS-FACTOR; ALPHA PROMOTER POLYMORPHISM; SEPTIC SHOCK; GENE POLYMORPHISM; SEVERE SEPSIS; ORGAN FAILURE; ARDS; MORTALITY; SUSCEPTIBILITY; ASSOCIATION AB The -308GA and TNFB1/2 polymorphisms of the tumour necrosis factor genes have been associated with increased susceptibility to, and mortality in sepsis, although, prior studies are not consistent. Their role in acute respiratory distress syndrome (ARDS) has not been evaluated. The current authors hypothesised that the -308A allele and TNFB22 genotype would be associated with increased susceptibility to, and mortality in ARDS. The above hypothesis was investigated in a nested case-control study of 441 Caucasian controls and 212 cases admitted to an intensive care unit with sepsis, trauma, aspiration or hypertransfusions. The -308A and TNFB1 alleles were in linkage disequilibrium. These polymorphisms were not associated with ARDS susceptibility on crude analysis. On subgroup analyses, they were associated with either increased or decreased odds of developing ARDS depending on whether the clinical risk for ARDS results in direct or indirect pulmonary injury. The -308A allele was associated with increased 60-day mortality in ARDS, with the strongest association found among younger patients. There was no association between the TNFB polymorphism and ARDS mortality. The -308GA, but not the TNFB12, polymorphism was associated with increased mortality in acute respiratory distress syndrome, but their association with acute respiratory distress syndrome susceptibility depended on the site of injury predisposing to acute respiratory distress syndrome. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Dept Med, Div Pulm & Crit Care Med, New York, NY 10029 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu NR 35 TC 54 Z9 62 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2005 VL 26 IS 3 BP 382 EP 389 DI 10.1183/09031936.05.00000505 PG 8 WC Respiratory System SC Respiratory System GA 963YZ UT WOS:000231844000005 PM 16135717 ER PT J AU Wanger, J Clausen, JL Coates, A Pedersen, OF Brusasco, V Burgos, F Casaburi, R Crapo, R Enright, P van der Grinten, CPM Gustafsson, P Hankinson, J Jensen, R Johnson, D MacIntyre, N McKay, R Miller, MR Navajas, D Pellegrino, R Viegi, G AF Wanger, J Clausen, JL Coates, A Pedersen, OF Brusasco, V Burgos, F Casaburi, R Crapo, R Enright, P van der Grinten, CPM Gustafsson, P Hankinson, J Jensen, R Johnson, D MacIntyre, N McKay, R Miller, MR Navajas, D Pellegrino, R Viegi, G TI Standardisation of the measurement of lung volumes SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE helium; lung function; lung physiology; lung volume measurements; nitrogen; radiology ID FUNCTIONAL RESIDUAL CAPACITY; THORACIC GAS VOLUME; PLETHYSMOGRAPHY; ABBREVIATIONS; FREQUENCY; SYMBOLS; UNITS C1 Univ Genoa, I-16132 Genoa, Italy. Pharmaceut Res Associates Inc, Lenexa, KS USA. Univ Calif San Diego, San Diego, CA 92103 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Aarhus, Aarhus, Denmark. Hosp Clin Villarroel, Barcelona, Spain. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. LDS Hosp, Salt Lake City, UT USA. Univ Hosp Maastricht, Maastricht, Netherlands. Queen Silvias Childrens Hosp, Gothenburg, Sweden. Hankinson Consulting Inc, Valdosta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Durham, NC USA. Occupat Med, Cincinnati, OH USA. Univ Hosp Birmingham NHS Trust, Birmingham, W Midlands, England. Univ Barcelona, IDIBAPS, Barcelona, Spain. Azienda Osped S Croce & Carle, Cuneo, Italy. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. RP Brusasco, V (reprint author), Univ Genoa, Vle Benedetto XV,6, I-16132 Genoa, Italy. EM vito.brusasco@unige.it RI Navajas, Daniel/E-4233-2010; Burgos, Felip/E-5734-2015 OI Navajas, Daniel/0000-0001-7150-9363; Burgos, Felip/0000-0002-4938-4581 NR 41 TC 925 Z9 953 U1 2 U2 33 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2005 VL 26 IS 3 BP 511 EP 522 DI 10.1183/09031936.05.00035005 PG 12 WC Respiratory System SC Respiratory System GA 963YZ UT WOS:000231844000024 PM 16135736 ER PT J AU Wolf, N Penn, P Pendergrass, W Van Remmen, H Bartke, A Rabinovitch, P Martin, GM AF Wolf, N Penn, P Pendergrass, W Van Remmen, H Bartke, A Rabinovitch, P Martin, GM TI Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE catarack; hormonal; hemizygous KO model; lens; mouse ID CELLULAR GLUTATHIONE-PEROXIDASE; MITOCHONDRIAL OXIDATIVE STRESS; RECEPTOR/BINDING PROTEIN GENE; SUPEROXIDE-DISMUTASE; NUCLEAR CATARACT; KNOCKOUT MICE; LIFE-SPAN; LIGHT EXPOSURE; LENS; DAMAGE AB Five mouse models with known alterations of resistance to oxidative damage were compared by slit lamp examination for the presence and degree of advancement of age-related cataract in young adult and old animals along with wild type controls. A group of young and old normal C57BL/6Jax mice were examined first to constitute a standard, and they were found to exhibit age-related cataract development. Following this, four models on the C57BL/6 background with imposed genetic alterations affecting anti-oxidant enzyme presence or activity, and one outbred model in which a deletion blocked the growth hormone/IGF-1 axis, were similarly examined. There was no evidence of foetal or juvenile cataract development in any of these models, and an age-related severity for lens opacities was shown between young adult and old mice in all groups. Model 1, mice null for the anti-oxidant gene glutathione peroxidase-1 (GPX1) had significantly advanced cataracts in older mice vs. same age controls. In mouse model 2 hemizygous knockout of SOD2 (MnSOD) did not affect age-related cataract development. In model 3 combining the GPX1 and SOD2 deficiencies in the same animal did not advance cataract development beyond that of the GPX1 null alone. In model 4 the addition of anti-oxidant protection in the lens by transfection of human catalase targeted only to the mitochondria resulted in a significant delay in cataract development. The 5th model, growth hormone receptor knockout (GHR-/-) mice, also demonstrated a significant reduction in age-related cataract development, as well as dwarfism. These findings, in general, support the oxidative theory of age-related cataract development. The exception, the partial deletion of SOD2 in the hemizygous KO model, probably did not represent a sufficiently severe deprivation of anti-oxidant protection to produce pathologic changes in the lens. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Washington, Dept Pathol, Sch Med, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. So Illinois Univ, Sch Med, Dept Internal Med, Springfield, IL USA. RP Wolf, N (reprint author), Univ Washington, Dept Pathol, Sch Med, Box 3557470, Seattle, WA 98195 USA. EM normwolf@u.washington.edu RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X FU NEI NIH HHS [R01 EY11733]; NIA NIH HHS [R01 AG19899]; PHS HHS [P01 01751] NR 52 TC 40 Z9 42 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 2005 VL 81 IS 3 BP 276 EP 285 DI 10.1016/j.exer.2005.01.024 PG 10 WC Ophthalmology SC Ophthalmology GA 965RG UT WOS:000231967400004 PM 16129095 ER PT J AU Rojas, B Cuhna, R Zafirakis, P Ramirez, JM Lizan-garciia, M Zhao, T Foster, CS AF Rojas, B Cuhna, R Zafirakis, P Ramirez, JM Lizan-garciia, M Zhao, T Foster, CS TI Cell populations and adhesion molecules expression in conjunctiva before and after bone marrow transplantation SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE bone marrow transplantation; graft-versus-host disease; dry eye; keratoconjunctivitis sicca; conjunctiva; lymphocytes; adhesion molecules ID VERSUS-HOST-DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC GRAFT; DRY EYE; T-CELLS; OCULAR MANIFESTATIONS; MONOCLONAL-ANTIBODIES; EFFECTOR MECHANISMS; SICCA SYNDROME; INFLAMMATION AB We were interested to analyse the composition of the cellular infiltrate and adhesion molecules expression in the conjunctiva before and at least one hundred days after autologous and allogenic bone marrow transplantation (BMT) and its relation with the presence of dry eye. We used immunohistochemistry on cryopreserved human conjunctiva with monoclonal antibodies to T-lymphocytes (CD3, CD4 and CD8), B-lymphocytes (CD19), macrophages (CD14), natural killer cells (NK, CD57), intercellular adhesion molecule 1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), lymphocyte function associated antigen-1 (LFA-1), very late antigen-4 (VLA-4), interleukin 2 receptor (IL2r, CD25) and HLA-DR. Our autologous recipients had no graft-versus-host disease (GVHD) but allogenic patients had chronic GVHD. After autologous BMT the conjunctiva had significantly more: (1) T lymphocytes (CD3+, CD4+, CD8+) in the epithelium; (2) CD4+ and CD 14+ cells in the stroma; and (3) VLA-4 expression in the stroma than before BMT. After allogenic BMT, the conjunctiva exhibited a significant increase of: (1) CD3+ and CD 14+ cells in the epithelium; (2) T lymphocytes (CD3+, CD4+, CD8+) and CD 14+ cells in the stroma; and (3) VLA-4 and LFA-1 expression in the stroma than before BMT. After the engraftment, the comparison between autologous and allogenic recipients revealed that: (1) there were no significant differences in adhesion molecule expression; (2) the epithelium of autologous recipients had significantly more CD3+ cells; and (3) the stroma of allogenic patients had significantly more CD3+ and CD8+ cells. Among allogenic recipients, CD14+ cells were significantly increased both in the epithelium and in the stroma of patients with signs or symptoms of dry eye in comparison with patients without ocular involvement. Additionally, those having keratoconjunetivitis sicca (KCS) had CD4/CD8 ratios significantly higher than those without KCS. In conclusion, in the conjunctiva after autologous BMT a subclinical cell mediated immune reaction seems to take place. The conjunctivitis of chronic GVHD is complex, with T cells and macrophages dramatically contributing to the process. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Complutense Madrid, Inst Invest Oftalmol Ramon Castroviejo, Fac Med, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Hilles Immunol Lab,Dept Ophthalmol, Boston, MA 02114 USA. Univ Fed Sao Paulo, Paulista Sch Med, Dept Ophthalmol, Sao Paulo, Brazil. Hosp Gen Albacete, Dept Prevent Med, Madrid, Spain. RP Rojas, B (reprint author), Univ Complutense Madrid, Inst Invest Oftalmol Ramon Castroviejo, Fac Med, Pabellon 6o,4a Planta, E-28040 Madrid, Spain. EM brojas@med.ucm.es; ramirezs@med.ucm.es; mlizan@sescam.org; Stephen_foster@meei.harvard.edu RI Ramirez, Jose /L-6325-2014; OI Ramirez, Jose /0000-0002-5145-5094; ROJAS LOPEZ, MARIA BLANCA/0000-0002-8980-4659 NR 81 TC 35 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 2005 VL 81 IS 3 BP 313 EP 325 DI 10.1016/j.exer.2005.02.004 PG 13 WC Ophthalmology SC Ophthalmology GA 965RG UT WOS:000231967400008 PM 16129099 ER PT J AU Lengerke, C Daley, GQ AF Lengerke, C Daley, GQ TI Patterning definitive hematopoietic stem cells from embryonic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE MARROW INJECTION; IN-VITRO GENERATION; WNT GENE FAMILY; MOUSE EMBRYO; YOLK-SAC; HOX GENES; LYMPHOHEMATOPOIETIC CELLS; MORPHOGENETIC PROTEIN-4; ENDOTHELIAL-CELLS; COMMON PRECURSOR AB Derived from the inner cell mass of blastocysts, embryonic stem cells (ESCs) retain the pluripotent features of early embryonic epiblast cells. In vitro, ESCs undergo spontaneous differentiation into a multitude of tissues, and thus are a powerful tool for the study of early developmental processes and a promising resource for cell-based therapies. We have pursued the derivation of functional, multipotent and engraftable hematopoietic stem cells (HSCs) from ESCs in order to investigate the genetic pathways specifying blood formation, as well as to lay the foundation for hematopoietic cell replacement therapies based on engineered ESCs. Theoretically, the generation of HSCs from patient-specific ESCs derived by nuclear transfer could provide for autologous hematopoietic therapies for the treatment of malignant and genetic bone marrow disorders. Although significant progress has been made in achieving hematopoietic differentiation from both murine and human ESCs, we have only a primitive understanding of the underlying mechanisms that specify hematopoietic cell fate, and a very limited capacity to direct the differentiation of the definitive HSC that would be suitable for clinical engraftment studies. Here we will review the progress to date and the significant problems that remain, and outline a strategy to achieve the directed differentiation of HSCs under conditions that might be appropriate for clinical scale-up and disease applications. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Harvard Stem Cell Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Univ Tubingen, Med Ctr 2, Dept Hematol & Oncol, Tubingen, Germany. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Lengerke, Claudia/0000-0001-5442-2805 NR 100 TC 16 Z9 16 U1 1 U2 2 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 SEP PY 2005 VL 33 IS 9 BP 971 EP 979 DI 10.1016/j.exphem.2005.06.004 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 971UD UT WOS:000232409400004 PM 16140144 ER PT J AU Berman, JN Kanki, JP Look, AT AF Berman, JN Kanki, JP Look, AT TI Zebrafish as a model for myelopoiesis during embryogenesis SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID T-CELL LEUKEMIA; CCAAT/ENHANCER-BINDING-PROTEIN; BONE MORPHOGENETIC PROTEINS; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELLS; INSERTIONAL MUTAGENESIS; TRANSGENIC ZEBRAFISH; VASCULAR DEVELOPMENT; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION AB Zebrafish produce nearly identical hematopoeitic cell lineages to those found in mammals and other higher vertebrates. As in mammals, blood cell development proceeds in distinct waves, constituting embryonic (primitive) and adult (definitive) hematopoiesis. The conservation of genes such as scl, pu.1, clebp alpha, mpo, l-plastic, and lysozyme C in myelopoiesis and the corresponding expression patterns in zebrafish suggests that shared genetic pathways regulate this complex developmental process. In the zebrafish model system, experimental approaches have been applied, including RNA in situ hybridzation, morpholino injections, and the analysis of mutant and transgenic fish lines, leading to improved understanding of the regulation in vivo of key molecular pathways with conserved roles in vertebrate myelopoiesis. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU NICHD NIH HHS [K12-HD00850] NR 96 TC 38 Z9 41 U1 1 U2 3 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 SEP PY 2005 VL 33 IS 9 BP 997 EP 1006 DI 10.1016/j.exphem.2005.06.010 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 971UD UT WOS:000232409400007 PM 16140147 ER PT J AU Mikkola, HKA Gekas, C Orkin, SH Dieterlen-Lievre, F AF Mikkola, HKA Gekas, C Orkin, SH Dieterlen-Lievre, F TI Placenta as a site for hematopoietic stem cell development SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MURINE YOLK-SAC; DEFINITIVE HEMATOPOIESIS; MOUSE EMBRYO; AGM REGION; CIRCULATION; COMMITMENT; EXPRESSION; ONTOGENY; ORIGIN; NICHE AB The discovery of a major hematopoietic stem cell (HSC) pool in mid-gestation mouse placenta has defined the placenta as yet another important anatomical site that participates in HSC development. Placental HSC activity starts in parallel with the AGM region, before HSCs are found in circulation or have colonized the fetal liver. Moreover, placental hematopoietic activity culminates in a rapid expansion of the definitive HSC pool, which occurs during the time when the fetal liver HSC reservoir begins to grow. Furthermore, hematopoietic cells in mid-gestation mouse placenta are not instructed for differentiation along the myeloerythroid lineage, as in the fetal liver. These findings suggest that the placenta provides a supportive niche where the definitive hematopoietic stem cell pool can be temporarily established during development. Future studies are needed to characterize the developmental events that lead to the establishment of placental HSC pool, and to define the microenvironmental signals that support this process. Furthermore, if the stem cell-promoting properties of the placental niche can be harnessed in vitro to support HSC formation, maturation, and/or expansion in culture, these assets may greatly improve hematopoietic stem cell-based therapies in the future. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. CNRS, Lab Embryol Cellulaire & Mol, Nogent Sur Marne, France. Coll France, Nogent Sur Marne, France. RP Mikkola, HKA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mikkola@bloodgroup.tch.harvard.edu RI Gekas, Christos/M-3209-2015 OI Gekas, Christos/0000-0002-3429-4145 NR 42 TC 68 Z9 74 U1 0 U2 4 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 SEP PY 2005 VL 33 IS 9 BP 1048 EP 1054 DI 10.1016/j.exphem.2005.06.011 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 971UD UT WOS:000232409400013 PM 16140153 ER PT J AU Chew, LD Nelson, KM Young, BA Bradley, KA AF Chew, LD Nelson, KM Young, BA Bradley, KA TI Association between alcohol consumption and diabetes preventive practices SO FAMILY MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med ID SELF-RATED HEALTH; RISK FACTOR SURVEILLANCE; PROBLEM DRINKING; CONTROLLED TRIAL; POPULATION; MELLITUS; MORTALITY; AUDIT; DISEASE; COMPLICATIONS AB Background and Objectives: Little is known about the effect of alcohol consumption on the quality of care among patients with diabetes. We evaluated the association between alcohol consumption and diabetes preventive practices. Methods: We analyzed data from the 2001 Behavioral Risk Factor Surveillance System. Based on self-reported alcohol consumption in the past 30 days, we categorized participants into the following groups: nondrinkers, moderate drinkers (average drinks/day: < one for women, < two for men), or heavy drinkers (average drinks/day: > one for women, > two for men). We then examined the association between alcohol consumption and participants' reports of diabetes preventive practices. Results: Of 10, 980 respondents with a self-reported diagnosis of diabetes, 70% were current nondrinkers, 28% moderate drinkers, and 2% heavy drinkers. Heavy drinkers compared with nondrinkers were more likely to report not performing daily glucose self monitoring and not having had an eye examination in the past year, adjusting for age, gender, race, education, income, marital status, health insurance, diabetes duration, health status, and insulin use. Moderate drinkers were more likely than nondrinkers to report not performing daily glucose self monitoring and not having had a provider visit for diabetes in the past year. Conclusions: Adults with diabetes who report moderate or heavy alcohol consumption may be at risk for adverse diabetes outcomes due to suboptimal preventive practices. C1 Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Chew, LD (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, 325 9Th Ave,Box 359780, Seattle, WA 98104 USA. EM lchew@u.washington.edu FU NIAAA NIH HHS [K23AA00313] NR 35 TC 13 Z9 13 U1 1 U2 2 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD SEP PY 2005 VL 37 IS 8 BP 589 EP 594 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 964DQ UT WOS:000231859300015 PM 16145630 ER PT J AU Paintlia, AS Paintlia, MK Khan, M Vollmer, T Singh, AK Singh, I AF Paintlia, AS Paintlia, MK Khan, M Vollmer, T Singh, AK Singh, I TI HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis SO FASEB JOURNAL LA English DT Article DE lovastatin; oligodendrocyte progenitors; spinal cord; encephalomyelitis; multiple sclerosis; remyelination ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEMYELINATING DISEASES; CNS REMYELINATION; NITRIC-OXIDE; GLIAL-CELLS; RHO; ACTIVATION; EXPRESSION; LOVASTATIN AB Impaired remyelination due to degeneration of both postmitotic oligodendrocytes and oligodendrocyte progenitors (OPs) is the major hallmark of inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomyelitis (EAE). Here, we have demonstrated the potential of lovastatin, a HMG-CoA reductase inhibitor, for the restoration of impaired remyelination mediated through enhanced survival and differentiation of OPs in the spinal cord of treated EAE animals. Lovastatin treatment significantly increased the level of myelin lipids in the spinal cord of treated EAE animals, coinciding with the attenuation of disease severity and inflammatory demyelination as compared with untreated EAE animals. The increased expression of myelin proteins and transcription factors associated with differentiating oligodendrocytes along with the increase in number of NG2(+)/BrdU(-) and NG2(+)/BrdU(+) cells, and the expression of proliferating OP-specific proteins, demonstrated the restoration of remyelination in the spinal cord of lovastatin-treated EAE animals. Corresponding to this, in vitro studies further corroborated the increased survival and differentiation of OPs in lovastatin-treated activated mixed glial cells suggesting that lovastatin protects against the degeneration of OPs and enhances their differentiation through induction of a pro-remyelinating environment in the spinal cord of treated EAE animals. Together, these data demonstrate that lovastatin has the potential to augment remyelination in MS lesions and other neuroinflammatory diseases. C1 Med Univ S Carolina, Children Res Inst, 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 29425 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Singh, I (reprint author), Med Univ S Carolina, Children Res Inst, Dept Pediat, 173 Ashley Ave,509 CRI,POB 250515, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NINDS NIH HHS [NS-37766, NS-34741, NS-40144, NS-22576] NR 48 TC 66 Z9 70 U1 0 U2 1 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 SEP PY 2005 VL 19 IS 11 BP 1407 EP 1421 DI 10.1096/fj.05-3861com PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700034 PM 16126908 ER PT J AU Astrakas, LG Goljer, I Yasuhara, S Padfield, KE Zhang, QH Gopalan, S Mindrinos, MN Dai, G Yu, YM Martyn, JAJ Tompkins, RG Rahme, LG Tzika, AA AF Astrakas, LG Goljer, I Yasuhara, S Padfield, KE Zhang, QH Gopalan, S Mindrinos, MN Dai, G Yu, YM Martyn, JAJ Tompkins, RG Rahme, LG Tzika, AA TI Proton NMR spectroscopy shows lipids accumulate in skeletal muscle in response to burn trauma-induced apoptosis SO FASEB JOURNAL LA English DT Article DE magnetic resonance spectroscopy; high-resolution magic angle spinning skeletal muscle; burn trauma; mitochondria; intramyocellular lipids ID MAGNETIC-RESONANCE-SPECTROSCOPY; CONTROLLING MITOCHONDRIAL BIOGENESIS; PROGRAMMED CELL-DEATH; IN-VIVO; INSULIN-RESISTANCE; THERMAL-INJURY; H-1-NMR SPECTROSCOPY; PROTEIN-TURNOVER; BRAIN-TUMORS; GENE-THERAPY AB Burn trauma triggers hypermetabolism and muscle wasting via increased cellular protein degradation and apoptosis. Proton nuclear magnetic resonance (H-1 NMR) spectroscopy can detect mobile lipids in vivo. To examine the local effects of burn in skeletal muscle, we performed in vivo H-1 NMR on mice 3 days after burn trauma; and ex vivo, high-resolution, magic angle spinning H-1 NMR on intact excised mouse muscle samples before and 1 and 3 days after burn. These samples were then analyzed for apoptotic nuclei using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. To confirm our NMR and cell biology results, we used transcriptome analysis to demonstrate that burn trauma alters the expression of genes involved in lipid metabolism and apoptosis. Our results demonstrate that burn injury results in a localized intramyocellular lipid accumulation, which in turn is accompanied by burn-induced apoptosis and mitochondrial dysfunction, as seen by the up-regulation of apoptotic genes and down-regulation of genes that encode lipid oxidation and the peroxisomal proliferator activator receptor gamma coactivator PGC-1 beta. Moreover, the increased levels of bisallylic methylene fatty acyl protons (2.8 ppm) and vinyl protons (5.4 ppm), in conjunction with the TUNEL assay results, further suggest that burn trauma results in apoptosis. Together, our results provide new insight into the local physiological changes that occur in skeletal muscle after severe burn trauma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burns Inst,Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Varian NMR Syst, Columbia, MD USA. Massachusetts Gen Hosp, Shriners Burns Inst, Dept Anesthesiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Dept Crit Care, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burns Inst,Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 FU NIGMS NIH HHS [P50GM021700, R01 GM055082, U54GM062119] NR 73 TC 27 Z9 28 U1 1 U2 2 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 SEP PY 2005 VL 19 IS 11 BP 1431 EP 1440 DI 10.1096/fj.04-2005com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700036 PM 16126910 ER PT J AU Imam, SZ Jankovic, J Ali, SF Skinner, JT Xie, WJ Conneely, OM Lee, WD AF Imam, SZ Jankovic, J Ali, SF Skinner, JT Xie, WJ Conneely, OM Lee, WD TI Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice SO FASEB JOURNAL LA English DT Article DE nitric oxide; dopamine; 3-NT; caspase; transcription; apoptosis ID ORPHAN NUCLEAR RECEPTOR; ISCHEMIC BRAIN-INJURY; ALPHA-SYNUCLEIN; EXPRESSION INCREASES; TRANSCRIPTION FACTOR; NEURONAL APOPTOSIS; CELL-DEATH; METHAMPHETAMINE; NEUROTOXICITY; GENE AB Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased expression of neuronal nitric oxide synthase and increased 3-nitrotyrosine were observed in striatum of Nurr1 heterozygous (Nurr1 +/-) mice as compared with wild-type. Increased cytochrome C activation and consecutive release of Smac/DIABLO were also observed in Nurr1 +/- mice. An induction of active Caspase-3 and p53, cleavage of poly-ADP (RNase) polymerase and reduced expression of bcl-2 were observed in Nurr1 +/- mice. Methamphetamine significantly increased these markers in Nurr1 +/- mice as compared with wild-type. The present data therefore suggest that nitric oxide plays a role as a modulating factor for the increased susceptibility, but not the potentiation, of the dopaminergic terminals in Nurr1 +/- mice. We also report that this increased neuronal nitric oxide synthase expression and increased nitration in Nurr1 +/- mice led to the activation of apoptotic cascade via the differential alterations in the DNA binding activity of transcription factors responsible for the propagation of growth arrest as well as apoptosis. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. UT Hlth Sci, Dept Med, San Antonio, TX USA. US FDA, Neurochem Lab, Div Neurotoxicol, NCTR, Jefferson, AR USA. Baylor Coll Med, Dept Cellular & Mol Biol, Houston, TX 77030 USA. RP Lee, WD (reprint author), Baylor Coll Med, Dept Neurol, NB 205,6501 Fannin St, Houston, TX 77030 USA. EM simam@satx.rr.com; Weidongl@bcm.tmc.edu FU NINDS NIH HHS [NS40370, NS043567] NR 48 TC 18 Z9 18 U1 0 U2 2 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 SEP PY 2005 VL 19 IS 11 BP 1441 EP 1450 DI 10.1096/fj.04-3362com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700037 PM 16126911 ER PT J AU Zhao, Z Ho, L Wang, J Qin, WP Festa, ED Mobbs, C Hof, P Rocher, A Masur, S Haroutunian, V Pasinetti, GM AF Zhao, Z Ho, L Wang, J Qin, WP Festa, ED Mobbs, C Hof, P Rocher, A Masur, S Haroutunian, V Pasinetti, GM TI Connective tissue growth factor (CTGF) expression in the brain is a downstream effector of insulin resistance-associated promotion of Alzheimer's disease beta-amyloid neuropathology SO FASEB JOURNAL LA English DT Article DE diabetes; IDE; secretase; IDE; AKT; MAPK ID GAMMA-SECRETASE ACTIVITY; HUMAN MESANGIAL CELLS; DEGRADING ENZYME; NEUROFIBRILLARY TANGLES; EXTRACELLULAR-MATRIX; STEREOLOGIC ANALYSIS; POTENTIAL MECHANISM; DIABETES-MELLITUS; PRECURSOR PROTEIN; NEURITIC PLAQUES AB The goal of this study was to further explore potential mechanisms through which diabetogenic dietary conditions that result in promotion of insulin resistance (IR), a feature of non-insulin dependant diabetes mellitus (type-2 diabetes), may influence Alzheimer's disease ( AD). Using genome-wide array technology, we found that connective tissue growth factor ( CTGF), a gene product described previously for its involvement in diabetic fibrosis, is elevated in brain tissue in an established mouse model of diet-induced IR. With this evidence we continued to explore the regulation of CTGF in postmortem AD brain tissue and found that CTGF expression correlated with the progression of AD clinical dementia and amyloid neuritic plaque (NP) neuropathology, but not neurofibrillary tangle (NFT) deposition. Consistent with this evidence, we also found that exposure of Tg2576 mice ( a model AD-type amyloid neuropathology) to a diabetogenic diet that promotes IR results in a similar to 2-fold elevation in CTGF steady-state levels in the brain, coincident with a commensurate promotion of AD-type amyloid plaque burden. Finally, using in vitro cellular models of amyloid precursor protein (APP)-processing and A beta generation/clearance, we confirmed that human recombinant (hr) CTGF may increase A beta(1-40) and A beta(1-42) peptide steady-state levels, possibly through a mechanism that involves gamma-secretase activation and decreased insulin-degrading enzyme (IDE) steady-state levels in a MAP kinase ( MAPK)/ phosphatidylinositol 3-kinase (PI-3K)/protein kinase-B (AKT) 1-dependent manner. The findings in this study tentatively suggest that increased CTGF expression in the brain might be a novel biological predicative factor of AD clinical progression and neuropathology in response to dietary regimens promoting IR conditions. C1 Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, GRECC, Translat Neurosci Labs, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIA NIH HHS [AG02219, AG13799] NR 59 TC 21 Z9 21 U1 1 U2 4 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 SEP PY 2005 VL 19 IS 11 BP 2081 EP + DI 10.1096/fj.05-4359fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700005 PM 16186174 ER PT J AU Styer, AK Gonzalez, RR Leavis, PC Petrozza, JC Rueda, BR AF Styer, AK Gonzalez, RR Leavis, PC Petrozza, JC Rueda, BR TI In vivo disruption of leptin receptor function impairs the establishment and viability of endometriosis-like lesions. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Boston Biomed Res Inst, Watertown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S389 EP S390 DI 10.1016/j.fertnstert.2005.07.1018 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601392 ER PT J AU Ogbureke, KUE Zhao, QX Li, YP AF Ogbureke, KUE Zhao, QX Li, YP TI Human osteopetroses and the osteoclast V-H+-atpase acidification system SO FRONTIERS IN BIOSCIENCE LA English DT Review DE human osteopetrosis; osteoclast V-H plus ATPase; genetic mouse models; osteopetrosis associated genes; osteoclast medicated acidification; review ID AUTOSOMAL-DOMINANT OSTEOPETROSIS; ANHYDRASE-II DEFICIENCY; VACUOLAR PROTON PUMP; ALBERS-SCHONBERG-DISEASE; INFANTILE MALIGNANT OSTEOPETROSIS; BONE-MARROW TRANSPLANTATION; CLCN7 GENE-MUTATIONS; OP OP MOUSE; RECESSIVE OSTEOPETROSIS; MOLECULAR-CLONING AB Osteopetroses are a heterogeneous group of human genetic diseases characterized by generalized increase in bone density due either to a lack of osteoclast population or defect in osteoclast function. Current knowledge of the pathogenesis suggests defects that may be either intrinsic to osteoclast-monocyte lineage or extrinsic to the mesenchymal cells that support osteoblast ontogeny and activation. Four clinically distinct forms of human osteopetroses currently recognized are the infantile malignant autosomal recessive form, the intermediate autosomal recessive form, the adult benign autosomal dominant osteopetrosis type I, and the autosomal dominant osteopetrosis type II. Propensity to fracture is high in all types of osteopetrosis, and other characteristic clinical problems include hematologic and metabolic abnormalities, infections of affected bone, and neurologic sequela. Among the infantile malignant clinical forms 50-60% of patients present with defects in the OC116-KDa (also refers to ATP6i, TCIRGI, a3) subunit of the osteoclast vacuolar H+-ATPase (V-H+-ATPase) proton pump. Approaches that have been applied to the treatment of osteopetrosis include those aimed at stimulating host osteoclasts. These approaches however have met with little success, and it would appear that the future for the successful treatment of osteopetrosis lies with bone marrow transplantation. Various animal models mimicking some of the clinical subtypes of osteopetrosis have been generated in efforts to elicit further understanding of the pathogenesis. This review is an update on the various phenotypic presentations of human osteopetroses alongside their known animal models. Further studies on these animal models will not only expand our basic understanding of the molecular mechanisms of osteopetroses, but will also aid our ability to develop therapeutic means of intervention in diseases involving osteopetroses. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02115 USA. Med Coll Georgia, Dept Oral Biol & Maxillofacial Pathol, Sch Dent, Augusta, GA 30912 USA. Zhejiang Cell Biomed Res Coll, Hangzhou, Peoples R China. Zhejiang Univ, Life Sci Coll, Hangzhou 310027, Peoples R China. RP Li, YP (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM kogbureke@mail.mcg.edu; ypli@forsyth.org FU NIAMS NIH HHS [AR-48133, AR44741] NR 113 TC 7 Z9 8 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 2940 EP U117 DI 10.2741/1750 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300077 PM 15970548 ER PT J AU Chiappelli, F Alwan, J Prolo, P Christensen, R Fiala, M Cajulis, OS Bernard, G AF Chiappelli, F Alwan, J Prolo, P Christensen, R Fiala, M Cajulis, OS Bernard, G TI Neuro-immunity in stress-related oral ulcerations: A fractal analysis SO FRONTIERS IN BIOSCIENCE LA English DT Article DE oral lichen planus (OLP); recurrent aphthous stomatitis (RAS); oral mucosa CD3+T cells; vesicles of monoamines transport; vesicles of acetylcholine transport; fractal dimension; euclidean dimension ID LICHEN-PLANUS; LYMPHOCYTES; INTERFACE; DIMENSION; CELLS AB By testing archival paraffinized biopsy blocks obtained from the oral pathology library with immunohistochemistry, we tested the hypothesis that substantial alterations are demonstrable in the cross-talk between sympathetic (VMAT) and para-sympathetic innervation (VAchT), and resident CD3+ T cells in the mucosa from oral lichen planus (OLP), compared to recurrent aphthous stomatitis (RAS) and control biopsies. We quantified fractal dimension and Euclidean dimension of CD3+ cells between the two pathologies, and across the set of CD3+ cells proximal to the vesicles of monoamines transport (VMAT)+ or the vesicles of acetylcholine transport (VAchT)+ innervation, compared to cells relatively distal to the nerve endings. The data show exquisite organization of the punctuate sympathetic and para-sympathetic staining about the resident CD3+ T cells in the OLP lesions, but not in the aphthous lesions or in control mucosa. Fractal analysis reveals that aphthous lesions are characterized by CD3+ T cells of larger size (Euclidean dimensional map), compared to control mucosa. CD3+ T cells in OLP lesions are also found to be significantly larger than those found in control lesions, when they are not proximal to sympathetic or para-sympathetic vesicles. The membrane of CD3+ T cells is overall more complex (fractal dimension) in aphthous lesions, compared to control sections. A similar trend is apparent, albeit not statistically significant, in CD3+ T cells resident in OLP lesions, whether or not they are located proximal to nerve endings. An overall decrease in the ratio of fractal dimension-over-topological dimension was also observed across the pathological lesions, compared to control. Taken together, these data indicate that as CD3+ T cells grow larger in the pathological conditions, they, in effect, stretch their plasma membrane, and that the cells may be at different stage of the cell cycle, relative to their position vis a vis nerve endings. Because fractal analysis is performed on individual cells, it has the potential of being developed in a novel diagnostic test, as well as a prognostic tool for monitoring the etiology and the course of treatment at the individual cellular level. Our findings also open new frontiers of fundamental, clinical and translational biosciences of OLP. C1 Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Loma Linda Univ, Sch Dent, Loma Linda, CA 92350 USA. RP Chiappelli, F (reprint author), Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, CHS 63-090, Los Angeles, CA 90095 USA. EM chiappelli@dent.ucla.edu NR 27 TC 3 Z9 6 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 3034 EP 3041 DI 10.2741/1760 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300087 PM 15970558 ER PT J AU Ku, NO Lim, JK Krams, SM Esquivel, CO Keeffe, EB Wright, TL Parry, DAD Omary, MB AF Ku, NO Lim, JK Krams, SM Esquivel, CO Keeffe, EB Wright, TL Parry, DAD Omary, MB TI Keratins as susceptibility genes for end-stage liver disease SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTERMEDIATE-FILAMENTS; INDUCED APOPTOSIS; G62C MUTATIONS; MICE; CYTOKERATINS; ASSOCIATION; RESISTANCE; HEPATITIS; INJURY AB Background & Aims: Keratins 8 and :18 protect the liver from stress. Keratin 8 and :18 variants in 17 of 467 liver disease explants and 2 of 349 blood bank controls were previously reported in 5 analyzed exonic regions. We asked whether mutations were present in the remaining 10 exons of keratins 8 and 18. Methods: Exonic regions were polymerase chain reaction-amplified from genomic DNA, isolated from the above-mentioned 2 cohorts, and analyzed for the presence of mutations. Mutant keratins were also studied biochemically. Results: We identified 10 novel keratin 8 and 18 heterozygous variants in 44 of 467 explants and 11 of 349 controls: keratin IS deletion (A64-71), a keratin 8 frameshift that truncates the last 14 amino acids; 8 missense keratin 8 and IS alterations; and several new polymorphisms. The most common variant, keratin 8 R340H, at the highly conserved R340 was found in 30 of 467 explants and 10 of 349 controls (P =.02) and was confirmed in the diseased livers by generation of an R3401-1-specific antibody. Germline transmission and variant protein expression were verified. The mutations involved a variety of liver diseases, and some variants had an ethnic background preponderance. Mutations that introduced disulfide bonds (keratin 8 G61C or R453C) decreased keratin solubility, particularly after oxidative stress, whereas others decreased keratin 8 phosphorylation (keratin 8 G433S). Conclusions: The overall frequency of keratin 8 and :18 variants was 12.4% in 467 liver disease explants and 3.7% in 349 blood bank controls (P < .0001). Variants can alter keratin solubility or phosphorylation and may render individuals susceptible to end-stage liver disease, depending on their genetic background and exposure to other insults, such as alcohol or viral infection. C1 Palo Alto VA Med Ctr, Dept Med, Palo Alto, CA 94304 USA. Palo Alto VA Med Ctr, Dept Surg, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massey Univ, Palmerston North, New Zealand. RP Ku, NO (reprint author), Palo Alto VA Med Ctr, Dept Med, Mail Code 154J,3801 Miranda Ave, Palo Alto, CA 94304 USA. FU NIDDK NIH HHS [DK47918, DK56339] NR 29 TC 49 Z9 52 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2005 VL 129 IS 3 BP 885 EP 893 DI 10.1053/j.gastro.2005.06.065 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 963PO UT WOS:000231816500016 PM 16143128 ER PT J AU Brugge, WR AF Brugge, WR TI Should all pancreatic cystic lesions be resected? Cyst-fluid analysis in the differential diagnosis of pancreatic cystic lesions: a meta-analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID FINE-NEEDLE-ASPIRATION; MUCINOUS TUMORS; NEOPLASMS C1 Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02114 USA. NR 16 TC 24 Z9 25 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 SEP PY 2005 VL 62 IS 3 BP 390 EP 391 DI 10.1016/j.gie.2005.04.036 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 960XY UT WOS:000231627700011 PM 16111957 ER PT J AU Waxmonsky, JA Thomas, MR Miklowitz, DJ Allen, MH Wisniewski, SR Zhang, HW Ostacher, MJ Fossey, MD AF Waxmonsky, JA Thomas, MR Miklowitz, DJ Allen, MH Wisniewski, SR Zhang, HW Ostacher, MJ Fossey, MD TI Prevalence and correlates of tobacco use in bipolar disorder: data from the first 2000 participants in the Systematic Treatment Enhancement Program SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE bipolar disorder; smoking; psychiatric comorbidity; substance use ID CIGARETTE-SMOKING; NICOTINE DEPENDENCE; PSYCHIATRIC OUTPATIENTS; MENTAL-ILLNESS; UNITED-STATES; STEP-BD; SCHIZOPHRENIA; MANIA; COMORBIDITY; WITHDRAWAL AB Objective: Only a few small descriptive studies have examined the prevalence and correlates of tobacco use among bipolar patients. We predicted that poorly controlled manic, depressed and mixed states, and the presence of psychotic symptoms, would be associated with a greater prevalence of smoking among patients with bipolar disorder. Method: We examined the prevalence of smoking in a cross-sectional sample of 1904 patients with bipolar disorder enrolled in the National Institute of Mental Health's Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) database. We also examined the relationship between smoking and other factors including: bipolar subtype, current clinical status, illness severity (e.g., number of prior mood episodes), age of bipolar onset, gender, education, socioeconomic status, and concurrent substance use. Results: At STEP-BD program entry, 31.2% of patients reported that they were smokers. Patients who were male, less educated, and/or had lower income were more likely to be smokers (P < .01). Additionally, patients with rapid cycling, comorbid psychiatric disorders, and/or substance abuse, and those experiencing a current episode of illness were more likely to be smokers (P < .0001). More lifetime depressive and manic episodes as well as greater severity of depressive and manic symptoms were associated with smoking (P < .001). Use of atypical antipsychotic medications was more prevalent among smokers (P = .04). Conclusions: Clinical and demographic variables are associated with smoking in this sample of bipolar patients. Longitudinal analyses are needed to determine how mood and bipolar symptoms interact with smoking over the episodic course of bipolar disorder. Additional studies should focus on whether controlling bipolar symptoms is associated with cessation of smoking. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80220 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Pittsburgh, Epidemiol Data Coordinating Ctr, Pittsburgh, PA 18261 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Oklahoma, Dept Psychiat, Tulsa, OK 74135 USA. RP Waxmonsky, JA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave, Denver, CO 80220 USA. EM jeanette.waxmonsky@uchsc.edu RI Waxmonsky, Jeanette/L-4739-2013; Allen, Michael/A-8776-2011; OI Wisniewski, Stephen/0000-0002-3877-9860; Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [N01MH80001] NR 33 TC 88 Z9 89 U1 1 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 SEP-OCT PY 2005 VL 27 IS 5 BP 321 EP 328 DI 10.1016/j.genhosppsych.2005.05.003 PG 8 WC Psychiatry SC Psychiatry GA 972JM UT WOS:000232450100004 PM 16168792 ER PT J AU Simon, GE Katon, WJ Lin, EHB Ludman, E VonKorff, M Ciechanowski, P Young, BA AF Simon, GE Katon, WJ Lin, EHB Ludman, E VonKorff, M Ciechanowski, P Young, BA TI Diabetes complications and depression as predictors of health service costs SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE diabetes; depression; cost; complications; utilization ID PRIMARY-CARE; MEDICAL ILLNESS; MYOCARDIAL-INFARCTION; COMORBID DEPRESSION; MEXICAN-AMERICANS; MAJOR DEPRESSION; MENTAL-DISORDERS; SELF-CARE; SYMPTOMS; POPULATION AB Objective: The aim of this study was to assess the relative contributions of diabetes complications, depression and comorbid medical disorders to health service costs in adults with diabetes. Methods: A total of 4398 adult health plan members with diabetes completed a mailed survey. Depression was assessed using the nine-item PHQ. Health service costs, diabetes complications, glycohemoglobin levels and comorbid medical conditions were assessed using computerized health plan records. Results: Total health service costs were approximately 70% higher for individuals with major depression than for those without any depressive disorder US$5361 over 6 months vs. US$3120, P < .001); this difference was consistent across all categories of health service costs. Diabetes complications were the strongest predictor of total costs (US$6845 for those with three or more complications vs. US$1719 for those with none), but depression remained strongly associated with increased costs at all levels of diabetes severity. Conclusions: Among people with diabetes, depression is associated with 50-75% increases in health service costs. This proportional difference is similar to that in general population samples, but the absolute dollar difference is much greater. The effect of depression on health service use is undoubtedly complex and not limited to unexplained physical symptoms among the worried well. (c) 2005 Elsevier Inc. All rights reserved. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Epidemioil Res & Informat Ctr, Seattle, WA 98108 USA. RP Simon, GE (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. EM simon.g@ghc.org FU NIMH NIH HHS [R01 MH41739] NR 36 TC 117 Z9 119 U1 1 U2 6 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 SEP-OCT PY 2005 VL 27 IS 5 BP 344 EP 351 DI 10.1016/j.genhosppsych.2005.04.008 PG 8 WC Psychiatry SC Psychiatry GA 972JM UT WOS:000232450100007 PM 16168795 ER PT J AU Talarek, N Maillet, L Cullin, C Aigle, M AF Talarek, N Maillet, L Cullin, C Aigle, M TI The [URE3] prion is not conserved among Saccharomyces species SO GENETICS LA English DT Article ID YEAST SUP35 PROTEIN; BAYANUS VAR. UVARUM; PODOSPORA-ANSERINA; GENETIC-VARIATION; MOLECULAR-BASIS; S-DOUGLASII; IN-VITRO; CEREVISIAE; DOMAIN; STRAINS AB The [URE3] prion of Saccharomyces cerevisiae is a self-propagating inactive form of the nitrogen catabolism regulator Ure2p. To determine whether the [URE3] prion is conserved in S. cerevisiae-related yeast species, we have developed genetic tools allowing the detection of [URE3] in Saccharomyces paradoxus and Saccharomyces uvarum. We found that [URE3] is conserved in S. uvarum. In contrast, [URE3] was not detected in S. paradoxus. The inability of S. paradoxus Ure2p to switch to a prion isoform results from the primary sequence of the protein and not from the lack of cellular cofactors as heterologous Ure2p can propagate [URE3] in this species. Our data therefore demonstrate that [URE3] is conserved only in a subset of Saccharomyces species. Implications of our finding on the physiological and evolutionary meaning of the yeast [URE3] prion are discussed. C1 Univ Victor Segalen Bordeaux 2, CNRS, IBGC, UMR 5095, F-33077 Bordeaux, France. RP Dana Farber Canc Inst, M620,44 Binney St, Boston, MA 02115 USA. EM nicolas_talarek@dfci.harvard.edu RI MAILLET, Laurent/K-7959-2015; OI MAILLET, Laurent/0000-0002-8169-060X; cullin, christophe/0000-0003-4110-4677 NR 70 TC 34 Z9 34 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 2005 VL 171 IS 1 BP 23 EP 34 DI 10.1534/genetics.105.043489 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 973AD UT WOS:000232494400003 PM 15956663 ER PT J AU Diener, AC Ausubel, FM AF Diener, AC Ausubel, FM TI RESISTANCE TO FUSARIUM OXYSPORUM 1, a dominant Arabidopsis disease-resistance gene, is not race specific SO GENETICS LA English DT Article ID KINASE-LIKE PROTEIN; RECEPTOR KINASE; SALICYLIC-ACID; DEFENSE RESPONSES; WILT RESISTANCE; PLANTS; EXPRESSION; THALIANA; TOMATO; FAMILY AB Arabidopsis thaliana ecotypes differ in their susceptibility to Fusarium wilt diseases. Ecotype Taynuilt-0 (Ty-0) is susceptible to Fusarium oxysporum forma specialis (f.) matthioli whereas Columbia-0 (Cot-0) is resistant. Segregation analysis of a cross between Ty-0 and Col-0 revealed six dominant RESISTANCE TO FUSARIUM OXYSPORUM (RFO) loci that significantly contribute to f. matthioli resistance in Col-0 relative to Ty-0. We refer to the locus with the strongest effect as RFO1. Ty-0 plants in which only the Col-0 allele of RFO1 (RFO1(col-0)) was introduced were resistant to f. matthioli. Surprisingly, RFO1(Col-0) also conferred resistance to f. raphani, demonstrating that RFO1-mediated resistance is not race specific. Expression of resistance by RFO2, RFO4, or RFO6 was dependent on RFO1(Col-0). Map-based cloning of RFO1(Col-0) showed that RFO1 is identical to the previously named Arabidopsis gene WAKL22 (WALL-ASSOCIATED KINASE-LIKE KINASE 22), which encodes a receptor-like kinase that does not contain an extracellular leucine-rich repeat domain. Consistent with these results, a Col-0 rfo1 loss-of-function mutant was more susceptible to f. matthioli, f. conglutinans, and f. raphani. Thus, RFO1 encodes a novel type of dominant disease-resistance protein that confers resistance to a broad spectrum of Fusarium races. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St,Wellman 10, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [5-F32-AI10634A-02, F32 AI010634]; NIGMS NIH HHS [R01 GM048707, GM48707, R37 GM048707] NR 66 TC 116 Z9 123 U1 4 U2 16 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2005 VL 171 IS 1 BP 305 EP 321 DI 10.1534/genetics.105.042218 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 973AD UT WOS:000232494400027 PM 15965251 ER PT J AU Ditman, T Kuperberg, GR AF Ditman, T Kuperberg, GR TI A source-monitoring account of auditory verbal hallucinations in patients with schizophrenia SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE auditory hallucinations; inner speech; reality monitoring; schizophrenia; source monitoring ID SPEECH-PERCEPTION; REALITY; IMAGERY; VOICES; PHENOMENOLOGY; DISCRIMINATION; SYMPTOMATOLOGY; IMPAIRMENTS; EXPERIENCES; DEFICITS AB Auditory verbal hallucinations are a common and distressing symptom experienced by patients with schizophrenia. They can be understood as arising from an impairment in reality monitoring-the process by which internally and externally generated events are distinguished. This impairment might arise through primary abnormalities in the reality-monitoring mechanism or through secondary mechanisms (abnormalities in the perceptual characteristics of internally generated events or in the perception of externally generated events). This article examines evidence for and against an association between abnormalities in reality monitoring and auditory verbal hallucinations in schizophrenia. A comprehensive review of the psychological literature suggests that there is little evidence for an association between auditory verbal hallucinations and secondary mechanisms leading to abnormalities in reality monitoring. There is some evidence suggesting that hallucinators show a primary reality-monitoring abnormality that is most apparent when patients are required to distinguish self from other in real time. To draw firmer conclusions, however, it is imperative that future studies select patient populations precisely, match control groups, and use consistent criteria for defining hallucinators. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM Tali.Ditman@tufts.edu FU NIMH NIH HHS [K23 MH 02034] NR 71 TC 72 Z9 72 U1 4 U2 21 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2005 VL 13 IS 5 BP 280 EP 299 DI 10.1080/10673220500326391 PG 20 WC Psychiatry SC Psychiatry GA 980GH UT WOS:000233002000003 PM 16251167 ER PT J AU Caplan, JE Beresin, E Prager, LA Schwartz, RS AF Caplan, JE Beresin, E Prager, LA Schwartz, RS TI The food preoccupations of a nine-year-old girl: What do they portend? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID EATING-DISORDERS; ANOREXIA-NERVOSA; PERFECTIONISM C1 Massachusetts Gen Hosp, Yawkey Outpatient Ctr 6900, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. Boston Psychoanalyt Soc & Inst, Boston, MA USA. RP Caplan, JE (reprint author), Massachusetts Gen Hosp, Yawkey Outpatient Ctr 6900, 55 Fruit St, Boston, MA 02115 USA. EM jecaplan@-partners.org NR 15 TC 0 Z9 1 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2005 VL 13 IS 5 BP 300 EP 311 DI 10.1080/10673220500326490 PG 12 WC Psychiatry SC Psychiatry GA 980GH UT WOS:000233002000004 PM 16251168 ER PT J AU Kurian, AW Hartman, AR Mills, MA Ford, JM Daniel, BL Plevritis, SK AF Kurian, AW Hartman, AR Mills, MA Ford, JM Daniel, BL Plevritis, SK TI Opinions of women with high inherited breast cancer risk about prophylactic mastectomy: an initial evaluation from a screening trial including magnetic resonance imaging and ductal lavage SO HEALTH EXPECTATIONS LA English DT Article DE BRCA; breast cancer; ductal lavage; magnetic resonance imaging; patient satisfaction; prophylactic; mastectomy ID BRCA2 MUTATION CARRIERS; SURGICAL ADJUVANT BREAST; FALSE-POSITIVE MAMMOGRAM; QUALITY-OF-LIFE; OVARIAN-CANCER; FAMILY-HISTORY; GENE MUTATION; MRI; OOPHORECTOMY; PREVENTION AB Objective Prophylactic mastectomy (PM) is often considered, but variably chosen by women at high inherited risk of breast cancer; few data exist on patient tolerance of intensive breast screening as an alternative to PM. We performed an evaluation of high-risk women's tolerance of a breast screening protocol using clinical breast examination, mammography, breast magnetic resonance imaging (MRI) and ductal lavage (DL), and of change in attitudes toward PM after screening. Design A questionnaire assessing tolerance of screening procedures and change in opinion towards PM was designed and administered to 43 study participants, after a median follow-up of 13 months. Responses were evaluated according to patient characteristics, including type of study-prompted interventions, BRCA mutation status, and prior history of cancer, via univariate analysis. Results Most patients [85.3% (68.9-95.1%)] were more opposed or unchanged in their attitudes towards PM after study participation, with only 14.7% (5.0-31.1%) less opposed (P = 0.017) despite a short-interval follow-up MRI rate of 71.7% and a biopsy rate of 37%. Lower rates of maximal discomfort were reported with mammogram [2.8% (0-14.5%)] and MRI [5.6% (0-18.7%)] than with DL [28.6% (14.6-46.3%)], with P = 0.035. Conclusions Most high-risk women tolerated intensive breast screening well; they were not more inclined towards PM after participating. Future studies should prospectively evaluate larger numbers of high-risk women via multivariate analysis, to determine characteristics associated with preference for breast screening vs. PM. C1 Stanford Univ, Sch Med, Div Oncol, Dept Med, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. RP Kurian, AW (reprint author), Stanford Univ, Sch Med, Div Oncol, Dept Med, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM akurian@stanford.edu FU NCI NIH HHS [R01 CA66785, R01 CA066785] NR 58 TC 11 Z9 11 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD SEP PY 2005 VL 8 IS 3 BP 221 EP 233 DI 10.1111/j.1369-7625.2005.00333.x PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 957BX UT WOS:000231345500004 PM 16098152 ER PT J AU Kerner, J Rimer, B Emmons, K AF Kerner, J Rimer, B Emmons, K TI Introduction to the Special Section on Dissemination - Dissemination research and research dissemination: How can we close the gap? SO HEALTH PSYCHOLOGY LA English DT Editorial Material DE dissemination research; knowledge translation AB One of the greatest challenges facing health promotion and disease prevention is translating research findings into evidence-based public health and clinical practices that are actively disseminated and widely adopted. Despite the tremendous strides made in developing effective disease prevention and control programs, there has been little study of effective dissemination of evidence-based programs to and adoption by community, public health, and clinical practice settings. This special section provides a venue in which to highlight exemplary dissemination research efforts while also identifying limitations in research to date and framing important future research questions. This issue establishes a resource for investigators interested in dissemination research, with relevance to health psychology. In this sense, it can serve as a benchmark by which to examine subsequent progress. The 6 articles reflect the state of the science in dissemination research for the promotion and adoption of health behavior change interventions. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Dana Farber Canc Inst, Dept Med Oncol Populat Sci, Boston, MA 02115 USA. RP Kerner, J (reprint author), NCI, Div Canc Control & Populat Sci, NIH, EPN 6144,6130 Execut Blvd, Bethesda, MD 20892 USA. EM kemerj@mail.nih.gov OI Kerner, Jon/0000-0002-8792-3830 NR 17 TC 156 Z9 157 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2005 VL 24 IS 5 BP 443 EP 446 DI 10.1037/0278-6133.24.5.443 PG 4 WC Psychology, Clinical; Psychology SC Psychology GA 962RN UT WOS:000231750000001 PM 16162037 ER PT J AU Turnbull, J Lohi, H Kearney, JA Rouleau, GA Delgado-Escueta, AV Meisler, MH Cossette, P Minassian, BA AF Turnbull, J Lohi, H Kearney, JA Rouleau, GA Delgado-Escueta, AV Meisler, MH Cossette, P Minassian, BA TI Sacred disease secrets revealed: the genetics of human epilepsy SO HUMAN MOLECULAR GENETICS LA English DT Article ID IDIOPATHIC GENERALIZED EPILEPSY; CHILDHOOD ABSENCE EPILEPSY; POTASSIUM CHANNEL GENE; FRONTAL-LOBE EPILEPSY; JUVENILE MYOCLONIC EPILEPSY; NICOTINIC ACETYLCHOLINE-RECEPTOR; LATERAL TEMPORAL EPILEPSY; EPISODIC ATAXIA TYPE-2; FEBRILE SEIZURES PLUS; FAMILIAL NEONATAL CONVULSIONS AB Neurons throughout the brain suddenly discharging synchronously and recurrently cause primarily generalized seizures. Discharges localized awhile in one part of the brain cause focal-onset seizures. A genetically determined generalized hyperexcitability had been predicted in primarily generalized seizures, but surprisingly the first epilepsy gene discovered, CHRNA4, was in a focal (frontal lobe)-onset syndrome. Another surprise with CHRNA4 was its encoding of an ion channel present throughout the brain. The reason why CHRNA4 causes focal-onset seizures is unknown. Recently, the second focal (temporal lobe)-onset epilepsy gene, LGI1 (unknown function), was discovered. CHRNA4 led the way to mutation identifications in 15 ion channel genes, most causing primarily generalized epilepsies. Potassium channel mutations cause benign familial neonatal convulsions. Sodium channel mutations cause generalized epilepsy with febrile seizures plus or, if more severe, severe myoclonic epilepsy of infancy. Chloride and calcium channel mutations are found in rare families with the common syndromes childhood absence epilepsy and juvenile myoclonic epilepsy (JME). Mutations in the EFHC1 gene (unknown function) occur in other rare JME families, and yet in other families, associations are present between JME (or other generalized epilepsies) and single nucleotide polymorphisms in the BRD2 gene (unknown function) and the malic enzyme 2 (ME2) gene. Hippocrates predicted the genetic nature of the 'sacred' disease. Genes underlying the 'malevolent' forces seizing 1% of humans have now been revealed. These, however, still account for a mere fraction of the genetic contribution to epilepsy. Exciting years are ahead, in which the genetics of this extremely common, and debilitating, neurological disorder will be solved. C1 Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Ctr Hosp Univ Montreal, Notre Dame Hosp, Ctr Study Brain Dis, Montreal, PQ H2L 4M1, Canada. Greater Los Angeles VA Healthcare Syst, Epilepsy Ctr Excellence, Los Angeles, CA 90073 USA. RP Minassian, BA (reprint author), Hosp Sick Children, Program Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM bminass@sickkids.ca OI Delgado-Escueta, Antonio V./0000-0002-1581-6999; Kearney, Jennifer/0000-0003-1726-4769 NR 95 TC 64 Z9 69 U1 5 U2 7 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 SEP 1 PY 2005 VL 14 IS 17 BP 2491 EP 2500 DI 10.1093/hmg/ddi250 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 958UI UT WOS:000231473300004 PM 16049035 ER PT J AU Hauser, R Godfrey-Bailey, L Chen, ZY AF Hauser, R Godfrey-Bailey, L Chen, ZY TI Does the potential for selection bias in semen quality studies depend on study design? Experience from a study conducted within an infertility clinic SO HUMAN REPRODUCTION LA English DT Article DE infertility; selection bias; semen quality ID TESTOSTERONE; POPULATION; VOLUNTEERS; FERTILITY; SPERM AB BACKGROUND: The low participation rates in human semen quality studies raises concern for the potential of differential participation based on semen quality (or a surrogate). To explore the potential for differential participation, we compared semen analysis results from study subjects with those of non-study subjects. METHODS: We obtained semen analysis results from 235 study subjects and retrospectively obtained results from a subset of 235 infertility clinic patients that were not study subjects but met the same eligibility criteria. The study was conducted at the Massachusetts General Hospital Infertility Clinic. All semen samples (study subjects and non-study subjects) were analysed for sperm concentration and motility by computer-aided semen analysis (CASA), and morphology was assessed using strict criteria. Semen analysis parameters for the non-study subjects were compared with the semen analysis results from study subjects. RESULTS: For all semen characteristics (sperm concentration, total sperm count, sperm motility and morphology), there were only marginal (non-significant) differences between study subjects and non-study subjects. CONCLUSIONS: Among men from an infertility clinic, we found no strong evidence of differential participation based on semen quality. This is reassuring since the potential for selection bias is of concern in semen quality studies. However, the potential for selection bias in other study designs remains unclear. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Androl Lab & Vitro Fertilizat Unit, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu FU NIEHS NIH HHS [ES09718, ES00002] NR 9 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2005 VL 20 IS 9 BP 2579 EP 2583 DI 10.1093/humrep/dei088 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 957IF UT WOS:000231362800036 PM 15890729 ER PT J AU Yadin, Y Bilenca, A Nazarathy, M AF Yadin, Y Bilenca, A Nazarathy, M TI Soft detection of multichip DPSK over the nonlinear fiber-optic channel SO IEEE PHOTONICS TECHNOLOGY LETTERS LA English DT Article DE differential phase-shift keying (DPSK); optical fiber communication; phase modulation; phase noise ID PHASE NOISE; TRANSMISSION; SYSTEMS AB We analyze the performance of a recently proposed multichip differential phase-shift-keying (DPSK) format over the nonlinear fiber-optic channel. For a single wavelength nonlinear phase-noise-limited channel, a multichip DPSK receiver based on a three-chip observation can attain more than two orders of magnitude bit-error-rate reduction relative to a standard DPSK receiver, or equivalently similar to 1-dB improvement in Q-factor, significantly exceeding the 0.2-dB improvement achieved by the same format over a linear optical channel. C1 Technion Israel Inst Technol, Dept Elect Engn, IL-32000 Haifa, Israel. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yadin, Y (reprint author), Technion Israel Inst Technol, Dept Elect Engn, IL-32000 Haifa, Israel. EM yadin@tx.technion.ac.il; abilenca@partners.org; nazarat@ee.technion.ac.il NR 7 TC 11 Z9 11 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1041-1135 J9 IEEE PHOTONIC TECH L JI IEEE Photonics Technol. Lett. PD SEP PY 2005 VL 17 IS 9 BP 2001 EP 2003 DI 10.1109/LPT.2005.852325 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 958MX UT WOS:000231453500080 ER PT J AU Hamalainen, M Nolte, G Worsley, K de Munck, JC AF Hamalainen, M Nolte, G Worsley, K de Munck, JC TI Editorial for the special section on signal processing aspects of brain imaging SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Fraunhofer FIRST, D-12489 Berlin, Germany. McGill Univ, Dept Math & Stat, Montreal, PQ H3A 2K6, Canada. Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands. RP Hamalainen, M (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD SEP PY 2005 VL 53 IS 9 BP 3357 EP 3358 DI 10.1109/TSP.2005.853096 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 956SA UT WOS:000231318900001 ER PT J AU Pillai, S AF Pillai, S TI Two lymphoid roads diverge - but does antigen bade B cells to take the road less traveled? SO IMMUNITY LA English DT Editorial Material ID POSITIVE SELECTION; IMMUNOGLOBULIN; LYMPHOCYTES AB The contribution of a self-antigen to marginal-zone B lymphocytes is described in this issue (Wen et al., 2005). Other interpretations of these important findings are considered here. C1 Massachusetts Gen Hosp, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Cambridge, MA 02139 USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2005 VL 23 IS 3 BP 242 EP 244 DI 10.1016/j.immuni.2005.09.001 PG 3 WC Immunology SC Immunology GA 971KJ UT WOS:000232382500002 PM 16169496 ER PT J AU Keefe, D Shi, LF Feske, S Massol, R Navarro, F Kirchhausen, T Lieberman, J AF Keefe, D Shi, LF Feske, S Massol, R Navarro, F Kirchhausen, T Lieberman, J TI Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis SO IMMUNITY LA English DT Article ID GRANULE-MEDIATED CYTOTOXICITY; T-CELL GRANULES; GRANZYME-B; TARGET-CELLS; CYTOSOLIC DELIVERY; CHANNEL FORMATION; PORE FORMATION; EXOCYTOSIS; DEATH; PURIFICATION AB Perforin delivers granzymes to induce target-cell apoptosis. At high concentrations, perforin multimerizes in the plasma membrane to form pores. However, whether granzymes enter target cells via membrane pores is uncertain. Here we find that perforin at physiologically relevant concentrations and during cell-mediated lysis creates pores in the target-cell membrane, transiently allowing Ca2+ and small dyes into the cell. The Ca2+ flux triggers a wounded membrane-repair response in which internal vesicles, including lysosomes and endosomes, donate their membranes to reseal the damaged membrane. Perforin also triggers the rapid endocytosis of granzymes into large EEA-1-staining vesicles. The restoration of target-cell membrane integrity by triggering the repair response is necessary for target cells subjected to cytotoxic T lymphocyte attack to avoid necrosis and undergo the slower process of programmed cell death. Thus, the target cell actively participates in determining its own fate during cell-mediated death. C1 CBR Inst Biomed Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Lieberman, J (reprint author), CBR Inst Biomed Res, Boston, MA 02215 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; OI Feske, Stefan/0000-0001-5431-8178 FU NHLBI NIH HHS [P01 HL 59561, T32 HL 66987]; NIAID NIH HHS [AI 45587, R21 AI 54933, U54 AI 57159] NR 38 TC 140 Z9 148 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2005 VL 23 IS 3 BP 249 EP 262 DI 10.1016/j.immuni.2005.08.001 PG 14 WC Immunology SC Immunology GA 971KJ UT WOS:000232382500004 PM 16169498 ER PT J AU Thomas, MD Kremer, CS Ravichandran, KS Rajewsky, K Bender, TP AF Thomas, MD Kremer, CS Ravichandran, KS Rajewsky, K Bender, TP TI c-Myb is critical for B cell development and maintenance of follicular B cells SO IMMUNITY LA English DT Article ID MOUSE BONE-MARROW; MARGINAL-ZONE; IN-VIVO; LYMPHOID TUMORS; EXPRESSION; RECEPTOR; MATURE; GENE; LYMPHOCYTES; PROLIFERATION AB The c-Myb transcription factor is crucial during definitive hematopoiesis. However, the embryonic lethality of Myb traditional null mutations has precluded analysis of c-Myb function in lymphocytes. Using tissue-specific inactivation at the Myb locus, we demonstrate that loss of Myb causes a partial block during B cell development at the pro-B to pre-B cell transition, resulting in greatly decreased output of new B cells from the bone marrow. Furthermore, we demonstrate that Myb is not essential for the proliferation of splenic B cells, but that loss of c-Myb function prevents normal B cell homeostasis due to decreased splenic B cell survival. Decreased survival is accompanied by hyporesponsiveness to the B cell survival factor BLyS (also termed BAFF), decreased expression of the BLyS receptor 3 (BR3), and altered regulation of PKC delta nuclear accumulation. Thus, c-Myb is important during multiple stages of B-lymphopoiesis. C1 Univ Virginia, Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Bender, TP (reprint author), Univ Virginia, Hlth Syst, Dept Microbiol, POB 800734, Charlottesville, VA 22908 USA. EM tpb3e@virginia.edu FU FIC NIH HHS [F06 TW002297]; NCI NIH HHS [CA 85842]; NIAID NIH HHS [AI 59294, AI 43425, R01 AI059294] NR 47 TC 105 Z9 109 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2005 VL 23 IS 3 BP 275 EP 286 DI 10.1016/j.immuni.2005.08.005 PG 12 WC Immunology SC Immunology GA 971KJ UT WOS:000232382500006 PM 16169500 ER PT J AU Park, JM Greten, FR Wong, A Westrick, RJ Arthur, JSC Otsu, K Hoffmann, A Montminy, M Karin, M AF Park, JM Greten, FR Wong, A Westrick, RJ Arthur, JSC Otsu, K Hoffmann, A Montminy, M Karin, M TI Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis - CREB and NF-kappa B as key regulators SO IMMUNITY LA English DT Article ID P38 MAP KINASE; STRESS-INDUCED PHOSPHORYLATION; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR; INFLAMMATORY GENES; CELL-SURVIVAL; MICE LACKING; ACTIVATION; TYPE-2; DEATH AB Certain microbes evade host innate immunity by killing activated macrophages with the help of virulence factors that target prosurvival pathways. For instance, infection of macrophages with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other pathogens induce macrophage apoptosis by preventing activation of NF-kappa B, which depends on I kappa B kinase beta (IKK beta). To better understand how p38 and NF-kappa B maintain macrophage survival, we searched for target genes whose products prevent TLR4-induced apoptosis and a p38-dependent transcription factor required for their induction. Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival. C1 Univ Calif San Diego, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Tech Univ Munich, Klinikum Rechts Isar, Dept Med, D-81675 Munich, Germany. Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Dundee, Prot Phosphorylat Unit, MRC, Dundee DD1 5EH, Scotland. Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Osaka 5650871, Japan. RP Karin, M (reprint author), Univ Calif San Diego, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. EM karinoffice@ucsd.edu RI Arthur, J. Simon/B-8058-2010 OI Arthur, J. Simon/0000-0002-8135-1958 FU NIAID NIH HHS [R01 AI 061712] NR 57 TC 184 Z9 195 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2005 VL 23 IS 3 BP 319 EP 329 DI 10.1016/j.immuni.2005.08.010 PG 11 WC Immunology SC Immunology GA 971KJ UT WOS:000232382500010 PM 16169504 ER PT J AU Chen, CC Louie, S McCormick, B Walker, WA Shi, HN AF Chen, CC Louie, S McCormick, B Walker, WA Shi, HN TI Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice SO INFECTION AND IMMUNITY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; DEPENDENT DIABETES-MELLITUS; MURINE COLONIC HYPERPLASIA; TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; SCHISTOSOMA-MANSONI; TOXOPLASMA-GONDII; BACTERIAL PATHOGEN; EFFACING PATHOGEN; ESCHERICHIA-COLI AB Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminth Heligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacterium Citrobacter rodentium infection, BALB/c and STAT 6 knockout (KO) mice were infected with H. polygyrus, C rodentium, or both. We found that only BALB/c mice coinfected with H. polygyrus and C. rodentium displayed a marked morbidity and mortality. The enhanced susceptibility to C rodentium and intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition, C rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promote C rodentium infection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude that H. polygyrus coinfection can promote C. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism. C1 Chang Gung Univ, Taoyuan, Taiwan. Chang Gung Childrens Hosp, Taoyuan, Taiwan. Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Shi, HN (reprint author), Bldg 114 16th St,Rm 3504, Charlestown, MA 02129 USA. EM shiha@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK70260, DK40561, K01 DK059996, KO1 DK059996, P01 DK033506, P01 DK33506, P30 DK040561, R01 DK056754, R01 DK070260, R01 DK56754] NR 47 TC 72 Z9 73 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 5468 EP 5481 DI 10.1128/IAI.73.9.5468-5481.2005 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000020 PM 16113263 ER PT J AU Nogueira, RD Alves, AC Napimoga, MH Smith, DJ Mattos-Graner, RO AF Nogueira, RD Alves, AC Napimoga, MH Smith, DJ Mattos-Graner, RO TI Characterization of salivary immunoglobulin A responses in children heavily exposed to the oral bacterium Streptococcus mutans: Influence of specific antigen recognition in infection SO INFECTION AND IMMUNITY LA English DT Article ID GLUCAN-BINDING-PROTEIN; NONTYPABLE HAEMOPHILUS-INFLUENZAE; BRAZILIAN NURSERY CHILDREN; DENTAL-CARIES; INITIAL ACQUISITION; PREDENTATE INFANTS; IMMUNE-RESPONSES; DISCRETE WINDOW; IGA ANTIBODY; OTITIS-MEDIA AB The initial infection of children by Streptococcus mutans, the main pathogen of dental caries, depends on the ability of S. mutans to adhere and accumulate on tooth surfaces. These processes involve the adhesin antigen I/II (AgI/II), glucosyltransferases (GTF) and glucan-binding protein B (GbpB), each a target for anticaries vaccines. The salivary immunoglobulin A (IgA) antibody responses to S. mulans antigens (Ags) were characterized in 21 pairs of 5- to 13-month-old children. Pairs were constructed with one early S. mutans-infected and one noninfected child matched by age, racial background, number of teeth, and salivary levels of IgA. Specific salivary IgA antibody response and S. mutans infection levels were then measured during a I-year follow-up. Robust responses to S. mutans were detected from 6 months of age. Salivary IgA antibody to AgI/II and GTF was commonly detected in salivas of all 42 children. However, GbpB-specific IgA antibody was seldom detected in the subset of infected children (38.1% at baseline). In contrast, most of the subset of noninfected children (76.2%) showed GbpB-reactive IgA antibody during the same period. Frequencies of GbpB responses increased with age, but differences in intensities of GbpB-IgA antibody reactions were sustained between the subsets. At baseline, GbpB-reactive IgA antibody accounted for at least half of the total salivary IgA S. mutans-reactive antibody in 33.3 and 9.5% of noninfected and infected children, respectively. This study provides evidence that a robust natural response to S. mutans Ags can be achieved by 1 year of age and that IgA antibody specificities may be critical in modulating initial S. mutans infection. C1 UNICAMP, Fac Odontol Piracicaba, Dept Microbiol & Imunol, Piracicaba Sch Dent, BR-13414903 Sao Paulo, Brazil. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Mattos-Graner, RO (reprint author), UNICAMP, Fac Odontol Piracicaba, Dept Microbiol & Imunol, Piracicaba Sch Dent, Av Limeira 901, BR-13414903 Sao Paulo, Brazil. EM rmgraner@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012; Napimoga, Marcelo/F-8789-2011; OI Mattos-Graner, Renata/0000-0001-8309-8135; Napimoga, Marcelo/0000-0003-4472-365X; Nogueira, Ruchele Dias/0000-0002-7706-1376 NR 42 TC 34 Z9 37 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 5675 EP 5684 DI 10.1128/IAI.73.9.5675-5684.2005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000042 PM 16113285 ER PT J AU Kudva, IT Griffin, RW Garren, JA Calderwood, SB John, M AF Kudva, IT Griffin, RW Garren, JA Calderwood, SB John, M TI Identification of a protein subset of the anthrax spore immunome in humans immunized with the anthrax vaccine adsorbed preparation SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; ESCHERICHIA-COLI; GENE-EXPRESSION; SALMONELLA-TYPHIMURIUM; FUMARATE REDUCTASE; HELICOBACTER-PYLORI; PROTECTIVE ANTIGEN; STRESS RESPONSE; LETHAL TOXIN; SSRA TMRNA AB We identified spore targets of Anthrax Vaccine Adsorbed (AVA)-induced immunity in humans by screening recombinant clones of a previously generated, limited genomic Bacillus anthracis Sterne (pXO1(+), pXO2(-)) expression library of putative spore surface (spore-associated [SA]) proteins with pooled sera from human adults immunized with AVA (immune sera), the anthrax vaccine currently approved for use by humans in the United States. We identified 69 clones that reacted specifically with pooled immune sera but not with pooled sera obtained from the same individuals prior to immunization. Positive clones expressed proteins previously identified as localized on the anthrax spore surface, proteins highly expressed during spore germination, orthollogs of proteins of diverse pathogens under investigation as drug targets, and orthologs of proteins contributing to the virulence of both gram-positive and gram-negative pathogens. Among the reactive clones identified by this immunological screen was one expressing a 15.2-kDa hypothetical protein encoded by a gene with no significant homology to sequences contained in databases. Further studies are required to define the subset of SA proteins identified in this study that contribute to the virulence of this pathogen. We hypothesize that optimal delivery of a subset of SA proteins identified by such studies to the immune system in combination with protective antigen (PA), the principal immunogen in AVA, might facilitate the development of defined, nonreactogenic, more-efficacious PA-based anthrax vaccines. Future studies might also facilitate the identification of SA proteins with potential to serve as targets for drug design, spore inactivation, or spore detection strategies. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP John, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mjohn1@partners.org FU NIAID NIH HHS [R21 AI055968-01, R21 AI055968] NR 83 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 5685 EP 5696 DI 10.1128/IAI.73.9.5685-5696.2005 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000043 PM 16113286 ER PT J AU Hamzaoglu, I Hodin, RA AF Hamzaoglu, I Hodin, RA TI Perianal problems in patients with ulcerative colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Review ID POUCH-ANAL ANASTOMOSIS; INFLAMMATORY-BOWEL-DISEASE; ANORECTAL ABSCESS FISTULA; QUALITY-OF-LIFE; CROHNS-DISEASE; INDETERMINATE COLITIS; RESTORATIVE PROCTOCOLECTOMY; SURGICAL MANAGEMENT; FOURNIERS GANGRENE; HEMORRHOIDS C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, GRB 504,55 Fruit St, Boston, MA 02114 USA. EM rhodin@partners.org RI hamzaoglu, ismail/F-5400-2016 NR 62 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2005 VL 11 IS 9 BP 856 EP 859 DI 10.1097/01.MIB.0000174373.75977.b9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961XR UT WOS:000231695600012 PM 16116321 ER PT J AU Bordeianou, L Hodin, RA AF Bordeianou, L Hodin, RA TI Expanding the role of strictureplasty: Can resections be made obsolete? SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID CROHNS-DISEASE; RECURRENCE C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2005 VL 11 IS 9 BP 861 EP 862 DI 10.1097/01.MIB.0000179214.88402.fb PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961XR UT WOS:000231695600014 PM 16116323 ER PT J AU Yang, XH Beerman, M Bergen, AW Parry, DM Sheridan, E Liebsch, NJ Kelley, MJ Chanock, S Goldstein, AM AF Yang, XH Beerman, M Bergen, AW Parry, DM Sheridan, E Liebsch, NJ Kelley, MJ Chanock, S Goldstein, AM TI Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE chordoma; linkage; single nucleotide polymorphism (SNP); genetic heterogeneity ID LINKAGE ANALYSIS; MICROSATELLITES; GENOME; MAPS; PROGRAM; MARKERS; TUMOR AB Chordoma, a rare bone tumor originating from notochordal remnants, has a genetic predisposition in some families. Previously, we performed linkage analysis using microsatellite (STR) markers on 3 unrelated chordoma kindreds (16 patients with chordoma) and reported significant evidence for linkage to chromosome 7q33 (Z(max) = 4.78) with a minimal disease gene region of 11 cM. In our present study, we performed linkage analysis in these 3 families using chromosome 7 single nucleotide polymorphisms (SNPs). Parametric and nonparametric multipoint analyses showed significant linkage to 7q markers with p < 0.001 and Z(max) = 2.77, respectively. The minimal disease gene region was not reduced by combined SNP and STIR haplotype analysis compared to the previous STR haplotype analysis alone. We genotyped members of a fourth chordoma family with SNP and STR markers for chromosome 7q and for 1p36, the location of a previously reported chordoma locus. Affected members of this family did not share a common haplotype on 7q, and the family did not show evidence of linkage to 1p36. Thus, we corroborated a chordoma locus on chromosome 7q in the 3 original families and demonstrated evidence for genetic heterogeneity in the fourth family. Our study also provided insights into some limitations and analytical complexities associated with using a dense SNP marker set in linkage analysis of complex pedigrees. (C) 2005 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Duke Univ, Dept Med, Durham, NC USA. RP Yang, XH (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7014, Rockville, MD 20852 USA. EM royang@mail.nih.gov OI Kelley, Michael/0000-0001-9523-6080; Bergen, Andrew/0000-0002-1237-7644 NR 28 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2005 VL 116 IS 3 BP 487 EP 491 DI 10.1002/ijc.21006 PG 5 WC Oncology SC Oncology GA 944YC UT WOS:000230466100022 ER PT J AU DeLuca, AK Lenze, EJ Mulsant, BH Butters, MA Karp, JF Dew, MA Pollock, BG Shear, MK Houck, PR Reynolds, CR AF DeLuca, AK Lenze, EJ Mulsant, BH Butters, MA Karp, JF Dew, MA Pollock, BG Shear, MK Houck, PR Reynolds, CR TI Comorbid anxiety disorder in late life depression: association with memory decline over four years SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; anxiety disorders; geriatrics; neuropsychological testing ID ELDERLY-PATIENTS; COGNITIVE DECLINE; ANXIOUS DEPRESSION; CONTROLLED-TRIAL; DOUBLE-BLIND; OLDER; NORTRIPTYLINE; QUESTIONNAIRE; PSYCHOTHERAPY; SYMPTOMS AB Objective In elderly persons with Major Depressive Disorder (MDD), coexisting Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) is associated with more severe symptoms and poorer short-term treatment outcomes. The purpose of this study was to determine whether comorbid GAD or PD was associated with poorer long-term outcomes of late-life MDD, in terms of symptoms, functional disability, and cognitive status. Methods Seventy-nine older subjects with major depressive disorder who had responded to initial treatment in clinical trials were followed at yearly intervals for up to four years with assessment of their symptoms, cognitive status, and functional disability. For this analysis, subjects were divided into two groups, anxious and non-anxious, based on presence (n = 37) or absence (n = 42) of a lifetime diagnosis of GAD and/or PD. Results The anxious group showed a greater decline in memory, but not in other cognitive measures or measures of functional status. Depression recurrence was similar in the anxious and non-anxious groups. Among those in the anxious group, a later age of onset (> 55) of the anxiety disorder was associated with worse overall cognition at baseline, but a similar rate of decline in cognition over time, compared with early-onset anxiety disorder. Conclusion We found evidence that comorbid GAD or PD is associated with a greater decline in memory in late-life MDD. The data also suggest that anxiety disorders with an onset later in life may be associated with cognitive impairment, although further study is needed to confirm this finding. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Clin Room E835, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Intervent Res Ctr Late Life Mood Disorders, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Western Psychiat Inst & Clin, 3811 O Hara St, Pittsburgh, PA 15213 USA. EM lenzeej@upmc.edu FU NIMH NIH HHS [K01 MH 01613, K01 MH 01684, K23 MH 64196, K24 MH 65416, P30 MH 52247, R01 MH 37869, R01 MH 43832] NR 36 TC 54 Z9 58 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD SEP PY 2005 VL 20 IS 9 BP 848 EP 854 DI 10.1002/gps.1366 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 967JV UT WOS:000232088400007 PM 16116585 ER PT J AU Spiryda, LB Fuller, AF Goodman, A AF Spiryda, LB Fuller, AF Goodman, A TI Aggressive locally recurrent vulvar cancer: review of cases presented to Massachusetts General Hospital 1990 to present SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE squamous cell vulvar cancer; recurrence; vulvar intraepithelial lesion; lichen sclerosis ID SQUAMOUS-CELL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; MANAGEMENT; SURVIVAL AB Isolated recurrences of squamous cell vulvar carcinoma treated by surgical reexcision have excellent outcomes. There is a subset of these patients who develop multiple local recurrences that are difficult to manage and have a high risk of dying from their cancers. We reviewed women presenting with vulvar cancer (200 patients) to Massachusetts General Hospital from 1990 to present and identified 12 women with aggressive, locally recurrent squamous cell carcinomas of the vulva. The identified women all had successful primary radical vulvectomy and groin node dissections with negative surgical margins (except patient 2) and lymph nodes with no lymphovascular space invasion. Seven women had underlying lichen sclerosis. Eight had a history of vulvar intraepithelial neoplasia or persistent carcinoma in situ. Ten patients had greater than three recurrences after primary surgical therapy. One died of recurrent vulvar cancer 10 months after her initial diagnosis. Two patients died after three recurrences. The only unifying clinicopathologic factor among these women was persistent lichen sclerosis and persistent carcinoma in situ. Understanding the underlying mechanisms that predisposed these premalignant lesions to transform into carcinomas will help predict in which women these are likely to reoccur and may help determine which women require more aggressive initial treatment. C1 Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Cox 5,100 Blossom St, Boston, MA 02114 USA. EM agoodman@partners.org NR 23 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 2005 VL 15 IS 5 BP 884 EP 889 DI 10.1111/j.1525-1438.2005.00151.x PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 963IW UT WOS:000231798800027 PM 16174240 ER PT J AU Lasser, RA Bossie, CA Gharabawi, GM Baldessarini, RJ AF Lasser, RA Bossie, CA Gharabawi, GM Baldessarini, RJ TI Clinical improvement in 336 stable chronically psychotic patients changed from oral to long-acting risperidone: a 12-month open trial SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE injectable long-acting risperidone; oral risperidone; schizoaffective disorder; schizophrenia ID CONVENTIONAL DEPOT ANTIPSYCHOTICS; BIPOLAR AFFECTIVE-DISORDER; INJECTABLE RISPERIDONE; SCHIZOAFFECTIVE DISORDER; MEDICATION ADHERENCE; SCHIZOPHRENIA; THERAPY; RISK; REHOSPITALIZATION; EFFICACY AB Modern atypical antipsychotics have advantages over older neuroleptics. We hypothesize that their utility may be further enhanced by sustained drug delivery without daily oral self-dosing. This report examines the effects of a year of treatment with long-acting risperidone for chronically psychotic patients previously stabilized with oral risperidone. This open trial of long-acting risperidone involved 336 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder judged clinically stable on a consistent daily oral dose of risperidone for >= 4 wk. Based on oral doses, subjects were assigned clinically to bi-weekly intramuscular injections of 25-75 mg of long-acting risperidone for up to 50 wk. Clinical assessments at regular intervals included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale, adverse event reports, and the Extrapyramidal Symptom Rating Scale (ESRS). PANSS total scores improved overall from a moderate baseline score of 64.5 +/- 17.7 to 58.8 +/- 19.9 at end-point (p < 0.001), by >= 20% in 50% of patients, with greatest improvement in negative symptoms. Prevalence of favourable CGI-Severity ratings increased by 2.4-fold (p < 0.0001). Ratings of extrapyramidal symptoms also improved [e.g. physician-rated parkinsonism scores decreased by 20% (p < 0.0001)]. Tissue reactions and other adverse effects of repeated intramuscular injections were rare and mild. Psychotic patients considered stable but symptomatic with oral risperidone treatment showed further improvements in symptom ratings and extrapyramidal dysfunction during a year of bi-weekly injections of long-acting risperidone. C1 Janssen Psychiat LLC, Off A20305, Titusville, NJ 08560 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Program Neurosci, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. RP Lasser, RA (reprint author), Janssen Psychiat LLC, Off A20305, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 USA. EM rlasser@janus.jnj.com NR 42 TC 28 Z9 30 U1 3 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2005 VL 8 IS 3 BP 427 EP 438 DI 10.1017/S1461145705005225 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 948IH UT WOS:000230708800011 PM 15804371 ER PT J AU Moran-Gates, T Zhang, K Baldessarini, RJ Tarazi, FI AF Moran-Gates, T Zhang, K Baldessarini, RJ Tarazi, FI TI Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE attention-deficit hyperactivity disorder; atomoxetine; 6-hydroxydopamine; juvenile animals; motor activity ID DEFICIT/HYPERACTIVITY DISORDER; EXTRACELLULAR DOPAMINE; NOREPINEPHRINE; SEROTONIN; BRAIN; METHYLPHENIDATE; TRANSPORTER; TOMOXETINE; AMPHETAMINE; INHIBITORS AB We recently reported that selective inhibitors of neuronal transport of norepinephrine (NE), desipramine and nisoxetine, reversed motor hyperactivity in an animal model of attention-deficit hyperactivity disorder (ADHD). In this study, we examined behavioural effects of atomoxetine, a potent new NE reuptake blocker, in juvenile male rats with neonatal 6-hydroxydopamine (6-OHDA) lesions of dopamine projections to the forebrain. 6-OHDA (100 mu g) was administered intracisternally on postnatal day (PD) 5 following desipramine (25 mg/kg s.c.) pretreatment to protect noradrenergic neurons. Atomoxetine (1 mg/kg) was given intraperitoneally before recording motor activity for 90 min at PD 23-26 in a novel environment. Atomoxetine greatly reduced motor hyperactivity in 6-OHDA-lesioned rats while exhibiting transient sedative effects in sham controls. The observed effects in this animal model for ADHD are consistent with the emerging clinical use of atomoxetine as a novel, non-stimulant treatment for ADHD. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, Mailman Res Ctr, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu FU NICHD NIH HHS [HD-043649]; NIMH NIH HHS [MH-068359, MH-068507] NR 26 TC 18 Z9 18 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2005 VL 8 IS 3 BP 439 EP 444 DI 10.1017/S1461145705005249 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 948IH UT WOS:000230708800012 PM 15817135 ER PT J AU Nonacs, RM Soares, CN Viguera, AC Pearson, K Poitras, JR Cohen, LS AF Nonacs, RM Soares, CN Viguera, AC Pearson, K Poitras, JR Cohen, LS TI Bupropion SR for the treatment of postpartum depression: a pilot study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antidepressant; bupropion; postpartum depression ID POSTNATAL DEPRESSION; CHILDBEARING; DISORDERS; WOMEN AB Despite the prevalence of postpartum depression, few studies have assessed the efficacy of antidepressants for the treatment of this disorder. Failure to treat postpartum depression (PPD) places the woman at risk for chronic depression and may have adverse effects on child wellbeing and development. Eight female outpatients aged 18-45 yr were enrolled in an 8-wk open-label trial of bupropion SR for PPD. All patients met DSM-IV criteria for major depression with onset within 3 months of delivery and scored 17 or greater on the Hamilton Depression Rating Scale (HAMD) at baseline. Those with onset of depressive symptoms during pregnancy, psychotic symptoms, or significant medical illness were excluded. Median scores on the HAMD declined from 20.5 (range 15-38) at baseline to 10.0 (range 1-20) at end-point (p < 0.05, Wilcoxon signed-ranks test; LOCF). Six out of the eight subjects demonstrated a >= 50% decrease in HAMD scores from baseline; three subjects achieved remission (HAMD score of <= 7) at week 8. Median final dosage of bupropion SR was 262.5 (range 37.5-300). Bupropion SR was well tolerated, and no subjects discontinued treatment as a result of medication side-effects. Bupropion SR represents an effective and well-tolerated antidepressant for the treatment of PPD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Nonacs, RM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. EM RNONACS@PARTNERS.ORG NR 16 TC 34 Z9 35 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2005 VL 8 IS 3 BP 445 EP 449 DI 10.1017/S1461145705005079 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 948IH UT WOS:000230708800013 PM 15817137 ER PT J AU Zamboni, M Mazzali, G Zoico, E Harris, TB Meigs, JB Di Francesco, V Fantin, F Bissoli, L Bosello, O AF Zamboni, M Mazzali, G Zoico, E Harris, TB Meigs, JB Di Francesco, V Fantin, F Bissoli, L Bosello, O TI Health consequences of obesity in the elderly: a review of four unresolved questions SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE aging; BMI; fat distribution; disability; sarcopenic obesity ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; FAT-FREE MASS; OBSTRUCTIVE SLEEP-APNEA; SIMPLE ANTHROPOMETRIC INDEXES; ABDOMINAL SAGITTAL DIAMETER; CARDIOVASCULAR RISK-FACTORS; VISCERAL ADIPOSE-TISSUE; CORONARY-HEART-DISEASE; SKELETAL-MUSCLE MASS AB Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity. C1 Univ Verona, Div Geriatr Med, I-37126 Verona, Italy. NIA, Off Geriatr Epidemiol, Epidemiol & Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Zamboni, M (reprint author), Univ Verona, Osped Maggiore, Piazzale Stefani 1, I-37126 Verona, Italy. EM mauro.zamboni@univr.it OI ZOICO, Elena/0000-0002-5235-1545; ZAMBONI, Mauro/0000-0001-6961-9483 NR 141 TC 286 Z9 291 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2005 VL 29 IS 9 BP 1011 EP 1029 DI 10.1038/sj.ijo.0803005 PG 19 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 954CC UT WOS:000231130700001 PM 15925957 ER PT J AU Hoffmann, U Butler, J AF Hoffmann, U Butler, J TI Noninvasive detection of coronary atherosclerotic plaque by multidetector row computed tomography SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT International Workshop of the European-Childhood-Obesity-Group CY SEP 29-OCT 01, 2005 CL Vienna, AUSTRIA SP European Childhood Obes Grp DE coronary artery; atherosclerosis; computed tomography; plaques ID OPTICAL COHERENCE TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; ARTERY CALCIUM MEASUREMENT; ELECTRON-BEAM TOMOGRAPHY; HEART-DISEASE EVENTS; INTRAVASCULAR ULTRASOUND; CHEST-PAIN; PROGNOSTIC VALUE; PREDICTIVE-VALUE; IN-VITRO AB BACKGROUND: Coronary artery disease continues to be one of the leading causes of death and disability around the globe, challenging the efficacy of currently applied schemes to predict the risk for future coronary events. In fact, algorithms such as the Framingham risk score that are based on traditional risk factors like hypertension and dyslipidemia are not very sensitive, leaving a majority of the population at intermediate risk. METHODS: Advances in multidetector computed tomography (MDCT) technology with submillimeter slice collimation (similar to 0.6 mm) and high temporal resolution now permit contrast-enhanced imaging of the coronary artery lumen and wall in a single breath hold. The current generation of MDCT provided in-plane resolution of 0.5 mm and a temporal resolution of 210 ms. The simultaneous acquisition of 16/64 parallel cross-sections reduces image acquisition time to about 10-20s using 60-80 ml of contrast agents to opacify the coronary artery lumen. CT imaging for coronary calcification is an established method with low radiation exposure. The amount of calcification is expressed as an Agatston Score (AS). RESULTS: The presence and amount of coronary calcification significantly increases the relative risk for future coronary events, independent from traditional risk factors (risk ratio 8.7 [95% Cl, 2.7-28.1]). Especially, individuals with a high AS (>400) who are at intermediate 10-y Framingham event risk may benefit from this additional risk stratification. However, calcification is rarely present in children and adolescents. However, there is a growing body of evidence suggesting that contrast-enhanced MDCT can detect both calcified and noncalcified plaques with high sensitivity and specificity for the detection of plaques >0.5 mm when compared to intravascular ultrasound. Moreover, initial data suggest that plaque characteristics such as plaque area, volume, quantify and coronary plaque remodeling index can be quantified in good agreement with IVUS. The composition of noncalcified plaque may be further stratified into predominantly fibrous or lipid-rich plaque. Noncalcified plaque may be present already in children and adolescents with multiple risk factors. CONCLUSION: The available data indicate that high resolution MDCT can reliably detect, quantify and characterize calcified and noncalcified coronary atherosclerotic plaque. With MDCT, we now have a unique opportunity to study the natural history and response to therapy of noncalcified coronary plaques, which may be already present in obese children or children with multiple risk factors. C1 Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA. RP Hoffmann, U (reprint author), Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 74 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2005 VL 29 SU 2 BP S46 EP S53 DI 10.1038/sj.ijo.0803083 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 979OD UT WOS:000232953800011 PM 16385752 ER PT J AU Dibart, S Warbington, M Su, MF Skobe, Z AF Dibart, S Warbington, M Su, MF Skobe, Z TI In vitro evaluation of the implant-abutment bacterial seal: The locking taper system SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE bacterial seal; implant-abutment connection ID DENTAL IMPLANTS; INTERFACE; COLONIZATION; COMPONENTS AB Purpose: To test in vitro whether the seal provided by the locking taper used in the implant-abutment connection was capable of preventing the invasion of oral microorganisms. Materials and Methods: Twenty-five wide-body implants (5 X 11 mm) and 25 abutments were divided into 2 groups for a 2-phase experiment. The first phase tested the ability of the seal to shield the implant well from outside bacteria; the second phase tested the ability of the seal to prevent bacteria present in the implant well from seeping out. For phase 1, 10 implant-abutment units were immersed in a bacterial broth for 24 hours. The abutments were then separated from the implants and bacterial presence was evaluated using scanning electron microscopy. In phase 2, the tested abutments were inoculated with a droplet of soft agar bacterial gel and assembled with the implant. These units were incubated in a sterile nutrient broth for 72 hours, sampled, and plated to assess bacterial presence. Results: In phase 1, no bacteria were detected in any of the implant wells. In phase 2, no bacteria were detected in the nutrient broth or on the agar plates at 72 hours. Discussion: In implants where a microgap is present, microbial leakage could lead to inflammation and bone loss; thus, it is important to minimize bacterial presence in and around the the implant-abutment junction. Conclusion: The seal provided by the locking taper design has been demonstrated to be hermetic with regard to bacterial invasion in vitro. C1 Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA USA. RP Dibart, S (reprint author), Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, 100 E Newton St, Boston, MA 02118 USA. EM sdibart@bu.edu NR 20 TC 97 Z9 104 U1 0 U2 4 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD SEP-OCT PY 2005 VL 20 IS 5 BP 732 EP 737 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 972LN UT WOS:000232455400009 PM 16274147 ER PT J AU Tran, A Wallner, K Merrick, G Seeberger, J Armstrong, J Mueller, A Cavanagh, W Lin, D Butler, W AF Tran, A Wallner, K Merrick, G Seeberger, J Armstrong, J Mueller, A Cavanagh, W Lin, D Butler, W TI Rectal fistulas after prostate brachytherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate carcinoma; brachytherapy; rectum; morbidity ID RANDOMIZED MULTICENTER TRIAL; MORBIDITY OUTCOMES; I-125; RISK; COMPLICATIONS; CANCER; PD-103 AB Purpose: To compare the rectal and prostatic radiation doses for a prospective series of 503 patients, 44 of whom developed persistent rectal bleeding, and 2 of whom developed rectal-prostatic fistulas. Methods and Materials: The 503 patients were randomized and treated by implantation with I-125 vs. Pd-103 alone (n = 290) or to Pd with 20 Gy vs. 44 Gy supplemental external beam radiotherapy (n = 213) and treated at the Puget Sound Veterans Affairs Medical Center (n = 227), Schiffler Cancer Center (n = 242) or University of Washington (n = 34). Patients were treated between September 1998 and October 2001 and had a minimum of 24 months of follow-up. The patient groups were treated concurrently. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urological Association and Radiation Therapy Oncology Group criteria, at 1, 3, 6, 12, 18, and 24 months. Patients who reported Grade 1 or greater Radiation Therapy Oncology Group rectal morbidity were interviewed by telephone to clarify details regarding their rectal bleeding. Those who reported persistent bleeding, lasting for > 1 month were included as having Grade 2 toxicity. Three of the patients with rectal bleeding required a colostomy, two of whom developed a fistula. No patient was lost to follow-up. The rectal doses were defined as the rectal volume in cubic centimeters that received > 50%, 100%, 200%, or 300% of the prescription dose. The rectum was considered as a solid structure defined by the outer wall, without attempting to differentiate the inner wall or contents. Results: Persistent rectal bleeding occurred in 44 of the 502 patients, 32 of whom (73%) underwent confirmatory endoscopy. In univariate analysis, multiple parameters were associated with late rectal bleeding, including all rectal brachytherapy indexes. In multivariate analysis, however, only the rectal volume that received > 100% of the dose was significantly predictive of bleeding. Rectal fistulas occurred in 2 patients(0.4%), both of whom had received moderate rectal radiation doses and extensive intervention for rectal bleeding. Conclusion: Partly on the basis of data from others and data presented here, we believe that the incidence of rectal fistulas can be much lower than in our series. High rectal radiation doses should be avoided a priori, to minimize the likelihood of rectal bleeding, and hence the likelihood that invasive procedures will be performed. (c) 2005 Elsevier Inc. C1 US Dept Vet Affairs, Dept Radiat Oncol, Seattle, WA 98108 USA. Puget Sound Hlth Care Syst, Dept Radiat Oncol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Dept Radiat Oncol, Seattle, WA 98121 USA. Schiffler Canc Ctr, Wheeling, WV USA. RP Wallner, K (reprint author), US Dept Vet Affairs, Dept Radiat Oncol, 174,1660 S Columbian Way, Seattle, WA 98108 USA. EM Kent.wallner@med.va.gov NR 23 TC 51 Z9 51 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 SEP 1 PY 2005 VL 63 IS 1 BP 150 EP 154 DI 10.1016/j.ijrobp.2005.01.021 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 956TK UT WOS:000231322500018 PM 16111583 ER PT J AU Offner, H Vandenbark, AA AF Offner, H Vandenbark, AA TI Congruent effects of estrogen and T-cell receptor peptide therapy on regulatory T cells in EAE and MS SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE T cell receptor; estrogen; multiple sclerosis; experimental autoimmune encephalomyelitis; therapy; FoxP3 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; BV8S2 TRANSGENIC MICE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; V-BETA-6.1 CDR2 PEPTIDES; DEMYELINATING DISEASES; SELF-TOLERANCE; TCR PEPTIDES; DOUBLE-BLIND AB Both estrogen (E2) and T-cell receptor (TCR) peptides have beneficial effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and possibly multiple sclerosis (MS) that involve distinct but congruent mechanisms. Of interest, these two approaches share an ability to enhance expression of the Fl gene and associated activity of regulatory T (Treg) cells. E2 increases the number and activity of FoxP3(+) T cells through Esr-1 signaling during TCR activation of CD4(+)CD25(-) T cells. In contrast, TCR peptide therapy appears to increase the frequency of regulatory FoxP3(+) T cells specific for self-TCR determinants expressed by targeted pathogenic T cells. The combined effects on Treg expansion and activation induced by these distinct immunoregulatory approaches may account for their potent effects on clinical EAE and argue for a similar combined therapeutic approach for MS. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd,Bldg 101,Rm 408, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NINDS NIH HHS [NS23221, NS23444, NS45445, NS49210] NR 82 TC 15 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD SEP-DEC PY 2005 VL 24 IS 5-6 BP 447 EP 477 DI 10.1080/08830180500371462 PG 31 WC Immunology SC Immunology GA 002NI UT WOS:000234617800009 PM 16318990 ER PT J AU Pawlyk, BS Smith, AJ Buch, PK Adamian, M Hong, DH Sandberg, MA Ali, RR Li, T AF Pawlyk, BS Smith, AJ Buch, PK Adamian, M Hong, DH Sandberg, MA Ali, RR Li, T TI Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID REGULATOR (RPGR)-INTERACTING PROTEIN; NUCLEOTIDE-EXCHANGE FACTOR; RETINITIS-PIGMENTOSA RP3; ADENOASSOCIATED VIRUS; ROD PHOTORECEPTORS; VIRAL VECTOR; TRANSDUCTION; IDENTIFICATION; SPECIFICITY; BLINDNESS AB PURPOSE. Retinitis pigmentosa GTPase regulator ( RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. METHODS. An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. RESULTS. Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. CONCLUSIONS. AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. UCL, Inst Ophthalmol, Div Mol Therapy, London, England. RP Li, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu RI Smith, Alexander/A-5142-2009 FU NEI NIH HHS [EY 14188, EY 14104, EY 10581] NR 32 TC 86 Z9 88 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 SEP PY 2005 VL 46 IS 9 BP 3039 EP 3045 DI 10.1167/iovs.05-0371 PG 7 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800005 PM 16123399 ER PT J AU Zernant, J Kulm, M Dharmaraj, S den Hollander, AI Perrault, I Preising, MN Lorenz, B Kaplan, J Cremers, FPM Maumenee, I Koenekoop, RK Allikmets, R AF Zernant, J Kulm, M Dharmaraj, S den Hollander, AI Perrault, I Preising, MN Lorenz, B Kaplan, J Cremers, FPM Maumenee, I Koenekoop, RK Allikmets, R TI Genotyping microarray (disease chip) for Leber congenital amaurosis: Detection of modifier alleles SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CONE-ROD DYSTROPHY; ARRAYED PRIMER EXTENSION; RETINITIS-PIGMENTOSA; TRANSCRIPTION FACTOR; MUTATION DETECTION; GUANYLYL CYCLASE; HOMEOBOX GENE; PHOTORECEPTOR; AIPL1; CRX AB PURPOSE. Leber congenital amaurosis (LCA) is an early-onset inherited disorder of childhood blindness characterized by visual impairment noted soon after birth. Variants in at least six genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) have been associated with a diagnosis consistent with LCA or early-onset retinitis pigmentosa ( RP). Genetically heterogeneous inheritance complicates the analyses of LCA cases, especially in patients without a family history of the disorder, and conventional methods are of limited value. METHODS. To overcome these limitations, arrayed primer extension ( APEX) technology was used to design a genotyping microarray for early-onset, severe retinal degenerations that includes all of the > 300 disease-associated variants currently described in eight genes ( in addition to the six just listed, the early-onset RP genes LRAT and MERTK were added). The resultant LCA array allows simultaneous detection of all known disease-associated alleles in any patient with early-onset RP. The array was validated by screening 93 confirmed patients with LCA who had known mutations. Subsequently, 205 novel LCA cases were screened on the array, followed by segregation analyses in families, if applicable. RESULTS. The microarray was > 99% effective in determining the existing genetic variation and yielded at least one disease-associated allele in approximately one third of the novel patients.More than two ( expected) variants were discovered in a substantial fraction (22/300) of the patients, suggesting a modifier effect from more than one gene. In support of the latter hypothesis, the third allele segregated with a more severe disease phenotype in at least five families. CONCLUSIONS. The LCA genotyping microarray is a robust and cost-effective screening tool, representing the prototype of a disease chip for genotyping patients with a genetically heterogeneous condition. Simultaneous screening for all known LCA-associated variants in large LCA cohorts allows systematic detection and analysis of genetic variation, facilitating prospective diagnosis and ultimately predicting disease progression. C1 Columbia Univ, Eye Res Inst, Dept Ophthalmol, New York, NY 10032 USA. Asper Biotech Ltd, Tartu, Estonia. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Pediat Ophthalmol, Boston, MA USA. Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands. Hop Enfants Malad, Paris, France. Klinikum Univ Regensburg, Dept Pediat Ophthalmol Strabismol & Ophthalmogene, D-8400 Regensburg, Germany. Johns Hopkins Univ, Baltimore, MD USA. McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. RP Allikmets, R (reprint author), Columbia Univ, Eye Res Inst, Dept Ophthalmol, Room 715,630 W 168th St, New York, NY 10032 USA. EM rla22@columbia.edu RI Hollander, Anneke/N-4911-2014; Cremers, Frans/A-5625-2014 FU NEI NIH HHS [EY 13435] NR 41 TC 104 Z9 109 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2005 VL 46 IS 9 BP 3052 EP 3059 DI 10.1167/iovs.05-0111 PG 8 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800007 PM 16123401 ER PT J AU Sandberg, MA Brockhurst, RJ Gaudio, AR Berson, EL AF Sandberg, MA Brockhurst, RJ Gaudio, AR Berson, EL TI The association between visual acuity and central retinal thickness in retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; DISEASE EXPRESSION; DEGENERATION; MUTATIONS; SUPPLEMENTATION; GENE AB PURPOSE. To determine whether visual acuity is related to central retinal thickness in patients with retinitis pigmentosa. METHODS. Visual acuities were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography (OCT3) was used to calculate retinal thicknesses and grade third high-reflectance bands in 162 patients with the typical forms of retinitis pigmentosa who had Snellen visual acuities of 20/20 to 20/200, minimal to no cataracts, and no visible macular cysts. Sixty-five patients were retested within 2 months to estimate the intervisit variability of retinal thickness measurements. RESULTS. ETDRS acuity was best related to retinal thickness measured at fixation and as the average value over the central 1 mm by a second-order polynomial (r(2) = 0.38 and P < 0.001 in both cases). Acuity was maximal for intermediate retinal thickness and appeared to decline for both lesser and greater retinal thicknesses. By linear regression, the decline in acuity for decreasing retinal thickness was steeper in eyes with an absent third high-reflectance band than for eyes with a partially distinct band. No decline was noted in eyes with an intact band. Assessment of intervisit variability of retinal thickness measurements showed 98% confidence limits of +/- 17 mu m at fixation and +/- 11 mu m for the central 1 mm. CONCLUSIONS. Both retinal thinning ( due to cell loss) and retinal thickening ( due to presumed edema) appear to be associated with lower visual acuity in patients with typical retinitis pigmentosa. The definition of the OCT third high-reflectance band may help to predict which patients are more likely to lose visual acuity as retinal thickness declines. An increase or decrease in retinal thickness of more than 17 mu m at fixation or 11 mu m over the central 1 mm at follow-up can be considered a significant ( P < 0.01) change in these patients. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM masandberg@aol.com NR 12 TC 99 Z9 100 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 SEP PY 2005 VL 46 IS 9 BP 3349 EP 3354 DI 10.1167/iovs.04-1383 PG 6 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800045 PM 16123439 ER PT J AU Harpold, TL Wozniak, J Kwon, A Gilbert, J Wood, J Smith, L Biederman, J AF Harpold, TL Wozniak, J Kwon, A Gilbert, J Wood, J Smith, L Biederman, J TI Examining the association between pediatric bipolar disorder and anxiety disorders in psychiatrically referred children and adolescents SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; mania; anxiety syndromes; pediatric; youth; comorbidity ID NATIONAL COMORBIDITY SURVEY; PANIC DISORDER; STRESS-DISORDER; ONSET MANIA; I DISORDER; PREVALENCE; DIAGNOSES; ILLNESS; ADHD; PHENOMENOLOGY AB Background: To examine the association between anxiety (ANX) and bipolar disorders (BPD) in a clinically referred pediatric sample. Methods: Subjects were consecutively referred youth aged < 18 years, with a DSM-III-R/DSM-IV diagnosis of BPD (n = 297) or a disruptive behavior disorder (DBD) (n = 1100) on structured interview. Results: Bipolar disorder in youth was associated with a significantly increased risk for most of the DSM-IV anxiety disorders and was not specifically linked to any one disorder in particular. Conclusions: Bipolar disorder in youth is a significant risk factor for anxiety comorbidity. Considering the morbidity and dysfunction as well as the differing therapeutic needs associated with bipolar and anxiety symptomatology, appropriate therapeutic approaches will be needed for the management of youth with this comorbidity. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Johnson & Johnson Ctr Study Pediat Psychopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Stanley Ctr Treatment Pediat Bipolar Disorder, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org NR 36 TC 35 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2005 VL 88 IS 1 BP 19 EP 26 DI 10.1016/j.jad.2005.05.016 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 965GS UT WOS:000231939200003 PM 16043229 ER PT J AU Clark, S Long, AA Gaeta, TJ Camargo, CA AF Clark, S Long, AA Gaeta, TJ Camargo, CA TI Multicenter study of emergency department visits for insect sting allergies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE insect sting allergy; emergency department; epinephrine; referral to allergist ID UNITED-STATES; ANAPHYLAXIS; EPIDEMIOLOGY; HYPERSENSITIVITY; HYMENOPTERA; MANAGEMENT; SENSITIVITY; POPULATION; SEVERITY; DISEASE AB Background: An earlier study of food-related anaphylaxis in the emergency department (ED) suggested low concordance with national guidelines for anaphylaxis management. Objective: To extend these findings, we performed a chart review study to describe current ED management of insect sting allergy. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 15 North American EDs. Investigators reviewed 617 charts of patients with insect sting allergy. Patients were identified by using International Classification of Diseases, 9th Revision, codes 989.5 (toxic effect of venom), 995.0 (other anaphylactic shock), and 995.3 (allergy, unspecified). Results: The cohort was 42% female and 61% white, with a mean age of 36 +/- 19 years. In this cohort, 58% had local reactions, 11% had mild systemic reactions, and 31% had anaphylactic reactions, as defined by multisystem organ involvement or hypotension. Among patients with systemic reactions (mild or anaphylaxis), most (75%) were stung within 6 hours of ED arrival. While in the ED, 69% of systemic reaction patients received antihistamines, 50% systemic corticosteroids, and 12% epinephrine. Almost all systemic reaction patients (95%) were discharged to home. At ED discharge, 27% (95% CI, 22% to 33%) of systemic reaction patients received a prescription for self-injectable epinephrine. Only 20% (95% CI, 15% to 26%) had documentation of referral to an allergist. Conclusions: Although guidelines suggest specific approaches for the emergency management of insect sting allergy, concordance with these guidelines appears low in patients with a severe insect sting reaction. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. New York Methodist Hosp, Dept Emergency Med, Brooklyn, NY USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02138 USA. RP Clark, S (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM sclark3@partners.org FU NIAID NIH HHS [AI52338]; NIEHS NIH HHS [T32 ES07069] NR 30 TC 96 Z9 98 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2005 VL 116 IS 3 BP 643 EP 649 DI 10.1016/j.jaci.2005.06.026 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 017IE UT WOS:000235686500027 PM 16159637 ER PT J AU Kaye, JA Moore, MM Dame, A Quinn, J Camicioli, R Howieson, D Corbridge, E Care, B Nesbit, G Sexton, G AF Kaye, JA Moore, MM Dame, A Quinn, J Camicioli, R Howieson, D Corbridge, E Care, B Nesbit, G Sexton, G TI Asynchronous regional brain volume losses in presymptomatic to moderate AD SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE aging; oldest-old; MRI; dementia; Alzheimer disease ID HEALTHY ELDERLY PERSONS; ALZHEIMERS-DISEASE; OLDEST-OLD; HIPPOCAMPAL ATROPHY; ENTORHINAL CORTEX; COGNITIVE DECLINE; TEMPORAL-LOBE; MRI; DEMENTIA AB To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled ill a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 -> Very Mild (CDR 0 -> 0.5 and 0.5 -> 0.5), Mild (CDR 0.5 -> 1.0 and 1.0 -> 1.0) and Moderate (CDR 1.0 -> 2.0 and 2.0 -> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p < 0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia. C1 Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr, Dept Med & Prevent Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr, Dept Radiol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. RP Kaye, JA (reprint author), Oregon Hlth Sci Univ, Layton Aging & Alzheimers Dis Ctr, Dept Neurol, CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kaye@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCCIH NIH HHS [P50 AT00066]; NCRR NIH HHS [M01 RR000334]; NIA NIH HHS [P30 AG08017] NR 29 TC 25 Z9 29 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD SEP PY 2005 VL 8 IS 1 BP 51 EP 56 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 039HT UT WOS:000237297300006 PM 16155349 ER PT J AU Giraud, GD Faber, JJ Jonker, S Davis, L Anderson, DF AF Giraud, GD Faber, JJ Jonker, S Davis, L Anderson, DF TI Intravascular infusions of plasma into fetal sheep cause arterial and venous hypertension SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE blood pressure; renin; angiotensin ID ANGIOTENSIN-II; BLOOD-PRESSURE; UMBILICAL CIRCULATION; PLACENTAL CIRCULATION; RENIN ACTIVITY; HEART-RATE; RESPONSES; LOSARTAN; SYSTEM; VOLUME AB Fetal volume control is driven by an equilibrium between fetal and maternal hydrostatic and oncotic pressures in the placenta. Renal contributions to blood volume regulation are minor because the fetal kidneys cannot excrete fluid from the fetal compartment. We hypothesized that an increase in fetal plasma protein would lead to an increase in plasma oncotic pressure, resulting in an increase in fetal arterial and venous pressures and decreased angiotensin levels. Plasma or lactated Ringer solution was infused into each of five, twin fetuses. After 7 days, fetal protein concentration was 71.2 +/- 4.2 g/l in the plasma-infused fetuses compared with 35.7 +/- 6.3 g/l in the lactated Ringer-solution-infused fetuses. Arterial pressure was 68.0 +/- 3.6 compared with 43.4 +/- 1.9 mmHg in the lactated Ringer solution-infused fetuses (P < 0.0003), whereas venous, pressure was 4.8 +/- 0.3 mmHg in the plasma-infused fetuses compared with 3.3 +/- 0.4. mmHg in the lactated Ringer solution-infused fetuses (P < 0.036). Six fetuses were studied on days 0, 7, and 14 of plasma protein infusion. Fetal protein concentration increased from 31.1 +/- 1.5 to 84.8 +/- 3.8 g/l after 14 days,(P < 0.01), and arterial pressure increased from 43.1 +/- 1.8 to 69.1 +/- 4.1 mmHg (P < 0.01). Venous pressure increased from 3.0 +/- 0.4 to 6.2 +/- 1.3 mmHg (P < 0.05). Fetal heart rate did not change. Angiotensin H concentration decreased, from 24.6 +/- 5.6 to 2.9 +/- 1.3 pg/l, after 14 days (P < 0.01). Fetal plasma infusions resulted in fetal arterial and venous hypertensions that could not be corrected by reductions in angiotensin II levels. C1 Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Giraud, GD (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Heart Res Ctr, L334, Portland, OR 97239 USA. EM giraudg@ohsu.edu OI Jonker, Sonnet/0000-0002-1097-2562 FU NHLBI NIH HHS [HL-45043]; NICHD NIH HHS [5PO1-HD-34430, HD-37376] NR 29 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2005 VL 99 IS 3 BP 884 EP 889 DI 10.1152/japplphysiol.01429.2004 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 959RW UT WOS:000231538000014 PM 15879162 ER PT J AU Manning, DW Ponce, BA Chiang, PP Harris, WH Burke, DW AF Manning, DW Ponce, BA Chiang, PP Harris, WH Burke, DW TI Isolated acetabular revision through the posterior approach: Short-term results after revision of a recalled acetabular component SO JOURNAL OF ARTHROPLASTY LA English DT Article DE acetabulum; revision; dislocation; piriformis; recall ID TOTAL HIP-ARTHROPLASTY; RISK-FACTORS; DISLOCATION; REPLACEMENT; REPAIR; CAPSULORRHAPHY; PREVALENCE; RATES AB Isolated acetabular revision is commonly associated with high rates of postoperative dislocation. We hypothesize that the dislocation rate in a series of isolated acetabular revisions for loosening of recalled acetabular components is low when strict intraoperative stability testing is Coupled with re-repair of the piriformis tendon. Twenty-six isolated revisions of aseptic, loose recalled acetabular components were performed through the posterior approach by a single surgeon. All piriformis tendon and posterior capsular repairs front the index operation were considered intact at the time of revision. The piriformis tendon was re-repaired in each revision case. The average revision acetabular component was 3 min larger than the index component. in this select group of isolated acetabular revisions, strict intraoperative stability testing and re-repair of the piriformis tendon yielded zero dislocations. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Univ Chicago, Med Ctr, Sect Orthopaed Surg, Chicago, IL 60637 USA. Colorado Permanente Med Grp PC, Denver, CO USA. RP Manning, DW (reprint author), Sect Orthopaed Surg, 5841 S Maryland Ave,MC 3079, Chicago, IL USA. NR 31 TC 12 Z9 13 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2005 VL 20 IS 6 BP 723 EP 729 DI 10.1016/j.arth.2004.11.009 PG 7 WC Orthopedics SC Orthopedics GA 966ID UT WOS:000232012400007 PM 16139708 ER PT J AU Dewhirst, FE Shen, ZL Scimeca, MS Stokes, LN Boumenna, T Chen, TT Paster, BJ Fox, JG AF Dewhirst, FE Shen, ZL Scimeca, MS Stokes, LN Boumenna, T Chen, TT Paster, BJ Fox, JG TI Discordant 16S and 23S rRNA gene phylogenies for the genus Helicobacter: Implications for phylogenetic inference and systematics SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPARATIVE SEQUENCE-ANALYSIS; COMPLETE GENOME SEQUENCE; INTERVENING SEQUENCES; WOLINELLA-SUCCINOGENES; BACTEROIDES-GRACILIS; HORIZONTAL TRANSFER; COMB-NOV; PYLORI; STRAINS; PROTEOBACTERIA AB Analysis of 16S rRNA gene sequences has become the primary method for determining prokaryotic phylogeny. Phylogeny is currently the basis for prokaryotic systematics. Therefore, the validity of 16S rRNA gene-based phylogenetic analyses is of fundamental importance for prokaryotic systematics. Discrepancies between 16S rRNA gene analyses and DNA-DNA hybridization and phenotypic analyses have been noted in the genus Helicobacter. To clarify these discrepancies, we sequenced the 23S rRNA genes for 55 helicobacter strains representing 41 taxa. (> 2,700 bases per sequence). Phylogenetic-tree construction using neighbor-joining, parsimony, and maximum likelihood methods for 23S rRNA gene sequence data yielded stable trees which were consistent with other phenotypic and genotypic methods. The 16S rRNA gene sequence-derived trees were discordant with the 23S rRNA gene trees and other data. Discrepant 16S rRNA gene sequence data for the helicobacters are consistent with the horizontal transfer of 16S rRNA gene fragments and the creation of mosaic molecules with loss of phylogenetic information. These results suggest that taxonomic decisions must be supported by other phylogenetically informative macromolecules, such as the 23S rRNA gene, when 16S rRNA gene-derived phylogeny is discordant with other credible phenotypic and genotypic methods. This study found Wolinella succinogenes to branch with the unsheathed-flagellum cluster of helicobacters by 23S rRNA gene analyses and whole-genome comparisons. This study also found intervening sequences (IVSs) in the 23S rRNA genes of strains of 12 Helicobacter species. IVSs were found in helices 10, 25, and 45, as well as between helices 31' and 27'. Simultaneous insertion of IVSs at three sites was found in H. mesocricetorum. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [R01 CA67529, R01 CA067529]; NIAID NIH HHS [R01 AI37750, R01 AI050952, R01 AI50952, R01 AI037750]; NIDCR NIH HHS [DE11443, DE 10374, R01 DE010374, R01 DE011443] NR 62 TC 78 Z9 81 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2005 VL 187 IS 17 BP 6106 EP 6118 DI 10.1128/JB.187.17.6106-6118.2005 PG 13 WC Microbiology SC Microbiology GA 957XF UT WOS:000231406000027 PM 16109952 ER PT J AU Nilsen, T Yan, AW Gale, G Goldberg, MB AF Nilsen, T Yan, AW Gale, G Goldberg, MB TI Presence of multiple sites containing polar material in spherical Escherichia coli cells that lack MreB SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ACTIN-LIKE PROTEINS; BACILLUS-SUBTILIS; CAULOBACTER-CRESCENTUS; UNIPOLAR LOCALIZATION; SHIGELLA-FLEXNERI; DIVISION-SITE; FLUORESCENT PROTEIN; O-ANTIGEN; SHAPE; ICSA AB In rod-shaped bacteria, certain proteins are specifically localized to the cell poles. The nature of the positional information that leads to the proper localization of these proteins is unclear. In a screen for factors required for the localization of the Shigella sp. actin assembly protein IcsA to the bacterial pole, a mutant carrying a transposon insertion in mreB displayed altered targeting of IcsA. The phenotype of cells containing a transposon insertion in mreB was indistinguishable from that of cells containing a nonpolar mutation in mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic derivative of IcsA localized to multiple sites. Secreted full-length native IcsA was present in multiple faint patches on the surfaces of these cells in a pattern similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio cholerae inner membrane protein, also localized to multiple sites in mreB cells and colocalized with IcsA, indicating that localization to multiple sites is not unique to IcsA. Our results are consistent with the requirement, either direct or indirect, for MreB in the restriction of certain polar material to defined sites within the cell and, in the absence of MreB, with the formation of ectopic sites containing polar material. C1 Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA USA. RP Bacterial Pathogenesis Labs, Univ Pk,65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [R01 AI035817, AI035817] NR 59 TC 42 Z9 42 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2005 VL 187 IS 17 BP 6187 EP 6196 DI 10.1128/JB.187.17.6187-6196.2005 PG 10 WC Microbiology SC Microbiology GA 957XF UT WOS:000231406000035 PM 16109960 ER PT J AU Mal, TK Liu, DJ Masutomi, Y Zheng, L Nakatani, Y Kokubo, T Ikura, M AF Mal, TK Liu, DJ Masutomi, Y Zheng, L Nakatani, Y Kokubo, T Ikura, M TI Resonance assignments of 30 kDa complexes of TFIID subunit TAF1 with TATA-binding protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article C1 OCI Toronto, Div Signaling Biol, Toronto, ON M5G 2M9, Canada. Nippon Shiyanku, Tsukuba, Ibaraki 3050003, Japan. Amgen Inc, Dept Pharmaceut, Newbury Pk, CA 91320 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yokohama City Univ, Div Mol & Cellular Biol, Yokohama, Kanagawa 2300045, Japan. RP Ikura, M (reprint author), OCI Toronto, Div Signaling Biol, Toronto, ON M5G 2M9, Canada. EM mikura@uhnres.utoronto.ca NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2005 VL 33 IS 1 BP 76 EP 76 DI 10.1007/s10858-005-1929-3 PG 1 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 973ZC UT WOS:000232560100015 PM 16222567 ER PT J AU Banerjee, S Suliman, G Juppner, H Bringhurst, FR Divieti, P AF Banerjee, S Suliman, G Juppner, H Bringhurst, FR Divieti, P TI Novel ligands for analysis of carboxyl-PTH receptors in bone cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S432 EP S432 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805265 ER PT J AU Bastepe, M Linglart, A Frohlich, LF Juppner, H AF Bastepe, M Linglart, A Frohlich, LF Juppner, H TI Different epigenetic variants of pseudohypoparathyroidism type-IB are associated with distinct mutations of GNAS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S10 EP S10 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800036 ER PT J AU Bergwitz, C Banerjee, S Abu-Zahra, H Kaji, H Sugimoto, T Chihara, K Miyauchi, A Juppner, H AF Bergwitz, C Banerjee, S Abu-Zahra, H Kaji, H Sugimoto, T Chihara, K Miyauchi, A Juppner, H TI A homozygous S129P missense mutation in FGF-23 causes tumoral calcinosis with Hhyperphosphatemia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Kobe Univ, Dept Endocrinol Metab, Kobe, Hyogo, Japan. Shimane Univ, Sch Med, Dept Endocrinol Metab, Shimane, Shimane, Japan. Natl Hyogo Chuo Hosp, Dept Med, Sanda, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S99 EP S99 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801105 ER PT J AU Bergwitz, C Roslin, NM Loredo-Osti, JC Tieder, M Abu-Zahra, H Fujiwara, M Morgan, K Tenenhouse, HS Juppner, H AF Bergwitz, C Roslin, NM Loredo-Osti, JC Tieder, M Abu-Zahra, H Fujiwara, M Morgan, K Tenenhouse, HS Juppner, H TI Homozygous loss-of-function mutation in the renal sodium-phosphate co-transporter NaPi-IIc (SLC34A3) leads to isolated renal phosphate-wasting in a large consanguineous kindred with hereditary hypophosphatemic rickets with hypercalciuria. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. McGill Univ, Inst Res, Ctr Hlth, Montreal, PQ, Canada. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S28 EP S28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800107 ER PT J AU Bischoff, DS Makhijani, NS Zhu, JH Yamaguchi, DT AF Bischoff, DS Makhijani, NS Zhu, JH Yamaguchi, DT TI ELR+ CXC chemokine secretion during human mesenchymal stem cell osteogenic differentiation is dependent on dexamethasone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S236 EP S237 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503803070 ER PT J AU Bounoutas, GS Tawfeek, H Abou-Samra, A AF Bounoutas, GS Tawfeek, H Abou-Samra, A TI Increased PTH anabolic effects in a mouse model expressing a phosphorylation-deficient PTH/PTHrP receptor (pdPTH1R). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S41 EP S41 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800160 ER PT J AU Bouxsein, ML Black, DM Muller, J Bilezikian, J Greenspan, S Ensrud, K Palermo, L Crawford, PM Rosen, CJ Keaveny, TM AF Bouxsein, ML Black, DM Muller, J Bilezikian, J Greenspan, S Ensrud, K Palermo, L Crawford, PM Rosen, CJ Keaveny, TM TI Combining biomechanical measures of vertebral strength with estimates of spinal loading to assess the effects of osteoporosis therapies on vertebral fracture: A pilot study in PaTH. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 BIDMC, Boston, MA USA. UCSF, San Francisco, CA USA. Columbia Univ, New York, NY USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Minnesota, Minneapolis, MN 55455 USA. ON diagnost, Berkeley, CA USA. MECORE, Bangor, ME USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S411 EP S411 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805175 ER PT J AU Briesacher, B Orwig, D Seton, M Omar, M Kristijan, K AF Briesacher, B Orwig, D Seton, M Omar, M Kristijan, K TI Costs of treating Paget's disease in a privately insured population. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA 01605 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, New England Reg Pagets Dis Bone, Boston, MA 02114 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S179 EP S179 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802132 ER PT J AU Burnett, SM Gunawardene, S Bringhurst, FR Jueppner, H Finkelstein, JS AF Burnett, SM Gunawardene, S Bringhurst, FR Jueppner, H Finkelstein, JS TI 1st vs. 2nd generation assays in detecting changes in blood FGF-23 with dietary phosphate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801222 ER PT J AU Cianferotti, L Demay, MB AF Cianferotti, L Demay, MB TI Adipogenesis is enhanced in bone marrow stromal cells lacking the vitamin D receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801123 ER PT J AU Gensure, RC Dean, T Gardella, TJ AF Gensure, RC Dean, T Gardella, TJ TI Cross-linking of modified PTH(1-15) antagonist analogs to the juxtamembrane portion of the PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Ochsner Clin Fdn, New Orleans, LA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S430 EP S430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805258 ER PT J AU Ghosh-Choudhury, N AF Ghosh-Choudhury, N TI Phosphatidylinositol 3 kinase (PI3K)-dependent Erk1/2 activation represents a novel mechanism of statin-induced BMP-2 expression and osteoblast differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S79 EP S79 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801028 ER PT J AU Gori, F Friedman, L Demay, B AF Gori, F Friedman, L Demay, B TI Wdr5, a BMP-2 induced gene, interacts with Ihh and Wnt signaling pathways during endochondral bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S62 EP S62 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800244 ER PT J AU Guo, J Schipani, E Liu, M Bringhurst, FR Kronenberg, HM AF Guo, J Schipani, E Liu, M Bringhurst, FR Kronenberg, HM TI Suppression of Dkk1 is not essential for PTH-mediated activation of canonical Wnt signaling in bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S2 EP S2 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800003 ER PT J AU Hershey, CL Lin, YL Bouxsein, ML Widlund, HR Fisher, DE AF Hershey, CL Lin, YL Bouxsein, ML Widlund, HR Fisher, DE TI Specific requirement for the microphthalmia transcription factor (Mitf) in osteoclast differentiation and bone development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Kentucky, Lexington, KY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S257 EP S257 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503803161 ER PT J AU Honjo, T Kurihara, N Windle, JJ Roodman, GD AF Honjo, T Kurihara, N Windle, JJ Roodman, GD TI Measles virus nucleocapsid protein increases TNF-alpha induced osteoclast differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S100 EP S100 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801112 ER PT J AU Iida-Klein, A Bischoff, DS Zhu, J Dempster, DW Hahn, TJ Yamaguchi, DT AF Iida-Klein, A Bischoff, DS Zhu, J Dempster, DW Hahn, TJ Yamaguchi, DT TI RNA interference with Gq and G11 proteins suppresses messenger RNA expression of osteoblast functional genes and induces changes in cellular morphology in mouse osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S364 EP S364 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804281 ER PT J AU Ishizuka, S Kurihara, N Roodman, GD AF Ishizuka, S Kurihara, N Roodman, GD TI The vitamin D receptor antagonist, (23S)-25-dehydro-1 alpha-hydroxyvitamin D-3-26,23-lactone, blocks RANK ligand induced osteoclast formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Teijin Inst Biomed Res, Tokyo, Japan. Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S184 EP S184 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802152 ER PT J AU Kamiya, N Ye, L Kobayashi, T Kronenberg, HM Feng, J Mishina, Y AF Kamiya, N Ye, L Kobayashi, T Kronenberg, HM Feng, J Mishina, Y TI Tamoxifen induced bone morphological protein receptor 1A (Bmpr1a) conditional knockout mice display an age-dependent phenotype in long bones different from calvariae SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Univ Missouri, Sch Dent, Kansas City, MO 64110 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S10 EP S10 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800037 ER PT J AU Kurihara, N Honjo, T Windle, JJ Roodman, GD AF Kurihara, N Honjo, T Windle, JJ Roodman, GD TI Inhibiting p62(ZIP) expression decreases OCL formation by blocking the effects of RANKL and TNF-alpha. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S55 EP S55 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800218 ER PT J AU Kurihara, N Yamana, K Roodman, GD AF Kurihara, N Yamana, K Roodman, GD TI Expression of TAF(II)-17 and IL-6 in osteoclast (OCL) precursors is sufficient for formation of Pagetic-like OCL. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Teijin Inst Biomed Res, Tokyo, Japan. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800208 ER PT J AU Leder, BZ Finkelstein, JS Miller, M Comeaux, S Cohen, R Lee, H AF Leder, BZ Finkelstein, JS Miller, M Comeaux, S Cohen, R Lee, H TI Effects of selective testosterone and estradiol withdrawal on skeletal sensitivity to parathyroid hormone in men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S28 EP S28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800108 ER PT J AU Li, YP Abe, Y Isoda, R Moroi, R Yang, S Shao, JZ Li, E Chen, W AF Li, YP Abe, Y Isoda, R Moroi, R Yang, S Shao, JZ Li, E Chen, W TI Cathepsin K-deficient mice exhibit pycnodysostosis geatures due to loss of cathepsin K-mediated osteoclast senescence for bone homeostasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Charlestown, MA USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S253 EP S253 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503803144 ER PT J AU Linglart, A Mahon, MJ Dean, T Gardella, TJ Hendy, GN Juppner, H Bastepe, M AF Linglart, A Mahon, MJ Dean, T Gardella, TJ Hendy, GN Juppner, H Bastepe, M TI Human XL alpha s (hXL alpha s) functions as a powerful alpha stimulatory G protein subunit. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801122 ER PT J AU Lu, G Maeda, H Reddy, SV Kurihara, N Roodman, GD AF Lu, G Maeda, H Reddy, SV Kurihara, N Roodman, GD TI Cloning and characterization of the annexin II receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Kyushu Univ Hosp, Kyushu, Japan. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S83 EP S83 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801045 ER PT J AU Napierala, D Sam, K Zheng, Q Zhou, G Shivdasani, RA Lee, B AF Napierala, D Sam, K Zheng, Q Zhou, G Shivdasani, RA Lee, B TI The role of the Trps1 transcriptional repressor in endochondral bone formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S9 EP S9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800033 ER PT J AU Nishimori, S Paruch, J Kronenberg, HM AF Nishimori, S Paruch, J Kronenberg, HM TI Systematic approach for gene screening within discrete compartments in the growth plate using DNA microarrays. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S326 EP S326 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804117 ER PT J AU Palacjos, VG Subler, MA Chung, HY Choi, SJ Patrene, K Blair, HC Windle, JJ Roodman, GD AF Palacjos, VG Subler, MA Chung, HY Choi, SJ Patrene, K Blair, HC Windle, JJ Roodman, GD TI Overexpression of ADAM8 in osteoclast precursors increases osteoclast formation and decreases trabecular bone volume in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S370 EP S370 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805006 ER PT J AU Panda, D Juppner, H Goltzmar, D Karaplis, AC AF Panda, D Juppner, H Goltzmar, D Karaplis, AC TI TIP39/parathyroid hormone receptor 2 signaling inhibits chondrocyte proliferation and differentiation by negatively regulating Sox9 gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 McGill Univ, Montreal, PQ, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802147 ER PT J AU Peterson, WJ Yamaguchi, DT AF Peterson, WJ Yamaguchi, DT TI Differential effect of indomethacin on cell number and alkaline phosphatase production during osteogenesis in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Grecc 691 11g, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv 691 151, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S350 EP S350 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804218 ER PT J AU Selim, A McKenna, B El-Difrawy, S Juppner, H Divieti, P Ehrlich, D Bringhurst, R AF Selim, A McKenna, B El-Difrawy, S Juppner, H Divieti, P Ehrlich, D Bringhurst, R TI Development of a novel cell-scanning system (cell track) for expression cloning of the carboxyl-terminal parathyroid hormone receptor (CPTHR). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. MIT, White Head Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802148 ER PT J AU Selim, A Mattioli, PM Scheinfeld, VL D'Angelo, M AF Selim, A Mattioli, PM Scheinfeld, VL D'Angelo, M TI A novel large latent complex of TGFb is produced by hypertrophic chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Philadelphia Coll Osteopath Med, Dept Anat, Philadelphia, PA USA. Philadelphia Coll Osteopath Med, Ctr Study Chron Dis Aging, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S131 EP S131 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801232 ER PT J AU Selim, AA Suliman, G Juppner, H Potts, J Bringhurst, R Divieti, P AF Selim, AA Suliman, G Juppner, H Potts, J Bringhurst, R Divieti, P TI The receptor for carboxyl-terminal parathyroid hormone regulates osteocyte cytoskeleton through calcium influx dependent mechanisms. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S184 EP S184 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802149 ER PT J AU Solomon, DH Avorn, J Polinski, J Arnold, M Finkelstein, JS Licari, A Canning, C Gauthier, S Katz, JN AF Solomon, DH Avorn, J Polinski, J Arnold, M Finkelstein, JS Licari, A Canning, C Gauthier, S Katz, JN TI A randomized controlled trial of mailed osteoporosis education to older adults: Survey results. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Arthrit Fdn, Newton, MA USA. Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S401 EP S401 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805136 ER PT J AU Solomon, DH Avorn, J Katz, JN Finkelstein, JS Polinski, J Arnold, M Brookhart, MA AF Solomon, DH Avorn, J Katz, JN Finkelstein, JS Polinski, J Arnold, M Brookhart, MA TI Compliance with osteoporosis medications among 40,000 Medicare beneficiaries. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S401 EP S401 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805135 ER PT J AU Tawfeek, HA Abou-Samra, AB AF Tawfeek, HA Abou-Samra, AB TI PTH/PTHrP receptor phosphorylation regulates PTH activation of ERK1/2 MAP kinases and gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S433 EP S433 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805271 ER PT J AU Wiren, KM Toombs, AS Matsumoto, AM Zhang, X AF Wiren, KM Toombs, AS Matsumoto, AM Zhang, X TI Androgen receptor transgenic mice have decreased body fat, reduced adipogensis and an increased osteoblast differentiation program. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S50 EP S50 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800199 ER PT J AU Wu, Y Ackerman, JL Dai, G Chelsler, DA Hrovat, M Snyder, BD Nazarian, A Glimcher, MJ AF Wu, Y Ackerman, JL Dai, G Chelsler, DA Hrovat, M Snyder, BD Nazarian, A Glimcher, MJ TI Solid bone matrix of rat femur imaged by water and fat suppressed proton magnetic resonance imaging. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Mirtech Inc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S223 EP S223 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503803012 ER PT J AU Wu, Y Ackerman, JL Graham, L Glimcher, MJ AF Wu, Y Ackerman, JL Graham, L Glimcher, MJ TI Hydroxyl ions in bone mineral observed by ID P-31-H-1 NMR spectroscopy. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S202 EP S203 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802231 ER PT J AU Yang, D Bouxsein, M Chiusaroli, R Schipani, E Pajevic, P Guo, J Singh, R Bringhurst, FR AF Yang, D Bouxsein, M Chiusaroli, R Schipani, E Pajevic, P Guo, J Singh, R Bringhurst, FR TI Signaling selective PTH (1-34) analogs accelerate bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S102 EP S102 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801118 ER PT J AU Yang, S Chen, W Li, Y AF Yang, S Chen, W Li, Y TI Gain and loss function study reveals that RGS10 expressed predominately in osteoclast is a critical mediator in [Ca2+]i ocillations and osteoclast differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2005 VL 20 IS 9 SU 1 BP S374 EP S374 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805024 ER PT J AU Lenzi, R Baile, WF Berek, J Back, A Buckman, R Cohen, L Parker, PA AF Lenzi, R Baile, WF Berek, J Back, A Buckman, R Cohen, L Parker, PA TI Design, conduct and evaluation of a communication course for oncology fellows SO JOURNAL OF CANCER EDUCATION LA English DT Article ID CANCER-PATIENTS; BAD-NEWS; SKILLS; PHYSICIAN; CARE; WORKSHOPS; CLINICIAN; MEDICINE; IMPACT; KEY AB Background. Training in the communication components of cancer care is necessary for the practice of oncology. We conducted a communication course for oncology fellows. Methods. Teaching methods included lectures, role playing and simulated patient interviews. We used self-reports, knowledge questionnaires and course/faculty evaluations. Results. A total of 17 fellows participated. Skills in dealing with bad news, denial and end-of-life issues improved. We obtained information on communication tasks commonly performed during patient interactions, various aspects of the course and faculty performance. Conclusions. Fellows' knowledge and self-efficacy improved postcourse. Information on challenges faced by trainees and their feedback may help focus the design of future courses. C1 Univ Texas, MD Anderson Canc Ctr, Dept GI Med Oncol, Unit 426, Houston, TX 77030 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Washington, Fred Hutchinson Canc Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. RP Lenzi, R (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept GI Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM rlenzi@mdanderson.org NR 29 TC 24 Z9 24 U1 3 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD FAL PY 2005 VL 20 IS 3 BP 143 EP 149 DI 10.1207/s15430154jce2003_7 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 961TN UT WOS:000231684800004 PM 16122361 ER PT J AU Keane, D Reddy, V Ruskin, J AF Keane, D Reddy, V Ruskin, J CA BAFS 2005 Fac TI Emerging concepts on catheter ablation of atrial fibrillation from the tenth annual Boston Atrial Fibrillation Symposium SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article C1 St James Hosp, Cardiac Arrhythmia Serv, Dublin 8, Ireland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Keane, D (reprint author), St James Hosp, Cardiac Arrhythmia Serv, Dublin 8, Ireland. EM dkeane@stjames.ie NR 0 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2005 VL 16 IS 9 BP 1025 EP 1028 DI 10.1111/j.1540-8167.2005.00270.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 959HI UT WOS:000231508400019 PM 16174029 ER PT J AU Chen, TC AF Chen, TC TI Brimonidine 0.15% versus apraclonidine 0.5% for prevention of intraocular pressure elevation after anterior segment laser surgery SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID PARA-AMINOCLONIDINE HYDROCHLORIDE; POSTERIOR CAPSULOTOMY; NEODYMIUM-YAG; ARGON; TRABECULOPLASTY; RISE; IRIDOTOMY; 1-PERCENT; EFFICACY; GLAUCOMA AB PURPOSE: To compare the efficacy and safety of brimonidine 0.15% with those of apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. SETTING: Massachusetts Eye and Ear Infirmary, Glaucoma Service, Boston, Massachusetts, USA. METHODS: This double-masked randomized trial 80 eyes of 80 patients who had laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:YAG laser capsulotomy. Eyes received 1 drop of brimonidine 0.15% or apraclonidine 0.5% before laser surgery. Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before laser treatment, 41 patients received brimonidine 0.15% and 39 received apraclonidine 0.5%. Thirteen (31.7%) patients in the brimonidine group and 11 (28.2%) in the apraclonidine group had postoperative IOP elevations of 5 mm Hg or more (P = .5). Four patients (9.8%) in the brimonidine group and 3 (7.7%) in the apraclonidine group had IOP increases of 10 mm Hg or more (P = .5). There were no statistically significant changes in mean heart rate or blood pressure in either group except a slight reduction in diastolic blood pressure at 1 hour in the brimonidine group (-4.7 +/- 9.2 mm Hg) compared with that in the apraclonidine group (-0.1 +/- 9.1 mm Hg) (P = .01). No clinically significant side effects were noted in either group. CONCLUSION: A single preoperative drop of brimonidine 0.15% had similar efficacy and safety as apraclonidine 0.5% in preventing IOP elevations immediately after anterior segment laser surgery. C1 Harvard Univ, Glaucoma Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Glaucoma Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu NR 40 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2005 VL 31 IS 9 BP 1707 EP 1712 DI 10.1016/j.jcrs.2005.02.035 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 982TH UT WOS:000233184000021 PM 16246772 ER PT J AU Zhao, WD Wu, Y Zhao, JB Guo, S Bauman, WA Cardozo, CP AF Zhao, WD Wu, Y Zhao, JB Guo, S Bauman, WA Cardozo, CP TI Structure and function of the upstream promotor of the human MAFbx gene: The proximal upstream promotor modulates tissue-specificity SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE muscle atrophy; ubiquitin ligase; promotor structure; developmental regulation ID SKELETAL-MUSCLE ATROPHY; FOXO TRANSCRIPTION FACTORS; UBIQUITIN LIGASES; RECEPTOR GENE; EXPRESSION; DIFFERENTIATION; DEGRADATION; DENERVATION; ATROGIN-1; PROTEINS AB Muscle loss has been linked to increased expression of an ubiquitin ligase termed muscle atrophy F-box (MAFbx), a nuclear protein involved in degradation of MyoD. To gain insights into mechanisms by which the human MAFbx gene is controlled, the structure of its upstream promotor were studied, and its expression in cultured cells was characterized. Expression of MAFbx was found only in cells of muscle lineage. A reporter gene controlled by 948 bases of human MAFbx upstream promotor displayed similar cell-type selectivity. MAFbx levels were greatly enhanced upon myogenic differentiation of C2C12 myoblasts, and differentiation markedly increased activity of a reporter gene constructed with 400 bp of upstream promotor from the MAFbx gene. The core promotor spanned approximately 160 bases beginning at -241 bp upstream of the first codon, included potential binding sites for MyoD and myogenin, and was highly conserved among mouse, rat, and humanMAFbx genes. The major transcription start site for the human MAFbx gene was 340 bases upstream of the ATG and was localized the highly conserved region of 140 bp. The findings indicate an important role for the immediate upstream promotor of the human MAFbxgene in mediating its developmental expression and tissue specificity. C1 Bronx Vet Adm Med Ctr, SCDRC, VA Rehabil Res & Dev Serv, Ctr Excellence, Bronx, NY 10468 USA. Mt Sinai Sch Med, Spinal Cord Damage Res Ctr, Dept Med, New York, NY USA. RP Cardozo, CP (reprint author), Bronx Vet Adm Med Ctr, SCDRC, VA Rehabil Res & Dev Serv, Ctr Excellence, Room 1E-02, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU NIDDK NIH HHS [DK 60598] NR 30 TC 13 Z9 14 U1 0 U2 5 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 SEP 1 PY 2005 VL 96 IS 1 BP 209 EP 219 DI 10.1002/jcb.20468 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 962NM UT WOS:000231739500021 PM 16052482 ER PT J AU Kishi, N Macklis, JD AF Kishi, N Macklis, JD TI Dissecting MECP2 function in the central nervous system SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Child-Neurology-Society CY OCT 13-16, 2004 CL Toronto, CANADA SP Child Neurol Soc ID CPG-BINDING PROTEIN-2; RETT-SYNDROME; DNA METHYLATION; TRANSCRIPTIONAL REPRESSOR; NEURONAL MATURATION; SODIUM-CHANNEL; RAT-BRAIN; EXPRESSION; MICE; CHROMATIN AB Rett syndrome is a neurodevelopmental disorder and an important cause of mental retardation and autistic behavior in girls and in a small group of boys. In 1999, mutation of the methyl-CpG binding protein 2 (MECP2) gene encoding a transcriptional repressor on the X chromosome was found to cause Rett syndrome. Since this discovery, significant research has focused on the elucidation of its specific role in the central nervous system. Recent studies revealed that MECP2 is expressed in more differentiated neurons rather than in less differentiated neuroblasts and that MECP2 is involved in the maturation and maintenance of neurons, including dendritic arborization and axonal projections, rather than in early cell fate decisions in the mammalian brain. In this review, we summarize recent findings regarding regional, temporal, and cell type-specific MECP2 expression in the central nervous system; neurobiologic abnormalities in MECP2-mutant mice; and MECP2 target genes in the central nervous system. C1 Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Nervous Syst Repair,Sch Med,Dept Neurosurg,Pr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Nervous Syst Repair,Sch Med,Dept Neurol,Progr, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Nervous Syst Repair,Sch Med,Dept Neurosurg,Pr, Edwards 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu RI Kishi, Noriyuki/L-1379-2013 FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41590, NS45523, NS49553] NR 56 TC 16 Z9 16 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2005 VL 20 IS 9 BP 753 EP 759 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 968UO UT WOS:000232188200009 PM 16225831 ER PT J AU Misra, M Miller, KK Stewart, V Hunter, E Kuo, K Herzog, DB Klibanski, A AF Misra, M Miller, KK Stewart, V Hunter, E Kuo, K Herzog, DB Klibanski, A TI Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE SECRETAGOGUE RECEPTOR; GH-RELEASING HORMONE; GROWTH-HORMONE; SECRETORY DYNAMICS; DENSITY; ACQUISITION; PREDICTORS; PEPTIDE; HUMANS; LEPTIN AB Context: Anorexia nervosa ( AN) in adolescents is associated with low bone mineral density (BMD) and increases in ghrelin secretion, an orexigenic GH secretagogue that stimulates osteoblast proliferation in vitro. Objective: We hypothesized that ghrelin may have independent effects on bone in AN adolescents. Study Design, Subjects, and Outcome Measures: Frequent sampling was performed overnight every 30 min for 12 h in 23 adolescent AN girls aged 12 - 18 yr and 21 controls of comparable maturity. Ghrelin, leptin, cortisol, and GH secretion were examined using Cluster and deconvolution. We measured BMD and body composition (dual-energy x-ray absorptiometry) and carboxy-terminal peptide of type I procollagen and N-telopeptide levels. Results: In healthy adolescents, ghrelin secretion strongly predicted BMD; secretory burst mass being the strongest predictor of lumbar spine (LS) bone mineral apparent density (BMAD) (r = 0.66, P = 0.003), LS BMAD z-scores (BMAD- z) (r = 0.59, P = 0.01), hip BMD (r = 0.55, P = 0.02), and hip BMD-z (r = 0.52, P = 0.03). When body composition measures ( body mass index, lean and fat mass), and hormonal predictors (GH, IGF-I, cortisol, leptin, and estradiol) were entered into a regression model with ghrelin secretion to determine independent BMD predictors, ghrelin was the strongest predictor of LS BMAD, BMAD- z, hip BMD, and hip BMD-z, contributing to 43, 30, 26, and 19% of the variability, respectively, independent of GH or cortisol effects. Conversely, in AN, ghrelin secretion did not predict LS BMAD or hip-z and weakly predicted LS BMAD-z and hip BMD. Ghrelin did not predict carboxy-terminal peptide of type I procollagen or N-telopeptide/creatinine, which were predicted by GH and cortisol. Conclusion: Ghrelin secretion predicts bone density independent of body composition, the GH-IGF-I axis, cortisol, or estradiol in healthy girls but not in those with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org NR 31 TC 78 Z9 81 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2005 VL 90 IS 9 BP 5082 EP 5087 DI 10.1210/jc.2005-0512 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200013 PM 15998770 ER PT J AU Al-Jenaidi, FA Wakim-Ghorayeb, SF Al-Abbasi, A Arekat, MR Irani-Hakime, N Najm, P Al-Ola, K Motala, AA Almawi, WY AF Al-Jenaidi, FA Wakim-Ghorayeb, SF Al-Abbasi, A Arekat, MR Irani-Hakime, N Najm, P Al-Ola, K Motala, AA Almawi, WY TI Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HLA-CLASS-II; DISEASE INCIDENCE; MELLITUS; POPULATION; DQ; RISK; IDENTIFICATION; POLYMORPHISM; FREQUENCIES; RESISTANCE AB Context: Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility of type 1 diabetes (T1D), and both susceptible and protective alleles were implicated with its pathogenesis, which varies among various ethnic/racial groups. Objective: This study investigated the heterogeneity in HLA class II haplotypes distribution among Bahraini and Lebanese T1D patients. Design: This was a cross-sectional retrospective study. Setting: The study was conducted at primary care private and public health centers. Patients and Other Participants: Subjects comprised 126 T1D patients and 126 healthy controls from Bahrain and 78 Lebanese T1D patients and 111 control subjects. Intervention(s): There were no interventions. Results: Although Lebanese and Bahraini patients share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini patients, and DRB1*130701 and DQB1*050101 were additional susceptible and protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were protective haplotypes in Bahraini and Lebanese. DRB1*040101DQB1* 0302 and DRB1*040101-DQB1*050101 displayed different associations: they were protective in Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of homozygous DRB1*03011-DQB1* 0201 was higher in Bahraini and to a lesser extent Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more frequent in Lebanese but not Bahraini controls, whereas DRB1*030101-DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients but not Lebanese subjects in whom it was present at very low frequencies. Conclusion: In view of these differences between Bahraini and Lebanese, this demonstrates that the contribution of HLA class II to the genetic susceptibility to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic origin and racial background. C1 Arabian Gulf Univ, Coll Med & Med Sci, Al Jawhara Coll Mol Med Genet & Inherited Dis, Manama, Bahrain. Arabian Gulf Univ, Dept Pediat, Manama, Bahrain. St Georges Univ Hosp, Beirut, Lebanon. Joslin Diabet Ctr, Manama, Bahrain. Univ Natal, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. RP Almawi, WY (reprint author), Arabian Gulf Univ, Coll Med & Med Sci, Al Jawhara Coll Mol Med Genet & Inherited Dis, POB 22979,Salmaniya Med Complex, Manama, Bahrain. EM wyalmawi@yahoo.co.uk NR 35 TC 26 Z9 27 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 SEP PY 2005 VL 90 IS 9 BP 5104 EP 5109 DI 10.1210/jc.2005-1166 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200016 PM 15985473 ER PT J AU Surks, MI Goswami, G Daniels, GH AF Surks, MI Goswami, G Daniels, GH TI The thyrotropin reference range should remain unchanged SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBCLINICAL THYROID-DISEASE; CARDIOVASCULAR RISK-FACTORS; FOLLOW-UP; STIMULATING-HORMONE; SERUM THYROTROPIN; LEVOTHYROXINE REPLACEMENT; ASSOCIATION GUIDELINES; BIOLOGICAL VARIATION; ATRIAL-FIBRILLATION; PLASMA THYROTROPIN AB Context: Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis. Study Subjects: The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease. Intervention: The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months. Results: About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine. Conclusion: Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr. C1 Montefiore Med Ctr, Div Endocrinol & Metab, Dept Med, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Surks, MI (reprint author), Montefiore Med Ctr, Div Endocrinol & Metab, Dept Med, 111 E 210th St, Bronx, NY 10467 USA. EM msurks@westnet.com NR 70 TC 144 Z9 151 U1 0 U2 4 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 SEP PY 2005 VL 90 IS 9 BP 5489 EP 5496 DI 10.1210/jc.2005-0170 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200078 PM 16148346 ER PT J AU O'Connell, JJ AF O'Connell, JJ TI Raging against the night: Dying homeless and alone SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID DEATH C1 Boston Hlth Care Homeless Program, Boston, MA USA. Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Connell, JJ (reprint author), Boston Hlth Care Homeless Program, Boston, MA USA. EM JOConnell@bhchp.org NR 4 TC 6 Z9 6 U1 0 U2 6 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2005 VL 16 IS 3 BP 262 EP 266 PG 5 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 006OT UT WOS:000234907500013 PM 16302552 ER PT J AU Rowan, PJ Al-Jurdi, R Tavakoli-Tabasi, S Kunik, ME Satrom, SL El-Serag, HB AF Rowan, PJ Al-Jurdi, R Tavakoli-Tabasi, S Kunik, ME Satrom, SL El-Serag, HB TI Physical and psychosocial contributors to quality of life in veterans with hepatitis C not on antiviral therapy SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatitis; chronic; quality of life; interview; psychological; depression; behavioral medicine ID CHRONIC LIVER-DISEASE; DEPRESSION; INFECTION; REDUCTION; HOSTILITY; SYMPTOMS; ANXIETY AB Background and Aims: Treatment-naive hepatitis C virus (HCV)infected patients report impaired health-related quality of life (HRQOL), although causes are unclear. Psychosocial factors may be major determinants of HRQOL. Methods: We administered a general (Short Form-36; SF-36) and a liver-specific (Chronic Liver Disease Questionnaire- CLDQ) HRQOL measure to 62 HCV-infected veterans being considered for antiviral therapy. Psychosocial assessment included the Structured Clinical Interview for DSM-IV Axis I Disorders/Non-Patient (SCI D-I/NP), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Abbreviated Cook-Medley (ACM) anger measure, and Medical Outcomes Study Social Support Measure (SSM). We examined the potential determinants of HRQOL, including psychosocial measures, demographic measures (age, sex, race/ethnicity), clinical measures (presence of cirrhosis, comorbid medical conditions), and viral data (quantitative PCR). Results: SF-36 scores were significantly lower in HCV-infected patients than published US. population norms but similar to those reported by previous studies of HCV-infected samples. CLDQ scores were very similar to those reported by previous studies. Demographic, clinical, and viral indicators were not statistically associated with HRQOL, and neither was the presence of a substance abuse or psychotic disorder. Lower BDI-II and BAI scores were associated with better general and disease-specific HRQOL. Lower SSM scores were associated with lower scores on SF-36 but not CLDQ; however, this effect did not persist in multiple linear regression analyses. In these, BDI-II was the strongest independent predictor of both SF-36 and CLDQ. Conclusions: Psychosocial factors, especially depression, are strong indicators of impaired HRQOL for HCV-infected veterans not receiving antiviral therapy. Screening and treatment of psychosocial factors is recommended. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Menminger Dept Psychiat & Behave Sci, Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Gastroenterol Sect, Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 23 TC 31 Z9 34 U1 2 U2 2 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 SEP PY 2005 VL 39 IS 8 BP 731 EP 736 DI 10.1097/01.mcg.0000173860.08478.a6 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 958ZR UT WOS:000231487200016 PM 16082286 ER PT J AU Gibbons, FK Israel, E Deykin, A Schaub, B He, HZ Perkins, DL Finn, PW AF Gibbons, FK Israel, E Deykin, A Schaub, B He, HZ Perkins, DL Finn, PW TI The combined effects of zafirlukast, prednisone, and inhaled budesonide on IL-13 and IFN-gamma secretion SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE asthma; cytokines; proliferation; allergen ID STEROID-RESISTANT ASTHMA; CYTOKINE GENE-EXPRESSION; ALLERGEN-SPECIFIC TH1; T-CELL-ACTIVATION; INTERFERON-GAMMA; PERIPHERAL-BLOOD; FLUTICASONE PROPIONATE; AIRWAY INFLAMMATION; LYMPHOCYTE-PROLIFERATION; ATOPIC-DERMATITIS AB Therapy for asthma often includes the combined use of glucocorticoids and leukotriene receptor antagonists. The short-term, combined effects of these drugs on cytokine secretion and lymphocyte proliferation are ill-defined. The aim of this study was to analyze allergen and mitogen-induced cytokine secretion and lymphocyte proliferation in asthmatics and to determine the effect of combined therapy on these immune responses. Peripheral blood mononuclear cells were isolated from mild, persistent adult asthmatics (n = 28) and analyzed for cat allergen (Fel d 1) and mitogen (phytohemagglutinin) induced IL-13 and IFN-gamma secretion and lymphocyte proliferation. Samples were analyzed before and after 10 days of therapy with oral zafirlukast, prednisone (0.5 mg/kg/day), and inhaled budesonide (1600 mcg/day). Both Fel d 1 and mitogen stimulation resulted in IL-13 and IFN-gamma secretion. Combination drug therapy resulted in a significant decrease in allergen-induced IFN-gamma secretion (p = 0.018) and allergen-specific lymphocyte proliferation (p = 0.02), while IL-13 secretion was unchanged (p = 0.109). This study indicates a role for Th1 cytokines as well as Th2 cytokines in the allergic response. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Pulm & Crit Care Div,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Pulm & Crit Care Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div,Lab Mol Immunol, Boston, MA 02115 USA. RP Gibbons, FK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Pulm & Crit Care Div,Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM fgibbons@partners.org FU NHLBI NIH HHS [5R01HL067684-02, 5U10HL051831]; NIAID NIH HHS [5R01AI045007-04] NR 41 TC 3 Z9 6 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2005 VL 25 IS 5 BP 437 EP 444 DI 10.1007/s10875-005-5625-6 PG 8 WC Immunology SC Immunology GA 964LO UT WOS:000231882800004 PM 16160912 ER PT J AU Potente, M Urbich, C Sasaki, K Hofmann, WK Heeschen, C Aicher, A Kollipara, R DePinho, RA Zeiher, AM Dimmeler, S AF Potente, M Urbich, C Sasaki, K Hofmann, WK Heeschen, C Aicher, A Kollipara, R DePinho, RA Zeiher, AM Dimmeler, S TI Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE B; ENDOTHELIAL-CELLS; GENE-REGULATION; GROWTH-FACTOR; FACTOR FKHR; IN-VIVO; APOPTOSIS; DIFFERENTIATION; SUPPRESSION AB Forkhead box O (Foxo) transcription factors are emerging as critical transcriptional integrators among pathways regulating differentiation, proliferation, and survival, yet the role of the distinct Foxo family members in angiogenic activity of endothelial cells and postnatal vessel formation has not been studied. Here, we show that Foxo1 and Foxo3a are the most abundant Foxo isoforms in mature endothelial cells and that overexpression of constitutively active Foxo1 or Foxo3a, but not Foxo4, significantly inhibits endothelial cell migration and tube formation in vitro. Silencing of either Foxo1 or Foxo3a gene expression led to a profound increase in the migratory and sprout-forming capacity of endothelial cells. Gene expression profiling showed that Foxo1 and Foxo3a specifically regulate a nonredundant but overlapping set of angiogenesis- and vascular remodeling-related genes. Whereas angiopoietin 2 (Ang2) was exclusively regulated by Foxo1, eNOS, which is essential for postnatal neovascularization, was regulated by Foxo1 and Foxo3a. Consistent with these findings, constitutively active Foxo1 and Foxo3a repressed eNOS protein expression and bound to the eNOS promoter. In vivo, Foxo3a deficiency increased eNOS expression and enhanced postnatal vessel formation and maturation. Thus, our data suggest an important role for Foxo transcription factors in the regulation of vessel formation in the adult. C1 Univ Frankfurt, Dept Internal Med 3, D-60590 Frankfurt, Germany. Free Univ Berlin, Dept Hematol & Oncol, D-1000 Berlin, Germany. 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 Dimmeler, S (reprint author), Univ Frankfurt, Dept Internal Med 3, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM Dimmeler@em.uni-frankfurt.de NR 43 TC 252 Z9 265 U1 1 U2 4 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 SEP PY 2005 VL 115 IS 9 BP 2382 EP 2392 DI 10.1172/JCI23126 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500015 PM 16100571 ER PT J AU Miao, DS He, B Jiang, YB Kobayashi, T Soroceanu, MA Zhao, J Su, HY Tong, XK Amizuka, N Gupta, A Genant, HK Kronenberg, HM Goltzman, D Karaplis, AC AF Miao, DS He, B Jiang, YB Kobayashi, T Soroceanu, MA Zhao, J Su, HY Tong, XK Amizuka, N Gupta, A Genant, HK Kronenberg, HM Goltzman, D Karaplis, AC TI Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; GROWTH-FACTOR; POSTMENOPAUSAL OSTEOPOROSIS; BLOMSTRAND-CHONDRODYSPLASIA; FACTOR RECEPTOR; CANCER CELLS; NULL MICE; PROTEIN; EXPRESSION AB Mice heterozygous for targeted disruption of Pthrp exhibit, by 3 months of age, diminished bone volume and skeletal microarchitectural changes indicative of advanced osteoporosis. Impaired bone formation arising from decreased BM precursor cell recruitment and increased apoptotic death of osteoblastic cells was identified as the underlying mechanism for low bone mass. The osteoporotic phenotype was recapitulated in mice with osteoblast-specific targeted disruption of Pthrp, generated using Cre-LoxP technology, and defective bone formation was reaffirmed as the underlying etiology. Daily administration of the 1-34 amino-terminal fragment of parathyroid hormone (PTH 1-34) to Pthrp(+/-) mice resulted in profound improvement in all parameters of skeletal microarchitecture, surpassing the improvement observed in treated WT littermates. These findings establish a pivotal role for osteoblast-derived PTH-related protein (PTHrP) as a potent endogenous bone anabolic factor that potentiates bone formation by altering osteoblast recruitment and survival and whose level of expression in the bone microenvironment influences the therapeutic efficacy of exogenous PTH 1-34. C1 McGill Univ, Dept Med, Sir Mortimer B Davis Jewish Hosp, Div Endocrinol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Lady Davis Inst Med Res, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Ctr Hlth, Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3T 1E2, Canada. McGill Univ, Ctr Hlth, Royal Victoria Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada. Univ Calif San Francisco, Osteoporosis & Arthritis Res Grp, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Niigata Univ, Grad Sch Med & Dent Sci, Dept Oral Biol Sci, Div Oral Anat, Niigata, Japan. Osta Biotechnol Inc, Montreal, PQ, Canada. RP Karaplis, AC (reprint author), McGill Univ, Dept Med, Sir Mortimer B Davis Jewish Hosp, Div Endocrinol, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM akarapli@ldi.jgh.mcgill.ca FU NIAMS NIH HHS [AR044855, P50 AR044855] NR 48 TC 155 Z9 163 U1 0 U2 4 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 SEP PY 2005 VL 115 IS 9 BP 2402 EP 2411 DI 10.1172/JCI24918 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500017 PM 16138191 ER PT J AU Turvey, SE Swart, E Denis, MC Mahmood, U Benoist, C Weissleder, R Mathis, D AF Turvey, SE Swart, E Denis, MC Mahmood, U Benoist, C Weissleder, R Mathis, D TI Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VASCULAR-PERMEABILITY; T-CELLS; SELF-TOLERANCE; ANTIBODY; MICE; MELLITUS; MOUSE; INSULITIS; AUTOIMMUNITY; PATHOGENESIS AB A major stumbling block for research on and treatment of type 1 diabetes is the inability to directly, but noninvasively, visualize the lymphocytic/inflammatory lesions in the pancreatic islets. One potential approach to surmounting this impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes in the microvasculature that invariably accompany inflammation. MNP-MRI did indeed detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions in vivo in real time. We demonstrate, in proof-of-principle experiments, that this strategy allows one to predict, within 3 days of completing treatment with an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are responding to therapy and may eventually be cured. Importantly, an essentially identical MNP-MRI strategy has previously been used with great success to image lymph node metastases in prostate cancer patients. This success strongly argues for rapid translation of these preclinical observations to prediction and/or stratification of type 1 diabetes and treatment of individuals with the disease; this would provide a crucially needed early predictor of response to therapy. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM dm@joslin.harvard.edu FU NCI NIH HHS [R24 CA092782, R24 CA92782] NR 41 TC 53 Z9 59 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2005 VL 115 IS 9 BP 2454 EP 2461 DI 10.1172/JCI20548 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500022 PM 16110329 ER PT J AU Williams, K Westmoreland, S Greco, J Ratai, E Lentz, M Kim, WK Fuller, RA Kim, JP Autissier, P Sehgal, PK Schinazi, RF Bischofberger, N Piatak, M Lifson, JD Masliah, E Gonzalez, RG AF Williams, K Westmoreland, S Greco, J Ratai, E Lentz, M Kim, WK Fuller, RA Kim, JP Autissier, P Sehgal, PK Schinazi, RF Bischofberger, N Piatak, M Lifson, JD Masliah, E Gonzalez, RG TI Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; CD8(+) T-CELLS; PROTON MR SPECTROSCOPY; HIV-POSITIVE PATIENTS; CEREBROSPINAL-FLUID; ANTIRETROVIRAL THERAPY; BLOOD MONOCYTES; RHESUS MACAQUES AB Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used H-1 magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non-CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte-depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte-depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease. C1 Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Emory Univ, Sch Med, Vet Affairs Med Ctr, Lab Biochem Pharmacol,Dept Pediat, Atlanta, GA 30322 USA. Gilead Sci, Foster City, CA 94404 USA. Sci Applicat Int Corp Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD USA. UCSD, Dept Neurosci, La Jolla, CA USA. RP Williams, K (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, RE113,330 Brookline Ave, Boston, MA 02215 USA. EM rggonzalez@partners.org RI Schinazi, Raymond/B-6777-2017 FU NCRR NIH HHS [RR00168, K01 RR000150, K26 RR000168, P41 RR014075, P51 RR000168, R24 RR016001, RR000150, RR13214, RR14075, RR16001]; NIAID NIH HHS [2P30-AI-50409, P30 AI050409]; NIMH NIH HHS [P50 MH045294]; NINDS NIH HHS [NS0050041, NS34626, NS40237, R01 NS034626, R01 NS040237, R01 NS050041] NR 90 TC 86 Z9 88 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 SEP PY 2005 VL 115 IS 9 BP 2534 EP 2545 DI 10.1172/JCI22953 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500031 PM 16110325 ER PT J AU Puglielli, L Friedlich, AL Setchell, KDR Nagano, S Opazo, C Cherny, RA Barnham, KJ Wade, JD Melov, S Kovacs, DM Bush, AI AF Puglielli, L Friedlich, AL Setchell, KDR Nagano, S Opazo, C Cherny, RA Barnham, KJ Wade, JD Melov, S Kovacs, DM Bush, AI TI Alzheimer disease beta-amyloid activity mimics cholesterol oxidase SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; A-BETA; LIPID-PEROXIDATION; PRECURSOR PROTEIN; TRANSGENIC MICE; CEREBROTENDINOUS XANTHOMATOSIS; MOUSE MODEL; STEREOCHEMICAL PROBLEMS; HYDROGEN-PEROXIDE; MASS SPECTROMETRY AB The abnormal accumulation of amyloid beta-peptide (A beta) in the form of senile (or amyloid) plaques is one of the main characteristics of Alzheimer disease (AD). Both cholesterol and Cu2+ have been implicated in AD pathogenesis and plaque formation. A beta binds Cu2+ with very high affinity, forming a redox-active complex that catalyzes H2O2 production from O-2 and cholesterol. Here we show that A beta:Cu2+ complexes oxidize cholesterol selectively at the C-3 hydroxyl group, catalytically producing 4-cholesten-3-one and therefore mimicking the activity of cholesterol oxidase, which is implicated in cardiovascular disease. A beta toxicity in neuronal cultures correlated with this activity, which was inhibited by Cu2+ chelators including clioquinol. Cell death induced by staurosporine or H2O2 did not elevate 4-cholesten-3-one levels. Brain tissue from AD subjects had 98% more 4-cholesten-3-one than tissue from age-matched control subjects. We observed a similar increase in the brains of Tg2576 transgenic mice compared with nontransgenic littermates; the increase was inhibited by in vivo treatment with clioquinol, which suggests that brain A beta accumulation elevates 4-cholesten-3-one levels in AD. Cu2+-mediated oxidation of cholesterol may be a pathogenic mechanism common to atherosclerosis and AD. C1 Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Howard Florey Inst Med Res, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA USA. Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Pathol, Cincinnati, OH USA. Buck Inst Age Res, Novato, CA USA. RP Bush, AI (reprint author), Univ Melbourne, Mental Hlth Res Inst Victoria, 155 Oak St, Parkville, Vic 3052, Australia. EM bush@helix.mgh.harvard.edu FU NIA NIH HHS [AG18679, AG12686, R01 AG012686, R01 AG018679]; NIMH NIH HHS [R24 MH068855, R24MH68855]; NINDS NIH HHS [F32 NS010874, F32NS10874] NR 65 TC 93 Z9 99 U1 0 U2 2 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 SEP PY 2005 VL 115 IS 9 BP 2556 EP 2563 DI 10.1172/JCI23610 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500033 PM 16127459 ER PT J AU Hamilton, GA Carroll, DL AF Hamilton, GA Carroll, DL TI To Draper P (2005) commentary on Hamilton G et al. (2004) - Response SO JOURNAL OF CLINICAL NURSING LA English DT Editorial Material ID QUALITY-OF-LIFE C1 Massachusetts Gen Hosp, Boston, MA USA. EM glenys@mac.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1067 J9 J CLIN NURS JI J. Clin. Nurs. PD SEP PY 2005 VL 14 IS 8 BP 1017 EP 1018 DI 10.1111/j.1365-2702.2005.00983.x PG 2 WC Nursing SC Nursing GA 952GW UT WOS:000230993000016 PM 16102156 ER PT J AU Krop, IE Winer, EP AF Krop, IE Winer, EP TI Ovarian suppression for breast cancer: An effective treatment in search of a home SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; PREMENOPAUSAL PATIENTS; TAMOXIFEN; THERAPY; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; WOMEN; EXPRESSION C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Krop, IE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 27 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 SEP 1 PY 2005 VL 23 IS 25 BP 5869 EP 5872 DI 10.1200/JCO.2005.06.002 PG 4 WC Oncology SC Oncology GA 960PT UT WOS:000231606300006 PM 16087947 ER PT J AU Herbst, RS Prager, D Hermann, R Fehrenbacher, L Johnson, BE Sandler, A Kris, MG Tran, HT Klein, P Li, X Ramies, D Johnson, DH Miller, VA AF Herbst, RS Prager, D Hermann, R Fehrenbacher, L Johnson, BE Sandler, A Kris, MG Tran, HT Klein, P Li, X Ramies, D Johnson, DH Miller, VA TI TRIBUTE: A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; GEFITINIB; INHIBITOR; MUTATIONS; COMBINATION; SMOKERS; TUMORS AB Purpose Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non-small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC. Patients and Methods TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response. Results There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P =.95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea). Conclusion Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Kaiser Permanente, Oakland, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Georgia Oncol Partners, Marietta, GA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Ingram Canc Ctr, Nashville, TN USA. RP Miller, VA (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM millerv@MSKCC.ORG RI Johnson, David/A-7437-2009; Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Kris, Mark/0000-0002-7317-5341 NR 22 TC 960 Z9 1009 U1 1 U2 25 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 SEP 1 PY 2005 VL 23 IS 25 BP 5892 EP 5899 DI 10.1200/JCO.2005.02.840 PG 8 WC Oncology SC Oncology GA 960PT UT WOS:000231606300012 PM 16043829 ER PT J AU Eberhard, DA Johnson, BE Amler, LC Goddard, AD Heldens, SL Herbst, RS Ince, WL Janne, PA Januario, T Johnson, DH Klein, P Miller, VA Ostland, MA Ramies, DA Sebisanovic, D Stinson, JA Zhang, YR Seshagiri, S Hillan, KJ AF Eberhard, DA Johnson, BE Amler, LC Goddard, AD Heldens, SL Herbst, RS Ince, WL Janne, PA Januario, T Johnson, DH Klein, P Miller, VA Ostland, MA Ramies, DA Sebisanovic, D Stinson, JA Zhang, YR Seshagiri, S Hillan, KJ TI Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT American-Association-for-Cancer-Research Conference on Molecular Targets and Cancer Therapeutics CY SEP 30, 2004 CL Geneva, SWITZERLAND SP Amer Assoc Canc Res ID K-RAS MUTATIONS; ADJUVANT THERAPY; GENE-MUTATIONS; TUMOR-CELLS; GEFITINIB; EGFR; ADENOCARCINOMA; TRIAL; SENSITIVITY; SURVIVAL AB Purpose Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung Cancer (NSCLC). The implications of EGFR mutations in patients treated with EGFR inhibitors, plus first-line chemotherapy are unknown. KRAS is frequently activated in NSCLC. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described. Patients and Methods Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival, response, and time to progression (TTP). EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients. Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses. Results EGFR mutations were detected in 13% of tumors and were associated with longer survival, irrespective of treatment (P <.001). Among erlotinib-treated patients, EGFR mutations were associated with improved response rate (P <.05) and there was a trend toward an erlotinib benefit on TTP (P =.092) but not improved survival (P =.96). KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients. Conclusion EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib, and may predict greater likelihood of response. Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy. Further studies are needed to confirm the findings of this retrospective subset analysis. C1 Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA. Genentech Inc, Dept Mol Diagnost, San Francisco, CA 94080 USA. Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. Genentech Inc, Dept Biostat & BioOncol, San Francisco, CA 94080 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. RP Hillan, KJ (reprint author), Genentech Inc, Dept Pathol, 1 DNA Way, San Francisco, CA 94080 USA. EM kjh@gene.com RI Johnson, David/A-7437-2009 NR 31 TC 974 Z9 1020 U1 2 U2 30 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 SEP 1 PY 2005 VL 23 IS 25 BP 5900 EP 5909 DI 10.1200/JCO.2005.02.857 PG 10 WC Oncology SC Oncology GA 960PT UT WOS:000231606300013 PM 16043828 ER PT J AU Davidson, NE O'Neill, AM Vukov, AM Osborne, CK Martino, S White, DR Abeloff, MD AF Davidson, NE O'Neill, AM Vukov, AM Osborne, CK Martino, S White, DR Abeloff, MD TI Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: Results from INT 0101 (E5188) 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 SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; RANDOMIZED-TRIALS; OVARIAN ABLATION; TAMOXIFEN; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; SUPPRESSION AB Purpose Chemotherapy, tamoxifen, and ovarian ablation/suppression (OA/OS) are effective adjuvant approaches for premenopausal, steroid hormone receptor-positive breast cancer. The value of combined therapy has not been clearly established. Patients and Methods Premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer (1,503 eligible patients) were randomly assigned to six cycles of cyclophosphamide, doxorubicin, and fluorouracil (CAF), CAF followed by 5 years of monthly goserelin (CAF-Z), or CAF followed by 5 years of monthly goserelin and daily tamoxifen (CAF-ZT). The primary end points were time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) for CAF-Z versus CAF, and CAF-ZT versus CAF-Z. Results With a median follow-up of 9.6 years, the addition of tamoxifen to CAF-Z improved TTR and DFS but not OS. There was no overall advantage for addition of goserelin to CAF. Conclusion Addition of tamoxifen to CAF-Z improves outcome for premenopausal node-positive, receptor-positive breast cancer. The role of OA/OS alone or with other endocrine agents should be studied more intensely. C1 Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Oncol Hematol Assoc Cent Illinois, Peoria, IL USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. John Wayne Canc Inst, Santa Monica, CA USA. Wake Forest Univ, Med Ctr, Winston Salem, NC 27109 USA. RP Davidson, NE (reprint author), Johns Hopkins Univ, Sidney Kimmel Canc Ctr, 1650 Orleans St,Room 409, Baltimore, MD 21231 USA. EM davidna@jhmi.edu FU NCI NIH HHS [CA21115, CA16116, CA38926, CA13650, CA66636, CA23318, CA32102, CA03927] NR 33 TC 132 Z9 141 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 SEP 1 PY 2005 VL 23 IS 25 BP 5973 EP 5982 DI 10.1200/JCO.2005.05.551 PG 10 WC Oncology SC Oncology GA 960PT UT WOS:000231606300021 PM 16087950 ER PT J AU Hamilton, AL Eder, JP Pavlick, AC Clark, JW Liebes, L Garcia-Carbonero, R Chachoua, A Ryan, DP Soma, V Farrell, K Kinchla, N Boyden, J Yee, H Zeleniuch-Jacquotte, A Wright, J Elliott, P Adams, J Muggia, FM AF Hamilton, AL Eder, JP Pavlick, AC Clark, JW Liebes, L Garcia-Carbonero, R Chachoua, A Ryan, DP Soma, V Farrell, K Kinchla, N Boyden, J Yee, H Zeleniuch-Jacquotte, A Wright, J Elliott, P Adams, J Muggia, FM TI Proteasome inhibition with bortezomib (PS-341): A phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER-THERAPY; P53 FUNCTION; MALIGNANCIES; APOPTOSIS; TRIAL; PHOSPHORYLATION; ASSOCIATION; DEGRADATION; ARREST; AGENTS AB Purpose We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. Patients and Methods Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m(2) on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. Results On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m(2) dose levels, most commonly in patients receiving individual total doses >= 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m(2); 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. Conclusion Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m(2)), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea. C1 NYU, Med Ctr, Sch Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Muggia, FM (reprint author), NYU, Med Ctr, Sch Med, 550 1St Ave, New York, NY 10016 USA. EM muggif01@gcrc.med.nyu.edu OI Muggia, Franco/0000-0003-0703-9146; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [P30 CA16087, U01 CA76642]; NCRR NIH HHS [M01 RR00096]; PHS HHS [U01 62490] NR 30 TC 69 Z9 69 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2005 VL 23 IS 25 BP 6107 EP 6116 DI 10.1200/JCO.2005.01.136 PG 10 WC Oncology SC Oncology GA 960PT UT WOS:000231606300035 PM 16135477 ER PT J AU Nahas, Z Marangell, LB Husain, MM Rush, AJ Sackeim, HA Lisanby, SH Martinez, JM George, MS AF Nahas, Z Marangell, LB Husain, MM Rush, AJ Sackeim, HA Lisanby, SH Martinez, JM George, MS TI Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 08-12, 2002 CL SAN JUAN, PR SP Amer Coll Neuropsychopharmacol ID RATING-SCALE; ELECTROCONVULSIVE-THERAPY; EFFICACY AB Background: Vagus nerve stimulation (VNS) had antidepressant effects in an initial open, acute phase pilot study of 59 participants in a treatment-resistant major depressive episode (MDE). We examined the effects of adjunctive VNS over 24 months in this cohort. Method: Adult outpatients (N = 59) with chronic or recurrent major depressive disorder or bipolar (1 or 11) disorder and experiencing a treatment-resistant, nonpsychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months. Response was defined as >= 50% reduction from the baseline 28-item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined as a HAM-D-28 score <= 10. Results: Based on last observation carried forward analyses, HAM-D-28 response rates were 31% (18/59) after 3 months, 44% (26/59) after 1 year, and 42% (25/59) after 2 years of adjunctive VNS. Remission rates were 15% (9/59) at 3 months, 27% (16/59) at 1 year, and 22% (13/59) at 2 years. By 2 years, 2 deaths (unrelated to VNS) had occurred, 4 participants had withdrawn from the study, and 81% (48/59) were still receiving VNS. Longer-term VNS was generally well tolerated. Conclusion: These results suggest that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS. C1 Med Univ S Carolina, Brain Simulat Lab, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Dept Psychiat, Charleston, SC USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. New York State Psychiat Inst & Hosp, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. RP Nahas, Z (reprint author), Inst Psychiat, Brain Stimulat Lab, 67 President St,Room 502 N, Charleston, SC 29403 USA. EM nahasz@musc.edu OI Rush, Augustus/0000-0003-2004-2382 NR 19 TC 162 Z9 165 U1 2 U2 5 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 SEP PY 2005 VL 66 IS 9 BP 1097 EP 1104 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 967TX UT WOS:000232115200002 PM 16187765 ER PT J AU Simon, NM Pollack, MH Fischmann, D Perlman, CA Muriel, AC Moore, CW Nierenberg, AA Shear, MK AF Simon, NM Pollack, MH Fischmann, D Perlman, CA Muriel, AC Moore, CW Nierenberg, AA Shear, MK TI Complicated grief and its correlates in patients with bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; PANIC-AGORAPHOBIC SPECTRUM; TRAUMATIC GRIEF; DIAGNOSTIC-CRITERIA; STEP-BD; CLINICAL-SIGNIFICANCE; SUICIDAL IDEATION; SEVERITY SCALE; RELIABILITY; SYMPTOMS AB Background: While the recent loss of a loved one has been identified as a risk factor for suicide in patients with bipolar disorder, and complicated grief (CG) has been associated with elevated rates of suicidality compared with loss without CG, little is known about the frequency or impact of CG in bipolar disorder. We investigated the frequency and implications of loss of loved ones in an ongoing study of bipolar disorder. Method: We conducted a survey of 120 patients with well-characterized DSM-IV bipolar disorder participating in Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a large naturalistic study, in order to identify frequency of loss and to examine the presence of CG and its clinical correlates. Survey data were gathered from October 2003 to March 2004. Results: A lifetime history of a significant loss was reported by 86% (103/120) of participants; 24.3% (25/103) of those met criteria for CG, defined as a score 25 on the Inventory of Complicated Grief (ICG), with a mean +/- SD ICG score of 33.7 +/- 6.9. The presence of CG was associated with elevated rates of panic disorder and alcohol abuse comorbidity, as well as other measures of panic symptoms and phobic avoidance. CG was also associated with a higher rate of lifetime suicide attempts, greater functional impairment, and poorer social support. Conclusion: Our findings suggest the presence of a substantial burden of comorbid grief-related illness and impairment in patients with bipolar disorder. Further research is needed to understand the overlap of anxiety disorders and phobic avoidance in bipolar patients with complicated grief. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org FU NIMH NIH HHS [MH01831-01] NR 29 TC 39 Z9 39 U1 4 U2 6 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 SEP PY 2005 VL 66 IS 9 BP 1105 EP 1110 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 967TX UT WOS:000232115200003 PM 16187766 ER PT J AU Henderson, DC Nguyen, DD Copeland, PM Hayden, DL Borba, CP Louie, PM Freudenreich, O Evins, AE Cather, C Goff, DC AF Henderson, DC Nguyen, DD Copeland, PM Hayden, DL Borba, CP Louie, PM Freudenreich, O Evins, AE Cather, C Goff, DC TI Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: Results of a 10-year naturalistic study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CORONARY HEART-DISEASE; INDUCED WEIGHT-GAIN; ANTIPSYCHOTIC TREATMENT; INSULIN-RESISTANCE; SMOKING-CESSATION; SERUM-CHOLESTEROL; UNITED-STATES; SCHIZOPHRENIA; ABNORMALITIES; OBESITY AB Objective: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease. Method: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals. Results: At the time of clozapine initiation, the mean +/- SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p =.09; OR = 11.3, p =.04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p <.01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p =.027) and African American (OR = 11.5, p =.0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p =.0006), total cholesterol level (OR = 1.006, p =.04), and serum triglyceride level (OR = 1.002, p =.04) modestly increased the odds ratio for the development of diabetes mellitus. Conclusions: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org NR 30 TC 113 Z9 116 U1 2 U2 9 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 SEP PY 2005 VL 66 IS 9 BP 1116 EP 1121 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 967TX UT WOS:000232115200005 PM 16187768 ER PT J AU Evins, AE Deckersbach, T Cather, C Freudenreich, O Culhane, MA Henderson, DC Green, MF Schoenfeld, DA Rigotti, NA Goff, DC AF Evins, AE Deckersbach, T Cather, C Freudenreich, O Culhane, MA Henderson, DC Green, MF Schoenfeld, DA Rigotti, NA Goff, DC TI Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; SMOKING-CESSATION; CIGARETTE-SMOKING; SUBCUTANEOUS NICOTINE; PSYCHIATRIC-SYMPTOMS; SUSTAINED-RELEASE; RATING-SCALE; DOUBLE-BLIND; ATTENTION AB Objective: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment oil cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. Method: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. Results: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. Conclusion: We conclude that I week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Treatment Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 69 TC 35 Z9 36 U1 2 U2 4 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 SEP PY 2005 VL 66 IS 9 BP 1184 EP 1190 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 967TX UT WOS:000232115200015 PM 16187778 ER PT J AU Cook, JM Coyne, JC AF Cook, JM Coyne, JC TI Re-envisioning the training and practice of clinical psychologists: Preserving science and research orientations in the face of change SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE boulder model; postdoctoral training ID CONSORT STATEMENT; TRIALS; MODEL; CARE AB We argue for preservation of an expectation of psychologists that approach human problems from an evidence-based perspective. Acquisition of the requisite knowledge, skills, and practical experience require access to resources outside of graduate psychology programs. Whether adhering to a scientist-practitioner or practitioner-scholar model, psychologists must be "scientifically literate." Deficiencies are noted in the training of scientist-practitioner psychologists for the conduct of clinical trials and the dissemination and sustained implementation of evidence-based interventions. (c) 2005 Wiley Periodicals, Inc. C1 Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Cook, JM (reprint author), Columbia Univ, State Psychiat Inst, 1051 Riverside Dr,Box 69, New York, NY 10032 USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2005 VL 61 IS 9 BP 1191 EP 1196 DI 10.1002/jclp.20163 PG 6 WC Psychology, Clinical SC Psychology GA 961EI UT WOS:000231644300029 PM 15965946 ER PT J AU Kim, YH Saini, S Blake, MA Harisinghani, M Chiou, YY Lee, WJ Yu, JS Hahn, PF AF Kim, YH Saini, S Blake, MA Harisinghani, M Chiou, YY Lee, WJ Yu, JS Hahn, PF TI Distinguishing hepatic metastases from hemangiomas - Qualitative and quantitative diagnostic performance through dual echo respiratory-triggered fast spin echo magnetic resonance imaging SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE liver; magnetic resonance; liver neoplasms; magnetic resonance; technology ID FOCAL LIVER-LESIONS; OPERATING CHARACTERISTIC CURVES; T2-WEIGHTED FAST; PULSE SEQUENCES; FAT-SUPPRESSION; UPPER ABDOMEN; DIFFERENTIATION; T2; TUMORS; AREAS AB Objective: To determine the relative value of qualitative (reader opinion) and quantitative (values derived from dual echo T2 fast spin echo [FSE]) measures in distinguishing hepatic metastases from hemangiomas. Methods: Forty-nine patients with hemangiomas and 23 with metastases were studied with dual echo respiratory-triggered FSE and dynamic 2-dimensional spoiled gradient echo (GRE) imaging. Lesion T2 was estimated from signal intensity ratios on the first and second echoes. Two experienced radiologists independently evaluated groups of images based on 5 separate qualitative measures: first echo FSE, second echo FSE, first and second echo FSE, dynamic GRE, and all images together. Results: The mean calculated T2s were 226 +/- 74 milliseconds for hemangiomas and 105 +/- 22 milliseconds for metastases (P < 0.001). A T2 cutoff of 130 milliseconds distinguished metastases from hemangiomas with a sensitivity of 94%, specificity of 91%, and accuracy of nearly 94%. There was no significant difference between the best quantitative measure and the best qualitative measure for either reader. Conclusion: Liver lesion T2 relaxation times calculated from dual echo FSE images provide information useful in discriminating metastases from hemangiomas, as does reader opinion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Radiol, Umass Mem Hlth Care, Worcester, MA USA. Emory Univ, Sch Med, Dept Radiol, Emory Univ Hosp, Atlanta, GA 30322 USA. Taipei Vet Gen Hosp, Dept Radiol, Taipei, Taiwan. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. Yonsei Univ, Dept Diagnost Radiol, YongDong Severance Hosp, Coll Med, Seoul 120749, South Korea. RP Hahn, PF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM phahn@partners.org NR 25 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2005 VL 29 IS 5 BP 571 EP 579 DI 10.1097/01.rct.0000172671.71446.33 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 968PA UT WOS:000232173300001 PM 16163021 ER PT J AU Bartlett, JD Dwyer, SE Beniash, E Skobe, Z Payne-Ferreira, TL AF Bartlett, JD Dwyer, SE Beniash, E Skobe, Z Payne-Ferreira, TL TI Fluorosis: A new model and new insights SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE apoptosis; cell signaling; fluorosis; tooth development; zebrafish ID TOOTH DEVELOPMENT; RAT INCISOR; FLUORIDE; ENAMEL; ALK8; ZEBRAFISH; TEETH; AMELOBLASTS; EXPRESSION; SECRETION AB Fluoride is an effective agent for the prevention of dental caries. However, the mechanism of how excessive fluoride exposure causes fluorosis remains uncertain. Zebrafish ( Danio rerio) exhibit periodic tooth replacement throughout their lives, thereby providing continuous access to teeth at developmental stages susceptible to fluoride exposure. Zebrafish teeth do not contain true enamel, but consist of a hard enameloid surface. Therefore, we asked whether zebrafish could be used as a model organism for the study of dental fluorosis. Scanning electron microscopy of fluoride-treated teeth demonstrated that the enameloid was pitted and rough, and FTIR analysis demonstrated that the teeth also contained a significantly higher organic content when compared with untreated controls. Furthermore, we demonstrate for the first time that decreased expression of an important signaling molecule (Alk8) in tooth development may contribute to the observed fluorotic phenotype, and that increased cell apoptosis may also play a role in the mechanism of fluorosis. C1 Harvard Univ, Sch Dent Med, Dept Biomineralizat, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Payne-Ferreira, TL (reprint author), Harvard Univ, Sch Dent Med, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM tpayne@forsyth.org FU NIDCR NIH HHS [DE13237, DE14084, K22 DE 14683-2, P01 DE013237, R01 DE014084] NR 29 TC 32 Z9 38 U1 0 U2 7 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 SEP PY 2005 VL 84 IS 9 BP 832 EP 836 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 956LU UT WOS:000231302100010 PM 16109993 ER PT J AU Onodera, H Mihm, MC Yoshida, A Akasaka, T AF Onodera, H Mihm, MC Yoshida, A Akasaka, T TI Drug-induced linear IgA bullous dermatosis SO JOURNAL OF DERMATOLOGY LA English DT Article DE linear IgA bullous dermatosis; vancomycin; drug-induced ID EPIDERMAL ANTIGENS; T-CELLS; DISEASE; VANCOMYCIN; PATIENT; ANTIBODIES; DEPOSITION; CARCINOMA; FEATURES AB We report the case of a 69-year-old Japanese woman with multiple blistering lesions covering almost her whole body. Linear IgA and C3 depositions were seen at the basement membrane zone on direct immunofluorescence (IF). Linear IgA bullous dermatosis (LABD) is one of the autoimmune diseases resulting in subepidermal blisters. It is clinically similar to bullous pemphigoid and IF is required to distinguish the two diseases. In this case, the blistering lesions appeared after vancomycin treatment. This drug was strongly suspected as a cause of LABD in light of the clinical course of the patient even though a drug-lymphocyte stimulating test was negative. Among the various implicated causative drugs, vancomycin is the most commonly associated with LABD. C1 Harvard Univ, Sch Med, Dermatopathol Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. Iwate Med Univ, Dept Dermatol, Morioka, Iwate 0208505, Japan. RP Onodera, H (reprint author), 19-1 Uchimaru, Morioka, Iwate 0208505, Japan. NR 51 TC 23 Z9 24 U1 0 U2 2 PU JAPANESE DERMATOLGICAL ASSOC PI TOKYO PA TAISEI-BLDG., 14-10 HONGO 3-CHOME, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD SEP PY 2005 VL 32 IS 9 BP 759 EP 764 PG 6 WC Dermatology SC Dermatology GA 969NZ UT WOS:000232242300012 PM 16361722 ER PT J AU Krieger, N Lowy, I Aronowitz, R Bigby, J Dickersin, K Garner, E Gaudilliere, JP Hinestrosa, C Hubbard, R Johnson, PA Missmer, SA Norsigian, J Pearson, C Rosenberg, CE Rosenberg, L Rosenkrantz, BG Seaman, B Sonnenschein, C Soto, AM Thornton, J Weisz, G AF Krieger, N Lowy, I Aronowitz, R Bigby, J Dickersin, K Garner, E Gaudilliere, JP Hinestrosa, C Hubbard, R Johnson, PA Missmer, SA Norsigian, J Pearson, C Rosenberg, CE Rosenberg, L Rosenkrantz, BG Seaman, B Sonnenschein, C Soto, AM Thornton, J Weisz, G TI Hormone replacement therapy, cancer, controversies, and women's health: historical, epidemiological, biological, clinical, and advocacy perspectives SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Review ID CORONARY-HEART-DISEASE; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; BREAST-CANCER; POLYCHLORINATED-BIPHENYLS; ENDOMETRIAL CARCINOMA; PREVENTIVE MEDICINE; UNITED-STATES; MENOPAUSAL; RISK AB Routine acceptance of use of hormone replacement therapy (HRT) was shattered in 2002 when results of the largest HRT randomised clinical trial, the women's health initiative, indicated that long term use of oestrogen plus progestin HRT not only was associated with increased risk of cancer but, contrary to expectations, did not decrease, and may have increased, risk of cardiovascular disease. In June 2004 a group of historians, epidemiologists, biologists, clinicians, and women's health advocates met to discuss the scientific and social context of and response to these findings. It was found that understanding the evolving and contending knowledge on hormones and health requires: ( 1) considering its societal context, including the impact of the pharmaceutical industry, the biomedical emphasis on individualised risk and preventive medicine, and the gendering of hormones; and ( 2) asking why, for four decades, since the mid-1960s, were millions of women prescribed powerful pharmacological agents already demonstrated, three decades earlier, to be carcinogenic? Answering this question requires engaging with core issues of accountability, complexity, fear of mortality, and the conduct of socially responsible science. C1 Harvard Univ, Sch Publ Hlth, Dept Soc & Human Dev & Hlth, Boston, MA 02130 USA. CERMES, INSERM, Villejuif, France. Univ Penn, Dept Hist & Sociol Sci, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Community Hlth Programs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Excellence Womens Hlth, Boston, MA USA. Brown Univ, Ctr Clin Trials & Evidence Based Healthcare, Providence, RI 02912 USA. Dana Farber Canc Ctr, Boston, MA USA. Natl Breast Canc Coalit, Washington, DC USA. Harvard Univ, Dept Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. Connors Ctr Womens Hlth & Gender Biol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Our Bodies Ourselves, Boston, MA USA. Natl Womens Hlth Network, Washington, DC USA. Harvard Univ, Dept Hist Sci, Cambridge, MA 02138 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA. McGill Univ, Montreal, PQ, Canada. RP Krieger, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc & Human Dev & Hlth, Kresge 717,677 Huntington Ave, Boston, MA 02130 USA. EM nkrieger@hsph.harvard.edu NR 152 TC 47 Z9 48 U1 1 U2 10 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2005 VL 59 IS 9 BP 740 EP 748 DI 10.1136/jech.2005.033316 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 955EV UT WOS:000231209100010 PM 16100311 ER PT J AU Modawal, A Ferrer, M Choi, HK Castle, JA AF Modawal, A Ferrer, M Choi, HK Castle, JA TI Hyaluronic acid injections relieve knee pain SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID CONTROLLED CLINICAL-TRIAL; INTRAARTICULAR TREATMENT; SODIUM HYALURONATE; DOUBLE-BLIND; OSTEOARTHRITIS; PLACEBO; VISCOSUPPLEMENTATION; METAANALYSIS; HYLAN; EFFICACY AB Objective To evaluate the efficacy of intra-articular viscosupplementation therapy with hyaluronic acid for pain relief of knee osteoarthritis, we conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials. Methods We searched systematically for randomized, double-blinded, placebo-controlled trials of hyaluronic acid (hyaluronan and hylan G-F20) for pain relief of knee osteoarthritis. Studies reporting pain visual analogue scale (VAS) differences were included in the meta-analysis. Changes in pain were measured by VAS for placebo and treatment, and summary estimates of the differences between the 2 arms were calculated at 1 week, 5 to 7 weeks, 8 to 12, and 15 to 22 weeks after the last intra-articular injection. Sources of heterogeneity were assessed using information on quality score, type of viscosupplementation, and VAS change in pain with activity or rest. Heterogeneity across the studies was significant in all analyses (P <.01); therefore a random effect model was used. Pain was measured either on activity or at rest. Results Eleven trials (9 hyaluronan and 2 hylan G-F 20) allowed calculation of the summary estimate of difference in change of VAS pain at 1 week, 6 of the 11 allowed the estimation between 5 to 7 weeks and 8 to 12 weeks, and only 3 at 15 to 22 weeks. The summary estimates of VAS differences between therapy and placebo injection: at 1 week, 4.4 (95% confidence interval [Cl], 1.1-7.2); at 5 to 7 weeks, 17.7 (7.5-28.0); at 8 to 12 weeks, 18.1 (6.3-29.9) and at 15 to 22 weeks, 4.4 (-15.3 to 24.1). Conclusion Intra-articular viscosupplementation was moderately effective in relieving knee pain in patients with osteoarthritis at 5 to 7 and 8 to 10 weeks after the last injection but not at 15 to 22 weeks. C1 Univ Cincinnati, Dept Family Med, Med Ctr, Geriatr Med Sect, Cincinnati, OH 45267 USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. Natl Naval Med Res Inst, Div Rheumatol, Bethesda, MD USA. RP Modawal, A (reprint author), Univ Cincinnati, Dept Family Med, Med Ctr, Geriatr Med Sect, POB 670582, Cincinnati, OH 45267 USA. EM modawaa@fammed.uc.edu RI Ferrer, Montserrat/A-5510-2010 OI Ferrer, Montserrat/0000-0001-9867-7391 NR 28 TC 54 Z9 59 U1 0 U2 3 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD SEP PY 2005 VL 54 IS 9 BP 758 EP 767 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 968IY UT WOS:000232157100007 PM 16144589 ER PT J AU Carr, PL Rothberg, MB Friedman, RH Felsenstein, D Pliskin, JS AF Carr, PL Rothberg, MB Friedman, RH Felsenstein, D Pliskin, JS TI "Shotgun" versus sequential testing - Cost-effectiveness of diagnostic strategies for vaginitis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE vaginitis; diagnosis; treatment; cost-effectiveness; decision analysis ID DETECTING CHLAMYDIA-TRACHOMATIS; DNA-PROBE; NEISSERIA-GONORRHOEAE; BACTERIAL VAGINOSIS; CELL-CULTURE; GRAM STAIN; GEN-PROBE; SPECIMENS; WOMEN; INFECTION AB BACKGROUND: Although vaginitis is a common outpatient problem, only 60% of patients can be diagnosed at the initial office visit of a primary care provider using the office procedures of pH testing, whiff tests, normal saline, and potassium hydroxide preps. OBJECTIVE: To determine the most cost-effective diagnostic and treatment approach for the medical management of vaginitis. DESIGN: Decision and cost-effectiveness analyses. PARTICIPANTS: Healthy women with symptoms of vaginitis undiagnosed after an initial pelvic exam, wet mount preparations, pH, and the four criteria to diagnose bacterial vaginosis. SETTING: General office practice. METHODS: We evaluated 28 diagnostic strategies comprised of combinations of pH testing. vaginal cultures for yeast and Trichomonas vaginalis. Gram's stain for bacterial vaginosis, and DNA probes for Neisseria gonorrhoeae and Chlamydia. Data sources for the study were confined to English language literature. MEASUREMENT: The outcome measures were symptom-days and costs. RESULTS: The least expensive strategy was to perform yeast culture, gonorrhoeae and Chlamydia probes at the initial visit, and Gram's stain and Trichomonas culture only when the vaginal pH exceeded 4.9 ($330, 7.30 symptom days). Other strategies cost $8 to $76 more and increased duration of symptoms by up to 1.3 days. In probabilistic sensitivity analysis. this strategy was always the most effective strategy and was also least expensive 58% of the time. CONCLUSIONS: For patients with vaginitis symptoms undiagnosed by pelvic examination, wet mount preparations and related office tests, a comprehensive. pH-guided testing strategy at the initial office visit is less expensive and more effective than ordering tests sequentially. C1 Boston Univ, Sch Med, Dept Med, Off Student Affairs, Boston, MA 02118 USA. Baystate Med Ctr, Dept Med, Div Gen Med & Geriatr, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Ben Gurion Univ Negev, Dept Ind Engn & Management, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Dept Hlth Syst Management, IL-84105 Beer Sheva, Israel. RP Carr, PL (reprint author), Boston Univ, Sch Med, Dept Med, Off Student Affairs, 715 Albany St,L-109, Boston, MA 02118 USA. EM plcarr@bu.edu OI Friedman, Robert/0000-0002-9440-2443 NR 39 TC 11 Z9 11 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2005 VL 20 IS 9 BP 793 EP 799 DI 10.1111/j.1525-1497.2005.0188.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 960MG UT WOS:000231596400001 PM 16117745 ER PT J AU Willett, LL Palonen, K Allison, JJ Heudebert, GR Kiefe, CI Massie, FS Wall, TC Houston, TK AF Willett, LL Palonen, K Allison, JJ Heudebert, GR Kiefe, CI Massie, FS Wall, TC Houston, TK TI Differences in preventive health quality by residency year - Is seniority better? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE internship and residency; quality indicators; health care; preventive health services ID INTERNAL-MEDICINE RESIDENTS; PRIMARY-CARE; GUIDELINES; FEEDBACK; RECORD AB BACKGROUND: It is assumed that the performance of more senior residents is superior to that of interns, but this has not been assessed objectively. OBJECTIVE: To determine whether adherence to national guidelines for outpatient preventive health services differs by year of residency training. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred twenty Internal Medicine residents, postgraduate year (PGY)-1 and PGY-2, attending a University Internal Medicine teaching clinic between June 2000 and May 2003. MEASUREMENTS: We studied 6 preventive health care services offered or received by patients by abstracting data from 1,017 patient records. We examined the differences in performance between PGY-1 and PGY-2 residents. RESULTS: Postgraduaute year-2 residents did not statistically outperform PGY-1 residents on any measure. The overall proportion of patients receiving appropriate preventive health services for pneumococcal vaccination. advising tobacco cessation, breast and colon cancer screening. and lipid screening was similar across levels of training. PGY-1s outperformed PGY-2s for tobacco use screening (58%, 51%, P=.03). These results were consistent after accounting for clustering of patients within provider and adjusting for patient age, gender. race and insurance. resident gender, and number of visits during the measurement year. CONCLUSIONS: Overall. patients cared for by PGY-2 residents did not receive more outpatient preventive health services than those cared for by PGY-1 residents. Efforts should be made to ensure quality patient care in the outpatient setting for all levels of training. C1 Univ Alabama, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA. UAB, Dept Med, Div Prevent Med, Birmingham, AL USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness A HSR&D REAP, Birmingham, AL USA. UAB, Outcome & Effectiveness Res & Educ, Birmingham, AL USA. UAB, Dept Pediat, Div Gen Pediat, Birmingham, AL USA. RP Willett, LL (reprint author), Univ Alabama, Dept Med, Div Gen Internal Med, Boshell Diabet Bldg 339,1530 3rd Ave S, Birmingham, AL 35294 USA. EM lwillett@uabmc.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 NR 15 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2005 VL 20 IS 9 BP 825 EP 829 DI 10.1111/j.1525-1497.2005.0158.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 960MG UT WOS:000231596400006 PM 16117750 ER PT J AU Weingart, SN Pagovich, O Sands, DZ Li, JM Aronson, MD Davis, RB Bates, DW Phillips, RS AF Weingart, SN Pagovich, O Sands, DZ Li, JM Aronson, MD Davis, RB Bates, DW Phillips, RS TI What can hospitalized patients tell us about adverse events? Learning from patient-reported incidents SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE medical error; adverse event; patient participation; incident reporting ID DRUG EVENTS; MEDICAL ERRORS; HEALTH-CARE; IATROGENIC INJURY; NEGLIGENT CARE; QUALITY; AUSTRALIA; COLORADO; BEHAVIOR; SAFETY AB PURPOSE: Little is known about how well hospitalized patients can identify errors or injuries in their care. Accordingly, the purpose of this study was to elicit incident reports from hospital inpatients in order to identify and characterize adverse events and near-miss errors. SUBJECTS: We conducted a prospective cohort study of 228 adult inpatients on a medicine unit of a Boston teaching hospital. METHODS: Investigators reviewed medical records and interviewed patients during the hospitalization and by telephone 10 days after discharge about "problems," "mistakes," and "injuries" that occurred. Physician investigators classified patients' reports. We calculated event rates and used multivariable Poisson regression models to examine the factors associated with patient-reported events. RESULTS: Of 264 eligible patients, 228 (86%) agreed to participate and completed 528 interviews. Seventeen patients (8%) experienced 20 adverse events; 1 was serious. Eight patients (4%) experienced 13 near misses; 5 were serious or life threatening. Eleven (55%) of 20 adverse events and 4 (31%) of 13 near misses were documented in the medical record, but none were found in the hospital incident reporting system. Patients with 3 or more drug allergies were more likely to report errors compared with patients without drug allergies (incidence rate ratio 4.7, 95% Cl 1.7, 13.4). CONCLUSION., Inpatients can identify adverse events affecting their care. Many patient-identified events are not captured by the hospital incident reporting system or recorded in the medical record. Engaging hospitalized patients as partners in identifying medical errors and injuries is a potentially promising approach for enhancing patient safety. C1 Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Zix Corp, Dallas, TX USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu FU AHRQ HHS [K08 HS011644, 1 K08 HS 11644] NR 33 TC 116 Z9 117 U1 5 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2005 VL 20 IS 9 BP 830 EP 836 DI 10.1111/j.1525-1497.2005.0180.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 960MG UT WOS:000231596400007 PM 16117751 ER PT J AU Gandhi, TK Weingart, SN Seger, AC Borus, J Burdick, E Poon, EG Leape, LL Bates, DW AF Gandhi, TK Weingart, SN Seger, AC Borus, J Burdick, E Poon, EG Leape, LL Bates, DW TI Outpatient prescribing errors and the impact of computerized prescribing SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 1st National Ambulatory Primary Care Research and Education Conference on Patient Safety CY 2003 CL Chicago, IL DE medication error; electronic prescribing; ambulatory care ID ADVERSE DRUG EVENTS; MEDICATION ERRORS; CARE; INTERVENTIONS; PREVENTION AB BACKGROUND: Medication errors are common among inpatients and many are preventable with computerized prescribing. Relatively little is known about outpatient prescribing errors or the impact of computerised prescribing in this setting. OBJECTIVE: To assess the rates, types, and severity of outpatient prescribing errors and understand the potential impact of computerized prescribing. DESIGN: Prospective cohort study in 4 adult primary care practices in Boston using prescription review, patient survey, and chart review to identify medication errors, potential adverse drug events (ADEs) and preventable ADEs. PARTICIPANTS: Outpatients over age 18 who received a prescription from 24 participating physicians. RESULTS: We screened 1879 prescriptions from 1202 patients, and completed 661 surveys (response rate 55%). Of the prescriptions, 143 (7.6%: 95% confidence interval (CI) 6.4% to 8.8%) contained a prescribing error. Three errors led to preventable ADEs and 62 (43%; 3% of all prescriptions) had potential for patient injury (potential ADEs); I was potentially life-threatening (2%) and 15 were serious (24%). Errors in frequency (n=77, 54%) and dose (n=26, 18%) were common. The rates of medication errors and potential ADEs were not significantly different at basic computerized prescribing sites (4.3% vs 11.0%, P=.31; 2.6% vs 4.0%. P=.16) compared to handwritten sites. Advanced checks (including dose and frequency checking) could have prevented 95% of potential ADEs. CONCLUSIONS: Prescribing errors occurred in 7.6% of outpatient prescriptions and many could have harmed patients. Basic computerized prescribing systems may not be adequate to reduce errors. More advanced systems with dose and frequency checking are likely needed to prevent potentially harmful errors. C1 Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02120 USA. Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Gandhi, TK (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM tgandhi@partners.org NR 22 TC 134 Z9 137 U1 3 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2005 VL 20 IS 9 BP 837 EP 841 DI 10.1111/j.1525-1497.2005.0194.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 960MG UT WOS:000231596400008 PM 16117752 ER PT J AU Adey, L Ring, D Jupiter, JB AF Adey, L Ring, D Jupiter, JB TI Health status after total wrist arthrodesis for posttraumatic arthritis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE wrist; arthrodesis; arthritis; trauma ID RHEUMATOID-ARTHRITIS; FUSION; ARTHROPLASTY; COLLAPSE; MOTION AB Purpose: Total wrist arthrodesis is regarded as the most predictable way to relieve the pain of posttraumatic wrist arthritis. Wrist arthrodesis also is believed to be compatible with a high level of upper-extremity function. This study evaluated the effect of total wrist arthrodesis on both general and upper-extremity-specific health status in patients treated for posttraumatic wrist arthritis. Methods: By using an institutional review board-approved protocol 22 patients were evaluated an average of 6 years after total wrist arthrodesis for posttraumatic arthritis. Upper-extremity-specific and general health status were measured using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short-Form 36 (SF-36) instruments, respectively. Patient satisfaction and interest in pursuing a wrist-mobilizing procedure should one become available also were assessed. Objective assessment included grip strength, digit range of motion, and radiographic fusion. Results: Grip strength averaged 79% of the uninvolved wrist. The average Disabilities of the Arm, Shoulder, and Hand questionnaire score was 25. The average physical component score of the Short-Form 36 was 39 and the average mental component score was 52. Fourteen patients complained of wrist pain, including severe pain in 4 patients. Fifteen patients were satisfied or very satisfied with the result of the fusion, 5 patients were neutral, and 2 patients were mildly dissatisfied. Twenty patients would elect to have a procedure that could make their wrist move again if one were available. Conclusions: Substantial dysfunction was noted on both upper-extremity-specific and general health status measures after total wrist arthrodesis for posttraumatic conditions. Pain was improved but not eliminated. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 27 Z9 29 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 SEP PY 2005 VL 30A IS 5 BP 932 EP 936 DI 10.1016/j.jhsa.2005.06.004 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 967VX UT WOS:000232120400007 PM 16182047 ER PT J AU Gradl, G Jupiter, JB Gierer, P Mittlmeier, T AF Gradl, G Jupiter, JB Gierer, P Mittlmeier, T TI Fractures of the distal radius treated with a nonbridging external fixation technique using multiplanar K-wires SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal radius fracture; external fixation; nonbridging; functional outcome; K-wire ID INTRAARTICULAR FRACTURES; UNSTABLE FRACTURES; OPEN REDUCTION; END AB Purpose: joint-bridging external fixation is a minimally invasive treatment option for distal radius fractures. Although radial length can be restored easily the anatomic reduction of articular fragments and restoration of the normal volar tilt proves to be more difficult. A method of nonbridging hybrid fixation of distal radius fractures facilitates fracture reduction and allows for free wrist movement. Methods: Twenty-five consecutive patients with fractures of the distal radius were treated with nonbridging external fixation for 6 weeks. The stepwise surgical technique comprised a preliminary joint-bridging construction for reduction purposes, the subsequent insertion of 3 to 4 K-wires in the distal fragment, the assembling of wires to a bar nearly parallel to the fracture line, and lastly the removal of the joint-bridging part. Clinical and radiologic evaluation was performed on the first and seventh days and at 6 weeks and 2 years after surgery. Results:All fractures united. Palmar tilt (>= 0 degrees) and articular surface (articular step-off < 2 mm) were restored in all patients whereas loss of radial length occurred in 4 patients having the distal fracture fragment secured with 3 K-wires. No radial shortening was seen in fractures with 4 K-wires inserted in the distal fragment. Functional results at 2 years after surgery showed an average extension of 55 degrees and flexion of 64 degrees without significant differences between extra-articular and intra-articular fractures. There was no extensor tendinitis or pin loosening in the distal fragment; however, 3 pin track infections of proximal pins occurred. Conclusions: This surgical technique of nonbridging external fixation is a good treatment option for distal radius fractures: it permits wrist movement. We recommend the insertion of 4 K-wires in the distal fracture fragment. C1 Univ Rostock, Chirurg Klin & Poliklin, Abt Unfall & Wiederherstellungschirurg, D-18055 Rostock, Germany. Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gradl, G (reprint author), Univ Rostock, Chirurg Klin & Poliklin, Abt Unfall & Wiederherstellungschirurg, Schillingallee 35, D-18055 Rostock, Germany. EM georg.gradl@med.uni-rostock.de NR 24 TC 19 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2005 VL 30A IS 5 BP 960 EP 968 DI 10.1016/j.jhsa.2005.04.014 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 967VX UT WOS:000232120400012 PM 16182052 ER PT J AU Smith, RN Brousaides, N Grazette, L Saidman, S Semigran, M Disalvo, T Madsen, J Dec, GW Perez-Atayde, AR Collins, AB AF Smith, RN Brousaides, N Grazette, L Saidman, S Semigran, M Disalvo, T Madsen, J Dec, GW Perez-Atayde, AR Collins, AB TI C4d deposition in cardiac allografts correlates with alloantibody SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID VASCULAR HUMORAL REJECTION; ANTIBODY-MEDIATED REJECTION; HEART-TRANSPLANTATION; CAPILLARY DEPOSITION; PERITUBULAR CAPILLARIES; PATHOLOGICAL FEATURES; COMPLEMENT FRAGMENT; RENAL-ALLOGRAFTS; MYOCARDIAL-INFARCTION; INTERNATIONAL-SOCIETY AB Background: The presence of C4d along the peritubular capillaries in kidney allografts correlates with the A presence of anti-donor serum alloantibodies. we applied C4d staining to cardiac allograft an non-allograft biopsies to determine if C4d staining in heart allografts correlates with anti-donor serum alloantibodies. Methods: We stained for C4d all available frozen tissue biopsies from cardiac transplant recipients between 1997 and 2002, including autopsies. Two hundred twenty-one tissue samples from 124 patients were analyzed. Included in both groups were a variety of International Society,for Heart and Lung Transplanatation (ISHLT) grades of rejection plus post-implant cardiac ischemic injury (PIMI), and biopsies from patients who had received OKT3. Patients were matched by age, gender and interval after transplantation. Forty-four additional controls were included from patients biopsied for non-transplant-related cardiac disease. Results: C4d staining of the myocardial capillaries correlated well with the presence of anti-donor alloantibodies. Twenty-one of 25 biopsies from patients with anti-donor allo antibodies showed C4d staining (84%), whereas only 7 of 60 without anti-donor alloantibodies stained for C4d. C4d staining did not correlate with ischemia or OKT3 therapy. Only 4 of 44 non-transplant biopsies stained for C4d (9%). An example of the clinical utility of C4d staining in patient care is presented. Conclusions: C4d staining of the capillaries in cardiac allografts correlates well with anti-donor serum alloantibodies, is a useful assay to verify alloantibody deposition, and can be used to establish one of the criteria for antibody-mediated cardiac rejections. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Smith, RN (reprint author), Massachusetts Gen Hosp, Dept Pathol, 501D Warren Bldg, Boston, MA 02114 USA. EM smith.rex@mgh.harvard.edu NR 52 TC 54 Z9 57 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2005 VL 24 IS 9 BP 1202 EP 1210 DI 10.1016/j.healun.2004.07.021 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 963FK UT WOS:000231788900005 PM 16143234 ER PT J AU Thompson, CA Reddy, VK Srinivasan, A Houser, S Hayase, M Davila, A Pomerantsev, E Vacanti, JP Gold, HK AF Thompson, CA Reddy, VK Srinivasan, A Houser, S Hayase, M Davila, A Pomerantsev, E Vacanti, JP Gold, HK TI Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID ENHANCES COLLATERAL PERFUSION; TRANSPLANTED HUMAN HEARTS; IMPROVES CARDIAC-FUNCTION; CARDIOMYOCYTE TRANSPLANTATION; CELLULAR CARDIOMYOPLASTY; ISCHEMIC MYOCARDIUM; REGIONAL FUNCTION; STEM-CELLS; INFARCTION; NEOVASCULARIZATION AB Background: The potential for cellular cardiomyoplasty to provide functional left ventricular recovery in the chronically injured heart remains unclear. Methods: Yorkshire swine (n = 10; 35-50 kg) had anterolateral myocardial infarction (MI) induced by coil embolization of the left anterior descending artery. Approximately 5 weeks post-MI, a composite, intravascular ultrasound-guided catheter system (TransAccess) was used to deliver an autologous, labeled, bone marrow-derived cell sub-population (similar to 3 x 10(8) cells) or saline control (similar to 50 injections/arm) through coronary veins directly into infarct and peri-infarct myocardium. Two months post-transplant, the animals had blinded endocardial and epicardial left ventricular electrical scar mapping and biventricular electrical stimulation. Coronary angiography and quantitative biplane ventriculography were performed at baseline, transplant, and sacrifice time-points. Results: Robust, viable, predominantly desmin-negative cell grafts were demonstrated post-mortem in all treatment animals. Baseline and pre-transplant global and regional wall motion was similar between groups. The cell treatment group demonstrated functional recovery with a left ventricular ejection fraction of 38.1% at the time of transplant increasing to 48.5% (P = 0.005) at sacrifice, whereas the control arm was unchanged (38.0% vs 34.3%, respectively; p = NS). The regional improvement corresponded with a reduction in percentage of hypokinetic (52.1%- 42.9%, p = 0.002) and percentage of akinetic (24.8%-17.7%, p = 0.04) segments in the cell-treated animals. Epicardial scar area was not different (37 cm(2) vs 23 cm(2), P = 0.37) between groups. Conclusions: Percutaneous, transvascular, direct intramyocardial bone marrow cell transplantation is safe and feasible in chronically infarcted tissue. In this pilot study, cell therapy improved overall left ventricular systolic function by recruiting previously hypokinetic or akinetic myocardial tissue. C1 Dartmouth Coll, Hitchcock Med Ctr, Cardiol Sect, Angiogenesis Res Ctr,Dartmouth Med Sch, Lebanon, NH 03756 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Tissue Engn Lab, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA USA. Cardiovasc Res Ctr, Charlestown, MA USA. RP Thompson, CA (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Cardiol Sect, Angiogenesis Res Ctr,Dartmouth Med Sch, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Craig.A.Thompson@Hitchcock.org NR 40 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2005 VL 24 IS 9 BP 1385 EP 1392 DI 10.1016/j.healun.2004.10.010 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 963FK UT WOS:000231788900032 PM 16143261 ER PT J AU Herrine, SK Friedman, LS AF Herrine, SK Friedman, LS TI Divining the role of liver biopsy in hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID BIOCHEMICAL MARKERS; VIRUS-INFECTION; PLUS RIBAVIRIN; FIBROSIS; VALIDATION; FIBROTEST; TESTS C1 Wellesley Hosp, Dept Med, Newton, MA 02462 USA. Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA USA. Newton Wellesley Hosp, Dept Med, Newton, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Friedman, LS (reprint author), Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 21 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2005 VL 43 IS 3 BP 374 EP 376 DI 10.1016/j.jhep.2005.06.014 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 958XJ UT WOS:000231481200001 PM 16046025 ER PT J AU Di Bisceglie, AM Sterling, RK Chung, RT Everhart, JE Dienstag, JL Bonkovsky, HL Wright, EC Everson, GT Lindsay, KL Lok, ASF Lee, WM Morgan, TR Ghany, MG Gretch, DR AF Di Bisceglie, AM Sterling, RK Chung, RT Everhart, JE Dienstag, JL Bonkovsky, HL Wright, EC Everson, GT Lindsay, KL Lok, ASF Lee, WM Morgan, TR Ghany, MG Gretch, DR CA HALT C Trial Grp TI Serum alpha-fetoprotein levels in patients with advanced hepatitis C: Results from the HALT-C Trial SO JOURNAL OF HEPATOLOGY LA English DT Article DE cirrhosis; hepatitis C; antiviral therapy; alpha-fetoprotein ID CHRONIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; DIAGNOSIS; CIRRHOSIS; INTERFERON; NECROSIS; UTILITY; ADULTS; ASSAYS; WOMEN AB Background/Aims: Alpha-fetoprotein (AFP) has been useful in the diagnosis of hepatocellular carcinoma (HCC) but lacks specificity. We assessed serum AFP among patients with chronic hepatitis C and advanced fibrosis to establish predictors of AFP elevations and changes with antiviral therapy. Methods: Serum AFP was measured at baseline and on therapy in patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C). AFP levels were correlated with patient demographic and clinical features. Results: Baseline AFP was >= 20 ng/mL in 191 of 1145 patients (16.6 %). Mean AFP values were significantly higher in patients with cirrhosis than in those with bridging fibrosis (22.5 vs. 11.4 ng/mL, P < 0.0001). Factors independently associated with raised serum AFP in patients with cirrhosis were female gender, black race, decreased platelet count, increased serum AST/ALT ratio, serum ferritin, and Mallory bodies in liver biopsies. Serum AFP levels decreased significantly during therapy with pegylated interferon alpha-2a and ribavirin. HCC was identified in six subjects, only three of whom had AFP > 20 ng/mL. Conclusions: Among patients with advanced chronic hepatitis C, serum AFP values are frequently elevated, even in the absence of HCC. Factors associated with raised AFP include severity of liver disease, female gender and black race. Serum AFP levels decline during antiviral therapy. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Dept Med, St Louis, MO 63110 USA. Virginia Commonwealth Univ, Hepatol Sect, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. Harvard Univ, Med Sch, Massachusetts Gen Hosp, Gastrointest Unit,Med Serv, Boston, MA USA. Harvard Univ, Med Sch, Dept Med, Boston, MA USA. NIH, Natl Inst Diabet & Digest & Kidney Dis, Dept Hlth & Human Serv, Div Digest Dis & Nutr, Bethesda, MD USA. Univ Connecticut, Hlth Ctr, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Hlth Ctr, Gen Clin Res Ctr, Farmington, CT USA. New England Res Inst, Watertown, MA USA. Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO USA. Univ So Calif, Div Gastroenterol & Liver Dis, Los Angeles, CA USA. Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. NIDDKD, Dept Hlth & Human Serv, Liver Dis Sect, Div Digest Dis & Nutr,NIH, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Dept Med, 3635 Vista Ave, St Louis, MO 63110 USA. EM dibiscam@slu.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01--DK-9-2326, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2327, N01-DK-9-2328] NR 35 TC 117 Z9 120 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2005 VL 43 IS 3 BP 434 EP 441 DI 10.1016/j.jhep.2005.03.019 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 958XJ UT WOS:000231481200010 PM 16136646 ER PT J AU Johnson, KR Johnson, KY Crellin, HG Ogretmen, B Boylan, AM Harley, RA Obeid, LM AF Johnson, KR Johnson, KY Crellin, HG Ogretmen, B Boylan, AM Harley, RA Obeid, LM TI Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE sphingosine kinase 1; immunolocalization; lung; non-small-cell lung cancer ID FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; GROWTH; CELLS; DIFFERENTIATION; PROLIFERATION; MODULATION; ACTIVATION AB Sphingosine kinase 1 (SK1) is a key enzyme critical to the sphingolipid metabolic pathway responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphate. SK1-mediated production of sphingosine-1-phosphate has been shown to stimulate such biological processes as cell growth, differentiation, migration, angiogenesis, and inhibition of apoptosis. In this study, cell type-specific immunolocalization of SK1 was examined in the bronchus/terminal bronchiole of the lung. Strong immunopositive staining was evident at the apical surface of pseudostratified epithelial cells of the bronchus and underlying smooth muscle cells, submucosal serous glands, immature chondrocytes, type 11 alveolar cells, foamy macrophages, endothelial cells of blood vessels, and neural bundles. Immunohistochemical screening for SK1 expression was performed in 25 samples of normal/tumor patient matched non-small-cell lung cancer tissue and found that 25 of 25 tumor samples (carcinoid [5 samples], squamous [10 samples], and adenocarcinoma tumors [10 samples]), exhibited overwhelmingly positive immunostaining for SK1 as compared with patient-matched normal tissue. In addition, an approximately 2-fold elevation of SK1 mRNA expression was observed in lung cancer tissue versus normal tissue, as well as in several other solid tumors. Taken together, these findings define the localization of SK1 in lung and provide clues as to how SK1 may play a role in normal lung physiology and the pathophysiology of lung cancer. C1 Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC USA. The Citadel, Dept Biol, Charleston, SC USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu FU NCI NIH HHS [P01 CA-097132]; NIGMS NIH HHS [GM-62887] NR 23 TC 92 Z9 104 U1 1 U2 2 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 2005 VL 53 IS 9 BP 1159 EP 1166 DI 10.1369/jhc.4A6606.2005 PG 8 WC Cell Biology SC Cell Biology GA 960HD UT WOS:000231580300011 PM 15923363 ER PT J AU Magen, E Viskoper, JR Mishal, J Priluk, R London, D Yosefy, C AF Magen, E Viskoper, JR Mishal, J Priluk, R London, D Yosefy, C TI Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE endothelial; aspirin; statins ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONVERTING ENZYME-INHIBITORS; RANDOMIZED-TRIAL; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; METAANALYSIS; THERAPY; RISK; VASODILATATION; PREVENTION AB The main objective of this study was to assess whether aspirin 100 mg QD can improve blood pressure ( BP) control and endothelial function in subjects with arterial hypertension (AH) and hypercholesterolaemia. In total, 21 patients of both sexes (52.1 +/- 11.5 years) with treated AH and hypercholesterolaemia on antihypertensive and statin therapy were included in the treatment group. In the control group, 20 matched patients of both sexes (51.3 +/- 12.7 years), but without statin therapy, were recruited. Treatment group subjects received aspirin (100 mg QD) for a duration of 12 weeks at randomization ( Treatment phase-1), followed by single blind matching placebo for 12 weeks ( Placebo phase) and then again received aspirin (100 mg QD) for an additional 12 weeks (Treatment phase-2). The control group participated in Treatment phase-1, but did not continue Placebo phase and Treatment phase-2. At randomization and at the end of each study phase, mean 24-h systolic BP (SBP) and diastolic BP (DBP) were assessed by 24-h ambulatory blood pressure monitoring (ABPM) and endothelium-dependent (flow mediated, FMD) and -independent ( nitroglycerin induced, NTG) vasodilatations of brachial artery were measured using high-resolution ultrasound. In Treatment phase-1, reduction of SBP and DBP (Delta SBP 5.7 +/- 2.6 mmHg, P=0.008; Delta DBP 3.8 +/- 1.7 mmHg, P=0.014) and improvement of FMD (4.1 +/- 0.6%, P=0.019), in Placebo phase an elevation of SBP and DBP (Delta SBP -6.2 +/- 2.9 mmHg, P=0.002; Delta DBP -4.2 +/- 1.9 mmHg, P=0.031) and worsening of FMD (-3.8 +/- 0.9%, P=0.027), and in Treatment phase-2 reduction of SBP and DBP (Delta SBP 4.9 +/- 2.3 mmHg, P=0.005; Delta DBP 4.1 +/- 1.3 mmHg, P=0.024) and improvement of FMD (4.5 +/- 1.3%, P=0.009) were observed in the treatment Group but not in the control group. Addition of low-dose aspirin to antihypertensive medications and statins in hypertensive and hypercholesterolaemic subjects can reduce both SBP and DBP by improvement of endothelial function. C1 Ben Gurion Univ Negev, Barzilai Med Ctr, WHO Collaborat Ctr Prevent CVD, Ashqelon, Israel. Massachusetts Gen Hosp, Non Invas Cardiac Lab, Boston, MA 02114 USA. RP Viskoper, JR (reprint author), Ben Gurion Univ Negev, Barzilai Hosp, WHO Collaborat Ctr Prevent CVD, IL-84105 Beer Sheva, Israel. EM elimgen2@netvision.net.il NR 31 TC 28 Z9 29 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD SEP PY 2005 VL 19 IS 9 BP 667 EP 673 DI 10.1038/sj.jhh.1001910 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 957LA UT WOS:000231370100002 PM 16034448 ER PT J AU Yang, M Hase, H Legarda-Addison, D Varughese, L Seed, B Ting, AT AF Yang, M Hase, H Legarda-Addison, D Varughese, L Seed, B Ting, AT TI B cell maturation antigen, the receptor for a proliferation-inducing ligand and B cell-activating factor of the TNF family, induces antigen presentation in B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR FAMILY; APRIL-DEFICIENT MICE; JURKAT T-CELLS; LYMPHOCYTE STIMULATOR; AUTOIMMUNE-DISEASE; PROTEIN-KINASE; IMMUNE-RESPONSES; CUTTING EDGE; BAFF-R AB B cell maturation Ag (BCMA), a member of the TNFR superfamily expressed on B cells, binds to a proliferation-inducing ligand (APRIL) and B cell-activating factor of the TNF family (BAFF) but the specific B cell responses regulated by BCMA remain unclear. This study demonstrates that ligation of A20 B cells transfected with BCMA induces the expression of CD40, CD80/B7-1, CD86/B7-2, MHC class II, and CD54/ICAM-1, which subsequently enhances the presentation of OVA peptide Ag to DO11.10 T cells. BCMA expression in murine splenic B cells can be induced with IL-4 and IL-6, allowing subsequent treatment with APRIL or agonist anti-BCMA to similarly induce Ag presentation. A comparative analysis of hybrid receptors of TNFR2 fused to the cytoplasmic domains of APRIL/BAFF receptors found that only BCMA, but not transmembrane activator and calcium-modulator and cyclophilin ligand interactor or BAFF-R, is capable of activating Ag presentation. Although all three receptors can trigger NF-kappa B signaling, only BCMA activates the JNK pathway conferring on BCMA the specific ability to activate this Ag presentation response. C1 CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ting, AT (reprint author), CUNY Mt Sinai Sch Med, Immunobiol Ctr, Box 1630,1 Gustave L Levy Pl, New York, NY 10029 USA. EM adrian.ting@mssm.edu FU NIAID NIH HHS [R01 AI052417, R21 AI057997] NR 54 TC 70 Z9 76 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 SEP 1 PY 2005 VL 175 IS 5 BP 2814 EP 2824 PG 11 WC Immunology SC Immunology GA 966HL UT WOS:000232010600009 PM 16116167 ER PT J AU Barrington, RA Zhang, M Zhong, XM Jonsson, H Holodick, N Cherukuri, A Pierce, SK Rothstein, TL Carroll, MC AF Barrington, RA Zhang, M Zhong, XM Jonsson, H Holodick, N Cherukuri, A Pierce, SK Rothstein, TL Carroll, MC TI CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAS-MEDIATED APOPTOSIS; DOMAIN-CONTAINING PROTEIN; FLICE-INHIBITORY PROTEIN; ANTIGEN RECEPTOR; TRANSGENIC MICE; C-FLIP; MOLECULAR ADJUVANT; LYMPHOCYTES-B; CUTTING EDGE; DEATH DOMAIN AB The adaptive immune response is tightly regulated to limit responding cells in an Ag-specific manner. On B cells, coreceptors CD21/CD19 modulate the strength of BCR signals, potentially influencing cell fate. The importance of the CD95 pathway was examined in response of B cells to moderate affinity Ag using an adoptive transfer model of lysozyme-specific Ig transgenic (HEL immunoglobulin transgene (MD4) strain) B cells. Although adoptively transferred Cr2(+/+) MD4 B cells are activated and persist within splenic follicles of duck egg lysozyme-immunized mice, Cr2(-/-) MD4 B cells do not. In contrast, Cr2(-/-) MD4 lpr B cells persist after transfer, suggesting that lack of CD21/CD35 signaling results in CD95-mediated elimination. Cr2 deficiency did not affect CD95 levels, but cellular FLIP (c-FLIP) protein and mRNA levels were reduced 2-fold compared with levels in Cr2(+/+) MD4 B cells. In vitro culture with Cr2(+/+) MD4 B cells demonstrated that equimolar amounts of rHEL-C3d(3) were more effective than hen egg lysozyme alone in up-regulating c-FLIP levels and for protection against CD95-mediated apoptosis. Collectively, this study implies a mechanism for regulating B cell survival in vivo whereby the strength of BCR signaling (including coreceptor) determines c-FLIP levels and protection from CD95-induced death. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Boston Univ, Med Ctr, Dept Immunobiol, Boston, MA 02118 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu FU NIAID NIH HHS [AI40181, AI39246] NR 71 TC 29 Z9 32 U1 1 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 SEP 1 PY 2005 VL 175 IS 5 BP 2859 EP 2867 PG 9 WC Immunology SC Immunology GA 966HL UT WOS:000232010600014 PM 16116172 ER PT J AU Cariappa, A Shoham, T Liu, HY Levy, H Boucheix, C Pillai, S AF Cariappa, A Shoham, T Liu, HY Levy, H Boucheix, C Pillai, S TI The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MARGINAL ZONE; LYMPHOCYTE DEVELOPMENT; POSITIVE SELECTION; POOR-PROGNOSIS; BREAST-CANCER; MOTILITY; MICE; EXPRESSION; PROTEINS; BTK AB The CD9 tetraspanin is known to be expressed at high levels on marginal zone (MZ) B cells, B-I B cells, and plasma cells, and its expression is believed to be dependent on signals' derived via Btk. In CD9 null mice, however, the development and survival of MZ B cells, B-1 B cells, and plasma cells all appear to be unaffected, and humoral immune responses to T-dependent and T-independent Ags are similar to those seen in wild-type littermate controls. In wild-type mice, CD9 levels may serve to distinguish between the presumed MZ precursor B cell population in the spleen and other IgD-expressing transitional B cells that express lower levels of CD21 and CD1d. These results suggest that CD9 is dispensable for B cell development and humoral immunity, but that this protein may serve as an additional marker for the presumed MZ precursor population of splenic B cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. Stanford Univ, Med Ctr, Div Oncol, Dept Med, Stanford, CA 94305 USA. Hop Paul Brousse, INSERM, U602, Villejuif, France. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NCI NIH HHS [CA102793]; NIAID NIH HHS [AI 033507, AI 054917, AI 45900] NR 35 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2005 VL 175 IS 5 BP 2925 EP 2930 PG 6 WC Immunology SC Immunology GA 966HL UT WOS:000232010600020 PM 16116178 ER PT J AU Li, LQ Greenwald, RJ Lafuente, EM Tzachanis, D Berezovskaya, A Freeman, GJ Sharpe, AH Boussiotis, VA AF Li, LQ Greenwald, RJ Lafuente, EM Tzachanis, D Berezovskaya, A Freeman, GJ Sharpe, AH Boussiotis, VA TI Rap1-GTP is a negative regulator of Th cell function and promotes the generation of CD4(+) CD103(+) regulatory T cells in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTEGRIN ACTIVATION; SUPPRESSOR ACTIVITY; PROTEIN RAP1; SMALL GTPASE; ADHESION; GENE; ANERGY; SIGNAL; TRANSCRIPTION; INHIBITION AB The small GTPase Rap1 is transiently activated during TCR ligation and regulates integrin-mediated adhesion. To understand the in vivo functions of Rap1 in regulating T cell immune responses, we generated transgenic (Tg) mice, which express the active GTP-bound mutant Rap1E63 in their T lymphocytes. Although Rap1E63-Tg T cells exhibited increased LFA-1-mediated adhesion, ERK1/2 activation and proliferation of Rap1E63-Tg CD4(+) T cells were defective. Rap1E63-Tg T cells primed in vivo and restimulated with specific Ag in vitro, exhibited reduced proliferation and produced reduced levels of IL-2. Rap1E63-Tg mice had severely deficient T cell-dependent B cell responses, as determined by impaired Ig class switching. Rap1E63-Tg mice had an increased fraction of CD4(+)CD103(+) regulatory T cells (Treg), which exhibited enhanced suppressive efficiency as compared with CD4(+)CD103(+) Treg from normal littermate control mice. Depletion of CD103(+) Treg significantly restored the impaired responses of Rap1E63-Tg CD4(+) T cells. Thus Rap1-GTP is a negative regulator of Th cell responses and one mechanism responsible for this effect involves the increase of CD103(+) Treg cell fraction. Our results show that Rapl-GTP promotes the generation of CD103(+) Treg and may have significant implications in the development of strategies for in vitro generation of Treg for the purpose of novel immunotherapeutic approaches geared toward tolerance induction. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Sch Med, Boston, MA 02129 USA. EM vassiliki_boussiotis@dfci.harvard.edu RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 FU NIAID NIH HHS [AI 43552, AI 46548] NR 33 TC 28 Z9 31 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2005 VL 175 IS 5 BP 3133 EP 3139 PG 7 WC Immunology SC Immunology GA 966HL UT WOS:000232010600045 PM 16116203 ER PT J AU Birdsall, HH Porter, WJ Trial, J Rossen, RD AF Birdsall, HH Porter, WJ Trial, J Rossen, RD TI Monocytes stimulated by 110-kDa fibronectin fragments suppress proliferation of anti-CD3-activated T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALVEOLAR MACROPHAGES; PERIPHERAL-BLOOD; ADHERENT CELLS; ACTIVATION; RESPONSES; GROWTH; INTERLEUKIN-10; EXPRESSION; PRODUCTS; CONTACT AB One hundred ten to 120-kDa fragments of fibronectin (FNf), generated by proteases released in the course of tissue injury and inflammation, stimulate monocytes to produce proinflammatory cytokines, promote mononuclear leukocytes (MNL) transendothelial migration, up-regulate monocyte CD11b and CD86 expression, and induce monocyte-derived dendritic cell differentiation. To investigate whether the proinflammatory consequences of FNf are offset by responses that can suppress proliferation of activated T lymphocytes, we investigated the effect of FNf-treated MNL on autologous T lymphocytes induced to proliferate by substrate-immobilized anti-CD3. FNf-stimulated MNL suppressed anti-CD3-induced T cell proliferation through both contact-dependent and contact-independent mechanisms. Contact-independent suppression was mediated, at least in part, by IL-10 and TGF-beta released by the FNf-stimulated MNL. After 24-48 h exposure to FNf, activated T cells and monocytes formed clusters displaying CD25, CD14, CD3, and CD4 that were not dissociable by chelation of divalent cations. Killing monocytes with L-leucine methyl ester abolished these T cell-monocyte clusters and the ability of the FNf-stimulated MNL to suppress anti-CD3 induced T cell proliferation. Thus, in addition to activating MNL and causing them to migrate to sites of injury, FNf appears to induce suppressor monocytes. C1 Michael E DeBakey Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, Immunol Res Lab, Houston, TX 77030 USA. Baylor Coll Med, Dept Otorhinolaryngol, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Birdsall, HH (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, Immunol Res Lab, Bldg 110,Room 328,2002 Holcombe Blvd, Houston, TX 77030 USA. EM birdsall@bcm.tmc.edu FU NIAID NIH HHS [R0-AI46285]; NIMH NIH HHS [R01-MH63035]; NINDS NIH HHS [R01-NS32583] NR 31 TC 10 Z9 10 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 SEP 1 PY 2005 VL 175 IS 5 BP 3347 EP 3353 PG 7 WC Immunology SC Immunology GA 966HL UT WOS:000232010600069 PM 16116227 ER PT J AU Uehara, S Chase, CM Kitchens, WH Rose, HS Colvin, RB Russell, PS Madsen, JC AF Uehara, S Chase, CM Kitchens, WH Rose, HS Colvin, RB Russell, PS Madsen, JC TI NK cells can trigger allograft vasculopathy: The role of hybrid resistance in solid organ allografts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSPLANTED MOUSE HEARTS; NATURAL-KILLER-CELLS; MIXED HEMATOPOIETIC CHIMERISM; CORONARY-ARTERY-DISEASE; INTERFERON-GAMMA; CARDIAC ALLOGRAFTS; REJECTION; ATHEROSCLEROSIS; MICE; ARTERIOSCLEROSIS AB Progressive arterial stenosis (cardiac allograft vasculopathy (CAV)) is a leading cause of long-term failure of organ transplants. CAV remains intractable, in part because its mechanisms are insufficiently understood. A central proposition is that MHC-driven alloimmune processes play a necessary role in CAV, as shown by the absolute requirement for histoincompatibility between donor and recipient for its production. Two immunological pathways have been implicated involving reactivity to donor MHC Ags by either T or B cells. In this study, we use a novel system of semiallogeneic cardiac transplants between parental donors and F1 hybrid recipients to provide evidence that NK cells, members of the innate immune system, also contribute to the generation of CAV in mice. This finding marks the first demonstration that the hybrid resistance phenomenon occurs in solid organ allografts. Extension of these experiments to recipients deficient in T cells demonstrates that this third pathway of CAV, the NK cell-triggered pathway, involves the recruitment of T cells not responsive to donor alloantigens. Finally, transplants performed with donors or recipients deficient in IFN-gamma revealed that recipient-derived IFN-gamma is necessary for CAV formation in parental to F1 transplants, suggesting a possible effector mechanism by which NK cells can promote CAV. Together, these results define a previously unknown pathway toward CAV and assign a novel role to NK cells in organ allograft rejection. C1 Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med,Transplantat Div, Boston, MA 02114 USA. Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med,Cardiac Surg Div, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med,Transplantat Div, BUL 119, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL071932] NR 38 TC 108 Z9 113 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 SEP 1 PY 2005 VL 175 IS 5 BP 3424 EP 3430 PG 7 WC Immunology SC Immunology GA 966HL UT WOS:000232010600079 PM 16116237 ER PT J AU Hirakawa, S Brown, LF Kodama, S Min, M Alitalo, K Detmar, M AF Hirakawa, S Brown, LF Kodama, S Min, M Alitalo, K Detmar, M TI Transgenic overexpression of VEGF-C does not enhance skin carcinogenesis but potently promotes tumor and lymph node lymphangiogenesis and metastasis to sentinel lymph nodes and beyond SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Helsinki, Mol Canc Biol Lab, FIN-00014 Helsinki, Finland. Swiss Fed Inst Technol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 346 BP A59 EP A59 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600344 ER PT J AU Schacht, V Meadows, K Hirakawa, S Bruckner-Tuderman, L Detmar, M AF Schacht, V Meadows, K Hirakawa, S Bruckner-Tuderman, L Detmar, M TI The lymphatic glycoprotein podoplanin enhances inflammation in a podoplanin transgenic mouse model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Univ Freiburg, D-7800 Freiburg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Swiss Fed Inst Technol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 206 BP A35 EP A35 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600204 ER PT J AU Zhang, JM Tachado, SD Patel, N Zhu, JP Imrich, A Manfruelli, P Cushion, M Kinane, TB Koziel, H AF Zhang, JM Tachado, SD Patel, N Zhu, JP Imrich, A Manfruelli, P Cushion, M Kinane, TB Koziel, H TI Negative regulatory role of mannose receptors on human alveolar macrophage proinflammatory cytokine release in vitro SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE innate immunity; host defense; immunology; phagocytosis ID PNEUMOCYSTIS-CARINII-PNEUMONIA; TUMOR-NECROSIS-FACTOR; HUMAN DENDRITIC CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; SCAVENGER RECEPTOR; FACTOR-ALPHA; INFLAMMATORY RESPONSES; MEDIATED PHAGOCYTOSIS; ESCHERICHIA-COLI; IL-12 PRODUCTION AB Alveolar macrophages (AM) are critical components of lung innate immunity and contribute to an effective host response to Pneumocystis pneumonia. Recognition of unopsonized Pneumocystis organisms by human AM is mediated predominantly via mannose receptors and results in phagocytosis, release of reactive oxygen species, and activation of the nuclear transcription factor (NF)-kappa B. However, the AM host defense genes activated by Pneumocystis have not been defined. In the present study, incubation of AM with unopsonized Pneumocystis organisms was not associated with release of interleukin (IL)-1 beta, IL-6, or tumor necrosis factor (TNF)-alpha (important cytokines in the host response to Pneumocystis) and did not induce IL-1 beta, IL-6, or TNF-alpha mRNA transcripts. These findings were not attributed to Pneumocystis-induced cytopathic changes, as these same AM released IL-8 and matrix metalloproteinase-9 in response to Pneumocystis. NF-kappa B-mediated IL-8 release was independent of Pneumocystis phagocytosis. The observed response was specific, as IL-1 beta, IL-6, and TNF-alpha release and mRNA induction were preserved in response to lipopolysaccharide or serum-opsonized Pneumocystis. The absence of IL-1 beta, IL-6, and TNF-alpha release in response to Pneumocystis was predominately influenced by AM mannose receptors, as blocking mannose receptors or targeted mannose receptor small interfering RNA functional gene silencing resulted in TNF-alpha release in response to unopsonized Pneumocystis organisms. Furthermore, ligation of AM mannose receptors by unopsonized Pneumocystis organisms reduced Toll-like receptor 4-mediated TNF-alpha release. Taken together, these data suggest that mannose receptors on human AM may suppress select proinflammatory cytokine release and may serve to regulate the innate inflammatory responses to infections challenge in the lungs. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Publ Hlth, Div Pulm & Crit Care Med,Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koziel, H (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Publ Hlth, Div Pulm & Crit Care Med,Dept Med, Room E-KSB-23,330 Brookline Ave, Boston, MA 02215 USA. EM hkoziel@bidmc.harvard.edu FU NHLBI NIH HHS [F32 HL71372, R01 HL63655] NR 57 TC 59 Z9 61 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2005 VL 78 IS 3 BP 665 EP 674 DI 10.1189/jlb.1204699 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 961TZ UT WOS:000231686000011 PM 16000387 ER PT J AU Lu, XM Lu, M Tompkins, RG Fischman, AJ AF Lu, XM Lu, M Tompkins, RG Fischman, AJ TI Site-specific detection of S-nitrosylated PKB alpha/Akt1 from rat soleus muscle using CapLC-Q-TOFmicro mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE PKB alpha/Akt1; S-nitrosylation; capillary LC/MS/MS; parent ion discovery; proteomics ID NITRIC-OXIDE; PROTEINS; PKB/AKT; CELLS; PEPTIDES; PATHWAY; SIGNAL; AKT AB Protein Kinase B alpha(PKB alpha, or Akt1) is believed to play a crucial role in programmed cell death, cancer progression and the insulin-signaling cascade. The protein is activated by phosphorylation at multiple sites and subsequently phosphorylates and activates eNOS. Free cysteine residues of the protein may capture reactive, endogenously produced nitric oxide (NO) as S-nitrosothiols. Site-specific detection of S-nitrosylated cysteine residues, usually at low stoichiometry, has been a major challenge in proteomic research largely due to the lack of mass marker for S-nitrosothiols that are very labile under physiologic conditions. In this report we describe a sensitive and specific MS method for detection of S-nitrosothiols in PKB alpha/Akt1 in rat soleus muscle. PKB a/Akt1 was isolated by immunoprecipitation and 2D-gel electrophoresis, subjected to in-gel tryptic digestion, and cysteinyl nitrosothiols were reacted with iodoacetic acids [2-C-12/C-13 = 50/50] under ascorbate reduction conditions. This resulted in the production of relatively stable carboxymethylcysteine (CMC) immonium ions (m/z 134.019 and m/z 135.019) within a narrow argon collision energy (CE = 30 +/- 5 V) in the high MS noise region. In addition, free and disulfide-linked cysteine residues were converted to carboxyamiclomethylcysteines (CAM). Tryptic S-nitrosylated parent ion was detected with a mass accuracy of 50 mDa for the two CMC immonium ions at the triggered elution time during capillary liquid chromatography (LC) separation. A peptide containing Cys(296) was discriminated from four co-eluting tryptic peptides under lock mass conditions (m/z 785.8426). S-nitrosothiol in the tryptic peptide, ITDFGLBKEGIK (B: CAM, [M + 2H](2+) = 690.86, Found: 690.83), is believed to be present at a very low level, since the threshold for the CMC immonium trigger ions was set at 3 counts/s in the MS survey. The high levels of NO that are produced under stress conditions may result in increased S-nitrosylation Of Cys(216) which blocks disulfide bond formation between Cys(296) and Cys(310) and suppresses the biological effects of PKB alpha/Akt1. With the procedures developed here, this process can be studied under physiological and pathological conditions. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Surg Serv, 55 Fruit St, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu FU NIGMS NIH HHS [P50 GM21000] NR 20 TC 25 Z9 25 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD SEP PY 2005 VL 40 IS 9 BP 1140 EP 1148 DI 10.1002/jms.885 PG 9 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 967FZ UT WOS:000232078200002 PM 16041729 ER PT J AU Pekary, AE Faull, KF Paulson, M Lloyd, RL Sattin, A AF Pekary, AE Faull, KF Paulson, M Lloyd, RL Sattin, A TI TRH-like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE TRH-like peptides; affinity chromatography; HPLC; mass spectrometry ID THYROTROPIN-RELEASING-HORMONE; PGLU-GLU-PRO-NH2 EEP; XENOPUS-LAEVIS; IN-VITRO; CLONING; CDNA; AMIDE; RECEPTORS; ANALOGS; SKIN AB We have previously reported the occurrence of pGlu-Glu-Pro-NH2(Glu-TRH, EEP), Val-TRH, Tyr-TRH, Leu-TRH, Phe-TRH, and Trp-TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross-react with the general structure pGlu-X-Pro-NH2 where 'X' maybe any amino acid residue (Peptides 2004; 25:647). This new family of TRH-like peptides, along with TRH (pGlu-His-Pro-NH2) has neuroprotective, anticonvulsant, antidepressant, euphoric, anti-amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr-TRH and Phe-TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr-TRH in rat brain. Furthermore, synthetic Tyr-TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Pasarow Mass Spect Lab, Dept Psychiat & Biobehav Sci, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90073 USA. Univ Minnesota, Dept Biol, Duluth, MN 55812 USA. Univ Minnesota, Dept Psychol, Duluth, MN 55812 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eugene.pekary@med.va.gov NR 54 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD SEP PY 2005 VL 40 IS 9 BP 1232 EP 1236 DI 10.1002/jms.904 PG 5 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 967FZ UT WOS:000232078200011 ER PT J AU Hutchin, T Gray, RGF Preece, MA Chakrapani, A Hardy, J Olpin, S Breuton, L Shih, VE Zeng, WQ Gao, H AF Hutchin, T Gray, RGF Preece, MA Chakrapani, A Hardy, J Olpin, S Breuton, L Shih, VE Zeng, WQ Gao, H TI Partial uniparental disomy in fumarase deficiency - A reassessment of recurrence risk SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 12-14, 2005 CL Univ York, York, ENGLAND SP British Soc Human Genet HO Univ York C1 Birmingham Childrens Hosp, Dept Clin Chem, Birmingham, W Midlands, England. Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. Birmingham Womens Hosp, Birmingham, W Midlands, England. Massachusetts Gen Hosp, Amino Acid Disorders Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. EM tim.hutchin@bch.nhs.uk 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 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2005 VL 42 SU 1 BP S59 EP S59 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 966GV UT WOS:000232009000122 ER PT J AU Quinones, MP Estrada, CA Kalkonde, Y Ahuja, SS Kuziel, WA Mack, M Ahuja, SS AF Quinones, MP Estrada, CA Kalkonde, Y Ahuja, SS Kuziel, WA Mack, M Ahuja, SS TI The complex role of the chemokine receptor CCR2 in collagen-induced arthritis: implications for therapeutic targeting of CCR2 in rheumatoid arthritis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE arthritis; collagen; antibody; leukocytes; chemokines ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; C57BL/6 H-2(B) MICE; T-CELLS; REGULATORY ACTIVITY; SYNOVIAL-FLUID; INFLAMMATORY ARTHRITIS; HUMAN CHONDROCYTES; DENDRITIC CELLS; CCR2(-/-) MICE; KNOCKOUT MICE AB CCR2 has been widely considered as a potential therapeutic target for autoimmune disease, particularly rheumatoid arthritis, and various CCR2 blocking agents have been developed, some of which have entered clinical trials. In this review, we examine the relevant information regarding the role of CCR2, and to a lesser extent of the closely related chemokine receptor CCR5, in the immunopathogenesis of collagen-induced arthritis, an animal model of rheumatoid arthritis. Experimental evidence showing that CIA is accelerated and exacerbated when CCR2 is genetically inactivated (knockout mice) or blocked with specific antibodies warrant additional investigations before the relevance of the findings in rodent models can be applied to human patients with RA. C1 Univ Munich, Med Policlin, D-80336 Munich, Germany. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med MC 7870, San Antonio, TX 78229 USA. Vet Adm, Ctr Res AIDS & HIV1 Infect, San Antonio, TX USA. Prot Design Lab Inc, Fremont, CA 94555 USA. RP Ahuja, SS (reprint author), Univ Munich, Med Policlin, Pettenkoferstr 8A, D-80336 Munich, Germany. EM ahuja@uthscsa.edu; mack@medpoli.med.uni-muenchen.de FU NIAID NIH HHS [AI48644] NR 67 TC 47 Z9 51 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD SEP PY 2005 VL 83 IS 9 BP 672 EP 681 DI 10.1007/s00109-005-0637-5 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 960OE UT WOS:000231602200003 PM 15827759 ER PT J AU Poon, CS Merfeld, DM AF Poon, Chi-Sang Merfeld, Daniel M. TI Internal models: the state of the art SO JOURNAL OF NEURAL ENGINEERING LA English DT Editorial Material C1 [Poon, Chi-Sang] MIT, Cambridge, MA 02139 USA. [Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Poon, CS (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD SEP PY 2005 VL 2 IS 3 SI SI DI 10.1088/1741-2552/2/3/E01 PG 5 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V23DV UT WOS:000208324400001 ER PT J AU Zupan, LH Merfeld, DM AF Zupan, L. H. Merfeld, D. M. TI An internal model of head kinematics predicts the influence of head orientation on reflexive eye movements SO JOURNAL OF NEURAL ENGINEERING LA English DT Article AB Our sense of self-motion and self-orientation results from combining information from different sources. We hypothesize that the central nervous system (CNS) uses internal models of the laws of physics to merge cues provided by different sensory systems. Different models that include internal models have been proposed; we focus herein on that referred to as the sensory weighting model (Zupan et al 2002 Biol. Cybern. 86 209-30). For simplicity, we isolate the portion of the sensory weighting model that estimates head angular velocity: it includes an inverse internal model of head kinematics and an 'idiotropic' vector aligned with the main body axis. Following a post-rotatory tilt in the dark, which is a rapid tilt following a constant-velocity rotation about an earth-vertical axis, the inverse internal model is applied to conflicting vestibular signals. Consequently, the CNS computes an inaccurate estimate of head angular velocity that shifts toward alignment with an estimate of gravity. Since reflexive eye movements known as vestibulo-ocular reflexes (VOR) compensate for this estimate of head angular velocity, the model predicts that the VOR rotation axis shifts toward alignment with this estimate of gravity and that the VOR time constant depends on final head orientation. These predictions are consistent with experimental data. C1 [Zupan, L. H.; Merfeld, D. M.] Harvard Univ, Dept Otol & Laryngol, Jenks Vestibular Physiol Lab, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02114 USA. RP Zupan, LH (reprint author), Harvard Univ, Dept Otol & Laryngol, Jenks Vestibular Physiol Lab, Massachusetts Eye & Ear Infirm,Sch Med, Suite 421,243 Charles St, Boston, MA 02114 USA. EM lionel_zupan@meei.harvard.edu FU NASA [NNJ04HF79G, NNJ04HB01G] FX This research was supported by NASA grants NNJ04HF79G (LHZ) and NNJ04HB01G (DMM). We thank Drs Dora Angelaki and Bernhard Hess for providing us with electronic versions of their original figures from Angelaki and Hess (1994) that we reprinted with the permission from the American Physiological Society. We thank Robert Ocampo for manually recovering experimental data sets via scanned figures from Angelaki and Hess (1994). We thank D Scott for help in improving the manuscript. NR 83 TC 11 Z9 11 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD SEP PY 2005 VL 2 IS 3 SI SI DI 10.1088/1741-2560/2/3/S03 PG 18 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V23DV UT WOS:000208324400004 PM 16135883 ER PT J AU Henson, JW Hobbs, W Chakravarti, A Louis, DN AF Henson, JW Hobbs, W Chakravarti, A Louis, DN TI Alterations in p53, p21, and MIB-1 labeling index in primary human astrocytomas following radiation therapy SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE EGFR; glioblastoma; glioma; p21; p53; radiation ID GLIOBLASTOMA-MULTIFORME; RECEPTOR; PROTEIN; GLIOMAS; CELLS AB Little is known about the cellular and genetic changes that occur in human astrocytomas following radiation therapy (RT). Experimental studies would suggest that early effects include induction of p53 and p21 expression, cell cycle arrest, and selection of tumor cells with molecular changes that correlate with radiation resistance. Unfortunately, tissue sampling of primary human astrocytomas closely following radiation therapy is uncommon, hindering comparative assessment of primary human tumors. Through local databases, we were able to collect eight cases in which tissue was resected within 8 weeks of RT because of bulky residual disease: two patients with grade II diffuse astrocytomas (LGA) and 6 patients with high-grade astrocytomas (HGA; 1 anaplastic astrocytoma, 5 glioblastomas). Routine histopathologic sections, MIB-1 labeling index (LI), p53 and p21 expression, and EGFR expression were compared between the pre- and post-RT samples. Only one tumor (52d post-RT) showed prominent radiation-induced histopathologic changes. p53 expression was detected in two tumors pre-RT and in six tumors post-RT. In the four tumors in which p53 expression was induced, the post-RT LI was lower in each case, and p21 expression had increased in 3/4 of these cases. No change in LI was detected in tumors in which p53 expression was unchanged. EGFR expression was not altered following RT. The results of this unique series document that some primary human astrocytomas increase expression of p53 and p21 and decrease proliferation in response to RT. However, the small size of the series argues for further studies of radiation induced molecular changes in primary human astrocytoma tissue. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Radiat Oncol Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA. EM henson@helix.mgh.harvard.edu NR 14 TC 5 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2005 VL 74 IS 2 BP 151 EP 154 DI 10.1007/s11060-004-6911-5 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 969TB UT WOS:000232256500007 PM 16193385 ER PT J AU Chu, CT Zhu, J Cao, GD Signore, A Wang, SP Chen, J AF Chu, CT Zhu, J Cao, GD Signore, A Wang, SP Chen, J TI Apoptosis inducing factor mediates caspase-independent 1-methyl-4-phenylpyridinium toxicity in dopaminergic cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopaminergic cells; mitochondria; neuronal cell death; Parkinson's disease; primary midbrain neurons; RNA interference ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PARKINSONS-DISEASE; DISTINCT MECHANISMS; NEURONAL CULTURES; FACTOR AIF; DEATH; ACTIVATION; MICE; 6-HYDROXYDOPAMINE AB Parkinson's disease is a debilitating neurodegenerative disease characterized by loss of midbrain dopaminergic neurons. These neurons are particularly sensitive to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes parkinsonian syndromes in humans, monkeys and rodents. Although apoptotic cell death has been implicated in MPTP/MPP+ toxicity, several recent studies have challenged the role of caspase-dependent apoptosis in dopaminergic neurons. Using the midbrain-derived MN9D dopaminergic cell line, we found that MPP+ treatment resulted in an active form of cell death that could not be prevented by caspase inhibitors or over-expression of a dominant negative inhibitor of apoptotic protease activating factor 1/caspase-9. Apoptosis inducing factor (AIF) is a mitochondrial protein that may mediate caspase-independent forms of regulated cell death following its translocation to the nucleus. We found that MPP+ treatment elicited nuclear translocation of AIF accompanied by large-scale DNA fragmentation. To establish the role of AIF in MPP+ toxicity, we constructed a DNA vector encoding a short hairpin sequence targeted against AIF. Reduction of AIF expression by RNA interference inhibited large-scale DNA fragmentation and conferred significant protection against MPP+ toxicity. Studies of primary mouse midbrain cultures further supported a role for AIF in caspase-independent cell death in MPP+-treated dopaminergic neurons. C1 Univ Pittsburgh, Sch Med, Dept Pathol, Div Neuropathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chu, CT (reprint author), UPMC Presbyterian, Room A-516,200 Lothrop St, Pittsburgh, PA 15213 USA. EM ctc4@pitt.edu RI Chu, Charleen/B-1601-2008 OI Chu, Charleen/0000-0002-5052-8271 FU NINDS NIH HHS [NS43802, NS40817, NS44178, R01 NS040817, R01 NS043802, R01 NS044178] NR 46 TC 65 Z9 70 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2005 VL 94 IS 6 BP 1685 EP 1695 DI 10.1111/j.1471-4159.2005.03329.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 959HS UT WOS:000231509400019 PM 16156740 ER PT J AU Brandstaedter, D Spieker, S Ulm, G Siebert, U Eichhorn, TE Krieg, JC Oertel, WH Eggert, K AF Brandstaedter, D Spieker, S Ulm, G Siebert, U Eichhorn, TE Krieg, JC Oertel, WH Eggert, K TI Development and evaluation of the Parkinson Psychosis Questionnaire - A screening-instrument for the early diagnosis of drug-induced psychosis in Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Parkinson Psychosis Questionnaire; drug-induced psychosis; Parkinson's disease; screening-instrument; BPRS; SCID ID RISK-FACTORS; HALLUCINATIONS; PREVALENCE; MORTALITY AB Objective Drug-induced psychosis is a frequent side-effect in the treatment of advanced Parkinson's disease (PD). We sought to develop and evaluate a brief instrument for early recognition of drug-induced psychosis in PD. Methods We developed the "Parkinson Psychosis Questionnaire" (PPQ), which consists of screening questions for typical early signs and psychotic symptoms in PD and which quantifies the frequency and severity of four clinical categories-sleep disturbances, hallucinations/illusions, delusions and orientation. We performed an internal validation of the PPQ in 50 unselected patients with parkinsonism. The Brief Psychiatric Rating Scale (BPRS) and the "Structurized Clinical Interview" (SCID) for DSM IV were applied to the same patients as external references. Results Of 50 subjects, 49 suffered from idiopathic PD and one from probable MSA-P. Hoehn and Yahr stages in "on" ranged from 1.5 to 4. Sensitivity of the PPQ test for drug-induced psychosis according to SCID was 100 % (95 % CI: 73.5%, 100%); while specificity was 92.1 % (95% CI: 78.6%, 98.3 %). The PPQ severity score was highly correlated with BPRS. We derived a linear prediction formula, which transformed PPQ into BPRS scores. Conclusion The PPQ appears to be a suitable, and easily administered instrument for early diagnosis of druginduced psychosis in routine PD care. Whether the PPQ could also be a valuable tool for monitoring follow-up studies and therapeutic intervention trials remains to be tested. C1 Univ Marburg, Dept Neurol, D-35039 Marburg, Germany. Paracelsus Elena Clin, Kassel, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Univ Marburg, Dept Psychiat & Psychotherapy, Marburg, Germany. RP Oertel, WH (reprint author), Univ Marburg, Dept Neurol, Rudolf Bultmann Str 8, D-35039 Marburg, Germany. EM oertelw@med.uni-marburg.de NR 28 TC 24 Z9 25 U1 1 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 2005 VL 252 IS 9 BP 1060 EP 1066 DI 10.1007/s00415-005-0816-x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 965TX UT WOS:000231974300009 PM 15789127 ER PT J AU Anderson, CA Arciniegas, DB Filley, CM AF Anderson, CA Arciniegas, DB Filley, CM TI Treatment of acute ischemic stroke: Does it impact neuropsychiatric outcome? SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Neuropsychiatric-Association CY FEB 21-24, 2004 CL Bal Harbour, FL SP Amer Neuropsychiat Assoc ID COMPLICATIONS; DEPRESSION; TRIALS AB Stroke is a leading cause of disability globally. Although neuropsychiatric symptoms are produced by stroke and adversely effect stroke outcome, it is unclear whether neuropsychiatric outcome can be improved by acute stroke treatment. The authors reviewed published acute ischemic stroke treatment trials to determine whether neuropsychiatric outcome measures were employed. Of the 190 trials reviewed, only seven included specific measures of neuropsychiatric outcome, usually a short test of cognition or mood. Further studies are needed to determine the potential benefits of acute stroke treatment on both poststroke neuropsychiatric symptoms and the relationship between such symptoms and stroke outcome. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO USA. RP Anderson, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. EM al.anderson@UCHSC.edu RI Arciniegas, David/A-3792-2009 NR 17 TC 5 Z9 5 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2005 VL 17 IS 4 BP 486 EP 488 DI 10.1176/appi.neuropsych.17.4.486 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 993PH UT WOS:000233966900007 PM 16387987 ER PT J AU Bracha, HS Garcia-Rill, E Mrak, RE Skinner, R AF Bracha, HS Garcia-Rill, E Mrak, RE Skinner, R TI Postmortem locus coeruleus neuron count in three American veterans with probable or possible war-related PTSD SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PARKINSONS-DISEASE; BRAIN COLLECTION; SENILE DEMENTIA; ALZHEIMER TYPE; NOREPINEPHRINE; SCHIZOPHRENIA; PROPRANOLOL; DEPRESSION; VICTIMS AB The authors investigated whether war-related posttraumatic stress disorder (WR-PTSD) is associated with a postmortem change in neuronal counts in the locus coeruleus (LC) since enhanced central nervous system (CNS) noradrenergic postsynaptic responsiveness has been previously shown to contribute to PTSD pathophysiology. Using postmortem neuromorphometry, the number of neurons in the right LC in seven deceased elderly male veterans was counted. Three veterans were classified as cases of probable or possible WR-PTSD. All three veterans with probable or possible WR-PTSD were found to have substantially lower LC neuronal counts compared to four comparison subjects (three nonpsychiatric veterans and one veteran with alcohol dependence and delirium tremens). To the authors' knowledge, this case series is the first report of LC neuronal counts in patients with PTSD or any other DSM-IV-TR anxiety disorder. Previous postmortem brain tissue studies of Alzheimer's Disease (AD) demonstrated an upregulation of NE biosynthetic capacity in surviving LC neurons. The finding reported is consistent with the similar upregulation of NE biosynthetic capacity of surviving LC neurons in veterans who developed WR-PTSD. Especially if replicated, this finding in WR-PTSD may provide further explanation of the dramatic effectiveness of propranolol and prazosin for the secondary prevention and treatment of PTSD, respectively. The LC neurons examined in this study are probably the origin of the first or second "leg" of what might be termed the PTSD candidate circuit. Larger neuromorphometric studies of the LC in veterans with WR-PTSD and in other development-stress-induced and fear-circuitry disorders are warranted, especially using VA registries. C1 US Dept Vet Affairs, VA Natl Ctr Posttraumat Stress Disorder, Pacific Isl Hlth Care Syst, Spark M Matsunaga VA Med Ctr, Honolulu, HI USA. Univ Arkansas Med Sci, Coll Med, Dept Neurobiol & Dev Sci, Ctr Translat Neurosci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. RP Bracha, HS (reprint author), Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Pacific Isl Hlth Care Syst, Spark M Matsunaga VA Med Ctr, 1132 Bishop St 307, Honolulu, HI 96822 USA. EM H.Bracha@med.va.gov OI Garcia-Rill, Edgar/0000-0003-1367-3071 FU NCRR NIH HHS [P20 RR020146]; NIMH NIH HHS [R01 MH 45729] NR 38 TC 25 Z9 28 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2005 VL 17 IS 4 BP 503 EP 509 DI 10.1176/appi.neuropsych.17.4.503 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 993PH UT WOS:000233966900010 PM 16387990 ER PT J AU Davalos, DB Kisley, MA Freedman, R AF Davalos, DB Kisley, MA Freedman, R TI Behavioral and electrophysiological indices of temporal processing dysfunction in schizophrenia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Cognitive-Neuroscience-Society CY APR, 2004 CL San Francisco, CA SP Cognit Neurosci Soc ID EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; TIME-ESTIMATION; AFFECTIVE-DISORDERS; INTERVAL DURATION; INTERNAL CLOCK; MEMORY; DEVIANCE; DEFICIT; BRAIN AB Timing deficits in schizophrenia have been noted in several behavioral studies. However, the involvement of mediating factors, such as inattention, has not been ruled out as contributing to these effects. Mismatch negativity (MMN), an electrophysiological measure, may provide a more direct index of stimulus processing ability in individuals with schizophrenia. The current study explored the relationship between behavioral time judgments and a time-based MMN paradigm. Participants were administered two MMN paradigms consisting of an "easy" or "difficult" deviant and an analogous behavioral measure of time processing. Matched against a healthy comparison group, patients exhibited decreased MMN amplitude on the "difficult" deviant interval only. However, on the behavioral paradigm, the patients made significantly more errors across all conditions. These results suggest that behavioral measures: of time processing may reflect different processes than those captured by preattentive physiological measures in this population. C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Colorado Springs, CO 80907 USA. RP Davalos, DB (reprint author), Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. EM Davalos@ColoState.Edu FU NIMH NIH HHS [MH 56539, MH 152442] NR 37 TC 27 Z9 28 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2005 VL 17 IS 4 BP 517 EP 525 DI 10.1176/appi.neuropsych.17.4.517 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 993PH UT WOS:000233966900012 PM 16387992 ER PT J AU Emery, DL Fulp, CT Saatman, KE Schutz, C Neugebauer, E McIntosh, TK AF Emery, DL Fulp, CT Saatman, KE Schutz, C Neugebauer, E McIntosh, TK TI Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE BrdU; hippocampus; mossy fiber pathway; neurogenesis; neuronal plasticity; progenitor cells; tract tracing; traumatic brain injury ID CENTRAL-NERVOUS-SYSTEM; TRANSIENT GLOBAL-ISCHEMIA; NMDA RECEPTOR ACTIVATION; ADULT-RAT; STEM-CELLS; ENHANCED NEUROGENESIS; SPINAL-CORD; PSA-NCAM; PROLIFERATION; NEURONS AB We investigated whether new neurons generated in the adult rat brain following lateral fluid percussion traumatic brain injury (TBI) are capable of projecting axons along the mossy fiber pathway to the CA3 region of the hippocampus. Dividing cells were labeled by intraperitoneal injection of bromodeoxyuridine (BrdU) on the day of surgery/injury, and neurons that extended axons to the CA3 region were retrogradely labeled by fluorescent tracers (FluoSpheres(R)), stereotactically injected into the CA3 region of both the ipsi- and contralateral hippocampus at I or 12 days following TBI (n = 12) or sham injury (n = 12) in anaesthetized rats. Animals (11 = 6 injured and n = 6 sham-injured controls per time point) were sacrificed at either 3 or 14 days post-injury. Another group of animals (n = 3) was subjected to experimental TBI and BrdU administration and sacrificed 3 days after TBI to be processed for BrdU and immunohistochemistry for polysialylated neural cell adhesion molecule (PSA-NCAM), a growth-related protein normally observed during CNS development. A fivefold bilateral increase in the number of mitotically active (BrdU+) cells was noted within the dentate gyrus when compared to uninjured controls as early as 3 days following TBI. A subgroup of dividing cells was also immunoreactive for PSA-NCAM at 3 days following TBI. By 2 weeks post-injury the number of BrdU+ cells within the dentate gyrus was increased twofold compared to the uninjured counterparts and a proportion of these newly generated cells showed cytoplasmic staining for the fluorescent tracer. These findings document rapid neurogenesis following TBI and show, for the first time, that newly generated granule neurons are capable of extending projections along the hippocampal mossy fiber pathway in the acute post-traumatic period. C1 Univ Kentucky, Spinal Cord & Brain Injury Ctr, Lexington, KY 40536 USA. Univ Penn, Sch Med, Traumat Brain Injury Lab, Dept Neurosurg, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Cologne, Dept Expt Surg, Cologne, Germany. RP Saatman, KE (reprint author), Univ Kentucky, Spinal Cord & Brain Injury Ctr, B367 BB3RB,741 S Limestone St, Lexington, KY 40536 USA. EM K.Saatman@uky.edu RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 FU NINDS NIH HHS [P50-NS08803, R01-NS40978]; PHS HHS [R01-45131] NR 83 TC 45 Z9 47 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2005 VL 22 IS 9 BP 978 EP 988 DI 10.1089/neu.2005.22.978 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 967HP UT WOS:000232082600005 PM 16156713 ER PT J AU Pellegrino, D Bonab, AA Dragotakes, SC Pitman, JT Mariani, G Carter, EA AF Pellegrino, D Bonab, AA Dragotakes, SC Pitman, JT Mariani, G Carter, EA TI Inflammation and infection: Imaging properties of F-18-FDG-Labeled white blood cells versus F-18-FDG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18-FDG-labeled white blood cells; infection; inflammation; biodistribution; microPET; phosphorimaging ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN-GRANULOCYTES; LEUKOCYTES; INJURY; FDG; BIODISTRIBUTION; RECRUITMENT; NEUTROPHILS; ABSCESSES; IN-111 AB F-18-FDG and F-18-FDG-labeled white blood cells (F-18-FDGWBCs) are valuable radiopharmaceuticals for imaging focal sites of inflammation and infection. In the present study, the imaging properties of both radiotracers were compared in sterile and septic inflammation models. Methods: Groups of adult male Sprague-Dawley rats (100-120 g) were injected in the left posterior thigh muscle with saline solution (group 1: controls, n = 15), 0.100 mL of turpentine oil (group 2: sterile inflammation, n 26), 109 viable Escherichia coli bacteria (group 3: E coli septic inflammation, n = 29), or 108 viable Pseudomonas aeruginosa bacteria (group 4: P. aeruginosa septic inflammation, n = 25). Twenty-four hours later, the animals were divided into 2 groups: One received 18F-FDG intravenously and the other received human white blood cells (WBCs) labeled in vitro with 18F-FDG injected intravenously. Biodistribution and microPET studies were performed 1 h after radiotracer injection. One hour after injection with celi-associated or free F-18-FDG, phosphorimaging of abscess and contralateral muscle was performed in specimens collected from animals in groups 1, 2, and 3. The region of interest was selected within the abscess wall and values were converted to kBq/g using a C-14 calibration standard curve. Thin-layer radiochromatography (TLRC) was performed to study the chemical forms of F-18 within the WBCs. Results: Whole-body biodistribution demonstrated a significantly higher uptake ratio of F-18-FDG-WBCs compared with 18F-FDG in all sterile and septic inflammation models (t test: sterile, P = 0.048; E coli, P = 0.040; P. aeruginosa, P = 0.037). microPET imaging confirmed the greater performance of 18F-FDG-WBCs versus 18F-FDG in the sterile inflammation model and in both E coli and P. aeruginosa septic models. Phosphorimaging analysi's showed higher F-18-FDG-WBC uptake than 18F-FDG in the sterile inflammation and P. aeruginosa septic models and similar tissue uptake in the E coli septic model. Time course labeling and TLRC of lysed WBCs demonstrated that 18F-FDG was retained as F-18-FDG-6-phosphate inside WBCs for at least 2 h, corresponding to the time frame of analysis. Conclusion: 18F-FDGWBCs gave better results compared with 18F-FDG in all sterile and septic inflammation models. These data suggest that F-18-FDG-WBC PET may be a useful technique for tracking focal inflammatory lesions in the body. C1 Univ Pisa, Sch Med, Dept Oncol, Div Nucl Med, I-56126 Pisa, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Nucl Med Div, Boston, MA USA. RP Mariani, G (reprint author), Univ Pisa, Sch Med, Reg Ctr Nucl Med, Via Roma 67, I-56126 Pisa, Italy. EM g.mariani@med.unipi.it NR 35 TC 56 Z9 57 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2005 VL 46 IS 9 BP 1522 EP 1530 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 962GZ UT WOS:000231720300022 PM 16157536 ER PT J AU Ulrich, BT Buerhaus, PI Donelan, K Norman, L Dittus, R AF Ulrich, BT Buerhaus, PI Donelan, K Norman, L Dittus, R TI How RNs view the work environment - Results of a national survey of registered nurses SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID INTENSIVE-CARE UNITS; SATISFACTION; EMPOWERMENT; BURNOUT; IMPACT AB Objective: To determine registered nurses' (RNs') views of the workplace environment. Background: Numerous studies have shown relationships between work environment, RN satisfaction and retention, and patient safety and outcomes. In 2002, NurseWeek Publishing and the American Organization of Nurse Executives completed a national survey on the views of RNs on the nursing shortage, workplace environments, and their future career intentions, which revealed areas needing improvement. Results from the follow-up survey conducted in 2004 provide new information on RNs' views of the work environment and a comparison of results to the previous survey. Methods: A nationally representative random sample of 3500 RNs licensed to practice in the United States was surveyed. Results: In the views of RNs, there have been improvements in a number of aspects of the work environment of nurses. While there are no areas of decline, there are areas in which little or no progress is apparent. Conclusions/Implications: Some strategies designed to improve the work environment have resulted in positive outcomes, but creative solutions must be continuously developed and implemented to build on recent successes. Results of this survey help identify areas for continued improvement efforts. C1 Nursing Spectrum, Professional & Editorial Serv, Dallas, TX 75234 USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ulrich, BT (reprint author), Nursing Spectrum, Professional & Editorial Serv, 2655 Villa Creek Dr,Suite 250, Dallas, TX 75234 USA. EM BUlrich@NursingSpectrum.com NR 39 TC 62 Z9 62 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2005 VL 35 IS 9 BP 389 EP 396 PG 8 WC Nursing SC Nursing GA 964OA UT WOS:000231889200008 PM 16200006 ER PT J AU Maag, M Fonteyn, M AF Maag, M Fonteyn, M TI Using a collaborative learning method to enhance mastery of pathophysiology content SO JOURNAL OF NURSING EDUCATION LA English DT Editorial Material C1 Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Maag, M (reprint author), Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. EM maag@usfca.edu NR 3 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD SEP PY 2005 VL 44 IS 9 BP 435 EP 436 PG 2 WC Nursing SC Nursing GA 972PX UT WOS:000232466800011 PM 16220654 ER PT J AU Liu, YC Woodin, MA Smith, TJ Herrick, RF Williams, PL Hauser, R Christiani, DC AF Liu, YC Woodin, MA Smith, TJ Herrick, RF Williams, PL Hauser, R Christiani, DC TI Exposure to fuel-oil ash and welding emissions during the overhaul of an oil-fired boiler SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE boilermakers; exposure assessment; occupational health; respiratory health; toxic metals; vanadium ID VANADIUM PENTOXIDE EXPOSURE; PARTICULATE MATTER; RESPIRATORY-TRACT; WORKERS AB The health effects of exposure to vanadium in fuel-oil ash are not well described at levels ranging from 10 to 500 mu g/m(3). As part of a larger occupational epidemiologic study, that assessed these effects during the overhaul of a large oilfired boiler, this study was designed to quantify boilermakers' exposures to fuel-oil ash particles, metals, and welding gases, and to identify determinants of these exposures. Personal exposure measurements were conducted on 18 boilermakers and 11 utility workers (referents) before and during a 3-week overhaul. Ash particles < 10 mu m in diameter (PM10, mg/m(3)) were sampled overfill work shifts using a one-stage personal size selective sampler containing a polytetrafluoroethylene filter. Filters were digested using the Parr bomb method and analyzed for the metals vanadium (V), nickel (Ni), iron (Fe), chromium (Cr), cadmium (Cd), lead (Pb), manganese (Mn), and arsenic (As) by inductively coupled plasma mass spectrometry. Nitrogen dioxide (NO2) was measured with an Ogawa passive badge-type sampler and ozone (O-3) with a personal active pump sampler. Time-weighted average (TWA) exposures were significantly higher (p < 0.05) for boilermakers than for utility workers for PM10 (geometric mean: 0.47 vs. 0.13 mg/m(3)), V (8.9 vs. 1.4 mu g/m(3)), Ni (7.4 vs. 1.8 mu g/m(3)) and Fe (56.2 vs. 11.2 mu g/m(3)). Exposures were affected by overhaul time periods, tasks, and work locations. No significant increases were found for O-3 or NO2 for boilermakers or utility workers regardless of overhaul period or task group. Fuel-oil ash was a major contributor to boilermakers' exposure to PM10 and metals. Vanadium concentrations sometimes exceeded the 2003 American Conference of Governmental Industrial Hygienists (ACGIII) threshold limit value. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Med Unit, Boston, MA USA. RP Liu, YC (reprint author), Yale Univ, Sch Med, Occupat & Environm Med Program, 135 Coll St, New Haven, CT 06510 USA. EM youcheng.liu@yale.edu NR 22 TC 12 Z9 12 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD SEP PY 2005 VL 2 IS 9 BP 435 EP 443 DI 10.1080/15459620591034529 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 961TW UT WOS:000231685700002 PM 16048845 ER PT J AU Halpern, LR Susarla, SM Dodson, TB AF Halpern, LR Susarla, SM Dodson, TB TI Injury location and screening questionnaires as markers for intimate partner violence SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DOMESTIC VIOLENCE; MAXILLOFACIAL INJURIES; EMERGENCY-DEPARTMENT; FACIAL INJURIES; WOMEN; ABUSE; TRAUMA; NECK; HEAD AB Purpose: We sought to evaluate the performance of 2 different screening questionnaires for intimate partner violence (IPV), in conjunction with injury location, as markers for IPV-related injuries. Methods: We implemented a cross-sectional study, and enrolled a sample of women presenting to the emergency department for evaluation and management of nonverifiable injuries. Study, subjects were randomly assigned to receive 1 of 2 IPV screening questionnaires: the Partner Violence Screen (PVS) or the short-Woman Abuse Screening Tool (short-WAST). We evaluated a combination of 2 markers of IPV-related injury: (1) injury location, classified as head/neck/facial (HNF) or other and (2) responses to the IPV questionnaires: positive or negative. Our predictor variable was the probability of self-report of IPV-related injury defined as (1) high probability (HNF injuries were present and there was a positive response to the IPV questionnaire) or (2) low probability (all other combinations of injury location and responses to the questionnaires). The outcome variable was self-reported injury etiology, IPV or other. Demographic variables were also recorded for our study sample. Univariate and bivariate statistical analyses were computed for the sample. Sensitivity, specificity, and positive and negative predictive values and odds ratios were calculated (P <.05). Results: The sample was composed of 200 women. The sensitivities/specificities for the PVS-injury location and short-WAST-injury location combinations were 0.75/0.70 and 0. 7/7/0.61, respectively. The odds ratios for IPV-related injury etiology were 10.2 (3 < OR < 41, P =.01) for the PVS-injury location combination and 3.7 (0.90 < OR < 15, P =.07) for the short-WAST-injury location combination. Conclusions: A set of markers composed of injury location and the PVS was statistically associated with the likelihood of reporting IPV-related injuries. The short-WAST did not perform as well as the PVS in the study ' s clinical setting. (c) 2005 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Halpern, LR (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM lhalpern1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 28 TC 21 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2005 VL 63 IS 9 BP 1255 EP 1261 DI 10.1016/j.joms.2005.05.295 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 961CJ UT WOS:000231639200002 PM 16122587 ER PT J AU Starks, H Pearlman, RA Hsu, C Back, AL Gordon, JR Bharucha, AJ AF Starks, H Pearlman, RA Hsu, C Back, AL Gordon, JR Bharucha, AJ TI Why now? Timing and circumstances of hastened deaths SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE death and dying; physician-assisted suicide; euthanasia; terminal care; qualitative research ID PHYSICIAN-ASSISTED SUICIDE; TERMINALLY-ILL PATIENTS; PATIENT REQUESTS; HOSPICE PATIENTS; EUTHANASIA; ATTITUDES; OREGON; ONCOLOGISTS; EXPERIENCES; CARE AB We interviewed 35 families to understand the liming and circumstances of hastened deaths. We estimated life expectancy for the 26 patients who hastened their deaths and used content analysis to identify patterns in their decisions. On average, patients had lived with their illness for 2.5 years and had actively planned their deaths for 3 months. Those with less than a week to live (n = 10) were 'dying and done, 'having experienced a final functional loss that signaled the end. Those with < 1 month (n = 8) were 'dying, but not fast enough.' Those with 1-6 months (n = 5) saw a 'looming crisis' on their horizon that would prohibit following through with their plans. The 3 patients with > 6 months were 'not recognized by others as dying, but suffering just the same.' Clinicians should regularly assess where patients perceive they are in the dying process and ask about their comfort with the pace of dying to identify for opportunities for intervention. C1 Univ Washington, Dept Med Hist, Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Eth, Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Hlth Adm, Natl Ctr Eth Hlth Care, Washington, DC USA. Grp Hlth Community Fdn, Seattle, WA USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Starks, H (reprint author), Univ Washington, Dept Med Hist, Hlth Serv, Seattle, WA 98195 USA. FU AHRQ HHS [T32 HS-013853] NR 37 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2005 VL 30 IS 3 BP 215 EP 226 DI 10.1016/j.jpainsymman.2205.03.012 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 974CP UT WOS:000232569200006 PM 16183005 ER PT J AU Rickerson, EM Somers, C Allen, CM Lewis, B Strumpf, N Casarett, D AF Rickerson, EM Somers, C Allen, CM Lewis, B Strumpf, N Casarett, D TI How well are we caring for caregivers? Prevalence of grief-related symptoms and need for bereavement support among long-term care staff SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE bereavement; palliative care; PACE; long-term care; hospice ID COMPLICATED GRIEF; DEPRESSION; RESUSCITATION; FAMILIES; DISTINCT; DEATH AB To define the prevalence and correlates of grief-related symptoms among long term care staff who care for patients near the end of life, a cross-sectional survey was conducted at six Program of All-inclusive Care for the Elderly (PACE) organizations that provide long-term care in the home and in institutions. All clinical and non-clinical program staff were surveyed to examine the prevalence of 20 grief-related symptoms and assess current sources of bereavement support, as well as willingness to use additional sources of support. Suveys were completed by 2031236 staff (86%), who described a wide variety of symptoms they attributed to the death of one of their patients in the past month. Most staff (147/203; 72%) reported at least one symptom. Staff with more symptoms had experienced more patient deaths in the past month (Spearman rho = 0. 20, P = 0.007), had worked for a longer time at a PACE organization (Spearman rho = 0. 16, P = 0. 03 1), and reported a closer and longer relationship with the last patient who died (Spearman rho = 0. 32, P < 0. 001; rho = 0. 24, P = 0.0001). Although staff identified several informal sources of bereavement support (mean 2.3 sources, range 0-6), almost all (n = 194; 96%) said they would use additional support services if they were offered. These community-based long-term care staff experience a variety of symptoms attributable to the deaths of their patients, and would welcome additional sources of bereavement support. C1 Univ Penn, Sch Nursing, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ & Promot, Philadelphia, PA USA. RP Rickerson, EM (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 22 TC 17 Z9 18 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2005 VL 30 IS 3 BP 227 EP 233 DI 10.1016/j.jpainsymman.2005.04.005 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 974CP UT WOS:000232569200007 PM 16183006 ER PT J AU Chen, TC Bhatia, LS Walton, DS AF Chen, TC Bhatia, LS Walton, DS TI Ahmed valve surgery for refractory pediatric glaucoma: A report of 52 eyes SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Academy-of-Ophthalmology/Annual Meeting of the ISRS CY NOV 14-18, 2003 CL ANAHEIM, CA SP Amer Acad Ophthalmol, ISRS ID INITIAL CLINICAL-EXPERIENCE; PLATE MOLTENO IMPLANT; COMPLICATED GLAUCOMAS; DRAINAGE IMPLANTS; ENDOPHTHALMITIS; SHUNT; DISK; TRIAL AB Purpose: To describe the results of Ahmed valve surgery for refractory pediatric glaucoma. Patients and Methods: We performed a retrospective review of patients younger than 18 years of age who had Ahmed valve surgery from November 1994 to January 2003. Success was defined as a reduction of the intraocular pressure (IOP) to 22, mm Hg or lower with or without medications at the last two follow-up visits, no additional glaucoma surgery, and no visually significant complications. Results: There were 52 eyes of 41 patients. The two most common diagnoses were congenital glaucoma (38.5%) and aphakic glaucoma (36.5%). The mean number of glaucoma surgeries before Ahmed valve implantation was 1.7 +/- 1.7. The mean age at the time of implantation was 4.9 +/- 6.5 years. The mean IOP decreased from 38.1 +/- 6.4 mm Hg to 20.7 +/- 8.2 mm Hg at last follow-up. The final visual acuity was improved or within one Snellen line in 81.5% of the eyes. Cumulative probabilities of success were 85.1%, 63.2%, 51.7%, and 41.8% at 1, 2, 3, and 4 years, respectively. The mean postoperative follow-up period or time to failure for all patients was 2.2 +/- 1.8 years (range, 3 months to 7.5 years). Conclusions: The Ahmed valve was found to be useful in the management of refractory pediatric glaucoma. Although our success rates were similar to those observed in adults, the rates of certain postoperative complications were different. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Glaucoma Serv, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 22 Z9 28 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD SEP-OCT PY 2005 VL 42 IS 5 BP 274 EP 283 PG 10 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 006ZS UT WOS:000234937200007 PM 16250216 ER PT J AU Findling, RL Biederman, J Wilens, TE Spencer, TJ McGough, JJ Lopez, FA Tulloch, SJ AF Findling, RL Biederman, J Wilens, TE Spencer, TJ McGough, JJ Lopez, FA Tulloch, SJ CA SLI381 301 Study Grp 302 Study Grp TI Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 14-19, 2003 CL Miami, FL SP Amer Acad Child & Adolescent Psychiat ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CLINICAL-PRACTICE GUIDELINE; SLI381 ADDERALL XR; BLOOD-PRESSURE; HEART-RATE; METHYLPHENIDATE; SCHOOL; FORMULATION; ADOLESCENTS AB Objective To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts' extended-release formulation (MAS XR; Adderall XR (R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). Study design Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weeldy during the short-term study, then monthly during long-term treatment. Results Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean, increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. Conclusions Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of <= 30 mg/day in otherwise healthy children. C1 Univ Hosp Cleveland, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Childrens Dev Ctr, Maitland, FL USA. Shire Pharmaceut Dev Inc, Rockville, MD USA. RP Findling, RL (reprint author), Univ Hosp Cleveland, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Robert.Findling@uhhs.com NR 25 TC 40 Z9 40 U1 2 U2 17 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2005 VL 147 IS 3 BP 348 EP 354 DI 10.1016/j.jpeds.2005.03.014 PG 7 WC Pediatrics SC Pediatrics GA 971VE UT WOS:000232412100018 PM 16182674 ER PT J AU Comeau, AM Parad, R Gerstle, R O'Sullivan, MP Dorkin, HL Dovey, M Haver, K Martin, T Eaton, RB AF Comeau, AM Parad, R Gerstle, R O'Sullivan, MP Dorkin, HL Dovey, M Haver, K Martin, T Eaton, RB TI Challenges in implementing a successful newborn cystic fibrosis screening program SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on Newborn Screening for Cystic Fibrosis CY NOV 20-21, 2003 CL Atlanta, GA SP Ctr Dis Control & Prevent, Cystic Fibrosis Fdn ID DIAGNOSIS AB Objective To identify necessary components of a successful cystic fibrosis (CF) newborn screening (NBS) program. Study design The approach to CF NBS used by the Massachusetts NBS program was examined. Results Several key components were identified that should be addressed when a state has made the decision to screen, kind well in advance of actual implementation. These components include (1) inclusion of CF center directors in the development process; (2) logistics of choosing a screening algorithm relative to practices in place and community wishes; (3) projections of medical service needs from specific algorithms; (4) identification of critical reporting components; (5) identification of critical follow-up components; and (6) recognition of educational needs. Conclusions Careful examination of a wide variety of issues is needed to ensure optimal implementation of NBS for CF. C1 Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02130 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Childrens Hosp, Baystate Med Ctr, Springfield, MA USA. Univ Massachusetts, Worcester, MA 01605 USA. RP Comeau, AM (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, 305 South St, Jamaica Plain, MA 02130 USA. EM anne.comeau@umassmed.edu RI Parad, Richard/E-8559-2010 NR 11 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2005 VL 147 IS 3 SU S BP S89 EP S93 DI 10.1016/j.jpeds.2005.08.006 PG 5 WC Pediatrics SC Pediatrics GA 973RT UT WOS:000232541000019 PM 16202791 ER PT J AU Comeau, AM Parad, R Gerstle, R O'Sullivan, BP Dorkin, HL Dovey, M Haver, K Martin, T Eaton, RB AF Comeau, AM Parad, R Gerstle, R O'Sullivan, BP Dorkin, HL Dovey, M Haver, K Martin, T Eaton, RB TI Communications systems and their models: Massachusetts parent compliance with recommended specialty care after positive cystic fibrosis newborn screening result SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on Newborn Screening for Cystic Fibrosis CY NOV 20-21, 2003 CL Atlanta, GA SP Ctr Dis Control & Prevent, Cystic Fibrosis Fdn AB Objective To evaluate compliance with recommendations for sweat testing/specialty evaluation and genetic counseling after a positive cystic fibrosis newborn screening (CF NBS) result. Study design All infants with positive CF NBS results require a diagnostic sweat test at a CF center. Results that were "screen positive and diagnosis negative" prompted family genetic counseling. Parent compliance with follow-up protocol recommendations was retrospectively analyzed relative to the communications model in place at a particular CF Center. Results At each of the 5 MA CF centers, 95% of the CF NBS-positive infants completed recommended sweat testing. In contrast, there was wide disparity in compliance (32%-90%) with completion of genetic counseling between CF centers. Conclusion CF centers that escorted parents through the 2 recommended follow-up steps in 1 day had higher compliance with the second step (genetic counseling) than centers that required a return visit for genetic counseling. C1 Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02130 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Boston, MA USA. Baystate Med Ctr, Childrens Hosp, Springfield, IL USA. Univ Massachusetts, Mem Hlth Care, Worcester, MA 01605 USA. RP Comeau, AM (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, 305 S St, Boston, MA 02130 USA. EM anne.comeau@umassmed.edu RI Parad, Richard/E-8559-2010 NR 6 TC 9 Z9 9 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2005 VL 147 IS 3 SU S BP S98 EP S100 DI 10.1016/j.jpeds.2005.08.007 PG 3 WC Pediatrics SC Pediatrics GA 973RT UT WOS:000232541000021 PM 16202793 ER PT J AU Parad, RB Comeau, AM Dorkin, HL Dovey, M Gerstle, R Martin, T O'Sullivan, BP AF Parad, RB Comeau, AM Dorkin, HL Dovey, M Gerstle, R Martin, T O'Sullivan, BP TI Sweat testing infants detected by cystic fibrosis newborn screening SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on Newborn Screening for Cystic Fibrosis CY NOV 20-21, 2003 CL Atlanta, GA SP Ctr Dis Control & Prevent, Cystic Fibrosis Fdn ID MUTATIONS AB Objective Describe and define limitations of early pilocarpine iontophoresis (sweat testing) for cystic fibrosis (CF) newborn screening (NBS). Study design Population-based results front follow-tip of CF NBS-positive newborns. Results Insufficient quantity of sweat is more likely if the sweat test is done too early. but testing is generally successful after 2 weeks of age. Sweat chloride levels drop over the first weeks of life. CF carriers have higher sweat chloride concentrations than non-carriers. Conclusions Sweat testing can be performed effectively after 2 weeks of age for CF NBS-positive newborns. Earlier testing has a higher risk of insufficient sweat for completing testing. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Newborn Med, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Baystate Med Ctr, Springfield, MA USA. Univ Massachusetts, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02130 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Parad, RB (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, Massachusetts Cyst Fibrosis Newborn Screening Pro, 305 South St, Jamaica Plain, MA 02130 USA. EM richard.parad@umassmed.edu RI Parad, Richard/E-8559-2010 NR 8 TC 32 Z9 33 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2005 VL 147 IS 3 SU S BP S69 EP S72 DI 10.1016/j.jpeds.2005.08.015 PG 4 WC Pediatrics SC Pediatrics GA 973RT UT WOS:000232541000015 PM 16202787 ER PT J AU McGuire, M Zhang, Y White, DP Ling, LM AF McGuire, M Zhang, Y White, DP Ling, LM TI Phrenic long-term facilitation requires NMDA receptors in the phrenic motonucleus in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID METHYL-D-ASPARTATE; CHRONIC INTERMITTENT HYPOXIA; OBSTRUCTIVE SLEEP-APNEA; AWAKE RATS; MOTOR OUTPUT; RESPIRATORY PLASTICITY; GENOMIC CONSEQUENCES; INSPIRATORY DRIVE; NERVE-STIMULATION; NREM SLEEP AB Exposure to episodic hypoxia induces a persistent augmentation of respiratory activity, known as long-term facilitation (LTF). LTF of phrenic nerve activity has been reported to require serotonin receptor activation and protein syntheses. However, the underlying cellular mechanism still remains poorly understood. NMDA receptors play key roles in synaptic plasticity (e.g. some forms of hippocampal long-term potentiation). The present study was designed to examine the role of NMDA receptors in phrenic LTF and test if the relevant receptors are located in the phrenic motonucleus. Integrated phrenic nerve activity was measured in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats before, during and after three episodes of 5 min isocapnic hypoxia (P-a,P-O2, = 30-45 mmHg), separated by 5 min hyperoxia (50% O-2). Either saline (as control) or the NMDA receptor antagonist MK-801 (0.2 mg kg(-1), I.P.) was systemically injected similar to 1 h before hypoxia. Phrenic LTF was eliminated by the MK-801 injection (vehicle, 32.8 +/- 3.7% above baseline in phrenic amplitude at 60 min post-hypoxia; MK-801, -0.5 +/- 4.1%, means S.E.M.), with little change in both the CO2-apnoeic threshold and the hypoxic phrenic response (HPR). Vehicle (saline, 5 X 100 nl) or MK-801 (10 mu m; 5 X 100 nl) was also microinjected into the phrenic motonucleus region in other groups. Phrenic LTF was eliminated by the MK-801 microinjection (vehicle, 34.2 +/- 3.4%; MK-801, -2.5 +/- 2.8%), with minimal change in HPR. Collectively, these results suggest that the activation of NMDA receptors in the phrenic motonucleus is required for the episodic hypoxia-induced phrenic LTF C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, BIDMC,Div Sleep Med, Boston, MA 02115 USA. RP Ling, LM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, BIDMC,Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM lling@partners.org FU NHLBI NIH HHS [R01 HL064912-04, R01 HL064912-05A1, R01 HL064912, HL64912] NR 51 TC 36 Z9 39 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2005 VL 567 IS 2 BP 599 EP 611 DI 10.1113/jphysiol.2005.087650 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 964XK UT WOS:000231914100021 PM 15932891 ER PT J AU Mozley, SL Miller, MW Weathers, FW Beckham, JC Feldman, ME AF Mozley, SL Miller, MW Weathers, FW Beckham, JC Feldman, ME TI Personality assessment inventory (PAI) profiles of male veterans with combat-related posttraumatic stress disorder SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE PTSD; Personality Assessment Inventory; assessment; trauma; veterans ID COMPENSATION SEEKING STATUS; SOMATIC COMPLAINTS; INITIAL VALIDATION; FOLLOW-UP; PTSD; MMPI-2; SCALE; COMORBIDITY; VALIDITY; RELIABILITY AB The Personality Assessment Inventory (PAI; L. C. Morey, 1991) is a promising tool for the assessment of Posttraumatic Stress Disorder ( PTSD), but few studies have examined the PAI profiles of individuals with the diagnosis. In this study, the PAI was administered to 176 combat veterans with PTSD. Results showed significant elevations on scales measuring depression, somatic complaints, anxiety, anxiety-related disorders, schizophrenia, and negative impression management. The Traumatic Stress subscale was the highest point in the mean score profile and was moderately correlated with several established measures of PTSD. Veterans with and without comorbid major depression differed on PAI scales assessing depression, anxiety, and warmth. Analysis of two-point codetypes for the PAI and the MMPI-2 revealed substantial heterogeneity in symptom endorsement on both instruments, suggesting that there may be no clear "PTSD profile" on either instrument. Results provide a reference point for future work with the PAI in PTSD samples. C1 Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. Auburn Univ, Auburn, AL 36849 USA. Duke Univ, Med Ctr, NC VA Med Ctr, Durham, NC USA. RP Mozley, SL (reprint author), Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. EM susannah.mozley2@med.va.gov NR 58 TC 11 Z9 11 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2005 VL 27 IS 3 BP 179 EP 189 DI 10.1007/s10862-005-0634-6 PG 11 WC Psychology, Clinical SC Psychology GA 909BB UT WOS:000227832800004 ER PT J AU Lu, J AF Lu, J TI Neuronal networks controlling sleep and wakefulness SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 BIDMC, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A8 EP A8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400031 ER PT J AU Perahia, DGS Kajdasz, DK Barradell, C Gandhi, P Wohlreich, M Fava, M AF Perahia, DGS Kajdasz, DK Barradell, C Gandhi, P Wohlreich, M Fava, M TI Abrupt switching from venlafaxine to duloxetine in the treatment of major depressive disorder SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Lilly Res Ctr Ltd, Surrey, England. Gordon Hosp, London, England. Lilly Res Labs, Indianapolis, IN USA. Eli Lilly & Co, Basingstoke, Hants, England. Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A46 EP A46 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400185 ER PT J AU Smith, DG Ehde, DM Hanley, MA Campbell, KM Jensen, MP Roffman, AJ Awan, AB Czerniecki, JM Robinson, LR AF Smith, DG Ehde, DM Hanley, MA Campbell, KM Jensen, MP Roffman, AJ Awan, AB Czerniecki, JM Robinson, LR TI Efficacy of gabapentin in treating chronic phantom limb and residual limb pain SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation; chronic pain; gabapentin; limb loss; pain; pain treatment; phantom limb pain; randomized clinical trial; residual limb pain; treatment ID RANDOMIZED CONTROLLED-TRIAL; NEUROPATHIC PAIN; DOUBLE-BLIND; AMPUTATION; AMPUTEES; REHABILITATION; AMITRIPTYLINE; OUTCOMES; SCALE AB Twenty-four adults with phantom limb pain (PLP) and/or residual limb pain (RLP) participated in a double-blind crossover trial. Participants were randomly assigned to receive gabapentin or placebo and later crossed over to the other treatment, with a 5-week washout interval in which they did not receive medication. Gabapentin was titrated from 300 mg to the maximum dose of 3,600 mg. Measures of pain intensity, pain interference, depression, life satisfaction, and functioning were collected throughout the study. Analyses revealed no significant group differences in pre- to posttreatment change scores on any of the outcome measures. More than half of the participants reported a meaningful decrease in pain during the gabapentin phase compared with about one-fifth who reported a meaningful decrease in pain during the placebo phase. In this trial, gabapentin did not substantially affect pain. More research on the efficacy of gabapentin to treat chronic PLP and RLP is needed. C1 Harborview Med Ctr, Dept Rehabil Med, Seattle, WA 98104 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Prosthet Res Study, Seattle, WA USA. Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Ehde, DM (reprint author), Harborview Med Ctr, Dept Rehabil 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] NR 28 TC 37 Z9 39 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2005 VL 42 IS 5 BP 645 EP 654 DI 10.1682/JRRD.2005.05.0082 PG 10 WC Rehabilitation SC Rehabilitation GA 036KD UT WOS:000237069100010 PM 16586190 ER PT J AU Ledoux, WR Shofer, JB Smith, DG Sullivan, K Hayes, SC Assal, M Reiber, GE AF Ledoux, WR Shofer, JB Smith, DG Sullivan, K Hayes, SC Assal, M Reiber, GE TI Relationship between foot type, foot deformity, and ulcer occurrence in the high-risk diabetic foot SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE diabetes mellitus; foot; foot deformity; foot type; hallux limitus; hallux valgus; hammer/claw toes; pes cavus; pes planus; ulcer ID PES PLANUS FEET; LIMITED JOINT MOBILITY; HALLUX-VALGUS; PRESSURE; MANAGEMENT; PREDICTORS; NEUROPATHY; MELLITUS; WALKING AB We hypothesized an association between foot type, foot deformity, and foot ulceration and conducted an analysis of a well-characterized, high-risk diabetic population of 398 subjects. The average age was 62 years of age and 74% of the study population were males. Foot-type distributions were 19.5% pes cavus (high arch), 51.5% neutrally aligned (normal arch), and 29.0% pes planus (low arch). We quantified the presence of hallux valgus (23.9%), hammer/claw toes (46.7%), and hallux limitus (24.4%). A significant association was found between foot type and hallux valgus (p = 0.003); pes planus feet had the highest prevalence as compared with neutrally aligned feet (odds ratio [OR] = 2.43, p = 0.0006). Foot type was also significantly associated with fixed hammer/claw toes (p = 0.01); pes cavus feet had the highest prevalence as compared with neutrally aligned feet (OR = 3.89, p = 0.001). Foot type was also significantly associated with hallux limitus (p = 0.006) with pes planus feet having the highest prevalence as compared with neutrally aligned feet (OR = 2.19, p = 0.003). However, foot type was not significantly related to any ulcer outcome (p = 0.7). Fixed hammer/claw toes (OR = 3.91, p = 0.003) and hallux limitus (OR = 3.02, p = 0.006) were associated with increased risk of any ulcer occurrence. This study affirms that foot type and foot deformity are related and that foot deformities are associated with ulcer occurrence. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU NIDDK NIH HHS [Y-1-DK-0066-01]; PHS HHS [RCD 98-353] NR 29 TC 30 Z9 33 U1 0 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2005 VL 42 IS 5 BP 665 EP 671 DI 10.1682/JRRD.2004.11.0144 PG 7 WC Rehabilitation SC Rehabilitation GA 036KD UT WOS:000237069100012 PM 16586192 ER PT J AU Aichmayer, B Margolis, HC Sigel, R Yamakoshi, Y Simmer, JP Fratzl, P AF Aichmayer, B Margolis, HC Sigel, R Yamakoshi, Y Simmer, JP Fratzl, P TI The onset of amelogenin nanosphere aggregation studied by small-angle X-ray scattering and dynamic light scattering SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE enamel; biomineralization; amelogenin; self-assembly; small-angle X-ray scattering; dynamic light scattering ID APATITE CRYSTAL-GROWTH; ENAMEL MATRIX PROTEINS; OCTACALCIUM PHOSPHATE; HYDROXYAPATITE CRYSTALS; ELECTRON-MICROSCOPY; TOOTH ENAMEL; ORGANIZATION; MOLECULES; INCISOR; BONE AB Proteins with predominantly hydrophobic character called amelogenins play a key role in the formation of the highly organized enamel tissue by forming nanospheres that interact with hydroxyapatite crystals. In the present investigation, we have studied the temperature and pH-dependent self-assembly of two recombinant mouse amelogenins, rM179 and rM166, the latter being an engineered version of the protein that lacks a 13 amino acid hydrophilic C-terminus. It has been postulated that this hydrophilic domain plays an important role in controlling the self-assembly behavior of rM179. By small-angle X-ray and neutron scattering, as well as by dynamic light scattering, we observed the onset of an aggregation of the rM179 protein nanospheres at pH 8. This behavior of the full-length recombinant protein is best explained by a core-shell model for the nanospheres, where hydrophilic and negatively charged side chains prevent the agglomeration of hydrophobic cores of the protein nanospheres at lower temperatures, while clusters consisting of several nanospheres start to form at elevated temperatures. In contrast, while capable of forming nanospheres, rM166 shows a very different aggregation behavior resulting in the formation of larger precipitates just above room temperature. These results, together with recent observations that rM179, unlike rM166, can regulate mineral organization in vitro, suggest that the aggregation of nanospheres of the full-length amelogenin rM179 is an important step in the self-assembly of the enamel matrix. (C) 2005 Elsevier Inc. All rights reserved. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA USA. Max Planck Inst Colloids & Interfaces, Potsdam, Germany. Univ Leoben, Dept Mat Phys, Austrian Acad Sci, Erich Schmid Inst, Leoben, Austria. Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, Boston, MA USA. EM hmargolis@forsyth.org; fratzl@mpikg.mpg.de RI Fratzl, Peter/H-9095-2012 OI Fratzl, Peter/0000-0003-4437-7830 FU NIDCR NIH HHS [P01-DE-13237] NR 44 TC 45 Z9 46 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2005 VL 151 IS 3 BP 239 EP 249 DI 10.1016/j.jsb.2005.06.007 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 973SI UT WOS:000232542500003 PM 16125972 ER PT J AU Aranyosi, AJ Freeman, DM AF Aranyosi, AJ Freeman, DM TI Two modes of motion of the alligator lizard cochlea: Measurements and model predictions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE-FIBER; BASILAR-MEMBRANE; HAIR-CELLS; FREESTANDING STEREOCILIA; TEMPORAL REPRESENTATION; TONOTOPIC ORGANIZATION; SIGNAL TRANSMISSION; INNER-EAR; BUNDLE; VIBRATION AB Measurements of motion of an in vitro preparation of the alligator lizard basilar papilla in response to sound demonstrate elliptical trajectories. These trajectories are consistent with the presence of both a translational and rotational mode of motion. The translational mode is independent of frequency, and the rotational mode has a displacement peak near 5 kHz. These measurements can be explained by a simple mechanical system in which the basilar papilla is supported asymmetrically on the basilar membrane. In a quantitative model, the translational admittance is compliant while the rotational admittance is second order. Best-fit model parameters are consistent with estimates based on anatomy and predict that fluid flow across hair bundles is a primary source of viscous damping. The model predicts that the rotational mode contributes to the high-frequency slopes of auditory nerve fiber tuning curves, providing a physical explanation for a low-pass filter required in models of this cochlea. The combination of modes makes the sensitivity of hair bundles more uniform with radial position than that which would result from pure rotation. A mechanical analogy with the organ of Corti suggests that these two modes of motion may also be present in the mammalian cochlea. (c) 2005 Acoustical Society of America. C1 MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Aranyosi, AJ (reprint author), MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM freeman@mit.edu OI Aranyosi, Alexander/0000-0002-8133-5026 FU NIDCD NIH HHS [R01-DC00238] NR 43 TC 5 Z9 5 U1 0 U2 3 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 SEP PY 2005 VL 118 IS 3 BP 1585 EP 1592 DI 10.1121/1.1993147 PN 1 PG 8 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 965PV UT WOS:000231963600036 PM 16240819 ER PT J AU Kratochvil, CJ Newcorn, JH Arnold, LE Duesenberg, D Emslie, GJ Quintana, H Sarkis, EH Wagner, KD Gao, HT Michelson, D Biederman, J AF Kratochvil, CJ Newcorn, JH Arnold, LE Duesenberg, D Emslie, GJ Quintana, H Sarkis, EH Wagner, KD Gao, HT Michelson, D Biederman, J TI Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; anxiety; depression; atomoxetine ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SEROTONIN REUPTAKE INHIBITORS; TOURETTES-SYNDROME; TIC DISORDER; CHILDREN; METHYLPHENIDATE; ADOLESCENTS; PLACEBO; DESIPRAMINE AB Objective: Symptoms of depression and anxiety are commonly comorbid with attention-deficit/hyperactivity disorder (ADHD). The authors assessed the safety and effectiveness of atomoxetine monotherapy compared with combined atomoxetine/fluoxetine therapy in a population of children and adolescents with ADHD and concurrent symptoms of depression or anxiety. Method: Patients were randomized to treatment with fluoxetine (n = 127) or placebo (n = 46) under double-blind conditions for 8 weeks, with concomitant atomoxetine use the last 5 weeks. Results: At end point, reductions in ADHD, depressive, and anxiety symptoms were marked for both treatment groups (p < .001 for the relevant scale in each symptom cluster). Some differences between treatment groups for depressive symptoms were significant, but the magnitudes of the differences were small and likely of limited clinical importance. Completion rates for the two groups were similar, as were discontinuation rates for adverse events. The combination group had greater increases in blood pressure and pulse than did the monotherapy group. Conclusions: In pediatric patients with ADHD and comorbid symptoms of depression or anxiety, atomoxetine monotherapy appears to be effective fortreating ADHD. Anxiety and depressive symptoms also improved, but the absence of a placebo-only arm does not allow us to conclude that these effects are specifically the result of treatment with atomoxetine. Combined atomoxetine/fluoxetine therapy was well tolerated. C1 Nebraska Med Ctr 985581, Dept Psychiat, Omaha, NE 68198 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Ohio State Univ, Columbus, OH 43210 USA. Mercy Hlth Res, Chesterfield, MO USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Louisiana Hlth Sci Ctr, New Orleans, LA USA. Sarkis Family Psychiat, Gainesville, FL USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kratochvil, CJ (reprint author), Nebraska Med Ctr 985581, Dept Psychiat, Omaha, NE 68198 USA. EM ckratoch@unmc.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 36 TC 61 Z9 62 U1 2 U2 3 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 SEP PY 2005 VL 44 IS 9 BP 915 EP 924 DI 10.1097/01.chi.0000169012.81536.38 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 958EZ UT WOS:000231428800012 PM 16113620 ER PT J AU Eason, SL Petersen, NJ Suarez-Almazor, M Davis, B Collins, TC AF Eason, SL Petersen, NJ Suarez-Almazor, M Davis, B Collins, TC TI Diabetes mellitus, smoking, and the risk for asymptomatic peripheral arterial disease: Whom should we screen? SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Article ID ANKLE-ARM INDEX; INTERMITTENT CLAUDICATION; VASCULAR-DISEASE; BLOOD-PRESSURE; OCCLUSIVE DISEASE; EDINBURGH ARTERY; LEG SYMPTOMS; PREVALENCE; POPULATION; WOMEN AB Objective: To describe coexisting medical conditions and lifestyle factors associated with asymptomatic peripheral arterial disease (PAD) in a population of white, African American, and Hispanic patients. Study Design and Setting: White, African American, and Hispanic patients 50 years or older were recruited for this cross-sectional study from 4 primary care clinics in Houston, TX. Patients with an ankle-brachial index (ABI) < 0.9 and without leg symptoms typical of PAD were diagnosed with asymptomatic PAD. Results: 403 patients were screened for PAD. Of these, 25 (6.2%) had asymptomatic PAD. Compared with patients without PAD, diabetes mellitus ([OR] 3.8; 95% CI 1.6, 9.0) and a history of smoking at least 1 pack of cigarettes per day ([OR] 2.5; 95% CI 1.1, 6.0) were significantly associated with asymptomatic PAD. An interaction effect existed between diabetes mellitus and smoking at least 1 pack of cigarettes per day. Diabetes mellitus combined with heavy smoking showed the highest predicted value positive (15%) and the highest specificity (92%). A lack of both demonstrated low rates for predicting asymptomatic PAD (predicted value positive, 1%). Conclusion: The ankle-brachial index could become routine screening among patients with diabetes mellitus and/or who smoke. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Houston, TX 77021 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. RP Collins, TC (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, 2450 Holcombe Blvd,Suite 01Y,152, Houston, TX 77021 USA. EM season@bcm.tmc.edu; tcollins@bcm.tmc.edu NR 36 TC 23 Z9 24 U1 0 U2 0 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD SEP-OCT PY 2005 VL 18 IS 5 BP 355 EP 361 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 962GL UT WOS:000231718900003 PM 16148245 ER PT J AU Schwartz, GF Meltzer, AJ Lucarelli, EA Cantor, JP Curcillo, PG AF Schwartz, GF Meltzer, AJ Lucarelli, EA Cantor, JP Curcillo, PG TI Breast conservation after neoadjuvant chemotherapy for stage II carcinoma of the breast SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PREOPERATIVE CHEMOTHERAPY; CANCER; RADIOTHERAPY; MASTECTOMY; WOMEN AB BACKGROUND: Neoadjuvant chemotherapy has become the standard treatment for stage III breast cancer. Gratifying results in these patients prompted this prospective, nonrandomized study of neoadjuvant chemotherapy in stage 11 breast cancer. This study presents our experience with neoadjuvant chemotherapy in 127 patients with stage 11 carcinoma of the breast. STUDY DESIGN: Patients with stages IIA (T > 3.0 cm) and IIB carcinoma were considered for this study and underwent treatment with cyclic chemotherapy until a plateau of response was achieved. Responders underwent breast conservation or mastectomy according to conventional assessment. Chemotherapy was continued in the adjuvant setting. Survival data were compared with historic controls. RESULTS: Between 1981 and 2001, 127 women between the ages of 22 and 80 years (mean age 52, median age 50), with stage II breast cancer were enrolled, with median followup of 60 months. One hundred twenty-two patients (96.1%) responded to chemotherapy. Of this group, 35 (29.2%) experienced complete pathologic responses or had only microscopic foci of disease after treatment. Sixty-two patients (52.5%) had negative lymph nodes at the time of the operation; 28 of these patients were previously considered N-1 clinically. Seventy-six patients (62%) underwent breast conservation. Overall survivals at 5 years for stage IIA and IIB disease were 94.7% and 88%, respectively. Disease-free survival at 5 years was 85.2% for stage IIA patients and 69.1% for stage IIB patients. CONCLUSIONS: Neoadjuvant chemotherapy can be effectively applied to patients with stage 11 disease, and breast conservation becomes feasible in the majority of patients. When compared with historic controls, the current study suggests a statistically significant overall survival advantage (p < 0.007) at 5 years. C1 Thomas Jefferson Univ Hosp, Dept Surg, Jefferson Med Coll, Philadelphia, PA 19107 USA. Breast Hlth Inst, Philadelphia, PA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Beth Israel Med Ctr, Dept Obstet & Gynecol, New York, NY 10003 USA. Drexel Univ, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. RP Schwartz, GF (reprint author), Thomas Jefferson Univ Hosp, Dept Surg, Jefferson Med Coll, 1015 Chestnut St,Suite 510, Philadelphia, PA 19107 USA. NR 18 TC 5 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 BP 327 EP 334 DI 10.1016/j.jamcollsurg.2005.03.015 PG 8 WC Surgery SC Surgery GA 960PY UT WOS:000231606800003 PM 16125064 ER PT J AU Barshes, NR Gay, AN Williams, B Patel, AJ Awad, SS AF Barshes, NR Gay, AN Williams, B Patel, AJ Awad, SS TI Support for the acutely failing liver: A comprehensive review of historic and contemporary strategies SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID FULMINANT HEPATIC-FAILURE; ADSORBENT RECIRCULATING SYSTEM; HYBRID ARTIFICIAL LIVER; EXTRACORPOREAL ALBUMIN DIALYSIS; PORCINE ENDOGENOUS RETROVIRUS; CROSS-SPECIES TRANSMISSION; EXCHANGE BLOOD-TRANSFUSION; HIGH-VOLUME PLASMAPHERESIS; CONTROLLED CLINICAL-TRIAL; 2-STAGE TOTAL HEPATECTOMY C1 Baylor Coll Med, Michael E De Bakey Dept Surg, Michael E DeBakey Vet Adm Med Ctr, Houston, TX 77030 USA. RP Awad, SS (reprint author), Baylor Coll Med, Michael E De Bakey Dept Surg, Michael E DeBakey Vet Adm Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 206 TC 19 Z9 23 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 BP 458 EP 476 DI 10.1016/j.jamcollsurg.2005.04.007 PG 19 WC Surgery SC Surgery GA 960PY UT WOS:000231606800021 PM 16125082 ER PT J AU Albadawi, H Entabi, F Conrad, M Stone, D Watkins, M AF Albadawi, H Entabi, F Conrad, M Stone, D Watkins, M TI Novel role of toll-like receptor 4 in limb ischemia-reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S101 EP S101 DI 10.1016/j.jamcollsurg.2005.06.239 PG 1 WC Surgery SC Surgery GA 962PX UT WOS:000231745800228 ER PT J AU Chang, SB Lu, X Gomes, R Iglehart, JD Richardson, A Wang, ZGC AF Chang, SB Lu, X Gomes, R Iglehart, JD Richardson, A Wang, ZGC TI Patterns of chromosomal instability in breast cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S43 EP S43 DI 10.1016/j.jamcollsurg.2005.06.087 PG 1 WC Surgery SC Surgery GA 962PX UT WOS:000231745800081 ER PT J AU Goldstein, A Brewer, K Doyle, A Roberts, D AF Goldstein, A Brewer, K Doyle, A Roberts, D TI Essential role for BMP signaling in enteric nervous system development SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S52 EP S52 DI 10.1016/j.jamcollsurg.2005.06.112 PG 1 WC Surgery SC Surgery GA 962PX UT WOS:000231745800103 ER PT J AU Guenther, DA Mezrich, JD Muniappan, A Shoji, T Houser, SL Hasse, R Bravard, M Allan, JS Madsen, JC AF Guenther, DA Mezrich, JD Muniappan, A Shoji, T Houser, SL Hasse, R Bravard, M Allan, JS Madsen, JC TI Mechanisms of tolerance in a large animal model of combined heart/kidney co-transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S91 EP S91 DI 10.1016/j.jamcollsurg.2005.06.214 PG 1 WC Surgery SC Surgery GA 962PX UT WOS:000231745800203 ER PT J AU Kumbhani, D Henderson, W Khuri, S AF Kumbhani, D Henderson, W Khuri, S TI Relationship of surgical volume to outcomes in the VA revisited SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S65 EP S66 DI 10.1016/j.jamcollsurg.2005.06.150 PG 2 WC Surgery SC Surgery GA 962PX UT WOS:000231745800141 ER PT J AU Stone, D Conrad, M AlBadawi, H Entabi, F Cambria, R Watkins, M AF Stone, D Conrad, M AlBadawi, H Entabi, F Cambria, R Watkins, M TI COX-2 inhibition enhances spinal cord mitochondrial activity in a murine model of thoracic aortic ischemia reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S106 EP S106 DI 10.1016/j.jamcollsurg.2005.06.252 PG 1 WC Surgery SC Surgery GA 962PX UT WOS:000231745800241 ER PT J AU Robbins, J Gangnon, RE Theis, SM Kays, SA Hewitt, AL Hind, JA AF Robbins, J Gangnon, RE Theis, SM Kays, SA Hewitt, AL Hind, JA TI The effects of lingual exercise on swallowing in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE deglutition; tongue; exercise; therapeutics; prevention ID PENETRATION-ASPIRATION SCALE; SKELETAL-MUSCLE; STROKE; PARKINSONISM; DYSPHAGIA; PNEUMONIA; MORTALITY; VALIDATION; PRESSURE; RISK AB OBJECTIVES: To determine the effects of an 8-week progressive lingual resistance exercise program on swallowing in older individuals, the most "at risk'' group for dysphagia. DESIGN: Prospective cohort intervention study. SETTING: Subjects were recruited from the community at large. PARTICIPANTS: Ten healthy men and women aged 70 to 89. INTERVENTION: Each subject performed an 8-week lingual resistance exercise program consisting of compressing an air-filled bulb between the tongue and hard palate. MEASUREMENTS: At baseline and Week 8, each subject completed a videofluoroscopic swallowing evaluation for kinematic and bolus flow assessment of swallowing. Swallowing pressures and isometric pressures were collected at baseline and Weeks 2, 4, and 6. Four of the subjects also underwent oral magnetic resonance imaging (MRI) to measure lingual volume. RESULTS: All subjects significantly increased their isometric and swallowing pressures. All subjects who had the MRI demonstrated increased lingual volume of an average of 5.1%. CONCLUSION: The findings indicate that lingual resistance exercise is promising not only for preventing dysphagia due to sarcopenia, but also as a treatment strategy for patients with lingual weakness and swallowing disability due to frailty or other age-related conditions. The potential effect of lingual exercise on reducing dysphagia-related comorbidities (pneumonia, malnutrition, and dehydration) and healthcare costs while improving quality of life is encouraging. C1 William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. Univ Wisconsin, Dept Biomed Engn, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace GRECC 11G, Madison, WI 53705 USA. EM jrobbin2@wisc.edu NR 39 TC 133 Z9 144 U1 3 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2005 VL 53 IS 9 BP 1483 EP 1489 DI 10.1111/j.1532-5415.2005.53467.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 959HO UT WOS:000231509000005 PM 16137276 ER PT J AU Naik, AD Gill, TM AF Naik, AD Gill, TM TI Underutilization of environmental adaptations for bathing in community-living older persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE bathing; disability; activities of daily living; geriatric epidemiology; adaptive devices ID ASSISTIVE DEVICES; DISABILITY; HOME; ADULTS; RISK; ASSISTANCE; PEOPLE; CARE; PERFORMANCE; TECHNOLOGY AB OBJECTIVES: To determine the prevalence and utilization of environmental adaptations (home modifications and assistive devices) for bathing in community-living older persons with and without bathing disability. DESIGN: Cross-sectional study. SETTING: General community of greater New Haven, Connecticut. PARTICIPANTS: Five hundred sixty-six community-living persons aged 73 and older. MEASUREMENTS: Trained research nurses performed a comprehensive assessment of bathing function, including an in-home evaluation of the bathing environment and self-reported utilization of environmental adaptations for bathing. RESULTS: The prevalence of most environmental adaptations for bathing was less than 50% and was only modestly greater in participants with bathing disability ( range 6-54%) than in those without bathing disability (2-44%), although important differences in prevalence and utilization were observed according to the type of bathing disability. Participants who had difficulty (without dependence) with bathing were significantly less likely to have most of the environmental adaptations than participants who needed personal assistance (dependence) with bathing. These differences persisted in analyses that specifically evaluated the utilization of environmental adaptations for bathing transfers according to the type of disability with bathing transfers (59% of those with difficulty vs 88% of those with dependence, P <. 001). CONCLUSION: Potentially valuable environmental adaptations are absent from the homes of many older persons with bathing disability and may be particularly underused by older persons reporting difficulty with bathing. To ameliorate or delay the progression of disability in community-living older persons, assessment and remediation strategies should be better targeted to bathing function across the continuum of disability. C1 Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey VA Med Ctr 152, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. RP Naik, AD (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU NIA NIH HHS [R37 AG017560, R01AG17560, K24AG021507, R01AG022993] NR 41 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2005 VL 53 IS 9 BP 1497 EP 1503 DI 10.1111/j.1532-5415.2005.53458.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 959HO UT WOS:000231509000007 PM 16137278 ER PT J AU Hajjar, ER Hanlon, JT Sloane, RJ Lindblad, CI Pieper, CF Ruby, CM Branch, LC Schmader, KE AF Hajjar, ER Hanlon, JT Sloane, RJ Lindblad, CI Pieper, CF Ruby, CM Branch, LC Schmader, KE TI Unnecessary drug use in frail older people at hospital discharge SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE unnecessary drug use; drug utilization; elderly ID MEDICATION APPROPRIATENESS INDEX; CONTROLLED TRIAL; PRESCRIPTION DATABASE; PRESCRIBING PATTERNS; GERIATRIC EVALUATION; POLYPHARMACY; MANAGEMENT; REGIMEN; IMPACT; BLACK AB OBJECTIVES: To determine the prevalence and predictors of unnecessary drug use at hospital discharge in frail elderly patients. DESIGN: Cross-sectional. SETTING: Eleven Veterans Affairs Medical Centers. PARTICIPANTS: Three hundred eighty-four frail older patients from the Geriatric Evaluation and Management Drug Study. MEASUREMENTS: Assessment of unnecessary drug use was determined by the consensus of a clinical pharmacist and physician pair applying the Medication Appropriateness Index to each regularly scheduled medication at hospital discharge. Those drugs that received an inappropriate rating for indication, efficacy, or therapeutic duplication were defined as unnecessary. RESULTS: Forty-four percent of patients had at least one unnecessary drug, with the most common reason being lack of indication. The most commonly prescribed unnecessary drug classes were gastrointestinal, central nervous system, and therapeutic nutrients/minerals. Factors associated (P < .05) with unnecessary drug use included hypertension (adjusted odds ratio (AOR) 50.61, 95% confidence interval (CI) = 0.38-0.96), multiple prescribers (AOR = 3.35, 95% CI = 1.16-9.68), and nine or more medications (AOR = 2.24, 95% CI = 1.25-3.99). CONCLUSION: A high prevalence of unnecessary drug use at discharge was found in frail hospitalized elderly patients. Additional studies are needed to identify predictors and prevalence of unnecessary drug use in non-veteran populations so that interventions can be designed to reduce the problem. C1 Univ Sci, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. Vet Affairs Pittsburgh Hlth Care Syst, Dept Geriatr Med, Sch Med, Pittsburgh, PA USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. Univ Minnesota, Coll Pharm, Inst Study Geriatr Pharmacotherapy, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Univ S Florida, Coll Publ Hlth, Tampa, FL USA. RP Hajjar, ER (reprint author), Univ Sci, Philadelphia Coll Pharm, 600 S 43rd St, Philadelphia, PA 19104 USA. EM e.hajjar@usip.edu FU NIA NIH HHS [R01-AG-14158]; NIAID NIH HHS [K24-AI-51324-01] NR 36 TC 79 Z9 80 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2005 VL 53 IS 9 BP 1518 EP 1523 DI 10.1111/j.1532-5415.2005.53523.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 959HO UT WOS:000231509000010 PM 16137281 ER PT J AU Castle, SC Uyemura, K Rafi, A Akande, O Makinodan, T AF Castle, SC Uyemura, K Rafi, A Akande, O Makinodan, T TI Comorbidity is a better predictor of impaired immunity than chronological age in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE immunosenescence; interleukin-10 and-12; comorbidity; CIRS; immunity; aging ID ILLNESS RATING-SCALE; SENIEUR PROTOCOL; VACCINE AB To determine whether high level of comorbidity, measured using a standardized instrument, can predict impaired immunity in older adults. Geriatric outpatient Clinic and Nursing Home Care Unit of Veterans Affairs Greater Los Angeles Healthcare System. Fifteen men aged 51 to 95 with varying levels of chronic illness. Disease burden was measured using the Cumulative Illness Rating Scale (CIRS) and immunity using proliferation of T cells induced by phytohemagglutinin (PHA) and production of interleukin (IL)-12, a proinflammatory cytokine that promotes T helper cell-dependent immune response, and IL-10, a cytokine that inhibits T helper cell-dependent immune response, in response to mitogenic stimulation of peripheral blood mononuclear cells. With increasing comorbidity (increase in CIRS score) in older adults, there is a proportional decrease in immune response (decrease in T cell proliferation and IL-12 production and increase in IL-10 production in response to PHA stimulation). Neither immune response nor CIRS score was significantly correlated with chronological age in this sample of older adults with varying degrees of chronic illness. This study demonstrates that the level of comorbidity correlates with the magnitude of immune response in older adults and suggests that the CIRS could be used to determine the magnitude of impaired immunity in older adults with different specific illnesses and different levels of severity. C1 VA Greater Los Angeles Healthcare Syst, GREEC 11G, Dept Vet Affairs, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Multicampus Div Geriatr & Gerontol, Los Angeles, CA 90024 USA. RP Castle, SC (reprint author), VA Greater Los Angeles Healthcare Syst, GREEC 11G, Dept Vet Affairs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM steven.castle@med.va.gov FU NIA NIH HHS [R03AG18497] NR 20 TC 26 Z9 26 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2005 VL 53 IS 9 BP 1565 EP 1569 DI 10.1111/j.1532-5415.2005.53512.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 959HO UT WOS:000231509000017 PM 16137288 ER PT J AU Ingelfinger, JR Schnaper, HW AF Ingelfinger, JR Schnaper, HW TI Renal endowment: Developmental origins of adult disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ISCHEMIC-HEART-DISEASE; BLOOD-PRESSURE; BIRTH-WEIGHT; FETAL ORIGINS; GROWTH; RAT; DETERMINANTS; HYPOTHESIS; CHILDHOOD; NUTRITION C1 Massachusetts Gen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Northwestern Univ, Sch Med, Dept Pediat, Childrens Mem Res Ctr, Chicago, IL 60611 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp Children, Yawkey 6C, Boston, MA 02114 USA. EM jingelfinger@partners.org FU NIDDK NIH HHS [R01 DK049362] NR 29 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2005 VL 16 IS 9 BP 2533 EP 2536 DI 10.1681/ASN.2005060622 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 959TV UT WOS:000231543100004 PM 16049065 ER PT J AU Shimizu, A Yamada, K Yamamoto, S Lavelle, JM Barth, RN Robson, SC Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Yamamoto, S Lavelle, JM Barth, RN Robson, SC Sachs, DH Colvin, RB TI Thrombotic microangiopathic glomerulopathy in human decay accelerating factor-transgenic swine-to-baboon kidney xenografts SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; MAJOR HISTOCOMPATIBILITY COMPLEX; VASCULAR ENDOTHELIAL-CELLS; MINIATURE SWINE; HEART-TRANSPLANTATION; TOLERANCE INDUCTION; ATP-DIPHOSPHOHYDROLASE; THYMIC TRANSPLANTATION; PORCINE KIDNEY; TISSUE FACTOR AB Models of pig-to-baboon xenografting were examined to identify the mechanisms and pathologic characteristics of acute humoral xenograft rejection (AHXR). Thymus and kidney (composite thymokidney) from human decay accelerating factor-transgenic swine were transplanted into baboons (n = 16) that were treated with an immunosuppressive regimen that included extracorporeal immunoadsorption of anti-alpha Gal antibody and inhibition of complement activation. Morphologic and immunohistochemical studies were performed on protocol biopsies and graftectomy samples. All renal xenografts avoided hyperacute rejection. However, graft rejection coincided with the increase of anti-aGal antibody in the recipient's circulation. The 16 xenografts studied were divided into two groups dependent on the rapid return (group 1) or gradual return (group 2) of anti-aGal antibody after immunoadsorption. In group I (n = 6), grafts were rejected to day 27 with development of typical AHXR, characterized by marked interstitial hemorrhage and thrombotic microangiopathy in the renal vasculature. In group 2 (n = 10), grafts also developed thrombotic microangiopathy affecting mainly the glomeruli by day 30 but also showed minimal evidence of interstitial injury and hemorrhage. In the injured glomeruli, IgM and C4d deposition, subsequent endothelial cell death and activation with upregulation of von Willebrand factor and tissue factor, and a decrease of CD39 expression developed with the formation of fibrin-platelet multiple microthrombi. In this model, the kidney xenografts, from human decay accelerating factor-transgenic swine, in baboons undergo AHXR. In slowly evolving AHXR, graft loss is associated with the development of thrombotic microangiopathic glomerulopathy. Also, anti-aGal IgM deposition and subsequent complement activation play an important role in the mechanism of glomerular endothelial injury and activation and the formation of multiple microthrombi. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Nippon Med Coll, Dept Pathol, Tokyo 113, Japan. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 225, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu RI Barth, Rolf/B-2542-2014 FU NIAID NIH HHS [5P01-AI45897] NR 51 TC 50 Z9 51 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2005 VL 16 IS 9 BP 2732 EP 2745 DI 10.1681/ASN.2004121148 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 959TV UT WOS:000231543100024 PM 16049072 ER PT J AU Ayus, JC Mizani, MR Achinger, SG Thadhani, R Go, AS Lee, SK AF Ayus, JC Mizani, MR Achinger, SG Thadhani, R Go, AS Lee, SK TI Effects of short daily versus conventional hemodialysis on left ventricular hypertrophy and inflammatory markers: A prospective, controlled study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; C-REACTIVE PROTEIN; NOCTURNAL HEMODIALYSIS; ESRD PATIENTS; MAINTENANCE HEMODIALYSIS; VASCULAR CALCIFICATION; CARDIOVASCULAR RISK; DIALYSIS PATIENTS; MORTALITY RISK; LONG-TERM AB Left ventricular hypertrophy (LVH) and inflammation independently increase risk for death in people who receive hemodialysis. A nonrandomized, controlled trial was conducted of the effect of short daily (6 sessions/wk of 3 h each) or conventional (three sessions/wk of 4 h each) hemodialysis on LVH and inflammatory factors. A total of 26 short daily hemodialysis and 51 matched conventional hemodialysis patients were enrolled, and baseline and 12-mo measures of echocardiographic left ventricular mass index (LVMI), serum C-reactive protein (CRP), serum calcium and phosphorus, and erythropoietin resistance index were collected. Baseline characteristics were similar between groups except that hemoglobin and serum calcium were lower and serum phosphorus was higher in the short daily hemodialysis group. At 12-mo follow-up, short daily hemodialysis patients experienced a 30% decrease in LVMI (154 +/- 33 to 108 +/- 25; P < 0.0001). After adjustment for potential confounders, short daily hemodialysis (beta = -41.63, P = 0.03) and percentage decrease in serum phosphorus (beta = -0.12, P = 0.04) predicted a 12-mo decrease in LVMI. Among short daily hemodialysis patients, there were significant reductions in median CRP levels [1.22 interquartile range (IQR) (0.37 to 3.70) to 0.05 IQR (0.05 to 1.17); P < 0.01] and erythropoietin resistance index [19.5 IQR (8.6 to 37.6) to 10.5 IQR (5.5 to 14.6); P < 0.001]. There were no significant changes in LVMI, CRP, or erythropoietin resistance index in the conventional hemodialysis group. Short daily hemodialysis is associated with improved fluid and phosphorus management and a reduction in LVH and inflammatory factors compared with conventional hemodialysis. Future trials are needed to determine whether short daily hemodialysis can reduce morbidity and mortality in this high-risk population. C1 Univ Texas, Hlth Sci Ctr, Texas Diabet Inst, Dialysis Serv,Div Nephrol, San Antonio, TX 78229 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. S Texas Vet Hlth Care Syst, Res & Dev Serv, Audie L Murphy Div, San Antonio, TX USA. RP Ayus, JC (reprint author), Univ Texas, Hlth Sci Ctr, Texas Diabet Inst, Dialysis Serv,Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ayus@uthscsa.edu NR 50 TC 165 Z9 176 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2005 VL 16 IS 9 BP 2778 EP 2788 DI 10.1681/ASN.2005040392 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 959TV UT WOS:000231543100029 PM 16033855 ER PT J AU Zhang, D Wells, MT Turnbull, BW Sparrow, D Cassano, PA AF Zhang, D Wells, MT Turnbull, BW Sparrow, D Cassano, PA TI Hierarchical graphical models: An application to pulmonary function and cholesterol levels in the normative aging study SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE EM algorithm; full-information maximum likelihood estimation; hierarchical models; high-density lipoprotein; low-density lipoprotein; random coefficient; reciprocal graph; total cholesterol ID NUTRITION-EXAMINATION-SURVEY; EM ALGORITHM; NATIONAL-HEALTH; MORTALITY; DISEASE; RISK AB There is continued debate regarding the exact relation between lower cholesterol levels and increased respiratory disease mortality. One of the goals of this study is to reveal the relationship between subcomponents of cholesterol and pulmonary function. We consider the subcomponents of total cholesterol, namely high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, to investigate the relationship of cholesterol levels with pulmonary function in a longitudinal study. To answer these questions, we propose new methodology for hierarchical reciprocal graphical models. We consider the identification and estimation of these models, and propose maximum likelihood estimation using a generalized EM algorithm. A simulation study of the algorithm and the corresponding estimates reveals excellent performance of the proposed procedures. Application of this methodology to the Normative Aging Study reveals complicated associations between pulmonary function and the subcomponents of total cholesterol. C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Cornell Univ, Ithaca, NY 14853 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Zhang, D (reprint author), Univ Rochester, Med Ctr, Rochester, NY 14642 USA. EM Dabao_Zhang@urmc.rochester.edu NR 24 TC 1 Z9 1 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2005 VL 100 IS 471 BP 719 EP 727 DI 10.1198/016214505000000114 PG 9 WC Statistics & Probability SC Mathematics GA 984NK UT WOS:000233311400001 ER PT J AU Stevanovic, RD Price, DA Lansang, MC Fisber, NDL Laffel, LMB Hollenberg, NK AF Stevanovic, RD Price, DA Lansang, MC Fisber, NDL Laffel, LMB Hollenberg, NK TI Renin release in response to renin system blockade: Activation of the renin system in type 1 diabetes mellitus SO JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM LA English DT Article DE diabetes; renin; renal plasma flow ID ANGIOTENSIN SYSTEM; RENAL PERFUSION; HYPERGLYCEMIA; CANDESARTAN; INHIBITION; CAPTOPRIL; PRESSURE; SODIUM; AGE AB Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2 +/- 1.5 years) and 37 normal subjects (37 +/- 2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6 +/- 1 ng/mL Ang I/hour in diabetic patients, and 1.7 0.9 ng/mL Ang I/hour in, normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1 +/- 17.6 ml/minute/1.73 m(2)). When it was above the median, the RPF response was also larger (62.2 +/- 13.9 ml/minute/1.73 m(2); p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Stevanovic, RD (reprint author), 141 Hazel Plain Rd, Woodbury, CT 06798 USA. EM rachko@aol.com FU NCRR NIH HHS [M01RR026376]; NHLBI NIH HHS [T32 HL-07609]; NIDDK NIH HHS [1 R01 DK54668-01]; PHS HHS [1P50 ML 53000-01, P01 AC00059916] NR 21 TC 3 Z9 3 U1 0 U2 0 PU J R A A S LTD PI BIRMINGHAM PA EDGBASTON HOUSE, 3 DUCHESS PLACE, EDGBASTON, BIRMINGHAM B16 8NH, ENGLAND SN 1470-3203 J9 J RENIN-ANGIO-ALDO S JI J. Renin-Angiotensin-Aldosterone Syst. PD SEP PY 2005 VL 6 IS 2 BP 78 EP 83 DI 10.3317/jraas.2005.013 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 983CB UT WOS:000233207600005 PM 16470486 ER PT J AU Maier, RV Bankey, P McKinley, B Freeman, B Harbrecht, BG Johnson, JL Minei, JP Moore, EE Moore, F Nathens, AB Shapiro, M Tompkins, RG West, M AF Maier, RV Bankey, P McKinley, B Freeman, B Harbrecht, BG Johnson, JL Minei, JP Moore, EE Moore, F Nathens, AB Shapiro, M Tompkins, RG West, M CA Inflammation Host Response Injury TI Inflammation and the host response to injury, a large-scale collaborative project: Patient-oriented research core-standard operating procedures for clinical care - Foreward SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material C1 Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Rochester, Dept Surg, Rochester, NY 14627 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. Univ Colorado, Dept Surg, Boulder, CO 80309 USA. Univ Texas, Sch Med, Dept Surg, Houston, TX 77025 USA. Univ Texas, Dept Surg, Dallas, TX 75230 USA. Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Div Trauma Burns & Surg Crit Care, Boston, MA USA. RP Maier, RV (reprint author), Harborview Med Ctr, Dept Surg, 325 9th Ave,Box 359796, Seattle, WA 98104 USA. EM ronmaier@u.washington.edu NR 0 TC 31 Z9 31 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 2005 VL 59 IS 3 BP 762 EP 763 DI 10.1097/01.ta.0000177656.85206.cd PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 014BZ UT WOS:000235455000041 ER PT J AU Tiffany, NM Ryan, CW Garzotto, M Wersinger, EM Beer, TM AF Tiffany, NM Ryan, CW Garzotto, M Wersinger, EM Beer, TM TI High dose pulse calcitriol, docetaxel and estramustine for androgen independent prostate cancer: A phase VII study SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; calcitriol; docetaxel; estramustine ID MITOXANTRONE PLUS PREDNISONE; VITAMIN-D; CELL-LINES; INHIBITION; GUIDELINES; ANALOGS; GROWTH AB Purpose: We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer. Materials and Methods: Patients were treated with 60, calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/mg(2) docetaxel on day 2 (70 mg/m(2) after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients. Results: A total of 24 patients, including 11 who were chemotherapy naive and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy naive patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria. Conclusions: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule. C1 Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCRR NIH HHS [3M01RR00334-33S2] NR 18 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2005 VL 174 IS 3 BP 888 EP 892 DI 10.1097/01.ju.0000169261.42298.e6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 956BU UT WOS:000231274700023 PM 16093981 ER PT J AU Tabatabaei, S Harisinghani, M McDougal, WS AF Tabatabaei, S Harisinghani, M McDougal, WS TI Regional lymph node staging using lymphotropic nanoparticle enhanced magnetic resonance imaging with ferumoxtran-10 in patients with penile cancer SO JOURNAL OF UROLOGY LA English DT Article DE ferumoxtran; magnetic resonance imaging; carcinoma; squamous cell; penis ID SQUAMOUS-CELL CARCINOMA; GROIN DISSECTION; LYMPHADENECTOMY; SURVIVAL AB Purpose: We evaluated lymphotropic nanoparticle enhanced magnetic resonance imaging (LNMRI) with ferumoxtran-10 in determining the presence of regional lymph node metastases in patients with penile cancer. Materials and Methods: Seven patients with squamous cell carcinoma of the penis underwent LNMRI. All patients subsequently underwent groin dissection and the nodal images were correlated with histology. Results: We found that LNMRI had sensitivity, specificity, and positive and negative predictive values of 100%, 97%, 81.2% and 100%, respectively, in predicting the presence of regional lymph node metastases in patients with penile cancer. Conclusions: Lymph node scanning using LNMRI accurately predicts the pathological status of regional lymph nodes in patients with cancer of the penis. LNMRI may accurately triage patients for regional lymphadenectomy. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 19 TC 73 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2005 VL 174 IS 3 BP 923 EP 927 DI 10.1097/01.ju.0000170234.14519.19 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 956BU UT WOS:000231274700033 PM 16093989 ER PT J AU Dahi, S Lee, JG Lovett, DH Sarkar, R AF Dahi, S Lee, JG Lovett, DH Sarkar, R TI Differential transcriptional activation of matrix metalloproteinase-2 and membrane type-1 matrix metalloproteinase by experimental deep venous thrombosis and thrombin SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID VEIN ENDOTHELIAL-CELLS; GELATINASE-A; MMP-2; MATRIX-METALLOPROTEINASE-2; ANGIOGENESIS; EXPRESSION; MICE; MIGRATION; PRO-MMP-2; ANEURYSMS AB Objective: Resolution of deep venous thrombosis (DVT) is involved in the pathogenesis of postthrombotic syndrome. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are critical in angiogenesis and tissue remodeling. We hypothesized that MMP-2 and its membrane-bound activator membrane type-1 matrix metalloproteinase (MT1-MMP) expression would be expressed and activated during the resolution of DVT Methods:. DVT was generated by caval ligation in wild-type and MMP-2 transgenic reporter mice. Ligated and sham-operated (control) cavae were analyzed for MMP-2 transcription (beta-galactosidase activity in MMP-2 reporter mice) and MT1-MMP mRNA by real-time polymerase chain reaction. MMP-2 activity was determined by zymography, and immunohistochemical staining for beta-galactosidase and MT1-MMP protein was used to localize expression. Human umbilical vascular endothelial cells (HUVEC) were treated with 10 U/mL thrombin and MMP-2 and MTI-MMP mRNA levels and MMP-2 activity was determined. Results. MMP-2 activity increased 71% (n = 5, P <.05) at day 8 in ligated vs control cavae by zymography. P-galactosidase activity showed a 1.2-fold (n = 8, P <.05) and 1.7-fold (n = 8, P <.05) induction in MMP-2 transcription at day 3 and day 8, respectively. No significant MT1-MMP gene induction was seen at day 3 in ligated vs control cavae, but MT1-MMP mRNA was upregulated 2.5-fold (n = 8, P <.05) in ligated cavae at day 8. Immunohistochemical staining localized MMP-2 and MT1-MMP expression to the vein wall and cellular infiltrates of the thrombus. Thrombin-treated HUVEC showed differential responses of MMP-2 and MTI-MMP. Zymography of conditioned media and cell lysates illustrated a 220% (152.6 +/- 8.6 vs 69.445 +/- 5.46 pixels/unit area, n = 5, P <.05) and 150% (74.1 +/- 7.3 vs 49.2 +/- 5.7 pixels/unit area, n = 5, P <.05) increases in MMP-2 activity respectively. MMP-2 mRNA levels were downregulated 30% (0.48 +/- 0.023 vs 0.63 +/- 0.035 copies of NUIP-2 mRNA/copy GA-PDH, n = 5, P <.05), whereas MT1-MMP message was upregulated 250% (0.147 +/- 0.009 vs 0.059 +/- 0.005 copies of MT1-MMP mRNA/copy GAPDH, n = 5, P <.05). Conclusions. Resolution of DVT is associated with increased MMP-2 transcription and activity as well as MT1-MMP expression. Thrombin may mediate the increase in MTI-MMP noted in DVT. This is the first article studying MMP-2 and MT1-MMP transcription in DVT. These findings add DVT resolution to the class of inflammatory and fibrotic disorders in which transcriptional activation of the MT1-MMP/MMP-2 genes occurs and identify a potential therapeutic target to modulate this clinically relevant process. Clinical Relevance: Postthrombotic syndrome remains a significant clinical problem after deep venous thrombosis (DVT), but the cellular and molecular mechanisms involved in thrombus resolution and vein wall fibrosis remain undefined. Matrix metalloproteinase (MMP) enzymes are critical to cell migration and matrix breakdown. We identify gene transcription and activity of two MMP isoforms, MMP-2 and MMP-14 (membrane type MMP 1, MT1-MMP) in the resolution phase of experimental DVT and in thrombin-treated endothelial cells. These studies define new proteases potentially important to resolution of DVT and development of postthrombotic syndrome. C1 Univ Calif San Francisco, Div Vasc Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Vasc Res Labs, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. RP Sarkar, R (reprint author), 4150 Clement St,112G, San Francisco, CA 94121 USA. EM sarkarR@surgery.ucsf.edu FU NHLBI NIH HHS [HL04435, P01 HL 68738] NR 28 TC 15 Z9 15 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2005 VL 42 IS 3 BP 539 EP 545 DI 10.1016/j.jvs.2005.04.051 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 966SZ UT WOS:000232043300028 PM 16171603 ER PT J AU Klein, RS Lin, E Zhang, B Luster, AD Tollett, J Samuel, MA Engle, M Diamond, MS AF Klein, RS Lin, E Zhang, B Luster, AD Tollett, J Samuel, MA Engle, M Diamond, MS TI Neuronal CXCL10 directs CD8(+) T-cell recruitment and control of West Nile virus encephalitis SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR EXPRESSION; COMPLEX ANTIGEN EXPRESSION; IFN-INDUCIBLE PROTEIN-10; MULTIPLE-SCLEROSIS; FLAVIVIRUS INFECTION; GENE-EXPRESSION; CLASS-I; ALPHA-CHEMOATTRACTANT; VIRAL-INFECTION AB The activation and entry of antigen-specific CD8(+) T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3(+) CD8(+) T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system. C1 Washington Univ, Sch Med, Dept Med, Div Infect Dis, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Klein, RS (reprint author), Washington Univ, Sch Med, Dept Med, Div Infect Dis, Campus Box 8051,660 S Euclid Ave, St Louis, MO 63110 USA. EM rklein@im.wustl.edu FU NCI NIH HHS [R01 CA069212, R01CA069212]; NINDS NIH HHS [K02NS045607, K02 NS045607, R01 NS052632, R01NS052632-01] NR 59 TC 223 Z9 233 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 17 BP 11457 EP 11466 DI 10.1128/JVI.79.17.11457-11466.2005 PG 10 WC Virology SC Virology GA 956ML UT WOS:000231303900060 PM 16103196 ER PT J AU Kasper, JS Kuwabara, H Arai, T Ali, SH DeCaprio, JA AF Kasper, JS Kuwabara, H Arai, T Ali, SH DeCaprio, JA TI Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation SO JOURNAL OF VIROLOGY LA English DT Article ID PRB-RELATED PROTEINS; LARGE TUMOR-ANTIGEN; SIMIAN VIRUS-40; EMBRYO FIBROBLASTS; J DOMAIN; P53; BINDING; P130; GENE; RAS AB Simian virus 40 large T antigen (T Ag) is capable of immortalizing and transforming rodent cells. The transforming activity of T Ag is due in large part to perturbation of the tumor suppressor proteins p53 and the retinoblastoma (pRB) family members. Inactivation of these tumor suppressors may not be sufficient for T Ag-mediated cellular transformation. It has been shown that T Ag associates with an SCF-like complex that contains a member of the cullin family of E3 ubiquitin ligases, CUL7, as well as SKP1, RBX1, and an F-box protein, FBXW8. We identified T Ag residues 69 to 83 as required for T Ag binding to the CUL7 complex. We demonstrate that Delta 69-83 T Ag, while it lost its ability to associate with CUL7, retained binding to p53 and pRB family members. In the presence of CUL7, wild-type (WT) T Ag but not Delta 69-83 T Ag was able to induce proliferation of mouse embryo fibroblasts, an indication of cellular transformation. In contrast, WT and Delta 69-83 T Ag enabled mouse embryo fibroblasts to proliferate to similarly high densities in the absence of CUL7. Our data suggest that, in addition to p53 and the pRB family members, T Ag serves to bind to and inactivate the growth-suppressing properties of CUL7. In addition, these results imply that, at least in the presence of T Ag, CUL7 may function as a tumor suppressor. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer Bldg 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01 CA93804, R01 CA093804] NR 33 TC 36 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 18 BP 11685 EP 11692 DI 10.1128/JVI.79.18.11685-11692.2005 PG 8 WC Virology SC Virology GA 961AI UT WOS:000231633900015 PM 16140746 ER PT J AU Pillay, T Zhang, HT Drijfhout, JW Robinson, N Brown, H Khan, M Moodley, J Adhikari, M Pfafferott, K Feeney, ME John, AS Holmes, EC Coovadia, HM Klenerman, P Goulder, PJR Phillips, RE AF Pillay, T Zhang, HT Drijfhout, JW Robinson, N Brown, H Khan, M Moodley, J Adhikari, M Pfafferott, K Feeney, ME John, AS Holmes, EC Coovadia, HM Klenerman, P Goulder, PJR Phillips, RE TI Unique acquisition of cytotoxic T-lymphocyte escape mutants in infant human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-I ALLELES; DISEASE PROGRESSION; PERIPHERAL-BLOOD; HIV-1 INFECTION; CELL RESPONSES; CHILDREN BORN; VIREMIA; AIDS; TRANSMISSION; EVOLUTION AB The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections. C1 John Radcliffe Hosp, Nuffield Dept Med, Oxford, England. Leiden Univ, Med Ctr, Dept Immunohaematol, Leiden, Netherlands. Univ Natal, Dept Obstet & Gynaecol, Nelson R Mandela Med Sch, Durban, South Africa. Univ Natal, Dept Paediat & Infant Hlth, Nelson R Mandela Med Sch, Durban, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Queen Elizabeth Hosp, Bridgetown, Barbados. Univ Oxford, Dept Evolut Biol, Oxford, England. Univ Natal, Ctr HIV & AIDS Networking, Durban, South Africa. Univ Oxford, Peter Medawar Bldg Pathogen Res, Oxford OX1 9SY, England. RP Phillips, RE (reprint author), Univ Oxford, Peter Medawar Bldg Pathogen Res, Oxford OX1 9SY, England. EM rodney.phillips@ndm.ox.ac.uk OI Holmes, Edward/0000-0001-9596-3552 NR 24 TC 32 Z9 32 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 18 BP 12100 EP 12105 DI 10.1128/JVI.79.18.12100-12105.2005 PG 6 WC Virology SC Virology GA 961AI UT WOS:000231633900056 PM 16140787 ER PT J AU Martin, KJ Juppner, H Sherrard, DJ Goodman, WG Kaplan, MR Nassar, G Campbell, P Curzi, M Charytan, C McCary, LC Guo, MD Turner, SA Bushinsky, DA AF Martin, KJ Juppner, H Sherrard, DJ Goodman, WG Kaplan, MR Nassar, G Campbell, P Curzi, M Charytan, C McCary, LC Guo, MD Turner, SA Bushinsky, DA TI First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl SO KIDNEY INTERNATIONAL LA English DT Article DE bio-intact PTH; cinacalcet HCl; dialysis; immunometric PTH assay; intact PTH; parathyroid hormone; PTH fragments; secondary hyperparathyroidism ID PARATHYROID-HORMONE PTH; INTERMITTENT CALCITRIOL THERAPY; RENAL BONE-DISEASE; SECONDARY HYPERPARATHYROIDISM; IMMUNORADIOMETRIC ASSAY; HEMODIALYSIS-PATIENTS; CLINICAL UTILITY; CALCIMIMETIC AMG-073; INTACT; FRAGMENTS AB First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl. Background. First-generation immunometric assays for "intact" parathyroid hormone (iPTH) also measure large N-terminally truncated PTH fragments, whereas second-generation assays, such as the "bio-intact" PTH (biPTH) assay, measure only full-length biologically active PTH(1-84). This study compared iPTH and biPTH assays during cinacalcet treatment in subjects with secondary HPT receiving dialysis. Methods. Four hundred and ten subjects were enrolled in a 26-week randomized, double-blind, placebo-controlled trial of oral cinacalcet (or placebo), 30 to 180 mg once daily, and efficacy was assessed using biPTH and iPTH assays. Results. Compared with control treatment, cinacalcet improved the management of secondary HPT. Both biPTH and iPTH decreased by 38%+/- 3% during weeks 13 to 26 in the cinacalcet group; biPTH increased by 23%+/- 4% and iPTH increased by 9.5%+/- 3% in the control group (P < 0.001). Fifty-six percent of cinacalcet subjects and 10% of control subjects had a >= 30% reduction in biPTH, and 61% and 11%, respectively, had a >= 30% reduction in iPTH. Significant correlations between biPTH and iPTH levels were observed throughout the study. Both assays correlated similarly with bone-specific alkaline phosphatase levels. The ratio of biPTH to iPTH was maintained at 56%+/- 1% after treatment in both treatment groups. Increasing serum calcium levels were associated with a decreasing ratio of biPTH to (iPTH-biPTH). Conclusion. These data show that PTH can be monitored with either iPTH or biPTH assays during therapy with cinacalcet, and that cinacalcet therapy does not exert a major influence on the ratio between PTH(1-84) and large, N-terminally truncated PTH fragments. C1 St Louis Univ, Div Nephrol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Nephrol Associates, Nashville, TN USA. Kidney Clin, Med Ctr, Houston, TX USA. Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. Diablo Clin Res, Walnut Creek, CA USA. New York Hosp, Queens Med Ctr, Flushing, NY USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Rochester, Rochester, NY 14627 USA. RP Martin, KJ (reprint author), St Louis Univ, Div Nephrol, 3635 Vista Ave, St Louis, MO 63110 USA. EM martinkj@slu.edu NR 37 TC 45 Z9 47 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2005 VL 68 IS 3 BP 1236 EP 1243 DI 10.1111/j.1523-1755.2005.00517.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 952RJ UT WOS:000231022900035 PM 16105056 ER PT J AU Aslam, S Hamill, R Musher, DM AF Aslam, S Hamill, R Musher, DM TI Treatment of Clostridium difficile-associated disease: old therapies and new strategies SO LANCET INFECTIOUS DISEASES LA English DT Review ID ANTIBIOTIC-ASSOCIATED COLITIS; CLINDAMYCIN-ASSOCIATED COLITIS; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; IN-VITRO ACTIVITY; PSEUDOMEMBRANOUS COLITIS; DOUBLE-BLIND; TOXIN-A; ORAL VANCOMYCIN; ANTIBODY-RESPONSE AB Clostridium difficile-associated disease (CDAD) causes substantial morbidity and mortality. The pathogenesis is multifactorial, involving altered bowel flora, production of toxins, and impaired host immunity, often in a nosocomial setting. Current guidelines recommend treatment with metronidazole; vancomycin is a second-line agent because of its potential effect on the hospital environment. We present the data that led to these recommendations and explore other therapeutic options, including antimicrobials, antibody to toxin A, probiotics, and vaccines. Treatment of CDAD has increasingly been associated with failure and recurrence. Recurrent disease may reflect relapse of infection due to the original infecting organism or infection by a new strain. Poor antibody responses to C difficile toxins have a permissive role in recurrent infection. Hospital infection control and pertinent use of antibiotics can limit the spread of CDAD. A vaccine directed against C difficile toxin may eventually offer a solution to the CDAD problem. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Aslam, S (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Room 4B-370,2002 Holocombe Blvd, Houston, TX 77030 USA. EM saslam@bcm.tmc.edu NR 143 TC 194 Z9 210 U1 3 U2 16 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2005 VL 5 IS 9 BP 549 EP 557 DI 10.1016/S1473-3099(05)70215-2 PG 9 WC Infectious Diseases SC Infectious Diseases GA 960AU UT WOS:000231563400017 PM 16122678 ER PT J AU Goemans, BF Zwaan, CM Miller, M Zimmermann, M Harlow, A Meshinchi, S Loonen, AH Hahlen, K Reinhardt, D Creutzig, U Kaspers, GJL Heinrich, MC AF Goemans, BF Zwaan, CM Miller, M Zimmermann, M Harlow, A Meshinchi, S Loonen, AH Hahlen, K Reinhardt, D Creutzig, U Kaspers, GJL Heinrich, MC TI Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia SO LEUKEMIA LA English DT Article DE KIT; RAS; CBF; AML; pediatric; exon 8 ID RECEPTOR TYROSINE KINASE; GASTROINTESTINAL STROMAL TUMORS; ACUTE MYELOGENOUS LEUKEMIA; C-KIT; N-RAS; ACTIVATING MUTATIONS; GENE-MUTATIONS; MYELODYSPLASTIC SYNDROME; CLINICAL-SIGNIFICANCE; DRUG-RESISTANCE AB Activating mutations in RAS and receptor tyrosine kinases such as KIT and FLT3 are hypothesized to cooperate with chimeric transcription factors in the pathogenesis of acute myeloid leukemia (AML). To test this hypothesis, we genotyped 150 pediatric AML samples for mutations in KIT (exons 8, 17), NRAS and KRAS ( exons 1, 2) and FLT3/ITD. This is the largest cohort of pediatric AML patients reported thus far screened for all four mutations. Of the children with AML, 40% had a mutation in KIT (11.3%), RAS (18%) or FLT3/ITD (11.1%), and 70% of cases of core-binding factor (CBF) leukemia were associated with a mutation of KIT or RAS. Mutations in RAS or FLT3/ITD were frequently found in association with a normal karyotype. Patients with a FLT3/ITD mutation had a significantly worse clinical outcome. However, the presence of a KIT or RAS mutation did not significantly influence clinical outcome. We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Our results demonstrate that abnormalities of signal transduction pathways are frequent in pediatric AML. Future clinical studies are needed to determine whether selective targeting of these abnormalities will improve treatment results. C1 VU Univ Med Ctr, Dept Pediat Hematol & Oncol, NL-1007 MB Amsterdam, Netherlands. Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Med Oncol, Dept Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Dutch Childhood Oncol Grp, The Hague, Netherlands. AML, BFM Study Grp, Munster, Germany. Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Hematol & Oncol, Rotterdam, Netherlands. RP Goemans, BF (reprint author), VU Univ Med Ctr, Dept Pediat Hematol & Oncol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM bf.goemans@vumc.nl RI Reinhardt, Dirk/D-3939-2011 OI Reinhardt, Dirk/0000-0003-4313-9056 NR 48 TC 153 Z9 155 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2005 VL 19 IS 9 BP 1536 EP 1542 DI 10.1038/sj.leu.2403870 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 958IV UT WOS:000231438800005 PM 16015387 ER PT J AU Kay, NE Bone, ND Lee, YK Jelinek, DF Leland, P Battle, TE Frank, DA Puri, RK AF Kay, NE Bone, ND Lee, YK Jelinek, DF Leland, P Battle, TE Frank, DA Puri, RK TI A recombinant IL-4-Pseudomonas exotoxin inhibits protein synthesis and overcomes apoptosis resistance in human CLL B cells SO LEUKEMIA RESEARCH LA English DT Article DE B-CLL; IL-4; IL-4R ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PSEUDOMONAS EXOTOXIN; CYTOTOXIN THERAPY; IN-VITRO; INTERLEUKIN-4; RECEPTOR; IL-4; EXPRESSION; SURVIVAL; PHOSPHORYLATION AB We have determined that CLL B cells consistently express type 3 membrane receptors for the Th2-derived cytokine IL-4 (IL-4R). Furthermore, when added to CLL B cells, IL-4 induces increased apoptosis resistance, increased protein synthesis in CLL B cells and rapid onset activation of STAT1, STAT5 and STAT6. Since the IL-4-IL-4R pathway is intact in CLL B cells and is related to apoptosis resistance, we considered whether we could target this pathway. A recombinant IL-4 Pseudomonas exotoxin fusion protein (IL-4PE), known to bind to IL-4R, was incubated with CLL B cells. IL-4PE (10 ng/ml) cultured with CLL B cells resulted in an increase of apoptosis/death from mean levels of 46.6 +/- 7.0 of non-exposed cells to 69 +/- 8.6 (n = 6). By measuring in vitro protein synthesis, two predominant patterns of sensitivity were observed. In one, CLL B cell clones (n = 4) were found to be extremely sensitive to IL-4PE (IC50's range = 6-25 ng/ml). In the second, low concentrations of IL-4PE induced agonist activity while increasing concentrations induced cytotoxicity in 6 of 21 patient-derived cells. These studies suggest that the IL-4R, on B-CLL cells, can serve as a unique molecular target for directing cytotoxic agents in the therapy of B-CLL. (c) 2005 Elsevier Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kay, NE (reprint author), Mayo Clin & Mayo Fdn, Stabile 628,200 1st St SW, Rochester, MN 55905 USA. EM kay.neil@mayo.edu FU NCI NIH HHS [CA91542] NR 38 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2005 VL 29 IS 9 BP 1009 EP 1018 DI 10.1016/j.leukres.2004.11.025 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 952MN UT WOS:000231007700006 PM 16038727 ER PT J AU Li, Y Feng, J AF Li, Y Feng, J TI A nonparametric comparison of conditional distributions with nonnegligible cure fractions SO LIFETIME DATA ANALYSIS LA English DT Article DE cure model; Cramer-von Mises statistics; asymptotic theory ID MIXTURE MODEL; MISES STATISTICS; SURVIVAL-DATA; REGRESSION; COMPONENTS; SAMPLE; ONSET AB Survival data with nonnegligible cure fractions are commonly encountered in clinical cancer clinical research. Recently, several authors (e.g. Kuk and Chen, Biometrika 79 (1992) 531; Maller and Zhou, Journal of Applied Probability, 30 (1993) 602; Peng and Dear, Biometrics, 56 (2000) 237; Sy and Taylor, Biometrics 56 (2000) 227) have proposed to use semiparametric cure models to analyze such data. Much of the existing work has been emphasized on cure detections and regression techniques. In contrast, this project focuses on the hypothesis testing in the presence of a cure fraction. Specifically, our interest lies in detecting whether there exists survival differences among noncured patients between treatment arms. For this purpose, we investigate the use of a modified Cramer-von Mises statistic for two-sample survival comparisons within the framework of cure models. Such a test has been studied by Tamura et al., (Statistics in Medicine 19, 2000, 2169) using bootstrap procedure. We will focus on developing asymptotic theory and convergent algorithms in this paper. We show that the limiting distributions of the Cramer-von Mises statistic under the null hypothesis can be represented by stochastic integrals and a weighted non-central chi-squares. Both representations lead to concrete numerical schemes for computing the limiting distributions. The algorithms can be easily implemented for data analysis and significantly reduce computing time compared to the bootstrap approach. For illustrative purposes, we apply the proposed test to a published clinical trial. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Dept Math & Stat, Amherst, MA 01002 USA. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM yili@jimmy.harvard.edu NR 29 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD SEP PY 2005 VL 11 IS 3 BP 367 EP 387 DI 10.1007/s10985-005-2968-5 PG 21 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 959FM UT WOS:000231502900005 PM 16133885 ER PT J AU Pawlik, TM Delman, KA Vauthey, JN Nagorney, DM Ng, IOL Ikai, I Yamaoka, Y Belghiti, J Lauwers, GY Poon, RT Abdalla, EK AF Pawlik, TM Delman, KA Vauthey, JN Nagorney, DM Ng, IOL Ikai, I Yamaoka, Y Belghiti, J Lauwers, GY Poon, RT Abdalla, EK TI Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma SO LIVER TRANSPLANTATION LA English DT Article; Proceedings Paper CT 6th World Congress of the International-Hepato-Pancreato-Biliary-Association CY JUN 03-06, 2004 CL Washington, DC SP Int Hepato-Pancreato Biliary Assoc ID LIVER-TRANSPLANTATION; RESECTION; SURVIVAL; IMPACT; CLASSIFICATION; RECURRENCE; CIRRHOSIS; FEATURES; CRITERIA; THERAPY AB Vascular invasion and high histologic grade predict poor outcome after surgical resection or liver transplantation for hepatocellular carcinoma (HCC). Despite the known association between tumor size and vascular invasion, a proportion of patients with large tumors can be treated surgically with excellent outcomes. Clarification of the association between tumor size, histologic grade, and vascular invasion has implications for patient selection for resection and transplantation. The objective of this study was to examine the relationship between HCC tumor size and microscopic (occult) vascular invasion and histologic grade in a multicenter international database of 1,073 patients who underwent resection of HCC. The incidence of microscopic vascular invasion increased with tumor size (<= 3 cm, 25%; 3.1-5 cm, 40%; 5.1-6.5 cm, 55%; > 6.5 cm, 63%) (P < 0.005). Both size and number of tumors were important factors predicting vascular invasion. Among all patients with tumors 5.1 to 6.5 cm, microscopic vascular invasion was present in 55% compared with 31% for all patients with tumors 5 cut or smaller (P < 0.001). Among patients with solitary tumors only, microscopic vascular invasion was significantly more common in tumors measuring 5.1 to 6.5 cm (41%) compared with 27% of tumors 5 cm or smaller (P < 0.003). Tumor size also predicted histologic grade: 36% of tumors 5 cm or smaller were high grade, compared with 54% of lesions 5.1 to 6.5 cm (P = 0.01). High histologic grade, an alpha-fetoprotein level of at least 1000 ng/mL, and multiple tumor nodules each predicted occult vascular invasion in tumors larger than 5 cm. The high incidence of occult vascular invasion and advanced histologic grade in HCC tumors larger than 5 cm, as well as biologic predictors of poor prognosis, should be considered before criteria for transplantation are expanded to include these patients. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA. Mayo Clin, Dept Gastroenterol & Gen Surg, Rochester, MN USA. Univ Hong Kong, Dept Surg, Med Ctr, Queen Marys Hosp, Hong Kong, Hong Kong, Peoples R China. Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan. Beaujon Hosp, Dept Surg, Paris, France. Massachusetts Gen Hosp, Dept Gastroenterol Pathol, Boston, MA 02114 USA. RP Abdalla, EK (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444,POB 301402, Houston, TX 77230 USA. EM eabdalla@mdanderson.org RI Poon, Ronnie/C-4383-2009 NR 34 TC 263 Z9 284 U1 0 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD SEP PY 2005 VL 11 IS 9 BP 1086 EP 1092 DI 10.1002/lt.20472 PG 7 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 960HW UT WOS:000231582200011 PM 16123959 ER PT J AU Sosnovik, DE Schellenberger, EA Nahrendorf, M Novikov, MS Matsui, T Dai, G Reynolds, F Grazette, L Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, DE Schellenberger, EA Nahrendorf, M Novikov, MS Matsui, T Dai, G Reynolds, F Grazette, L Rosenzweig, A Weissleder, R Josephson, L TI Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; cardiomyocyte; apoptosis; reperfusion; nanoparticle ID ACUTE MYOCARDIAL-INFARCTION; IN-VIVO DETECTION; CELL-DEATH; ANNEXIN-V; NONINVASIVE DETECTION; MYOCYTE APOPTOSIS; HEART; VISUALIZATION; REPERFUSION; DYSFUNCTION AB The ability to image cardiomyocyte apoptosis in vivo with high-resolution MRI could facilitate the development of novel cardioprotective therapies. The sensitivity of the novel nanoparticle AnxCLIO-Cy5.5 for cardiomyocyte apoptosis was thus compared in vitro to that of annexin V-FITC and showed a high degree of colocalization. MRI was then performed, following transient coronary artery (LAD) occlusion, in five mice given AnxCLIO-Cy5.5 and in four mice given an identical dose (2 mg Fe/kg) of CLIO-Cy5.5. MR signal intensity and myocardial T-2* were evaluated, in vivo, in hypokinetic regions of myocardium in the LAD distribution. Ex vivo fluorescence imaging was performed to confirm the in vivo findings. Myocardial T2* was significantly lower in the mice given AnxCLIO-Cy5.5 (8.1 versus 13.2 ms, P < 0.01), and fluorescence target to background ratio was significantly higher (2.1 versus 1.1, P < 0.01). This study thus demonstrates the feasibility of obtaining high-resolution MR images of cardiomyocyte apoptosis in Vivo with the novel nanoparticle, AnxCLIO-Cy5.5. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,5403 13th St, Charlestown, MA 02129 USA. EM Sosnovik@nmr.mgh.harvard.edu FU NCI NIH HHS [CA91807, P50CA86355, R01CA86782, R24 CA92782] NR 20 TC 153 Z9 160 U1 1 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2005 VL 54 IS 3 BP 718 EP 724 DI 10.1002/mrm.20617 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 959CH UT WOS:000231494000026 PM 16086367 ER PT J AU Li, Z Korzh, S Mudumana, SP Wan, H Korzh, V Gong, Z AF Li, Z. Korzh, S. Mudumana, S. P. Wan, H. Korzh, V Gong, Z. TI Generation of exocrine pancreas-specific GFP transgenic zebrafish and analyses of pancreas development SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Li, Z.; Korzh, S.; Mudumana, S. P.; Wan, H.; Gong, Z.] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore. [Mudumana, S. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Wan, H.] NICHHD, NIH, Bethesda, MD 20892 USA. [Korzh, V] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. RI Gong, Zhiyuan/H-8794-2012 OI Gong, Zhiyuan/0000-0002-9660-5260 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S64 EP S65 PG 2 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100238 ER PT J AU Reece-Hoyes, JS Shingles, J Dupuy, D Walhout, AJM Vidal, M Hope, IA AF Reece-Hoyes, J. S. Shingles, J. Dupuy, D. Walhout, A. J. M. Vidal, M. Hope, I. A. TI The Caenorhabditis elegans transcription factor localizome SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Reece-Hoyes, J. S.; Shingles, J.; Hope, I. A.] Univ Leeds, Dept Biol, Leeds, W Yorkshire, England. [Dupuy, D.; Vidal, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Walhout, A. J. M.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA. RI Dupuy, Denis/M-7299-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S151 EP S151 PG 1 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100570 ER PT J AU Stineman, MG Kallen, MA Thompson, C Gage, B AF Stineman, MG Kallen, MA Thompson, C Gage, B TI Challenges in paying for effective stays SO MEDICAL CARE LA English DT Editorial Material ID MIX CLASSIFICATION-SYSTEM; MEDICAL REHABILITATION; PAYMENT C1 Univ Penn, Inst Aging, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Ctr Biostat & Epidemiol, Clin Epidemiol Unit, Philadelphia, PA 19104 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Design & Anal Div, Houston, TX USA. RP Stineman, MG (reprint author), Univ Penn, Inst Aging, Dept Phys Med & Rehabil, Room 101,Ralston Penn Ctr,3615 Chestnut St, Philadelphia, PA 19104 USA. EM mstinema@mail.med.upenn.edu NR 18 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2005 VL 43 IS 9 BP 841 EP 843 DI 10.1097/01.mlr.0000178392.96014.cf PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959BU UT WOS:000231492700001 PM 16116348 ER PT J AU Souchek, J Byrne, MM Kelly, PA O'Malley, K Richardson, M Pak, C Nelson, H Suarez-Almazor, ME AF Souchek, J Byrne, MM Kelly, PA O'Malley, K Richardson, M Pak, C Nelson, H Suarez-Almazor, ME TI Valuation of arthritis health states across ethnic groups and between patients and community members SO MEDICAL CARE LA English DT Article DE utilities; quality of life; arthritis; QALYs ID RACIAL DISPARITIES; JOINT REPLACEMENT; KNEE ARTHROPLASTY; DECISION-MAKING; OUTCOMES; CANCER; OSTEOARTHRITIS; METAANALYSIS; PREFERENCES; PERCEPTIONS AB Objective: We sought to examine differences in valuation of health by individuals from different ethnic backgrounds and between patients and community members. Research Design: We surveyed 193 community members identified by random-digit dialing (ie, 64 white, 65 black, and 64 Hispanic) and 198 patients with osteoarthritis (OA), 66 per ethnic group, drawn sequentially from clinic lists of an outpatient institution. Measures: Participants were interviewed and asked to rate 2 scenarios describing arthritis (mild and severe) using visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO). Differences were adjusted for cohort, age, gender, and education. Results: Members of the public had higher preference scores for the 2 health states than patients (SG severe state: 0.77 public, 0.66 patients; SG mild state: 0.90 public, 0.84 patients). The difference score between the mild and severe states was smaller for black than white subjects (P < 0.001) by SG and TTO. Scores for Hispanics and whites did not differ. Preference scores increased with age (SG, TTO). Conclusions: Significant differences were observed in the valuation of health between members of the public and patients, among ethnic groups, and in relation to educational status and age, with the difference between utilities of health states being a more efficient measure of preference than the utility of a single state. Utilities elicited through valuation of hypothetical health scenarios are dependent on sociodemographic traits, experience of disease, and method used. These findings suggest that utilities cannot be used interchangeably across populations, with implications for economic analyses. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Pittsburgh, Ctr Bioeth & Hlth Law, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Miami, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA. RP Souchek, J (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM jsouchek@bcm.tmc.edu FU AHRQ HHS [P01HS10876] NR 38 TC 18 Z9 18 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2005 VL 43 IS 9 BP 921 EP 928 DI 10.1097/01.mlr.0000173600.53788.13 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959BU UT WOS:000231492700010 PM 16116357 ER PT J AU Egede, LE Dagogo-Jack, S AF Egede, LE Dagogo-Jack, S TI Epidemiology of type 2 diabetes: Focus on ethnic minorities SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID URBAN AFRICAN-AMERICANS; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; NON-HISPANIC WHITES; HEALTH MAINTENANCE ORGANIZATION; INFLUENZA VACCINATION COVERAGE; IMPROVES GLYCEMIC CONTROL; CHRONIC ILLNESS; PRIMARY-CARE; SELF-MANAGEMENT AB African Americans and other ethnic minority groups suffer disproportionately from type 2 diabetes and its complications than do white Americans. Genetic and environmental factors contribute to the ethnic disparities in diabetes and its complications, The key elements of a comprehensive diabetes management strategy include monitoring, education, dietary modification, exercise, and medications. The progressive nature of diabetes requires the use of more than one agent. Drug combinations should be selected for their therapeutic firepower and complementary mechanisms of action, and exogenous insulin need not be delayed unnecessarily if oral agents are ineffective. C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Dagogo-Jack, S (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Endocrinol Diabet & Metab, 951 Court Ave,Room 335M, Memphis, TN 38163 USA. EM sdj@utmem.edu FU AHRQ HHS [5K08HS11418]; NCRR NIH HHS [M01 RR00211]; NIDDK NIH HHS [U01 DK048400, U01 DK048400-06, U01 DK048489] NR 110 TC 57 Z9 60 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2005 VL 89 IS 5 BP 949 EP + DI 10.1016/j.mcna.2005.03.004 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA 968GL UT WOS:000232149800005 PM 16129107 ER PT J AU Gurmankin, AD Helweg-Larsen, M Armstrong, K Kimmel, SE Volpp, KGM AF Gurmankin, AD Helweg-Larsen, M Armstrong, K Kimmel, SE Volpp, KGM TI Comparing the standard rating scale and the magnifier scale for assessing risk perceptions SO MEDICAL DECISION MAKING LA English DT Article DE magnifier scale; standard rating scale; risk perceptions ID BREAST-CANCER RISK; SMOKING CESSATION PROGRAM; SELF-PROTECTIVE BEHAVIOR; FAMILY-HISTORY; RANDOMIZED TRIAL; FIELD EXPERIMENT; WOMEN; INFORMATION; MAMMOGRAPHY; MOOD AB Objective. A new risk perception rating scale ("magnifier scale") was recently developed to reduce elevated perceptions of low-probability health events, but little is known about its performance. The authors tested whether the magnifier scale lowers risk perceptions for low-probability (in 0%-1% magnifying glass section of scale) but not high-probability (> 1%) events compared to a standard rating scale (SRS). Method. In studies 1 (n = 463) and 2 (n = 105), undergraduates completed a survey assessing risk perceptions of high- and low-probability events in a randomized 2 x 2 design: in study 1 using the magnifier scale or SRS, numeric risk information provided or not, and in study 2 using the magnifier scale or SRS, high- or low-probability event. In study 3, hypertension patients at the Philadelphia Veterans Affairs hospital completed a similar survey (n = 222) assessing risk perceptions of 2 self-relevant high-probability events-heart attack and stroke-with the magnifier scale or the SRS. Results. In study 1, when no risk information was provided, risk perceptions for both high- and low-probability events were significantly lower (P < 0.0001) when using the magnifier scale compared to the SRS, but risk perceptions were no different by scale when risk information was provided (interaction term: P = 0.003). In studies 2 and 3, risk perceptions for the high-probability events were significantly lower using the magnifier scale than the SRS (P = 0.015 and P = 0.014, respectively). Conclusions. The magnifier scale lowered risk perceptions but did so for low- and high-probability events, suggesting that the magnifier scale should not be used for assessments of risk perceptions for high-probability events. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dickinson Coll, Dept Psychol, Carlisle, PA 17013 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Cardiovasc, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Ctr Hlth Equity Res & Pr, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Gurmankin, AD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Smith 253, Boston, MA 02115 USA. EM andrea_gurmankin@dfci.harvard.edu NR 54 TC 14 Z9 14 U1 3 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2005 VL 25 IS 5 BP 560 EP 570 DI 10.1177/0272989X05280560 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 967ZC UT WOS:000232129100009 PM 16160211 ER PT J AU Bert, C Metheany, KG Doppke, K Chen, GTY AF Bert, C Metheany, KG Doppke, K Chen, GTY TI A phantom evaluation of a stereo-vision surface imaging system for radiotherapy patient setup SO MEDICAL PHYSICS LA English DT Article DE radiotherapy; patient positioning; photogrammetry; quality assurance ID MOTION ANALYSIS; CANCER AB External beam irradiation requires precise positioning of the target relative to the treatment planning coordinate system. A three-dimensional (3D) surface imaging system for patient positioning has recently been installed in one of our linear accelerator (linac) rooms. The device utilizes close-range photogrammetry to generate a 3D model of the patient's surface. This geometric model can be made to look like a digital camera image if wrapped with a gray-level image (texture mapping) that shows surface coloration. The system is calibrated to the linac coordinate system and has been designed as a patient setup device. To reproduce patient position in fractionated radiotherapy, the daily patient surface model is registered to a previously recorded reference surface. Using surface registration, the system calculates the rigid-body transformation that minimizes the distance between the treatment and the reference surface models in a region-of-interest (ROI). This transformation is expressed as a set of new couch coordinates at which the patient position best matches with the reference data. If respiratory motion is a concern, the surface can be obtained with a gated acquisition at a specified phase of the respiratory cycle. To analyze the accuracy of the system, we performed several experiments with phantoms to assess stability, alignment accuracy, precision of the gating function, and surface topology. The reproducibility of surface measurements was tested for periods up to 57 h. Each recorded frame was registered to the reference surface to calculate the required couch adjustment. The system stability over this time period was better than 0.5 mm. To measure the accuracy of the system to detect and quantify patient shift relative to a reference image, we compared the shift detected by the surface imaging system with known couch transitions in a phantom study. The maximum standard deviation was 0.75 mm for the three translational degrees of freedom, and less than 0.1 degrees for each rotation. Surface model precision was tested against computed tomography (CT)-derived surface topology. The root-mean-square rms of the distance between the surfaces was 0.65 mm, excluding regions where beam hardening caused artifacts.in the CT data. Measurements were made to test the gated acquisition mode. The time-dependent amplitude was measured with the surface imaging system and an established respiratory gating system based on infrared (IR)-marker detection. The measured motion trajectories from both systems were compared to the known trajectory of the stage. The standard deviations of the amplitude differences to the motor trajectory were 0.04 and 0.15 mm for the IR-marker system and the 3D surface imaging system, respectively. A limitation of the surface-imaging device is the frame rate of 6.5 Hz, because rapid changes of the motion trajectory cannot be detected. In conclusion, the system is accurate and sufficiently stable to be used in the clinic. The errors computed when comparing the surface model with CT geometry were submillimeter, and deviations in the alignment and gating-signal tests were of the same magnitude. (C) 2005 American Association of Physicists in Medicine. C1 Gesell Schwerionenforsch mbH, D-64291 Darmstadt, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bert, C (reprint author), Gesell Schwerionenforsch mbH, Planckstr 1, D-64291 Darmstadt, Germany. RI Bert, Christoph/C-2585-2013 OI Bert, Christoph/0000-0002-8539-6600 NR 16 TC 104 Z9 107 U1 1 U2 11 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2005 VL 32 IS 9 BP 2753 EP 2762 DI 10.1118/1.1984263 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 967FK UT WOS:000232076700003 PM 16266088 ER PT J AU Gau, V Ma, SC Wang, H Tsukuda, J Kibler, J Haake, DA AF Gau, V Ma, SC Wang, H Tsukuda, J Kibler, J Haake, DA TI Electrochemical molecular analysis without nucleic acid amplification SO METHODS LA English DT Article DE electrochemical detection; cyclic enzymatic reaction; bionanotechnology; genetic assay; immunoassay; simultaneous multi-channel detection ID RECOGNITION; MONOLAYERS AB Electrochemical biosensors have revolutionized glucose monitoring but have not yet fulfilled their promise of a low cost, direct detection replacement for genetic amplification tests such as PCR [K. Kerman, M. Kobayashi, E. Tamiya, Recent trends in electrochemical DNA biosensor technology, Meas. Sci. Technol. 15 (2004) R1-R11; A. Chaubey, B.D. Malhotra, Mediated biosensors. Biosens. Bioelectron. 17 (6-7) (2002) 441-456]. It has been anticipated that the integration of nanoscale chemical structures such as self-assembled monolayers with electrochemical biosensors would increase sensitivity by decreasing inherent system noise. We have designed a novel biosensing approach incorporating such integration and achieved rapid, ultra-low concentration sensitivities without target amplification. Raw samples are mixed with lysis buffer to allow hybridization of nucleic acid targets with anchor and signal probes before immobilizing a signaling enzyme proximate to the biosensor surface. A bias potential is subsequently applied and the secondary byproduct of a cyclic peroxidase reaction measured. Further studies have demonstrated the application of our approach in protein, clinical chemistry, and ionic assays. (c) 2005 Elsevier Inc. All rights reserved. C1 GeneFluid Inc, Monterrey Pk, CA 91754 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Gau, V (reprint author), GeneFluid Inc, 2540 Corp Pl,B101, Monterrey Pk, CA 91754 USA. EM vgau@genefluidics.com FU NIBIB NIH HHS [R01 EB000127-03, R01 EB000127-05, R01 EB000127-04, R01 EB000127-02, EB00127, R01 EB000127, R01 EB000127-01] NR 11 TC 66 Z9 66 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD SEP PY 2005 VL 37 IS 1 BP 73 EP 83 DI 10.1016/j.ymeth.2005.05.008 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979MG UT WOS:000232945500009 PM 16213156 ER PT J AU Dadras, SS Lange-Asschenfeldt, B Velasco, P Nguyen, L Vora, A Muzikansky, A Jahnke, K Hauschild, A Hirakawa, S Mihm, MC Detmar, M AF Dadras, SS Lange-Asschenfeldt, B Velasco, P Nguyen, L Vora, A Muzikansky, A Jahnke, K Hauschild, A Hirakawa, S Mihm, MC Detmar, M TI Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes SO MODERN PATHOLOGY LA English DT Article DE LYVE-1; lymphangiogenesis; angiogenesis; sentinel lymph node; VEGF-C and VEGF-D ID GROWTH-FACTOR-C; 30-YEAR CLINICAL-EXPERIENCE; SQUAMOUS-CELL CARCINOMAS; CUTANEOUS MELANOMA; LETHAL CHARACTERISTICS; PROGNOSTIC VALUE; THIN MELANOMAS; CANCER; ANGIOGENESIS; EXPRESSION AB Cutaneous melanoma is a common melanocytic neoplasm that can quickly metastasize to regional lymph nodes. Currently, prognosis is determined by measuring tumor thickness but more reliable markers for metastatic spread are urgently needed. We investigated whether the extent of tumor lymphangiogenesis can predict melanoma metastasis to sentinel lymph nodes. We quantified the extent of tumor lymphangiogenesis, as well as other factors, in excised primary tumors and in sentinel lymph node biopsy samples from 45 patients with primary cutaneous melanoma. The results were correlated with histological and clinical outcome. Primary melanomas from patients whose tumors had metastasized to the sentinel lymph nodes contained prominent 'hot spots' of increased lymphatic vessel density, compared to nonmetastatic tumors. Multivariate risk analysis revealed that the lymphatic vascular area of primary melanomas, an index of tumor lymphangiogenesis, was the most sensitive prognostic marker for sentinel lymph node metastasis, and was even able to more accurately predict which tumors were metastatic to sentinel lymph nodes than the currently used method of measuring tumor thickness. Highly lymphangiogenic melanomas maintained their lymphangiogenic activity after metastasis to the sentinel lymph node. The extent of tumor lymphangiogenesis is a highly sensitive (83%) and specific (89%) prognostic marker of lymph node metastasis. Assessment of lymphangiogenesis in primary melanomas may be a more effective approach than the currently used technique of measuring tumor thickness in selecting patients with early metastatic disease for aggressive therapy. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dadras, SS (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sdadras@partners.org RI Hauschild, Axel/B-3185-2010 FU NCI NIH HHS [CA69184, CA86410, CA91861] NR 28 TC 207 Z9 219 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2005 VL 18 IS 9 BP 1232 EP 1242 DI 10.1038/modpathol.3800410 PG 11 WC Pathology SC Pathology GA 956LP UT WOS:000231301600011 PM 15803182 ER PT J AU Kadri, Z Maouche-Chretien, L Rooke, HM Orkin, SH Romeo, PH Mayeux, P Leboulch, P Chretien, S AF Kadri, Z Maouche-Chretien, L Rooke, HM Orkin, SH Romeo, PH Mayeux, P Leboulch, P Chretien, S TI Phosphatidylinositol 3-kinase/Akt induced by erythropoietin renders the erythroid differentiation factor GATA-1 competent for TIMP-1 gene transactivation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; HUMAN-TISSUE INHIBITOR; EMBRYONIC STEM-CELLS; POTENTIATING ACTIVITY; CYTOPLASMIC DOMAIN; TYROSINE RESIDUES; PROTEIN-KINASE; RECEPTOR; PROGENITORS; EXPRESSION AB The contribution of erythropoietin to the differentiation of the red blood cell lineage remains elusive, and the demonstration of a molecular link between erythropoietin and the transcription of genes associated with erythroid differentiation is lacking. In erythroid cells, expression of the tissue inhibitor of matrix metalloproteinase (TIMP-1) is strictly dependent on erythropoietin. We report here that erythropoietin regulates the transcription of the TIMP-1 gene upon binding to its receptor in erythroid cells by triggering the activation of phosphatidylinositol 3-kinase (PI3K)/Akt. We found that Akt directly phosphorylates the transcription factor GATA-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the TIMP-1 promoter. This chain of events can be recapitulated in nonerythroid cells by transfection of the implicated molecular partners, resulting in the expression of the normally silent endogenous TIMP-1 gene. Conversely, TIMP-1 secretion is profoundly decreased in erythroid cells from fetal livers of transgenic knock-in mice homozygous for a GATA(S310A) gene, which encodes a GATA-1 mutant that cannot be phosphorylated at Ser(310). Furthermore, retrovirus-mediated expression of GATA(S310A) into GATA-1(null)-derived embryonic stem cells decreases the rate of hemoglobinization by more than 50% compared to expressed wild-type GATA-1. These findings provide the first example of a chain of coupling mechanisms between the binding of erythropoietin to its receptor and GATA-1-dependent gene expression. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Paris 05, Hop Cochin, CNRS, Dept Hematol,Inst Cochin,INSERM,U567,UMR 8104, F-75014 Paris, France. RP Chretien, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, New Res Bldg,Rm 455,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM schretien@rics.bwh.harvard.edu RI maouche, leila/E-3887-2017 NR 38 TC 41 Z9 44 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2005 VL 25 IS 17 BP 7412 EP 7422 DI 10.1128/MCB.25.17.7412-7422.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956VY UT WOS:000231329300002 PM 16107690 ER PT J AU An, JB Rettig, MB AF An, JB Rettig, MB TI Mechanism of von Hippel-Lindau protein-mediated suppression of nuclear factor kappa B activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; TRANSFORMING-GROWTH-FACTOR; TUMOR-ASSOCIATED MACROPHAGES; HYPOXIA-INDUCIBLE FACTORS; FACTOR RECEPTOR; FACTOR-ALPHA; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; GENE-EXPRESSION; CANCER-THERAPY AB Biallelic inactivating mutations of the von Hippel-Lindau tumor suppressor gene (VHL) are a hallmark of clear cell renal cell carcinoma (CCRCC), the most common histologic subtype of RCC. Biallelic VHL loss results in accumulation of hypoxia-inducible factor alpha (HIF alpha). Restoring expression of the wild-type protein encoded by VHL (pVHL) in tumors with biallelic VHL inactivation (VHL-/-) suppresses tumorigenesis, and pVHL-mediated degradation of HIF alpha is necessary and sufficient for VHL-mediated tumor suppression. The downstream targets of HIF alpha that promote renal carcinogenesis have not been completely elucidated. Recently, VHL loss was shown to activate nuclear factor kappa B (NF-kappa B), a family of transcription factors that promotes tumor growth. Here we show that VHL loss drives NF-kappa B activation by resulting in HIF alpha accumulation, which induces expression of transforming growth factor alpha, with consequent activation of an epidermal growth factor receptor/phosphatidylinositol-3-OH kinase/protein kinase B (AKT)/I kappa B-kinase alpha/NF-kappa B signaling cascade. We also show that components of this signaling pathway promote the growth of VHL-/- tumor cells. Members of this pathway represent viable drug targets in VHL-/- tumors, such as those associated with CCRCC. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Div Hematol Oncol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Hematol Oncol, 11301 Wilshire Blvd,Bldg 304,Room E1-113, Los Angeles, CA 90073 USA. EM matthew.rettig@med.va.gov NR 63 TC 57 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2005 VL 25 IS 17 BP 7546 EP 7556 DI 10.1128/MCB.25.17.7546-7556.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956VY UT WOS:000231329300014 PM 16107702 ER PT J AU Tranah, GJ Chan, AT Giovannucci, E Ma, J Fuchs, C Hunter, DJ AF Tranah, GJ Chan, AT Giovannucci, E Ma, J Fuchs, C Hunter, DJ TI Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study SO MOLECULAR CARCINOGENESIS LA English DT Article DE epoxide hydrolase; CYP2C9; colorectal cancer; SNP; cigarette ID MICROSOMAL CYTOCHROME P4502C9; DNA ADDUCT FORMATION; LUNG-CANCER RISK; IN-VITRO; ADENOMA; METABOLISM; GENOTYPES; ASSOCIATION; CELECOXIB; GENE AB Microsomal epoxide hydrolase (mEH) and cytochrome P450 2C9 (CYP2C9) are involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons (PAHs) derived from tobacco smoke. Two coding-region mEH variants (Tyr113His, His139Arg) and CYP2C9 variants (Arg144Cys, Ile359Leu) have been described and affect enzyme specific activity. We investigated these polymorphisms and tested interactions with smoking in relationship to risk of colorectal carcinoma in two case-control studies nested in the Nurses' Health Study (NHS) and Physicians' Health Study (PHS) cohorts. mEH Tyr113His and His139Arg polymorphisms were not associated with the risk of cancer among 197 incident cases and 490 controls from the NHS. Among 273 incident cases and 453 controls from the PHS, carrying one or two copies of the 'rapid' 139Arg allele was associated with a significantly reduced risk of colorectal cancer (OR=0.70, 95% Cl 0.49-0.99) when compared with His`139 wild-type individuals. Risk of colorectal cancer was significantly reduced among men carrying the CYP2C9 *1/*2 genotype (OR=0.62, 95% Cl 0.42-0.92) or at least one CYP2C9 variant allele (OR=0.72, 95% Cl 0.52-1.00)when compared with *1/*1 wild-type individuals. For women, carrying at least one variant CYP2C9 allele was inversely associated with the risk of colorectal cancer (OR = 0.85, 95% Cl, 0.57-1.27) when compared with *1/*1 wild-type individuals. No statistically significant genotype-smoking or gene-gene interactions were found in this study. Our results indicate that individuals exposed to tobacco carcinogens were at increased risk of colorectal cancer and that overall risk is related to mEH and CYP2C9 genotype, although the results were not consistent between men and women. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Program Genet & Mol Epidemiol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. RP Tranah, GJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. FU NCI NIH HHS [CA87969, CA58684, CA90598, CA70817, CA42182, CA 09001-27] NR 45 TC 26 Z9 27 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2005 VL 44 IS 1 BP 21 EP 30 DI 10.1002/mc.20112 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 959XK UT WOS:000231552600003 PM 15924351 ER PT J AU Wang, QB Carroll, JS Brown, M AF Wang, QB Carroll, JS Brown, M TI Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking SO MOLECULAR CELL LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; ENHANCER-BLOCKING ACTIVITY; LIGAND-BINDING DOMAIN; BETA-GLOBIN INSULATOR; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; REGULATED ACTIVITY; NUCLEAR RECEPTORS; HORMONE-RECEPTOR; COMPLEX AB Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer, where it is a key therapeutic target. Here we report that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes rise over a 16 hr period and then slowly decline. AR regulation of the prostate specific antigen (PSA) gene involves both a promoter-proximal sequence as well as an enhancer similar to 4 kb upstream. Recruitment of AR and its essential coactivators at both sites creates a chromosomal loop that allows RNA polymerase II (pol II) to track from the enhancer to the promoter. Phosphorylation of the pol II C-terminal domain is required for pol II tracking but not chromosomal looping. Development of improved hormonal therapies for prostate cancer must take in account the specific spatial and temporal modes of AR-mediated gene regulation. C1 Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Wang, Qianben/E-4267-2011; OI Brown, Myles/0000-0002-8213-1658 NR 49 TC 272 Z9 275 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP PY 2005 VL 19 IS 5 BP 631 EP 642 DI 10.1016/j.mokcel.2005.07.018 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 961WQ UT WOS:000231692900005 PM 16137620 ER PT J AU Talusan, P Bedri, S Yang, SP Kattapuram, T Silva, N Roughley, PJ Stone, JR AF Talusan, P Bedri, S Yang, SP Kattapuram, T Silva, N Roughley, PJ Stone, JR TI Analysis of intimal proteoglycans in atherosclerosis-prone and atherosclerosis-resistant human arteries by mass spectrometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID KERATAN SULFATE PROTEOGLYCAN; AMERICAN-HEART-ASSOCIATION; SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; CORONARY-ARTERIES; ARTICULAR-CARTILAGE; ENDOTHELIAL-CELLS; VASCULAR-LESIONS; LUMICAN; EXPRESSION AB The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/ PRELP ( proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis. C1 Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. McGill Univ, Dept Surg, Dept Surg Res, Montreal, PQ H3G 1A6, Canada. RP Stone, JR (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Warren 501B,55 Fruit St, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [HL074324, R01 HL074324, R01 HL074324-02, R01 HL074324-03] NR 41 TC 42 Z9 43 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2005 VL 4 IS 9 BP 1350 EP 1357 DI 10.1074/mcp.M500088-MCP200 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 963WE UT WOS:000231836100014 PM 15970583 ER PT J AU Kornitzer, B Ronan, E Rifkin, MR AF Kornitzer, B Ronan, E Rifkin, MR TI Improving the adjustment of educationally disadvantaged students to medical school : The Summer Enrichment Program SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE underrepresented students; educationally disadvantaged; pre-matriculation program; adjustment to medical school; first-year performance ID PREMATRICULATION PROGRAM; MINORITY-STUDENTS; COLLEGE AB The Summer Enrichment Program (SEP) is a 6-week pre-matriculation program that targets students who may be at an educational disadvantage and/or may have difficulties adjusting to the rigors of medical school. The objective of the current study was to determine whether the SEP (a) eased the transition to the first year of medical school and (b) had an impact on academic performance during the first year of medical school. All students from groups underrepresented in medicine, who had been invited to participate in the SEP, and all Humanities and Medicine Program students who matriculated at Mount Sinai School of Medicine between 1999 and 2003 and were still matriculated during the 2003 - 2004 academic year were asked to respond to a survey distributed in the spring of 2004. In addition, student academic profiles were reviewed. Responses to the survey indicated that the SEP provided important emotional benefits for those students who chose to attend the program. Virtually all students who had attended had praise for the program and felt that it eased the transition to medical school, helped build confidence and facilitated social connections. In addition, those students from groups underrepresented in medicine who attended the SEP had less academic difficulty (fewer course failures) in their first year of medical school. C1 CUNY Mt Sinai Sch Med, Dept Med Educ, Humanities & Med Program, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rifkin, MR (reprint author), CUNY Mt Sinai Sch Med, Dept Med Educ, Humanities & Med Program, Box 1623,1 E 100th St, New York, NY 10029 USA. NR 5 TC 7 Z9 7 U1 0 U2 6 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD SEP PY 2005 VL 72 IS 5 BP 317 EP 321 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 961HJ UT WOS:000231652200008 PM 16184295 ER PT J AU Weintraub, D Morales, KH Moberg, PJ Bilker, WB Balderston, C Duda, JE Katz, IR Stern, MB AF Weintraub, D Morales, KH Moberg, PJ Bilker, WB Balderston, C Duda, JE Katz, IR Stern, MB TI Antidepressant studies in Parkinson's disease: A review and meta-analysis SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; depression; antidepressive agent; treatment; effect size; meta-analysis ID DOUBLE-BLIND PLACEBO; MAJOR DEPRESSION; CONTROLLED TRIAL; OPEN-LABEL; L-DOPA; SELEGILINE; CITALOPRAM; SCALE; MULTICENTER; PREVALENCE AB The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson's disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and anti depressant use in PD, controlled treatment research has been almost nonexistent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD. (C)005 Movement Disorder Society. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu OI McGuiness, Catherine/0000-0002-5367-6472 FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04, MH067894] NR 66 TC 96 Z9 99 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1161 EP 1169 DI 10.1002/mds.20555 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000010 PM 15954137 ER PT J AU Cristian, A Katz, M Cutrone, E Walker, RH AF Cristian, A Katz, M Cutrone, E Walker, RH TI Evaluation of acupuncture in the treatment of Parkinson's disease: A double-blind pilot study SO MOVEMENT DISORDERS LA English DT Article DE acupuncture; Parkinson's disease; double-blind ID VALIDATION; THERAPIES; TRENDS AB As many as 40% of patients with Parkinson's disease (PD) use some form of complementary medicine during the course of their illness, and many try acupuncture. One nonblinded study of the effects of acupuncture in PD suggested that it might be helpful for some aspects of PD. We performed a double-blind, randomized, pilot study comparing acupuncture to a control nonacupuncture procedure to determine the effects of acupuncture upon a variety of PD-associated symptoms. Fourteen patients with Stage II or III PD received acupuncture or a control nonacupuncture protocol. Before and after treatment, patients were evaluated using the Motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale. There were no statistically significant changes for the outcomes measured. In the patients who received acupuncture, nonsignificant trends toward improvement were noted in the Activities of Daily Living score of the PDQ-39, the PDQ-39 Summary Index, and the Motor subscale of the UPDRS. (C) 2005 Movement Disorder Society. C1 Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. RP Walker, RH (reprint author), Bronx Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu NR 11 TC 43 Z9 48 U1 4 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1185 EP 1188 DI 10.1002/mds.20503 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000013 PM 15884039 ER PT J AU Karamohamed, S Golbe, LI Mark, MH Lazzarini, AM Suchowersky, O Labelle, N Guttman, M Currie, LJ Wooten, GF Stacy, M Saint-Hilaire, M Feldman, RG Liu, J Shoemaker, CM Wilk, JB DeStefano, AL Latourelle, JC Xu, G Watts, R Growdon, J Lew, M Waters, C Vieregge, P Pramstaller, PP Klein, C Racette, BA Perlmutter, JS Parsian, A Singer, C Montgomery, E Baker, K Gusella, JF Herbert, A Myers, RH AF Karamohamed, S Golbe, LI Mark, MH Lazzarini, AM Suchowersky, O Labelle, N Guttman, M Currie, LJ Wooten, GF Stacy, M Saint-Hilaire, M Feldman, RG Liu, J Shoemaker, CM Wilk, JB DeStefano, AL Latourelle, JC Xu, G Watts, R Growdon, J Lew, M Waters, C Vieregge, P Pramstaller, PP Klein, C Racette, BA Perlmutter, JS Parsian, A Singer, C Montgomery, E Baker, K Gusella, JF Herbert, A Myers, RH TI Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; genetic risk factors; GenePD study ID ALPHA-SYNUCLEIN; MUTATION AB Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of the probands are affected approximately 4 times as frequently as relatives of control subjects. Several genes have been implicated as genetic risk factors for PD. We investigated the presence of six reported genetic variations in the SCNA, NR4A2, and DJ-1 genes in 292 cases of familial Parkinson's disease from the GenePD study. None of the variants were found in the GenePD families. Our results suggest that other variants or genes account for the familial risk of PD within the GenePD study. (C) 2005 Movement Disorder Society. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. Barrow Clin, Dept Neurol, Phoenix, AZ USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Univ So Calif, Dept Neurol, Los Angeles, CA USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Louisville, Hlth Sci Ctr, Dept Mol & Cellular Biol, Louisville, KY 40292 USA. Univ Miami, Dept Neurol, Miami, FL 33152 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. RP Karamohamed, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, Boston, MA 02118 USA. EM samer@bu.edu RI Pramstaller, Peter/C-2357-2008; OI Saint-Hilaire, Marie-Helene/0000-0002-2355-5979; Latourelle, Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674 FU NINDS NIH HHS [R0-1 NS36711-05] NR 10 TC 11 Z9 12 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1188 EP 1191 DI 10.1002/mds.20515 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000014 PM 15966003 ER PT J AU Zabetian, CP Samii, A Mosley, AD Roberts, JW Leis, BC Yearout, D Raskind, WH Griffith, A AF Zabetian, CP Samii, A Mosley, AD Roberts, JW Leis, BC Yearout, D Raskind, WH Griffith, A TI A clinic-based study of the LRRK2 gene in Parkinson's disease yields new mutations SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 19th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY SEP 25, 2005 CL San Diego, CA SP Parkinson Study Grp, Huntington Study Grp, Tourettes Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Virginia Mason Med Ctr, Neurol Sect, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1235 EP 1235 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000030 ER PT J AU Sadri-Vakili, G Yohrling, GJ Menon, AS Farrell, LA Keller-McGandy, CE Standaert, DG Augood, SJ Cha, JHJ AF Sadri-Vakili, G Yohrling, GJ Menon, AS Farrell, LA Keller-McGandy, CE Standaert, DG Augood, SJ Cha, JHJ TI Neuronal intranuclear inclusions do not cause transcriptional dysregulation in Huntington's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 19th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY SEP 25, 2005 CL San Diego, CA SP Parkinson Study Grp, Huntington Study Grp, Tourettes Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1239 EP 1239 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000043 ER PT J AU Kim, HM Samii, A Griffith, A Roberts, JW Mosley, AD Leis, BC Yearout, D Payami, H Zabetian, CP AF Kim, HM Samii, A Griffith, A Roberts, JW Mosley, AD Leis, BC Yearout, D Payami, H Zabetian, CP TI Protective effect of the HFE C282Y mutation in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 19th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY SEP 25, 2005 CL San Diego, CA SP Parkinson Study Grp, Huntington Study Grp, Tourettes Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2005 VL 20 IS 9 BP 1245 EP 1245 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 963WW UT WOS:000231838000061 ER PT J AU Illes, Z Stern, JNH Keskin, DB Reddy, J Brosnan, CF Waldner, H Santambrogio, L Kuchroo, VK Strominger, JL AF Illes, Z Stern, JNH Keskin, DB Reddy, J Brosnan, CF Waldner, H Santambrogio, L Kuchroo, VK Strominger, JL TI Effects of novel amino acid copolymers on microglia and T cells within the central nervous system of humanised mice SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 21st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/10th Annual Meeting of Rehabilitation in MS CY SEP 28-OCT 01, 2005 CL Thessaloniki, GREECE SP European Comm Treatment & Res Multiple Sclerosis C1 Univ Pecs, Pecs, Hungary. Harvard Univ, Sch Med, Boston, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2005 VL 11 SU 1 BP S50 EP S51 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 969QO UT WOS:000232249900183 ER PT J AU Polanczyk, M Hopke, C Huan, J Vandenbark, A Offner, H AF Polanczyk, M Hopke, C Huan, J Vandenbark, A Offner, H TI Enhanced FOXP3 expression and Treg cell function in pregnant and oestrogen-treated mice SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 21st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/10th Annual Meeting of Rehabilitation in MS CY SEP 28-OCT 01, 2005 CL Thessaloniki, GREECE SP European Comm Treatment & Res Multiple Sclerosis C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2005 VL 11 SU 1 BP S50 EP S50 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 969QO UT WOS:000232249900181 ER PT J AU Vandenbark, A Huan, J Bartholomew, R Offner, H Bourdette, D AF Vandenbark, A Huan, J Bartholomew, R Offner, H Bourdette, D TI TCR peptide vaccination in MS induces high levels of IL-10 and restores decreased FOXP3 levels SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 21st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/10th Annual Meeting of Rehabilitation in MS CY SEP 28-OCT 01, 2005 CL Thessaloniki, GREECE SP European Comm Treatment & Res Multiple Sclerosis C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Immune Response Corp, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2005 VL 11 SU 1 BP S173 EP S173 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 969QO UT WOS:000232249900626 ER PT J AU Zhu, L van de Lavoir, MC Albanese, J Beenhouwer, DO Cardarelli, PM Cuison, S Deng, DF Deshpande, S Diamond, JH Green, L Halk, EL Heyer, BS Kay, RM Kerchner, A Leighton, PA Mather, CM Morrison, SL Nikolov, ZL Passmore, DB Pradas-Monne, A Preston, BT Rangan, VS Shi, MX Srinivasan, M White, SG Winters-Digiacinto, P Wong, S Zhou, W Etches, RJ AF Zhu, L van de Lavoir, MC Albanese, J Beenhouwer, DO Cardarelli, PM Cuison, S Deng, DF Deshpande, S Diamond, JH Green, L Halk, EL Heyer, BS Kay, RM Kerchner, A Leighton, PA Mather, CM Morrison, SL Nikolov, ZL Passmore, DB Pradas-Monne, A Preston, BT Rangan, VS Shi, MX Srinivasan, M White, SG Winters-Digiacinto, P Wong, S Zhou, W Etches, RJ TI Production of human monoclonal antibody in eggs of chimeric chickens SO NATURE BIOTECHNOLOGY LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; EMBRYONIC STEM-CELLS; N-GLYCAN STRUCTURES; TRANSGENIC CHICKENS; OVALBUMIN GENE; MASS-SPECTROMETRY; DOMESTIC-FOWL; OLIGOSACCHARIDES; EXPRESSION; IGG1 AB The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization. C1 Origen Therapeut, Burlingame, CA 94010 USA. Medarex Inc, Milpitas, CA 95035 USA. Texas A&M Univ, Dept Agr & Biol Engn, College Stn, TX 77843 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. RP Etches, RJ (reprint author), Origen Therapeut, 1450 Rollins Rd, Burlingame, CA 94010 USA. EM retches@origentherapeutics.com FU NIAID NIH HHS [AI29470, AI39187, AI51415]; NIGMS NIH HHS [GM064261] NR 49 TC 114 Z9 132 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2005 VL 23 IS 9 BP 1159 EP 1169 DI 10.1038/nbt1132 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 963GA UT WOS:000231790600033 PM 16127450 ER PT J AU Chan, AT Fuchs, CS AF Chan, AT Fuchs, CS TI Do cyclo-oxygenase 2 inhibitors increase the risk of cardiovascular events? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE cardiovascular events; celecoxib; colorectal cancer; colorectal adenoma; COX2 inhibitors ID COLORECTAL ADENOMA; ROFECOXIB; TRIAL C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Harvard Canc Ctr, Gastrointestinal Malignancies Program, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-722, Boston, MA 02116 USA. EM achan@partners.org NR 5 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD SEP PY 2005 VL 2 IS 9 BP 434 EP 435 DI 10.1038/ncponc0291 PG 2 WC Oncology SC Oncology GA 962QQ UT WOS:000231747700004 PM 16265007 ER PT J AU Goldhirsch, A Gelber, RD Coates, AS AF Goldhirsch, A Gelber, RD Coates, AS TI What are the long-term effects of chemotherapy and hormonal therapy for early breast cancer? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE breast cancer; hormonal therapy; meta-analysis; recurrence; survival C1 European Inst Oncol, Dept Med, I-20141 Milan, Italy. Univ Bern, Bern, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Sydney, Sydney, NSW 2006, Australia. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org NR 6 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD SEP PY 2005 VL 2 IS 9 BP 440 EP 441 DI 10.1038/ncponc0296 PG 2 WC Oncology SC Oncology GA 962QQ UT WOS:000231747700007 PM 16265010 ER PT J AU Bromley, SK Thomas, SY Luster, AD AF Bromley, SK Thomas, SY Luster, AD TI Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics SO NATURE IMMUNOLOGY LA English DT Article ID LYMPHOID-ORGAN CHEMOKINE; HIGH ENDOTHELIAL VENULES; MICE LACKING EXPRESSION; MATURE DENDRITIC CELLS; TRANSGENIC MICE; LEUKOTRIENE B-4; CUTTING EDGE; MEMORY; EFFECTOR; LUNG AB T cell circulation between peripheral tissues and the lymphoid compartment is critical for immunosurveillance and host defense. However, the factors that determine whether T cells remain in peripheral tissue or return to the circulation are undefined. Here we demonstrate that the chemokine receptor CCR7 is a critical signal that determines T cell exit from peripheral tissue. Both CCR7 (-) and CCR7(+) effector T cells entered mouse asthmatic lung and while CCR7 (-) T cells accumulated, CCR7(+) T cells continued to migrate into afferent lymph. Delivery of both CCR7(+) and CCR7(-) T cells directly into the airways showed that only CCR7(+) T cells exited the lung and entered draining lymph nodes. Our study establishes a molecular basis for T cell exit from peripheral tissues. C1 Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Sch Med, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Sch Med, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NIAID NIH HHS [R01-AI40618, F32-AI054107] NR 37 TC 257 Z9 264 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2005 VL 6 IS 9 BP 895 EP 901 DI 10.1038/ni1240 PG 7 WC Immunology SC Immunology GA 957KX UT WOS:000231369800019 PM 16116469 ER PT J AU Mizukami, Y Jo, WS Duerr, EM Gala, M Li, JN Zhang, XB Zimmer, MA Iliopoulos, O Zukerberg, LR Kohgo, Y Lynch, MP Rueda, BR Chung, DC AF Mizukami, Y Jo, WS Duerr, EM Gala, M Li, JN Zhang, XB Zimmer, MA Iliopoulos, O Zukerberg, LR Kohgo, Y Lynch, MP Rueda, BR Chung, DC TI Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells SO NATURE MEDICINE LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; NF-KAPPA-B; TUMOR-GROWTH; GENE-EXPRESSION; TRANSCRIPTION FACTOR; COLORECTAL-CANCER; OXYGEN; HIF-1; RAS; TUMORIGENESIS AB Hypoxia inducible factor- 1 ( HIF- 1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis(1-4). It represents an attractive therapeutic target(5,6) in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy(7). But it is unclear whether inhibition of HIF- 1 alone is sufficient to block tumor angiogenesis(8,9). In HIF- 1 alpha knockdown DLD- 1 colon cancer cells ( DLD- 1(HIF- kd)), the hypoxic induction of vascular endothelial growth factor ( VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD- 1 tumors that had wild- type HIF- 1 alpha ( DLD- 1(HIF-wt)). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin ( IL)- 8 was induced by hypoxia in DLD- 1(HIF-kd) but not DLD- 1(HIF- wt) cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-kappa B. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL- 8. A neutralizing antibody to IL- 8 substantially inhibited angiogenesis and tumor growth in DLD- 1HIF- kd but not DLD-1(HIF-) (wt) xenografts, verifying the functional significance of this IL- 8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF- 1 alpha may be most effective when IL- 8 is simultaneously targeted. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Oncol Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Asahikawa Med Coll, Dept Internal Med 3, Asahikawa, Hokkaido 0788510, Japan. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu FU NCI NIH HHS [CA92594, CA098333, CA104574] NR 30 TC 259 Z9 270 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2005 VL 11 IS 9 BP 992 EP 997 DI 10.1038/nm1294 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 962IL UT WOS:000231724700028 PM 16127434 ER PT J AU Ny, A Koch, M Schneider, M Neven, E Tong, RT Maity, S Fischer, C Plaisance, S Lambrechts, D Heligon, C Terclavers, S Ciesiolka, M Kalin, R Man, WY Senn, I Wyns, S Lupu, F Brandli, A Vleminckx, K Collen, D Dewerchin, M Conway, EM Moons, L Jain, RK Carmeliet, P AF Ny, A Koch, M Schneider, M Neven, E Tong, RT Maity, S Fischer, C Plaisance, S Lambrechts, D Heligon, C Terclavers, S Ciesiolka, M Kalin, R Man, WY Senn, I Wyns, S Lupu, F Brandli, A Vleminckx, K Collen, D Dewerchin, M Conway, EM Moons, L Jain, RK Carmeliet, P TI A genetic Xenopus laevis tadpole model to study lymphangiogenesis SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LYMPHATIC-SYSTEM; VASCULAR DEVELOPMENT; TYROSINE KINASES; VEGF-C; VEINS; ANGIOGENESIS; METASTASIS; ZEBRAFISH; EMBRYOS AB Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino- mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C ( VEGF- C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF- C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis. C1 Katholieke Univ Leuven VIB, Ctr Trasgene Technol & Gene Therapy, B-3000 Louvain, Belgium. Univ Ghent, Dept Mol Biomed Res, B-9052 Ghent, Belgium. Harvard Univ, Sch Med, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol,Massachusetts Gen Hosp, Boston, MA 02114 USA. Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, CH-8057 Zurich, Switzerland. Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA. RP Carmeliet, P (reprint author), Katholieke Univ Leuven VIB, Ctr Trasgene Technol & Gene Therapy, Campus Gasthuisberg O&N,Herestr 49, B-3000 Louvain, Belgium. EM peter.carmeliet@med.kuleuven.be RI Lupu, Florea/C-3162-2009; Schneider, Martin/H-3745-2011; Verdrengh, Evelien/H-4571-2012; Brandli, Andre/N-1620-2013; Plaisance, Stephane/B-3488-2009; Vleminckx, Kris/J-5699-2013; OI Lupu, Florea/0000-0003-1249-9278; Brandli, Andre/0000-0002-8932-3644; Maity, Sunit/0000-0001-6667-3249; Plaisance, Stephane/0000-0002-1651-241X; Moons, Lieve (Godelieve)/0000-0003-0186-1411; Conway, Edward/0000-0003-0081-0305 FU NCI NIH HHS [CA-85140] NR 28 TC 141 Z9 145 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2005 VL 11 IS 9 BP 998 EP 1004 DI 10.1038/nm1285 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 962IL UT WOS:000231724700029 PM 16116431 ER PT J AU Rivera, MN Haber, DA AF Rivera, MN Haber, DA TI Wilms' tumour: Connecting tumorigenesis and organ development in the kidney SO NATURE REVIEWS CANCER LA English DT Review ID BECKWITH-WIEDEMANN-SYNDROME; DENYS-DRASH-SYNDROME; SUPPRESSOR GENE WT1; ROUND-CELL TUMOR; MICE LACKING GDNF; EWS-WT1 TRANSLOCATION PRODUCT; DOMINANT-NEGATIVE FASHION; GOLABI-BEHMEL-SYNDROME; DNA-BINDING SITE; TRANSCRIPTIONAL ACTIVATION AB Wilms' tumour, or nephroblastoma, is a common childhood tumour that is intimately linked to early kidney development and is often associated with persistent embryonic renal tissue and other kidney abnormalities. WT1, the first gene found to be inactivated in Wilms' tumour, encodes a transcription factor that functions as both a tumour suppressor and a critical regulator of renal organogenesis. Our understanding of the roles of WT1 in tumour formation and organogenesis have advanced in parallel, providing a striking example of the intersection between tumour biology, cellular differentiation and normal organogenesis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. RP Rivera, MN (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM mnrivera@partners.org; helix@mgh.harvard.edu NR 190 TC 172 Z9 176 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2005 VL 5 IS 9 BP 699 EP 712 DI 10.1038/nrc1696 PG 14 WC Oncology SC Oncology GA 960WI UT WOS:000231623500013 PM 16110318 ER PT J AU Sato, F Fukuhara, H Basilion, JP AF Sato, F Fukuhara, H Basilion, JP TI Effects of hormone deprivation and 2-methoxyestradiol combination therapy on hormone-dependent prostate cancer in vivo SO NEOPLASIA LA English DT Article DE 2-methoxyestradiol; androgen deprivation therapy; androgen-dependent cancer; microvessel density; combination therapy ID TUMOR-GROWTH; NUDE-MICE; APOPTOSIS; ANGIOGENESIS; CELLS; 2-METHOXYOESTRADIOL; ACTIVATION; INHIBITOR; PATHWAYS; HONDA AB 2-Methoxyestradiol (2-ME) has potent antiproliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgen-dependent and independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay and measuring microvessel density (MVD) in excised tumors. Animals harboring hormone-dependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, and 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis and a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo and combination therapy resulted in a significant increase in efficacy compared to no treatment controls and trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Anal & Imaging, Dept Radiol, NFCR, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Oita Univ, Fac Med, Dept Urol, Oita 87011, Japan. Univ Tokyo, Fac Med, Dept Urol, Tokyo, Japan. RP Basilion, JP (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Boston, MA 02129 USA. EM basilion@helix.mgh.harvard.edu NR 34 TC 10 Z9 10 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP PY 2005 VL 7 IS 9 BP 838 EP 846 DI 10.1593/neo.05145 PG 9 WC Oncology SC Oncology GA 989MH UT WOS:000233677500005 PM 16229806 ER PT J AU Reichardt, W Hu-Lowe, D Torres, D Weissleder, R Bogdanov, A AF Reichardt, W Hu-Lowe, D Torres, D Weissleder, R Bogdanov, A TI Imaging of VEGF receptor kinase inhibitor-induced antiangiogenic effects in drug-resistant human adenocarcinoma model SO NEOPLASIA LA English DT Article DE VEGFR2 inhibitor; angiogenesis; MRI; tumor blood volume; iron oxide ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL BLOOD-VOLUME; ANTI-ANGIOGENIC THERAPY; TYROSINE KINASE; TUMOR ANGIOGENESIS; PROSTATE-CANCER; CONTRAST AGENT; WATER EXCHANGE; MRI; BIODISTRIBUTION AB Small molecule vascular endothelial growth factor (VEGF) receptor tyrosinase kinase inhibitors (VEGFR-TKIs) show great promise in inducing antiangiogenic responses in tumors. We investigated whether antiangiogenic tumor responses induced by an experimental VEGFR-TKI (AG013925; Pfizer Global Research and Development) could be reported by magnetic resonance imaging (MRI) during the initial phase of treatment. We used MRI and superparamagnetic nano-particles for measuring relative vascular volume fraction (rVVF) in a drug-resistant colon carcinoma model. Athymic mice harboring MV522 xenografts were treated with VEGFR-TKI (25 mg/kg, p.o., with a 12-hour interval in between treatments) and were imaged after three consecutive treatments. Relative tumor blood volume fractions were calculated using Delta R-2* maps that were scaled by the known VVF value of an in-plane skeletal muscle (1.9%). There was a pronounced and statistically significant (P < .001) decrease of tumor rVVF in treated animals (0.95 +/- 0.24%; mean +/- SEM, n = 66 slices, eight mice) compared to mice that received a placebo (2.91 +/- 0.24%; mean +/- SEM, n = 66 slices, nine mice). Tumor histology confirmed a three-fold decrease of vascular density and a concomitant increase of apoptotic cell index. Hence, we demonstrated that: 1) the VEGFR-TKI resulted in antiangiogenic effects that were manifested by a decrease or rVVF; and 2) iron oxide nanoparticles and steady-state MRI enable an early detection of tumor response to antiangiogenic therapies. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Pfizer Global Res & Dev, San Diego, CA USA. RP Bogdanov, A (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM alexei.bogdanov@umassmed.edu RI Reichardt, Wilfried/K-6727-2013 FU NCI NIH HHS [5R01 CA74424-01, 1P50CA86355-01, P50 CA086355] NR 45 TC 17 Z9 18 U1 0 U2 5 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP PY 2005 VL 7 IS 9 BP 847 EP 853 DI 10.1593/neo.05139 PG 7 WC Oncology SC Oncology GA 989MH UT WOS:000233677500006 PM 16229807 ER PT J AU Okatan, M Wilson, MA Brown, EN AF Okatan, M Wilson, MA Brown, EN TI Analyzing functional connectivity using a network likelihood model of ensemble neural spiking activity SO NEURAL COMPUTATION LA English DT Article ID TRAIN DATA-ANALYSIS; COOPERATIVE FIRING ACTIVITY; POINT PROCESS SYSTEMS; UNIT-ACTIVITY; NEURONS; HIPPOCAMPUS; PATTERNS; IDENTIFICATION; SLEEP; RAT AB Analyzing the dependencies between spike trains is an important step in understanding how neurons work in concert to represent biological signals. Usually this is done for pairs of neurons at a time using correlation-based techniques. Chornoboy, Schramm, and Karr (1988) proposed maximum likelihood methods for the simultaneous analysis of multiple pair-wise interactions among an ensemble of neurons. One of these methods is an iterative, continuous-time estimation algorithm for a network likelihood model formulated in terms of multiplicative conditional intensity functions. We devised a discrete-time version of this algorithm that includes a new, efficient computational strategy, a principled method to compute starting values, and a principled stopping criterion. In an analysis of simulated neural spike trains from ensembles of interacting neurons, the algorithm recovered the correct connectivity matrices and interaction parameters. In the analysis of spike trains from an ensemble of rat hippocampal place cells, the algorithm identified a connectivity matrix and interaction parameters consistent with the pattern of conjoined firing predicted by the overlap of the neurons' spatial receptive fields. These results suggest that the network likelihood model can be an efficient tool for the analysis of ensemble spiking activity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. MIT, Picower Ctr Learning & Memory, Riken MIT Neurosci Res Ctr, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM murat@neurostat.mgh.harvard.edu; wilson@ai.mit.edu; brown@neurostat.mgh.harvard.edu FU NIDA NIH HHS [DA-015644]; NIMH NIH HHS [MH-61637, MH-59733] NR 70 TC 127 Z9 127 U1 0 U2 9 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0899-7667 EI 1530-888X J9 NEURAL COMPUT JI Neural Comput. PD SEP PY 2005 VL 17 IS 9 BP 1927 EP 1961 DI 10.1162/0899766054322973 PG 35 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 944VS UT WOS:000230459600005 PM 15992486 ER PT J AU Hui, KKS Liu, J Marina, O Napadow, V Haselgrove, C Kwong, KK Kennedy, DN Makris, N AF Hui, KKS Liu, J Marina, O Napadow, V Haselgrove, C Kwong, KK Kennedy, DN Makris, N TI The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI SO NEUROIMAGE LA English DT Review DE acupuncture; negative BOLD; limbic; cerebrum; cerebellum; sensations; pain; affect; cognition ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; ANATOMICALLY SPECIFIED METHOD; EMOTION-INDUCED CHANGES; HUMAN BRAIN ACTIVITY; HEALTHY-SUBJECTS; CEREBRAL-CORTEX; FUNCTIONAL MRI; CEREBELLAR CONTRIBUTION; ELECTRICAL-STIMULATION AB Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Charlestown, MA 02129 USA. RP Hui, KKS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM hui@nmr.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCCIH NIH HHS [K01-AT-002166-01, R21AT00978]; NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [NS 34189]; PHS HHS [1-P01-002048-01] NR 116 TC 227 Z9 271 U1 3 U2 31 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2005 VL 27 IS 3 BP 479 EP 496 DI 10.1016/j.neuroimage.2005.04.037 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 959UA UT WOS:000231543600001 PM 16046146 ER PT J AU Zhu, ZT Munhall, A Shen, KZ Johnson, SW AF Zhu, ZT Munhall, A Shen, KZ Johnson, SW TI NMDA enhances a depolarization-activated inward current in subthalamic neurons SO NEUROPHARMACOLOGY LA English DT Article DE NMDA; subthalamic nucleus; whole-cell voltage clamp; depolarization; Ca2+-activated non-selective cation current ID ACTION-POTENTIAL GENERATION; SINGLE-SPIKE ACTIVITY; NUCLEUS NEURONS; IN-VITRO; CATION CHANNEL; BASAL GANGLIA; PARKINSONS-DISEASE; CALCIUM-CHANNELS; GLOBUS-PALLIDUS; NERVOUS-SYSTEM AB Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor stimulation evokes Ca2+- and Na+-dependent burst firing in subthalamic nucleus (STN) neurons. Using whole-cell patch pipettes to record currents under voltage-clamp, we identified a time-dependent depolarization-activated inward current (DIC) that may underlie NMDA-induced burst firing in STN neurons in rat brain slices. Continuous superfusion with NMDA (20 mu M) elicited a marked TTX-insensitive inward current when the membrane was depolarized to the level of -70 or -50 mV, from a holding potential of -100 mV. This current had a long duration, and its peak amplitude occurred at a test potential of -60 mV. DIC could not be evoked using the non-NMDA receptor agonist D,L-alpha-amino-3-hydroxy-5-methylisoxalone-4-propionic acid (AMPA). DIC was blocked by either intracellular BAPTA or by removal of extracellular Ca2+, but selective blockers of T-type (mibefradil), L-type (nifedipine) and N-type (omega-conotoxin GVIA) Ca2+ channels did not. Perfusing slices with a low extracellular concentration of sodium abolished the NMDA-induced DIC, implying that both Ca2+ and Na+ are necessary for the expression of DIC. Transient receptor potential (TRP) channel blockers flufenamic acid and SKF96365 severely reduced DIC amplitude, whereas NMDA-gated currents were either increased or were unchanged. These results suggest that the activation of NMDA receptors enhances a Ca2+-activated non-selective cation current that may be mediated by a member of the TRP channel family in STN neurons. (c) 2005 Elsevier Ltd. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), SW US Vet Hosp, Portland VA Med Ctr, R&D61, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NINDS NIH HHS [NS38715] NR 46 TC 15 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2005 VL 49 IS 3 BP 317 EP 327 DI 10.1016/j.neuropharm.2005.03.018 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 960DN UT WOS:000231570500005 PM 15993436 ER PT J AU Cheung, AC Kalkanis, SN Ogilvy, CS AF Cheung, AC Kalkanis, SN Ogilvy, CS TI Paraplegia after tethered cord surgery: An uncommon combined anomaly of spinal arteriovenous fistula and sacral lipoma: Case report SO NEUROSURGERY LA English DT Article DE melanocytic tumor; melanocytoma; melanoma; pituitary; primary; sellar C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. RP Cheung, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2005 VL 57 IS 3 BP 598 EP 599 DI 10.1227/01.NEU.0000171028.96829 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 963DB UT WOS:000231782400043 ER PT J AU Di Giammarino, L Dienstag, JL AF Di Giammarino, L Dienstag, JL TI Hepatitis A - The price of progress SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COST-EFFECTIVENESS; OUTBREAK; IMMUNIZATION; VACCINATION; ADOLESCENTS; MULTISTATE; ADULTS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Dept Med, Boston, MA 02115 USA. RP Di Giammarino, L (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. NR 12 TC 14 Z9 14 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 2005 VL 353 IS 9 BP 944 EP 946 DI 10.1056/NEJMe058152 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 959WX UT WOS:000231551100015 PM 16135841 ER PT J AU Buerhaus, PI Donelan, K Ulrich, BT Norman, L Williams, M Dittus, R AF Buerhaus, PI Donelan, K Ulrich, BT Norman, L Williams, M Dittus, R TI Hospital RNs' and CNOs' perceptions of the impact of the nursing shortage on the quality of care SO NURSING ECONOMICS LA English DT Article ID PATIENT SAFETY; MORTALITY; OUTCOMES AB RN and CNO perceptions of he effects of the nursing shortage on quality of care are particularly significant in the context of the overall quality movement in health care, attention to patient safety, and appreciation for nurse-sensitive outcomes. In general, RNs perceive the negative effects of the shortage on quality as more severe than CNOs, perhaps attributable to their daily intimacy with patient care. RNs (79%) and CNOs (68%) perceived the shortage as a major problem impacting quality in hospitals; RNs in other care settings such as long-term care, ambulatory care, and student health care also felt that quality of care was impacted. Several care delivery processes were cited as being impacted by the shortage including delays in nurse responses to pages or calls, increased communication problems, delays in discharge, and increased wait time for surgery, tests, and procedures. Ninety-three percent of hospital RNs reported major problems with having enough time for patients with the majority also noting major problems with having enough time to maintain patient safety, detect complications early, and collaborate with team members. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Nursing Spectrum NurseWeek, Pearland, TX USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Sch Nursing, 221 Kirkland Hall, Nashville, TN 37240 USA. NR 26 TC 33 Z9 33 U1 0 U2 2 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD SEP-OCT PY 2005 VL 23 IS 5 BP 214 EP 221 PG 8 WC Nursing SC Nursing GA 046HM UT WOS:000237802200002 PM 16315651 ER PT J AU Rempusheski, VF O'Hara, CT AF Rempusheski, VF O'Hara, CT TI Psychometric properties of the grandparent perceptions of family scale (GPFS) SO NURSING RESEARCH LA English DT Article DE family; grandparents; psychometric testing ID RAISING GRANDCHILDREN; GRANDMOTHERS; PROFILE; EXPERIENCES; CAREGIVER; SUPPORT; HISTORY; ADULTS AB Background: For the majority of grandparents, rarely are their perceptions of family assessed, acknowledged, or viewed in the context of potential effect on individual and family health. Objective: To develop and test an instrument to measure grandparent perceptions of family. Method. An inductively derived semantic differential instrument comprising 112 items, 8 stimuli, and 27 adjective pairs within 2 domains and framed by the Becoming a Grandparent theoretical model was content validated by an expert panel, revised, and evaluated on a convenience sample of 306 community-dwelling grandparents, aged 41-92 years (M = 64, SD = 9.8), 72% female, 93% U.S. born, 62% college educated, 55% economically comfortable, and 71% living with a spouse or partner. Assessment procedures included I internal consistency reliability, item and scale correlation coefficients, and principal components factor analysis with varimax rotation to evaluate construct validity, structure, and magnitude of the scale. Results: The final scale consists of 25 items using 3 stimuli (grandparent's view of grandchild, mother of grandchild, father of grandchild) measuring a single domain (overall view of family). The Grandparent Perceptions of Family Scale (GPFS) includes 5 factors for a total explained variance of 60%. Coefficient a for the total scale is .90. Discussion: The GPFS should be helpful to clinicians and researchers in their assessment of grandparents within multigenerational families and in planning appropriate interventions to address the roles and relationships of grandparents within families. Further GPFS evaluation is suggested with grandparents of diverse racial or ethnic identification; social economic position; education; and family definition, roles, composition, and structure. C1 Univ Kansas, Sch Nursing, Kansas City, KS 66160 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. RP Rempusheski, VF (reprint author), Univ Kansas, Sch Nursing, Mail Stop 4043,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM vrempusheski@kumc.edu NR 49 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 2005 VL 54 IS 5 BP 363 EP 371 DI 10.1097/00006199-200509000-00011 PG 9 WC Nursing SC Nursing GA 972NQ UT WOS:000232460900011 PM 16224323 ER PT J AU Wolfberg, AJ Berkowitz, RS Goldstein, DP Feltmate, C Lieberman, E AF Wolfberg, AJ Berkowitz, RS Goldstein, DP Feltmate, C Lieberman, E TI Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; HYDATIDIFORM MOLE; SCORING SYSTEM; EVACUATION; DISEASE; MANAGEMENT; PROGRESS AB Objectives: Women diagnosed with complete hydatidi-form molar pregnancy are at 15% to 28% risk of developing persistent gestational trophoblastic neoplasia (GTN) requiring further management with chemotherapy. Our objective was to develop human chorionic gonadotropin (hCG) criteria that establish a patient's risk of developing persistent GTN or achieving remission from their baseline risk within a few weeks of molar evacuation. Methods: We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 1,029 women with complete molar pregnancies. We conducted a retrospective cohort study using data from 1973 to 2001. Results: Women whose hCG level declined below 50 mIU/mL during their follow-up were found to be at no more than 1.11% risk for developing persistent GTN, irrespective of when this level was reached. Women whose hCG levels was below 200 mIU/mL in the fourth week after evacuation (59.80% of all women), or below 100 mIU/mL in the sixth week after evacuation (65.8%, of all women), had a risk of persistence below 90%. hCG levels above 2,000 mIU/mL in the fourth week after evacuation (13.3% of women) were associated with a 63.8% risk of developing persistent disease. Conclusion: These data may allow clinicians to evaluate the risk of persistence that their patients with complete molar pregnancy have based on early hCG, results after molar evacuation. In the fourth week after molar evacuation, 59.8%. of women may be counseled that theit, risk of developing persistent GTN is substantially reduced from their baseline, whereas of women may be warned that their risk of developing persistent GTN is greater than 501%. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, New England Trophoblast Dis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Clin & Epidemiol Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. RP Wolfberg, AJ (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM awolfberg@partners.org NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2005 VL 106 IS 3 BP 548 EP 552 DI 10.1097/01.AOG.0000174583.51617.25 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 959BW UT WOS:000231492900015 PM 16135585 ER PT J AU Leykin, I Kao, MCJ Wong, WH AF Leykin, I Kao, MCJ Wong, WH TI HumanUpstream and MouseUpstream: Databases of promoter sequences in the human and mouse genomes SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID FACTOR-BINDING SITES; TIGR GENE INDEXES; COREGULATED GENES; ENSEMBL; MOTIFS; DISCOVERY; TOOLS; INFORMATION; ALGORITHM; ALIGNMENT AB Large-scale genome annotations, based largely on gene prediction programs, may be inaccurate in their predictions of transcription start sites, so that the identification of promoter regions remains unreliable. Here we focus on the identification of reliable gene promoter regions, critical to the understanding of transcriptional regulation. We report the construction of databases of upstream sequences HumanUpstream and MouseUpstream based on information from both the human and mouse genomes and the database of expressed sequence tags (dbEST). Using the ENSEMBL generic genome annotation system, our approach allows more reliable identification of transcript start sites, and therefore extraction of more reliable promoters regions. The HumanUpstream and MouseUpstream databases are available free of charge. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. RP Leykin, I (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Igor.Leykin@joslin.harvard.edu FU NCI NIH HHS [P20-CA 96970] NR 38 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD FAL PY 2005 VL 9 IS 3 BP 220 EP 224 DI 10.1089/omi.2005.9.220 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 975GR UT WOS:000232649500002 PM 16209636 ER PT J AU Ishitsuka, K Hideshima, T Hamasaki, M Raje, N Kumar, S Podar, K Le Gouill, S Shiraishi, N Yasui, H Roccaro, AM Tai, YZ Chauhan, D Fram, R Tamura, K Jain, J Anderson, KC AF Ishitsuka, K Hideshima, T Hamasaki, M Raje, N Kumar, S Podar, K Le Gouill, S Shiraishi, N Yasui, H Roccaro, AM Tai, YZ Chauhan, D Fram, R Tamura, K Jain, J Anderson, KC TI Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway SO ONCOGENE LA English DT Article DE multiple myeloma; IMPDH inhibitor; VX-944; apoptosis; AIF/Endo G pathway ID GUANINE-NUCLEOTIDE DEPLETION; MYCOPHENOLIC-ACID; BENZAMIDE RIBOSIDE; DRUG-RESISTANCE; IMPDH INHIBITOR; CLINICAL-TRIAL; T-LYMPHOCYTES; GROWTH-FACTOR; DEATH; EXPRESSION AB Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme required for the de novo synthesis of guanine nucleotides from IMP. VX-944 (Vertex Pharmaceuticals, Cambridge, MA, USA) is a small-molecule, selective, noncompetitive inhibitor directed against human IMPDH. In this report, we show that VX-944 inhibits in vitro growth of human multiple myeloma (MM) cell lines via induction of apoptosis. Interleukin-6, insulin-like growth factor-1, or co-culture with bone marrow stromal cells (BMSCs) do not protect against VX-944-induced MM cell growth inhibition. VX-944 induced apoptosis in MM cell lines with only modest activation of caspases 3, 8, and 9. Furthermore, the pan-caspase inhibitor z-VAD-fmk did not inhibit VX-944-induced apoptosis and cell death. During VX-944-induced apoptosis, expressions of Bax and Bak were enhanced, and both apoptosis-inducing factor (AIF) and endonuclease G (Endo G) were released from the mitochondria to cytosol, suggesting that VX-944 triggers apoptosis in MM cells primarily via a caspase-independent, Bax/AIF/Endo G pathway. Importantly, VX-944 augments the cytotoxicity of doxorubicin and melphalan even in the presence of BMSCs. Taken together, our data demonstrate a primarily non-caspase-dependent apoptotic pathway triggered by VX-944, thereby providing a rationale to enhance MM cell cytotoxicity by combining this agent with conventional agents which trigger caspase activation. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vertex Pharmaceut Inc, Cambridge, MA 02139 USA. Fukuoka Univ, Dept Internal Med 1, Fukuoka 8140180, Japan. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [1P50 CA10070-01, R01- CA50947]; PHS HHS [P0-1 78378] NR 45 TC 43 Z9 47 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 2005 VL 24 IS 38 BP 5888 EP 5896 DI 10.1038/sj.onc.1208739 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 960KW UT WOS:000231590400011 PM 15940263 ER PT J AU del Carmen, MG Joffe, S AF del Carmen, MG Joffe, S TI Informed consent for medical treatment and research: A review SO ONCOLOGIST LA English DT Article DE informed consent; treatment; autonomy; ethics; law ID PATIENT; TRIALS AB The practice of informed consent has historical roots in various disciplines, including medicine, moral philosophy, and the law. It is closely tied to philosophical notions of respect for persons and respect for individual autonomy. Consent to treatment is rooted in case law. Consent to research, in contrast, has its basis in ethical codes, statutes, and administrative regulations, with the courts playing a lesser role. In this article, we define the elements of informed consent in the treatment setting, outline its ethical and legal foundations, and explore some of its limitations. We contend that informed consent plays a critical role in clinical medicine but that other models of decision making deserve consideration under particular circumstances. We also delineate the current federal regulatory schemes guiding human subject research in the U.S., highlight how consent to research differs from consent to treatment, and explore the difficulties that arise in research involving cancer patients and certain vulnerable populations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Gillette Ctr Womens Canc, 55 Fruit St,Cox Bldg,5th Floor, Boston, MA 02114 USA. EM mdelcarmen@partners.org OI Joffe, Steven/0000-0002-0667-7384 NR 31 TC 43 Z9 48 U1 1 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2005 VL 10 IS 8 BP 636 EP 641 DI 10.1634/theoncologist.10-8-636 PG 6 WC Oncology SC Oncology GA 971AB UT WOS:000232352400010 PM 16177288 ER PT J AU Penson, RT Partridge, RA Rudd, P Seiden, MV Nelson, JE Chabner, BA Lynch, TJ AF Penson, RT Partridge, RA Rudd, P Seiden, MV Nelson, JE Chabner, BA Lynch, TJ TI Laughter: The best medicine? SO ONCOLOGIST LA English DT Article DE oncology; cancer; support; psychosocial; personal; communication; connection ID LIFE STRESS; HUMOR; SENSE; MODERATOR; ONCOLOGY; EMOTION AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (NIGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The diagnosis of cancer is incredibly stressful, and treatments are arduous. Humor may help to ease the pain, show the human side of the health care team, and help everyone cope. Whether the patient uses humor to lighten the mood of a difficult consultation with their physician, or health care workers use it to help cheer each other through the day, humor and laughter can be valuable tools. Humor can soften the isolation experienced by both patients and staff. When used sensitively, respecting the gravity of the situation, humor can build the connection among the caregiver, patient, and family. However, insensitive joking is offensive and distressing, and experience suggests a variable acceptance of humor by patients with life-threatening illnesses, making humor a high-risk strategy, and it can be a pejorative maker of an adversive power differential. The medical literature contains little on humor, and very little research has been conducted on this common aspect of human communication. Through an examination of physician and nurse experiences, the role of humor in medicine is reviewed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 51 TC 34 Z9 35 U1 6 U2 24 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2005 VL 10 IS 8 BP 651 EP 660 DI 10.1634/theoncologist.10-8-651 PG 10 WC Oncology SC Oncology GA 971AB UT WOS:000232352400012 PM 16177290 ER PT J AU Ponte, PR Hayes, C Coakley, A Stanghellini, E Gross, A Perryman, S Hanley, D Hickey, N Somerville, J AF Ponte, PR Hayes, C Coakley, A Stanghellini, E Gross, A Perryman, S Hanley, D Hickey, N Somerville, J TI Partnering with schools of nursing: An effective recruitment strategy SO ONCOLOGY NURSING FORUM LA English DT Editorial Material ID CARE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Brigham & Womens Hosp, Hematol Oncol Bone Transplantat Nursing & Clin Se, Boston, MA USA. Dana Farber Brigham & Womens Canc Ctr, Clin Initiat, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM pat_reid_ponte@dfci.harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD SEP PY 2005 VL 32 IS 5 BP 901 EP 903 DI 10.1188/05.ONF.901-903 PG 3 WC Oncology; Nursing SC Oncology; Nursing GA 965QQ UT WOS:000231965800003 ER PT J AU Bauer-Wu, S AF Bauer-Wu, S TI Seeds of hope, blossoms of meaning SO ONCOLOGY NURSING FORUM LA English DT Article C1 Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Bauer-Wu, S (reprint author), Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. EM susan_bauer_wu@dfci.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD SEP PY 2005 VL 32 IS 5 BP 927 EP 933 DI 10.1188/O5.ONF.927-933 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 965QQ UT WOS:000231965800005 PM 16136191 ER PT J AU Koo, L Hatton, MP Rubin, PAD AF Koo, Lily Hatton, Mark P. Rubin, Peter A. D. TI "Pseudo-pseudochalazion": Giant chalazion mimicking eyelid neoplasm SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB A 33-year-old man presented with a solid lesion encompassing the entire left upper eyelid. Multiple biopsies revealed lipogranuloma consistent with chalazion. The induration resolved after multiple triamcinolone injections. This is the only case report to our knowledge of a chalazion that involved the entire upper eyelid. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Eye_plastics@meei.harvarcl.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP PY 2005 VL 21 IS 5 BP 391 EP 392 DI 10.1097/01.iop.0000176266.14388.6b PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA V43VS UT WOS:000202963200018 PM 16234710 ER PT J AU Hong, JE Hatton, MP Leib, ML Fay, AM AF Hong, JE Hatton, MP Leib, ML Fay, AM TI Endocanalicular laser dacryocystorhinostomy - Analysis of 118 consecutive surgeries SO OPHTHALMOLOGY LA English DT Article ID EXTERNAL DACRYOCYSTORHINOSTOMY; ASSISTED DACRYOCYSTORHINOSTOMY; ENDONASAL DACRYOCYSTORHINOSTOMY; FAILED DACRYOCYSTORHINOSTOMY; SUMP SYNDROME; YAG LASER; REVISION; CONS; PROS AB Purpose: To describe the outcomes of endocanalicular laser dacryocystorhinostomy (ECL DCR) for patients with nasolacrimal duct obstruction (NLDO). Design: Retrospective, noncomparative, interventional case series. Participants: One hundred eight consecutive patients who underwent ECL DCR. Methods: The records of the patients who underwent ECL DCR at 1 of 2 academic centers were reviewed and the data analyzed. Main Outcome Measures: Success was defined as the resolution of symptoms or unobstructed lacrimal irrigation. Results: One hundred eighteen consecutive ECL DCR surgeries performed on 108 patients between June 1997 and June 2003 were reviewed, excluding 6 lost to follow-up. Endocanalicular laser DCR was the initial surgical intervention for all cases except 6 that had previously undergone surgery (external or endonasal DCR) at outside hospitals. Twenty-seven of the surgeries were considered failures on the basis of recurrent epiphora or discharge, or reflux on nasolacrimal irrigation. One of the failures was permanently corrected with balloon dacryoplasty. Nine of the other failures had a repeat procedure, with 7 remaining patent after one repeat procedure and an additional one remaining patent after a third procedure. All 6 ECL DCR procedures that were performed after external or endonasal DCR at an outside institution remained patent. Among the 102 initial lacrimal surgeries in this series, there was a 73.6% success rate. The overall success, including repeat procedures, was 81.5%. The success of this technique as a repeat procedure after previous external, endonasal, or ECL DCRs was 87.5%. Conclusions: Endocanalicular laser DCR offers a minimally invasive alternative procedure for the treatment of NLDO. In our series, the success rates are comparable to those previously reported. The technique had a high success rate when used to treat recurrent NLDO after previous lacrimal surgery. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. New York Presbyterian Med Ctr, Edward S Harkness Eye Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY USA. RP Fay, AM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 29 TC 44 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2005 VL 112 IS 9 BP 1629 EP 1633 DI 10.1016/j.ophtha.2005.04.015 PG 5 WC Ophthalmology SC Ophthalmology GA 959UG UT WOS:000231544200026 PM 16087238 ER PT J AU Engel, SM Berkowitz, GS Wolff, MS Yehuda, R AF Engel, SM Berkowitz, GS Wolff, MS Yehuda, R TI Psychological trauma associated with the World Trade Center attacks and its effect on pregnancy outcome SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID NEW-YORK-CITY; SEPTEMBER-11 TERRORIST ATTACKS; POSTTRAUMATIC-STRESS-DISORDER; BECK DEPRESSION INVENTORY; CENTER DISASTER; PSYCHOMETRIC PROPERTIES; MANHATTAN RESIDENTS; HEAD CIRCUMFERENCE; PRETERM DELIVERY; BIRTH OUTCOMES AB The destruction of the World Trade Center (WTC) on 11 September 2001 was a source of enormous psychological trauma that may have consequences for the health of pregnant women and their fetuses. In this report, we describe the impact of extreme trauma on the birth outcomes of women highly exposed to the WTC. We enrolled 187 women who were pregnant and living or working within close proximity to the WTC on 11 September. Among women with singleton pregnancies, 52 completed at least one psychological assessment prior to delivery. In adjusted multivariable models, both post-traumatic stress symptomatology (PTSS) and moderate depression were associated with longer gestational durations, although only PTSS was associated with decrements in infant head circumference at birth (beta = -0.07, SE = 0.03, P = 0.01). The impact of stress resulting from extreme trauma may be different from that which results from ordinary life experiences, particularly with respect to cortisol production. As prenatal PTSS was associated with decrements in head circumference, this may influence subsequent neurocognitive development. Long-term follow-up of infants exposed to extreme trauma in utero is needed to evaluate the persistence of these effects. C1 Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY 10029 USA. RP Engel, SM (reprint author), Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1043, New York, NY 10029 USA. EM Stephanie.Engel@mssm.edu FU NIEHS NIH HHS [P42 ES07384]; NIMH NIH HHS [5 R01 MH64675-03] NR 52 TC 63 Z9 65 U1 5 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD SEP PY 2005 VL 19 IS 5 BP 334 EP 341 DI 10.1111/j.1365-3016.2005.00676.x PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 957SJ UT WOS:000231393300001 PM 16115284 ER PT J AU Kohno, T Ji, RR Ito, N Allchorne, AJ Befort, K Karchewski, LA Woolf, CJ AF Kohno, T Ji, RR Ito, N Allchorne, AJ Befort, K Karchewski, LA Woolf, CJ TI Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord SO PAIN LA English DT Article DE pain; analgesia; spinal cord; opioid receptors; nerve injury ID ROOT GANGLION NEURONS; RAT DORSAL-HORN; CONTROLLED-RELEASE OXYCODONE; RANDOMIZED CONTROLLED-TRIAL; PRIMARY AFFERENT NEURONS; PRIMARY SENSORY NEURONS; SPARED NERVE INJURY; NEUROPATHIC PAIN; POSTHERPETIC NEURALGIA; SUBSTANTIA-GELATINOSA AB In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the It opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only in those spinal cord segments innervated by injured primary afferents. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons, but again only in segments receiving injured afferent input. The inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons is also reduced in affected segments following nerve injury. MOR expression decreases substantially in injured dorsal root ganglion neurons (DRG), while intact neighboring DRGs are unaffected. Decreased activation of MOR on injured primary afferent central terminals and the second order neurons they innervate may minimize any reduction by opioids of the spontaneous pain mediated by ectopic input from axotomized small diameter afferents. Retention of MOR expression and activity in nearby non-injured afferents will enable, however, an opioid-mediated reduction of stimulus-evoked and spontaneous pain carried by intact nociceptor afferents and we find that intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL. Axotomy-induced changes in MOR may contribute to opioid- insensitive components of neuropathic pain while the absence of these changes in intact afferents may contribute to the opioid sensitive components. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Boston, MA 02129 USA. EM cwoolf@partners.org FU NINDS NIH HHS [R01 NS39518, R01 NS40698] NR 55 TC 91 Z9 93 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2005 VL 117 IS 1-2 BP 77 EP 87 DI 10.1016/j.pain.2005.05.035 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 968NA UT WOS:000232168000009 PM 16098668 ER PT J AU Gallagher, RM AF Gallagher, RM TI Do patient expectations and diagnostic specificity affect outcomes in pharmacological trials in pain medicine SO PAIN MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; PERIPHERAL NEUROPATHY; AMITRIPTYLINE; EFFICACY C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP-OCT PY 2005 VL 6 IS 5 BP 331 EP 333 DI 10.1111/j.1526-4637.2005.00065.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 975LP UT WOS:000232664300001 PM 16266352 ER PT J AU Laffel, LMB AF Laffel, LMB TI Type 2 diabetes SO PEDIATRIC ANNALS LA English DT Editorial Material ID UNITED-STATES; MELLITUS; CHILDREN; ADOLESCENTS C1 Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 2005 VL 34 IS 9 BP 669 EP 672 PG 4 WC Pediatrics SC Pediatrics GA 970UP UT WOS:000232337100002 ER PT J AU Corrales-Yauckoes, KM Higgins, LA AF Corrales-Yauckoes, KM Higgins, LA TI Nutritional management of the overweight child with type 2 diabetes SO PEDIATRIC ANNALS LA English DT Article ID INSULIN-RESISTANCE; FOOD-CONSUMPTION; WEIGHT-GAIN; ADOLESCENTS; OBESITY; AMERICAN; DIET; YOUTH; FAT; RECOMMENDATIONS C1 Joslin Diabet Ctr, Pediat & Adolescent Unit, Pediat & Adolescent Sect, Boston, MA 02215 USA. RP Corrales-Yauckoes, KM (reprint author), Joslin Diabet Ctr, Pediat & Adolescent Unit, Pediat & Adolescent Sect, 1 Joslin Pl, Boston, MA 02215 USA. NR 31 TC 6 Z9 6 U1 3 U2 8 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 2005 VL 34 IS 9 BP 701 EP 709 PG 9 WC Pediatrics SC Pediatrics GA 970UP UT WOS:000232337100006 PM 16222947 ER PT J AU Norris, AW Svoren, BM AF Norris, AW Svoren, BM TI Complications and comorbidities of type 2 diabetes SO PEDIATRIC ANNALS LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; OBESE ADOLESCENTS; BLOOD-PRESSURE; CARDIOVASCULAR RISK; METABOLIC SYNDROME; WEIGHT-LOSS; CHILDREN; HYPERTENSION; PREVALENCE; METFORMIN C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Norris, AW (reprint author), Univ Iowa, Carver Coll Med, Dept Pediat, 2857 JCP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM andrew-norris@uiowa.edu FU NIDDK NIH HHS [K08 DK064906, K08-DK064906] NR 29 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 2005 VL 34 IS 9 BP 710 EP 718 PG 9 WC Pediatrics SC Pediatrics GA 970UP UT WOS:000232337100007 PM 16222948 ER PT J AU Fleischman, A Mansfield, J AF Fleischman, A Mansfield, J TI Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance SO PEDIATRIC ANNALS LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; METABOLIC SYNDROME; DIABETES-MELLITUS; ADOLESCENT GIRLS; ACANTHOSIS NIGRICANS; PREMATURE PUBARCHE; NONOBESE WOMEN; DOUBLE-BLIND; FOLLOW-UP; METFORMIN C1 Joslin Diabet Ctr, Pediat & Adolescent Sect, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Mansfield, J (reprint author), Joslin Diabet Ctr, Pediat & Adolescent Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM joan.mansfield@joslin.harvard.edu NR 61 TC 8 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 2005 VL 34 IS 9 BP 733 EP + PG 10 WC Pediatrics SC Pediatrics GA 970UP UT WOS:000232337100009 PM 16222950 ER PT J AU Staab, D Pariser, D Gottlieb, AB Kaufmann, R Eichenfield, LF Langley, RG Scott, G Ebelin, ME Barilla, D Schmidli, H Burtin, P AF Staab, D Pariser, D Gottlieb, AB Kaufmann, R Eichenfield, LF Langley, RG Scott, G Ebelin, ME Barilla, D Schmidli, H Burtin, P TI Low systemic absorption and good tolerability of pimecrolimus, administered as 1% cream (Elidel (R)) in infants with atopic dermatitis - A multicenter, 3-week, open-label study SO PEDIATRIC DERMATOLOGY LA English DT Article ID ANTIINFLAMMATORY DRUG; SKIN DISEASES; SDZ ASM-981; ECZEMA; PHARMACOLOGY; SDZ-ASM-981; MANAGEMENT; EFFICACY; EXPOSURE AB Pimecrolimus cream 1%, a nonsteroid inhibitor of inflammatory cytokines, offers an alternative to corticosteroids in the treatment of atopic dermatitis. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10-92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure. C1 Novartis Pharma AG, CH-4002 Basel, Switzerland. Dept Pediat Pneumol & Immunol, Berlin, Germany. Eastern Virginia Med Sch, Div Dermatol, Norfolk, VA 23501 USA. Virginia Clin Res, Norfolk, VA USA. UMDNJ Robert Wood Johnson Med Sch, Clin Res Ctr, New Brunswick, NJ USA. Univ Frankfurt, Ctr Dermatol & Venereol, D-6000 Frankfurt, Germany. Childrens Hosp, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Clin Invest Unit, Boston, MA USA. Novartis Pharmaceut, Horsham, W Sussex, England. Novartis Pharmaceut, E Hanover, NJ USA. RP Ebelin, ME (reprint author), Novartis Pharma AG, WSJ-386-14-41, CH-4002 Basel, Switzerland. EM marieeve.ebelin@pharma.novartis.com NR 23 TC 20 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2005 VL 22 IS 5 BP 465 EP 471 DI 10.1111/j.1525-1470.2005.00128.x PG 7 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 966VM UT WOS:000232050600017 PM 16191004 ER PT J AU Brown, SD vanSonnenberg, E Morrison, PR Diller, L Shamberger, RC AF Brown, SD vanSonnenberg, E Morrison, PR Diller, L Shamberger, RC TI CT-guided radiofrequency ablation of pediatric Wilms tumor in a solitary kidney SO PEDIATRIC RADIOLOGY LA English DT Article DE kidney neoplasms; radiofrequency ablation; CT guidance; child ID RENAL-CELL CARCINOMA AB Although recent results of percutaneous imaging-guided radio-frequency ablation (RFA) of various tumors in adults are promising, RFA of tumors in children has been performed in only a small number of cases. We describe the treatment of Wilms tumor in a solitary kidney in a 5-year-old girl using percutaneous CT-guided RFA. The procedure provided short-term palliation in this child for whom partial or total nephrectomy carried high risk and low likelihood of success. Although it might only be useful ultimately as a temporizing measure, oncologists and surgeons might wish to consider RFA in children who would otherwise require dialysis and renal transplantation or who are poor surgical candidates. Various specific technical issues differentiate pediatric from adult tumor ablation, including the amount of intra-abdominal fat, need for smaller grounding pads, and potential systemic effects of tissue heating. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Brown, SD (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Stephen.brown@childrens.harvard.edu NR 11 TC 12 Z9 13 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2005 VL 35 IS 9 BP 923 EP 928 DI 10.1007/s00247-005-1510-y PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 956QA UT WOS:000231313700018 PM 15928925 ER PT J AU Bordeianou, L Ryan, DP Goldstein, AM AF Bordeianou, L Ryan, DP Goldstein, AM TI Focal nodular hyperplasia in a child with Beckwith-Wiedemann syndrome SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Article DE Beckwith-Wiedemann syndrome; focal nodular hyperplasia ID NATURAL-HISTORY; LIVER; LESIONS; FORMS; TUMOR; RISK; CT AB Beckwith-Wiedemann Syndrome (BWS) is associated with somatic overgrowth and a high risk for embryonal tumors, including hepatoblastoma, a highly malignant liver tumor of childhood. Focal nodular hyperplasia (FNH), on the other hand, is a benign tumor of the liver that is uncommon in childhood. Herein we describe a case of FNH in a child with BWS, the first such report in the literature. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org NR 14 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD SEP PY 2005 VL 21 IS 9 BP 742 EP 744 DI 10.1007/s00383-005-1469-7 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 976GY UT WOS:000232722300015 PM 15965690 ER PT J AU Tan, WH Eichler, FS Hoda, S Lee, MS Baris, H Hanley, CA Grant, E Krishnamoorthy, KS Shih, VE AF Tan, WH Eichler, FS Hoda, S Lee, MS Baris, H Hanley, CA Grant, E Krishnamoorthy, KS Shih, VE TI Isolated sulfite oxidase deficiency: A case report with a novel mutation and review of the literature SO PEDIATRICS LA English DT Review DE sulfite; sulfite oxidase; SUOX gene; molybdenum cofactor; inborn error of metabolism ID MOLYBDENUM COFACTOR DEFICIENCY; PRENATAL-DIAGNOSIS; BIOCHEMICAL FEATURES; URINARY THIOSULFATE; TOTAL HOMOCYSTEINE; DIETARY THERAPY; MILD FORM; PATIENT; METALLOPROTEINASES; INTERFERENCE AB Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite C1 Harvard Univ, Sch Med, Genet Training Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Combined Med Pediat Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Amino Acid Disorders Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nutr Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. RP Shih, VE (reprint author), Amino Acid Disorders Lab, Bldg 149,13th St, Boston, MA 02129 USA. EM vshih@partners.org NR 50 TC 57 Z9 58 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2005 VL 116 IS 3 BP 757 EP 766 DI 10.1542/peds.2004-1897 PG 10 WC Pediatrics SC Pediatrics GA 960FW UT WOS:000231576600054 PM 16140720 ER PT J AU Kawakubo, K Akiba, Y Adelson, D Guth, PH Engel, E Tache, Y Kaunitz, JD AF Kawakubo, K Akiba, Y Adelson, D Guth, PH Engel, E Tache, Y Kaunitz, JD TI Role of gastric mast cells in the regulation of central TRH analog-induced hyperemia in rats SO PEPTIDES LA English DT Article DE mast cell; thyrotropin releasing hormone; mucosal blood flow; histamine ID THYROTROPIN-RELEASING-HORMONE; CONNECTIVE-TISSUE-TYPE; MUCOSAL BLOOD-FLOW; ACID-SECRETION; GASTROINTESTINAL MUCOSA; COMPOUND 48/80; HISTAMINE; STOMACH; STIMULATION; ACTIVATION AB RX 77368 (RX) increases gastric mucosal blood flow by a vagal cholinergic mechanism. The relative roles of mucosal and connective tissue mast cells (MMC and CTMC) were investigated in RX-injected rats. Blood flow and mast cell degranulation were measured after intracisternal RX. RX significantly increased gastric mucosal blood flow, and sequentially degranulated CTMC and MMC. Ketotifen or doxantrazole inhibited the hyperemic response. Ondansetron, RS-039604-90, or famotidine, but not ketanserin or pyrilamine, reduced hyperemia. Mast cells mediate RX-induced gastric hyperemia via 5-HT3, 5-HT4, and H-2 receptors; initial increase depends upon CTMC whereas MMC contributes to the later response. Published by Elsevier Inc. C1 Univ Calif Los Angeles, Vet Adm Med Ctr, Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Div Digest Dis, Digest Dis Res Ctr,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 114,Room 217, Los Angeles, CA 90073 USA. EM jake@ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [R01 DK 33061, R01 DK 44221, DK41301] NR 42 TC 4 Z9 5 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 SEP PY 2005 VL 26 IS 9 BP 1580 EP 1589 DI 10.1016/j.peptides.2005.05.023 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 966RU UT WOS:000232039600007 PM 16112396 ER PT J AU Mantena, SK Roy, AM Katiyar, SK AF Mantena, SK Roy, AM Katiyar, SK TI Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of anglogenic factors and activation of CD8(+) T cells in tumors SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NONMELANOMA SKIN-CANCER; GREEN TEA POLYPHENOLS; MATRIX METALLOPROTEINASES; INDUCED IMMUNOSUPPRESSION; CONTACT HYPERSENSITIVITY; ULTRAVIOLET-RADIATION; HYDROPHILIC CREAM; MOUSE SKIN; (-)-EPIGALLOCATECHIN-3-GALLATE AB There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG (approximate to 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Skin Dis Res Ctr, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCI NIH HHS [CA105368]; NIAMS NIH HHS [AR050948-01] NR 27 TC 38 Z9 40 U1 0 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2005 VL 81 IS 5 BP 1174 EP 1179 DI 10.1562/2005-04-11-RA-487 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 975CS UT WOS:000232639200021 PM 15938647 ER PT J AU Carino, C Yoo, H Rueda, BR Gonzalez, RR AF Carino, C Yoo, H Rueda, BR Gonzalez, RR TI Functional role of leptin signaling pathways in human endometrial epithelial cells SO PLACENTA LA English DT Meeting Abstract C1 Boston Biomed Res Inst, Watertown, MA USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Nacl Ciencias Med & Nutr, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD SEP-OCT PY 2005 VL 26 IS 8-9 MA P1304 BP A57 EP A57 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 959DG UT WOS:000231496500217 ER PT J AU Go, AS Fang, MC Singer, DE AF Go, AS Fang, MC Singer, DE TI Antithrombotic therapy for stroke prevention in atrial fibrillation SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID HIGH-RISK PATIENTS; APPENDAGE TRANSCATHETER OCCLUSION; THROMBIN INHIBITOR XIMELAGATRAN; RANDOMIZED CONTROLLED-TRIALS; LEFT-VENTRICULAR DYSFUNCTION; ORAL ANTICOAGULANT-THERAPY; FIXED MINIDOSE WARFARIN; ADJUSTED-DOSE WARFARIN; MAJOR VASCULAR EVENTS; BYPASS GRAFT-SURGERY C1 Kaiper Permanente No Calif, Div Res, Oakland, CA 94612 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Div Gen Internal Med, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Go, AS (reprint author), Kaiper Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. EM alan.s.go@kp.org FU NIA NIH HHS [AG15478] NR 86 TC 7 Z9 7 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 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2005 VL 48 IS 2 BP 108 EP 124 DI 10.1016/j.pcad.2005.06.007 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 983HP UT WOS:000233222400003 PM 16253651 ER PT J AU Filley, CM AF Filley, CM TI Neurobehavioral aspects of cerebral white matter disorders SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; DISEASE; DEMENTIA; EVOLUTION; BRAIN; MRI; LEUKOENCEPHALOPATHY; DYSFUNCTION AB White matter comprises nearly half the volume of the brain, increasingly can be well visualized by modern neuroradiologic techniques, and plays a key role in development, aging, and a wide range of neurologic and psychiatric disorders across the lifespan. Understanding the neurobehavioral aspects of cerebral white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain-behavior relationships. These considerations justify the notion of a behavioral neurology of white matter based on the concept of distributed neural networks in which white matter connectivity is crucial. C1 Univ Colorado, Hlth Sci Ctr, Behav Neurol Sect, Dept Neurol,Sch Med, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), Univ Colorado, Hlth Sci Ctr, Behav Neurol Sect, Dept Neurol,Sch Med, 4200 E 9th Ave,B-183, Denver, CO 80262 USA. EM Christopher.Filley@uchsc.edu NR 64 TC 9 Z9 10 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2005 VL 28 IS 3 BP 685 EP + DI 10.1016/j.psc.2005.05.008 PG 18 WC Psychiatry SC Psychiatry GA 965YZ UT WOS:000231988100011 PM 16122574 ER PT J AU Freudenreich, O Herz, L Deckersbach, T Evins, AE Henderson, DC Cather, C Goff, DC AF Freudenreich, O Herz, L Deckersbach, T Evins, AE Henderson, DC Cather, C Goff, DC TI Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial SO PSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; donepezil; acetylcholinesterase inhibitor; cholinergic system; cognition; muscarinic; nicotinic; clinical trial ID ALZHEIMERS-DISEASE; CIGARETTE-SMOKING; NEGATIVE SYMPTOMS; NUCLEUS BASALIS; RATING-SCALE; ACETYLCHOLINE; ENHANCEMENT; RELIABILITY; IMPAIRMENT; POSTMORTEM AB Rationale: Schizophrenia is a disorder with cognitive deficits that could stem from cholinergic dysfunction. Objectives: Our aim was to examine if donepezil administered to stable, medicated outpatients with schizophrenia improves cognition and psychopathology. Methods: We conducted a double-blind placebo-controlled trial of donepezil up to 10 mg/day added for 8 weeks to ongoing antipsychotic treatment in 36 typical community-treated schizophrenia patients not selected for cognitive impairment. Results: Donepezil did not improve measures of cognition or psychopathology. It was well tolerated. Conclusion: Consistent with other studies, addition of donepezil to stable patients with schizophrenia did not improve cognition or measures of psychopathology. This result does not support the hypothesis that residual symptoms and cognitive problems result from a cholinergic deficit that can be remedied by an acetylcholinesterase inhibitor. A donepezil add-on strategy might make sense in selected schizophrenia cases where a pathological process is known to affect cholinergic neurons (e.g., history of head injury or comorbid dementia). C1 Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. Edith Nourse Rogers Mem VA Hosp, Boston, MA USA. RP Freudenreich, O (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreud@massmed.org FU NIMH NIH HHS [K24 MH0205] NR 49 TC 54 Z9 55 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2005 VL 181 IS 2 BP 358 EP 363 DI 10.1007/s00213-005-2235-1 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 966VU UT WOS:000232051700018 PM 15778880 ER PT J AU Large, CH Webster, EL Goff, DC AF Large, CH Webster, EL Goff, DC TI The potential role of lamotrigine in schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Review DE anticonvulsant; sodium channels; glutamate release; schizophrenia; NMDA antagonist model ID METHYL-D-ASPARTATE; TREATMENT-RESISTANT SCHIZOPHRENIA; ANTIEPILEPTIC DRUG LAMOTRIGINE; NMDA RECEPTOR HYPOFUNCTION; RAT PREFRONTAL CORTEX; IN-VIVO MICRODIALYSIS; PHENCYCLIDINE-INDUCED DEFICITS; MIDBRAIN DOPAMINERGIC-NEURONS; SENSORIMOTOR GATING DEFICITS; PREPULSE INHIBITION DEFICITS AB Rationale: Atypical antipsychotic drugs are the drugs of choice for the treatment of schizophrenia. However, despite advances, no treatments have been established for patients who fail to improve with the most effective of these, clozapine. The inhibition of dopamine transmission through blockade of dopamine D2 receptors is considered to be essential for antipsychotic efficacy, but it is postulated that modulation of glutamate transmission may be equally important. In support of this, symptoms similar to schizophrenia can be induced in healthy volunteers using N-methyl-D-aspartate (NMDA) antagonist drugs that are also known to enhance glutamate transmission. Furthermore, lamotrigine, which can modulate glutamate release, may add to or synergise with atypical antipsychotic drugs, some of which may themselves modulate glutamate transmission. Objectives: We examine the evidence for the efficacy of lamotrigine. We consider how this fits with a glutamate neuron dysregulation hypothesis of the disorder. We discuss mechanisms by which lamotrigine might influence neuronal activity and glutamate transmission, and possible ways in which the drug might interact with antipsychotic medications. Results: Data from four clinical studies support the efficacy of adjunctive lamotrigine in the treatment of schizophrenia. In addition, and consistent with a glutamate neuron dysregulation hypothesis of schizophrenia, lamotrigine can prevent the psychotic symptoms or behavioural disruption induced by NMDA receptor antagonists in healthy volunteers or rodents. Conclusions: The efficacy of lamotrigine is most likely explained within the framework of a glutamate neuron dysregulation hypothesis, and may arise primarily through the drugs ability to influence glutamate transmission and neural activity in the cortex. The drug is likely to act through inhibition of voltage-gated sodium channels, though other molecular interactions cannot be ruled out. Lamotrigine may add to or synergise with some atypical antipsychotic drugs acting on glutamate transmission; alternatively, they may act independently on glutamate and dopamine systems to bring about a combined therapeutic effect. We propose new strategies for the treatment of schizophrenia using a combination of anti-dopaminergic and anti-glutamatergic drugs. C1 GlaxoSmithKline SpA, Dept Neuropharmacol Psychiat CEDD, I-37135 Verona, Italy. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA USA. RP Large, CH (reprint author), GlaxoSmithKline SpA, Dept Neuropharmacol Psychiat CEDD, Via Fleming 4, I-37135 Verona, Italy. EM Charles.H.Large@gsk.com NR 274 TC 46 Z9 46 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2005 VL 181 IS 3 BP 415 EP 436 DI 10.1007/s00213-005-0020-9 PG 22 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 975BE UT WOS:000232635200001 PM 16001126 ER PT J AU Iosifescu, DV Clementi-Craven, N Fraguas, R Papakostas, GI Petersen, T Alpert, JE Nierenberg, AA Fava, M AF Iosifescu, DV Clementi-Craven, N Fraguas, R Papakostas, GI Petersen, T Alpert, JE Nierenberg, AA Fava, M TI Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder SO PSYCHOSOMATIC MEDICINE LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc DE major depressive disorder; treatment outcome; cardiovascular risk factors ID DEFINED VASCULAR DEPRESSION; ILLNESS RATING-SCALE; MYOCARDIAL-INFARCTION; SERUM-CHOLESTEROL; MEDICAL ILLNESS; LATER-LIFE; PREVALENCE; FLUOXETINE; DISEASE; STROKE AB Objective: An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). Method: We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male :45, female >= 55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (>= 50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17 <= 7). Results: In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. Conclusion: Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [K23 MH 067111, R01-MH48483] NR 39 TC 32 Z9 35 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 2005 VL 67 IS 5 BP 703 EP 706 DI 10.1097/01.psy.0000170338.75346.d0 PG 4 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 970GT UT WOS:000232294000005 PM 16204427 ER PT J AU Hilsenroth, MJ Blagys, MD Ackerman, SJ Bonge, DR Blais, MA AF Hilsenroth, MJ Blagys, MD Ackerman, SJ Bonge, DR Blais, MA TI Measuring psychodynamic-interpersonal and cognitive-behavioral techniques: Development of the Comparative Psychotherapy Process Scale SO PSYCHOTHERAPY LA English DT Article DE psychotherapy process; therapist technique; adherence; psychodynamic-interpersonal; cognitive-behavioral AB Many instruments have been developed to assess techniques and interventions in a variety of psychotherapies. However, existing scales are limited by several factors such as relatively weak psychometric properties, applicability to only a single form of treatment or manual, and extensive time required for completion. The authors report on the development of a new measure, the Comparative Psychotherapy Process Scale (CPPS). The CPPS is designed to assess the distinctive features of psychodynamic-interpersonal and cognitive-behavioral treatments. Data are presented on the psychometric properties, reliability, and validity of the CPPS. The findings suggest that the scale possesses excellent interrater reliability and internal consistency as well as promising validity. Clinical utility, potential limitations, and future research of the CPPS are discussed. C1 Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hilsenroth, MJ (reprint author), Adelphi Univ, Derner Inst Adv Psychol Studies, 220 Weinberg Bldg,158 Cambridge Ave, Garden City, NY 11530 USA. EM hilsenro@adelphi.edu NR 64 TC 70 Z9 71 U1 1 U2 12 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD FAL PY 2005 VL 42 IS 3 BP 340 EP 356 DI 10.1037/0033-3204.42.3.340 PG 17 WC Psychology, Clinical SC Psychology GA 980ON UT WOS:000233027900007 ER PT J AU Asch, SM Stoto, M Mendes, M Valdez, RB Gallagher, ME Halverson, P Lurie, N AF Asch, SM Stoto, M Mendes, M Valdez, RB Gallagher, ME Halverson, P Lurie, N TI A review of instruments assessing public health preparedness SO PUBLIC HEALTH REPORTS LA English DT Review ID MEDICAL-CARE; QUALITY; PERFORMANCE AB Objectives. The purpose of this study was to review instruments that assess the level of preparedness of state and local public health departments to respond to health threats such as bioterrorism. Methods. The authors examined 27 published population-based instruments for planning or evaluating preparedness that were mostly unavailable in the peer-reviewed literature. Using the Essential Public Health Services framework, the instruments were evaluated for (1) clarity of measurement parameters, (2) balance between structural and process measures, (3) evidence of effectiveness, and (4) specification of an accountable entity. Results. There was a great deal of overlap but little consistency in what constitutes "preparedness" or how it should be measured. Most instruments relied excessively on subjective or structural measures, lacked scientific evidence for measures assessed, and failed to clearly define what entity was accountable for accomplishing the task or function. Conclusion. Strategies for improvement include measure standardization, better interagency communication, and investment in public health practice research to develop the underlying evidence base required for developing quality measures and assessments. C1 RAND Hlth, Santa Monica, CA USA. RAND Ctr Domest & Int Hlth Secur, Santa Monica, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Arkansas, Fayetteville, AR 72701 USA. RP Asch, SM (reprint author), W Los Angeles VA, 11301 Wilshire Blvd,Mail Code 111G,11301 Wilshire, Los Angeles, CA 90073 USA. EM steven_asch@rand.org NR 60 TC 26 Z9 26 U1 1 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2005 VL 120 IS 5 BP 532 EP 542 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 959JI UT WOS:000231513600009 PM 16224986 ER PT J AU Sachs, RK Chan, M Hlatky, L Hahnfeldt, P AF Sachs, RK Chan, M Hlatky, L Hahnfeldt, P TI Modeling intercellular interactions during carcinogenesis SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; CLONAL EXPANSION MODEL; LUNG-TUMOR RISK; RADIATION CARCINOGENESIS; MATHEMATICAL-MODEL; 2-MUTATION MODEL; CANCER INCIDENCE; SOLID CANCER; GENOMIC INSTABILITY; DOSE-RESPONSE AB By modulating the microenvironment of malignant or premalignant cells, inhibitory or stimulatory signals from nearby cells can play a key role in carcinogenesis. However, current commonly used quantitative models for induction of cancers by ionizing radiation focus on single cells and their progeny. Intercellular interactions are neglected or assumed to be confined to unidirectional radiation bystander effect signals from cells of the same tissue type. We here formulate a parsimoniously parameterized two-stage logistic (TSL) carcinogenesis model that incorporates some effects of intercellular interactions during the growth of premalignant cells. We show that for baseline tumor rates, involving no radiation apart from background radiation, this TSL model gives acceptable fits to a number of data sets. Specifically, it gives the same baseline hazard function, using the same number of adjustable parameters, as does the commonly used two-stage clonal expansion (TSCE) model, so it is automatically applicable to the many data sets on baseline cancer that have been analyzed using the TSCE model. For perturbations of baseline rates due to radiation, the models differ. We argue from epidemiological and laboratory evidence, especially results for the atomic bomb survivors, that for radiation carcinogenesis the TSL model gives results at least as realistic as the TSCE or similar models, despite involving fewer adjustable parameters in many cases. (c) 2005 by Radiation Research Society. C1 Univ Calif Berkeley, Dept Math & Phys, Berkeley, CA 94720 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math & Phys, 970 Evans Hall,MC 3840, Berkeley, CA 94720 USA. EM sachs@math.berkeley.edu FU NCI NIH HHS [1R01-CA78496-04]; NIGMS NIH HHS [R01-GM68423-01] NR 59 TC 23 Z9 23 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD SEP PY 2005 VL 164 IS 3 BP 324 EP 331 DI 10.1667/RR3413.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 959XB UT WOS:000231551500013 PM 16137206 ER PT J AU Rubin, GD Bradley, WG Foley, WD Herold, CJ Jaramillo, D Seeger, LL AF Rubin, GD Bradley, WG Foley, WD Herold, CJ Jaramillo, D Seeger, LL TI Image interpretation session - Sunday, November 27, 2005 SO RADIOGRAPHICS LA English DT Article AB The Sunday afternoon Image Interpretation Session has been a high point of the annual meeting of the Radiological Society of North America for over 65 years. A panel of five experts has been selected, representing the very best from the fields of neurologic, abdominal, thoracic, pediatric, and musculoskeletal radiology. Each panelist will dazzle us with an insightful analysis of two difficult cases in their area of expertise. The panelists are to be lauded for their bravery in subjecting their diagnostic acumen to the scrutiny of the thousands of radiologists in the audience. The cases, representing a diverse spectrum of diseases and disease manifestations, were selected from recent clinical imaging studies performed at the Stanford University Medical Center or the Lucille Salter Packard Children's Hospital. This session celebrates the skills of diagnostic radiologists worldwide, who are called on daily to amalgamate disparate clinical information with complex imaging data into focused differential diagnoses and effective treatment planning. We hope that these cases will serve to illustrate the central role that expert image interpretation plays in the care of patients. We welcome our audience of RSNA attendees, readers of RadioGraphics, and cyberspace denizens to join with our experts in solving these medical puzzles and to enjoy the excitement of unraveling the unknown. (c) RSNA, 2005. C1 Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. Univ Calif San Diego, Dept Radiol, Milwaukee, WI USA. Froedtert Mem Lutheran Hosp, Dept Radiol, Milwaukee, WI USA. Univ Hosp Vienna, Dept Radiol, Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. RP Rubin, GD (reprint author), Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. RI Rubin, Geoff/D-2557-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2005 VL 25 IS 5 BP 1437 EP 1447 DI 10.1148/rg.255055941 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 034SQ UT WOS:000236951300024 PM 16163794 ER PT J AU Chen, GTY Hawthorne, J Wolfgang, JA AF Chen, GTY Hawthorne, J Wolfgang, JA TI Geometric and dosimetric gains from IGRT SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 8th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 24-29, 2005 CL Lisbon, PORTUGAL C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2005 VL 76 SU 2 BP S102 EP S102 DI 10.1016/S0167-8140(05)81186-7 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 984RT UT WOS:000233322700229 ER PT J AU Chen, GTY Riboldi, M Gierga, D Turcotte, J Jiang, SB Sharp, GC Wolfgang, JA AF Chen, GTY Riboldi, M Gierga, D Turcotte, J Jiang, SB Sharp, GC Wolfgang, JA TI Clinical implementation of IGRT techniques SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 8th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 24-29, 2005 CL Lisbon, PORTUGAL C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2005 VL 76 SU 2 BP S10 EP S10 DI 10.1016/S0167-8140(05)80978-8 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 984RT UT WOS:000233322700023 ER PT J AU Stojanovic, MP Dey, D Hord, ED Zhou, YL Cohen, SP AF Stojanovic, MP Dey, D Hord, ED Zhou, YL Cohen, SP TI A prospective crossover comparison study of the single-needle and multiple-needle techniques for facet-joint medial branch block SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE facet joint; zygapophyseal joint; low back pain; diagnostic block ID LOW-BACK-PAIN; LUMBAR ZYGAPOPHYSIAL JOINTS; DOUBLE-BLIND; RADIOFREQUENCY NEUROTOMY; INTRAVENOUS LIDOCAINE; CLINICAL-FEATURES; DENERVATION; EFFICACY; SCIATICA; PLACEBO AB Background and objectives: Medial branch blocks have been widely described in the literature as a diagnostic tool for facet joint pain. Recently, a new "single-needle' technique was described that is purported to be equally accurate, and in some respects, superior to the standard multiple-needle technique. To date, no studies have been performed that compared these 2 techniques. Methods: In a multicenter setting, 24 subjects underwent 2 separate diagnostic medial-branch blocks in a randomized, single-blind crossover comparison of the single-needle and multiple-needle techniques. Multiple variables were compared between the 2 techniques, including procedure-related discomfort, postprocedure pain relief, volume of local anesthetic required, accuracy as determined by final needle position and contrast-media spread, and time needed to perform the procedure. Results: In this pilot study, the single-needle technique resulted in less procedure-related pain (P = .0003), required less superficial local anesthesia (P = .0006), and took less time to complete (P < .0001) than did the multiple-needle approach. With regard to final needle position, contrast spread, and postprocedure pain relief (P = .8), no differences were noted between the 2 techniques. Conclusions: Our results indicate that the single-needle technique takes less time to perform and causes less patient discomfort than does the standard technique but provides the same degree of accuracy. More studies with larger sample sizes are needed to corroborate these results and explore the effect the single-needle approach has on the rate of false-positive medial branch blocks. C1 Harvard Univ, Intervent Pain Program, MGH Pain Ctr,Dept Anesthesia & Crit Care, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MD USA. RP Stojanovic, MP (reprint author), Harvard Univ, Intervent Pain Program, MGH Pain Ctr,Dept Anesthesia & Crit Care, Sch Med,Massachusetts Gen Hosp, ACC-324,Fruit St, Boston, MA 02114 USA. EM mstojanovic@partners.org NR 23 TC 9 Z9 9 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 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD SEP-OCT PY 2005 VL 30 IS 5 BP 484 EP 490 DI 10.1016/j.rapm.2005.05.007 PG 7 WC Anesthesiology SC Anesthesiology GA 964YA UT WOS:000231915700011 PM 16135354 ER PT J AU Jenkins, NT Eagar, TW AF Jenkins, NT Eagar, TW TI Fume formation from spatter oxidation during arc welding SO SCIENCE AND TECHNOLOGY OF WELDING AND JOINING LA English DT Article DE welding; fume; spatter; formation rate; heat balance; droplet; vaporisation ID STAINLESS-STEEL; VAPORIZATION; GENERATION; PARTICLES; METALS; RATES; PHASE AB Spatter and fume formation rates during arc welding both increase and decrease in a similar manner as welding parameters change. Previously, this fume - spatter relationship has been attributed to evaporation of the spatter caused by oxidation. In this work, a simulated spatter oxidation test did not detect significant fume formation, but high speed videography showed fume trails behind large spatter droplets. Heat balance calculations show that only spatter droplets larger than a few millimeters evaporate and produce fume in significant amounts. Since most spatter particles are smaller than 2 mm, it is not likely that evaporation from spatter contributes significantly to fume. It is proposed that the correlation between spatter and welding fume is instead related to how the temperature of the welding surface affects formation rates of both spatter and fume. C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Cambridge, MA 02139 USA. RP Jenkins, NT (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM rood@alum.mit.edu NR 35 TC 8 Z9 8 U1 0 U2 6 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 1362-1718 J9 SCI TECHNOL WELD JOI JI Sci. Technol. Weld. Join. PD SEP PY 2005 VL 10 IS 5 BP 537 EP 543 DI 10.1179/174329305X48310 PG 7 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Materials Science; Metallurgy & Metallurgical Engineering GA 999KJ UT WOS:000234387900004 ER PT J AU Thomas, RJ AF Thomas, RJ TI Fatigue in the executive cortical network demonstrated in narcoleptics using functional magnetic resonance imaging - a preliminary study SO SLEEP MEDICINE LA English DT Article DE executive functions; fatigue narcolepsy; functional imaging ID TOTAL SLEEP-DEPRIVATION; WORKING-MEMORY DYSFUNCTION; PREFRONTAL CORTEX; MAJOR DEPRESSION; COGNITIVE PERFORMANCE; BRAIN ACTIVITY; ACTIVATION; HUMANS; SCHIZOPHRENIA; WAKEFULNESS AB Background and purpose: To demonstrate dynamic changes in cerebral functional activation during a working memory task in a state of severe excessive daytime sleepiness. Patients and methods: Omitting the usual morning dose of stimulants in three narcoleptics induced sleepiness. Functional magnetic resonance imaging (fMRI) was used to map cerebral activation during the performance of a 2-back verbal working memory task. Repeated 9.5 min scans were performed, until the subjects felt they could not continue. This was the functional imaging equivalent of the maintenance of wakefulness test. Results: Bilateral and widespread activation in known nodes of the executive network were seen during the first scan in all subjects, including the lateral prefrontal, posterior parietal and anterior cingulate cortex. There was a reduction in cerebral activation, especially but not exclusively in the prefrontal cortex, associated with slowing of performance from the first to the last tolerated scan. On stimulants, subjective alertness, activation and objective performance were readily maintained. Conclusion: This preliminary study suggests that fatigue in the executive cortical network may be demonstrated by a progressive reduction in regional cerebral activation across scans, which may be prevented by stimulant use. Averaging multiple scan runs, a typical practice in fMRI, could blur important dynamic components of activation. (c) 2005 Elsevier B.V. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Thomas, RJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. EM rthomas1@caregroup.harvard.edu NR 41 TC 22 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD SEP PY 2005 VL 6 IS 5 BP 399 EP 406 DI 10.1016/j.sleep.2005.04.005 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 975QD UT WOS:000232676100005 PM 15996898 ER PT J AU Acevedo-Garcia, D Pan, J Jun, HJ Osypuk, TL Emmons, KM AF Acevedo-Garcia, D Pan, J Jun, HJ Osypuk, TL Emmons, KM TI The effect of immigrant generation on smoking SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE immigrants; smoking; USA ID GLOBAL TOBACCO EPIDEMIC; CIGARETTE-SMOKING; UNITED-STATES; ASIAN-AMERICAN; ACCULTURATION; PREVALENCE; PATTERNS; LATINO; WOMEN; HISPANICS AB Immigrants to the US are not only an increasingly significant demographic group but overall they also have lower socioeconomic status (SES) than the native-born. It is known that tobacco use is a major health risk for groups that have low SES. However, there is some evidence that tobacco use among certain immigrant groups is lower than among the respective native-born ethnic group, and that immigrant assimilation is positively related to tobacco use. We investigated the relationship between immigrant generation and daily smoking, using the Tobacco Use Supplement of the Current Population Survey (TUS-CPS), 1995-96, a national data set representative of the US general and immigrant populations. Our multivariate logistic regression analysis of the relationship between immigrant generation and daily smoker status (n = 221, 798) showed that after controlling for age, gender, race/ethnicity, SES variables (i.e. equivalized household income, education, occupation), and central-city residence, the odds of being a daily smoker were highest among US-born individuals of US-born parents (reference group) and lowest among foreign-born individuals (95% CI: 0.54-0.62). Being a second-generation immigrant (i.e. US born) with two immigrant parents also conferred a protective effective from smoking (95% Cl: 0.64-0.77). However, having only one foreign-born parent was not protective against smoking. Testing for interaction effects, we also found that being foreign born and being second generation with two immigrant parents were especially protective against smoking among females (vis-a-vis males); racial/ethnic minorities (vis-a-vis whites); and low-income individuals (vis-a-vis high-income individuals). We discuss possible mechanisms that may explain the protective effect against smoking of being foreign born and being second generation with two immigrant parents, including differences in the stage of the tobacco epidemic between immigrants' countries of origin and the US, the "healthy immigrant effect", and anti-smoking socialization in immigrant families. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Acevedo-Garcia, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,7th Floor, Boston, MA 02115 USA. EM dacevedo@hsph.harvard.edu FU NCI NIH HHS [1 R03 CA093198-01] NR 81 TC 74 Z9 74 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 2005 VL 61 IS 6 BP 1223 EP 1242 DI 10.1016/j.socscimed.2005.01.027 PG 20 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 946FG UT WOS:000230557200009 PM 15970233 ER PT J AU Rosand, J AF Rosand, J TI Epistasis is coming - Are we ready? SO STROKE LA English DT Editorial Material DE amyloid; angiography; genetics; intracerebral hemorrhage ID CEREBRAL AMYLOID ANGIOPATHY; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; EPSILON-2 C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. FU NINDS NIH HHS [K23 NS42695-01, R01 NS042147-02] NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2005 VL 36 IS 9 BP 1879 EP 1880 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 958JR UT WOS:000231441200019 PM 16120843 ER PT J AU Tsuji, K Aoki, T Tejima, E Arai, K Lee, SR Atochin, DN Huang, PL Wang, XY Montaner, J Lo, EH AF Tsuji, K Aoki, T Tejima, E Arai, K Lee, SR Atochin, DN Huang, PL Wang, XY Montaner, J Lo, EH TI Tissue plasminogen activator promotes matrix metalloproteinase-9 upregulation after focal cerebral ischemia SO STROKE LA English DT Article DE blood; brain barrier; brain edema; metalloproteinases; mice; tissue plasminogen activator ID BLOOD-BRAIN-BARRIER; MATRIX METALLOPROTEINASES; HEMORRHAGIC TRANSFORMATION; THROMBOLYTIC THERAPY; REPERFUSION INJURY; GENE KNOCKOUT; STROKE; PROTEOLYSIS; DISRUPTION; TPA AB Background and Purpose - Thrombolytic therapy with tissue plasminogen activator (tPA) in ischemic stroke is limited by increased risks of cerebral hemorrhage and brain injury. In part, these phenomena may be related to neurovascular proteolysis mediated by matrix metalloproteinases (MMPs). Here, we used a combination of pharmacological and genetic approaches to show that tPA promotes MMP-9 levels in stroke in vivo. Methods - In the first experiment, spontaneously hypertensive rats were subjected to 3 hours of transient focal cerebral ischemia. The effects of tPA (10 mg/kg IV) on ischemic brain MMP-9 levels were assessed by zymography. In the second experiment, wild-type (WT) and tPA knockout mice were subjected to 2 hours of transient focal cerebral ischemia, and MMP-9 levels and brain edema during reperfusion were assessed. Phenotype rescue was performed by administering tPA to the tPA knockout mice. Results - In the first experiment, exogenous tPA did not change infarct size but amplified MMP-9 levels in ischemic rat brain at 24 hours. Coinfusion of the plasmin inhibitor tranexamic acid (300 mg/kg) did not ameliorate this effect, suggesting that it was independent of plasmin. In the second experiment, ischemic MMP-9 levels, infarct size, and brain edema in tPA knockouts were significantly lower than WT mice. Administration of exogenous tPA (10 mg/kg IV) did not alter infarction but reinstated the ischemic MMP-9 response back up to WT levels and correspondingly worsened edema. Conclusions - These data demonstrate that tPA upregulates brain MMP-9 levels in stroke in vivo, and suggest that combination therapies targeting MMPs may improve tPA therapy. C1 Harvard Univ, Sch Med, Neurprotect Res Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. Kinku Univ, Sch Med, Osaka, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. Hosp Univ Hebron, Neurvasc Res Lab, Barcelona, Spain. Hosp Univ Hebron, Stroke Unit, Barcelona, Spain. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neurprotect Res Lab, Massachusetts Gen Hosp, MGH E 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Atochin, Dmitriy/Q-3150-2016 FU NHLBI NIH HHS [R01 HL057818, R01 HL057818-09]; NINDS NIH HHS [R01 NS048426-04, P50 NS010828, P50 NS010828-320037, P50-NS10828, R01 NS033335, R01 NS033335-13, R01 NS048426, R01-NS37074, R01-NS38731, R01-NS40529, R01-NS48422] NR 35 TC 135 Z9 147 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2005 VL 36 IS 9 BP 1954 EP 1959 DI 10.1161/01.STR.0000177517.01203.eb PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 958JR UT WOS:000231441200035 PM 16051896 ER PT J AU Hinchey, JA Shephard, T Furie, K Smith, D Wang, D Tonn, S AF Hinchey, JA Shephard, T Furie, K Smith, D Wang, D Tonn, S CA Stroke Practice Improvement Networ TI Formal dysphagia screening Protocols prevent pneumonia SO STROKE LA English DT Article DE complications; dysphagia; outcome assessment ID ACUTE STROKE; CONTROLLED TRIAL; QUALITY; ASPIRATION; MANAGEMENT AB Background - Pneumonia is an important complication of ischemic stroke and increases mortality 3-fold. Five guidelines recommend a dysphagia screen before oral intake. What constitutes an adequate dysphagia screen and which patients should receive it remain unclear. Methods - Fifteen acute care institutions prospectively collected data on all admitted patients with acute ischemic stroke. Sites were required to collect data on demographics and 4 quality indicators. Optional data included stroke severity and complications. We measured adherence to a screen for dysphagia, the type of screen, and development of in-hospital pneumonia. Results - Between December 2001 and January 2003, 2532 cases were collected. In-hospital complications were recorded on 2329 (92%) of cases. Stroke severity was captured on 1361 (54%). Adherence to a dysphagia screen was 61%. Six sites had a formal dysphagia screen, and their adherence rate was 78% compared with 57% at sites with no formal screen. The pneumonia rate at sites with a formal dysphagia screen was 2.4% versus 5.4% (P = 0.0016) at sites with no formal screen. There was no difference in median stroke severity (5 versus 4; P = 0.84) between the sites with and without a formal screen. A formal dysphagia screen prevented pneumonia even after adjusting for stroke severity. Conclusions - A formal dysphagia screen is associated with a higher adherence rate to dysphagia screens and a significantly decreased risk of pneumonia. A formal screening protocol should be offered to all stroke patients, regardless of stroke severity. C1 St Elizabeths Med Ctr, Dept Neurol, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stoke Syst Consulting, Charlottesville, VA USA. Swedish Med Ctr, Englewood, CO 80110 USA. St Francis Med Ctr, OSF Stoke Ctr, Peoria, IL USA. IDaSTAT Consulting, St Paul, MN USA. RP Hinchey, JA (reprint author), Tufts Univ, New England Med Ctr, Inst Clin Res & Hlth Policy Studies, 750 Washington St,Box 63, Boston, MA 02111 USA. EM Jhinchey@tufts-nemc.org FU NINDS NIH HHS [K23NS02163] NR 18 TC 173 Z9 193 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2005 VL 36 IS 9 BP 1972 EP 1976 DI 10.1161/01.STR.0000177529.8686.8d PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 958JR UT WOS:000231441200038 PM 16109909 ER PT J AU Daggett, WM AF Daggett, WM TI A dqv in the life ... SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Daggett, WM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,BUL119, Boston, MA 02114 USA. EM wdaggett@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2005 VL 138 IS 3 BP 538 EP 539 DI 10.1016/j.surg.2005.01.002 PG 2 WC Surgery SC Surgery GA 974XV UT WOS:000232625600026 PM 16213910 ER PT J AU Peters, AS Schnaidt, KN Seward, SJ Rubin, RM Feins, A Fletcher, RH AF Peters, AS Schnaidt, KN Seward, SJ Rubin, RM Feins, A Fletcher, RH TI Teaching care management in a longitudinal primary care clerkship SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID SETTINGS; STUDENTS AB Background. Harvard Medical School developed a longitudinal primary care clerkship as an opportunity to teach 7 themes of modem medicine: care over time, evidence-based medicine, prevention, uncertainty, cost effectiveness, teamwork, and shared decision making. Purpose: To evaluate the effectiveness of the longitudinal experience. Methods: Students followed 1 patient throughout a 9-month clerkship and integrated the 7 themes into their management plans. We coded their written reports for number and duration of student-patient encounters; characteristics of students, preceptors, sites, and patients related to encounter frequency; and integration of themes into management plans. Results: The median number of student-patient contacts was 4.0, as was the median number of months that students maintained contact with the patients. Patients with complex diagnoses were seen more times. No characteristics of patient, student, preceptor, or site limited the number or duration of contacts. Proportions of students integrating each theme into their plans ranged from 66% (care overtime) to 11% (cost effectiveness). Those who had a greater number of patient contacts integrated more themes into their plans. Conclusions: Longitudinal relationships with patients can be achieved with a variety of patients and drive integration of some themes. C1 Harvard Univ, Sch Med, Off Educ Dev, Div Infect Dis & Int Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Vanguard Med Associates, Dept Med, Boston, MA 02115 USA. Harvard Univ, Vanguard Med Associates, Dept Pediat, Boston, MA 02115 USA. RP Peters, AS (reprint author), Harvard Univ, Sch Med, Off Educ Dev, Div Infect Dis & Int Hlth, 384 TMEC,260 Longwood Ave, Boston, MA 02115 USA. EM toni_peters@hms.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD FAL PY 2005 VL 17 IS 4 BP 322 EP 327 DI 10.1207/s15328015tlm1704_2 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 972GZ UT WOS:000232443600002 PM 16197317 ER PT J AU Hansen, JE Weisbart, RH Nishimura, RN AF Hansen, James E. Weisbart, Richard H. Nishimura, Robert N. TI Antibody mediated transduction of therapeutic proteins into living cells SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE antibody; antibodies; autoantibody; autoantibodies; single-chain Fv; protein therapy; gene therapy; p53; dystrophin; cancer; muscular dystrophy; protein transduction; ptd; Tat; penetratin; Herpes Simplex VP22 ID DUCHENNE MUSCULAR-DYSTROPHY; CANCER-CELLS; MONOCLONAL-ANTIBODY; MONONUCLEAR-CELLS; GENE-THERAPY; MUTANT P53; DELIVERY; PEPTIDE; EXPRESSION; FUSION AB Protein therapy refers to the direct delivery of therapeutic proteins to cells and tissues with the goal of ameliorating or modifying a disease process. Current techniques for delivering proteins across cell membranes include taking advantage of receptor-mediated endocytosis or using protein transduction domains that penetrate directly into cells. The most commonly used protein transduction domains are small cell-penetrating peptides derived from such proteins as the HIV-1 Tat protein. A novel protein-transduction domain developed as the single-chain fragment (Fv) of a murine anti-DNA autoantibody, mAb 3E10, has recently been developed and used to deliver biologically active proteins to living cells in vitro. This review will provide a brief overview of the development of the Fv fragment and provide a summary of recent studies using Fv to deliver therapeutic peptides and proteins (such as a C-terminal p53 peptide, C-terminal p53 antibody fragment, full-length p53, and microdystrophin) to cells. C1 Univ Calif Los Angeles, San Fernando Valley Program, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Res, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Hansen, JE (reprint author), Univ Calif Los Angeles, San Fernando Valley Program, Dept Med, Los Angeles, CA 90095 USA. EM jameshansen2004@hotmail.com; rweisbar@ucla.edu; rnishimu@ucla.edu NR 36 TC 2 Z9 2 U1 0 U2 2 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PD SEP PY 2005 VL 5 BP 782 EP 788 DI 10.1100/tsw.2005.98 PG 7 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 110NL UT WOS:000242385500010 PM 16170440 ER PT J AU Hunninghake, GM Kanarek, DJ AF Hunninghake, GM Kanarek, DJ TI Pulmonary sequestration supplied by a coronary artery SO THORAX LA English DT Article C1 Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Crit Care Med, Boston, MA 02114 USA. RP Hunninghake, GM (reprint author), Brigham & Womens Hosp, Div Pulm, 75 Francis St, Boston, MA 02115 USA. EM ghunninghake@partners.org NR 2 TC 7 Z9 8 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD SEP PY 2005 VL 60 IS 9 BP 792 EP 792 DI 10.1136/thx.2005.040832 PG 1 WC Respiratory System SC Respiratory System GA 959ZS UT WOS:000231559200021 PM 16135687 ER PT J AU Milas, M Mensah, A Alghoul, M Berber, E Stephen, A Siperstein, A Weber, CJ AF Milas, M Mensah, A Alghoul, M Berber, E Stephen, A Siperstein, A Weber, CJ TI The impact of office neck ultrasonography on reducing unnecessary thyroid surgery in patients undergoing parathyroidectomy SO THYROID LA English DT Article ID PRIMARY HYPERPARATHYROIDISM; DISEASE; LOCALIZATION; ULTRASOUND AB Background: Some have suggested that thyroid disease is even more prevalent among patients with hyperparathyroidism (HPT) than in the general population. We sought to define the incidence and optimal management strategies of thyroid disease in patients undergoing surgery for HPT. Methods: Clinical characteristics were reviewed for 1200 consecutive HPT patients treated at two endocrine surgery referral centers from 1992-2003. Both centers practice bilateral neck exploration, and one routinely obtains preoperative neck ultrasound (US) performed by surgeons. Results: Forty percent (477/1195) of HPT patients had coexisting thyroid disease, whether identified at parathyroidectomy (39%; 327/845) or by US (43%; 150/350). Colloid nodules/goiters accounted for nearly half of thyroid pathology, followed by follicular adenomas, papillary cancer, thyroiditis, and intrathyroidal parathyroids. Thyroid malignancy was found in 4.6% of HPT patients versus less than 1% in autopsy reports. Thyroid pathology was similar among single adenomas, multigland, and renal HPT. Unexpected thyroid disease first encountered at parathyroidectomy required partial or total thyroidectomy in 30% (257/845). US-detected thyroid nodules prompted fine-needle biopsy in 20%, which was cost effective in limiting concomitant thyroid surgery to fewer patients (6%; 21/350). Overall low incidence (< 0.5%) of persistent/recurrent HPT, nerve injury, and neck hematoma was unaffected by thyroid abnormalities. Conclusions: The high prevalence of thyroid disease, especially malignancies, among HPT patients mandates vigilant diagnosis and preparation for possible simultaneous parathyroid-thyroid surgery. Without appropriate preoperative screening, focal explorations for HPT may be prone to delayed diagnosis of thyroid tumors. Ultrasound performed by surgeons or endocrinologists preoperatively is an excellent diagnostic tool and minimizes unnecessary thyroidectomy in patients with subclinical thyroid disease. C1 Cleveland Clin Fdn, Dept Gen Surg, Cleveland, OH 44195 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Milas, M (reprint author), Cleveland Clin Fdn, Dept Gen Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM milasm@ccf.org NR 16 TC 34 Z9 36 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 2005 VL 15 IS 9 BP 1055 EP 1059 DI 10.1089/thy.2005.15.1055 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 975FW UT WOS:000232647400011 PM 16187914 ER PT J AU Chen, P Marsilio, E Goldstein, RH Yannas, IV Spector, M AF Chen, P Marsilio, E Goldstein, RH Yannas, IV Spector, M TI Formation of lung alveolar-like structures in collagen-glycosaminoglycan scaffolds in vitro SO TISSUE ENGINEERING LA English DT Article ID SMOOTH MUSCLE ACTIN; II EPITHELIAL-CELLS; FETAL-RAT LUNG; EXTRACELLULAR-MATRIX; GAG MATRICES; PRIMARY CULTURE; CROSS-LINKING; DIFFERENTIATION; EXPRESSION; MODEL AB The objective of this study was to investigate the histology of tissue formed when fetal rat lung cells were grown in a collagen-glycosaminoglycan ( GAG) tissue-engineering scaffold. The goal was the formation of lung histotypic structures in the tissue-engineering scaffolds in vitro. Achieving this goal would facilitate future investigations of the effects of selected scaffold design parameters on processes that may underlie aspects of lung regeneration in vivo. Lung cells were obtained from Sprague-Dawley rats after 16 and 19 days of gestation. These dissociated cells were seeded into type I collagen-chondroitin 6-sulfate matrices, 8 mm in diameter by 2 mm in thickness, cross-linked and sterilized by dehydrothermal treatment. Approximately 28 million cells were seeded into each spongelike sample. Histological and immunohistochemical studies were performed at termination periods of 2 days and 1, 2, and 3 weeks. The enzymatically dissociated 19-day gestation fetal rat lung cells formed and maintained alveolar-like structures, 50-60 mu m in diameter, in the collagen-GAG scaffold. A novel finding was that all of the cell-seeded scaffolds underwent cell-mediated contraction that appeared to be associated with the finding by immunohistochemistry of expression of alpha-smooth muscle actin in some cells. These results demonstrate the capability of dissociated lung cells to form lung histotypic structures in collagen-GAG tissue-engineering scaffolds in vitro. This culture system may be of value in facilitating exploration of strategies for preparing such scaffolds for the regeneration of lung tissue in vivo. C1 VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Div Pulm, Boston, MA USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL46902] NR 42 TC 43 Z9 43 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SEP PY 2005 VL 11 IS 9-10 BP 1436 EP 1448 DI 10.1089/ten.2005.11.1436 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 985AA UT WOS:000233347300015 PM 16259599 ER PT J AU Rajagopalan, P Berthiaume, F Tilles, AW Toner, M Yarmush, ML AF Rajagopalan, P Berthiaume, F Tilles, AW Toner, M Yarmush, ML TI Selective enhancement of cytochrome P-450 activity in rat hepatocytes by in vitro heat shock SO TISSUE ENGINEERING LA English DT Article ID ARTIFICIAL LIVER SUPPORT; NITRIC-OXIDE SYNTHASE; PROTEOLYTIC DEGRADATION; SANDWICH CONFIGURATION; GENE-EXPRESSION; STRESS-RESPONSE; PROTEINS; FIBROBLASTS; CHAPERONES; INDUCTION AB We investigated the effect of heat shock on cytochrome P-450 activity in rat hepatocytes and report a significant, selective, and time-dependent enhancement of cytochrome P-450 activity in heat-shocked hepatocytes. Stable long-term cultures of rat hepatocytes were heat shocked ( 42.5 degrees C) for 1 to 3 h and allowed to recover at 37 degrees C. Cytochrome P-450-dependent ethoxyresorufin O-dealkylase ( EROD) and benzyloxyresorufin O-dealkylase ( BROD) activities were measured up to 48 h after heat shock treatment. In general, the optimal heat shock exposure time was between 2 and 3 h. BROD activity ( induced by sodium phenobarbital) increased approximately 6-fold in hepatocytes heat shocked for 3 h in comparison with hepatocytes maintained at 37 degrees C. EROD activity ( induced by 3-methylcholanthrene) increased 2-fold on exposure to heat shock for 2 h. The expression of inducible heat shock proteins Hsp70 and Hsp32 was verified by Western immunoblot analyses. In the absence of the appropriate inducer, heat shock treatment did not enhance cytochrome P-450 activity. Furthermore, enhanced P-450 enzyme activity was delayed for heat-shocked hepatocytes. It is hypothesized that heat shock treatment attenuates the negative effects triggered by the addition of the toxic inducers and possibly stabilizes the levels of cytochrome P-450 proteins. These results suggest that heat shock treatment may be used to enhance the functionality of hepatocytes, specifically, in bioartificial liver assist devices. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA 02115 USA. RP Yarmush, ML (reprint author), Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. EM ireis@sbi.org FU NIBIB NIH HHS [P41-EB002503]; NIDDK NIH HHS [R01 DK43371] NR 39 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SEP PY 2005 VL 11 IS 9-10 BP 1527 EP 1534 DI 10.1089/ten.2005.11.1527 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 985AA UT WOS:000233347300023 PM 16259607 ER PT J AU Young, CS Abukawa, H Asrican, R Ravens, M Troulis, MJ Kaban, LB Vacanti, JP Yelick, PC AF Young, CS Abukawa, H Asrican, R Ravens, M Troulis, MJ Kaban, LB Vacanti, JP Yelick, PC TI Tissue-engineered hybrid tooth and bone SO TISSUE ENGINEERING LA English DT Article ID PERIODONTAL-LIGAMENT; BIOENGINEERED TEETH; ROOT-FORMATION; IN-VITRO; EXPRESSION; FIBROBLASTS; COLLAGEN; GENES; MICE; RAT AB Tooth loss accompanied by alveolar bone resorption presents a significant clinical problem. We have investigated the utility of a tissue-engineering approach to provide corrective therapies for tooth-bone loss. Hybrid tooth-bone tissues were bioengineered as follows. Tooth implants were generated from pig third molar tooth bud cells seeded onto polyglycolide ( PGA) and polyglycolide-co-lactide ( PLGA) scaffolds, and grown for 4 weeks in the omenta of adult rat hosts. Bone implants were generated from osteoblasts induced from bone marrow progenitor cells obtained from the same pig, seeded onto PLGA fused wafer scaffolds, and grown for 10 days in a rotational oxygen-permeable bioreactor system. The tooth and bone implants were harvested, sutured together, reimplanted, and grown in the omenta for an additional 8 weeks. Histological and immunohistochemical analyses of the excised hybrid tooth-bone constructs revealed the presence of tooth tissues, including primary and reparative dentin and enamel in the tooth portion of hybrid tooth - bone implants, and osteocalcin and bone sialoprotein-positive bone in the bone portion of hybrid tooth-bone constructs. Collagen type III-positive connective tissue resembling periodontal ligament and tooth root structures were present at the interface of bioengineered tooth and bone tissues. These results demonstrate the utility of a hybrid tooth-bone tissue-engineering approach for the eventual clinical treatment of tooth loss accompanied by alveolar bone resorption. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Yelick, PC (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM pyelick@forsyth.org NR 45 TC 93 Z9 100 U1 3 U2 22 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SEP PY 2005 VL 11 IS 9-10 BP 1599 EP 1610 DI 10.1089/ten.2005.11.1599 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 985AA UT WOS:000233347300029 PM 16259613 ER PT J AU Haspel, RL Kao, GS Yeap, BY Ritz, J Antin, JH Ballen, KK AF Haspel, RL Kao, GS Yeap, BY Ritz, J Antin, JH Ballen, KK TI Order of product infusion predicts the dominant allograft in the setting of non-myeloablative double cord blood transplant (DCBT) SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM haspelr@yahoo.com NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 2A EP 2A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600006 ER PT J AU Sands, BE Sandborn, WJ Wolf, DC Katz, S Safdi, M Schwartz, DA Hanauer, SB AF Sands, BE Sandborn, WJ Wolf, DC Katz, S Safdi, M Schwartz, DA Hanauer, SB TI Pilot study on safely and effectiveness of selective granulocyte/monocyte apheresis in patients with inflammatory bowel disease SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, GI Dept, Rochester, MN USA. Atlanta Gastroenterol Assoc, Atlanta, GA USA. Long Isl Res Assoc, Great Neck, NY USA. Consultants Clin Res, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, GI Dept, Nashville, TN USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. EM BSANDS@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 40A EP 40A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600134 ER PT J AU Darabi, K Dzik, WH AF Darabi, K Dzik, WH TI Current indications and usage of IVIG SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kamrandarabi@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 72A EP 72A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600248 ER PT J AU Abdel-Wahab, O Healy, B Dzik, WH AF Abdel-Wahab, O Healy, B Dzik, WH TI Effect of fresh-frozen plasma (FFP) transfusion on prothrombin time (PT) and bleeding in patients with mild coagulation abnormalities SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM oabdelwahab@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 141A EP 141A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600496 ER PT J AU Dzik, WH Wiklund, R Sunder, N Freiberg, A Muzzy, P Thall, I AF Dzik, WH Wiklund, R Sunder, N Freiberg, A Muzzy, P Thall, I TI Radio-frequency (RF) tags for improved patient identification and safety: Development of a prototype system SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lattice Corp, Wheaton, LA USA. Precis Dynam Corp, San Frenando, CA USA. EM Sdzik@partners.org NR 0 TC 4 Z9 4 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 143A EP 144A PG 2 WC Hematology SC Hematology GA 963ME UT WOS:000231807600506 ER PT J AU Segal, JB Dzik, WH AF Segal, JB Dzik, WH CA Transfusion MedHemostasis Clinical TI Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review SO TRANSFUSION LA English DT Review ID FRESH-FROZEN PLASMA; TRANSJUGULAR LIVER-BIOPSY; IMPAIRED COAGULATION; FIBEROPTIC BRONCHOSCOPY; NEEDLE; COAGULOPATHY; GUIDELINES; DISEASE; SAFETY; AUDIT AB BACKGROUND: The literature was systematically reviewed to determine whether a prolonged prothrombin time or elevated international normalized ratio predicts bleeding during invasive diagnostic procedures. STUDY DESIGN AND METHODS: MEDLINE and CENTRAL were searched through August 2004, with no language restriction, and reference lists were reviewed. For inclusion, articles must have reported on bleeding in more than five patients with abnormal test results undergoing diagnostic procedures. RESULTS: One trial and 24 observational studies were included. In 2 studies of bronchoscopy, the bleeding rates were similar among those with normal and abnormal tests, with wide confidence intervals (CIs) around the risk differences. During central vein cannulation (3 studies), bleeding rates among those with abnormal tests was unlikely to exceed 2.3 percent. The largest of 3 studies of arteriography found equivalent bleeding rates in patients with and without abnormal tests (risk difference, 0%; 95% CI, -3% to 2%). In the 3 studies of liver biopsy with plugging, bleeding rates were 0, 4, and 5 percent with the upper bounds of the CI as high as 17 percent. In the largest study of transjugular biopsy, the bleeding rate was 1.5 percent (95% CI, 0.3%-4%) in patients with abnormal tests. The highest bleeding rate in the 3 studies of percutaneous liver biopsy was 5.3 percent (95% CI, 1%-13%), similar to the rate in patients with normal test results. CONCLUSION: There is insufficient evidence to conclude that abnormal test results predict bleeding. Randomized controlled trials should be performed to provide stronger evidence for clinical decision making regarding preprocedure transfusion. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Segal, JB (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 1830 E Monument St,8th Floor, Baltimore, MD 21205 USA. EM jsegal@jhmi.edu RI Segal, Jodi/A-2863-2009 OI Segal, Jodi/0000-0003-3978-9662 FU NHLBI NIH HHS [5U01 HL 072268-02] NR 35 TC 275 Z9 282 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 9 BP 1413 EP 1425 DI 10.1111/j.1537-2995.2005.00546.x PG 13 WC Hematology SC Hematology GA 957SD UT WOS:000231392700005 PM 16131373 ER PT J AU McAleer, SJ Schultz, D Whittington, R Malkowicz, SB Renshaw, A Wein, A Richie, JP D'Amico, AV AF McAleer, SJ Schultz, D Whittington, R Malkowicz, SB Renshaw, A Wein, A Richie, JP D'Amico, AV TI PSA outcome following radical prostatectomy for patients with localized prostate cancer stratified by prostatectomy findings and the preoperative PSA level SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; prostate specific antigen; biochemical failure; prostatectomy ID BIOCHEMICAL RECURRENCE; GLEASON SCORE; RETROPUBIC PROSTATECTOMY; ANTIGEN RECURRENCE; MARGIN STATUS; PROBABILITY; PROGRESSION; EXPRESSION; THERAPY; FAILURE AB Purpose: Algorithms have been developed to predict time to biochemical failure (BF) following radical prostatectomy (RP) for patients with clinically localized prostate cancer. The purpose of this study was to validate an algorithm based on prostatectomy findings and to evaluate whether the preoperative serum prostate specific antigen (PSA) enhances the predictive ability of the algorithm. Materials and Methods: Between 1988 and 2002, 2417 patients underwent RP for clinically localized prostate cancer at one of 2 large university hospitals. Patients were retrospectively stratified into 4 risk groups based upon prostatectomy grade, stage, and margin status, and were then dichotomized by the preoperative PSA level (cut point 10 ng/mL). Cox regression multivariable analyses were performed to evaluate the ability of the risk group and preoperative PSA level to predict time to BF (PSA more than 0.2 ng/mL) following RP. Results: The preoperative PSA level (P < 0.0001) and risk group (P < 0.0001) were significant predictors of time to BF following RP. Estimates of the BF rates 7 years following RP were 13%, 30%, 51%, and 72% for groups 1-4, respectively (pairwise P values <= 0.0002). Further stratification within each risk group using the preoperative PSA level with a cut point at 10 ng/mL revealed BF rates of 8% versus 35%, 25% versus 54%, 31% versus 73%, and 63% versus 86% for risk groups 1-4, respectively (all P values < 0.0001). Conclusions: An algorithm to predict BF based on prostatectomy findings has been validated, and the addition of the preoperative PSA level improved its ability to identify high risk patients who may benefit from entry into adjuvant treatment trials. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Baptist Hosp Miami, Dept Pathol, Miami, FL 33176 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP McAleer, SJ (reprint author), Brigham & Womens Hosp, Dept Urol, 75 Francis St, Boston, MA 02115 USA. EM smcaleer@partners.org NR 22 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD SEP-OCT PY 2005 VL 23 IS 5 BP 311 EP 317 DI 10.1016/j.urolonc.2004.12.013 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 970PU UT WOS:000232322900001 PM 16144663 ER PT J AU D'Amico, AV Chen, MH Cox, MC Dahut, W Figg, WD AF D'Amico, AV Chen, MH Cox, MC Dahut, W Figg, WD TI Prostate-specific antigen response duration and risk of death for patients with hormone-refractory metastatic prostate cancer SO UROLOGY LA English DT Article ID PHASE-II TRIAL; PLACEBO-CONTROLLED TRIAL; THALIDOMIDE; SURVIVAL; MEN AB Objectives. To evaluate whether the time to return to the baseline prostate-specific antigen (PSA) level (PSA response duration) is significantly associated with the time to death after randomization for men with hormone-refractory metastatic prostate cancer. Methods. The study (n = 213) and validation (n = 281) cohorts constituted 494 men with hormone-refractory metastatic prostate cancer treated in four prospective randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether a significant association existed between the PSA response duration and the time to death after randomization, controlling for treatment and known prognostic factors. Results. A decreasing PSA response duration was significantly associated with a shorter survival after randomization in the study (P = 0.001) and validation (P = 0.02) cohorts, controlling for treatment and known prognostic factors, which included serum PSA, lactate dehydrogenase, alkaline phosphatase, and hemoglobin levels and the Eastern Cooperative Oncology Group performance status. The adjusted hazard ratio for death was 1.9 (95% confidence interval 1.4 to 2.6; P = 0.0002) and 2.1 (95% Cl 1.2 to 3.5; P = 0.01) for men in the study and validation cohorts, respectively, whose PSA response duration was shorter than the median value of 3 months. The PSA response duration dichotomized about the median remained significantly associated with death whether patients in the validation cohort experienced at least a 50% reduction (P = 0.05) in the PSA level or not (P = 0.03). Conclusions. The duration of the PSA response to treatment is significantly associated with length of survival for men with hormone-refractory metastatic prostate cancer. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu RI Figg Sr, William/M-2411-2016 NR 13 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 SEP PY 2005 VL 66 IS 3 BP 571 EP 576 DI 10.1016/j.urology.2005.03.083 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 968JC UT WOS:000232157700021 PM 16140080 ER PT J AU Fujiwara, RT Vale, AM da Silvaa, JCF Martins-Filho, OA Reis, AB Oliveira, RC Machado-Coelho, GL Bueno, LL Bethony, JM Frank, G Nascimento, E Genaro, O Mayrink, W Reed, S Campos-Neto, A AF Fujiwara, RT Vale, AM da Silvaa, JCF Martins-Filho, OA Reis, AB Oliveira, RC Machado-Coelho, GL Bueno, LL Bethony, JM Frank, G Nascimento, E Genaro, O Mayrink, W Reed, S Campos-Neto, A TI Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis SO VETERINARY RESEARCH LA English DT Article DE visceral leishmaniasis; dogs; vaccine; Leishmania chagasi ID AMERICAN TEGUMENTARY LEISHMANIASIS; WORLD CUTANEOUS LEISHMANIASIS; HUMORAL IMMUNE-RESPONSES; MOLECULAR CHARACTERIZATION; DERMAL LEISHMANIASIS; CYTOKINE PROFILE; ENDEMIC AREA; FIELD TRIAL; KALA-AZAR; EFFICACY AB Control of canine visceral leishmaniasis (VL) remains a difficult and serious problem mostly because there is no reliable and effective vaccine available to prevent this disease. A mixture of three recombinant leishmanial antigens (TSA, LeIF and LmSTI1) encoded by three genes highly conserved in the Leishmania genus have been shown to induce excellent protection against infection in both murine and simian models of cutaneous leishmaniasis. A human clinical trial with these antigens is currently underway. Because of the high degree of conservation, these antigens might be useful vaccine candidates for VL as well. In the present study, using the dog model of the visceral disease, we evaluated the immunogenicity of these three antigens formulated with two different adjuvants, MPL-SE(R) and AdjuPrime(R). The results were compared with a whole parasite vaccine formulated with BCG as the adjuvant. In order to investigate if sensitization with the recombinant antigens would result in recognition of the corresponding native parasite antigens upon infection, the animals were exposed for four weeks after the termination of the immunization protocol with the recombinant antigens to a low number of L. chagasi promastigotes, an etiological agent of VL. Immune response was evaluated by quantitative ELISA in the animal sera before and after exposure to the viable parasites. Both antigen specific IgG1 and IgG2 antibody levels were measured. Immunization of dogs with the recombinant antigens formulated in either MPL-SE(R) or AdjuPrime(R) resulted in high antibody levels particularly to LmSTI1. In addition, this immunization although to low levels, resulted in the development of antibody response to the whole parasite lysate. Importantly, experimental exposure with low numbers of culture forms of L. chagasi promastigotes caused a clear boost in the immune response to both the recombinant antigens and the corresponding native molecules. The boost response was predominantly of the IgG2 isotype in animals primed with the recombinant antigens plus MPL-SE(R). In contrast, animals primed with the recombinant antigens formulated in AdjuPrime(R) as well as animals vaccinated with crude antigen preparation responded with mixed IgG1/IgG2 isotypes. These results point to the possible use of this antigen cocktail formulated with the adjuvant MPL-SE(R) in efficacy field trials against canine VL. C1 Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Lab Leishmanioses & Vacinas, BR-31270901 Belo Horizonte, MG, Brazil. FIOCRUZ MG, Ctr Pesquisas Rene Rachou, Lab Doenca Chagas, BR-30190002 Belo Horizonte, MG, Brazil. FIOCRUZ MG, Ctr Pesquisas Rene Rachou, Lab Imunol Celular & Mol, BR-30190002 Belo Horizonte, MG, Brazil. Univ Fed Ouro Preto, Escola Farm, BR-35400000 Ouro Preto, MG, Brazil. George Washington Univ, Washington, DC 20037 USA. Heska Corp, Ft Collins, CO USA. Infect Dis Res Inst, Seattle, WA 98104 USA. Forsyth Inst, Boston, MA 02115 USA. RP Fujiwara, RT (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Lab Leishmanioses & Vacinas, BR-31270901 Belo Horizonte, MG, Brazil. EM mtmrtf@gwumc.edu RI Fujiwara, Ricardo/J-7579-2012 OI Fujiwara, Ricardo/0000-0002-4713-575X NR 46 TC 48 Z9 49 U1 0 U2 2 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0928-4249 J9 VET RES JI Vet. Res. PD SEP-DEC PY 2005 VL 36 IS 5-6 BP 827 EP 838 DI 10.1051/vetres:2005033 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA 958NK UT WOS:000231454800013 PM 16120256 ER PT J AU Louder, MK Sambor, A Chertova, E Hunte, T Barrett, S Ojong, F Sanders-Buell, E Zolla-Pazner, S McCutchan, FE Roser, JD Gabuzda, D Lifson, JD Mascola, JR AF Louder, MK Sambor, A Chertova, E Hunte, T Barrett, S Ojong, F Sanders-Buell, E Zolla-Pazner, S McCutchan, FE Roser, JD Gabuzda, D Lifson, JD Mascola, JR TI HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity SO VIROLOGY LA English DT Article DE HIV-1; vaccines; neutralizing antibodies; pseudovirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; HUMAN LYMPHOID-TISSUE; TYPE-1 INFECTION; HOST ICAM-1; PRIMARY ISOLATE; CHIMERIC VIRUS; ENV GENES; T-CELLS; HLA-DR AB Recombinant lentiviral vectors pseudotyped with heterologous HIV-1 envelope glycoproteins allow rapid and accurate measurement of antibody-mediated HIV-1 neutralization. However, the neutralization phenotypes of envelope pseudoviruses have not been directly compared to isogenic replication competent HIV-1. We produced pseudoviruses expressing three different HIV-1 envelope glycoproteins and subdoned the same three env genes into a replication competent NL4-3 molecular clone. For each of the antibodies tested, the neutralization dose-response curves of pseudoviruses and corresponding replication competent viruses were similar. Thus, envelope pseudoviruses can be used to study the anti-HIV-1 neutralizing antibody response. A single passage of replication competent virus derived from 293T cells through peripheral blood mononuclear cells (PBMC) caused a substantial decrease in sensitivity to neutralizing antibodies. This was associated with an increase in average virion envelope glycoprotein content of the PBMC-derived virus. Replication competent HIV-1 and isogenic envelope pseudoviruses have similar neutralization characteristics, but passage into PBMC is associated with decreased sensitivity to neutralization. Published by Elsevier Inc. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Henry M Jackson Fdn, Rockville, MD 20850 USA. New York Vet Affairs Med Ctr, New York, NY USA. NYU, Sch Med, New York, NY USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@nih.gov FU NCI NIH HHS [N01-CO-124000]; NINDS NIH HHS [NS37277] NR 59 TC 54 Z9 55 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2005 VL 339 IS 2 BP 226 EP 238 DI 10.1016/j.virol.2005.06.003 PG 13 WC Virology SC Virology GA 960ZO UT WOS:000231631900008 PM 16005039 ER PT J AU Yang, YG AF Yang, YG TI Mixed chimerism and tolerization of human T cells to pig xenoantigens SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 369 EP 369 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500039 ER PT J AU Shimizu, A Hisashi, Y Kuwaki, K Tseng, YL Dor, FJMF Houser, S Wong, BS Schuurman, HJ Robson, SC Yamada, K Sachs, DH Cooper, DKC Colvin, RB AF Shimizu, A Hisashi, Y Kuwaki, K Tseng, YL Dor, FJMF Houser, S Wong, BS Schuurman, HJ Robson, SC Yamada, K Sachs, DH Cooper, DKC Colvin, RB TI Thrombotic microangiopathy due to humoral rejection in cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs in baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 378 EP 379 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500069 ER PT J AU Hisashi, Y Kuwaki, K Tseng, YL Dor, FJMF Houser, S Wong, BS Schuurman, HJ Robson, SC Cooper, DKC Sachs, DH Colvin, RB Yamada, K Shimizu, A AF Hisashi, Y Kuwaki, K Tseng, YL Dor, FJMF Houser, S Wong, BS Schuurman, HJ Robson, SC Cooper, DKC Sachs, DH Colvin, RB Yamada, K Shimizu, A TI Acute and chronic rejection in cardiac xenografts from alpha 1,3galactosyltransferase gene-knockout (GalT-KO) pigs in baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 379 EP 379 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500070 ER PT J AU Shimizu, I Kawahara, T Bardwell, PD Carroll, MC Sykes, M AF Shimizu, I Kawahara, T Bardwell, PD Carroll, MC Sykes, M TI Cell extrinsic complement receptor 1/2 is required for natural antibody production and for tolerization of B-1 cells producing anti-alpha GAL via mixed chimerism induction SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 385 EP 385 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500087 ER PT J AU Wong, BS O'Malley, PE Tseng, YL Dor, FJMF Cooper, DKC Saidman, SL Yamada, K Sachs, DH AF Wong, BS O'Malley, PE Tseng, YL Dor, FJMF Cooper, DKC Saidman, SL Yamada, K Sachs, DH TI Absence of correlation between the degree of anti-human panel reactive antibodies and reactivity to cells from GalT knock-out swine in patients awaiting cadaveric renal transplants SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 385 EP 385 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500089 ER PT J AU Hisashi, Y Shimizu, A Wong, B Yurkow, E Subasinghe, N Crysler, C Khalil, E Travins, J Nobori, S Okumi, M Moran, S Weiner, J Molloy, C Sachs, D Yamada, K AF Hisashi, Y Shimizu, A Wong, B Yurkow, E Subasinghe, N Crysler, C Khalil, E Travins, J Nobori, S Okumi, M Moran, S Weiner, J Molloy, C Sachs, D Yamada, K TI Roles of classical and alternative pathways of complement activation in hyperacute rejection of pig-to baboon kidney xenografts identified by specific complement pathway inhibitors SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johnson & Johnson Pharmaceut, Res & Dev, Raritan, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 409 EP 409 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500164 ER PT J AU Shimizu, I Smith, RN Zhao, GL Medof, E Sykes, M AF Shimizu, I Smith, RN Zhao, GL Medof, E Sykes, M TI DAF prevents acute humoral rejection induced by low titers of anti-alpha Gal antibodies in GalT KO mice SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 8th International Xenotransplantation Congress/2nd International Symposium on ABO Incompatibility in Transplantation CY SEP 10-14, 2005 CL Goteborg, SWEDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2005 VL 12 IS 5 BP 410 EP 410 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 952IP UT WOS:000230997500170 ER PT J AU Wang, HB Kohno, T Amaya, F Brenner, GJ Ito, N Allchorne, A Ji, RR Woolf, CJ AF Wang, HB Kohno, T Amaya, F Brenner, GJ Ito, N Allchorne, A Ji, RR Woolf, CJ TI Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission SO JOURNAL OF NEUROSCIENCE LA English DT Article DE bradykinin; spinal cord; pain; synaptic transmission; glutamate; neuromodulator ID CENTRAL SENSITIZATION; DORSAL-HORN; PERIPHERAL AXOTOMY; AFFERENT-FIBERS; NMDA-RECEPTOR; B-2 RECEPTOR; RAT; PLASTICITY; CAPSAICIN; LOCALIZATION AB Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B-2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B-2-specific agonist, augments AMPA- and NMDA-induced, and primary afferent-evoked EPSCs, and increases the frequency and amplitude of miniature EPSCs in superficial dorsal horn neurons in vitro. Administration of bradykinin to the spinal cord in vivo produces, moreover, an NMDA-dependent hyperalgesia. We also demonstrate that nociceptive inputs result in the production of bradykinin in the spinal cord and that an intrathecal B-2-selective antagonist suppresses behavioral manifestations of central sensitization, an activity-dependent increase in glutamatergic synaptic efficacy. Primary afferent-evoked central sensitization is, in addition, reduced in B-2 receptor knock-out mice. We conclude that bradykinin is released in the spinal cord in response to nociceptor inputs and acts as a synaptic neuromodulator, potentiating glutamatergic synaptic transmission to produce pain hypersensitivity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Brigham & Womens Hosp, Pain Res Ctr, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. EM cwoolf@partners.org OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [R01 NS040698, NS039518, R01 NS038253, K08 NS044139] NR 36 TC 61 Z9 68 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 AUG 31 PY 2005 VL 25 IS 35 BP 7986 EP 7992 DI 10.1523/JNEUROSCI.2393-05.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 960BL UT WOS:000231565100011 PM 16135755 ER PT J AU Blom, AS Mukherjee, R Pilla, JJ Lowry, AS Yarbrough, WM Mingoia, JT Hendrick, JW Stroud, RE McLean, JE Affuso, J Gorman, RC Gorman, JH Acker, MA Spinale, FG AF Blom, AS Mukherjee, R Pilla, JJ Lowry, AS Yarbrough, WM Mingoia, JT Hendrick, JW Stroud, RE McLean, JE Affuso, J Gorman, RC Gorman, JH Acker, MA Spinale, FG TI Cardiac support device modifies left ventricular geometry and myocardial structure after myocardial infarction SO CIRCULATION LA English DT Article DE collagen; contractility; myocardial infarction; matrix metalloproteinases; heart-assist device ID MATRIX-METALLOPROTEINASE INHIBITION; HEART-FAILURE; SYSTOLIC DYSFUNCTION; TISSUE INHIBITOR; MATRIX-METALLOPROTEINASE-9; MYOFIBROBLASTS; ENLARGEMENT; PROGRESSION; ENALAPRIL; EXPANSION AB Background - Whether mechanical restraint of the left ventricle ( LV) can influence remodeling after myocardial infarction ( MI) remains poorly understood. This study surgically placed a cardiac support device ( CSD) over the entire LV and examined LV and myocyte geometry and function after MI. Methods and Results - Post- MI sheep ( 35 to 45 kg; MI size, 23 +/- 2%) were randomized to placement of the CorCap CSD ( Acorn Cardiovascular, Inc) ( MI + CSD; n = 6) or remained untreated ( MI only; n = 5). Uninstrumented sheep ( n = 10) served as controls. At 3 months after MI, LV end- diastolic volume ( by MRI) was increased in the MI only group compared with controls ( 98 +/- 8 versus 43 +/- 4 mL; P < 0.05). In the MI + CSD group, LV end- diastolic volume was lower than MI only values ( 56 +/- 7 mL; P < 0.05) but remained higher than controls ( P < 0.05). Isolated LV myocyte shortening velocity was reduced by 35% from control values ( P < 0.05) in both MI groups. LV myocyte beta-adrenergic response was reduced with MI but normalized in the MI + CSD group. LV myocyte length increased in the MI group and was reduced in the MI + CSD group. Relative collagen content was increased and matrix metalloproteinase- 9 was decreased within the MI border region of the CSD group. Conclusions - A CSD beneficially modified LV and myocyte remodeling after MI through both cellular and extracellular mechanisms. These findings provide evidence that nonpharmacological strategies can interrupt adverse LV remodeling after MI. C1 Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA USA. Univ Penn, Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC USA. Ralph H Johnson Dept Vet Affairs, Charleston, SC USA. RP Acker, MA (reprint author), Hosp Univ Penn, Div Cardiothorac Surg, 6th Floor Silverstein Pavil, Philadelphia, PA 19104 USA. EM macker@mail.med.upenn.edu FU NHLBI NIH HHS [R01 HL071137, HL-59165, P01-HL-48788-08, R01 HL063954] NR 36 TC 62 Z9 63 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 30 PY 2005 VL 112 IS 9 BP 1274 EP 1283 DI 10.1161/CIRCULATIONAHA.104.499202 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 959IJ UT WOS:000231511100007 PM 16129812 ER PT J AU Murrell, JR Randall, JD Rosoff, J Zhao, JL Jensen, RV Gullans, SR Haupert, GT AF Murrell, JR Randall, JD Rosoff, J Zhao, JL Jensen, RV Gullans, SR Haupert, GT TI Endogenous ouabain - Upregulation of steroidogenic genes in hypertensive hypothalamus but not adrenal SO CIRCULATION LA English DT Article DE brain; genes; hormones; hypertension; inhibitors ID BOVINE ADRENOCORTICAL-CELLS; DIGITALIS-LIKE FACTORS; K+-ATPASE INHIBITOR; BLOOD-PRESSURE; BIOSYNTHESIS; NA+; QUANTIFICATION; DEHYDROGENASE; EXPRESSION; RELEASE AB Background - Mammalian tissues contain a presumed endogenous Na+, K+- ATPase inhibitor that binds reversibly to the Na+ pump with high affinity and specificity. The inhibitor has been linked to the pathogenesis of experimental volume-expanded and human essential hypertension. This compound has been isolated from mammalian hypothalamus and appears to be an isomer of the plant-derived cardiac glycoside ouabain, if not ouabain itself. The objective of this study was to test the hypothesis that a biosynthetic pathway exists in mammalian tissues to produce a steroid derivative closely related to plant cardiac glycosides. Methods and Results - Using bioinformatics and genomic techniques, Milan hypertensive rat tissues were studied because this strain has a 10-fold increase in hypothalamic ouabain-like compound that is linked to the pathogenesis of the hypertension. A putative steroid biosynthetic pathway was constructed and candidate genes encoding enzymes in this pathway were identified from sequence databases. Differential expression of selected genes in the pathway was studied by microarray analysis and quantitative polymerase chain reaction, with functional validation by gene silencing using small interfering RNAs. Marked upregulation of genes coding for P450 side chain cleavage and Delta 5-3 beta- hydroxysteroid dehydrogenase/Delta 5-Delta 4-isomerase enzymes in hypertensive hypothalamus but not adrenal was found, compared with normotensive Milan rats. Knockdown of the latter gene decreased production of ouabain- like factor from neural tissue. Conclusions - Our findings support the possibility that a unique steroid biosynthetic circuit exists in Milan rat brain, functioning independently from adrenal, which could account for the overproduction of the hypothalamic ouabain-like compound in this species. C1 Massachusetts Gen Hosp, Renal Unit, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Funct Genom, Boston, MA USA. Univ Massachusetts, Dept Phys, Boston, MA USA. Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. Univ Massachusetts, Dept Math, Boston, MA USA. RP Haupert, GT (reprint author), Massachusetts Gen Hosp, Renal Unit, Med Serv, CNY-8,149 13th St, Charlestown, MA 02129 USA. EM gthaupert@partners.org FU NHLBI NIH HHS [R01 HL52282] NR 32 TC 40 Z9 44 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 AUG 30 PY 2005 VL 112 IS 9 BP 1301 EP 1308 DI 10.1161/CIRCULATIONAHA.105.554071 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 959IJ UT WOS:000231511100011 PM 16116051 ER PT J AU Ikonomidis, JS Barbour, JR Amani, Z Stroud, RE Herron, AR McClister, DM Camens, SE Lindsey, ML Mukherjee, R Spinale, FG AF Ikonomidis, JS Barbour, JR Amani, Z Stroud, RE Herron, AR McClister, DM Camens, SE Lindsey, ML Mukherjee, R Spinale, FG TI Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms SO CIRCULATION LA English DT Article DE aneurysm; aorta; thorax; MMP-9; MMP-2 ID MATRIX-METALLOPROTEINASE INHIBITION; PERIARTERIAL APPLICATION; MMP-9 EXPRESSION; CALCIUM-CHLORIDE; ANGIOGENESIS; COLLAGENASE; PROTEOLYSIS; ACTIVATION; GENERATION AB Background-The matrix metalloproteinases (MMPs) contribute to cardiovascular remodeling, and MMPs, such as the gelatinases (MMP-9 and MMP-2), have been identified in thoracic aortic aneurysmal (TAA) tissue, but a cause-effect relationship has not been clearly established. Accordingly, this study examined TAA progression in mice devoid of the MMP-9 gene. Methods and Results-The descending thoracic aortas of wild-type (WT) FVB (n = 17) and MMP-9 gene knockout (KO, n = 11) mice were exposed to 0.5 mol/L of CaCl2 for 15 minutes with terminal studies performed at 4 weeks. Aortic lumen diameter was measured using video micrometry at baseline and at 4 weeks (TAA) followed by aortic tissue analysis. In WT mice, aortic diameter increased by 138 +/- 5% at 4 weeks (P < 0.05), consistent with TAA formation. In the KO mice, aortic diameter increased from baseline by 120 +/- 4% (P < 0.05) but was attenuated from WT TAA values (P < 0.05). Gelatin zymography performed on TAA segments confirmed the absence of MMP-9 in the KO mice but a > 8-fold relative increase in the active form of MMP-2 compared with WT (P < 0.05). Despite this, MMP-2 activity was relatively increased (P < 0.05) and colocalized to smooth muscle cell actin in a differential pattern favoring medial distruction in the WT TAA compared with the KO TAA segments. Conclusions-These results demonstrate that MMP-9 gene deletion attenuated TAA formation despite an increase in the zymographic levels of MMP-2. These unique findings suggest that an interaction between these 2 MMPs is necessary to facilitate TAA progression. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Suite 409 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu RI Lindsey, Merry/B-2650-2012 FU NHLBI NIH HHS [R01 HL 075360, R01 HL075488-01, R01 HL 059165-07, R01 HL075360, R01 HL 66029] NR 28 TC 13 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 30 PY 2005 VL 112 IS 9 SU S BP I242 EP I248 DI 10.1161/CIRCULATIONAHA.104.526152 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962OH UT WOS:000231741600038 PM 16159824 ER PT J AU Schroder, JN Williams, ML Hata, JA Muhlbaier, LH Swaminathan, M Mathew, JP Glower, DD O'Connor, CM Smith, PK Milano, CA AF Schroder, JN Williams, ML Hata, JA Muhlbaier, LH Swaminathan, M Mathew, JP Glower, DD O'Connor, CM Smith, PK Milano, CA TI Impact of mitral valve regurgitation evaluated by intraoperative transesophageal echocardiography on long-term outcomes after coronary artery bypass grafting SO CIRCULATION LA English DT Article DE CABG surgery; coronary artery disease; mitral regurgitation; transesophageal echocardiography ID ACUTE MYOCARDIAL-INFARCTION; PROGNOSTIC-SIGNIFICANCE; SURGERY; SURVIVAL; COMPLICATIONS; INTERVENTION; SEVERITY; DISEASE AB Background-It is unclear if mild or moderate mitral valve regurgitation (MR) should be repaired at the time of coronary artery bypass grafting (CABG). We sought to determine the long-term effect of uncorrected MR, measured by intraoperative transesophageal echocardiography (TEE), in CABG patients. Methods and Results-Between May 1999 and September 2003, data were gathered for 3264 consecutive patients who underwent isolated CABG and had MR graded by intraoperative TEE. MR was graded on the following 5 levels: none, trace, mild, moderate, and severe. Patients who had severe MR or who underwent mitral valve surgery were eliminated from the analysis. The remaining patients were combined into the following 3 groups: none or trace, mild, and moderate MR. Preoperative and follow-up data were 99% complete. The median length of follow-up was 3.0 years. Multivariable analysis controlling for important preoperative risk factors was performed to determine predictors of death and death/hospitalization for heart failure. Increasing MR was a risk factor for death [hazard ratio (HR), 1.44; P<0.001] and death/heart failure hospitalization (HR, 1.34; P<0.01). When patients with moderate MR were eliminated from the analysis, mild MR was a risk factor for death (HR, 1.34; P=0.011) and death/hospitalization for heart failure (HR, 1.34; P<0.001). Conclusions-Even mild MR, identified by intraoperative TEE, predicts worse outcomes after CABG. Revascularization alone did not eliminate the negative long-term effects of mild MR. CABG patients with uncorrected mild or moderate MR are at increased risk for death and heart-failure hospitalization; consideration for surgical repair or more aggressive medical management and follow-up is warranted. C1 Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Anesthesiol, Div Cardiac Anesthesia, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Div Cardiol, Durham, NC 27703 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Duke Univ, Clin Res Inst, Durham, NC 27703 USA. RP Milano, CA (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Box 3043, Durham, NC 27703 USA. EM milan002@mc.duke.edu NR 21 TC 21 Z9 22 U1 1 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 AUG 30 PY 2005 VL 112 IS 9 SU S BP I293 EP I298 DI 10.1161/CIRCULATIONAHA.104.523472 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962OH UT WOS:000231741600047 PM 16159834 ER PT J AU Williams, ML Muhlbaier, LH Schroder, JN Hata, JA Peterson, ED Smith, PK Landolfo, KP Messier, RH Davis, RD Milano, CA AF Williams, ML Muhlbaier, LH Schroder, JN Hata, JA Peterson, ED Smith, PK Landolfo, KP Messier, RH Davis, RD Milano, CA TI Risk-adjusted short- and long-term outcomes for on-pump versus off-pump coronary artery bypass surgery SO CIRCULATION LA English DT Article DE CABG surgery; off-pump surgery; OPCAB; long-term ID BEATING-HEART; GRAFT-SURGERY; MORTALITY; MORBIDITY; EVOLUTION; THERAPY; DISEASE AB Background-Surgeons have adopted off-pump coronary artery bypass grafting (OPCAB) in an effort to reduce the morbidity of surgical revascularization. However, long-term outcome of OPCAB compared with conventional coronary artery bypass grafting (CABG) remains poorly defined. Methods and Results-Using logistic regression analysis and proportional hazards modeling, short-term and long-term outcomes (perioperative mortality and complications, risk-adjusted survival, and survival/freedom from revascularization) were investigated for patients who underwent OPCAB (641 patients) and CABG-cardiopulmonary bypass (5026 patients) from 1998 to 2003 at our institution. For these variables, follow-up was 98% complete. OPCAB patients were less likely to receive transfusion (odds ratio for OPCAB, 0.80; P=0.037), and there were trends toward improvement in other short-term outcomes compared with CABG-cardiopulmonary bypass. Lono-term outcomes analysis demonstrated no difference in survival, but OPCAB patients were more likely to require repeat revascularization (OPCAB hazard ratio, 1.29; P=0.020). Conclusions-OPCAB patients were less likely to receive transfusion during their hospitalization for surgery but had higher risk for revascularization in follow-up. These results highlight the need for a large randomized, controlled trial to compare these 2 techniques. C1 Duke Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27703 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27703 USA. Duke Univ, Clin Res Inst, Durham, NC USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Med Coll Georgia, Coll Med, Sect Cardiothorac Surg, Dept Surg, Augusta, GA 30912 USA. RP Milano, CA (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, Box 3043, Durham, NC 27703 USA. EM milan002@mc.duke.edu NR 24 TC 9 Z9 9 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 AUG 30 PY 2005 VL 112 IS 9 SU S BP I366 EP I370 DI 10.1161/CIRCULATIONAHA.104.526012 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962OH UT WOS:000231741600059 PM 16159847 ER PT J AU Zhu, F Otsuji, Y Yotsumoto, G Yuasa, T Ueno, T Yu, B Koriyama, C Hamasaki, S Biro, S Kisanuki, A Minagoe, S Levine, RA Sakata, R Tei, C AF Zhu, F Otsuji, Y Yotsumoto, G Yuasa, T Ueno, T Yu, B Koriyama, C Hamasaki, S Biro, S Kisanuki, A Minagoe, S Levine, RA Sakata, R Tei, C TI Mechanism of persistent ischemic mitral regurgitation after annuloplasty - Importance of augmented posterior mitral leaflet tethering SO CIRCULATION LA English DT Article DE mitral valve; echocardiography; valuloplasty ID LEFT-VENTRICULAR DYSFUNCTION; PAPILLARY-MUSCLE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; REPAIR; MOTION; CARDIOMYOPATHY; DETERMINANTS; INSIGHTS AB Background-We hypothesized that surgical annuloplasty for ischernic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischernic MR after the annuloplasty were investigated. Methods and Results-In 31 patients with surgical annuloplasty for ischernic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P < 0.01), no improvement in AML tethering, greater worsening in PML tethering (P < 0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r(2) = 0.46, P < 0.0001), increased PML tethering was the primary determinant afterward (r(2) = 0.60, P < 0.0001). Conclusion-Although tethering of both leaflets is the major determinant of ischernic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the ammuloplasty. C1 Kagoshima Univ, Grad Sch Med, Dept Cardiovasc Resp & Metab Med, Kagoshima 8908520, Japan. Kagoshima Univ, Grad Sch Med, Dept Publ Hlth, Kagoshima 8908520, Japan. Kagoshima Univ, Grad Sch Med, Dept Cardiovasc Surg, Kagoshima 8908520, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Otsuji, Y (reprint author), Kagoshima Univ, Grad Sch Med, Dept Cardiovasc Resp & Metab Med, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM yutaka@m.kufm.kagoshima-u.ac.jp NR 23 TC 26 Z9 26 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 AUG 30 PY 2005 VL 112 IS 9 SU S BP I396 EP I401 DI 10.1161/CIRCULATIONAHA.104.524561 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962OH UT WOS:000231741600064 PM 16159853 ER PT J AU Stanger, BZ Datar, R Murtaugh, LC Melton, DA AF Stanger, BZ Datar, R Murtaugh, LC Melton, DA TI Direct regulation of intestinal fate by Notch SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differentiation; intestine; lineage; stem cells ID CRE-MEDIATED RECOMBINATION; GAMMA-SECRETASE INHIBITOR; STEM-CELLS; EPITHELIAL PROGENITORS; ENDOCRINE DEVELOPMENT; SELF-RENEWAL; DIFFERENTIATION; LINEAGE; GUT; SPECIFICATION AB The signals that maintain the proper balance between adult intestinal cell types are poorly understood. Loss-of-function studies have implicated the Notch pathway in the regulation of intestinal fate during development. However, it is unknown whether Notch has a role in maintaining the balance of different cell types in the adult intestine and whether it acts reversibly. To determine whether Notch has a direct effect on intestinal development and adult intestinal cell turnover, we have used a gain-of-function approach to activate Notch. Ectopic Notch signaling in adult intestinal progenitor cells leads to a bias against secretory fates, whereas ectopic Notch activation in the embryonic foregut results in reversible defects in villus morphogenesis and loss of the proliferative progenitor compartment. We conclude that Notch regulates adult intestinal development by controlling the balance between secretory and absorptive cell types. In the embryo, Notch activation perturbs morphogenesis, possibly through effects on stem or progenitor cells. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. RP Melton, DA (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA. EM dmelton@mcb.harvard.edu FU NIDDK NIH HHS [K08 DK064136] NR 33 TC 146 Z9 151 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 2005 VL 102 IS 35 BP 12443 EP 12448 DI 10.1073/pnas.0505690102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961QC UT WOS:000231675900030 PM 16107537 ER PT J AU Ohmura, K Johnsen, A Ortiz-Lopez, A Desany, P Roy, M Besse, W Rogus, J Bogue, M Puech, A Lathrop, M Mathis, D Benoist, C AF Ohmura, K Johnsen, A Ortiz-Lopez, A Desany, P Roy, M Besse, W Rogus, J Bogue, M Puech, A Lathrop, M Mathis, D Benoist, C TI Variation in IL-1 beta gene expression is a major determinant of genetic differences in arthritis aggressivity in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; autoimmunity; inflammation; Mouse Phenome Project ID COLLAGEN-INDUCED ARTHRITIS; QUANTITATIVE TRAIT LOCI; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; LABORATORY MICE; INBRED STRAINS; ANIMAL-MODELS; INTERLEUKIN-1; MOUSE; ASSOCIATION AB in humans and in animal models, susceptibility to arthritis is under complex genetic control, reflecting influences on the immunological processes that initiate autoimmunity and on subsequent inflammatory mechanisms in the joints. The effector phases are conveniently modeled by the K/BxN serum transfer system, a robust model well suited for genetic analysis where arthritis is initiated by pathogenic Ig. Here, we mapped the genetic loci distinguishing the high-responder BALIB/c vs. low-responder SA strains. After computational modeling of potential breeding schemes, we adapted a stepwise selective breeding strategy, with a whole-genome scan performed on a limited number of animals. Several genomic regions proved significantly associated with high sensitivity to arthritis. One of these regions, on distal chr2, was centered on the interleukin 1 gene family. Quantitation of transcripts of the II1a and II1b candidate genes revealed a 10-fold greater induction of II1b mRNA in BALB/c than in SA splenocytes after injection of LPS, whereas II1a showed much less difference. The differential activity of the II1b gene was associated with a particular sequence haplotype of noncoding polymorphisms. The BALB/c haplotype was found in 75% of wild-derived strains but was rare among conventional inbred strains (4/33 tested, one of which is DBA/1, the prototype arthritis-susceptible strain) and was associated with vigorous II1b responses in a panel of inbred strains. Inbred strains carrying this allele were far more responsive to serum-transferred arthritis, confirming its broad importance in controlling arthritis severity. C1 Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr,Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Sect Genet & Epidemiol, Joslin Diabet Ctr,Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Ctr Natl Genotypage, F-91057 Evry, France. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr,Brigham & Womens Hosp, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu RI PUECH, Anne/A-7470-2013 NR 39 TC 20 Z9 21 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 2005 VL 102 IS 35 BP 12489 EP 12494 DI 10.1073/pnas.0504325102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961QC UT WOS:000231675900038 PM 16113081 ER PT J AU Shin, JB Adams, D Paukert, M Siba, M Sidi, S Levin, M Gillespie, PG Grunder, S AF Shin, JB Adams, D Paukert, M Siba, M Sidi, S Levin, M Gillespie, PG Grunder, S TI Xenopus TRPN1 (NOMPC) localizes to microtubule-based cilia in epithelial cells, including inner-ear hair cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ciliary; mechanosensory; transduction; transient receptor potential channel ID TRANSDUCTION CHANNEL; MECHANOELECTRICAL-TRANSDUCTION; MECHANOSENSORY TRANSDUCTION; MECHANOTRANSDUCER CHANNEL; INTRAFLAGELLAR TRANSPORT; LATERAL-LINE; TIP LINKS; POLYCYSTIN-1; STEREOCILIA; CADHERIN-23 AB In vertebrates, the senses of hearing and balance depend on hair cells, which transduce sounds with their hair bundles, containing actin-based stereocilia and microtubule-based kinocilia. A longstanding question in auditory science is the identity of the mechanically sensitive transduction channel of hair cells, thought to be localized at the tips of their stereocilia. Experiments in zebrafish implicated the transient receptor potential (TRP) channel NOMPC (drTRPN1) in this role; TRPN1 is absent from the genomes of higher vertebrates, however, and has not been localized in hair cells. Another candidate for the transduction channel, TRPA1, apparently is required for transduction in mammalian and nonmammalian vertebrates. This discrepancy raises the question of the relative contribution of TRPN1 and TRPA1 to transduction in nonmammalian vertebrates. To address this question, we cloned the TRPN1 ortholog from the amphibian Xenopus laevis, generated an antibody against the protein, and determined the protein's cellular and subcellular localization. We found that TRPN1 is prominently located in lateral-line hair cells, auditory hair cells, and ciliated epidermal cells of developing Xenopus embryos. In ciliated epidermal cells TRPN1 staining was enriched at the tips and bases of the cilia. In saccular hair cells, TRPN1 was located prominently in the kinocilial bulb, a component of the mechanosensory hair bundles. Moreover, we observed redistribution of TRPN1 upon treatment of hair cells with calcium chelators, which disrupts the transduction apparatus. This result suggests that although TRPN1 is unlikely to be the transduction channel of stereocilia, it plays an essential role, functionally related to transduction, in the kinocilium. C1 Oregon Hearing Res Ctr, Portland, OR 97239 USA. Vollum Inst, Portland, OR 97239 USA. Harvard Univ, Sch Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dev & Craniofacial Biol, Boston, MA 02115 USA. Univ Tubingen, Dept Otolaryngol, D-72076 Tubingen, Germany. Univ Tubingen, Dept Physiol 2, D-72076 Tubingen, Germany. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. Univ Wurzburg, Dept Physiol 2, D-97070 Wurzburg, Germany. RP Grunder, S (reprint author), Oregon Hearing Res Ctr, Portland, OR 97239 USA. EM gruender@mail.uni-wuerzburg.de OI Grunder, Stefan/0000-0002-7635-9883; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [R01 DC002368, P30 DC005983]; NIDCR NIH HHS [K22 DE016633, K22 DE016633-01A1, T32 DE007327, T32-DE-07327]; NIGMS NIH HHS [R01 GM06227] NR 33 TC 52 Z9 58 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 2005 VL 102 IS 35 BP 12572 EP 12577 DI 10.1073/pnas.0502403102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961QC UT WOS:000231675900052 PM 16116094 ER PT J AU Ongur, D Zalesak, M Weiss, AP Ditman, T Titone, D Heckers, S AF Ongur, D Zalesak, M Weiss, AP Ditman, T Titone, D Heckers, S TI Hippocampal activation during processing of previously seen visual stimulus pairs SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE hippocampus; neuroimaging; fMRI; paired object recognition; configural memory ID RECOGNITION MEMORY; EPISODIC MEMORY; WORKING; CORTEX; PERFORMANCE; MONKEYS; DAMAGE; ROLES; FMRI AB Activity in the hippocampus is modulated by novelty detection, and by the processing of conjunctions between two stimuli. We investigated whether the hippocampus is activated by discrimination of stimulus-stimulus relationships in novel versus familiar pairs of visual stimuli in 15 healthy subjects using functional magnetic resonance imaging. Subjects were asked to recognize the previously rewarded stimulus in each case. We found significantly greater activation of the right hippocampus when discriminating previously seen compared with novel pairs of visual stimuli. This activation was evident in individual subjects and was not related to stimulus novelty, reward contingency, or task instruction. Right hippocampal activation during discrimination of previously seen pairs of objects was correlated with activity in the anteromedial thalamus, cingulate cortex, and contralateral hippocampus. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. McGill Univ, Dept Psychol, Montreal, PQ, Canada. RP Ongur, D (reprint author), McLean Hosp, Schizophrenia & Bipolar Disorder Program, 115 Mill St,AB 347, Belmont, MA 02478 USA. EM dongur@partners.org RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [MH01763-01, MH60272] NR 27 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2005 VL 139 IS 3 BP 191 EP 198 DI 10.1016/j.pscychresns.2005.05.006 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 960PL UT WOS:000231605500003 PM 16055310 ER PT J AU Kong, JH Fish, DR Rockhill, RL Masland, RH AF Kong, JH Fish, DR Rockhill, RL Masland, RH TI Diversity of ganglion cells in the mouse retina: Unsupervised morphological classification and its limits SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE regina; ganglion cell; type; mouse ID RABBIT RETINA; AMACRINE CELLS; MAMMALIAN RETINA; BIPOLAR CELLS; NEURONS; ARCHITECTURE; POPULATION; RECEPTORS; ORDER; MICE AB The dendritic structures of retinal ganglion cells in the mouse retina were visualized by particle-mediated transfer of DiI, microinjection of Lucifer yellow, or visualization of green fluorescent protein expressed in a transgenic strain. The cells were imaged in three dimensions and the morphologies of a series of 219 cells were analyzed quantitatively. A total of 26 parameters were studied and automated cluster analysis was carried out using the k-means methods. An effective clustering, judged by silhouette analysis, was achieved using three parameters: level of stratification, extent of the dendritic field, and density of branching. An 11-cluster solution is illustrated. The cells within each cluster are visibly similar along morphological dimensions other than those used statistically to form the clusters. They could often be matched to ganglion cell types defined by previous studies. For reasons that are discussed, however, this classification must remain provisional. Some steps toward more definitive methods of unsupervised classification are pointed out. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. EM masland@helix.mgb.harvard.edu NR 34 TC 142 Z9 145 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 29 PY 2005 VL 489 IS 3 BP 293 EP 310 DI 10.1002/cne.20631 PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 948JY UT WOS:000230713300002 PM 16025455 ER PT J AU Larsson, J Karlsson, S AF Larsson, J Karlsson, S TI The role of Smad signaling in hematopoiesis SO ONCOGENE LA English DT Review DE Smad signaling; hematopoiesis; stem cells ID GROWTH-FACTOR-BETA; PROGENITOR-CELL PROLIFERATION; TRANSCRIPTION FACTOR GATA-1; EMBRYONIC STEM-CELLS; BONE MORPHOGENETIC PROTEIN-4; RETROVIRAL GENE-TRANSFER; NECROSIS-FACTOR-ALPHA; EX-VIVO EXPANSION; RECEPTOR-TYPE-II; C-KIT LIGAND AB The TGF-beta family of ligands, including TGF-b, bone morphogenetic protein (BMP) and activin, signal through Smad pathways to regulate the fate of hematopoietic progenitor and stem cells during development and postnatally. BMP regulates hematopoietic stem cell (HSC) specification during development, while TGF-beta 1, 2 and 3 are not essential for the generation of HSCs. BMP4 can increase proliferation of human hematopoietic progenitors, while TGF-beta acts as a negative regulator of hematopoietic progenitor and stem cells in vitro. In contrast, TGF-beta signaling deficiency in vivo does not affect proliferation of HSCs and does not affect lineage choice either. Therefore, the outcome of Smad signaling is very context dependent in hematopoiesis and regulation of hematopoietic stem and progenitor cells is more complicated in the bone marrow microenvironment in vivo than is seen in liquid cultures ex vivo. Smad signaling regulates hematopoiesis by crosstalk with other regulatory signals and future research will de. ne in more detail how the various pathways interact and how the knowledge obtained can be used to develop advanced cell therapies. C1 Lund Univ, Inst Lab Med, S-22184 Lund, Sweden. Lund Univ, Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, S-22184 Lund, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. RP Karlsson, S (reprint author), Lund Univ, Inst Lab Med, BMC A12, S-22184 Lund, Sweden. EM Stefan.karlsson@molmed.lu.se NR 192 TC 98 Z9 103 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 29 PY 2005 VL 24 IS 37 BP 5676 EP 5692 DI 10.1038/sj.onc.1208920 PG 17 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 958MQ UT WOS:000231452800003 PM 16123801 ER PT J AU Handschin, C Lin, JD Rhee, J Peyer, AK Chin, S Wu, PH Meyer, UA Spiegelman, BM AF Handschin, C Lin, JD Rhee, J Peyer, AK Chin, S Wu, PH Meyer, UA Spiegelman, BM TI Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1 alpha SO CELL LA English DT Article ID SYNTHASE GENE-EXPRESSION; DELTA-AMINOLEVULINATE SYNTHASE; FORKHEAD TRANSCRIPTION FACTOR; ACUTE INTERMITTENT PORPHYRIA; ACTIVATED PROTEIN-KINASE; 5-AMINOLEVULINATE SYNTHASE; COACTIVATOR PGC-1; ACID SYNTHASE; MITOCHONDRIAL BIOGENESIS; RAT HEPATOCYTES AB Inducible hepatic porphyrias are inherited genetic disorders of enzymes of heme biosynthesis. The main clinical manifestations are acute attacks of neuropsychiatric symptoms frequently precipitated by drugs, hormones, or fasting, associated with increased urinary excretion of delta-aminolevulinic acid (ALA). Acute attacks are treated by heme infusion and glucose administration, but the mechanisms underlying the precipitating effects of fasting and the beneficial effects of glucose are unknown. We show that the rate-limiting enzyme in hepatic heme biosynthesis, 5-amino-levulinate synthase (ALAS-1), is regulated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha). Elevation of PGC-1 alpha in mice via adenoviral vectors increases the levels of heme precursors in vivo as observed in acute attacks. The induction of ALAS-1 by fasting is lost in liver-specific PGC-1 alpha knockout animals, as is the ability of porphyrogenic drugs to dysregulate heme biosynthesis. These data show that PGC-1 alpha links nutritional status to heme biosynthesis and acute hepatic porphyria. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Basel, Biozentrum, Div Pharmacol & Neurobiol, CH-4056 Basel, Switzerland. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [1K01DK065584, DK54477, DK61562, R01DK060837] NR 43 TC 164 Z9 170 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 26 PY 2005 VL 122 IS 4 BP 505 EP 515 DI 10.1016/j.cell.2005.06.040 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 959YI UT WOS:000231555100007 PM 16122419 ER PT J AU Zinkel, SS Hurov, KE Ong, C Abtahl, FM Gross, A Korsmeyer, SJ AF Zinkel, SS Hurov, KE Ong, C Abtahl, FM Gross, A Korsmeyer, SJ TI A role for proapoptotic BID in the DNA-damage response SO CELL LA English DT Article ID NORMAL HUMAN FIBROBLASTS; CHECKPOINT KINASE ATR; IONIZING-RADIATION; CASEIN KINASE-2; STRAND BREAKS; BLM HELICASE; S-PHASE; PHOSPHORYLATION; REPAIR; P53 AB The BCL-2 family of apoptotic proteins encompasses key regulators proximal to irreversible cell damage The BH3-only members of this family act as sentinels interconnecting specific death signals to the core apoptotic pathway. Our previous data demonstrated a role for BH3-only BID in maintaining myeloid homeostasis and suppressing leukemogenesis. In the absence of Bid, mice accumulate chromosomal aberrations and develop a fatal myeloproliferative disorder resembling chronic myelomonocytic leukemia. Here, we describe a role for BID in preserving genomic integrity that places BID at an early point in the path to determine the fate of a cell. We show that BID plays an unexpected role in the intra-S phase checkpoint downstream of DNA damage distinct from its proapoptotic function. We further demonstrate that this role is mediated through BID phosphorylation by the DNA-damage kinase ATM. These results establish a link between proapoptotic Bid and the DNA-damage response. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Regulat Biol, IL-7610 Rehovot, Israel. RP Zinkel, SS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM sandra.zinkel@vanderbilt.edu FU NCI NIH HHS [CA098394, P01 CA92625, R37 CA50239] NR 53 TC 158 Z9 167 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 26 PY 2005 VL 122 IS 4 BP 579 EP 591 DI 10.1016/j.cell.2005.06.022 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 959YI UT WOS:000231555100013 PM 16122425 ER PT J AU Thomson, AM Cahill, CM Cho, HH Kassachau, KD Epis, MR Bridges, KR Leedman, PJ Rogers, JT AF Thomson, AM Cahill, CM Cho, HH Kassachau, KD Epis, MR Bridges, KR Leedman, PJ Rogers, JT TI The acute box cis-element in human heavy ferritin mRNA 5 '-untranslated region is a unique translation enhancer that binds poly(C)-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IRON-RESPONSIVE ELEMENT; 3' UNTRANSLATED REGION; 3'-UNTRANSLATED REGION; REGULATORY PROTEIN; POSTTRANSCRIPTIONAL REGULATION; 3-UNTRANSLATED REGION; SECONDARY STRUCTURE; RIBOSOMAL-SUBUNIT; OXIDATIVE STRESS; H-FERRITIN AB Intracellular levels of the light (L) and heavy (H) ferritin subunits are regulated by iron at the level of message translation via a modulated interaction between the iron regulatory proteins (IRP1 and IRP2) and a 5'-untranslated region. Iron-responsive element (IRE). Here we show that iron and interleukin-1 beta (IL-1 beta) act synergistically to increase H- and L-ferritin expression in hepatoma cells. A GC-rich cis-element, the acute box (AB), located downstream of the IRE in the H- ferritin mRNA 5'-untranslated region, conferred a substantial increase in basal and IL-1 beta-stimulated translation over a similar time course to the induction of endogenous ferritin. A scrambled version of the AB was unresponsive to IL-1. Targeted mutation of the AB altered translation; reverse orientation and a deletion of the AB abolished the wild-type stem-loop structure and abrogated translational enhancement, whereas a conservative structural mutant had little effect. Labeled AB transcripts formed specific complexes with hepatoma cell extracts that contained the poly( C)binding proteins, iso-alpha CP1 and -alpha CP2, which have well defined roles as translation regulators. Iron influx increased the association of alpha CP1 with ferritin mRNA and decreased the alpha CP2-ferritin mRNA interaction, whereas IL-1 beta reduced the association of alpha CP1 and alpha CP2 with H-ferritin mRNA. In summary, the H-ferritin mRNA AB is a key cis-acting translation enhancer that augments H- subunit expression in Hep3B and HepG2 hepatoma cells, in concert with the IRE. The regulated association of H- ferritin mRNA with the poly(C)-binding proteins suggests a novel role for these proteins in ferritin translation and iron homeostasis in human liver. C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Mol Biol, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. Univ Western Australia, Lab Canc Med, Sch Med & Pharmacol, Med Res Ctr,Western Australian Inst Med Res, Perth, WA 6000, Australia. Univ Western Australia, Royal Perth Hosp, Perth, WA 6000, Australia. RP Rogers, JT (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Rm 3580,Mass Gen E,Bldg 114 16th St 3850, Charlestown, MA 02129 USA. EM jtrogers@rics.bwh.harvard.edu RI Leedman, Peter/O-4044-2014 FU NIA NIH HHS [AG20181] NR 59 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 26 PY 2005 VL 280 IS 34 BP 30032 EP 30045 DI 10.1074/jbc.M502951200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957IC UT WOS:000231362500008 PM 15967798 ER PT J AU Caetano, SC Fonseca, M Olvera, RL Nicoletti, M Hatch, JP Stanley, JA Hunter, K Lafer, B Pliszka, SR Soares, JC AF Caetano, SC Fonseca, M Olvera, RL Nicoletti, M Hatch, JP Stanley, JA Hunter, K Lafer, B Pliszka, SR Soares, JC TI Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients SO NEUROSCIENCE LETTERS LA English DT Article DE choline-containing compounds; myo-inositol; major depression; children; dorsolateral prefrontal cortex; proton spectroscopy ID MAGNETIC-RESONANCE-SPECTROSCOPY; ANTERIOR CINGULATE CORTEX; LIFE MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; UNIPOLAR DEPRESSION; BIPOLAR DISORDER; MR SPECTROSCOPY; MOOD DISORDERS; FRONTAL-LOBE; EARLY-ONSET AB The dorsolateral prefrontal cortex (DLPFC) plays an essential role in mood regulation and integration of cognitive functions that are abnormal in major depressive disorder (MDD). Few neuroimaging studies have evaluated the still maturing DLPFC in depressed children and adolescents. We conducted single voxel proton magnetic resonance spectroscopy (H-1 MRS) of the left DLPFC in 14 depressed children and adolescents (13.3 +/- 12.3 years old, 10 males) and 22 matched healthy controls (13.6 +/- 2.8 years old, 13 males). Depressed subjects had significantly lower levels of glycerophosphocholine plus phosphocholine (GPC + PC; or choline-containing compounds) and higher myo-inositol levels in the left DLPFC compared to healthy controls. In the depressed subjects, we found significant inverse correlations between glutamate levels and both duration of illness and number of episodes. In healthy controls there was a significant direct correlation between age and glutamine levels, which was not present in the patient group. Lower GPC + PC levels in pediatric MDD may reflect lower cell membrane content per volume in the DLPFC. Increased myo-inositol levels in MDD may represent a disturbed secondary messenger system. GPC + PC and myo-inositol abnormalities further demonstrate the involvement of DLPFC in pediatric MDD. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Inst, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78285 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78285 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 Lafer, Beny/C-1055-2012; Caetano, Sheila/H-5010-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Caetano, Sheila/0000-0001-8403-7078; Lafer, Beny/0000-0002-6132-9999 FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH01736, MH068662] NR 41 TC 45 Z9 45 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 26 PY 2005 VL 384 IS 3 BP 321 EP 326 DI 10.1016/j.neulet.2005.04.099 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 944XF UT WOS:000230463700022 PM 15936878 ER PT J AU Eichhorn, JH Brauns, TA Gelfand, JA Crothers, BA Wilbur, DC AF Eichhorn, JH Brauns, TA Gelfand, JA Crothers, BA Wilbur, DC TI A novel automated screening and interpretation process for cervical cytology using the Internet transmission of low-resolution images - A feasibility study SO CANCER CYTOPATHOLOGY 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 cervical cytology; automation; Internet; teleparthology; telecytology; FocalPoint ID CANCER STATISTICS; ACCURACY; SYSTEM; TRIAL AB BACKGROUND. Transmission over the Internet of low-resolution images acquired by automated screening of cervical cytology specimens has the potential to provide remote interpretation and, hence, centralization of a cytology workforce, METHODS. Liquid-based cervical cytology slides were scanned using the Focal-Point (R) System. Ten black-and-white images that had the greatest probability of containing abnormality were acquired from each of 32 reference slides (16 negative samples, 3 samples of atypical squamous cells of uncertain significance, 5 samples of low-grade squamous intraepithelial lesions [LSIL], 5 samples of high-grade squamous intraepithelial lesions [HSIL], 1 adenocarcinoma in situ sample, and 2 carcinoma samples) and were transmitted as e-mail attachments in JPEG format to remote reading stations. The slides were interpreted independently by two pathologists and were assigned to either of two groups: 1) suspicious for HSIL or 2) LSIL. The interpretations were compared with the reference diagnoses. The specimens were then randomized, and the image sets were redistributed to the pathologists for another round of interpretation and scoring. RESULTS. The initial and subsequent trials yielded similar results. Pooling the interpretations of the two pathologists, the concordance rate between reference and assigned diagnostic groups for each of the two trials was 84%, the false-positive rate was 8.3%, and the false-negative rate was 37.5%. Review of the discrepant slides revealed subtle cellular changes that may be utilized to reduce errors and, with training, to optimize sensitivity and specificity. CONCLUSIONS. This procedure showed promise for allowing remote interpretation of device-selected images. The procedure may represent an effective way to centralize cervical cytology services and to allow the provision of services to previously unscreened populations that lack an effective cytology infrastructure. C1 Massachusetts Gen Hosp, Cytopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Partners Hlth Care, Ctr Integrat Med & Innovat Technol, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Uniformed Serv Sch Med, Walter Reed Army Med Ctr, Dept Pathol, Washington, DC USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Cytopathol Unit, Warren 120,55 Blossom St, Boston, MA 02114 USA. EM dwilbur@partners.org NR 17 TC 10 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 2005 VL 105 IS 4 BP 199 EP 206 DI 10.1002/cncr.21098 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 955WB UT WOS:000231257200003 PM 15937917 ER PT J AU Gasser, S Orsulic, S Brown, EJ Raulet, DH AF Gasser, S Orsulic, S Brown, EJ Raulet, DH TI The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor SO NATURE LA English DT Article ID GENOMIC INSTABILITY; NK CELLS; CHECKPOINT; ATM; TUMORIGENESIS; ACTIVATION; REPAIR; CHK1; IMMUNORECEPTOR; MACROPHAGES AB Some stimulatory receptors of the innate immune system, such as the NKG2D receptor ( also called KLRK1) expressed by natural killer cells and activated CD8(+) T cells, recognize self-molecules that are upregulated in diseased cells by poorly understood mechanisms(1). Here we show that mouse and human NKG2D ligands are upregulated in non-tumour cell lines by genotoxic stress and stalled DNA replication, conditions known to activate a major DNA damage checkpoint pathway initiated by ATM ( ataxia telangiectasia, mutated) or ATR (ATM- and Rad3-related) protein kinases(2). Ligand upregulation was prevented by pharmacological or genetic inhibition of ATR, ATM or Chk1 ( a downstream transducer kinase in the pathway). Furthermore, constitutive ligand expression by a tumour cell line was inhibited by targeting short interfering RNA to ATM, suggesting that ligand expression in established tumour cells, which often harbour genomic irregularities, may be due to chronic activation of the DNA damage response pathway. Thus, the DNA damage response, previously shown to arrest the cell cycle and enhance DNA repair functions, or to trigger apoptosis, may also participate in alerting the immune system to the presence of potentially dangerous cells. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Raulet, DH (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. EM raulet@uclink.berkeley.edu RI gasser, stephan /A-2309-2013; OI Gasser, Stephan/0000-0002-5616-0914 FU NCI NIH HHS [R01 CA093678]; NIAID NIH HHS [R01 AI039642] NR 27 TC 650 Z9 677 U1 5 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 25 PY 2005 VL 436 IS 7054 BP 1186 EP 1190 DI 10.1038/nature03884 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 958AK UT WOS:000231416600052 PM 15995699 ER PT J AU Binder, WD Fifer, MA King, ME Stone, JR Harris, NL Das, S AF Binder, WD Fifer, MA King, ME Stone, JR Harris, NL Das, S TI A man with loss of consciousness while jogging - Hypertrophic cardiomyopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SUDDEN CARDIAC DEATH; OBSTRUCTIVE CARDIOMYOPATHY; IMPLANTABLE CARDIOVERTER; YOUNG-PATIENTS; HEART-DISEASE; PRIMARY-CARE; SYNCOPE; RISK; FIBROSIS; PATIENT C1 Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Cardiol, 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 Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Binder, WD (reprint author), Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. NR 46 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 25 PY 2005 VL 353 IS 8 BP 824 EP 832 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 957YK UT WOS:000231409300013 PM 16120863 ER PT J AU Aiello, LP AF Aiello, LP TI Angiogenic pathways in diabetic retinopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NEOVASCULARIZATION C1 Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Eye Res Sect, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA 02115 USA. NR 15 TC 97 Z9 101 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 25 PY 2005 VL 353 IS 8 BP 839 EP 841 DI 10.1056/NEJMe058142 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 957YK UT WOS:000231409300016 PM 16120866 ER PT J AU Venegas, JG Schroeder, T Harris, S Winkler, RT Melo, MFV AF Venegas, JG Schroeder, T Harris, S Winkler, RT Melo, MFV TI The distribution of ventilation during bronchoconstriction is patchy and bimodal: A PET imaging study SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Hot Topics in Peer-to-Peer Systems CY JUL 21, 2005 CL San Diego, CA SP Italian FIRB WebMINDS Project, IEEE Comp Soc DE ventilation; bronchoconstriction; PET ID PERFUSION INEQUALITY; ASTHMA; METHACHOLINE AB Recent PET imaging data from bronchoconstricted sheep (Vidal Melo et al., 2005) showed that V/Q distributions were bimodal and topographically patchy but including a substantial heterogeneity at scales <2.2 ml. In this paper, we reanalyze the experimental data to establish the contribution of ventilation (V-r) heterogeneity to the bimodality in V/Q. This analysis demonstrates that the distribution of V, during bronchoconstriction was bimodal with large patches of severe hypoventilation occupying an average of 41 % of the imaged lung. The degree of hypoventilation to these regions was highly correlated with the degree of oxygenation impairment, but was quite variable amongst animals in spite of consistent degrees of mechanical obstruction. Remarkably, those regions were found to be hyperventilated before methacholine and their degree of hyperventilation was correlated with their degree of hypoventilation during bronchoconstriction. These data suggest that improving the uniformity of ventilation at baseline may be a desirable therapeutic target if the risk of severe hypoxemia during asthma attacks is to be minimized and/or the distribution of inhaled pharmaceuticals is to be optimized. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthet, 55 Fruit St, Boston, MA 02114 USA. EM jvenegas@vqpet.mgh.harvard.edu OI Schroeder, Tobias/0000-0002-4439-8060 FU NHLBI NIH HHS [HL068011] NR 14 TC 48 Z9 49 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 EI 1878-1519 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD AUG 25 PY 2005 VL 148 IS 1-2 BP 57 EP 64 DI 10.1016/j.resp.2005.05.023 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 962DB UT WOS:000231710100005 PM 15994134 ER PT J AU Spencer, KM Banich, MT AF Spencer, KM Banich, MT TI Hemispheric biases and the control of visuospatial attention: an ERP study SO BMC NEUROSCIENCE LA English DT Article ID PERCEPTUAL ASYMMETRIES; UNILATERAL NEGLECT; EXTINGUISHED FIELD; LATERAL ASYMMETRY; SPATIAL ATTENTION; VISUAL-ATTENTION; LINE BISECTION; BRAIN; STIMULI; TASK AB Background: We examined whether individual differences in hemispheric utilization can interact with the intrinsic attentional biases of the cerebral hemispheres. Evidence suggests that the hemispheres have competing biases to direct attention contralaterally, with the left hemisphere (LH) having a stronger bias than the right hemisphere. There is also evidence that individuals have characteristic biases to utilize one hemisphere more than the other for processing information, which can induce a bias to direct attention to contralateral space. We predicted that LH-biased individuals would display a strong rightward attentional bias, which would create difficulty in selectively attending to target stimuli in the left visual field (LVF) as compared to right in the performance of a bilateral flanker task. Results: Consistent with our hypothesis, flanker interference effects were found on the N2c event-related brain potential and error rate for LH-biased individuals in the Attend-LVF condition. The error rate effect was correlated with the degree of hemispheric utilization bias for the LH-Bias group. Conclusion: We conclude that hemispheric utilization bias can enhance a hemisphere's contralateral attentional bias, at least for individuals with a LH utilization bias. Hemispheric utilization bias may play an important and largely unrecognized role in visuospatial attention. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02401 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Illinois, Urbana, IL 61801 USA. RP Spencer, KM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02401 USA. EM kevin_spencer@hms.harvard.edu; mbanich@psych.colorado.edu FU NIMH NIH HHS [F31 MH011516]; PHS HHS [11516] NR 43 TC 3 Z9 3 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD AUG 24 PY 2005 VL 6 AR 51 DI 10.1186/1471-2202-6-51 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 964KU UT WOS:000231880800001 PM 16120226 ER PT J AU Chan, AT Giovannucci, EL Meyerhardt, JA Schernhammer, ES Curhan, GC Fuchs, CS AF Chan, AT Giovannucci, EL Meyerhardt, JA Schernhammer, ES Curhan, GC Fuchs, CS TI Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; LOW-DOSE ASPIRIN; NF-KAPPA-B; COLON-CANCER; RANDOMIZED-TRIAL; LARGE-BOWEL; PRIMARY PREVENTION; ANALGESIC USE; REDUCED RISK; ADENOMA AB Context Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) remain limited. Objective To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. Design, Setting, and Participants Prospective cohort study of 82 911 women enrolled in the Nurses' Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. Main Outcome Measure Incident colorectal cancer. Results Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (>= 2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [01, 0.67-0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P <=.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% Cl, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% Cl, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% Cl, 0.62-0.97) for 6 to 14 aspirin per week, and 0.68 (95% Cl, 0.49-0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95 % Cl, 0.31-0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P=.007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week. Conclusions Regular, long-term aspirin use reduces risk of colorectal cancer. Non-aspirin NSAIDs appear to have a similar effect. However, a significant benefit of aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week. These results suggest that optimal chemoprevention for colorectal cancer requires long-term use of aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA 87969, CA107412, CA55075, K07 CA107412, P01 CA055075, P01 CA087969] NR 66 TC 250 Z9 265 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 24 PY 2005 VL 294 IS 8 BP 914 EP 923 DI 10.1001/jama.294.8.914 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 957JM UT WOS:000231366100021 PM 16118381 ER PT J AU Ullrich, C Wu, A Armsby, C Rieber, S Wingerter, S Brugnara, C Shapiro, D Bernstein, H AF Ullrich, C Wu, A Armsby, C Rieber, S Wingerter, S Brugnara, C Shapiro, D Bernstein, H TI Screening healthy infants for iron deficiency using reticulocyte hemoglobin content SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID THALASSEMIA TRAIT; LABORATORY TESTS; CLINICAL UTILITY; UNITED-STATES; RET-Y; DIAGNOSIS; ANEMIA; INDEXES; ERYTHROPOIESIS; THERAPY AB Context Current clinical practice relies on hemoglobin to detect iron deficiency, which misses infants not yet anemic and places them at higher risk for neurocognitive impairment. Reticulocyte hemoglobin content (CHr) has never been compared with hemoglobin for screening healthy infants. Objectives To evaluate CHr for detecting iron deficiency without anemia in healthy 9- to 12-month-old infants and to compare CHr with hemoglobin in screening for iron deficiency in this population. A secondary objective was to explore the association between CHr and subsequent development of anemia. Design, Setting, and Patients A prospective observational cohort study of 202 healthy 9- to 12-month-old infants from an urban, hospital-based, primary care clinic in Boston, Mass, who were screened for iron deficiency between June 2000 and April 2003, and followed up for a median of 5.6 months. Main Outcome Measures Iron deficiency (transferrin saturation <10%) and anemia (hemoglobin < 11 g/dL). Results Of 202 infants enrolled, 23 (11.4%) had iron deficiency and 6 (3%) had iron deficiency and anemia. Iron-deficient and non-iron-deficient infants had significantly different values for all measured hematological and biochemical markers for iron deficiency. Optimal CHr cutoff for detecting iron deficiency was 27.5 pg (sensitivity, 83% and specificity, 72%); a hemoglobin level of less than 11 g/dL resulted in a sensitivity of 26% and a specificity of 95%. Reticulocyte hemoglobin content was more accurate overall than hemoglobin was for detecting iron deficiency (area under the receiver operating characteristic curve, 0.85 vs 0.73; P=.007). A CHr of less than 27.5 pg without anemia at initial screening was associated with subsequent anemia when screened again in the second year of life (risk ratio, 9.1; 95% confidence interval, 1.04-78.9; P=.01). Conclusions A CHr of less than 27.5 pg is a more accurate hematological indicator of iron deficiency compared with hemoglobin of less than 11 g/dL in these healthy 9- to 12-month-old infants. Further studies are warranted to determine whether CHr should be the preferred screening tool in the early detection of iron deficiency in infants. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dept Infect Dis & Emergency Med, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med & Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Ullrich, C (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM christina.ullrich@childrens.harvard.edu RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 41 TC 69 Z9 78 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 24 PY 2005 VL 294 IS 8 BP 924 EP 930 DI 10.1001/jama.294.8.924 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 957JM UT WOS:000231366100022 PM 16118382 ER PT J AU Naylor, DE Liu, HT Wasterlain, CG AF Naylor, DE Liu, HT Wasterlain, CG TI Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) receptor trafficking; status epilepticus; epilepsy; hippocampus; math model; synaptic inhibition ID CEREBELLAR GRANULE CELLS; GAMMA-AMINOBUTYRIC-ACID; SUSTAINING STATUS EPILEPTICUS; KINASE-C ACTIVITY; ELECTRICAL-STIMULATION; HIPPOCAMPAL-NEURONS; SYNAPTIC INHIBITION; A RECEPTORS; GABAERGIC INHIBITION; CALCINEURIN ACTIVITY AB During status epilepticus ( SE), GABAergic mechanisms fail and seizures become self-sustaining and pharmacoresistant. During lithium-pilocarpine-induced SE, our studies of postsynaptic GABA(A) receptors in dentate gyrus granule cells show a reduction in the amplitude of miniature IPSCs (mIPSCs). Anatomical studies show a reduction in the colocalization of the beta 2/beta 3 and gamma 2 subunits of GABA(A) receptors with the presynaptic marker synaptophysin and an increase in the proportion of those subunits in the interior of dentate granule cells and other hippocampal neurons with SE. Unlike synaptic mIPSCs, the amplitude of extrasynaptic GABA(A) tonic currents is augmented during SE. Mathematical modeling suggests that the change of mIPSCs with SE reflects a decrease in the number of functional postsynaptic GABA(A) receptors. It also suggests that increases in extracellular [GABA] during SE can account for the tonic current changes and can affect postsynaptic receptor kinetics with a loss of paired-pulse inhibition. GABA exposure mimics the effects of SE on mIPSC and tonic GABA(A) current amplitudes in granule cells, consistent with the model predictions. These results provide a potential mechanism for the inhibitory loss that characterizes initiation of SE and for the pharmacoresistance to benzodiazepines, as a reduction of available functional GABA(A) postsynaptic receptors. Novel therapies for SE might be directed toward prevention or reversal of these losses. C1 Vet Adm Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Naylor, DE (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Dept Neurol, Bldg 500 Neurol 127,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dnaylor@ucla.edu FU PHS HHS [N13515] NR 60 TC 200 Z9 205 U1 2 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 24 PY 2005 VL 25 IS 34 BP 7724 EP 7733 DI 10.1523/JNEUROSCI.4944-04.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 958JA UT WOS:000231439300003 PM 16120773 ER PT J AU Josephson, K Hartman, MCT Szostak, JW AF Josephson, K Hartman, MCT Szostak, JW TI Ribosomal synthesis of unnatural peptides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SITE-SPECIFIC INCORPORATION; TRANSFER-RNA-SYNTHETASE; IN-VITRO SELECTION; NONNATURAL AMINO-ACIDS; ESCHERICHIA-COLI; GENETIC-CODE; 4-BASE CODONS; PROTEINS; ANALOGS; SPECIFICITY AB Combinatorial libraries of nonbiological polymers and drug-like peptides could in principle be synthesized from unnatural amino acids by exploiting the broad substrate specificity of the ribosome. The ribosomal synthesis of such libraries would allow rare functional molecules to be identified using technologies developed for the in vitro selection of peptides and proteins. Here, we use a reconstituted E coli translation system to simultaneously reassign 35 of the 61 sense codons to 12 unnatural amino acid analogues. This reprogrammed genetic code was used to direct the synthesis of a single peptide containing 10 different unnatural amino acids. This system is compatible with mRNA-display, enabling the synthesis of unnatural peptide libraries of 10(14) unique members for the in vitro selection of functional unnatural molecules. We also show that the chemical space sampled by these libraries can be expanded using mutant aminoacyl-tRNA synthetases for the incorporation of additional unnatural amino acids or by the specific posttranslational chemical derivitization of reactive groups with small molecules. This system represents a first step toward a platform for the synthesis by enzymatic tRNA aminoacylation and ribosomal translation of cyclic peptides comprised of unnatural amino acids that are similar to the nonribosomal peptides. 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 NR 60 TC 122 Z9 126 U1 3 U2 43 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 AUG 24 PY 2005 VL 127 IS 33 BP 11727 EP 11735 DI 10.1021/ja0515809 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 958ND UT WOS:000231454100058 PM 16104750 ER PT J AU McDermott, DH Yang, Q Kathiresan, S Cupples, LA Massaro, JM Keaney, JF Larson, MG Vasan, RS Hirschhorn, JN O'Donnell, CJ Murphy, PM Benjamin, EJ AF McDermott, DH Yang, Q Kathiresan, S Cupples, LA Massaro, JM Keaney, JF Larson, MG Vasan, RS Hirschhorn, JN O'Donnell, CJ Murphy, PM Benjamin, EJ TI CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the framingham heart study SO CIRCULATION LA English DT Article DE epidemiology; genetics; inflammation; myocardial infarction; risk factors ID CORONARY-ARTERY DISEASE; E-DEFICIENT MICE; MCP-1 GENE; ATHEROSCLEROTIC LESIONS; REDUCES ATHEROSCLEROSIS; PLASMA-LEVELS; EXPRESSION; RESTENOSIS; ALLELE; RISK AB Background - Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory. Methods and Results - We analyzed the association of genetic variation in the MCP-1 gene (CCL2) with prevalent myocardial infarction and serum MCP-1 levels in the community-based Framingham Heart Study Offspring Cohort (50% women; mean age, 62 years). MCP-1 levels and CCL2 genotypes were determined in 3236 and 1797 individuals, respectively. Significant clinical correlates of MCP-1 levels were age, cigarette smoking, triglycerides, body mass index, and waist-to-hip ratio. The MCP-1-2578G allele located in the CCL2 regulatory region was significantly associated with both higher serum MCP-1 levels in a recessive genetic model (358 +/- 10 versus 328 +/- 3 pg/mL; P = 0.002) and higher prevalence of myocardial infarction in a dominant genetic model (adjusted odds ratio, 2.0; 95% CI, 1.2 to 3.3; P = 0.005). We also defined the linkage disequilibrium structure at the CCL2 locus and observed 6 common haplotypes in whites. We performed haplotype-based association analysis and found that only the most frequent haplotype, defined by the MCP-1-2578G allele, was associated with prevalent MI. Conclusions - Our data are consistent with the hypothesis that MCP-1 is involved in the pathogenesis of human atherosclerosis and myocardial infarction. C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. RP McDermott, DH (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N111, Bethesda, MD 20892 USA. EM dmcdermott@niaid.nih.gov; emelia@bu.edu RI Yang, Qiong/G-5438-2014; OI Massaro, Joseph/0000-0002-2682-4812; Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254; McDermott, David/0000-0001-6978-0867; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [R01 HL-64753, N01-HC 25195, R01 HL-076784, U01 HL-66582] NR 42 TC 143 Z9 155 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 23 PY 2005 VL 112 IS 8 BP 1113 EP 1120 DI 10.1161/CIRCULATIONAHA.105.543579 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 957LM UT WOS:000231371300010 PM 16116069 ER PT J AU Schinzel, AC Takeuchi, O Huang, ZH Fisher, JK Zhou, ZP Rubens, J Hetz, C Danial, NN Moskowitz, MA Korsmeyer, SJ AF Schinzel, AC Takeuchi, O Huang, ZH Fisher, JK Zhou, ZP Rubens, J Hetz, C Danial, NN Moskowitz, MA Korsmeyer, SJ TI Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; oxidative stress; calcium homeostasis ID ADENINE-NUCLEOTIDE TRANSLOCASE; CYCLOSPORINE-A; CYTOCHROME-C; ENDOPLASMIC-RETICULUM; OXIDATIVE STRESS; APOPTOSIS; PORE; NECROSIS; CALCIUM; CA2+ AB Mitochondrial permeability transition (PT) is a phenomenon induced by high levels of matrix calcium and is characterized by the opening of the PT pore (PTP). Activation of the PTP results in loss of mitochondrial membrane potential, expansion of the matrix, and rupture of the mitochondrial outer membrane. Consequently, PT has been implicated in both apoptotic and necrotic cell death. Cyclophilin D (CypD) appears to be a critical component of the PTP. To investigate the role of CypD in cell death, we created a CypD-deficient mouse. In vitro, CypD-deficient mitochondria showed an increased capacity to retain calcium and were no longer susceptible to PT induced by the addition of calcium. CypD-deficient primary mouse embryonic fibroblasts (MEFs) were as susceptible to classical apoptotic stimuli as the WT, suggesting that CypD is not a central component of cell death in response to these specific death stimuli. However, CypD-deficient MEFs were significantly less susceptible than their WT counterparts to cell death induced by hydrogen peroxide, implicating CypD in oxidative stress-induced cell death. Importantly, CypD-deficient mice displayed a dramatic reduction in brain infarct size after acute middle cerebral artery occlusion and reperfusion, strongly supporting an essential role for CypD in an ischemic injury model in which calcium overload and oxidative stress have been implicated. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Schinzel, AC (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. EM anna_schinzel@dfci.harvard.edu; michael-moskowitz@mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011; Takeuchi, Osamu/D-6007-2011; Hetz, Claudio/I-1900-2013 OI Hetz, Claudio/0000-0001-7724-1767 FU NCI NIH HHS [R37 CA050239, CA 50239, R01 CA050239]; NINDS NIH HHS [F32 NS010828, NS 10828, NS 37141, P01 NS010828, P50 NS010828, R01 NS037141] NR 50 TC 455 Z9 479 U1 0 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 23 PY 2005 VL 102 IS 34 BP 12005 EP 12010 DI 10.1073/pnas.0505294102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 958VO UT WOS:000231476500011 PM 16103352 ER PT J AU Tuch, DS Salat, DH Wisco, JJ Zaleta, AK Hevelone, ND Rosas, HD AF Tuch, DS Salat, DH Wisco, JJ Zaleta, AK Hevelone, ND Rosas, HD TI Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diffusion tensor MRI ID HUMAN BRAIN; ALZHEIMERS-DISEASE; SPATIAL ATTENTION; PROCESSING SPEED; TRACT INTEGRITY; WATER DIFFUSION; SPIN-ECHO; TENSOR; MRI; MICROSTRUCTURE AB Humans exhibit significant interindividual variability in behavioral reaction time (RT) performance yet the underlying neural mechanisms for this variability remain largely unknown. It has been proposed that interindividual variability in RT performance may be due to differences in white matter (WM) physiological properties, although such a relationship has never been demonstrated in cortical projection or association pathways in healthy young adults. Using diffusion tensor MRI (DTI), we sought to test whether diffusion tensor fractional anisotropy (FA), a measure of the orientational coherence of water self-diffusion, is regionally correlated with RT on a visual self-paced choice RT (CRT) task. CRT was found to be significantly correlated with FA in projection and association pathways supporting visuospatial attention including the right optic radiation, right posterior thalamus, and right medial precuneus WM. Significant correlations were also observed in left superior temporal sulcus WM and the left parietal operculum. The lateralization of the CRT-FA correlation to right visual and parietal WM pathways is consistent with the specialization of right visual and parietal cortices for visuospatial attention. The localization of the CRT-FA correlations to predominately visual and parietal WM pathways, but not to motor pathways or the corpus callosum indicates that individual differences in visual CRT performance are associated with variations in the WM underlying the visuospatial attention network as opposed to pathways supporting motor movement or interhemispheric transmission. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Tuch, DS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM dtuch@nmr.mgh.harvard.edu OI Hevelone, Nathanael/0000-0003-4740-2085 FU NCI NIH HHS [T32 CA009502, CA 09502]; NCRR NIH HHS [RR 14075, P41 RR014075]; NIA NIH HHS [AG 15134, F32 AG005886, P50 AG005134, AG 05886]; NIBIB NIH HHS [U54 EB 05149, U54 EB005149]; NINDS NIH HHS [NS 02069, K25 NS046532, NS 46532] NR 59 TC 199 Z9 203 U1 4 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 23 PY 2005 VL 102 IS 34 BP 12212 EP 12217 DI 10.1073/pnas.0407259102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 958VO UT WOS:000231476500046 PM 16103359 ER PT J AU Huang, W Fileta, JB Dobberfuhl, A Filippopolous, T Guo, Y Kwon, G Grosskreutz, CL AF Huang, W Fileta, JB Dobberfuhl, A Filippopolous, T Guo, Y Kwon, G Grosskreutz, CL TI Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE retina; optic nerve; apoptosis ID OPEN-ANGLE GLAUCOMA; SPINAL-CORD-INJURY; OPTIC-NERVE CRUSH; RAT MODEL; IRIS ATROPHY; DBA/2J MICE; ADULT-RATS; FK506; APOPTOSIS; ACTIVATION AB Increased intraocular pressure (IOP) leads, by an unknown mechanism, to apoptotic retinal ganglion cell (RGC) death in glaucoma. We now report cleavage of the autoinhibitory domain of the protein phosphatase calcineurin (CaN) in two rodent models of increased IOP. Cleaved CaN was not detected in rat or mouse eyes with normal IOP. In in vitro systems, this constitutively active cleaved form of CaN has been reported to lead to apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member, Bad. in a rat model of glaucoma, we similarly detect increased Bad dephosphorylation, increased cytoplasmic cytochrome c (cyt c), and RGC death. Oral treatment of rats with increased IOP with the CaN inhibitor FK506 led to a reduction in Bad dephosphorylation and cyt c release. In accord with these biochemical results, we observed a marked increase in both RGC survival and optic nerve preservation. These data are consistent with a CaN-mediated mechanism of increased IOP toxicity. CaN cleavage was not observed at any time after optic nerve crush, suggesting that axon damage alone is insufficient to trigger cleavage. These findings implicate this mechanism of CaN activation in a chronic neurodegenerative disease. These data demonstrate that increased IOP leads to the initiation of a CaN-mediated mitochondrial apoptotic pathway in glaucoma and support neuroprotective strategies for this blinding disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU NEI NIH HHS [R01 EY013399, P30 EY 14104, P30 EY014104, R01 EY 13399] NR 55 TC 88 Z9 91 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 23 PY 2005 VL 102 IS 34 BP 12242 EP 12247 DI 10.1073/pnas.0505138102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 958VO UT WOS:000231476500051 PM 16103353 ER PT J AU Berbeco, RI Nishioka, S Shirato, H Chen, GTY Jiang, SB AF Berbeco, RI Nishioka, S Shirato, H Chen, GTY Jiang, SB TI Residual motion of lung tumours in gated radiotherapy with external respiratory surrogates SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION-THERAPY; ORGAN MOTION; DEEP INSPIRATION; BREATH-HOLD; MOVEMENT; TRACKING; SYSTEM; FEASIBILITY; MANAGEMENT; PANCREAS AB Due to respiration, many tumours in the thorax and abdomen may move as much as 3 cm peak-to-peak during radiation treatment. To mitigate motion-induced irradiation of normal lung tissue, clinics have employed external markers to gate the treatment beam. This technique assumes that the correlation between the external surface and the internal tumour position remains constant inter-fractionally and intra-fractionally. In this work, a study has been performed to assess the validity of this correlation assumption for external surface based gated radiotherapy, by measuring the residual tumour motion within a gating window. Eight lung patients with implanted fiducial markers were studied at the NTT Hospital in Sapporo, Japan. Synchronized internal marker positions and external abdominal surface positions were measured during the entire course of treatment. Stereoscopic imaging was used to find the internal markers in four dimensions. The data were used retrospectively to assess conventional external surrogate respiratory-gated treatment. Both amplitude- and phase- based gating methods were investigated. For each method, three gating windows were investigated, each giving 40%, 30% and 20% duty cycle, respectively. The residual motion of the internal marker within these six gating windows was calculated. The beam-to-beam variation and day-to-day variation in the residual motion were calculated for both gating modalities. We found that the residual motion (95th percentile) was between 0.7 and 5.8 mm, 0.8 and 6.0 mm, and 0.9 and 6.2 mm for 20%, 30% and 40% duty cycle windows, respectively. Five of the eight patients showed less residual motion with amplitude-based gating than with phase-based gating. Large fluctuations (> 300%) were seen in the residual motion between some beams. Overall, the mean beam-to-beam variation was 37% and 42% from the previous treatment beam for amplitude- and phase-based gating, respectively. The day-to-day variation was 29% and 34% from the previous day for amplitude- and phase-based gating, respectively. Although gating reduced the total tumour motion, the residual motion behaved unpredictably. Residual motion during treatment could exceed that which might have been considered in the treatment plan. Treatment margins that account for motion should be individualized and daily imaging should be performed to ensure that the residual motion is not exceeding the planned motion on a given day. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NTT Hosp, Dept Radiol, Sapporo, Hokkaido, Japan. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. RP Berbeco, RI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM rberbeco@partners.org RI Shirato, Hiroki/A-7068-2010 NR 29 TC 160 Z9 161 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2005 VL 50 IS 16 BP 3655 EP 3667 DI 10.1088/0031-9155/50/16/001 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 962YU UT WOS:000231770300001 PM 16077219 ER PT J AU Berbeco, RI Neicu, T Rietzel, E Chen, GTY Jiang, SB AF Berbeco, RI Neicu, T Rietzel, E Chen, GTY Jiang, SB TI A technique for respiratory-gated radiotherapy treatment verification with an EPID in cine mode SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TRANSTHORACIC NEEDLE-BIOPSY; ORGAN MOTION; PULMONARY NODULES; TUMOR TRACKING; CT; MOVEMENT; LUNG; PNEUMOTHORAX; FEASIBILITY; ASPIRATION AB Respiratory gating based on external surrogates is performed in many clinics. We have developed a new technique for treatment verification using an electronic portal imaging device (EPID) in cine mode for gated 3D conformal therapy. Implanted radiopaque fiducial markers inside or near the target are required for this technique. The markers are contoured on the planning CT set, enabling us to create digitally reconstructed radiographs (DRRs) for each treatment beam. During the treatment, a sequence of EPID images can be acquired without disrupting the treatment. Implanted markers are visualized in the images and their positions in the beam's eye view are calculated off-line and compared to the reference position by matching the field apertures in corresponding EPID and DRR images. The precision of the patient setup, the placement of the beam-gating window, as well as the residual tumour motion can be assessed for each treatment fraction. This technique has been demonstrated with a case study patient, who had three markers implanted in his liver. For this patient, the intra-fractional variation of all marker positions in the gating window had a 95% range of 4.8 mm in the SI direction (the primary axis of motion). This was about the same (5 mm) as the residual motion considered in the planning process. The inter-fractional variation of the daily mean positions of the markers, which indicates the uncertainty in the set-up procedure, was within +8.3 mm/-4.5 mm (95% range) in the SI direction for this case. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berbeco, RI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM rberbeco@partners.org NR 51 TC 57 Z9 57 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2005 VL 50 IS 16 BP 3669 EP 3679 DI 10.1088/0031-9155/50/16/002 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 962YU UT WOS:000231770300002 PM 16077220 ER PT J AU Jayaraman, A Roberts, KA Yoon, J Yarmush, DM Duan, XB Lee, K Yarmush, ML AF Jayaraman, A Roberts, KA Yoon, J Yarmush, DM Duan, XB Lee, K Yarmush, ML TI Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1 beta: a proteomic analysis SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE hepatocytes; cytokines; proteomics; secreted proteins; NGAL ID ACUTE-PHASE RESPONSE; MULTIPLE ORGAN DYSFUNCTION; C-REACTIVE PROTEIN; BURN INJURY; SANDWICH CONFIGURATION; ALBUMIN PROMOTER; HEPG2 CELLS; RAT; CYTOKINE; SERUM AB The liver is the major source of proteins used throughout the body for various functions. Upon injury or infection, an acute phase response (APR) is initiated in the liver that is primarily mediated by inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and interleukin-6. Among others, the APR is characterized by an altered protein synthetic profile. We used two-dimensional gel electrophoresis to study the dynamics of changes in protein synthesis in hepatocytes exposed to these inflammatory cytokines. Protein profiles were quantified using image analysis and further analyzed using multivariate statistical methods. Our results indicate that IL-1 beta and IL-6 each induces secreted protein responses with distinct dynamics and dose-dependence. Parallel stimulation by IL-1 beta and IL-6 results in a protein pattern indistinguishable from the IL-1 beta pattern, indicating a dominant effect of IL-1 beta over IL-6 at the doses tested. Multidimensional scaling (MDS) of correlation distances between protein secretion levels revealed two protein pairs that are robustly co-secreted across the various cytokine stimulation conditions, suggesting shared regulatory pathways. Finally, we also used multivariate alternating conditional expectation (MACE) to identify transformation functions that discriminated the cytokine-stimulated and untreated hepatocyte-secreted protein profiles. Our analysis indicates that the expression of neutrophil gelatinase-associated lipocalin (NGAL) was sufficient to discriminate between IL-1 beta and IL-6 stimulation. The combination of proteomics and multivariate analysis is expected to provide new information on the cellular regulatory networks involved in generating specific cellular responses. (c) 2005 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Surg, Ctr Engn Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Dept Biol & Chem Engn, Medford, MA 02155 USA. RP Jayaraman, A (reprint author), Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA. EM arulj@tamu.edu RI Lee, Kyongbum/D-9230-2013 FU CSR NIH HHS [RG-01-0117]; NIGMS NIH HHS [5R01-GM-65474] NR 61 TC 37 Z9 37 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD AUG 20 PY 2005 VL 91 IS 4 BP 502 EP 515 DI 10.1002/bit.20535 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 951FT UT WOS:000230915400013 PM 15918168 ER PT J AU Garcia-Carbonero, R Supko, JG Maki, RG Manola, J Ryan, DP Harmon, D Puchalski, TA Goss, G Seiden, MV Waxman, A Quigley, MT Lopez, T Sancho, MA Limeno, J Guzman, C Demetri, GD AF Garcia-Carbonero, R Supko, JG Maki, RG Manola, J Ryan, DP Harmon, D Puchalski, TA Goss, G Seiden, MV Waxman, A Quigley, MT Lopez, T Sancho, MA Limeno, J Guzman, C Demetri, GD TI Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: Multicenter phase II and pharmacokinetic study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol ID CONTINUOUS INTRAVENOUS-INFUSION; DOXORUBICIN PLUS IFOSFAMIDE; EUROPEAN-ORGANIZATION; SOLID MALIGNANCIES; CLINICAL-TRIALS; COMPOUND; CANCER; ACTIVATION; TURBINATA; REGIMENS AB Purpose To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). Patients and Methods Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m(2) of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. Results One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1 % (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P =.21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. Conclusion ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. PharmaMar SA, Clin Res & Dev, Madrid, Spain. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 43 TC 120 Z9 126 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2005 VL 23 IS 24 BP 5484 EP 5492 DI 10.1200/JCO.2005.05.028 PG 9 WC Oncology SC Oncology GA 957LQ UT WOS:000231371700019 PM 16110008 ER PT J AU Campos, S Hamid, C Seiden, MV Oza, A Plante, M Potkul, RK Lenehan, PF Kaldjian, EP Varterasian, ML Jordan, C Charbonneau, C Hirte, H AF Campos, S Hamid, C Seiden, MV Oza, A Plante, M Potkul, RK Lenehan, PF Kaldjian, EP Varterasian, ML Jordan, C Charbonneau, C Hirte, H TI Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; EPIDERMAL GROWTH-FACTOR; LIPOSOMAL DOXORUBICIN; EXPRESSION; PACLITAXEL; CARCINOMA; RECEPTOR; OVEREXPRESSION; CHEMOTHERAPY; TRASTUZUMAB AB Purpose To evaluate the antitumor activity and toxicity platinum-refractory or recurrent ovarian cancer, epidermal growth factor receptor in tumor cells. of two doses of CI-1033 in patients with and to determine baseline expression of epidermal growth factor receptor in tumor cells. Patients and Methods This phase 11, open-label clinical trial evaluated Cl-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CH 033 were evaluated-a 50-mg and a 200-mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. Results One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. Conclusion CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability. C1 Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. Hamilton Canc Ctr, Hamilton, ON, Canada. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Pavillon Hotel Dieu, Quebec City, PQ, Canada. Princess Margaret Hosp, Toronto, ON, Canada. RP Campos, S (reprint author), Dana Farber Canc Inst, Massachusetts Gen Hosp, 44 Binney St, Boston, MA 02115 USA. EM Susana_Campos@dfci.harvard.edu NR 26 TC 78 Z9 80 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2005 VL 23 IS 24 BP 5597 EP 5604 DI 10.1200/JCO.2005.08.091 PG 8 WC Oncology SC Oncology GA 957LQ UT WOS:000231371700032 PM 16110019 ER PT J AU Marcucci, G Mrozek, K Ruppert, AS Maharry, K Kolitz, JE Moore, JO Mayer, RJ Pettenati, MJ Powell, BL Edwards, CG Sterling, LJ Vardiman, JW Schiffer, CA Carroll, AJ Larson, RA Bloomfield, CD AF Marcucci, G Mrozek, K Ruppert, AS Maharry, K Kolitz, JE Moore, JO Mayer, RJ Pettenati, MJ Powell, BL Edwards, CG Sterling, LJ Vardiman, JW Schiffer, CA Carroll, AJ Larson, RA Bloomfield, CD TI Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE CYTARABINE; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE NONLYMPHOCYTIC LEUKEMIA; RESISTANCE MODULATOR PSC-833; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; GENE-EXPRESSION PROFILES; FRENCH AML INTERGROUP; CUMULATIVE INCIDENCE AB Purpose Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia these cytogenetic groups are often treated (AML) and confer relatively favorable prognoses, similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint. Patients and Methods We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (CIS) and cumulative incidence of relapse (CIR) between the two groups. Results With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with inv(16). Unexpectedly, race was an important predictor for t(8;12) AML, in that nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had shorter OS than whites when certain secondary cytogenetic abnormalities were present. In patients with t(8;21) younger than 60 years, type of induction also correlated with relapse risk. For inv(16) AML, secondary cytogenetic abnormalities (especially +22) and male sex predicted better outcome. Conclusion When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be distinct clinical entities and should be stratified and reported separately. C1 Ohio State Univ, Ctr Comprehens Canc, Div Hematol & Oncol, Dept Internal Med, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. CALGB Stat Ctr, Durham, NC USA. N Shore Univ Hosp, Manhasset, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Chicago, Chicago, IL 60637 USA. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. Univ Alabama, Birmingham, AL USA. RP Marcucci, G (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Hematol & Oncol, Dept Internal Med, A433B Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM marcucci-1@medctr.osu.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA101140, CA31946, CA77658, K08-CA90469, P30-CA16058] NR 50 TC 156 Z9 171 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2005 VL 23 IS 24 BP 5705 EP 5717 DI 10.1200/JCO.2005.15.610 PG 13 WC Oncology SC Oncology GA 957LQ UT WOS:000231371700045 PM 16110030 ER PT J AU Pavletic, SZ Khouri, IF Haagenson, M King, RJ Bierman, PJ Bishop, MR Carston, M Giralt, S Molina, A Copelan, EA Ringden, O Roy, V Ballen, K Adkins, DR McCarthy, P Weisdorf, D Montserrat, E Anasetti, C AF Pavletic, SZ Khouri, IF Haagenson, M King, RJ Bierman, PJ Bishop, MR Carston, M Giralt, S Molina, A Copelan, EA Ringden, O Roy, V Ballen, K Adkins, DR McCarthy, P Weisdorf, D Montserrat, E Anasetti, C TI Unrelated donor marrow transplantation for B-Cell chronic lymphocytic leukemia after using myeloablative conditioning: Results from the center for international blood and marrow transplant research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 19-23, 2000 CL NEW ORLEANS, LA SP Amer Soc Clin Oncol ID GRAFT-VERSUS-LEUKEMIA; MINIMAL RESIDUAL DISEASE; BONE-MARROW; HOST-DISEASE; LYMPHOID MALIGNANCIES; PERIPHERAL-BLOOD; ALLOGENEIC BLOOD; SALVAGE THERAPY; FLUDARABINE; PROGRAM AB Purpose To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL). Patients and Methods A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients. Results Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively. Conclusion These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRIM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens. C1 NCI, Graft Versus Host & Autoimmuni Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Minnesota, Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN 55455 USA. Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. City Hope Natl Canc Ctr, Duarte, CA USA. Ohio State Univ, Columbus, OH 43210 USA. Karolinska Univ Hosp, Huddinge, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Jacksonville, FL USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Barcelona, IDIBAPS, Hosp & Clin, Barcelona, Spain. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmuni Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike,Bldg 10,Room CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov NR 42 TC 61 Z9 63 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2005 VL 23 IS 24 BP 5788 EP 5794 DI 10.1200/JCO.2005.03.962 PG 7 WC Oncology SC Oncology GA 957LQ UT WOS:000231371700054 PM 16043827 ER PT J AU Weylandt, KH Kang, JX AF Weylandt, KH Kang, JX TI Rethinking lipid mediators SO LANCET LA English DT Editorial Material ID POLYUNSATURATED FATTY-ACIDS; ANTI-INFLAMMATION; IMMUNE-RESPONSES; RESOLVIN E1; RECEPTOR; PROSTAGLANDINS; EXPRESSION; ASPIRIN; BRAIN; CELLS C1 Charite Univ Hosp, Dept Gastroenterol & Hepatol, D-13353 Berlin, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. RP Weylandt, KH (reprint author), Charite Univ Hosp, Dept Gastroenterol & Hepatol, Campus Virchow, D-13353 Berlin, Germany. EM karsten.weylandt@charite.de NR 19 TC 39 Z9 43 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 AUG 20 PY 2005 VL 366 IS 9486 BP 618 EP 620 DI 10.1016/S0140-6736(05)67119-X PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 958EB UT WOS:000231426400010 PM 16112288 ER PT J AU Li, B Gallin, WJ AF Li, B Gallin, WJ TI Computational identification of residues that modulate voltage sensitivity of voltage-gated potassium channels SO BMC STRUCTURAL BIOLOGY LA English DT Article ID SHAKER K+ CHANNEL; GENE-EXPRESSION DATA; ION CHANNELS; ELECTROSTATIC INTERACTIONS; STRUCTURAL ELEMENTS; CRYSTAL-STRUCTURE; RAT-BRAIN; CLONING; CANCER; S4 AB Background: Studies of the structure-function relationship in proteins for which no 3D structure is available are often based on inspection of multiple sequence alignments. Many functionally important residues of proteins can be identified because they are conserved during evolution. However, residues that vary can also be critically important if their variation is responsible for diversity of protein function and improved phenotypes. If too few sequences are studied, the support for hypotheses on the role of a given residue will be weak, but analysis of large multiple alignments is too complex for simple inspection. When a large body of sequence and functional data are available for a protein family, mature data mining tools, such as machine learning, can be applied to extract information more easily, sensitively and reliably. We have undertaken such an analysis of voltage-gated potassium channels, a transmembrane protein family whose members play indispensable roles in electrically excitable cells. Results: We applied different learning algorithms, combined in various implementations, to obtain a model that predicts the half activation voltage of a voltage-gated potassium channel based on its amino acid sequence. The best result was obtained with a k-nearest neighbor classifier combined with a wrapper algorithm for feature selection, producing a mean absolute error of prediction of 7.0 mV. The predictor was validated by permutation test and evaluation of independent experimental data. Feature selection identified a number of residues that are predicted to be involved in the voltage sensitive conformation changes; these residues are good target candidates for mutagenesis analysis. Conclusion: Machine learning analysis can identify new testable hypotheses about the structure/ function relationship in the voltage-gated potassium channel family. This approach should be applicable to any protein family if the number of training examples and the sequence diversity of the training set that are necessary for robust prediction are empirically validated. The predictor and datasets can be found at the VKCDB web site [ 1]. C1 Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2E9, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Gallin, WJ (reprint author), Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. EM bli4@partners.org; wgallin@ualberta.ca NR 68 TC 10 Z9 10 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD AUG 19 PY 2005 VL 5 AR 16 DI 10.1186/1472-6807-5-16 PG 17 WC Biophysics SC Biophysics GA 997YN UT WOS:000234285000001 PM 16111489 ER PT J AU Kamimura, M Viedt, C Dalpke, A Rosenfeld, ME Mackman, N Cohen, DM Blessing, E Preusch, M Weber, CM Kreuzer, J Bea, F AF Kamimura, M Viedt, C Dalpke, A Rosenfeld, ME Mackman, N Cohen, DM Blessing, E Preusch, M Weber, CM Kreuzer, J Bea, F TI Interleukin-10 suppresses tissue factor expression in lipopolysaccharide-stimulated macrophages via inhibition of Egr-1 and a serum response element/MEK-ERK1/2 pathway SO CIRCULATION RESEARCH LA English DT Article DE atherosclerosis; tissue factor; interleukin; early growth response gene; macrophages ID ANTIINFLAMMATORY CYTOKINE INTERLEUKIN-10; HUMAN ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; HUMAN MONOCYTIC CELLS; TNF-ALPHA PRODUCTION; GROWTH-FACTOR-BETA; E-DEFICIENT MICE; FACTOR-KAPPA-B; TRANSCRIPTIONAL REGULATION; MEK-ERK1/2 PATHWAY AB Atherosclerosis is considered to be an inflammatory disease. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play an essential role in thrombus formation after atherosclerotic plaque rupture. Recent studies suggest that the antiinflammatory cytokine interleukin-10 (IL-10) has many antiatherosclerotic properties. Therefore, the effects of IL-10 on TF expression in response to inflammation were investigated. Mouse macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of IL-10. Pretreatment with IL-10 resulted in a 50% decrease in TF mRNA expression and TF promoter activity. Binding of early growth response gene-1 (Egr-1) to the consensus DNA sequence, a key transcriptional activator of TF expression in response to inflammation, and the expression of Egr-1 mRNA were also inhibited by IL-10. This inhibition was independent of the induction of suppressor of cytokine signaling protein-3 by IL-10. Macrophages that had been transfected with luciferase reporter constructs containing the murine Egr-1 5'-flanking sequence exhibited reduced reporter gene activity in response to LPS stimulation with IL-10 pretreatment. Studies with deletion constructs of the Egr-1 promoter identified the proximal serum response element SRE3 as a potential regulatory site for the IL-10 mediated suppression of Egr-1 expression. Furthermore, activation of the upstream signal-transduction elements, such as mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase 1/2, and Elk-1 were also inhibited by IL-10 pretreatment. Taken together, these results demonstrate a pathway for the IL-10 mediated inhibition of TF expression during inflammation and may explain the antiatherosclerotic effects of IL-10. C1 Univ Heidelberg, Dept Internal Med 3, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Hyg & Med Microbiol, D-69120 Heidelberg, Germany. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Interdisciplinary Grad Program Nutr Sci, Seattle, WA 98195 USA. Scripps Res Inst, La Jolla, CA USA. Oregon Hlth Sci Univ, Dept Hypertens & Nephrol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Bea, F (reprint author), Univ Heidelberg, Dept Internal Med 3, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM florian.bea@med.uni-heidelberg.de RI Katus, Hugo/P-1712-2016 NR 44 TC 34 Z9 36 U1 2 U2 5 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 AUG 19 PY 2005 VL 97 IS 4 BP 305 EP 313 DI 10.1161/01.RES.0000177893.24574.13 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 956JS UT WOS:000231296600003 PM 16037570 ER PT J AU Fu, MF Wang, CG Rao, M Wu, XF Bouras, T Zhang, XP Li, ZP Jiao, XM Yang, JG Li, AP Perkins, ND Thimmapaya, B Kung, AL Munoz, A Giordano, A Lisanti, MP Pestell, RG AF Fu, MF Wang, CG Rao, M Wu, XF Bouras, T Zhang, XP Li, ZP Jiao, XM Yang, JG Li, AP Perkins, ND Thimmapaya, B Kung, AL Munoz, A Giordano, A Lisanti, MP Pestell, RG TI Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; RUBINSTEIN-TAYBI-SYNDROME; MAMMARY-GLAND DEVELOPMENT; CREB-BINDING PROTEIN; NF-KAPPA-B; TRANSCRIPTIONAL REPRESSION; HISTONE ACETYLTRANSFERASE; ANDROGEN RECEPTOR; ESTROGEN-RECEPTOR; DNA-BINDING AB Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor gamma-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk-and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300. C1 Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Univ Dundee, Div Gene Regulat & Express, Dundee DD1 5EH, Scotland. Northwestern Univ, Feinberg Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Autonoma Madrid, Inst Invest Biomed Alberto Sols, CSIC, E-28029 Madrid, Spain. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol, Philadelphia, PA 19107 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Pestell, RG (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Res Bldg,Rm E501,3970 Reservoir Rd NW,Box 571468, Washington, DC 20057 USA. EM pestell@georgetown.edu RI Lisanti, Michael/C-6866-2013; Munoz, Alberto/O-6393-2014; Giordano, Antonio/F-1927-2010; OI Munoz, Alberto/0000-0003-3890-4251; Giordano, Antonio/0000-0002-5959-016X; Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [R01CA93596, CA51008-14, R01CA107382, R01CA70896, R01CA75503, R01CA86072]; NIDDK NIH HHS [1R21DK065220-02] NR 88 TC 54 Z9 56 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 2005 VL 280 IS 33 BP 29728 EP 29742 DI 10.1074/jbc.M503188200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 954SX UT WOS:000231176200043 PM 15951563 ER PT J AU Babitt, JL Zhang, Y Samad, TA Xia, Y Tang, J Campagna, JA Schneyer, AL Woolf, CJ Lin, HY AF Babitt, JL Zhang, Y Samad, TA Xia, Y Tang, J Campagna, JA Schneyer, AL Woolf, CJ Lin, HY TI Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E3 UBIQUITIN LIGASE; GROWTH-FACTOR-BETA; VERTEBRATE DEVELOPMENT; EXPRESSION PATTERN; SIGNALING PATHWAYS; DIRECT BINDING; I RECEPTOR; MOUSE; GENE; MEMBRANE AB Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta( TGF-beta) superfamily of ligands, which regulate many mammalian physiologic and pathophysiologic processes. BMPs exert their effects through type I and type II serine/threonine kinase receptors and the Smad intracellular signaling pathway. Recently, the glycosylphosphatidylinositol (GPI)anchored protein DRAGON was identified as a co-receptor for BMP signaling. Here, we investigate whether a homologue of DRAGON, repulsive guidance molecule (RGMa), is similarly involved in the BMP signaling pathway. We show that RGMa enhances BMP, but not TGF-beta, signals in a ligand-dependent manner in cell culture. The soluble extracellular domain of RGMa fused to human Fc ( RGMa. Fc) forms a complex with BMP type I receptors and binds directly and selectively to radiolabeled BMP-2 and BMP-4. RGMa mediates BMP signaling through the classical BMP signaling pathway involving Smad1, 5, and 8, and it up-regulates endogenous inhibitor of differentiation (Id1) protein, an important downstream target of BMP signals. Finally, we demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These data are consistent with a role for RGMa as a BMP co-receptor. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Neural Plastic Res Gr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Reprod Endocrine Unit, Boston, MA 02129 USA. RP Lin, HY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. EM hlin@partners.org FU NIDDK NIH HHS [DK-57521, DK-071837, F32 DK-068997, F32 DK068997-02, F32 DK068997-01, F32 DK068997] NR 49 TC 125 Z9 136 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 2005 VL 280 IS 33 BP 29820 EP 29827 DI 10.1074/jbc.M503511200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 954SX UT WOS:000231176200053 PM 15975920 ER PT J AU Woda, JM Calzonetti, T Hilditch-Maguire, P Duyao, MP Conlon, RA MacDonald, ME AF Woda, JM Calzonetti, T Hilditch-Maguire, P Duyao, MP Conlon, RA MacDonald, ME TI Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; PRIMORDIAL GERM-CELLS; VISCERAL ENDODERM; EXTRAEMBRYONIC TISSUES; PRIMITIVE STREAK; NEURODEGENERATIVE DISEASE; TARGETED DISRUPTION; MESODERM FORMATION; POSTERIOR SIGNALS; HOMEOBOX GENE AB Background: Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5) huntingtin deficient embryos. Results: In the absence of huntingtin, expression of nutritive genes appears normal but E7.0 - 7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/ posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion: Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Charlestown, MA 02129 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Univ Queensland, Fac Hlth Sci, St Lucia, Qld 4072, Australia. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, CNY-149,13th St, Charlestown, MA 02129 USA. EM jwoda@partners.org; tcalzon@verizon.net; p.hilditch-maguire@uniquest.com; mabel_duyao@hms.harvard.edu; rac14@po.cwru.edu; macdonam@helix.mgh.harvard.edu FU NINDS NIH HHS [NS16367, NS32765, P50 NS016367, R01 NS032765] NR 56 TC 29 Z9 29 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD AUG 18 PY 2005 VL 5 AR 17 DI 10.1186/1471-213X-5-17 PG 12 WC Developmental Biology SC Developmental Biology GA 997WH UT WOS:000234279000001 PM 16109169 ER PT J AU Wingert, RA Galloway, JL Barut, B Foott, H Fraenkel, P Axe, JL Weber, GJ Dooley, K Davidson, AJ Schmidt, B Paw, BH Shaw, GC Kingsley, P Palis, J Schubert, H Chen, O Kaplan, J Zon, LI AF Wingert, RA Galloway, JL Barut, B Foott, H Fraenkel, P Axe, JL Weber, GJ Dooley, K Davidson, AJ Schmidt, B Paw, BH Shaw, GC Kingsley, P Palis, J Schubert, H Chen, O Kaplan, J Zon, LI CA Tubingen 2000 Screen Consortium TI Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis SO NATURE LA English DT Article ID IRON-SULFUR CLUSTERS; GRX5 MONOTHIOL GLUTAREDOXIN; LINKED SIDEROBLASTIC ANEMIA; PROTEIN; GENE; MITOCHONDRIA; MUTATION; ATAXIA; YEAST; ABC7 AB Iron is required to produce haem and iron - sulphur ( Fe - S) clusters, processes thought to occur independently(1,2). Here we show that the hypochromic anaemia in shiraz ( sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5), a gene required in yeast for Fe - S cluster assembly. We found that grx5 was expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of Delta grx5 yeast Fe - S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes(1,2). We found that loss of Fe - S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 50 iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2 including the iron response element did not. Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings uncover a connection between haem biosynthesis and Fe - S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe - S cluster assembly. C1 Harvard Univ, Sch Med, Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. Univ Rochester, Dept Pediat, Med Ctr, Rochester, NY 14642 USA. Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84132 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Fraenkel, Paula/0000-0001-8894-0117 NR 30 TC 222 Z9 236 U1 0 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 18 PY 2005 VL 436 IS 7053 BP 1035 EP 1039 DI 10.1038/nature03887 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955XQ UT WOS:000231263900054 PM 16110529 ER PT J AU Kasper, DL Sahani, D Misdraji, J Harris, NL Ivers, L McIntosh, K Basgoz, N AF Kasper, DL Sahani, D Misdraji, J Harris, NL Ivers, L McIntosh, K Basgoz, N TI A man with prolonged fever and weight loss - Portal-vein thrombosis due to B-fragilis infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID YERSINIA-ENTEROCOLITICA; ACUTE APPENDICITIS; PERFORATED APPENDICITIS; SALMONELLA; CHILDREN; POLYSACCHARIDES; PYLEPHLEBITIS; BACTERIOLOGY; THERAPY; ABSCESS C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Kasper, DL (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 35 TC 9 Z9 9 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 18 PY 2005 VL 353 IS 7 BP 713 EP 722 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 955UW UT WOS:000231254100011 PM 16107625 ER PT J AU Li, HW Corrales, CE Wang, ZM Zhao, YL Wang, YC Liu, H Heller, S AF Li, HW Corrales, CE Wang, ZM Zhao, YL Wang, YC Liu, H Heller, S TI BMP4 signaling is involved in the generation of inner ear sensory epithelia SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; DIFFERENTIAL EXPRESSION; CELL-PROLIFERATION; COCHLEA; MOUSE; PAX2; IDENTIFICATION; HOMOLOGS; SERRATE; MEMBERS AB Background: The robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments. Results: Here we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation. Conclusion: Our results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Fudan Univ, Shanghai Med Coll, Ear Throat & Nose Hosp, Cent Lab Eye,Dept Otolaryngol, Shanghai 200031, Peoples R China. RP Li, HW (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. EM hwli@shmu.edu.cn; eduardo_corrales@meei.harvard.edu; entwzm@yahoo.com.cn; wych199771@yahoo.com.cn; wych199771@yahoo.com.cn; hwli@shmu.edu.cn; hellers@stanford.edu FU NIDCD NIH HHS [DC006167, DC04563, P30 DC005209, P30 DC05209, R01 DC004563, R01 DC006167] NR 28 TC 47 Z9 53 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD AUG 17 PY 2005 VL 5 AR 16 DI 10.1186/1471-213X-5-16 PG 11 WC Developmental Biology SC Developmental Biology GA 997WG UT WOS:000234278900001 PM 16107213 ER PT J AU Kajiya, K Hirakawa, S Ma, BJ Drinnenberg, I Detmar, M AF Kajiya, K Hirakawa, S Ma, BJ Drinnenberg, I Detmar, M TI Hepatocyte growth factor promotes lymphatic vessel formation and function SO EMBO JOURNAL LA English DT Article DE angiogenesis; HGF; integrins; lymphangiogenesis; tissue repair ID ENDOTHELIAL-CELLS; TUMOR LYMPHANGIOGENESIS; CANCER METASTASIS; TYROSINE KINASE; FACTOR-C; VEGF-C; MET; INDUCTION; MICE; ANGIOGENESIS AB The lymphatic vascular system plays a pivotal role in mediating tissue fluid homeostasis and cancer metastasis, but the molecular mechanisms that regulate its formation and function remain poorly characterized. A comparative analysis of the gene expression of purified lymphatic endothelial cells (LEC) versus blood vascular endothelial cells (BVEC) revealed that LEC express significantly higher levels of hepatocyte growth factor receptor (HGF-R). Whereas little or no HGF-R expression was detected by lymphatic vessels of normal tissues, HGF-R was strongly expressed by regenerating lymphatic endothelium during tissue repair and by activated lymphatic vessels in inflamed skin. Treatment of cultured LEC with HGF promoted LEC proliferation, migration and tube formation. HGF-induced proliferation of LEC did not require vascular endothelial growth factor receptor-3 activation, and HGF-induced cell migration was partially mediated via integrin alpha-9. Transgenic or subcutaneous delivery of HGF promoted lymphatic vessel formation in mice, whereas systemic blockade of HGF-R inhibited lymphatic function. These results identify HGF as a novel, potent lymphangiogenesis factor, and also indicate that HGF-R might serve as a new target for inhibiting pathological lymphangiogenesis. C1 Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Detmar, M (reprint author), Swiss Fed Inst Technol, Inst Pharmaceut Sci, Wolfgang Pauli Str 10,HCI H303, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [P01 CA092644, R01 CA069184, CA69184, CA92644, R01 CA086410, CA86410] NR 41 TC 180 Z9 200 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 17 PY 2005 VL 24 IS 16 BP 2885 EP 2895 DI 10.1038/sj.emboj.7600763 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 963FN UT WOS:000231789300005 PM 16052207 ER PT J AU Mukohara, T Engelman, JA Hanna, NH Yeap, BY Kobayashi, S Lindeman, N Halmos, B Pearlberg, J Tsuchihashi, Z Cantley, LC Tenen, DG Johnson, BE Janne, PA AF Mukohara, T Engelman, JA Hanna, NH Yeap, BY Kobayashi, S Lindeman, N Halmos, B Pearlberg, J Tsuchihashi, Z Cantley, LC Tenen, DG Johnson, BE Janne, PA TI Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; COLORECTAL-CARCINOMA; ACTIVATING MUTATIONS; SOMATIC MUTATIONS; CLINICAL-RESPONSE; GENE-MUTATIONS; FACTOR-ALPHA; EGFR; ANTIBODY AB Background. Many patients with non-small-cell lung cancer (NSCLC) who achieve radiographic responses to treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib have somatic mutations in the EGFR tyrosine kinase domain. However, little is known about the efficacy of cetuximab, an antibody against the EGFR extracellular domain, in EGFR mutant NSCLC. Methods: NSCLC cell lines carrying wild-type EGFR (A549, H441, and H1666) or mutant EGFR (H3255, DFCILU-011, PC-9, and HCC827) were treated with various dilutions of gefitinib or cetuximab relative to maximal achievable serum concentration. Cell growth was analyzed by the NITS assay, with differences between dose-response curves analyzed non-parametrically. Apoptosis was analyzed by propidium iodide staining and immunoblotting for PARP. Phosphorylation of EGFR and the downstream signaling components ERK1/2 and Akt were analyzed by immunoblotting. Statistical tests were two-sided. Results: Growth of NSCLC lines with wildtype EGFR was slightly (A549 and H441) or moderately (H1666) inhibited by gefitinib and cetuximab, and the effects of the two agents were similar. Both agents also induced no (H441) or moderate (H1666) apoptosis in NSCLC cells with wild-type EGFR. By contrast, gefitinib was statistically significantly more effective than cetuximab at inhibiting growth of EGFR mutant cells (H3255: P = .003, DFCILU-011: P = .011, and PC-9: P = .003), and gefitinib-treated EGFR mutant cells had higher levels of apoptosis than cetuximab-treated cells (mean fold increase in apoptosis by 1 mu M of gefitinib and 10 mu g/mL of cetuximab relative to control, H3255: 8.3 [95% confidence interval {CI} = 4.8 to 11.8] and 2.1 [95% CI = 2.0 to 2.2], respectively, P = .025; DFCILU-011: 5.7 [95% CI = 5.1 to 6.3] and. 0.9 [95% CI = 0.3 to 1.5], respectively, P < .001). Gefitinib treatment decreased EGFR, ERK1/2, and Akt phosphorylation in EGFR mutant cell lines whereas cetuximab had relatively little effect. Both gefitinib and cetuximab inhibited the growth of HCC827 cells, but gefitinib inhibited growth to a greater extent (P = .003). Conclusions: EGFR mutations in NSCLC cells are associated with sensitivity to gefitinib but not to cetuximab. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Indiana Univ, Dept Med, Indianapolis, IN 46204 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Hosp Cleveland, Case Sch Med, Ireland Canc Ctr, Cleveland, OH 44106 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org RI Cantley, Lewis/D-1800-2014; Mendez, Pedro /J-8955-2016; OI Cantley, Lewis/0000-0002-1298-7653; Mendez, Pedro /0000-0001-6713-7907; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [1K12CA87723-01, 5T32CA09172-30, P01 CA089021, P20CA90578-02, T32 CA009172]; NIGMS NIH HHS [GM41890] NR 45 TC 223 Z9 230 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 17 PY 2005 VL 97 IS 16 BP 1185 EP 1194 DI 10.1093/jnci/dji238 PG 10 WC Oncology SC Oncology GA 969YT UT WOS:000232272800008 PM 16106023 ER PT J AU Baldwin, LM Dobie, SA Billingsley, K Cai, Y Wright, GE Dominitz, JA Barlow, W Warren, JL Taplin, SH AF Baldwin, LM Dobie, SA Billingsley, K Cai, Y Wright, GE Dominitz, JA Barlow, W Warren, JL Taplin, SH TI Explaining black-white differences in receipt of recommended colon cancer treatment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AFRICAN-AMERICAN WOMEN; SEER-MEDICARE DATA; QUALITY-OF-CARE; RACIAL-DIFFERENCES; COLORECTAL-CANCER; LUNG-CANCER; ADJUVANT CHEMOTHERAPY; UNITED-STATES; RENAL-TRANSPLANTATION; PROSTATE CARCINOMA AB Background. Black-white disparities exist in receipt of recommended medical care, including colorectal cancer treatment. This retrospective cohort study examines the degree to which health systems (e.g., physician, hospital) factors explain black-white disparities in colon cancer care. Methods: Data from the Surveillance, Epidemiology, and End Results program; Medicare claims; the American Medical Association Masterfile; and hospital surveys were linked to examine chemotherapy receipt after stage III colon cancer resection among 5294 elderly ( >= 66 years of age) black and white Medicare-insured patients. Logistic regression analysis was used to identify factors associated with black-white differences in chemotherapy use. All statistical tests were two-sided. Results: Black and white patients were equally likely to consult with a medical oncologist, but among patients who had such a consultation, black patients were less likely than white patients (59.3% versus 70.4%, difference = 10.9%, 95% confidence interval [CI] = 5.1% to 16.4%, P < .001) to receive chemotherapy. This black-white disparity was highest among patients aged 66-70 years (black patients 65.7%, white patients 86.3%, difference = 20.6%, 95% CI = 10.7% to 30.4%, P < .001) and decreased with age. The disparity among patients aged 66-70 years also remained statistically significant in the regression analysis. Overall, patient, physician, hospital, and environmental factors accounted for approximately 50% of the disparity in chemotherapy receipt among patients aged 66-70 years; surgical length of stay and neighborhood socioeconomic status accounted for approximately 27% of the disparity in this age group, and health systems factors accounted for 12%. Conclusions: Black and white Medicare-insured colon cancer patients have an equal opportunity to learn about adjuvant chemotherapy from a medical oncologist but do not receive chemotherapy equally. Little disparity was explained by health systems; more was explained by illness severity, social support, and environment. Further qualitative research is needed to understand the factors that influence the lower receipt of chemotherapy by black patients. C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Canc Res & Biostat, Seattle, WA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Baldwin, LM (reprint author), Univ Washington, Dept Family Med, Box 354982, Seattle, WA 98195 USA. EM lmb@fammed.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 FU NCI NIH HHS [R01 CA089544, R01 CA089544-01, R01CA089544] NR 71 TC 124 Z9 125 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 17 PY 2005 VL 97 IS 16 BP 1211 EP 1220 DI 10.1093/jnci/dji241 PG 10 WC Oncology SC Oncology GA 969YT UT WOS:000232272800011 PM 16106026 ER PT J AU Higashi, T Shekelle, PG Adams, JL Kamberg, CJ Roth, CP Solomon, DH Reuben, DB Chiang, L MacLean, CH Chang, JT Young, RT Saliba, DM Wenger, NS AF Higashi, T Shekelle, PG Adams, JL Kamberg, CJ Roth, CP Solomon, DH Reuben, DB Chiang, L MacLean, CH Chang, JT Young, RT Saliba, DM Wenger, NS TI Quality of care is associated with survival in vulnerable older patients SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MEDICAL-CARE; HEALTH-CARE; COMMUNITY; MORTALITY; ELDERS AB Background: Although assessment of the quality of medical care often relies on measures of process of care, the linkage between performance of these process measures during usual clinical care and subsequent patient outcomes is unclear. Objective: To examine the link between the quality of care that patients received and their survival. Design: Observational cohort study. Setting: Two managed care organizations. Patients: Community-dwelling high-risk patients 65 years of age or older who were continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999. Measurements: Quality of care received by patients (as measured by a set of quality indicators covering 22 clinical conditions) and their survival over the following 3 years. Results: The 372 vulnerable older patients were eligible for a mean of 21 quality indicators (range, 8 to 54) and received, on average, 53% of the care processes prescribed in quality indicators (range, 27% to 88%). Eighty-six (23%) persons died during the 3-year follow-up. There was a graded positive relationship between quality score and 3-year survival. After adjustment for sex, health status, and health service use, quality score was not associated with mortality for the first 500 days, but a higher quality score was associated with lower mortality after 500 days (hazard ratio, 0.64 [95% Cl, 0.49 to 0.84] for a 10% higher quality score). Limitations: The observational design limits causal inference regarding the effect of quality of care on survival. Conclusions: Better performance on process quality measures is strongly associated with better survival among community-dwelling vulnerable older adults. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Wenger, NS (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA 90407 USA. NR 23 TC 130 Z9 132 U1 2 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 16 PY 2005 VL 143 IS 4 BP 274 EP 281 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 955PA UT WOS:000231237100004 PM 16103471 ER PT J AU Arnlov, J Evans, JC Meigs, JB Wang, TJ Fox, CS Levy, D Benjamin, EJ D'Agostino, RB Vasan, RS AF Arnlov, J Evans, JC Meigs, JB Wang, TJ Fox, CS Levy, D Benjamin, EJ D'Agostino, RB Vasan, RS TI Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals - The Framingham heart study SO CIRCULATION LA English DT Article DE endothelium; epidemiology; mortality; risk factors ID CLINICALLY HEALTHY-SUBJECTS; DEPENDENT DIABETES-MELLITUS; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; ARTERIAL-HYPERTENSION; KIDNEY-DISEASE; FOLLOW-UP; MICROALBUMINURIA; EXCRETION; RISK AB Background - Data are limited with regard to the relations of low-grade albuminuria ( below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. Methods and Results - We examined the association of urinary albumin excretion ( spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants ( mean age, 55 years; 58% women) free of CVD. On follow-up ( median, 6 years), 54 participants ( 20 women) developed a first CVD event, and 49 ( 19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD ( hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death ( HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (>= 3.9 mu g/ mg for men, >= 7.5 mu g/mg for women) experienced a nearly 3-fold risk of CVD ( adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P < 0.001) and a borderline significantly increased risk of death ( adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P = 0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n = 1470) and in subgroups with intermediate ( n = 1469) and low ( n = 1186) pretest probabilities of CVD. Conclusions - In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR < 30 mu g/mg indicates "normal" albumin excretion. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA 02114 USA. Uppsala Univ, Dept Publ Hlth & Caring Sci, Sect Geriatr, S-75105 Uppsala, Sweden. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24-HL-04334, K23-HL-074077, N01-HC-25195] NR 50 TC 422 Z9 442 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 16 PY 2005 VL 112 IS 7 BP 969 EP 975 DI 10.1161/CIRCULATIONAHA.105.538132 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 955OM UT WOS:000231235600007 PM 16087792 ER PT J AU Rodriguez, AE Baldi, J Pereira, CF Navia, J Alemparte, MR Delacasa, A Vigo, F Vogel, D O'Neill, W Palacios, IF AF Rodriguez, AE Baldi, J Pereira, CF Navia, J Alemparte, MR Delacasa, A Vigo, F Vogel, D O'Neill, W Palacios, IF CA ERACI II Investigators TI Five-year follow-up of the argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MULTIVESSEL DISEASE; ARTERY-DISEASE; GRAFT-SURGERY; BALLOON ANGIOPLASTY; UNSTABLE ANGINA; RISK-FACTORS; REVASCULARIZATION; INTERVENTION; IMPLANTATION; IMMEDIATE AB OBJECTIVES The purpose of the present study is to report the five-year follow-up results of the ERACI II trial. BACKGROUND Immediate and one-year follow-up results of the ERACI II study showed a prognosis advantage of percutaneous coronary intervention (PCI) with stents over coronary artery bypass grafting (CABG). METHODS A total of 450 patients were randomly assigned to undergo either PCI (n = 225); or CABG (n = 225). Only patients with multi-vessel disease were enrolled. Clinical follow-up during five years was obtained in 92% of the total population after hospital discharge. The primary end point of the study was to compare freedom from major adverse cardiovascular events (MACE) at 30 days, 1 year, 3 years, and 5 years of follow-up. RESULTS At five years of follow-up, patients initially treated with PCI had similar survival and freedom from non-fatal acute myocardial infarction than those initially treated with CABG (92.8% vs. 88.4% and 97.3% vs. 94% respectively, p = 0.16). Freedom from repeat revascularization procedures (PCI/CABG) was significantly lower with PCI compared with CABG (71.5% vs. 92.4%, p = 0.0002). Freedom from MACE was also significantly lower with PCI compared with CABG (65.3% vs. 76.4%; p = 0.013). At five years similar numbers of patients randomized to each revascularization procedure were asymptomatic or with class I angina. CONCLUSIONS At five years of follow-up, in the ERACI II study, there were no survival benefits from any revascularization procedure; however patients initially treated with CABG had better freedom from repeat revascularization procedures and from MACE. (c) 2005 by the American College of Cardiology Foundation C1 Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. Otamendi Hosp, Buenos Aires, DF, Argentina. Sanatorio Belgrano, Mar Del Plata, Argentina. William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. EM ipalacios@partners.org NR 31 TC 131 Z9 149 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 16 PY 2005 VL 46 IS 4 BP 582 EP 588 DI 10.1016/j.jacc.2004.12.081 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 955MK UT WOS:000231229800003 PM 16098419 ER PT J AU Beasley, CM Mitchell, MI Dmitrienko, AA Emmick, JT Shen, W Costigan, TM Bedding, AW Turik, MA Bakhtyari, A Warner, MR Ruskin, JN Cantilena, LR Kloner, RA AF Beasley, CM Mitchell, MI Dmitrienko, AA Emmick, JT Shen, W Costigan, TM Bedding, AW Turik, MA Bakhtyari, A Warner, MR Ruskin, JN Cantilena, LR Kloner, RA TI The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-RATE CORRECTION; TORSADES-DE-POINTES; ERECTILE DYSFUNCTION; HEALTHY-VOLUNTEERS; DRUG DEVELOPMENT; PROLONGATION; VARIABILITY; PATIENT; GENDER AB OBJECTIVES This study was designed to evaluate effects of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction (ED), on the QT interval. BACKGROUND Cardiovascular disease is common in men with ED. Men with cardiovascular disease and ED may have decreased cardiac repolarization reserve. METHODS Effects of tadalafil (100 mg by mouth), ibutilide (0.002 mg/kg intravenously), and placebo on the QT interval in healthy men were compared (placebo and tadalafil [n = 90], with a subset [n = 61] receiving all treatments; mean age 30 years, range 19 to 53 years), Electrocardiographic sampling was done for two days before treatment and on treatment days, The QT was corrected for RR interval with five correction methods, including an individual correction (QTcI). Plasma concentrations of tadalafil were measured to evaluate concentration-QT effect relationships. RESULTS At the time corresponding to maximum plasma concentration of tadalafil, the mean difference in the change in QTcI between tadalafil and placebo was 2.8 ms; tadalafil was equivalent to placebo (a priori, upper limit of 90 % confidence interval < 10 ms [actual = 4.4 ms]; post hoc, upper limit of 95 % confidence interval < 5 ms [actual 4.8]). The active control, ibutilide, significantly increased QTcI by 6.9 and 8.9 ms compared with tadalafil and placebo, respectively. Similar statistical results were obtained with four additional QT correction methods. No subject had a QTcI :450 ins or an increase in QTcI :30 Ins with any treatment. CONCLUSIONS Based on the a priori statistical test of equivalence, plaecbo and high-dose tadalafil produced equivalent effects on the QT interval. This study, reliably discerned 5- to 10-ms changes in corrected QT in the ibutilide active control group. (c) 2005 by the American College of Cardiology Foundation. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Lilly Clin, Windlesham, Surrey, England. Lilly Clin, Indianapolis, IN USA. Simbee Res Ltd, Merthyr Tydfil, M Glam, Wales. Massachusetts Gen Hosp, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Univ So Calif, Good Samaritan Hosp, Keck Sch Med, Heart Inst,Div Cardiovasc Med, Los Angeles, CA USA. RP Beasley, CM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM cmbeasleyj@lilly.com RI Kloner, Robert/B-2971-2012; OI Beasley, Charles/0000-0001-8743-7691 NR 33 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 16 PY 2005 VL 46 IS 4 BP 678 EP 687 DI 10.1016/j.jacc.2005.05.036 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 955MK UT WOS:000231229800019 PM 16098435 ER PT J AU Xie, F Tsutsui, JM McGrain, AC DeMaria, A Cotter, B Becher, H Lebleu, C Labovitz, A Picard, MH O'Leary, EL Porter, TR AF Xie, F Tsutsui, JM McGrain, AC DeMaria, A Cotter, B Becher, H Lebleu, C Labovitz, A Picard, MH O'Leary, EL Porter, TR TI Comparison of Dobutamine stress echocardiography with and without real-time perfusion imaging for detection of coronary artery disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; EMISSION COMPUTED-TOMOGRAPHY; WALL-MOTION; DIPYRIDAMOLE; EXERCISE; DIAGNOSIS; ISCHEMIA; HEART AB in a pilot study of 27 patients, those who presented with chest pain underwent 2 dobutamine stress echocardiographic studies, 1 with high mechanical index harmonic imaging to analyze wall motion without contrast and I with real-time low mechanical index perfusion imaging with intravenous Optison to assess myocardial perfusion and wall motion. All patients then underwent quantitative coronary angiography. Two independent reviewers demonstrated an improvement in sensitivity when analyzing myocardial perfusion. In the 21 patients who had significant coronary stenoses, 14 had abnormal myocardial perfusion detected at peak stress and 7 had abnormal wall motion detected by standard dobutamine stress echocardiography. There was decreased specificity with perfusion imaging by I reviewer. The addition of real-time perfusion imaging after intravenous contrast during dobutamine stress echocardiography has the potential to improve detection of coronary artery disease. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Nebraska, Med Ctr, Omaha, NE 68583 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Oxford, Oxford, England. Connex MD, Bothell, WA USA. St Louis Univ, Med Ctr, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Porter, TR (reprint author), Univ Nebraska, Med Ctr, Omaha, NE 68583 USA. EM trporter@unmc.edu OI Picard, Michael/0000-0002-9264-3243 NR 19 TC 20 Z9 20 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 AUG 15 PY 2005 VL 96 IS 4 BP 506 EP 511 DI 10.1016/j.amjcard.2005.04.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 955VG UT WOS:000231255100007 PM 16098301 ER PT J AU Davidson, MH Maki, KC Pearson, TA Pasternak, RC Deedwania, PC McKenney, JM Fonarow, GC Maron, DJ Ansell, BJ Clark, LT Ballantyne, CM AF Davidson, MH Maki, KC Pearson, TA Pasternak, RC Deedwania, PC McKenney, JM Fonarow, GC Maron, DJ Ansell, BJ Clark, LT Ballantyne, CM TI Results of the National Cholesterol Education (NCEP) Program Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TREATMENT PANEL-III; THERAPY; ADULTS AB The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, >= 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations >= 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 2.7%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (401%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of < 70 mg/dl (< 1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients, with CHD risk. equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach,the new optional treatment goals. (c) 2005 Elsevier Inc. All rights reserved. C1 Radiant Dev, Chicago, IL USA. Univ Rochester, Sch Med, Rochester, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Med Educ & Consultat, Fresno, CA USA. Natl Clin Res, Richmond, VA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Davidson, MH (reprint author), Radiant Dev, Chicago, IL USA. EM michaeldavidson@radiantresearch.com RI Ballantyne, Christie/A-6599-2008 NR 6 TC 196 Z9 199 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2005 VL 96 IS 4 BP 556 EP 563 DI 10.1016/j.amjcard.2005.04.019 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 955VG UT WOS:000231255100017 PM 16098311 ER PT J AU Shannon, J Tewoderos, S Garzotto, M Beer, TM Derenick, R Palma, A Farris, PE AF Shannon, J Tewoderos, S Garzotto, M Beer, TM Derenick, R Palma, A Farris, PE TI Statins and prostate cancer risk: A case-control study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper 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 DE case-control studies; cholesterol; hydroxymethylglutaryl-CoA reductase inhibitors; mevalonic acid; prostate-specific antigen; prostatic neoplasms; veterans ID A REDUCTASE INHIBITORS; SCANDINAVIAN SIMVASTATIN SURVIVAL; COA REDUCTASE; LIPID RAFTS; FOLLOW-UP; CELLS; LOVASTATIN; APOPTOSIS; 4S AB Observational studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use may be associated with reduced cancer risk. The purpose of this case-control study was to elucidate the association between statin use and prostate cancer risk. Prostate cancer cases (n = 100), recruited upon referral for prostate biopsy, and frequency age-matched, prostate-specific antigen-normal clinic controls (n = 202) were recruited from the Portland,. Oregon, Veterans Affairs Medical Center. Information on any use of statins from May 1997 through August 2004 was obtained from an electronic pharmacy database. Days of use, type of statin, dose, and prescription changes were recorded. Duration and intensity were calculated for each statin type on the basis of days of use and prescribed dose. Thirty-six percent of cases and 49 percent of controls had a record of any statin use. Following adjustment for other potential risk factors, statin use was associated with a significant reduction in prostate cancer risk (odds ratio = 0.38, 95% confidence interval: 0.21, 0.69). Furthermore, in analyses stratified by Gleason score, the inverse association with statin use was maintained only among men with Gleason scores of >= 7 (odds ratio = 0.24, 95% confidence interval: 0.11, 0.53). The results of this case-control study suggest that statins may reduce the risk of total prostate cancer and, specifically, more aggressive prostate cancer. C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Shannon, J (reprint author), Oregon Hlth Sci Univ, 3181 SW Sam Jackson Pk Rd CSB669, Portland, OR 97239 USA. EM shannoja@ohsu.edu FU NCRR NIH HHS [M01 RR000334] NR 24 TC 151 Z9 158 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2005 VL 162 IS 4 BP 318 EP 325 DI 10.1093/aje/kwi203 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 954JE UT WOS:000231150600004 PM 16014776 ER PT J AU Cody, JD Semrud-Clikeman, M Hardies, LJ Lancaster, J Ghidoni, PD Schaub, RL Thompson, NM Wells, L Cornell, JE Love, TM Fox, PT Leach, RJ Kaye, CI Hale, DE AF Cody, JD Semrud-Clikeman, M Hardies, LJ Lancaster, J Ghidoni, PD Schaub, RL Thompson, NM Wells, L Cornell, JE Love, TM Fox, PT Leach, RJ Kaye, CI Hale, DE TI Growth hormone benefits children with 18q deletions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 18q-; growth hormone treatment; cognitive development; myelination; chromosome abnormalities ID MYELIN BASIC-PROTEIN; DEFICIENT; HAPLOINSUFFICIENCY AB Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals. (c) 2005 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA. Univ Texas, Dept Educ Psychol, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Anesthesiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Washington, Dept Psychiat & Behav Hlth Sci, Seattle, WA 98195 USA. Iowa State Univ, Dept Stat, Ames, IA USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Cody, JD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cody@uthscsa.edu RI Love, Tanzy/F-3954-2010; Fox, Peter/B-4725-2010 OI Love, Tanzy/0000-0002-7154-0229; Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [M01-RR-01346] NR 26 TC 11 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG 15 PY 2005 VL 137A IS 1 BP 9 EP 15 DI 10.1002/ajmg.a.30848 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 952ND UT WOS:000231009900002 PM 16007630 ER PT J AU McLoud, TC AF McLoud, TC TI Role of high-resolution computed tomography in idiopathic pulmonary fibrosis - The final word? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID INTERSTITIAL PNEUMONIA; ALVEOLITIS; PROGNOSIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2005 VL 172 IS 4 BP 408 EP 409 DI 10.1164/rccm.2506004 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 953DL UT WOS:000231056500004 PM 16081552 ER PT J AU Richter, T Bellani, G Harris, RS Melo, MFV Winkler, T Venegas, LG Musch, G AF Richter, T Bellani, G Harris, RS Melo, MFV Winkler, T Venegas, LG Musch, G TI Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE adult respiratory distress syndrome; emission-computed tomography; nitrogen isotopes; prone position; pulmonary gas exchange ID RESPIRATORY-DISTRESS-SYNDROME; BLOOD-FLOW DISTRIBUTION; POSITRON-EMISSION-TOMOGRAPHY; OLEIC-ACID MODEL; GAS-EXCHANGE; PULMONARY PERFUSION; BODY POSITION; NITRIC-OXIDE; DOG LUNGS; VENTILATION AB Rationale: The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined. Methods:We used positron emission tomography imaging of [N-13]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions. Results: In the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction. Conclusion: In a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dresden Univ Technol, Univ Clin Carl Gustav Carus, Clin Anesthesiol & Intens Care Med, Dresden, Germany. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 309, Boston, MA 02114 USA. EM gmusch@partners.org RI Torsten, Richter/E-3708-2010; Bellani, Giacomo/D-2379-2010; Winkler, Tilo/B-5337-2009 OI Bellani, Giacomo/0000-0002-3089-205X; Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [HL-68011]; NIGMS NIH HHS [GM-07592] NR 40 TC 68 Z9 78 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2005 VL 172 IS 4 BP 480 EP 487 DI 10.1164/rccm.200501-004OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 953DL UT WOS:000231056500020 PM 15901611 ER PT J AU Choi, HK Seeger, JD AF Choi, HK Seeger, JD TI Glucocorticoid use and serum lipid levels in US adults: The Third National Health and Nutrition Examination Survey SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE glucocorticoid; prednisone; corticosteroid; lipid profiles; HDL-cholesterol; apolipoprotein A-I ID ACUTE-PHASE RESPONSE; HIGH-DENSITY-LIPOPROTEIN; LOW-DOSE CORTICOSTEROIDS; RHEUMATOID-ARTHRITIS; RENAL-TRANSPLANTATION; PREDNISONE THERAPY; PLASMA-LIPIDS; DISEASE; CHOLESTEROL; TERM AB Objective. It has been generally perceived that glucocorticoids adversely affect serum lipid levels, although results of prospective studies have suggested the contrary. In this study, we sought to examine the relationship between glucocorticoid use and lipid profiles in a nationally representative sample of subjects Methods. Using data from 15,004 participants ages 20 years and older in The Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between glucocorticoid use and serum lipid profiles. Glucocorticoid use was determined from the household interview regarding prescription medication use. We used multivariate linear regression to adjust for age, sex, race or ethnicity, education, smoking status, body mass index, physical activity, alcohol consumption, energy fraction from protein and carbohydrates, and total energy intake. Results. Glucocorticoid use was associated with a higher serum high-density lipoprotein (HDL) cholesterol level and a lower ratio of total cholesterol-to-HDL cholesterol among subjects ages 60 years or older (multivariate difference 9.0 mg/dl [95% confidence interval (95% Cl) 3.9, 14.11 and -0.6 mg/dl [95% Cl -0.9, -0.31, respectively) but not among those younger than age 60 years (multivariate difference -1.5 mg/dl [95% Cl -5.4, 2.51 and 0.1 mg/dl [95% CI -0.3, 0.51, respectively). Correspondingly, glucocorticoid use was associated with a higher serum apolipoprotein A-I (Apo A-I) level and a lower Apo A-I:Apo B ratio (multivariate difference 12.1 mg/dl [95% Cl 2.9, 21.31 and 0.16 mg/dI 195% Cl 0.03, 0.291, respectively) only among subjects ages 60 years or older. Inhalation/intranasal glucocorticoid use was also associated with a higher serum HDL cholesterol level (multivariate difference 4.9 mg/dl [95% CI 0.3, 9.5]) only among subjects ages 60 years or older. Conclusion. Our results suggest that glucocorticoid use is not associated with an adverse lipid profile in the US population and may be associated with a favorable lipid profile among persons ages 60 years or older, in concordance with previous prospective studies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit, Boston, MA 02114 USA. Ingenix Epidemiol, Auburndale, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 36 TC 35 Z9 38 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2005 VL 53 IS 4 BP 528 EP 535 DI 10.1002/art.21329 PG 8 WC Rheumatology SC Rheumatology GA 952YI UT WOS:000231041900009 PM 16082633 ER PT J AU Flagg, SD Meador, R Hsia, E Kitumnuaypong, T Schumacher, HR AF Flagg, SD Meador, R Hsia, E Kitumnuaypong, T Schumacher, HR TI Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: An open-label trial SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE synovium; chlamydia; etanercept; polymerase chain reaction ID TUMOR-NECROSIS-FACTOR; ALPHA MONOCLONAL-ANTIBODY; POLYMERASE-CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; TNF-ALPHA; CYTOKINES; TISSUE; INHIBITION AB Objective. Elevated levels of tumor necrosis factor alpha (TNF alpha) have been identified in the synovium of patients with reactive and undifferentiated arthritis, implicating TNF alpha in the pathogenesis of these disorders. This finding has provided a rationale for the use of TNF alpha antagonists in the treatment of reactive arthritis; however, the possibility that the triggering microorganism might persist in affected joints and become activated with use of these agents has been of concern. Methods. The efficacy and safety of etanercept (25 mg subcutaneous twice weekly) in 16 patients with undifferentiated or reactive arthritis was assessed in a 6-month open-label trial. Synovial biopsies were performed before and after treatment with etanercept. Polymerase chain reaction (PCR) analysis was performed on the synovial biopsy samples to evaluate for the presence of nucleic acid material of bacterial organisms. Outcome measures including tender and swollen joint counts, pain assessment on a 10-point visual analog scale, and functional ability as measured by the Health Assessment Questionnaire were determined before and after etanercept therapy. Results. Ten of 16 patients completed the trial. Six patients withdrew, but none had a worsening of arthritis or infection. Of the 10 completers, 9 could be classified as treatment responders, despite the evidence of bacterial organisms on PCR analysis prior to initiating etanercept in 3 patients; 2 patients became PCR negative on etanercept. Five of 6 patients with adequate synovial biopsy specimens showed improvement, but not normalization of histology. Conclusion. Etanercept was well-tolerated without clinical exacerbation of any suspected underlying infections and appeared to provide therapeutic benefit in our cohort of patients with reactive and undifferentiated arthritis. C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Affairs Med Ctr, 38th St & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu NR 20 TC 32 Z9 34 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2005 VL 53 IS 4 BP 613 EP 617 DI 10.1002/art.21323 PG 5 WC Rheumatology SC Rheumatology GA 952YI UT WOS:000231041900021 PM 16082643 ER PT J AU Shin, JM Sachs, G AF Shin, JM Sachs, G TI Differences in binding properties of two proton pump inhibitors on the gastric H+, K+-ATPase in vivo (vol 68, pg 2117, 2004) SO BIOCHEMICAL PHARMACOLOGY LA English DT Correction C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 15 PY 2005 VL 70 IS 4 BP 648 EP 648 DI 10.1016/j.bcp.2004.07.035 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 951RY UT WOS:000230949700018 ER PT J AU Abramson, JS Shipp, MA AF Abramson, JS Shipp, MA TI Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach SO BLOOD LA English DT Review ID NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; 3-WEEKLY CHOP CHEMOTHERAPY; DETUDE-DES-LYMPHOMES; P53 GENE-MUTATIONS; ELDERLY-PATIENTS; AGGRESSIVE LYMPHOMA; CHROMOSOMAL-ABNORMALITIES; CONVENTIONAL CHEMOTHERAPY AB Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic, and molecular levels. Clinical prognostic models can define a population at high risk for relapse following empiric chemotherapy, although such models do not account for underlying biologic differences among tumors. Commonly observed genetic abnormalities that likely contribute to pathogenesis include translocations of BCL6, BCL2, cMYC, and FAS(CD95) mutations, and aberrant somatic hypermutation. Despite recent advances in empiric chemotherapy, including interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a significant proportion of patients still die of their disease. Gene expression profiling has shed light on the molecular heterogeneity within DLBCL by highlighting similarities between subsets of tumors and normal 13 cells, identifying features associated with unfavorable responses to empiric combination chemotherapy, and defining robust subtypes with comprehensive transcriptional signatures. Such strategies have suggested distinct routes to lymphoma genesis and have identified promising rational therapeutic targets. Additional novel therapies under investigation include those targeting BCL6 and BCL2, as well as development of novel monoclonal antibody-based therapies. Our increasing molecular understanding of the heterogeneous subsets within DLBCL will likely improve the current empiric therapy of DLBCL by identifying rational therapeutic targets in specific disease subtypes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu NR 100 TC 120 Z9 128 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2005 VL 106 IS 4 BP 1164 EP 1174 DI 10.1182/blood-2005-02-0687 PG 11 WC Hematology SC Hematology GA 954PT UT WOS:000231167700012 PM 15855278 ER PT J AU Austin, KM Leary, RJ Shimamura, A AF Austin, KM Leary, RJ Shimamura, A TI The Shwachman-Diamond SBDS protein localizes to the nucleolus SO BLOOD LA English DT Article ID DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; FANCONIS ANEMIA; HUMAN-DISEASE; MUTATIONS; GENE; HYPOPLASIA; PREDICTION; COMPONENT; INSIGHTS AB Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure, The gene for this syndrome, SBDS, encodes a highly conserved novel protein. We characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization in 7 patients with SDS and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T>C splice donor mutation, expressed scant levels of SBDS protein. Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation. Patient DF269, who carried no detectable gene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body of evidence for additional gene(s) that might contribute to the pathogenesis of the disease phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell-cycle dependent, with nucleolar localization during G(1) and G(2) and diffuse nuclear localization during S phase. SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar localization of SBDS provides further Supportive evidence for its Postulated role in rRNA processing. C1 Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shimamura, A (reprint author), Karp Family Res Facil, 300 Longwood Ave, Boston, MA 02115 USA. EM akiko.shimamura@childrens.harvard.edu FU NHLBI NIH HHS [1 K23 HL68632-01, 1 R01 HL079582-01] NR 42 TC 75 Z9 79 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 AUG 15 PY 2005 VL 106 IS 4 BP 1253 EP 1258 DI 10.1182/blood-2005-02-0807 PG 6 WC Hematology SC Hematology GA 954PT UT WOS:000231167700026 PM 15860664 ER PT J AU Halin, C Scimone, ML Bonasio, R Gauguet, JM Mempel, TR Quackenbush, E Proia, RL Mandala, S von Andrian, UH AF Halin, C Scimone, ML Bonasio, R Gauguet, JM Mempel, TR Quackenbush, E Proia, RL Mandala, S von Andrian, UH TI The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell-expressed S1P(1) amplifies integrin activation in peripheral lymph nodes but not in Peyer patches SO BLOOD LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTORS; CIRCULATING MATURE LYMPHOCYTES; PROTEIN-COUPLED RECEPTOR; HIGH ENDOTHELIAL VENULES; SKIN ALLOGRAFT SURVIVAL; VASCULAR MATURATION; IN-VIVO; SPHINGOSINE-1-PHOSPHATE; IMMUNOSUPPRESSANT; CHEMOKINE AB Sphingosine-1-phosphate (S1P) and its receptor S1P, control T-cell egress from thymus and secondary lymphoid organs (SLOs). To further define the role of S1P, in lymphocyte trafficking, we performed adoptive transfer experiments and intravital microscopy (IVM) using both S1P(1)(-/-) lymphocytes and recipient wild-type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P receptors. S1P, deficiency and FTY720 caused rapid disappearance of T cells from blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed by multiphoton IVM. However, S1P(1)(-/-) lymphocytes displayed reduced short-term homing to PLNs due to attenuated integrin-mediated firm arrest in high endothelial venules (HEVs). By contrast, S1P(1)(-/-) T cells homed normally to Peyer patches (PPs), whereas S1P(1)(-/-) B cells had a marked defect in homing to PPs and arrested poorly in PP HEVs. Therefore, S1P, not only controls lymphocyte egress from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin activation during homing. Interestingly, FTY720 treatment enhanced accumulation of both S1P(1) sufficient and S1P(1)(-/-) T cells in PPs by enhancing integrin-mediated arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that are independent of T-cell-expressed S1P(1). C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Merck Res Labs, Dept Immunol & Rheumatol, Rahway, NJ USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP von Andrian, UH (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI Proia, Richard/A-7908-2012; von Andrian, Ulrich/A-5775-2008; Bonasio, Roberto/P-1356-2014 OI Bonasio, Roberto/0000-0002-0767-0889 FU NHLBI NIH HHS [HL48675, HL54936, HL56949, P01 HL056949] NR 43 TC 68 Z9 70 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 AUG 15 PY 2005 VL 106 IS 4 BP 1314 EP 1322 DI 10.1182/blood-2004-09-3687 PG 9 WC Hematology SC Hematology GA 954PT UT WOS:000231167700034 PM 15870184 ER PT J AU Tassone, P Neri, P Kutok, JL Tournilhac, O Santos, DD Hatjiharissi, E Munshi, V Venuta, S Anderson, KC Treon, SP Munshi, NC AF Tassone, P Neri, P Kutok, JL Tournilhac, O Santos, DD Hatjiharissi, E Munshi, V Venuta, S Anderson, KC Treon, SP Munshi, NC TI A SCID-hu in vivo model of human Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID MULTIPLE-MYELOMA CELLS; HUMAN BONE-MARROW; MICE; RITUXIMAB; THERAPY; MOUSE; CLASSIFICATION; LYMPHOMA; ANTIBODY; BIOLOGY AB The preclinical evaluation of investigational agents for Waldenstrom macroglobulinemia (WM) has been limited by the lack of in vivo models that enable the use of explanted patient cells. We describe here a novel in vivo model of human WM in severe combined immunodeficient (SCID) mice implanted with human fetal bone chips (SCID-hu mice) into which WM cells from patient bone marrow are engrafted directly into the human bone marrow (huBM) microenvironment. WM cells in SCID-hu mice produced human monoclonal paraprotein (immunoglobulin M [IgM] and/or kappa or lambda chain) detectable in mice sera. Immunohistochemical analysis of human bone retrieved from SCID-hu mice showed infiltration with CD20(+), IgM(+), and monotypic light chain(+) lymphoplasmacytic cells. Mast cells were observed to be associated with the infiltrate in these sections. Treatment of SCID-hu mice bearing WM with rituximab induced tumor regression, associated with a decrease in serum paraprotein. This model, therefore, recapitulates the in vivo biology of WM and allows the study of novel investigational drugs targeting WM cells in the huBM milieu. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vet Adm Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Magna Graecia, Catanzaro, Italy. Ctr Canc, Catanzaro, Italy. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU NCI NIH HHS [K23-CA087977]; PHS HHS [P01-78378, P50-100707, R01-50947] NR 26 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2005 VL 106 IS 4 BP 1341 EP 1345 DI 10.1182/blood-2004-11-4477 PG 5 WC Hematology SC Hematology GA 954PT UT WOS:000231167700038 PM 15886318 ER PT J AU Feuerhake, F Kutok, JL Monti, S Chen, W LaCasce, AS Cattoretti, G Kurtin, P Pinkus, GS de Leval, L Harris, NL Savage, KJ Neuberg, D Habermann, TM Dalla-Favera, R Golub, TR Aster, JC Shipp, MA AF Feuerhake, F Kutok, JL Monti, S Chen, W LaCasce, AS Cattoretti, G Kurtin, P Pinkus, GS de Leval, L Harris, NL Savage, KJ Neuberg, D Habermann, TM Dalla-Favera, R Golub, TR Aster, JC Shipp, MA TI NF kappa B activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes SO BLOOD LA English DT Article ID CLASSICAL HODGKIN LYMPHOMA; C-FLIP; HLA-F; INDUCED APOPTOSIS; STERNBERG CELLS; REL GENE; T-CELLS; EXPRESSION; ALPHA; AMPLIFICATION AB Primary mediastinal large B-cell lymphoma (MLBCL) shares important clinical and molecular features with classic Hodgkin lymphoma, including nuclear localization of the nuclear factor kappa B (NF kappa B) subunit c-REL (reticuloendotheliosis viral oncogene homolog) in a pilot series. Herein, we analyzed c-REL subcellular localization in additional primary MLBCLs and characterized NF kappa B activity and function in a MLBCL cell line. The new primary MLBCLs had prominent c-REL nuclear staining, and the MLBCL cell line exhibited high levels of NF kappa B binding activity. MLBCL cells expressing a superrepressor form of inhibitor of kappa B alpha signaling (I kappa B alpha) had a markedly higher rate of apoptosis, implicating constitutive NF kappa B activity in MLBCL cell survival. The transcriptional profiles of newly diagnosed primary MLBCLs and diffuse large B-cell lymphomas (DLBCLs) were then used to characterize the NF kappa B target gene signatures of MLBCL and specific DLBCL subtypes. MLBCLs expressed increased levels of NF kappa B targets that promote cell survival and favor antiapoptotic tumor necrosis factor alpha (TNF alpha) signaling. In contrast, activated B cell (ABC)-like DLBCLs had a more restricted, potentially developmentally regulated, NF kappa B target gene signature. Of interest, the newly characterized host response DLBCL subtype had a robust NF kappa B target gene signature that partially overlapped that of primary MLBCL. In this large series of primary MLBCLs and DLBCLs, NF kappa B activation was not associated with amplification of the cREL locus, suggesting alternative pathogenetic mechanisms. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. Columbia Univ, Inst Canc Genet, New York, NY USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Med, Rochester, MN USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu OI Monti, Stefano/0000-0002-9376-0660 NR 50 TC 140 Z9 145 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2005 VL 106 IS 4 BP 1392 EP 1399 DI 10.1182/blood-2004-12-4901 PG 8 WC Hematology SC Hematology GA 954PT UT WOS:000231167700045 PM 15870177 ER PT J AU Cahn, JY Klein, JP Lee, SJ Milpied, N Blaise, D Antin, JH Leblond, V Ifrah, N Jouet, JP Loberiza, F Ringden, O Barrett, AJ Horowitz, MM Socie, G AF Cahn, JY Klein, JP Lee, SJ Milpied, N Blaise, D Antin, JH Leblond, V Ifrah, N Jouet, JP Loberiza, F Ringden, O Barrett, AJ Horowitz, MM Socie, G TI Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study SO BLOOD LA English DT Article ID SEVERITY INDEX; DISEASE AB The most commonly used grading system for acute graft-versus-host disease (aGVHD) was introduced 30 years ago by Glucksberg; a revised system was developed by the International Bone Marrow Transplant Registry (IBMTR) in 1997. To prospectively compare the 2 classifications and to evaluate the effect of duration and severity of aGVHD on survival, we conducted a multicenter study of 607 patients receiving T-cell-replete allografts, scored weekly for aGVHD in 18 transplantation centers. Sixty-nine percent of donors were HLA-identical siblings and 28% were unrelated donors. The conditioning regimen included total body irradiation in 442 (73%) patients. The 2 classifications performed similarly in explaining variability in survival by aGVHD grade, although the Glucksberg classification predicted early survival better. There was less physician bias or error in assigning grades with the IBMTR scoring system. With either system, only the maximum observed grade had prognostic significance for survival; neither time of onset nor progression from an initially lower grade of aGVHD was associated with survival once maximum grade was considered. Regardless of scoring system, aGVHD severity accounted for only a small percentage of observed variation in survival. Validity of these results in populations receiving peripheral blood transplants or nommyeloalblative conditioning regimens remains to be tested. C1 CHU Grenoble, Dept Hematol, F-38043 Grenoble, France. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHU Nantes, Dept Hematol, F-44035 Nantes, France. Inst J Paoli I Calmettes, Dept Hematol, F-13009 Marseille, France. Hop La Pitie Salpetriere, Dept Hematol, Paris, France. Dept Hematol, Angers, France. Dept Hematol, Lille, France. Huddinge Univ Hosp, Stockholm, Sweden. NIH, Bethesda, MD 20892 USA. Hop St Louis, Paris, France. RP Cahn, JY (reprint author), CHU Grenoble, INSERM,EMI 353, Hop Michallon, Dept Oncohematol, F-38700 Grenoble, France. EM jycahn@chu-grenoble.fr RI Cahn, Jean-Yves/M-6493-2014 FU NCI NIH HHS [U24-CA76518] NR 9 TC 83 Z9 86 U1 2 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 AUG 15 PY 2005 VL 106 IS 4 BP 1495 EP 1500 DI 10.1182/blood-2004-11-4557 PG 6 WC Hematology SC Hematology GA 954PT UT WOS:000231167700060 PM 15878974 ER PT J AU Marina, N Chang, KW Malogolowkin, M London, WB Frazier, AL Womer, RB Rescorla, F Billmire, DF Davis, MM Perlman, EJ Giller, R Lauer, SJ Olson, TA AF Marina, N Chang, KW Malogolowkin, M London, WB Frazier, AL Womer, RB Rescorla, F Billmire, DF Davis, MM Perlman, EJ Giller, R Lauer, SJ Olson, TA TI Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors - A children's Oncology Group study SO CANCER LA English DT Article DE pediatric germ-cell tumors; high-dose cisplatin; etoposide; bleomycin ID DISSEMINATED TESTICULAR CANCER; COMBINATION CHEMOTHERAPY; TRIAL; TOXICITY; WR-2721; CARBOPLATIN; CYCLOPHOSPHAMIDE; MEDULLOBLASTOMA; ADOLESCENTS; CHILDHOOD AB Background. High-dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event-free survival (EFS) in advanced pediatric germ-cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity decreased. Methods. Eligibility criteria included age <15 years and unresectable Stage III/IV extracranial, extragonadal PGCT. Patients received bleomycin 15 IU/m(2) on Day 1, then etoposide 100 mg/m(2) per day, amifostine 825 mg/m(2) per day, and cisplatin 40 mg/m(2) per day on Days 1-5, intravenously. The cycles were repeated every 3-4 weeks with imaging evaluation after 4 cycles. Patients with residual radiographic abnormalities underwent resection. Patients with residual tumor received two additional HDPEB cycles. Hearing evaluations were required at diagnosis and after two and four cycles. Audiologic results were reviewed and compared with historical controls treated with HDPEB. Results. Twenty-five eligible patients were enrolled between April 2000 and April 2002. Their median age was 1.6 years (range, 0.64-13.9 years), 17 patients were female, 11 had metastases, and 24 had a yolk sac carcinoma component histologically. Primary sites included sacrococcygeal area/pelvis (n=15), vagina (n=5), and other (n=5). Two-year EFS and overall survival were 83.5%+/- 12.8% and 85.6%+/- 12.3%, respectively. Eight patients were removed from the study (four had progressive disease/disease recurrence and four had ototoxicity). Grade 3/4 toxicities included neutropenia (n=20), thrombocytopenia (n=14), electrolyte imbalances (n=14), and gastrointestinal toxicity (n=12). Twenty-four of 25 patients received hearing evaluations, and 75% had significant hearing loss. Conclusions. Amifostine did not protect against HDPEB-associated ototoxicity. C1 Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Otolaryngol, Stanford, CA 94305 USA. Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Childrens Oncol Grp, Gainesville, FL USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Indiana Univ, James Whitcomb Riley Hosp Children, Dept Pediat Surg, Indianapolis, IN USA. Indiana Univ, James Whitcomb Riley Hosp Children, Dept Pediat Pathol, Indianapolis, IN USA. Childrens Mem Med Ctr Chicago, Dept Pathol, Chicago, IL USA. Childrens Hosp, Dept Hematol Oncol, Denver, CO 80218 USA. Childrens Healthcare Atlanta Egleston, Dept Pediat Hematol Oncol, Atlanta, GA USA. RP Marina, N (reprint author), Stanford Univ, Med Ctr, Dept Pediat, 1000 Welsh Rd,Suite 300, Palo Alto, CA 94304 USA. EM Neyssa.marina@stanford.edu OI Chang, Kay/0000-0002-8446-5299 NR 41 TC 52 Z9 57 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2005 VL 104 IS 4 BP 841 EP 847 DI 10.1002/cncr.21218 PG 7 WC Oncology SC Oncology GA 952XV UT WOS:000231040500023 PM 15999362 ER PT J AU Kobayashi, S Ji, HB Yuza, Y Meyerson, M Wong, KK Tenen, DG Halmos, B AF Kobayashi, S Ji, HB Yuza, Y Meyerson, M Wong, KK Tenen, DG Halmos, B TI An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; KINASE INHIBITOR; TYROSINE KINASE; EGFR MUTATIONS; ACHILLES HEAL; GEFITINIB; IMATINIB; THERAPY; GENE; SENSITIVITY AB Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in non-small cell lung cancer specimens from patients responding to anilinoquinazoline EGFR inhibitors. However, clinical resistance to EGFR inhibitor therapy is commonly observed. Previously, we showed that such resistance can be caused by a second mutation of the EGFR gene, leading to a T790M amino acid change in the EGFR tyrosine kinase domain and also found that CL-387,785, a specific and irreversible anilinoquinazoline EGFR inhibitor, was able to overcome this resistance on the biochemical level. Here, we present the successful establishment of a stable Ba/F3 cell line model system for the study of oncogenic EGFR signaling and the functional consequences of the EGFR T790M resistance mutation. We show the ability of gefitinib to induce growth arrest and apoptosis in cells transfected with wild-type or L858R EGFR, whereas the T790M mutation leads to high-level functional resistance against gefitinib and erlotinib. In addition, CL-387,785 is able to overcome resistance caused by the T790M mutation on a functional level, correlating with effective inhibition of downstream signaling pathways. Similar data was also obtained with the use of the gefitinib-resistant H1975 lung cancer cell line. The systems established by us should prove useful for the large-scale screening of alternative EGFR inhibitor compounds against the T790M or other EGFR mutations. These data also support the notion that clinical investigations of compounds similar to CL-387,785 may be useful as a treatment strategy for patients with resistance to EGFR inhibitor therapy caused by the T790M mutation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 77 Ave Louis Pasteur Ave, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [P20-CA090578-01A1] NR 20 TC 174 Z9 179 U1 0 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 AUG 15 PY 2005 VL 65 IS 16 BP 7096 EP 7101 DI 10.1158/0008-5472.CAN-05-1346 PG 6 WC Oncology SC Oncology GA 954XK UT WOS:000231188600012 PM 16103058 ER PT J AU Yang, XP Liu, LY Sternberg, D Tang, LR Galinsky, I DeAngelo, D Stone, R AF Yang, XP Liu, LY Sternberg, D Tang, LR Galinsky, I DeAngelo, D Stone, R TI The FLT3 internal tandem duplication mutation prevents apoptosis in interleukin-3-deprived BaF3 cells due to protein kinase A and ribosomal S6 kinase 1-mediated BAD phosphorylation at serine 112 SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROME; CONSTITUTIVE ACTIVATION; MYELOGENOUS LEUKEMIA; HEMATOPOIETIC-CELLS; MAP KINASE; 32D CELLS; WILD-TYPE; SURVIVAL; GENE AB Internal tandem duplication (ITD) mutations in the FLT3 tyrosine kinase have been detected in similar to 20% of acute myeloid leukemia (AML) patients. Patients harboring FLT3/ITD mutations have a relatively poor prognosis. FLT3/ITD results in constitutive autophosphorylation of the receptor and factor-independent survival. Previous studies have shown that FLT3/ITD activates the signal transducers and activators of transcription 5 (STAT5), p42/p44 mitogen-activated protein kinase [MAPK; extracellular signal-regulated kinase (ERK) 1/2], and phosphatidylinositol 3-kinase/Akt pathways. We herein provide biochemical and biological evidence that ribosomal S6 kinase I (RSK1) and protein kinase A (PKA) are the two principal kinases that mediate the antiapoptotic function of FLT3/ITD via phosphorylation of BAD at Ser(112). Inhibiting both MAPK kinase (MEK)/ERK and PKA pathways by a combination of U0126 (10 mu mol/L) and H-89 (5 mu mol/L) reduced most of BAD phosphorylation at Ser(112) and induced apoptosis to a level comparable with that induced by FLT3 inhibitor AG1296 (5 mu mol/L) in BaF3/FLT3/ITD cells. RNA interference of RSK1 or PKA catalytic subunit reduced BAD phosphorylation and induced apoptosis. The MEK inhibitor U0126 and/or the PKA inhibitor H-89 greatly enhanced the efficacy of the FLT3 inhibitor AG1296, suggesting that combining FLT3/ITD downstream pathway inhibition with FLT3 inhibitors may be a viable therapeutic strategy for AML caused by a FLT3/ITD mutation. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA USA. Mt Sinai Sch Med, Div Hematol Oncol, New York, NY USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Stone, R (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rstone@partners.org FU NCI NIH HHS [2PO1CA66996-06] NR 44 TC 27 Z9 31 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2005 VL 65 IS 16 BP 7338 EP 7347 DI 10.1158/0008-5472.CAN-04-2263 PG 10 WC Oncology SC Oncology GA 954XK UT WOS:000231188600040 PM 16103085 ER PT J AU Yasui, H Hideshima, T Raje, N Roccaro, AM Shiraishi, N Kumar, S Hamasaki, M Ishitsuka, K Tai, YT Podar, K Catley, L Mitsiades, CS Richardson, PG Albert, R Brinkmann, V Chauhan, D Anderson, KC AF Yasui, H Hideshima, T Raje, N Roccaro, AM Shiraishi, N Kumar, S Hamasaki, M Ishitsuka, K Tai, YT Podar, K Catley, L Mitsiades, CS Richardson, PG Albert, R Brinkmann, V Chauhan, D Anderson, KC TI FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; IMMUNOSUPPRESSIVE AGENT; THERAPEUTIC IMPLICATIONS; SIGNAL-TRANSDUCTION; CYTOCHROME-C; BONE-MARROW; MM CELLS; GROWTH; INTERLEUKIN-6; CANCER AB The novel immunomodulator FTY720 down-modulates sphingosine-1-phosphate receptor 1 on lymphocytes at low nanomolar concentrations, thereby inhibiting sphingosine-1-phosphate receptor I-dependent egress of lymphocytes from lymph nodes into efferent lymphatics and blood. At high micromolar concentration, FTY720 has been shown to induce growth inhibition and/or apoptosis in human cancer cells in vitro. In this study, we investigated the biological effects of FTY720 on multiple myeloma cells. We found that FTY720 induces potent cytotoxicity against drug-sensitive and drug-resistant multiple myeloma cell lines as well as freshly isolated tumor cells from multiple myeloma patients who do not respond to conventional agents. FTY720 triggers activation of caspase-8, -9, and -3, followed by poly(ADPribose) polymerase cleavage. Interestingly, FTY720 induces alterations in mitochondrial membrane potential (AT.) and Bax cleavage, followed by translocation of cytochrome c and Smac/Diablo from mitochondria to the cytosol. In combination treatment studies, both dexamethasone and anti-Fas antibodies augment anti-multiple myeloma activity induced by FTY720. Neither interleukin-6 nor insulin-like growth factor-I, which both induce multiple myeloma cell growth and abrogate dexamethasone-induced apoptosis, protect against FTY720-induced growth inhibition. Importantly, growth of multiple myeloma cells adherent to bone marrow stromal cells is also significantly inhibited by FTY720. Finally, it down-regulates interleukin-6-induced phosphorylation of Akt, signal transducers and activators of transcription 3, and p42/44 mitogen-activated protein kinase; insulin-like growth factor-l-triggered Akt phosphorylation; and tumor necrosis factor alpha-induced I kappa B alpha and nuclear factor-kappa B p65 phosphorylation. These results suggest that FTY720 overcomes drug resistance in multiple myeloma cells and provide the rationale for its clinical evaluation to improve patient outcome in multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Novartis Pharma, Basel, Switzerland. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [P0-1-CA50947, 1P50 CA10070-01, R0-1 CA50947] NR 58 TC 73 Z9 78 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2005 VL 65 IS 16 BP 7478 EP 7484 DI 10.1158/0008-5472.CAN-05-0850 PG 7 WC Oncology SC Oncology GA 954XK UT WOS:000231188600057 PM 16103102 ER PT J AU Freedman, ML Penney, KL Stram, DO Riley, S McKean-Cowdin, R Le Marchand, L Altshuler, D Haiman, CA AF Freedman, ML Penney, KL Stram, DO Riley, S McKean-Cowdin, R Le Marchand, L Altshuler, D Haiman, CA TI A haplotype-based case-control study of BRCA1 and sporadic breast cancer risk SO CANCER RESEARCH LA English DT Article ID MULTIETHNIC COHORT; FAMILIAL BREAST; LINKAGE DISEQUILIBRIUM; OVARIAN-CANCER; HUMAN GENOME; LOS-ANGELES; MUTATIONS; GENE; SUSCEPTIBILITY; POLYMORPHISMS AB Rare, highly penetrant germ line mutations in BRCA1 strongly predispose women to a familial form of breast and ovarian cancer. Whether common variants (either coding or noncoding) at this locus contribute to the more common form of the disease is not yet known. We tested common variation across the BRCA1 locus in African American, Native Hawaiian, Japanese, Latino, and White women in the Multiethnic Cohort Study. Specifically, 28 single nucleotide polymorphisms (SNPs) spanning the BRCA1 gene were used to define patterns of common variation in these populations. The majority of SNPs were in strong linkage disequilibrium with one another, indicating that our survey captured most of the common inherited variation across this gene. Nine tagging SNPs, including five missense SNPs, were selected to predict the common BRCA1 variants and haplotypes among the non-African American groups (five additional SNPs were required for African Americans) and genotyped in a breast cancer case-control study nested in the Multiethnic Cohort Study (cases, n = 1,715; controls, n = 2,502). We found no evidence for significant associations between common variation in BRCA1 and risk of breast cancer. Given the large size of our study population and detailed analysis of the locus, this result indicates either that common variants in BRCA1 do not substantially influence sporadic breast cancer risk, or that unmeasured heterogeneity in the breast cancer phenotype or unmeasured interactions with genetic or environmental exposures obscure our ability to detect any influence that may be present. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Biol & Diabet Unit, Boston, MA 02114 USA. Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Honolulu, HI 96822 USA. RP Haiman, CA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Room 4441,1441 Eastlake Ave, Los Angeles, CA 90089 USA. EM Haiman@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 33 TC 39 Z9 40 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2005 VL 65 IS 16 BP 7516 EP 7522 DI 10.1158/0008-5472.CAN-05-0132 PG 7 WC Oncology SC Oncology GA 954XK UT WOS:000231188600062 PM 16103107 ER PT J AU Milan, DJ MacRae, CA AF Milan, DJ MacRae, CA TI Animal models for arrhythmias SO CARDIOVASCULAR RESEARCH LA English DT Review DE arrhythmias; modeling; genetics; drugs ID SUDDEN CARDIAC DEATH; LONG-QT SYNDROME; SUSTAINED ATRIAL-FIBRILLATION; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; POLYMORPHIC VENTRICULAR-TACHYCARDIA; HEALED MYOCARDIAL-INFARCTION; PARKINSON-WHITE-SYNDROME; RECTIFYING K+ CURRENT; MOUSE MODEL; TRANSGENIC MICE AB The complex pathophysiology of human arrhythmias has proven difficult to model. Direct correlations between the traditional arrhythmia mechanisms, including abnormal excitability, conduction, or repolarization and underlying molecular or cellular biology are poorly defined, as the primary etiologies of many human arrhythmias remain unknown. Since the causes of several arrhythmic syndromes have been identified, genetic models reproducing the mechanisms of these arrhythmias have become feasible. Initial murine modeling has revealed that in many cases the pathophysiology of the respective human disease is more complex than had been suspected. Insights from human genetic studies and animal models strongly suggest that the primary molecular defects may contribute at many stages in the causal chain leading to arrhythmia. The comprehensive analysis of each arrhythmia will require knowledge not only of the membrane effects of the primary defects, but also downstream intracellular signals, the developmental results of these perturbations, and the integration of compensatory responses and environmental factors. Precise modeling will require not only the mutation of specific residues in known disease genes, but also the systematic study of each of the many steps in arrhythmogenesis. Ultimately, such models will enable unbiased screens for disease mechanisms and novel therapies. (C) 2005 European Society of Cardiology. Published by Elsevier B.V. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA USA. EM cmacrae@partners.org FU NHLBI NIH HHS [K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 117 TC 28 Z9 29 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG 15 PY 2005 VL 67 IS 3 BP 426 EP 437 DI 10.1016/j.cardiores.2005.06.012 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 952WQ UT WOS:000231037000010 PM 16009355 ER PT J AU Sequist, LV Haber, DA Lynch, TJ AF Sequist, LV Haber, DA Lynch, TJ TI Epidermal growth factor receptor mutations in non-small cell lung cancer: Predicting clinical response to kinase inhibitors SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PHASE-III TRIAL; INTRON-1 POLYMORPHISM; ACTIVATING MUTATIONS; RANDOMIZED-TRIAL; TYROSINE KINASE; EGFR MUTATIONS; NEVER-SMOKERS; GEFITINIB; ADENOCARCINOMAS; RESISTANCE C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY7,Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu NR 29 TC 18 Z9 20 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 AUG 15 PY 2005 VL 11 IS 16 BP 5668 EP 5670 DI 10.1158/1078-0432.CCR-05-1055 PG 3 WC Oncology SC Oncology GA 956SL UT WOS:000231320000004 PM 16115901 ER PT J AU Jones, J Otu, H Spentzos, D Kolia, S Inan, M Beecken, WD Fellbaum, C Gu, XS Joseph, M Pantuck, AJ Jonas, D Libermann, TA AF Jones, J Otu, H Spentzos, D Kolia, S Inan, M Beecken, WD Fellbaum, C Gu, XS Joseph, M Pantuck, AJ Jonas, D Libermann, TA TI Gene signatures of progression and metastasis in renal cell cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MESSENGER-RNA EXPRESSION; MOLECULAR SIGNATURE; CARCINOMA; TUMORS; GROWTH; SURVIVAL; IDENTIFICATION; NEPHRECTOMY; DISCOVERY; STAGE AB Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC. C1 Beth Israel Deaconess Med Ctr, Genom Ctr, Bioinformat Core, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr Proteom Core, Boston, MA USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Univ Frankfurt, Dept Urol & Pediat Urol, D-6000 Frankfurt, Germany. Univ Frankfurt, Inst Pathol, D-6000 Frankfurt, Germany. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Urol, Kidney Canc Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Libermann, TA (reprint author), Beth Israel Deaconess Med Ctr, Genom Ctr, Bioinformat Core, 4 Blackfan Circle, Boston, MA 02115 USA. EM tliberma@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NCI NIH HHS [1R01CA85467, P50 CA090381, P50 CA101942] NR 56 TC 184 Z9 189 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2005 VL 11 IS 16 BP 5730 EP 5739 DI 10.1158/1078-0432.CCR-04-2225 PG 10 WC Oncology SC Oncology GA 956SL UT WOS:000231320000013 PM 16115910 ER PT J AU Yamanaka, K Yawalkar, N Jones, DA Hurwitz, D Ferenczi, K Eapen, S Kupper, TS AF Yamanaka, K Yawalkar, N Jones, DA Hurwitz, D Ferenczi, K Eapen, S Kupper, TS TI Decreased T-cell receptor excision circles in cutaneous T-cell lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RECENT THYMIC EMIGRANTS; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MARROW-TRANSPLANTATION; STAPHYLOCOCCUS-AUREUS; MYCOSIS-FUNGOIDES; PERIPHERAL-BLOOD; HIV-INFECTION; REPERTOIRE; INDIVIDUALS; DIVERSITY AB Purpose: The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naive T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naive T cells relative to T cells that have undergone expansion. Experimental Design: We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells. Results: We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells. Conclusions: We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity. C1 Harvard Univ, Inst Med, Brigham & Womens Hosp, Dept Dermatol,Skin Dis Res Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Dana Farber Harvard Canc Ctr, Biostat Core Facil, Boston, MA 02115 USA. RP Kupper, TS (reprint author), Harvard Univ, Inst Med, Brigham & Womens Hosp, Dept Dermatol,Skin Dis Res Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tskupper@rics.bwh.harvard.edu NR 34 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2005 VL 11 IS 16 BP 5748 EP 5755 DI 10.1158/1078-0432.CCR-04-2514 PG 8 WC Oncology SC Oncology GA 956SL UT WOS:000231320000015 PM 16115912 ER PT J AU Weihrauch, MR Ansen, S Jurkiewicz, E Geisen, C Xia, ZN Anderson, KS Gracien, E Schmidt, M Wittig, B Diehl, V Wolf, J Bohlen, H Nadler, LM AF Weihrauch, MR Ansen, S Jurkiewicz, E Geisen, C Xia, ZN Anderson, KS Gracien, E Schmidt, M Wittig, B Diehl, V Wolf, J Bohlen, H Nadler, LM TI Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; FLUOROURACIL PLUS LEUCOVORIN; CPG OLIGONUCLEOTIDES ENHANCE; T-CELL RESPONSES; IMMUNE-RESPONSE; DENDRITIC CELLS; TUMOR-CELLS; VACCINE; ADJUVANT; CARCINOMA AB Purpose: We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen - derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. Experimental Design: HLA-A2 - positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, humanT-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity. Results: Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1 - specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1 - specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen - specific CD8+ cells decreased by an average 14%. Conclusions: The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Med Expt, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Univ Cologne, Dept Internal Med 1, D-5000 Cologne, Germany. Axiogenesis GmbH, Cologne, Germany. Mologen AG, Berlin, Germany. Charite Univ Med Berlin, Ctr Biochem & Biophys, Inst Mol Biol & Bioinformat, Berlin, Germany. Aventis Pharma Deutschland GmbH, Bad Soden, Germany. RP Weihrauch, MR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Med Expt, Room D542,44 Binney St, Boston, MA 02115 USA. EM martin.weihrauch@uni-koeln.de NR 36 TC 41 Z9 44 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2005 VL 11 IS 16 BP 5993 EP 6001 DI 10.1158/1078-0432.CCR-05-0018 PG 9 WC Oncology SC Oncology GA 956SL UT WOS:000231320000047 PM 16115944 ER PT J AU Bhasin, M Zhang, H Reinherz, EL Reche, PA AF Bhasin, M Zhang, H Reinherz, EL Reche, PA TI Prediction of methylated CpGs in DNA sequences using a support vector machine SO FEBS LETTERS LA English DT Article DE DNA; CpG; methylation; support vector machine; prediction ID MAMMALIAN DEVELOPMENT; ISLAND METHYLATION; BINDING; CANCER; PROMOTER; HYPOMETHYLATION; TRANSCRIPTION; TUMORS AB DNA methylation plays a key role in the regulation of gene expression. The most common type of DNA modification consists of the methylation of cytosine in the CpG dinucleotide. At the present time, there is no method available for the prediction of DNA methylation sites. Therefore, in this study we have developed a support vector machine (SVM)-based method for the prediction of cytosine methylation in CpG dinucleotides. Initially a SVM module was developed from human data for the prediction of human-specific methylation sites. This module achieved a MCC and AUC of 0.501 and 0.814, respectively, when evaluated using a 5-fold cross-validation. The performance of this SVM-based module was better than the classifiers built using alternative machine learning and statistical algorithms including artificial neural networks, Bayesian statistics, and decision trees. Additional SVM modules were also developed based on mammalian- and vertebrate-specific methylation patterns. The SVM module based on human methylation patterns was used for genome-wide analysis of methylation sites. This analysis demonstrated that the percentage of methylated CpGs is higher in UTRs as compared to exonic and intronic regions of human genes. This method is available on line for public use under the name of Methylator at http://bio.dfci.harvard.edu/Methylator/. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reche, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM reche@research.dfci.harvard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI57330] NR 41 TC 49 Z9 53 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 15 PY 2005 VL 579 IS 20 BP 4302 EP 4308 DI 10.1016/j.febslet.2005.07.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 957DX UT WOS:000231350900017 PM 16051225 ER PT J AU Potolicchio, A Carven, GJ Xu, XN Stipp, C Riese, RJ Stern, LJ Santambrogio, L AF Potolicchio, A Carven, GJ Xu, XN Stipp, C Riese, RJ Stern, LJ Santambrogio, L TI Proteomic analysis of microglia-derived exosomes: Metabolic role of the aminopeptidase CD13 in neuropeptide catabolism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; ANTIGEN PRESENTATION; INVARIANT CHAIN; B-LYMPHOCYTES; SYNTAXIN 8; RAT-BRAIN; PROTEIN; CELLS; COMPARTMENT; VESICLES AB Vesicle transport is a fundamental mechanism of communication in the CNS. In this study we characterized a novel type of vesicle released by murine brain microglial cells: microglial exosomes. Analysis of their protein content identified several enzymes, chaperones, tetraspanins, and membrane receptors previously reported in B cells and dendritic cell-derived exosomes. Additionally, microglia-derived exosomes expressed the aminopeptidase CD13 and the lactate transporter MCT-1. Exosomal CD13 was metabolically active in cleaving leucine- and methionine-enkephalins peptides by releasing the N-terminal tyrosine. Cleaved neuropeptides were unable to bind to the neuronal opioid receptor as assessed by cAMP response. Microglial exosomal vesicles may represent an important, previously unrecognized, cellular communication system in an organ in which cell motility is highly restricted. C1 Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Albert Einstein Coll Med, Dept Pathol, Forchheimer 538,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM lsantamb@aecom.yu.edu FU NCI NIH HHS [CA86712]; NIAID NIH HHS [K08AI01555, R01AI048832, R01AI38996] NR 37 TC 75 Z9 79 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2005 VL 175 IS 4 BP 2237 EP 2243 PG 7 WC Immunology SC Immunology GA 966HJ UT WOS:000232010400028 PM 16081791 ER PT J AU Gandhi, RT Altfeld, M AF Gandhi, RT Altfeld, M TI The quest for an HIV-1 therapeutic vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; TYPE-1 INFECTION; VIRAL DIVERSITY; SUBTYPE-E; CD8(+); CD4(+); VIREMIA C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,AIDS Res 5214, Charlestown, MA 02129 USA. EM maltfeld@partners.org NR 32 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2005 VL 192 IS 4 BP 556 EP 559 DI 10.1086/432014 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952QB UT WOS:000231019500002 PM 16028123 ER PT J AU Woodberry, T Suscovich, TJ Henry, LM Martin, JN Dollard, S O'Connor, PG Davis, JK Osmond, D Lee, TH Kedes, DH Khatri, A Lee, J Walker, BD Scadden, DT Brander, C AF Woodberry, T Suscovich, TJ Henry, LM Martin, JN Dollard, S O'Connor, PG Davis, JK Osmond, D Lee, TH Kedes, DH Khatri, A Lee, J Walker, BD Scadden, DT Brander, C TI Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHVORF73 and ORF65 proteins SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International AIDS Malignancy Conference CY APR, 2003 CL Bethesda, MD ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-HERPESVIRUS-8 INFECTION; VIRAL LOAD; LYMPHOCYTE EPITOPES; SEXUAL TRANSMISSION; IMMUNE-RESPONSES; SEROLOGIC ASSAYS; DNA-SEQUENCES; IDENTIFICATION AB Cellular immune responses to Kaposi sarcoma-associated herpesvirus ( KSHV), the etiological agent of KS and several other malignancies, are incompletely characterized. We assessed KSHV-specific interferon-gamma enzyme-linked immunospot responses in a cohort of 154 individuals, using overlapping peptide sets spanning the KSHV-encoded latency-associated nuclear antigen (ORF73) and the minor capsid glycoprotein (ORF65). Among KSHV-seropositive subjects, ORF73-specific responses dominated over responses to ORF65 and were preferentially detected in human immunodeficiency virus-coinfected individuals who had elevated levels of cell-associated KSHV DNA, indicating that the viral antigen burden may have been driving these responses. Responses to both ORF73 and ORF65 were also detected in several KSHV-seronegative subjects who were at increased risk for KSHV infection, which demonstrates that cellular immunity can be found in the absence of detectable humoral responses. These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Endocrine Unit, Charlestown, MA 02129 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Blood Syst Res Inst, San Francisco, CA USA. Univ Virginia, Myles H Thaler Ctr AIDS Res, Hlth Syst, Dept Microbiol, Charlottesville, VA USA. Univ Virginia, Myles H Thaler Ctr AIDS Res, Hlth Syst, Dept Med, Charlottesville, VA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Alabama, AIDS Malignancy Consortium, Birmingham, AL USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 5th Fl,5239,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org FU NCI NIH HHS [CA73580, CA71375, U01 CA78124]; NIAID NIH HHS [P30 AI27763]; NIDCR NIH HHS [P01 DEO1438-01]; NIMH NIH HHS [P30 MH62246] NR 45 TC 23 Z9 23 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2005 VL 192 IS 4 BP 622 EP 629 DI 10.1086/432103 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952QB UT WOS:000231019500010 PM 16028131 ER PT J AU Dunn, AK Devor, A Dale, AM Boas, DA AF Dunn, AK Devor, A Dale, AM Boas, DA TI Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex SO NEUROIMAGE LA English DT Article DE hemodynamic changes; hemoglobin; oxygen metabolism ID CEREBRAL-BLOOD-FLOW; CONSUMPTION FOLLOWING ACTIVATION; LASER-SPECKLE FLOWMETRY; RODENT BARREL CORTEX; NEURAL ACTIVITY; NEURONAL-ACTIVITY; VISUAL-CORTEX; HEMOGLOBIN CONCENTRATION; SPECTROSCOPIC ANALYSIS; OXIDATIVE-METABOLISM AB The spatial extent of the changes in oxy-hemoglobin (HbO), deoxyhemoglobin (HbR), total hemoglobin concentration (HbT), cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen (CMRO2) in response to forepaw and whisker stimulation were compared in the rat somatosensory cortex using a combination of multi-wavelength reflectance imaging and laser speckle contrast imaging of cerebral blood flow. The spatial extents of the response of each hemodynamic parameter and CMRO2 were found to be comparable at the time of peak response, and at early times following stimulation onset, the spatial extent of the change in HbR was smaller than that of HbO, HbT, CBF, and CMR02- In addition, a slight spatial dependence was found in the power law coefficient relating changes in CBF and HbT. Although the CMRO2 response is a metabolic measure and thus expected to have a more localized response than the hemodynamic parameters, the results presented here suggest that this may not be the case in general, possibly due to the increased sensitivity of optical imaging techniques to superficial cortical layers where the lateral extent of the metabolic and neuronal activation is larger compared to that in layer IV. In addition, we found that the measured spatial extent of the CMRO2 changes was insensitive to assumptions made in the calculation of the CMRO2 changes such as baseline hemoglobin concentrations, vascular weighting constants, and wavelength dependence of tissue scattering. Multi-parameter full field imaging of the functional response provides a more complete picture of the hemodynamic response to functional activation including the spatial and temporal estimation of CMRO2 changes. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Dunn, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM adunn@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Dunn, Andrew/I-9527-2014 FU NIBIB NIH HHS [R01 EB000790] NR 59 TC 159 Z9 159 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2005 VL 27 IS 2 BP 279 EP 290 DI 10.1016/j.neuroimage.2005.04.024 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 954KV UT WOS:000231154900003 PM 15925522 ER PT J AU Pekkonen, E Jaaskelainen, IP Kaakkola, S Ahveninen, J AF Pekkonen, E Jaaskelainen, IP Kaakkola, S Ahveninen, J TI Cholinergic modulation of preattentive auditory processing in aging SO NEUROIMAGE LA English DT Article DE acetylcholine; scopolamine; aging; Alzheimer's disease; event-related potentials; mismatch negativity; electroencephalography (EEG); magnetoencephalography (MEG) ID ALZHEIMERS-DISEASE; MISMATCH NEGATIVITY; EVOKED-RESPONSES; SENSORY MEMORY; SCOPOLAMINE; BRAIN; AGE; HYPERSENSITIVITY; POTENTIALS; TASK AB Auditory event-related potential (ERP) components P50 and N100 are thought to index preattentive auditory processing underlying stimulus detection, whereas a subsequent component termed mismatch negativity (MMN) has been proposed to reflect comparison of incoming stimuli to a short-lived sensory memory trace of preceding sounds. Existing evidence suggests impairment of preattentive auditory processing in aging, which appears to be accompanied by decline of cholinergic activity. Previous studies indicate that scopolamine, which is a centrally acting muscarinic receptor antagonist, modulates preattentive auditory processing in young subjects. It has remained elusive, however, to which extent scopolamine affects preattentive auditory processing in aged subjects. We measured auditory responses simultaneously with electroencephalogram (EEG) and magnetoencephalogram (MEG) from nine non-demented elderly subjects after intravenous injection of scopolamine or glycopyrrolate, the latter being a peripherally acting cholinergic antagonist, using a double blind protocol. Scopolamine significantly delayed electric P50, both electric and magnetic N100 responses, whereas subsequent MMN and P200 responses were not altered by scopolamine. Our results indicate that the cholinergic system modulates auditory processing underlying stimulus detection in aging. In addition, auditory evoked responses appear to have different age-related sensitivity to cholinergic modulation. The combined MEG/EEG measurements using particularly auditory N100 response might offer an objective tool to monitor cholinergic activity in aging and Alzheimer's disease (AD). (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Helsinki, Dept Neurol, FIN-00029 Helsinki, Finland. Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, SF-00100 Helsinki, Finland. Univ Helsinki, Cent Hosp, Med Engn Ctr, BioMag Lab, Helsinki, Finland. Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Pekkonen, E (reprint author), Univ Helsinki, Dept Neurol, POB 340, FIN-00029 Helsinki, Finland. EM eero.pekkonen@hus.fi RI Jaaskelainen, Iiro/C-7392-2012; OI Jaaskelainen, Iiro/0000-0001-6001-6950; Pekkonen, Eero/0000-0003-1621-8752 NR 33 TC 36 Z9 38 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2005 VL 27 IS 2 BP 387 EP 392 DI 10.1016/j.neuroimage.2005.04.018 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 954KV UT WOS:000231154900012 PM 15921933 ER PT J AU Joo, C Akkin, T Cense, B Park, BH de Boer, JE AF Joo, C Akkin, T Cense, B Park, BH de Boer, JE TI Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging SO OPTICS LETTERS LA English DT Article ID TOMOGRAPHY AB We describe a novel microscopy technique for quantitative phase-contrast imaging of a transparent specimen. The technique is based on depth-resolved phase information provided by common path spectral-domain optical coherence tomography and can measure minute phase variations caused by changes in refractive index and thickness inside the specimen. We demonstrate subnanometer level path-length sensitivity and present images obtained on reflection from a known phase object and human epithelial cheek cells. (c) 2005 Optical Society of America. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM cmjoo@mit.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976 FU NCRR NIH HHS [R01 RR19768] NR 15 TC 159 Z9 161 U1 1 U2 15 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD AUG 15 PY 2005 VL 30 IS 16 BP 2131 EP 2133 DI 10.1364/OL.30.002131 PG 3 WC Optics SC Optics GA 953JO UT WOS:000231072700027 PM 16127933 ER PT J AU Beaubien, BP Derincek, A Lew, WD Wood, KB AF Beaubien, BP Derincek, A Lew, WD Wood, KB TI In vitro, biomechanical comparison of an anterior lumbar interbody fusion with an anteriorly placed, low-profile lumbar plate and posteriorly placed pedicle screws or translaminar screws SO SPINE LA English DT Article DE anterior lumbar interbody fusion; anterior lumbar plate; pedicle screws; translaminar screws ID FIXATION; COMPLICATIONS; SPINE; SPONDYLOLISTHESIS; SYSTEM; INSTRUMENTATION; INSTABILITY; PAIN AB Study Design. An in vitro biomechanical comparison of anteriorly placed lumbar plates, pedicle screws, and translaminar screws in the anterior lumbar interbody fusion ( ALIF) setting. Objectives. To determine whether an anteriorly placed lumbar plate reduces the flexibility in terms of neutral zone and range of motion of a simulated ALIF, and to compare this reduction in flexibility to that provided by posteriorly placed pedicle screws and translaminar screws. Summary of Background Data. Pedicular and translaminar facet fixation add stability and increase fusion rates, compared with ALIF alone. An anteriorly placed lumbar plate has been introduced to provide stability without the need for a secondary approach. However, this plate has not been evaluated biomechanically. Methods. Seven intact, cadaveric lumbar motion segments were tested to +/- 7.5 Nm in flexion-extension, lateral bending, and axial torsion. Specimens were retested after ALIF, and after subsequent instrumentation with pedicle screws, translaminar screws, and anterior lumbar plates. The range of motion and neutral zone were measured from resulting flexibility curves. Results. Mean ( +/- standard deviation) flexion-extension range of motion for intact segments ( 9.9 degrees +/- 3.1 degrees) was significantly reduced to 7.7 degrees +/- 1.8 degrees after ALIF ( P = 0.02), and was further reduced to 3.0 +/- 0.9 with lumbar plates ( P < 0.001), 1.5 degrees +/- 0.6 degrees with pedicle screws ( P < 0.001), and 0.9 degrees +/- 0.4 degrees with translaminar screws ( P < 0.001). All 3 devices also reduced flexion-extension neutral zone and torsion neutral zone and range of motion, compared with ALIF alone ( P < 0.05). Lumbar plates did not decrease lateral bending range of motion or neutral zone ( P > 0.05), whereas pedicle and translaminar screws did ( P < 0.05). Conclusions. Although not as rigid as pedicle or translaminar screws, anterior lumbar plating does add significant stability to an ALIF and may provide a valuable, single-approach alternative to supplemental posterior fixation. C1 Minneapolis Med Res Fdn Inc, Orthopaed Biomech Lab, Minneapolis, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Beaubien, BP (reprint author), 914 S 8th St,Mail Code 860C, Minneapolis, MN 55414 USA. EM bbeaubien@mmrf.org NR 34 TC 40 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD AUG 15 PY 2005 VL 30 IS 16 BP 1846 EP 1851 DI 10.1097/01.brs.0000174275.95104.12 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 956JW UT WOS:000231297000008 PM 16103854 ER PT J AU Cole, BF Bonetti, M Zaslavsky, AM Gelber, RD AF Cole, BF Bonetti, M Zaslavsky, AM Gelber, RD TI A multistate Markov chain model for longitudinal, categorical quality-of-life data subject to non-ignorable missingness SO STATISTICS IN MEDICINE LA English DT Article DE generalized logit model; incomplete data; informative missing data; logistic regression; proportional odds model; repeated measurements ID LOGISTIC-REGRESSION MODELS; NONIGNORABLE NONRESPONSE; BREAST-CANCER; RESPONSE DATA; DROP-OUT AB Quality-of-life (QOL) is an important outcome in clinical research, particularly in cancer clinical trials. Typically, data are collected longitudinally from patients during treatment and subsequent follow-up. Missing data are a common problem, and missingness may arise in a non-ignorable fashion. In particular, the probability that a patient misses an assessment may depend on the patient's QOL at the time of the scheduled assessment. We propose a Markov chain model for the analysis of categorical outcomes derived from QOL measures. Our model assumes that transitions between QOL states depend on covariates through generalized logit models or proportional odds models. To account for non-ignorable missingness, we incorporate logistic regression models for the conditional probabilities of observing measurements, given their actual values. The model can accommodate time-dependent covariates. Estimation is by maximum likelihood, summing over all possible values of the missing measurements. We describe options for selecting parsimonious models, and we study the finite-sample properties of the estimators by simulation. We apply the techniques to data from a breast cancer clinical trial in which QOL assessments were made longitudinally, and in which missing data frequently arose. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Dartmouth Coll Sch Med, Dept Community & Family Med, Epidemiol & Biostat Sect, Lebanon, NH 03756 USA. Univ Bocconi, Ist Metodi Quantitativi, Milan, Italy. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cole, BF (reprint author), Dartmouth Coll Sch Med, Dept Community & Family Med, Dartmouth Hitchcock Med Ctr, 7927 Rubin Bldg, Lebanon, NH 03756 USA. EM bernard.cole@dartmouth.edu OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA-06516, CA-75362]; NIAID NIH HHS [1 R01 AI51164] NR 21 TC 8 Z9 9 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 15 PY 2005 VL 24 IS 15 BP 2317 EP 2334 DI 10.1002/sim.2122 PG 18 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 952AY UT WOS:000230974900004 PM 15977292 ER PT J AU Wong, WC Venetz, JP Tolkoff-Rubin, N Pascual, M AF Wong, WC Venetz, JP Tolkoff-Rubin, N Pascual, M TI 2005 immunosuppressive strategies in kidney transplantation: Which role for the calcineurin inhibitors? SO TRANSPLANTATION LA English DT Editorial Material DE calcineurin inhibitors; cyclosporine; tacrolimus; kidney transplantation; immunosuppression ID CHRONIC ALLOGRAFT NEPHROPATHY; CARDIOVASCULAR RISK PROFILE; EARLY CYCLOSPORINE WITHDRAWAL; IMPROVED RENAL-FUNCTION; MYCOPHENOLATE-MOFETIL; PROTOCOL BIOPSIES; CHRONIC REJECTION; RANDOMIZED-TRIAL; INDIRECT ALLORECOGNITION; ANTITHYMOCYTE GLOBULIN AB The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus have been the cornerstones of immunosuppressive strategies in clinical transplantation. Currently, regimens that are most widely used for induction and maintenance therapy include CNIs. However, many clinical trials aiming at reducing or eliminating CNIs have been performed in recent years. Here, we review and discuss current and future immunosuppressive strategies with a special emphasis on the role of CNIs, in the light of recent studies in the field of kidney transplantation. In the current era, CNIs still play an important role. C1 CHU Vaudois, Transplantat Ctr, CH-1011 Lausanne, Switzerland. Fac Biol & Med, Lausanne, Switzerland. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pascual, M (reprint author), CHU Vaudois, Transplantat Ctr, BH 10-226, CH-1011 Lausanne, Switzerland. EM mpascual@hospvd.ch NR 69 TC 27 Z9 29 U1 1 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 AUG 15 PY 2005 VL 80 IS 3 BP 289 EP 296 DI 10.1097/01.tp.0000168436.76784.45 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 952UA UT WOS:000231029800001 PM 16082321 ER PT J AU Falutz, J Allas, S Kotler, D Thompson, M Koutkia, P Albu, J Trottier, B Routy, JP Cote, P Abribat, T Grinspoon, S AF Falutz, J Allas, S Kotler, D Thompson, M Koutkia, P Albu, J Trottier, B Routy, JP Cote, P Abribat, T Grinspoon, S TI A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation SO AIDS LA English DT Article DE HIV; growth hormone releasing hormone; abdominal fat accumulation; lipodystrophy ID VISCERAL ADIPOSE-TISSUE; RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; BODY-COMPOSITION; DISEASE RISK; LIPODYSTROPHY; MEN; GLUCOSE; INSULIN; REDISTRIBUTION AB Objective: To investigate the effects of TH9507, a novel growth hormone releasing factor, on abdominal fat accumulation, metabolic and safety parameters in HIV-infected patients with central fat accumulation. Design and methods: Randomized, double-blind, placebo-controlled trial enrolling 61 HIV-infected patients with increased waist circumference and waist-to-hip ratio. Participants were randomized to placebo or 1 or 2 mg TH9507 subcutaneously, once daily for 12 weeks. The primary outcome was change in abdominal fat, assessed by dual energy X-ray absorptiometry and cross-sectional computerized tomography scan. Secondary endpoints included change in insulin-like growth factor-l (IGF-l), metabolic, quality of life, and safety parameters. Results: TH9507 resulted in dose-related physiological increases in IGF-l (P < 0.01 for 1 mg (+48%) and 2 mg (+65%) versus placebo). Trunk fat decreased in the 2 mg group versus placebo (0.8, -4.6 and -9.2%; placebo, 1 and 2 mg, respectively, P = 0.014 for 2 mg versus placebo), without significant change in limb fat. Visceral fat (VAT) decreased most in the 2 mg group (-5.4, -3.6 and -15.7%; placebo, 1 and 2 mg, respectively) but this change was not significant versus placebo. Subcutaneous fat (SAT) was preserved and did not change between or within groups. Lean body mass and the ratio of VAT to SAT improved significantly in both treatment groups versus placebo. Triglyceride and the cholesterol to high-density lipoprotein ratio decreased significantly in the 2 mg group versus placebo. Treatment was generally well tolerated without changes in glucose. Conclusions: TH9507 reduced truncal fat, improved the lipid profile and did not increase glucose levels in HIV-infected patients with central fat accumulation. TH9507 may be a beneficial treatment strategy in this population, but longer-term studies with more patients are needed to determine effects on VAT, treatment durability, and safety. (c) 2005 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Clin Med Actuel, Montreal, PQ, Canada. Clin Med Quartier Latin, Montreal, PQ, Canada. Royal Victoria Hosp, Div Hematol, Montreal, PQ, Canada. Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ, Canada. Theratechnologies, St Laurent, PQ, Canada. ARCA, Atlanta, GA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. St Lukes Roosevelt Hosp, Div Gastroenterol, New York, NY 10025 USA. St Lukes Roosevelt Hosp, Div Endocrinol, New York, NY 10025 USA. McGill Univ, Ctr Hlth, Montreal Gen Hosp, Immunodeficiency Treatment Ctr, Montreal, PQ, Canada. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON207,Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 31 TC 49 Z9 50 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 12 PY 2005 VL 19 IS 12 BP 1279 EP 1287 DI 10.1097/01.aids.0000180099.35146.30 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 956RF UT WOS:000231316800006 PM 16052083 ER PT J AU Yazdanpanah, Y Losina, E Anglaret, X Goldie, SJ Walensky, RP Weinstein, MC Toure, S Smith, HE Kaplan, JE Freedberg, KA AF Yazdanpanah, Y Losina, E Anglaret, X Goldie, SJ Walensky, RP Weinstein, MC Toure, S Smith, HE Kaplan, JE Freedberg, KA CA Global AIDS Policy Model Invest TI Clinical impact and cost-effectiveness of co-trimoxazole prophylaxis in patients with HIVAIDS in Cote d'Ivoire: a trial-based analysis SO AIDS LA English DT Article DE HIV/AIDS; co-trimoxazole prophylaxis; cost-effectiveness; sub-Saharan Africa ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUB-SAHARAN AFRICA; TRIMETHOPRIM-SULFAMETHOXAZOLE PROPHYLAXIS; OPPORTUNISTIC INFECTIONS; STREPTOCOCCUS-PNEUMONIAE; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED ADULTS; BACTERIAL DISEASES; HIV-INFECTION; SOUTH-AFRICA AB Background: In 2000, WHO/UNAIDS recommended co-trimoxazole prophylaxis for persons at early stages of HIV infection (WHO stage > 2) in sub-Saharan Africa. Objective: To assess the cost-effectiveness of alternative strategies for initiation of cotrimoxazole in Cote d'lvoire. Design: Cost-effectiveness analysis with an HIV simulation model using clinical and cost data from a randomized trial of co-trimoxazole in HIV-infected adults. Methods: The study included HIV-infected patients in Cote d'lvoire, with median age 33 years. Thirty-four percent were classified as WHO stage 2, 59% as stage 3, and 7% as stage 4. The mean CD4 cell count was 331 X 10(6) cells/l. The interventions were no prophylaxis, clinical criteria-based co-trimoxazole initiation (early: WHO stage > 2; late: WHO stage >= 3), CD4-based co-trimoxazole initiation (< 500, < 200, < 50 x 10(6) CD4 cells/l). The outcome measures were life expectancy, lifetime costs, and incremental cost-effectiveness. Results: The most effective strategy, initiation of co-trimoxazole prophylaxis at WHO stage > 2, increased undiscounted life expectancy by 5.2 months, discounted life expectancy by 4.4 months, and lifetime costs by US$ 60, compared with no prophylaxis. Delaying prophylaxis initiation until WHO stage > 3 was. less costly and less effective. All CD4-based strategies were dominated. The incremental cost-effectiveness of early versus late co-trimoxazole prophylaxis initiation was US$ 200/year of life gained. Results were stable despite wide variations in plausible assumptions about bacterial resistance and the prophylaxis efficacy on co-trimoxazole-resistant strains. Conclusions: For HIV-infected adults in Cote d'lvoire, co-trimoxazole prophylaxis is reasonably cost-effective and most effective if initiated when WHO stage >= 2. Early co-trimoxazole prophylaxis will prevent complications prior to antiretroviral therapy initiation and should be considered an essential component of care for early HIV in sub-Saharan Africa. (c) 2005 Lippincott Williams & Wilkins. C1 Ctr Hosp Tourcoing, Fac Med Lille, Serv Univ Malad Infect & Voyageur, F-59208 Tourcoing, France. CNRS, URA 362, Lab Rech Econ & Sociales, Lille, France. Boston Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. INSERM U593, Bordeaux, France. Programme PAC CI, Abidjan, Cote Ivoire. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Yazdanpanah, Y (reprint author), Ctr Hosp Tourcoing, Fac Med Lille, Serv Univ Malad Infect & Voyageur, 135 Rue President Coty,BP 619, F-59208 Tourcoing, France. EM yyazdan@yahoo.com RI Anglaret, Xavier/F-7333-2013 FU NIAID NIH HHS [K23 AI001794, AI058736, K23 AI0794, K24 AI062476, K25 AI050436, K25 AI50436, P30 AI042851, P30 AI42851, R01 AI058736]; ODCDC CDC HHS [U64/CCU 114927, U64/CCU 119525] NR 42 TC 54 Z9 55 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 12 PY 2005 VL 19 IS 12 BP 1299 EP 1308 DI 10.1097/01.aids.0000180101.80888.c6 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 956RF UT WOS:000231316800008 PM 16052085 ER PT J AU Gunton, JE Kulkarni, RN Yim, SH Okada, T Hawthorne, WJ Tseng, YH Roberson, RS Ricordi, C O'Connell, PJ Gonzalez, FJ Kahn, CR AF Gunton, JE Kulkarni, RN Yim, SH Okada, T Hawthorne, WJ Tseng, YH Roberson, RS Ricordi, C O'Connell, PJ Gonzalez, FJ Kahn, CR TI Loss of ARNT/HIF1 beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes SO CELL LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; INSULIN-RESISTANCE; BETA-CELLS; SKELETAL-MUSCLE; MICE LACKING; MELLITUS; TRANSCRIPTION; PATHOGENESIS; HYPOXIA; GLUCOSE AB beta cell dysfunction is a central component of the pathogenesis of type 2 diabetes. Using oligonucleotide microarrays and real-time PCR of pancreatic islets isolated from humans with type 2 diabetes versus normal glucose-tolerant controls, we identified multiple changes in expression of genes known to be important in beta cell function, including major decreases in expression of HNF4 alpha, insulin receptor, IRS2, Akt2, and several glucose-metabolic-pathway genes. There was also a 90% decrease in expression of the transcription factor ARNT Reducing ARNT levels in Min6 cells with small interfering RNA (siRNA) resulted in markedly impaired glucose-stimulated insulin release and changes in gene expression similar to those in human type 2 islets. Likewise, beta cell-specific ARNT knockout mice exhibited abnormal glucose tolerance, impaired insulin secretion, and changes in islet gene expression that mimicked those in human diabetic islets. Together, these data suggest an important role for decreased ARNT and altered gene expression in the impaired islet function of human type 2 diabetes. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Univ Sydney, Westmead Hosp, Natl Pancreas Transplant Unit, Sydney, NSW 2145, Australia. Univ Miami, Diabet Res Inst, Miami, FL 33136 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Ricordi, Camillo/0000-0001-8092-7153 FU NCRR NIH HHS [RR16603]; NIDDK NIH HHS [DK60837-02, K08 DK02885, R01 DK33201, R01 DK67536] NR 56 TC 280 Z9 284 U1 4 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 12 PY 2005 VL 122 IS 3 BP 337 EP 349 DI 10.1016/j.cell.2005.05.027 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 955UZ UT WOS:000231254400007 PM 16096055 ER PT J AU Strissel, KJ Lishko, PV Trieu, LH Kennedy, MJ Hurley, JB Arshavsky, VY AF Strissel, KJ Lishko, PV Trieu, LH Kennedy, MJ Hurley, JB Arshavsky, VY TI Recoverin undergoes light-dependent intracellular translocation in rod photoreceptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLASE-ACTIVATING PROTEINS; GUANYLATE-CYCLASE; MOUSE RETINA; RHODOPSIN PHOSPHORYLATION; SIGNAL-TRANSDUCTION; ELECTRON-MICROSCOPY; MAMMALIAN RETINAS; MYRISTOYL SWITCH; RAT RETINA; ADAPTATION AB Photoreceptor cells have a remarkable capacity to adapt the sensitivity and speed of their responses to ever changing conditions of ambient illumination. Recent studies have revealed that a major contributor to this adaptation is the phenomenon of light-driven translocation of key signaling proteins into and out of the photoreceptor outer segment, the cellular compartment where phototransduction takes place. So far, only two such proteins, transducin and arrestin, have been established to be involved in this mechanism. To investigate the extent of this phenomenon we examined additional photoreceptor proteins that might undergo light-driven translocation, focusing on three Ca2+-binding proteins, recoverin and guanylate cyclase activating proteins 1 (GCAP1) and GCAP2. The changes in the subcellular distribution of each protein were assessed quantitatively using a recently developed technique combining serial tangential sectioning of mouse retinas with Western blot analysis of the proteins in the individual sections. Our major finding is that light causes a significant reduction of recoverin in rod outer segments, accompanied by its redistribution toward rod synaptic terminals. In both cases the majority of recoverin was found in rod inner segments, with similar to 12% present in the outer segments in the dark and less than 2% remaining in that compartment in the light. We suggest that recoverin translocation is adaptive because it may reduce the inhibitory constraint that recoverin imposes on rhodopsin kinase, an enzyme responsible for quenching the photoexcited rhodopsin during the photoresponse. To the contrary, no translocation of rhodopsin kinase itself or either GCAP was identified. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Arshavsky, VY (reprint author), Duke Univ, Med Ctr, Dept Ophthalmol, 5008 AERI,Erwin Rd, Durham, NC 27710 USA. EM vadim.arshavsky@duke.edu FU NEI NIH HHS [EY06641, EY10336, EY14104] NR 56 TC 59 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 2005 VL 280 IS 32 BP 29250 EP 29255 DI 10.1074/jbc.M501789200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 952QT UT WOS:000231021300054 PM 15961391 ER PT J AU Hong, JH Hwang, ES McManus, MT Amsterdam, A Tian, Y Kalmukova, R Mueller, E Benjamin, T Spiegelman, BM Sharp, PA Hopkins, N Yaffe, MB AF Hong, JH Hwang, ES McManus, MT Amsterdam, A Tian, Y Kalmukova, R Mueller, E Benjamin, T Spiegelman, BM Sharp, PA Hopkins, N Yaffe, MB TI TAZ, a transcriptional modulator of mesenchymal stem cell differentiation SO SCIENCE LA English DT Article ID MARROW STROMAL CELLS; OSTEOBLAST DIFFERENTIATION; BONE-MARROW; PPAR-GAMMA; ADIPOSE-TISSUE; ADIPOGENESIS; OSTEOPOROSIS; CBFA1; COACTIVATOR; PATHWAY AB Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPAR gamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription white repressing PPAR gamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation. C1 MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Yaffe, MB (reprint author), MIT, Ctr Canc Res, Dept Biol, 77 Massachusetts Ave,E18-580, Cambridge, MA 02139 USA. EM myaffe@mit.edu FU NCI NIH HHS [CA042063]; NIGMS NIH HHS [GM60594, GM68762] NR 28 TC 475 Z9 506 U1 10 U2 62 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 12 PY 2005 VL 309 IS 5737 BP 1074 EP 1078 DI 10.1126/science.1110955 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955MN UT WOS:000231230100046 PM 16099986 ER PT J AU de Souza, NJ Gupte, SV Deshpande, PK Desai, VN Bhawsar, SB Yeole, RD Shukla, MC Strahilevitz, J Hooper, DC Bozdogan, B Appelbaum, PC Jacobs, MR Shetty, N Patel, MV Jha, R Khorakiwala, HF AF de Souza, NJ Gupte, SV Deshpande, PK Desai, VN Bhawsar, SB Yeole, RD Shukla, MC Strahilevitz, J Hooper, DC Bozdogan, B Appelbaum, PC Jacobs, MR Shetty, N Patel, MV Jha, R Khorakiwala, HF TI A chiral benzoquinolizine-2-carboxylic acid arginine salt active against vancomycin-resistant Staphylococcus aureus SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIBACTERIAL AGENTS; ANTIMICROBIAL RESISTANCE; WCK-771; (S)-(-)-NADIFLOXACIN; FLUOROQUINOLONE; INFECTIONS AB There is an urgent medical need for novel antibacterial agents to treat hospital infections, specially those caused by multidrug-resistant Gram-positive pathogens. The need may also be fulfilled by either exploring antibacterial agents having new mechanism of action or expanding known classes of antibacterial drugs. The paper describes a new chemical entity, compound 21, derived from hitherto little known "floxacin". The choice of the entity was made from a series of synthesized prodrugs and salts of the active chiral benzoquinolizine carboxylic acid, S-H-nadifloxacin. The chemistry, physicochemical characteristics, and essential bioprofile of 21 qualifies it for serious consideration as a novel drug entity against hospital infections of multi-drug-resistant Staphylococcus aureus, and its progress up to clinical phase I trials in humans is described. C1 Wockhardt Ltd, Wockhardt Res Ctr, Aurangabad 431210, Maharashtra, India. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Hershey Med Ctr, Hershey, PA 17033 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Patel, MV (reprint author), Wockhardt Ltd, Wockhardt Res Ctr, D-4,MIDC, Aurangabad 431210, Maharashtra, India. EM mpatel@wockhardtin.com NR 45 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 11 PY 2005 VL 48 IS 16 BP 5232 EP 5242 DI 10.1021/jm050035f PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 953DB UT WOS:000231055300019 PM 16078842 ER PT J AU Gunsalus, KC Ge, H Schetter, AJ Goldberg, DS Han, JDJ Hao, T Berriz, GF Bertin, N Huang, J Chuang, LS Li, N Mani, R Hyman, AA Sonnichsen, B Echeverri, CJ Roth, FP Vidal, M Piano, F AF Gunsalus, KC Ge, H Schetter, AJ Goldberg, DS Han, JDJ Hao, T Berriz, GF Bertin, N Huang, J Chuang, LS Li, N Mani, R Hyman, AA Sonnichsen, B Echeverri, CJ Roth, FP Vidal, M Piano, F TI Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis SO NATURE LA English DT Article ID PROTEIN-INTERACTION NETWORKS; C-ELEGANS; CENTROSOME DUPLICATION; SACCHAROMYCES-CEREVISIAE; CELL POLARITY; MAPPING DATA; INTERACTOME; CENTRIOLAR; MAP; TRANSCRIPTOME AB Although numerous fundamental aspects of development have been uncovered through the study of individual genes and proteins, system-level models are still missing for most developmental processes. The first two cell divisions of Caenorhabditis elegans embryogenesis constitute an ideal test bed for a system-level approach. Early embryogenesis, including processes such as cell division and establishment of cellular polarity, is readily amenable to large-scale functional analysis. A first step toward a system-level understanding is to provide 'first-draft' models both of the molecular assemblies involved(1) and of the functional connections between them. Here we show that such models can be derived from an integrated gene/protein network generated from three different types of functional relationship(2): protein interaction(3), expression profiling similarity(4) and phenotypic profiling similarity(5), as estimated from detailed early embryonic RNA interference phenotypes systematically recorded for hundreds of early embryogenesis genes(6). The topology of the integrated network suggests that C. elegans early embryogenesis is achieved through coordination of a limited set of molecular machines. We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo. C1 NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. Cenix Biosci GmbH, D-01307 Dresden, Germany. RP Roth, FP (reprint author), NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. EM fritz_roth@hms.harvard.edu; marc_vidal@dfci.harvard.edu; fp1@nyu.edu RI Bertin, Nicolas/C-3025-2008; Roth, Frederick/H-6308-2011; Hyman, Anthony/B-3917-2017; OI Bertin, Nicolas/0000-0002-9835-9606; Hyman, Anthony/0000-0003-3664-154X; Roth, Frederick/0000-0002-6628-649X; Chuang, Ling-shiang/0000-0001-5054-1305 NR 30 TC 179 Z9 210 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 11 PY 2005 VL 436 IS 7052 BP 861 EP 865 DI 10.1038/nature03876 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953XG UT WOS:000231116500049 PM 16094371 ER PT J AU Ryan, PD Kopans, DB Sgroi, DC AF Ryan, PD Kopans, DB Sgroi, DC TI Case records of the Massachusetts General Hospital: Case 24-2005: A 58-year-old woman with early-stage estrogen-receptor-positive breast cancer - Invasive ductal carcinoma, T2N0, positive for estrogen receptor and progesterone receptor, negative for HER2/neu amplification. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID 20-YEAR FOLLOW-UP; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; EXPRESSION PROFILES; TAMOXIFEN THERAPY; ADJUVANT THERAPY; PROGRESSION; RECURRENCE; MASTECTOMY; PREDICTION C1 Massachusetts Gen Hosp, Dept Hematol & 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 Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Ryan, PD (reprint author), Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. NR 25 TC 1 Z9 1 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 11 PY 2005 VL 353 IS 6 BP 617 EP 622 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 953ST UT WOS:000231101500014 PM 16093471 ER PT J AU Corless, CL Schroeder, A Griffith, D Town, A McGreevey, L Harrell, P Shiraga, S Bainbridge, T Morich, J Heinrich, MC AF Corless, CL Schroeder, A Griffith, D Town, A McGreevey, L Harrell, P Shiraga, S Bainbridge, T Morich, J Heinrich, MC TI PDGFRA mutations in gastrointestinal stromal tumors: Frequency, spectrum and in vitro sensitivity to imatinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR-RECEPTOR-ALPHA; KINASE INHIBITORS; C-KIT; WILD-TYPE; SYSTEMIC MASTOCYTOSIS; EXPRESSION PROFILES; D816V MUTATION; PROTEIN-KINASE; PRIMARY SITE; SOFT-TISSUE AB Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT tyrosine kinase, which is a target for the kinase inhibitor imatinib. A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro. Little is known of the other types of PDGFRA mutations that occur in GISTs. Materials and Methods We determined the KIT and PDGFRA mutation status of 1,105 unique GISTS using a combination of denaturing high-performance liquid chromatography and direct sequencing. Results There were 80 tumors (7.2%) with a PDGFRA mutation: 66 in exon 18, 11 in exon 12, and three in exon 14. Transient expression of representative PDGFRA isoforms in CHO cells revealed imatinib sensitivity of exon 12 mutations (SPDHE566-571R and insertion ER561-562) and an exon 14 substitution (N659K). However, most isoforms with a substitution involving codon D842 in exon 18 (D842V, RD841-842KI, D1842-8431M) were resistant to the drug, with the exception of D842Y. Interestingly, other mutations in exon 18 (D846Y, N848K, Y849K and HDSN845-848P) were all imatinib sensitive. Proliferation studies with BA/F3 cell lines stably expressing selected PDGFRA mutant isoforms supported these findings. Conclusion Including our cases, there are 289 reported PDGFRA-mutant GISTS, of which 181 (62.6%) had the imatinib-resistant substitution D842V. However, our findings suggest that more than one third of GISTS with PDGFRA mutations may respond to imatinib and that mutation screening may be helpful in the management of these tumors. C1 Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Oncol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), R&D-19 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM heinrich@ohsu.edu NR 42 TC 380 Z9 407 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2005 VL 23 IS 23 BP 5357 EP 5364 DI 10.1200/JCO.2005.14.068 PG 8 WC Oncology SC Oncology GA 955NG UT WOS:000231232100009 PM 15928335 ER PT J AU Scholz, J Broom, DC Youn, DH Mills, CD Kohno, T Suter, MR Moore, KA Decosterd, I Coggeshall, RE Woolf, CJ AF Scholz, J Broom, DC Youn, DH Mills, CD Kohno, T Suter, MR Moore, KA Decosterd, I Coggeshall, RE Woolf, CJ TI Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE caspase-3; glutamate excitotoxicity; GABA; spinal inhibition; dorsal horn; neuropathic pain ID RAT SPINAL-CORD; CHRONIC CONSTRICTION INJURY; NEUROPATHIC PAIN; CELL-DEATH; GABA-IMMUNOREACTIVITY; GABAERGIC INHIBITION; SELECTIVE LOSS; SCIATIC-NERVE; MODEL; DEGENERATION AB We show that transsynaptic apoptosis is induced in the superficial dorsal horn (laminas I-III) of the spinal cord by three distinct partial peripheral nerve lesions: spared nerve injury, chronic constriction, and spinal nerve ligation. Ongoing activity in primary afferents of the injured nerve and glutamatergic transmission cause a caspase-dependent degeneration of dorsal horn neurons that is slow in onset and persists for several weeks. Four weeks after spared nerve injury, the cumulative loss of dorsal horn neurons, determined by stereological analysis, is >20%. GABAergic inhibitory interneurons are among the neurons lost, and a marked decrease in inhibitory postsynaptic currents of lamina II neurons coincides with the induction of apoptosis. Blocking apoptosis with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) prevents the loss of GABAergic interneurons and the reduction of inhibitory currents. Partial peripheral nerve injury results in pain-like behavioral changes characterized by hypersensitivity to tactile or cold stimuli. Treatment with zVAD, which has no intrinsic analgesic properties, attenuates this neuropathic pain-like syndrome. Preventing nerve injury-induced apoptosis of dorsal horn neurons by blocking caspase activity maintains inhibitory transmission in lamina II and reduces pain hypersensitivity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Lausanne Hosp, Dept Anesthesiol, Anesthesiol Pain Res Grp, CH-1005 Lausanne, Switzerland. Univ Lausanne, Fac Biol & Med, Inst Cell Biol & Morphol, CH-1005 Lausanne, Switzerland. Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM scholz.joachim@mgh.harvard.edu FU NINDS NIH HHS [NS045459, NS10161, NS11076, NS038253] NR 49 TC 204 Z9 218 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 10 PY 2005 VL 25 IS 32 BP 7317 EP 7323 DI 10.1523/JNEUROSCI.1526-05.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 954BZ UT WOS:000231130400006 PM 16093381 ER PT J AU Weitzman, M Cook, S Auinger, P Florin, TA Daniels, S Nguyen, M Winickoff, JP AF Weitzman, M Cook, S Auinger, P Florin, TA Daniels, S Nguyen, M Winickoff, JP TI Tobacco smoke exposure is associated with the metabolic syndrome in adolescents SO CIRCULATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 2004 CL San Francisco, CA SP Pediat Acad Soc DE adolescent; metabolic syndrome; obesity; smoking; tobacco ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; INSULIN-RESISTANCE SYNDROME; CORONARY-HEART-DISEASE; SYNDROME SYNDROME-X; BLOOD-PRESSURE; CIGARETTE-SMOKING; SERUM-LIPIDS; RISK-FACTORS; COMPENSATORY HYPERINSULINEMIA AB Background - The metabolic syndrome predicts future coronary artery disease and type II diabetes and often emerges in childhood. Tobacco smoke potentially contributes to insulin resistance in this syndrome. This study evaluates the association of environmental tobacco smoke (ETS) exposure and active smoking with the prevalence of the metabolic syndrome in US adolescents. Methods and Results - Data from 2273 subjects 12 to 19 years of age were examined from the National Health and Nutrition Examination Survey III ( NHANES III, 1988 to 1994). Serum cotinine levels, presence of household smokers, and self-report of smoking were used to determine ETS exposure and active smoking. The metabolic syndrome was defined as having >= 3 criteria from the National Cholesterol Education Panel definition. Bivariate and multivariable analyses were conducted. Among adolescents, 5.6% met the criteria for metabolic syndrome, and prevalence increased with tobacco exposure: 1.2% for nonexposed, 5.4% for those exposed to ETS, and 8.7% for active smokers ( P < 0.001). In adolescents at risk for overweight and overweight adolescents ( body mass index above the 85th percentile), a similar relationship was observed: 5.6% for nonexposed, 19.6% for those exposed to ETS, and 23.6% for active smokers ( P = 0.01). In multivariable logistic regression analyses among all adolescents, ETS exposure was independently associated with the metabolic syndrome ( ETS exposure: odds ratio, 4.7, 95% CI, 1.7 to 12.9; active smoking: odds ratio, 6.1; 95% CI, 2.8 to 13.4). Conclusions - Considering that tobacco and obesity are the 2 leading causes of preventable death in the United States, these findings of a dose-response, cotinine-confirmed relationship between tobacco smoke and metabolic syndrome among adolescents may have profound implications for the future health of the public. C1 Univ Rochester, Sch Med & Dent, Ctr Child Hlth Res, Dept Pediat, Rochester, NY 14620 USA. Univ Rochester, Sch Med & Dent, Strong Childrens Res Ctr, Rochester, NY 14620 USA. Amet Acad Pediat Ctr Child Hlth Res, Rochester, NY USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Washington Univ, St Louis Childrens Hosp, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Div Gen Pediat, MGH Ctr Child & Adolscent Hlth Policy, Boston, MA 02114 USA. Tobacco Res & Treatment Ctr, Boston, MA USA. RP Weitzman, M (reprint author), Univ Rochester, Sch Med & Dent, Ctr Child Hlth Res, Dept Pediat, 1351 Mt Hope Ave, Rochester, NY 14620 USA. EM michael_weitzman@urmc.rochester.edu FU PHS HHS [T32HP12002] NR 46 TC 135 Z9 146 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 9 PY 2005 VL 112 IS 6 BP 862 EP 869 DI 10.1161/CIRCULATIONAHA.104.520650 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 953HN UT WOS:000231067300014 PM 16061737 ER PT J AU Nadkarni, SK Bouma, BE Helg, T Chan, R Halpern, E Chau, A Minsky, MS Motz, JT Houser, SL Tearney, GJ AF Nadkarni, SK Bouma, BE Helg, T Chan, R Halpern, E Chau, A Minsky, MS Motz, JT Houser, SL Tearney, GJ TI Characterization of atherosclerotic plaques by laser speckle imaging SO CIRCULATION LA English DT Article DE atherosclerosis; diagnosis; imaging; lasers ID OPTICAL COHERENCE TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; VISUALIZATION; ELASTOGRAPHY; ATHEROMA; ARTERIES; COLLAGEN; RUPTURE; DISEASE; BLOOD AB Background - A method capable of determining atherosclerotic plaque composition and measuring plaque viscoelasticity can provide valuable insight into intrinsic features associated with plaque rupture and can enable the identification of high-risk lesions. In this article, we describe a new optical technique, laser speckle imaging (LSI), that measures an index of plaque viscoelasticity. We evaluate the potential of LSI for characterizing atherosclerotic plaque. Methods and Results - Time-varying helium-neon laser speckle images were acquired from 118 aortic plaque specimens from 14 human cadavers under static and deforming conditions ( 0 to 200 mu m/s). Temporal fluctuations in the speckle patterns were quantified by exponential fitting of the normalized cross-correlation of sequential frames in each image series of speckle patterns to obtain the exponential decay time constant, tau. The decorrelation time constants of thin-cap fibroatheromas (TCFA) ( tau = 47.5 +/- 19.2 ms) were significantly lower than those of other atherosclerotic lesions ( P < 0.001), and the sensitivity and specificity of the LSI technique for identifying TCFAs were > 90%. Speckle decorrelation time constants demonstrated strong correlation with histological measurements of plaque collagen ( R = 0.73, P < 0.0001), fibrous cap thickness ( R = 0.87, P < 0.0001), and necrotic core area ( R = - 0.81, P < 0.0001). Under deforming conditions ( 10 to 200 mu m/s), tau correlated well with cap thickness in necrotic core fibroatheromas ( P > 0.05). Conclusions - The measurement of speckle decorrelation time constant from laser speckle images provides an index of plaque viscoelasticity and facilitates the characterization of plaque type. Our results demonstrate that LSI is a highly sensitive technique for characterizing plaque and identifying thin-cap fibroatheromas. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Wellman Ctr Photmed, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 40 Blossom St,BAR 718, Boston, MA 02114 USA. EM snadkarni@hms.harvard.edu FU NHLBI NIH HHS [R01 HL070039, R01 HL076398, R01 HL076398-01, R01-HL70039] NR 37 TC 38 Z9 39 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 9 PY 2005 VL 112 IS 6 BP 885 EP 892 DI 10.1161/CIRCULATIONAHA.104.520098 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 953HN UT WOS:000231067300017 PM 16061738 ER PT J AU Field, SJ Madson, N Kerr, ML Galbraith, KAA Kennedy, CE Tahiliani, M Wilkins, A Cantley, LC AF Field, SJ Madson, N Kerr, ML Galbraith, KAA Kennedy, CE Tahiliani, M Wilkins, A Cantley, LC TI PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis SO CURRENT BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE; ALPHA-ACTININ; LIPID PRODUCTS; FISSION YEAST; BINDING; 4,5-BISPHOSPHATE; IDENTIFICATION; PROTEINS; PROFILIN; DOMAINS AB Phosphoinositides play important roles in regulating the cytoskeleton and vesicle trafficking, potentially important processes at the cleavage furrow. However, it remains unclear which, if any, of the phosphoinositides play a role during cytokinesis. A systematic analysis to determine if any of the phosphoinositides might be present or of functional importance at the cleavage furrow has not been published. Several studies hint at a possible role for one or more phosphoinositides at the cleavage furrow. The best of these are genetic data identifying mutations in phosphoinositide-modifying enzymes (a Ptdlns(4)P-5-kinase in S. pombe [1, 2] and a PI-4-kinase in D. melanogaster [3]) that interfere with cytokinesis. The genetic nature of these experiments leaves questions as to how direct may be their contribution to cytokinesis. Here we show that a single phosphoinositide, PtdIns(4,5)P2, specifically accumulates at the furrow. Interference with PtdIns(4,5)P2 interferes with adhesion of the plasma membrane to the contractile ring at the furrow. Finally, four distinct interventions to specifically interfere with Ptdlns(4,5)P2 each impair cytokinesis. We conclude that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal cytokinesis at least in part because of a role in adhesion between the contractile ring and the plasma membrane. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr,Div Signal Transduc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Field, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr,Div Signal Transduc, Boston, MA 02115 USA. EM sjfield@ucsd.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [K08 DK065108] NR 22 TC 111 Z9 111 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 9 PY 2005 VL 15 IS 15 BP 1407 EP 1412 DI 10.1016/j.cub.2005.06.059 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 955MO UT WOS:000231230200027 PM 16085494 ER PT J AU Dickerson, BC Salat, DH Greve, DN Chua, EF Rand-Giovannetti, E Rentz, DM Bertram, L Mullin, K Tanzi, RE Blacker, D Albert, MS Sperling, RA AF Dickerson, BC Salat, DH Greve, DN Chua, EF Rand-Giovannetti, E Rentz, DM Bertram, L Mullin, K Tanzi, RE Blacker, D Albert, MS Sperling, RA TI Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD SO NEUROLOGY LA English DT Article ID FUNCTIONAL MRI STUDY/; ALZHEIMERS-DISEASE; EPSILON-4 ALLELE; APOLIPOPROTEIN-E; HEMODYNAMIC-RESPONSE; BRAIN ACTIVITY; FMRI RESPONSE; DOWN-SYNDROME; MEMORY; DEMENTIA AB Objective: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). Methods: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease ( AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. Results: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon 4 allele than in the 16 noncarriers. Conclusions: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Memory Disorders Unit, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NCRR NIH HHS [P41 RR014075, P41-RR14075]; NIA NIH HHS [K23 AG022509, K23-AG22509, P01 AG004953, P01-AG04953, P50 AG005134, P50-AG05134]; NINDS NIH HHS [K23 NS002189, K23-NS02189] NR 53 TC 384 Z9 397 U1 6 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 9 PY 2005 VL 65 IS 3 BP 404 EP 411 DI 10.1212/01.wnl.0000171450.97464.49 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 953HM UT WOS:000231067200013 PM 16087905 ER PT J AU Takeuchi, O Fisher, J Suh, H Harada, H Malynn, BA Korsmeyer, SJ AF Takeuchi, O Fisher, J Suh, H Harada, H Malynn, BA Korsmeyer, SJ TI Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAMILY-MEMBER BIM; BH3-ONLY PROTEINS; IMMUNE-SYSTEM; TRANSGENIC MICE; BH3 DOMAINS; CYCLE ENTRY; IN-VIVO; BCL-2; APOPTOSIS; BAX AB B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX and BAK are essential for regulating the number of B cells at both immature and mature developmental stages. BAX and BAK are critical mediators of B cell death induced by multiple stimuli. In addition, BAX- and BAK-deficient B cells display defective cell cycle progression to B cell receptor crosslinking and lipopolysaccharide, but not to CpG-DNA. Furthermore, inducible deletion of Bax and Bak in adult mice results in the development of severe autoimmune disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan. Virginia Commonwealth Univ, Massey Canc Ctr, Dept Internal Med, Richmond, VA 23298 USA. RP Takeuchi, O (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM otake@biken.osaka-u.ac.jp RI Takeuchi, Osamu/D-6007-2011 NR 38 TC 109 Z9 109 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 9 PY 2005 VL 102 IS 32 BP 11272 EP 11277 DI 10.1073/pnas.0504783102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400028 PM 16055554 ER PT J AU Grossi, M Hiou-Feiget, A Di Vignano, AT Calautti, E Ostano, P Lee, S Chiorino, G Dotto, GP AF Grossi, M Hiou-Feiget, A Di Vignano, AT Calautti, E Ostano, P Lee, S Chiorino, G Dotto, GP TI Negative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epithelial cell differentiation; gene expression; Rho signaling; stem cell potential ID CITRON KINASE; RHO-GTPASES; BINDING PROTEIN; LIM PROTEIN; DOMAIN; P21(CIP1/WAF1); CYTOSKELETON; CYTOKINESIS; ADHESION; FAMILY AB Rho GTPases integrate control of cell structure and adhesion with downstream signaling events. In keratinocytes, RhoA is activated at early times of differentiation and plays an essential function in establishment of cell-cell adhesion. We report here that, surprisingly, Rho signaling suppresses downstream gene expression events associated with differentiation. Similar inhibitory effects are exerted by a specific Rho effector, CRIK (Citron kinase), which is selectively down-modulated with differentiation, thereby allowing the normal process to occur. The suppressing function of Rho/CRIK on differentiation is associated with induction of KyoT1/2, a LIM domain protein gene implicated in integrin-mediated processes and/or Notch signaling. Like activated Rho and CRIK, elevated KyoT1/2 expression suppresses differentiation. Thus, Rho signaling exerts an unexpectedly complex role in keratinocyte differentiation, which is coupled with induction of KyoT1/2, a LIM domain protein gene with a potentially important role in control of cell self renewal. C1 Univ Lausanne, Dept Chem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fondo Edo Tempia, Lab Canc Pharmacogen, I-13900 Biella, Italy. RP Dotto, GP (reprint author), Univ Lausanne, Dept Chem, CH-1066 Epalinges, Switzerland. EM gdotto@partners.org RI Chiorino, Giovanna/K-5037-2016; OI Chiorino, Giovanna/0000-0002-9502-6400; CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NCI NIH HHS [CA16038, CA73796, P01 CA016038, R01 CA073796]; NIAMS NIH HHS [R01 AR039190, AR39190] NR 30 TC 22 Z9 23 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 9 PY 2005 VL 102 IS 32 BP 11313 EP 11318 DI 10.1073/pnas.0505011102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400035 PM 16061799 ER PT J AU Signoretti, S Pires, MM Lindauer, M Horner, JW Grisanzio, C Dhar, S Majumder, P McKeon, F Kantoff, PW Sellers, WR Loda, M AF Signoretti, S Pires, MM Lindauer, M Horner, JW Grisanzio, C Dhar, S Majumder, P McKeon, F Kantoff, PW Sellers, WR Loda, M TI p63 regulates commitment to the prostate cell lineage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE animal model; development; stem cell; urothelium; mouse model ID P53 HOMOLOG; EPITHELIAL-CELLS; URINARY-BLADDER; DIFFERENTIATION; PROLIFERATION; MOUSE; BASAL; RAT; HEMATOPOIESIS; UROTHELIUM AB Molecular mechanisms underlying prostate and urothelial development remain unclear. This situation presents major limitations in identifying the cell type(s) and molecular events involved in the development of prostate and bladder cancer. It has been shown that mice lacking the basal cell marker p63 present several epithelial defects, including epidermis and prostate buds agenesis and urothelial abnormalities. Here, we use the p63-/- mouse as a tool to define cell lineages in the prostate epithelium and urothelium. By complementing p63(-/-) blastocysts with p63+/+ beta-galactosiclase (beta-gal)- positive ES cells, we show that secretory cells of the prostate originate from p63-positive basal progenitor cells. Importantly, our urogenital sinus transplantation studies demonstrate that p63 prevents intestinal differentiation of the urogenital sinus endoderm and is therefore required to maintain commitment to the prostate cell lineage. Finally, in contrast with the prostate findings, analysis of the urothelium from rescued p63-/- chimeras shows that umbrella (superficial) cells can develop and be maintained independently from p63-positive basal and intermediate cells. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, MIT, Broad Inst, Cambridge, MA 02141 USA. Whitehead Inst Biomed Res, Cambridge, MA 02141 USA. RP Loda, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu NR 28 TC 106 Z9 110 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 9 PY 2005 VL 102 IS 32 BP 11355 EP 11360 DI 10.1073/pnas.0500165102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400042 PM 16051706 ER PT J AU Benarafa, C Remold-O'Donnell, E AF Benarafa, C Remold-O'Donnell, E TI The ovalbumin serpins revisited: Perspective from the chicken genome of clade B serpin evolution in vertebrates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ov-serpin; multigene locus; maspin; MNEI; zebrafish ID REACTIVE CENTER LOOP; CRYSTAL-STRUCTURE; PROTEASE INHIBITORS; SEQUENCE ALIGNMENT; CROSS-LINKING; HINGE REGION; S-OVALBUMIN; EXON-INTRON; GENE; INSERTION AB Serpin superfamily proteins, most of which are serine protease inhibitors, share an unusual mechanism rooted in their conserved metastable tertiary structure. Although serpins have been identified in isolated members of archea, bacteria, and plants, a remarkable expansion is found in vertebrates. The chicken protein ovalbumin, a storage protein from egg white, lacking protease inhibitory activity, is an historical member of the superfamily and the founding member of the subgroup known as ov-serpins (ovalbumin-related serpins) or clade B serpins. In the human, ov-serpins include 13 proteins involved in the regulation of inflammation, apoptosis, angiogenesis, and embryogenesis. Here, a detailed analysis of the chicken (Gallus gallus) genome identified 10 clade B serpin genes that map to a single approximate to 150-kb locus and contain the signature protein sequence of serpins and the gene structure of ov-serpins, with either seven or eight exons. Orthologues of PAI-2 (SERPINB2), MNEI (SERPINB1), Pl-6 (SERPINB6), and maspin (SERPINB5) are highly conserved. Comparison with human ov-serpins identified avian-specific and mammal-specific genes. Importantly, a unique model of mammalian ov-serpin evolution is revealed from the comparative analysis of the chicken and human loci. The presence of a subset of ov-serpin genes in zebrafish (Danio rerio) gives insight into the ancestral locus. This comparative genomic study provides a valuable perspective on the evolutionary pathway for the clade B serpins, allowing the identification of genes with functions that may have been conserved since the origin of vertebrates. In addition, it suggests that "newer" serpins, such as ovalbumin, have contributed to vertebrate adaptation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Benarafa, C (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM benarafa@cbr.med.harvard.edu; remold@cbr.med.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU NHLBI NIH HHS [HL66548, R01 HL066548] NR 44 TC 53 Z9 53 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 9 PY 2005 VL 102 IS 32 BP 11367 EP 11372 DI 10.1073/pnas.0502934102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400044 PM 16055559 ER PT J AU DeMasi, J Huh, KW Nakatani, Y Munger, K Howley, PM AF DeMasi, J Huh, KW Nakatani, Y Munger, K Howley, PM TI Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; oncoprotein ID GROWTH-FACTOR RECEPTOR; OPEN READING FRAME; E6 ONCOPROTEIN; MOUSE CELLS; TYPE-1 E6; E5; GENE; PAXILLIN; INVITRO; VIRUS AB The E7 oncoprotein of bovine papillomavirus type 1 (BPV-1) is required for the full transformation activity of the virus. However, the mechanism by which E7 contributes to cellular transformation is unknown. To address this question, we used the proteomic approach of tandem affinity purification to identify cellular proteins that are in complex with E7, and identified the 600-kDa protein, p600, as a binding partner of E7. The ability of E7 to complex with p600 correlated with its ability to enhance anchorage independence of BPV-1 E6-expressing cells. Furthermore, E7 mutant proteins impaired in their ability to bind p600 were transformation defective. Additionally, knockdown of p600 reduced transformation of cells expressing both BPV-1 E6 and ET as well as E6 alone, suggesting that the ability of E7 to transformed cells is mediated, at least in part, through its ability to bind p600. These data complement work that shows that HPV16 E7 also interacts with p600, and that this interaction correlates with the ability of HPV16 E7 to transform cells. These studies thus identify p600 as a shared target of the E7 proteins of multiple papillomaviruses. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Howley, PM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM peter_howley@hms.harvard.edu OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA050661, CA081135, P01 CA050661, R01 CA081135] NR 35 TC 50 Z9 54 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 AUG 9 PY 2005 VL 102 IS 32 BP 11486 EP 11491 DI 10.1073/pnas.0505322102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400064 PM 16081543 ER PT J AU Huh, KW DeMasi, J Ogawa, H Nakatani, Y Howley, PM Munger, K AF Huh, KW DeMasi, J Ogawa, H Nakatani, Y Howley, PM Munger, K TI Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; cervical carcinogensis; retinoblastoma tumor suppressor ID CARCINOMA CELL-LINES; N-END RULE; TUMOR-SUPPRESSOR; MOLECULAR TARGETS; HPV16 E7; PATHWAY; CANCER; RB; DEGRADATION; SEQUENCES AB The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Munger, K (reprint author), Brigham & Womens Hosp, Channing Lab, 75 Francis St, Boston, MA 02115 USA. EM kmunger@rics.bwh.harvard.edu OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [P01 CA050661, P01-CA050661, R01 CA081135, R01-CA081135] NR 42 TC 99 Z9 106 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 9 PY 2005 VL 102 IS 32 BP 11492 EP 11497 DI 10.1073/pnas.0505337102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955UP UT WOS:000231253400065 PM 16061792 ER PT J AU Bailey, FA Burgio, KL Woodby, LL Williams, BR Redden, DT Kovac, SH Durham, RM Goode, PS AF Bailey, FA Burgio, KL Woodby, LL Williams, BR Redden, DT Kovac, SH Durham, RM Goode, PS TI Improving processes of hospital care during the last hours of life SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the VA-Health-Services-Research-and-Development-Program CY FEB 16-18, 2005 CL Baltimore, DC SP VA Hlth Serv Res Dev Program ID OF-LIFE; PHYSICIAN PERFORMANCE; ILL PATIENTS; CANCER; PERSPECTIVES; PROGNOSES; SURVIVAL; OUTCOMES; SUPPORT; DEATH AB Background: Known for excellence in care in the last days and hours of life, hospice programs can help individuals have a "good death" and lead to higher family satisfaction with quality of care. Our objective was to evaluate the effectiveness of a multicomponent palliative care intervention based on the best practices of home hospice and designed to improve the quality of care provided for patients dying in an acute care inpatient setting. Methods: This study was a before-after intervention trial conducted between 2001 and 2003. Participants included physician, nursing, and ancillary staff on inpatient services of an urban, tertiary care Veterans Affairs medical center. The palliative care intervention included staff education and support to identify patients who were actively dying and implement care plans guided by a comfort care order set template for the last days or hours of life. Data abstracted from computerized medical records of 203 veterans who died during a 6-month period before (n = 108) and after (n = 95) intervention were used to determine the impact of intervention on symptom documentation and 5 process of care indicators. Results: There was a significant increase in the mean (SD) number of symptoms documented from 1. 7 (2.1) to 4.4 (2.7) (P < .001), and the number of care plans increased from 0.4 (0.9) to 2.7 (2.3) (P < .001). Opioid medication availability increased from 57.1% to 83.2% (P < .001), and do-not-resuscitate orders increased from 61.9% to 85.1% (P < .001). There were nonsignificant changes in the proportion of deaths that occurred in intensive care units (P =. 17) and in the use of nasogastric tubes (P =. 40), and there was a significant increase in the use of restraints (P < .001). Conclusion: Our results indicate that end-of-life care improved after the introduction of the palliative care program. C1 Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Dept Vet Affairs Med Ctr, Res Enhancement Award Program, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Dept Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Dept Med, Durham, NC USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, GRECC-11G,700 19th St S, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu NR 40 TC 68 Z9 68 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 8 PY 2005 VL 165 IS 15 BP 1722 EP 1727 DI 10.1001/archinte.165.15.1722 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 952VW UT WOS:000231034800008 PM 16087819 ER PT J AU Zhu, BH Jaffer, FA Ntziachristos, V Weissleder, R AF Zhu, BH Jaffer, FA Ntziachristos, V Weissleder, R TI Development of a near infrared fluorescence catheter: operating characteristics and feasibility for atherosclerotic plaque detection SO JOURNAL OF PHYSICS D-APPLIED PHYSICS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; LASER-INDUCED FLUORESCENCE; INTRAVASCULAR ULTRASOUND; DOPPLER TOMOGRAPHY; IN-VIVO; SPECTROSCOPY; NM AB We present a one-dimensional optical fibre-based imaging catheter specifically developed for the atherosclerotic plaque detection of emerging novel near infrared fluorescence imaging agents. We show that femtomole amounts of fluorochromes can be detected, especially in the presence of a blood-free medium. We further studied the catheter responses for a wide range of laser powers and biologically relevant concentrations of fluorochrome. In vitro tissue-like phantoms and human carotid plaque specimen measurements further demonstrate the feasibility of atherosclerotic plaque detection. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, Boston, MA 02114 USA. RP Zhu, BH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5406, Boston, MA 02129 USA. OI Jaffer, Farouc/0000-0001-7980-384X NR 26 TC 26 Z9 26 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0022-3727 J9 J PHYS D APPL PHYS JI J. Phys. D-Appl. Phys. PD AUG 7 PY 2005 VL 38 IS 15 BP 2701 EP 2707 DI 10.1088/0022-3727/38/15/024 PG 7 WC Physics, Applied SC Physics GA 957XN UT WOS:000231406800025 ER PT J AU Mariappan, MM Senthil, D Natarajan, KS Choudhury, GG Kasinath, BS AF Mariappan, MM Senthil, D Natarajan, KS Choudhury, GG Kasinath, BS TI Phospholipase C gamma-Erk axis in vascular endothelial growth factor-induced eukaryotic initiation factor 4E phosphorylation and protein synthesis in renal epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE PATHWAYS; TRANSLATION INITIATION; ANGIOTENSIN-II; MESSENGER-RNA; SMOOTH-MUSCLE; TYROSINE PHOSPHORYLATION; DIABETIC-NEPHROPATHY; DEPENDENT ACTIVATION; FACTOR EIF-4E; PLC-GAMMA AB Vascular endothelial growth factor ( VEGF) increases protein synthesis and induces hypertrophy in renal tubular epithelial cells ( Senthil, D., Choudhury, G. G., McLaurin, C., and Kasinath, B. S. ( 2003) Kidney Int. 64, 468 - 479). We examined the role of Erk1/2 MAP kinase in protein synthesis induced by VEGF. VEGF stimulated Erk phosphorylation that was required for induction of protein synthesis. VEGF-induced Erk activation was not dependent on phosphoinositide ( PI) 3-kinase activation but required sequential phosphorylation of type 2 VEGF receptor, PLC gamma and c-Src, as demonstrated by inhibitors SU1498, U73122, and PP1, respectively. c-Src phosphorylation was inhibited by U73122, indicating it was downstream of phospholipase ( PL)C gamma. Studies with PP1/2 showed that phosphorylation of c-Src was required for tyrosine phosphorylation of Raf-1, an upstream regulator of Erk. VEGF also stimulated phosphorylation of Pyk-2; VEGF-induced phosphorylation of Pyk2, c-Src and Raf-1 could be abolished by BAPTA/AM, demonstrating requirement for induction of intracellular calcium currents. We examined the downstream events following the phosphorylation of Erk. VEGF stimulated phosphorylation of Mnk1 and eIF4E and induced Mnk1 to shift from the cytoplasm to the nucleus upon phosphorylation. VEGF-induced phosphorylation of Mnk1 and eIF4E required phosphorylation of PLC gamma, c-Src, and Erk. Expression of dominant negative Mnk1 abrogated eIF4E phosphorylation and protein synthesis induced by VEGF. VEGF-stimulated protein synthesis could be blocked by inhibition of PLC gamma by a chemical inhibitor or expression of a dominant negative construct. Our data demonstrate that VEGF-stimulated protein synthesis is Erk-dependent and requires the activation of VEGF receptor 2, PLC gamma, c-Src, Raf, and Erk pathway. VEGF also stimulates Erk-dependent phosphorylation of Mnk1 and eIF4E, crucial events in the initiation phase of protein translation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. O Brien Kidney Res Ctr, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. EM Kasinath@uthscsa.edu FU NIDDK NIH HHS [DK 55815, P50-DK 061597, DK 50190] NR 50 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 2005 VL 280 IS 31 BP 28402 EP 28411 DI 10.1074/jbc.M504861200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 950KZ UT WOS:000230857300029 PM 15919658 ER PT J AU Elkin, SK Ivanov, D Ewalt, M Ferguson, CG Hyberts, SG Sun, ZYJ Prestwich, GD Yuan, JY Wagner, G Oettinger, MA Gozani, OP AF Elkin, SK Ivanov, D Ewalt, M Ferguson, CG Hyberts, SG Sun, ZYJ Prestwich, GD Yuan, JY Wagner, G Oettinger, MA Gozani, OP TI A PHD finger motif in the C terminus of RAG2 modulates recombination activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-PROTEIN LIGASES; HUMAN V(D)J RECOMBINATION; FYVE DOMAIN; B-CELL; MEDIATED TRANSPOSITION; NUCLEAR-LOCALIZATION; JOINT FORMATION; BINDING; MUTATIONS; IDENTIFICATION AB The RAG1 and RAG2 proteins catalyze V( D) J recombination and are essential for generation of the diverse repertoire of antigen receptor genes and effective immune responses. RAG2 is composed of a "core" domain that is required for the recombination reaction and a C-terminal nonessential or "non-core" region. Recent evidence has emerged arguing that the non-core region plays a critical regulatory role in the recombination reaction, and mutations in this region have been identified in patients with immunodeficiencies. Here we present the first structural data for the RAG2 protein, using NMR spectroscopy to demonstrate that the C terminus of RAG2 contains a noncanonical PHD finger. All of the non-core mutations of RAG2 that are implicated in the development of immunodeficiencies are located within the PHD finger, at either zinc-coordinating residues or residues adjacent to an alpha-helix on the surface of the domain that participates in binding to the signaling molecules, phosphoinositides. Functional analysis of disease and phosphoinositide-binding mutations reveals novel intramolecular interactions within the noncore region and suggests that the PHD finger adopts two distinct states. We propose a model in which the equilibrium between these states modulates recombination activity. Together, these data identify the PHD finger as a novel and functionally important domain of RAG2. C1 Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Univ Utah, Dept Med Chem, Salt Lake City, UT 84108 USA. Echelon Biosci Inc, Salt Lake City, UT 84108 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Wagner, G (reprint author), Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. EM wagner@hms.harvard.edu; oettinger@frodo.mgh.harvard.edu; ogozani@stanford.edu RI Ivanov, Dmitri/B-4600-2011; OI Ewalt, Mark/0000-0003-4245-752X FU NIA NIH HHS [KO8AG19245, R01 AG16674]; NIAID NIH HHS [R01 AI37587]; NIGMS NIH HHS [R01 GM48026, R44 GM065683]; NINDS NIH HHS [R01 NS29632] NR 64 TC 50 Z9 51 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 2005 VL 280 IS 31 BP 28701 EP 28710 DI 10.1074/jbc.M504731200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 950KZ UT WOS:000230857300061 PM 15964836 ER PT J AU Zhu, BM Ramachandran, B Gulick, T AF Zhu, BM Ramachandran, B Gulick, T TI Alternative pre-mRNA splicing governs expression of a conserved acidic transactivation domain in myocyte enhancer factor 2 factors of striated muscle and brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR MEF2C; PROTEIN SECONDARY STRUCTURE; II HISTONE DEACETYLASES; MYOSIN HEAVY-CHAIN; T-CELL APOPTOSIS; SKELETAL-MUSCLE; GENE-EXPRESSION; DNA-BINDING; MADS-BOX; FACTOR 2A AB Myocyte enhancer factor 2 ( MEF2) transcription factors play pivotal roles in striated muscle, neuron, and lymphocyte gene expression and are targets of stress- and calcium-mediated signaling. All MEF2 gene products have a common DNA binding and dimerization domain, but MEF2 transcripts are alternatively spliced among coding exons to produce splicing isoforms. In vertebrate MEF2A, -C, and -D, a splice versus no-splice option gives forms that include or exclude a short domain that we designate beta. We show that mRNAs containing beta are expressed predominantly in striated muscle and brain and that splicing to include beta is induced during myocyte differentiation. MEF2 beta+ isoforms are more robust than beta+ forms in activating MEF2-responsive reporters despite similar expression levels. One-hybrid transcription assays using Gal4-MEF2 fusions show similar distinctions in the transactivation produced by beta+ versus beta+ isoforms in all cell types tested, including myocytes. beta function is position-independent and exists in all MEF2 splicing variant contexts. The activity is not due to cis effects on MEF2 DNA binding or dimerization nor are established transcription factor or coactivator interactions involved. Each MEF2 beta domain contains multiple acidic residues, mutation of which abolishes function. Despite a location between the p38 MAPK docking domain and Thr phosphoacceptors of MEF2A and MEF2C, inclusion of beta does not influence responses of these factors to this signaling pathway. Thus, a conserved pattern of alternative splicing in vertebrate MEF2 genes generates an acidic activation domain in MEF2 proteins selectively in tissues where MEF2 target genes are highly expressed. C1 Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, CNY 1498219, Charlestown, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL72713]; NIDDK NIH HHS [DK02461, DK55875, P30 DK40561] NR 95 TC 48 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 2005 VL 280 IS 31 BP 28749 EP 28760 DI 10.1074/M502491200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 950KZ UT WOS:000230857300066 PM 15834131 ER PT J AU Dotto, GP Cotsarelis, G AF Dotto, GP Cotsarelis, G TI Developmental biology - Rac1 up for epidermal stem cells SO SCIENCE LA English DT Editorial Material ID HAIR FOLLICLE; EXPRESSION; DIFFERENTIATION; SKIN; RHO C1 Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Dermatol, Kligman Labs, Philadelphia, PA 19104 USA. RP Dotto, GP (reprint author), Univ Lausanne, Inst Biochem, Chemin Bovaresses 155, CH-1066 Epalinges, Switzerland. EM cotsarel@mail.med.upenn.edu NR 13 TC 9 Z9 9 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 5 PY 2005 VL 309 IS 5736 BP 890 EP 891 DI 10.1126/science.1117192 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953SS UT WOS:000231101400033 PM 16081726 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, NE DePinho, RA TI Cancer - Crime and punishment SO NATURE LA English DT Editorial Material ID CELLULAR SENESCENCE; CULTURE; P53 C1 Univ N Carolina, Sch Med, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM ron_depinho@dfci.harvard.edu NR 12 TC 96 Z9 102 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 4 PY 2005 VL 436 IS 7051 BP 636 EP 637 DI 10.1038/436636a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 951XA UT WOS:000230964500026 PM 16079829 ER PT J AU Peng, ZC Houser, CR AF Peng, ZC Houser, CR TI Temporal patterns of fos expression in the dentate gyrus after spontaneous seizures in a mouse model of temporal lobe epilepsy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pilocarpine; hippocampus; granule cells; interneurons; immunohistochemistry; GABA neurons ID C-FOS; GRANULE CELLS; KAINIC ACID; STATUS EPILEPTICUS; RAT HIPPOCAMPUS; NERVOUS-SYSTEM; MESSENGER-RNA; SYNAPTIC REORGANIZATION; GENE-EXPRESSION; MOSSY FIBERS AB Identifying the brain regions and neuronal cell types that become active at the time of spontaneous seizures remains an important challenge for epilepsy research, and the involvement of dentate granule cells in early seizure events continues to be debated. Although Fos expression is commonly used to evaluate patterns of neuronal activation, there have been few studies of Fos localization after spontaneous seizures. Thus, in a pilocarpine model of recurrent seizures in C57BL/6 mice, Fos expression was examined at multiple time points after spontaneous seizures to follow the temporal and spatial patterns of Fos activation. By 15 min after the beginning of a spontaneous behavioral seizure, Fos labeling was evident in dentate granule cells. This labeling was particularly striking because of its wide extent and relatively uniform appearance in the granule cell layer. At later time points, from 30 min to 4 h after a spontaneous seizure, Fos labeling was also detected in interneurons within the dentate gyrus and in widespread regions of the temporal lobe. Interestingly, the timing of Fos activation appeared to differ among different types of GABAergic interneurons in the dentate gyrus, with labeling of parvalbumin neurons along the base of the granule cell layer preceding that of GABA neurons in the molecular layer. The findings in this mouse model are consistent with previous suggestions that spontaneous seizures in temporal lobe epilepsy may result from a periodic breakdown of the normal filter functions of the dentate gyrus and a resulting increase in hypersynchronous activity of dentate granule cells. C1 Univ Calif Los Angeles, Dept Neurobiol, Ctr Hlth Sci 73235, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Dept Neurobiol, Ctr Hlth Sci 73235, David Geffen Sch Med, 10833 LeConte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU BLRD VA [I01 BX000404]; NINDS NIH HHS [NS046524] NR 56 TC 51 Z9 54 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 AUG 3 PY 2005 VL 25 IS 31 BP 7210 EP 7220 DI 10.1523/JNEUROSCI.0838-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 952FB UT WOS:000230987300014 PM 16079403 ER PT J AU Spires, TL Meyer-Luehmann, M Stern, EA McLean, PJ Skoch, J Nguyen, PT Bacskai, BJ Hyman, BT AF Spires, TL Meyer-Luehmann, M Stern, EA McLean, PJ Skoch, J Nguyen, PT Bacskai, BJ Hyman, BT TI Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer; dendritic spine; senile plaque; Tg2576; dystrophic neurite; multiphoton ID ALZHEIMERS-DISEASE; IN-VIVO; NEURONAL LOSS; QUANTITATIVE ASSESSMENT; COGNITIVE IMPAIRMENT; DYSTROPHIC NEURITES; SYNAPTIC DENSITY; NEUROPIL CHANGES; BETA DEPOSITION; SENILE DEMENTIA AB Accumulation of amyloid-beta( A beta) into senile plaques in Alzheimer's disease ( AD) is a hallmark neuropathological feature of the disorder, which likely contributes to alterations in neuronal structure and function. Recent work has revealed changes in neurite architecture associated with plaques and functional changes in cortical signaling in amyloid precursor protein ( APP) expressing mouse models of AD. Here we developed a method using gene transfer techniques to introduce green fluorescent protein ( GFP) into neurons, allowing the investigation of neuronal processes in the vicinity of plaques. Multiphoton imaging of GFP-labeled neurons in living Tg2576 APP mice revealed disrupted neurite trajectories and reductions in dendritic spine density compared with age-matched control mice. A profound deficit in spine density ( similar to 50%) extends similar to 20 mu m from plaque edges. Importantly, a robust decrement ( similar to 25%) also occurs on dendrites not associated with plaques, suggesting widespread loss of postsynaptic apparatus. Plaques and dendrites remained stable over the course of weeks of imaging. Postmortem analysis of axonal immunostaining and colocalization of synaptophysin and postsynaptic density 95 protein staining around plaques indicate a parallel loss of presynaptic and postsynaptic partners. These results show considerable changes in dendrites and dendritic spines in APP transgenic mice, demonstrating a dramatic synaptotoxic effect of dense-cored plaques. Decreased spine density will likely contribute to altered neural system function and behavioral impairments observed in Tg2576 mice. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimers Dis Res Lab, 114 16th St,Room 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Meyer-Luehmann, Melanie/0000-0003-3661-2220 FU NIA NIH HHS [R01 AG020570, 5-T32-AG00277, AG020570, AG08487, P50 AG005134, R01 AG008487, T32 AG000277]; NIBIB NIH HHS [R01 EB000768] NR 63 TC 314 Z9 321 U1 4 U2 27 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 3 PY 2005 VL 25 IS 31 BP 7278 EP 7287 DI 10.1523/JNEUROSCI.1879-05.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 952FB UT WOS:000230987300021 PM 16079410 ER PT J AU Kaushal, R Blumenthal, D Poon, EG Jha, AK Franz, C Middleton, B Glaser, J Kuperman, G Christino, M Fernandopulle, R Newhouse, JP Bates, DW AF Kaushal, R Blumenthal, D Poon, EG Jha, AK Franz, C Middleton, B Glaser, J Kuperman, G Christino, M Fernandopulle, R Newhouse, JP Bates, DW CA Cost Natl Hlth Info Network Wkng Grp TI The costs of a national health information network SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONSENSUS; DELPHI; CARE AB Background: The use of information technology may result in a safer and more efficient health care system. However, consensus does not exist about the structure or costs of a national health information network (NHIN). Objectives: To describe the potential structure and estimate the costs of an NHIN. Design: Cost estimates of an NHIN model developed by an expert panel. Setting: U.S. health care system. Measurements: An expert panel estimated the existing and the expected prevalence in 5 years of critical information technology functionalities. They then developed a model of an achievable NHIN by defining key providers, functionalities, and interoperability functions. By using these data and published cost estimates, the authors determined the cost of achieving this model NHIN in 5 years given the current state of information technology infrastructure. Results: To achieve an NHIN would cost $156 billion in capital investment over 5 years and $48 billion in annual operating costs. Approximately two thirds of the capital costs would be required for acquiring functionalities and one third for interoperability. ongoing costs would be more evenly divided between functionality and interoperability. If the current trajectory continues, the health care system will spend $24 billion on functionalities over the next 5 years or about one quarter of the cost for functionalities of a model NHIN. Limitations: Because of a lack of primary data, the authors relied on expert estimates. Conclusions: While an NHIN will be expensive, $156 billion is equivalent to 2% of annual health care spending for 5 years. Assessments such as this one may assist policymakers; in determining the level of investment that the United States should make in an NHIN. C1 Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02120 USA. Eastern Res Grp Inc, Lexington, MA USA. Cornell Med Sch, New York, NY USA. RP Kaushal, R (reprint author), Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Inst Hlth Policy, 1620 Tremont St, Boston, MA 02120 USA. EM rkaushal@partners.org RI Tao, Youyou/D-2367-2014 NR 27 TC 64 Z9 65 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 2 PY 2005 VL 143 IS 3 BP 165 EP 173 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 951TM UT WOS:000230953900001 PM 16061914 ER PT J AU Levine, RA Schwammenthal, E AF Levine, RA Schwammenthal, E TI Ischemic mitral regurgitation on the threshold of a solution - From paradoxes to unifying concepts SO CIRCULATION LA English DT Review DE echocardiography; mitral valve; myocardial infarction; regurgitation; surgery ID LEFT-VENTRICULAR DYSFUNCTION; PAPILLARY-MUSCLE DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CARDIAC RESYNCHRONIZATION THERAPY; LEAFLET 2ND-ORDER CHORDAE; EXERCISE-INDUCED CHANGES; CORONARY-ARTERY-DISEASE; ACUTE PULMONARY-EDEMA; MILD-TO-MODERATE C1 Harvard Univ, Sch Med, Dept Med,Cardiac Ultrasound Lab, Massachusetts Gen Hosp,Cardiol Div, Boston, MA 02114 USA. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Chaim Sheba Med Ctr, Cardiac Rehabil Inst, IL-52621 Tel Hashomer, Israel. RP Levine, RA (reprint author), Harvard Univ, Sch Med, Dept Med,Cardiac Ultrasound Lab, Massachusetts Gen Hosp,Cardiol Div, YOCC 5068, Boston, MA 02114 USA. EM rlevine@partners.org FU NHLBI NIH HHS [K24 HL67434, R21 HL72353, HL72265, R01 HL38176] NR 142 TC 207 Z9 212 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 AUG 2 PY 2005 VL 112 IS 5 BP 745 EP 758 DI 10.1161/CIRCULATIONAHA.104.486720 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 950YM UT WOS:000230895200018 PM 16061756 ER PT J AU Borovecki, F Lovrecic, L Zhou, J Jeong, H Then, F Rosas, HD Hersch, SM Hogarth, P Bouzou, B Jensen, RV Krainc, D AF Borovecki, F Lovrecic, L Zhou, J Jeong, H Then, F Rosas, HD Hersch, SM Hogarth, P Bouzou, B Jensen, RV Krainc, D TI Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microarrays; neurodegeneration; polyglutamine diseases ID GENE-EXPRESSION; MOUSE MODEL; POLYGLUTAMINE; MARKERS; BRAIN AB Huntington's disease (HID) is an autosomal dominant disorder caused by an expansion of glutamine repeats in ubiquitously distributed huntingtin protein. Recent studies have shown that mutant huntingtin interferes with the function of widely expressed transcription factors, suggesting that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Affymetrix and Amersham Biosciences oligonucleotide microarrays were used to analyze global gene expression in blood samples of HD patients and matched controls. We identified 322 mRNAs that showed significantly altered expression in HID blood samples, compared with controls (P < 0.0005), on two different microarray platforms. A subset of up-regulated mRNAs selected from this group was able to distinguish controls, presymptomatic individuals carrying the HD mutation, and symptomatic HD patients. In addition, early presymptomatic subjects showed gene expression profiles similar to those of controls, whereas late presymptomatic subjects showed altered expression that resembled that of symptomatic HID patients. These elevated mRNAs were significantly reduced in HID patients involved in a dose-finding study of the histone deacetylase inhibitor sodium phenylbutyrate. Furthermore, expression of the marker genes was significantly up-regulated in postmortem HID caudate, suggesting that alterations in blood mRNAs may reflect disease mechanisms observed in HD brain. In conclusion, we identified changes in blood mRNAs that clearly distinguish HID patients from controls. These alterations in mRNA expression correlate with disease progression and response to experimental treatment. Such markers may provide clues to the state of HID and may be of predictive value in clinical trials. C1 Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. Univ Zagreb, Med Sch, Ctr Funct Genom, Zagreb 10000, Croatia. Univ Zagreb, Clin Hosp Ctr, Zagreb 10000, Croatia. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Brigham & Womens Hosp, Lab Funct Genom, Boston, MA 02128 USA. Harvard Univ, Sch Med, Boston, MA 02128 USA. Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. RP Krainc, D (reprint author), Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, 114 16th St,Room 208, Charlestown, MA 02129 USA. EM dkrainc@partners.org FU NCRR NIH HHS [5M01 RR 000334, M01 RR000334]; NINDS NIH HHS [K08 NS002174, NS 002174, NS 045242, P01 NS045242]; Parkinson's UK [K-1206] NR 19 TC 234 Z9 240 U1 1 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 AUG 2 PY 2005 VL 102 IS 31 BP 11023 EP 11028 DI 10.1073/pnas.0504921102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953TC UT WOS:000231102400053 PM 16043692 ER PT J AU Vallet-Gely, I Donovan, KE Fang, R Joung, JK Dove, SL AF Vallet-Gely, I Donovan, KE Fang, R Joung, JK Dove, SL TI Repression of phase-variable cup gene expression by H-NS-like proteins in Pseudomonas aeruginosa SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MvaT; phase-variation ID ESCHERICHIA-COLI; BIOFILM FORMATION; TRANSCRIPTIONAL ACTIVATOR; PHENOTYPIC VARIATION; BACTERIAL BIOFILMS; CYSTIC-FIBROSIS; STPA; DNA; REGULATOR; MVAT AB The cupA gene cluster of Pseudomonas aeruginosa encodes components of a putative fimbrial structure that enable this opportunistic human pathogen to form biofilms on abiotic surfaces. In A aeruginosa, cupA gene expression is repressed by MvaT, a putative transcription regulator thought to belong to the H-NS family of nucleoid-associated proteins that typically function by repressing transcription. Here, we present evidence that MvaT controls phase-variable (ON/OFF) expression of the cupA fimbrial gene cluster. Using a directed proteomic approach, we show that MvaT associates with a related protein in A aeruginosa called MvaU. Analysis with a bacterial two-hybrid system designed to facilitate the study of protein dimerization indicates that MvaT and MvaU can form both heteromeric and homomeric complexes, and that formation of these complexes is mediated through the N-terminal regions of MvaT and MvaU, both of which are predicted to adopt a coiled-coil conformation. We show further that, like MvaT, MvaU can repress phase-variable expression of the cupA gene cluster. Our findings suggest that fimbrial genes important for biofilm formation can be expressed in a phase-variable manner in A aeruginosa, provide insight into the molecular mechanism of MvaT-dependent gene control, and lend further weight to the postulate that MvaT proteins are H-NS-like in nature. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Dove, SL (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. EM simon.dove@childrens.harvard.edu RI vallet-gely, isabelle/A-1568-2013 FU NIH HHS [DP1 OD006862] NR 30 TC 63 Z9 66 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 AUG 2 PY 2005 VL 102 IS 31 BP 11082 EP 11087 DI 10.1073/pnas.0502663102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953TC UT WOS:000231102400063 PM 16043713 ER PT J AU Smithline, HA Rowe, BH Radeos, MS Cydulka, RK Camargo, CA AF Smithline, HA Rowe, BH Radeos, MS Cydulka, RK Camargo, CA CA Working Grp Emergency Management TI Research opportunities in the management of acute exacerbations of chronic obstructive pulmonary disease SO ACADEMIC EMERGENCY MEDICINE LA English DT Review DE chronic obstructive pulmonary disease; acute exacerbation; emergency department ID ACUTE RESPIRATORY-FAILURE; POSITIVE-PRESSURE VENTILATION; EXHALED NITRIC-OXIDE; EXPIRATORY FLOW-RATE; OXYGEN-THERAPY; LUNG HEALTH; BORG SCALE; BRONCHODILATOR REVERSIBILITY; AIRWAY INFLAMMATION; NATRIURETIC PEPTIDE AB Acute exacerbations of chronic obstructive pulmonary disease are a common problem in the emergency department. Despite considerable research involving the management of this disease over the past decade, much remains unclear from an emergency medicine perspective. Increased research would better guide the management of these complex patients from the perspectives of the patient, the caregiver, and society. The major areas of research can be divided into diagnosis, therapy, and education. The reliability and validity of different definitions of acute exacerbations of chronic obstructive pulmonary disease need to be assessed. The utility and performance characteristics of diagnostic testing need to be determined for this difficult patient population. Specific diagnostic tests include measures of dyspnea, spirometry and exercise tolerance, measures of gas exchange, airway inflammation, and chest imaging. It remains unclear which patient-specific therapies (oxygen, bronchodilators, corticosteroids, antibiotics, non-invasive positive pressure ventilation, and methylxanthines) should be used and monitored. Finally, the utility of education of both health care providers and patients and how it may be applied to the acute setting need to be addressed. C1 Baystate Med Ctr, Dept Emergency Med, Springfield, MA 01199 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. Capital Hlth, Edmonton, AB, Canada. Lincoln Med & Mental Hlth Ctr, Dept Emergency Med, Bronx, NY 10451 USA. Case Western Reserve Univ, Dept Emergency Med, Metrohlth Med Ctr, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Smithline, HA (reprint author), Baystate Med Ctr, Dept Emergency Med, 759 Chestnut St, Springfield, MA 01199 USA. EM howard.smithline@bhs.org FU NHLBI NIH HHS [HL-63841] NR 112 TC 3 Z9 3 U1 2 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2005 VL 12 IS 8 BP 742 EP 750 DI 10.1197/j.aem.2005.03.528 PG 9 WC Emergency Medicine SC Emergency Medicine GA 951TL UT WOS:000230953800009 PM 16079428 ER PT J AU Jagsi, R Shapiro, J Weinstein, DF AF Jagsi, R Shapiro, J Weinstein, DF TI Perceived impact of resident work hour limitations on medical student clerkships: A survey study SO ACADEMIC MEDICINE LA English DT Article ID DUTY HOURS; CARE; PERCEPTIONS; OVERWORK; SLEEP AB Purpose To assess medical students' perceptions of the impact of recent Accreditation Council for Graduate Medical Education policies limiting resident work hours on students' clerkship experiences, resident teaching, and quality of patient care. Method In May/June 2003 and May/June 2004, an original questionnaire was administered to 252 medical students completing required clinical rotations at two teaching hospitals to assess students' perceptions of endpoints that might be affected by resident work hours limits. Response data were analyzed to determine statistical significance of differences between the two years studied. Results Questionnaires were completed by 129 students in 2003 (98%) and 112 students in 2004 (93%), for an overall response rate of 96%. A higher proportion of students perceived limits on work hours in 2004 [46 (41%)] than 2003 [36 (28%), p =.03]. Ratings of resident availability and primary resident's interest in teaching improved in 2004. Otherwise, ratings of the interest, skill, and availability of resident teachers and attending physicians remained stable between 2003 and 2004. Students reported spending similar amounts of time in formal teaching sessions and rated feedback similarly between 2003 and 2004. In 2004, ewer students [28 (25%)] reported considering leaving medicine due to long hours in training than in 2003 [49 (38%), p = .04]. No significant differences in the proportion of students reporting suboptimal care were found [44 (34%) in 2003, 34 (35%) in 2004, p = .57]. Conclusion This small, early study suggests that reductions in resident work hours might be implemented without a significant negative impact upon medical students' self-assessed learning experiences, and that limiting resident work hours may even have a positive impact on medical students. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Off Grad Med Educ, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Sch Med, Boston, MA 02115 USA. RP Weinstein, DF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Off Grad Med Educ, Bulfinch 2,10 Fruit St, Boston, MA 02114 USA. EM dweinstein@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 19 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD AUG PY 2005 VL 80 IS 8 BP 752 EP 757 DI 10.1097/00001888-200508000-00011 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 949PP UT WOS:000230800900008 PM 16043532 ER PT J AU Yogavel, M Velmurugan, D Murugan, P Raj, SSS Fun, HK AF Yogavel, M Velmurugan, D Murugan, P Raj, SSS Fun, HK TI 10-benzyl-3,3,6,6,9-pentamethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H, 5H)-dione SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID MOLECULAR-STRUCTURE; DERIVATIVES; CRYSTAL; ACRIDINEDIONE; MONOHYDRATE; ACETATE AB The title compound, C25H31NO2, crystallizes with two molecules in the asymmetric unit. In both molecules, the central dihydropyridine ring adopts a flattened boat conformation. In molecule A, the outer rings adopt sofa conformations, whereas in molecule B, one of the outer rings is disordered and the other ring adopts a sofa conformation. In the crystal structure, C-H center dot center dot center dot O interactions link the molecules to form a tape that runs along the b axis. C1 Univ Madras, Dept Crystallog & Biophys, Madras 600025, Tamil Nadu, India. Univ Madras, Dept Organ Chem, Madras 600025, Tamil Nadu, India. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Univ Sains Malaysia, XRay Crystallog Unit, George Town 11800, Malaysia. RP Velmurugan, D (reprint author), Univ Madras, Dept Crystallog & Biophys, Guindy Campus, Madras 600025, Tamil Nadu, India. EM d_velu@yahoo.com RI Fun, Hoong-Kun/A-3561-2009; OI Fun, Hoong Kun/0000-0001-9970-067X NR 26 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD AUG PY 2005 VL 61 BP O2761 EP O2763 DI 10.1107/S1600536805023500 PN 8 PG 3 WC Crystallography SC Crystallography GA 951QL UT WOS:000230945400280 ER PT J AU O'Brien, CP AF O'Brien, CP TI Opiate detoxification: what are the goals? SO ADDICTION LA English DT Editorial Material C1 Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP O'Brien, CP (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM obrien@mail.trc.upenn.edu NR 1 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD AUG PY 2005 VL 100 IS 8 BP 1035 EP 1035 DI 10.1111/j.1360-0443.2005.01213.x PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 949FC UT WOS:000230769400001 PM 16042623 ER PT J AU Oslin, DW Slaymaker, VJ Blow, FC Owen, PL Colleran, C AF Oslin, DW Slaymaker, VJ Blow, FC Owen, PL Colleran, C TI Treatment outcomes for alcohol dependence among middle-aged and older adults SO ADDICTIVE BEHAVIORS LA English DT Article DE treatment; alcohol dependence; aged ID USE DISORDERS; RELIABILITY; CARE AB Aims: The purpose of this study was to examine differences in the clinical presentation and treatment outcomes of older adults with a diagnosis of alcohol dependence compared to middle-aged adults. Design: The study is a prospective naturalistic study. Participants included 1358 patients admitted to a residential rehabilitation program for alcohol dependence. Results: Older adults entering an alcohol rehabilitation program are less impaired on a number measures of psychiatric distress and addiction severity but more impaired in somatic health. While there were no significantly different outcomes in abstinence rates at I month, older adults engaged in formal post-discharge aftercare less than middle-aged adults. Conclusions: These results confirm impressions that older adults seeking alcohol treatment may have a lower severity of alcohol dependence compared to those at younger ages. However, results suggest that traditional outpatient substance abuse care is not accepted at the same rates as middle-aged adults. The low rates of engagement suggest the need for age appropriate treatment options and are potentially of concern if treatment is necessary to maintain short-term success. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Penn, Sect Geriatr Psychiat, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ, Philadelphia, PA USA. Philadelphia VA Med Ctr, Ctr Clin, Philadelphia, PA USA. Hazelden Fdn, Butler Ctr Res, Ctr City, MN USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Ann Arbor VA Healthcare Syst, SMITREC, Hlth Serv Res & Dev, Ann Arbor, MI USA. Hanley Ctr, W Palm Beach, FL USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, Dept Psychiat, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu FU NIMH NIH HHS [1K08 MH01599-01] NR 8 TC 17 Z9 17 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2005 VL 30 IS 7 BP 1431 EP 1436 DI 10.1016/j.addbeh.2005.01.007 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 952CR UT WOS:000230980000014 PM 16022937 ER PT J AU Giordano, TP Visnegarwala, F White, AC Troisi, CL Frankowski, RF Hartman, CM Grimes, RM AF Giordano, TP Visnegarwala, F White, AC Troisi, CL Frankowski, RF Hartman, CM Grimes, RM TI Patients referred to an urban HIV clinic frequently fail to establish care: factors predicting failure SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article; Proceedings Paper CT 2nd International-AIDS-Society Conference on HIV Pathogenesis and Treatment CY JUL 13-16, 2003 CL Paris, FRANCE SP Int AIDS Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; INFECTED WOMEN; MEDICAL-CARE; ADHERENCE; SERVICES; SEX AB To measure the success with which patients newly entering outpatient care establish regular care, and assess whether race/ethnicity was a predictive factor, we conducted a medical record review of new patients seen 20 April 1998 to 31 December 1998 at The Thomas Street Clinic, a county clinic for uninsured persons. Patients were considered 'not established' if they never saw a physician in the 6 months after intake ( the 'initial period'), 'poorly established' if seen but a > 6-month gap in care began in the initial period, and 'established' if there were no such gaps. Of 404 patients, 11% were 'not established', 37% 'poorly established', and 53% 'established'. Injection drug use as HIV risk factor (IDU), admitted current alcohol and drug use, age <35 years, and CD4 count / = 200 cells/mm(3) were most common in the 'not established' group and least common in the 'established' group. In multivariate ordinal logistic regression, difficulty establishing care was associated with IDU, admitted current alcohol use, and admitted former drug use. Age > 35 years was protective. Half the indigent patients entering care in this single-site study fail to establish regular care. Substance use and younger age are predictors of failure to establish care. C1 Vet Affairs Med Ctr, Houston, TX 77030 USA. Harris Cty Hosp Dist, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Houston Sch Publ Hlth, Houston, TX USA. RP Giordano, TP (reprint author), Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu OI White, A Clinton/0000-0002-9668-4632 FU NIAID NIH HHS [T32AI07456]; NIMH NIH HHS [K23MH67505] NR 23 TC 88 Z9 88 U1 0 U2 2 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD AUG PY 2005 VL 17 IS 6 BP 773 EP 783 DI 10.1080/09540120412331336652 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 945CI UT WOS:000230478600012 PM 16036264 ER PT J AU Kumarasamy, N Safren, SA Raminani, SR Pickard, R James, R Krishnan, AKS Solomon, S Mayer, KH AF Kumarasamy, N Safren, SA Raminani, SR Pickard, R James, R Krishnan, AKS Solomon, S Mayer, KH TI Barriers and facilitators to antiretroviral medication adherence among patients with HIV in Chennai, India: A qualitative study SO AIDS PATIENT CARE AND STDS LA English DT Article ID VIRAL LOAD; THERAPY; RESISTANCE; INFECTION AB Antiretroviral therapy (ART) for HIV is increasingly being introduced and utilized in diverse areas of the world. However, little research exists on adherence to ART in different cultural settings, particularly in developing countries such as India. This formative qualitative study examined barriers and facilitators of ART adherence among 60 (49 men, 11 women; 33 taking ART, 27 not currently taking ART) patients receiving HIV primary care at YRG CARE, a non-governmental organization, in Chennai, India. The average participant reported becoming HIV infected through heterosexual transmission, was between 31 and 40 years old, had over ninth class standard education, was married, and generally had access to medical care; however, we obtained some qualitative data from various other risk categories. Trained ethnographers at the study site conducted in-depth interviews in the local language. These interviews were analyzed for content and ethnographic data. Almost all of the participants discussed the cost of ART as a barrier, with many reporting extended drug holidays, turning to family and/or friends, or taking drastic measures (i. e., selling family jewels, property) for financial assistance. Other barriers centered on privacy and stigma issues, such as disclosure of HIV inhibiting pill-taking and social support. Frequently discussed facilitators of adherence included perceived benefits of ART and proper adherence, perceptions about the consequences of nonadherence, and social support, if available. These data highlight the importance of reducing the cost of antiretroviral medications, involving family members in HIV care, and addressing privacy issues and stigma in counseling interventions in this setting. C1 Fenway Community Hlth, Res Dept, Boston, MA 02115 USA. YRG CARE, Madras, Tamil Nadu, India. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Miriam Hosp, Providence, RI USA. RP Safren, SA (reprint author), Fenway Community Hlth, Res Dept, 7 Haviland St, Boston, MA 02115 USA. EM ssafren@partners.org FU FIC NIH HHS [TW00237]; NIAID NIH HHS [U01 AI48040-03] NR 18 TC 97 Z9 103 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD AUG PY 2005 VL 19 IS 8 BP 526 EP 537 DI 10.1089/apc.2005.19.526 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 961WI UT WOS:000231692100007 PM 16124847 ER PT J AU Gazdzinski, S Durazzo, TC Studholme, C Song, E Banys, P Meyerhoff, DJ AF Gazdzinski, S Durazzo, TC Studholme, C Song, E Banys, P Meyerhoff, DJ TI Quantitative brain MRI in alcohol dependence: Preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; cigarette smoking; regional brain volumes; magnetic resonance; brain structure-function relationship ID WHITE-MATTER CHANGES; COGNITIVE PERFORMANCE; NICOTINE DEPENDENCE; SUBSTANCE USE; DRINKING HISTORY; ADOLESCENT BRAIN; GRAY-MATTER; AGE; ATROPHY; ADULTS AB Background: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. Methods: High-resolution T-1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. Results: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. Conclusions: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. No Calif Inst Res & Educ, San Francisco, CA USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Gazdzinski, S (reprint author), Univ Calif San Francisco, Dept Vet Affairs Med Ctr, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM spg@itsa.ucsf.edu FU NIAAA NIH HHS [AA10788] NR 78 TC 104 Z9 105 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2005 VL 29 IS 8 BP 1484 EP 1495 DI 10.1097/01.alc.0000175018.72488.61 PG 12 WC Substance Abuse SC Substance Abuse GA 962XY UT WOS:000231767900016 PM 16131857 ER PT J AU Biddinger, SB Ludwig, DS AF Biddinger, SB Ludwig, DS TI The insulin-like growth factor axis: a potential link between glycemic index and cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID BINDING-PROTEINS; FACTOR (IGF)-I; APOPTOSIS; CELLS; RISK; LOAD C1 Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ludwig, DS (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM david.ludwig@childrens.harvard.edu NR 9 TC 19 Z9 22 U1 1 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2005 VL 82 IS 2 BP 277 EP 278 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 956IJ UT WOS:000231293100002 PM 16087968 ER PT J AU Guadagnolo, BA Haddad, RI Posner, MR Weeks, L Wirth, LJ Norris, CM Sullivan, CA Goguen, L Busse, PM Tishler, R AF Guadagnolo, BA Haddad, RI Posner, MR Weeks, L Wirth, LJ Norris, CM Sullivan, CA Goguen, L Busse, PM Tishler, R TI Organ preservation and treatment toxicity with induction chemotherapy followed by radiation therapy or chemoradiation for advanced laryngeal cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE larynx cancer; induction chemotherapy; organ preservation; radiation therapy; swallowing dysfunction ID SQUAMOUS-CELL CARCINOMA; PHASE-I/II TRIAL; NECK-CANCER; RANDOMIZED-TRIAL; ADVANCED HEAD; II TRIAL; DOCETAXEL; CISPLATIN; RADIOTHERAPY; FLUOROURACIL AB Objectives: The authors reviewed records of patients with advanced laryngeal cancer treated with induction chemotherapy (IC) and hyperfractionated radiation therapy (RT) or chemoradiation (CRT) to determine the rates of organ preservation and function. Methods: A total of 29 patients with stage 111 (45%) and stage IV (55%) squamous cell carcinoma of the larynx (SCCL), were treated with IC and RT or CRT in I of 7 consecutive trials. Fifty-five percent had clinically node-positive disease. Fifty-five percent and 45% had T3 or T4 tumors, respectively. All received 3 cycles of platinum-based IC. Daily RT was given to 48%, twice-daily RT to 45%, and concomitant boost RT to 7%. CRT was carboplatin (28%) or docetaxel (28%). Those treated with twice-daily RT did not receive CRT. Results: The median follow-up is 52 months. Overall survival is 66%. Relapse occurred in 12 patients (41%), and 6 underwent salvage laryngectomy (5 stage III, I stage IV). Fifty-nine percent of patients (17 of 29) are alive at last follow-up with an anatomically intact larynx, and 48% (14 of 29) are alive with a functional larynx. Of the 23 patients for whom detailed information on gastrostomy tube (g-tube) placement/removal was available, median time with g-tube was 12 months, and 15 of 23 patients (65%) had a g-tube for 6 months or more. Twenty-three of all 29 patients (79%) retained an anatomically intact larynx, but 7 of 23 (30%) never resumed their pretreatment organ function. The overall rate of functional organ preservation, regardless of survival, was 55% (16/29). The 7 of 29 patients (26%) who retained a nonfunctional larynx required permanent g-tube or were unable to return to pretreatment oral intake capability. Nine of 13 with T4 SCCL (69%) compared with 7 of 16 (44%) T3 SCCL retained a functional larynx. Conclusion: The rate of larynx preservation is high, but toxicity remains significant with IC followed by hyperfractionated RT or CRT in advanced laryngeal cancer. Half of all patients were alive, able to retain their larynx, and return to pretreatment function. Advanced stage was not an indicator of poor outcome. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Guadagnolo, BA (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, 375 Longwood Ave, Boston, MA 02215 USA. EM aguadagnolo@lroc.harvard.edu NR 24 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 2005 VL 28 IS 4 BP 371 EP 378 DI 10.1097/01.coc.0000162423.13431.8d PG 8 WC Oncology SC Oncology GA 953MK UT WOS:000231080300009 PM 16062079 ER PT J AU Quinn, TR Duncan, LM Zembowicz, A Faquin, WC AF Quinn, TR Duncan, LM Zembowicz, A Faquin, WC TI Cutaneous metastases of follicular thyroid carcinoma - A report of four cases and a review of the literature SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE cutaneous metastasis; follicular thyroid carcinoma; Hurthle cell; insular carcinoma; metastatic tumors ID APOCRINE CARCINOMA; SALIVARY-GLANDS; SKIN; ONCOCYTOMAS; ADENOMA; TUMORS AB Cutaneous metastasis of follicular carcinoma of the thyroid is very rare, and when it occurs, can exhibit a variety of histologic appearances. The 4 cases presented here were identified from the surgical pathology files of the James Homer Wright Laboratories of Pathology at the Massachusetts General Hospital (NIGH). The cases consisted of 4 patients, 3 men and I woman, aged 52 to 75 years, with cutaneous metastasis of follicular thyroid carcinoma. The tumors include a conventional follicular carcinoma, a follicular carcinoma with anaplastic transformation following initial metastasis, the first reported cutaneous metastases of a follicular carcinoma with oncocytic features (Hurthle cell carcinoma), and a follicular carcinoma with a prominent insular carcinoma component. All 4 tumors were widely invasive within the thyroid gland. Sites of dermal metastases included a post-thyroidectomy scar, scalp, and sacral skin. Three metastases retained the morphologic and immunocytochemical features of the primary thyroid tumors. However, in one case there was high-grade transformation to anaplastic carcinoma following treatment of a sacral metastasis with accompanying loss of the characteristic immunophenotype of follicular thyroid carcinoma. Awareness of the varied morphologies of metastatic follicular thyroid carcinoma to the skin may prompt immunohistochemical analysis and the request for a complete clinical history, ultimately preventing misdiagnosis. C1 Pathol Serv Inc, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Quinn, TR (reprint author), Pathol Serv Inc, 640 Mem Dr, Cambridge, MA 02139 USA. EM tquinn@pathsrv.com NR 26 TC 17 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD AUG PY 2005 VL 27 IS 4 BP 306 EP 312 DI 10.1097/01.dad.0000164606.33779.6f PG 7 WC Dermatology SC Dermatology GA 960DS UT WOS:000231571000006 PM 16121050 ER PT J AU Strate, LL Saltzman, JR Ookubo, R Mutinga, ML Syngal, S AF Strate, LL Saltzman, JR Ookubo, R Mutinga, ML Syngal, S TI Validation of a clinical prediction rule for severe acute lower intestinal bleeding SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID UPPER-GASTROINTESTINAL HEMORRHAGE; LOW-RISK PATIENTS; METHODOLOGICAL STANDARDS; URGENT COLONOSCOPY; HOSPITAL LENGTH; SCORING SYSTEM; STAY; MANAGEMENT; DIAGNOSIS; CARE AB OBJECTIVES: Acute lower intestinal bleeding is a heterogeneous disorder and identification of high-risk patients is challenging. We previously retrospectively identified predictors of severity in patients with acute lower intestinal bleeding. The aim of this study was to prospectively validate a clinical prediction rule for severe acute lower intestinal bleeding. METHODS: This was a prospective, observational cohort study of consecutive patients admitted to an academic, tertiary care or a community-based teaching hospital for management of acute lower intestinal bleeding. Data were collected on seven previously identified predictors of severe bleeding: heart rate >= 100/min, systolic blood pressure <= 115 mmHg, syncope, nontender abdominal exam, rectal bleeding in the first 4 h of evaluation, aspirin use, and > 2 comorbid conditions. Severe bleeding was defined as transfusion of >= 2 units of red blood cells, and/or a decrease in hematocrit of >= 20% in the first 24 h, and/or recurrent rectal bleeding after 24 h of stability (accompanied by a further decrease in hematocrit of >= 20%, and/or additional blood transfusions, and/or readmission for acute lower intestinal bleeding within 1 wk of discharge). Patients were stratified into 3 risk groups according to the previously developed prediction rule: low (no risk factors), moderate (1-3 risk factors), and high (> 3 risk factors). RESULTS: A total of 275 patients with acute lower intestinal bleeding were identified. The risk of severe bleeding in each risk category was similar in the validation and derivation cohorts (p values > 0.05): low risk 6%versus 9%, moderate risk 43%versus 43%, and high risk 79%versus 84%. The area under the receiver operating characteristic curve was 0.754 for the validation cohort and 0.761 for the derivation cohort. The magnitude of the risk score was significantly correlated with major clinical outcomes including surgery, death, blood transfusions, and length of stay. CONCLUSION: We have developed and prospectively validated a clinical prediction rule for acute severe lower intestinal bleeding. This prediction rule could improve the triage of patients to appropriate levels of care and interventions, and guide a more standardized approach to acute lower intestinal bleeding. C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Faulkner Hosp, Div Gastroenterol, Boston, MA USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Strate, LL (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 40 Z9 41 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2005 VL 100 IS 8 BP 1821 EP 1827 DI 10.1111/j.1572-0241.2005.41755.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952GN UT WOS:000230992100027 PM 16086720 ER PT J AU Edwards, MS Wilson, DB Craven, TE Stafford, J Fried, LF Wong, TY Klein, R Burke, GL Hansen, KJ AF Edwards, MS Wilson, DB Craven, TE Stafford, J Fried, LF Wong, TY Klein, R Burke, GL Hansen, KJ TI Associations between retinal microvascular abnormalities and declining renal function in the elderly population: The Cardiovascular Health Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE retina; chronic kidney disease (CKD); microvascular; epidemiology; elderly ID DIALYSIS-FREE SURVIVAL; DIABETIC-RETINOPATHY; OLDER POPULATION; BLOOD-PRESSURE; RISK-FACTORS; ATHEROSCLEROSIS RISK; ISCHEMIC NEPHROPATHY; VESSEL DIAMETERS; SURGICAL REPAIR; HYPERTENSION AB Background: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. Methods: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. Results: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 mu mol/L] versus -0.21 mg/dL [-19 mu mol/L] and -0.48 mL/min/1.73 m(2) [-0.01 mL/s/1.73 m(2)] versus +1.74 mL/min/1.73 m(2) [+0.03 mL/s/1.73 m(2)], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-mu mol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. Conclusion: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Winston Salem, NC 27157 USA. Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. Univ Wisconsin, Dept Optometry & Visual Sci, Madison, WI 53706 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Edwards, MS (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM medwards@wfubmc.edu FU NHLBI NIH HHS [N-01-HL-85079]; NIDDK NIH HHS [1-R01-DK-47414] NR 32 TC 81 Z9 83 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2005 VL 46 IS 2 BP 214 EP 224 DI 10.1053/j.ajkd.2005.05.005 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 951JM UT WOS:000230926100004 PM 16112039 ER EF