FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Orlander, JD AF Orlander, Jay D. TI Twelve Tips for use of a white board in clinical teaching: Reviving the chalk talk SO MEDICAL TEACHER LA English DT Editorial Material AB Little has been written on the art of using a board in clinical teaching. The technological development of the white board appears to have coincided with that of the laptop computer and accompanying LCD projector, so that fewer and fewer teaching sessions appear to utilize the board as an efficient teaching tool. I have observed this most commonly among younger faculty who are most comfortable with technology and who may lack training and experience with a blank board. This paper offers suggestions on using the board in clinical teaching in order to enhance the educational process through better engagement of the learners. C1 Boston Univ, Sch Med, VA Boston Hlth Care Syst, Med Serv, Boston, MA 02130 USA. RP Orlander, JD (reprint author), Boston Univ, Sch Med, VA Boston Hlth Care Syst, Med Serv, 150 S Huntington Ave,MAV-111, Boston, MA 02130 USA. EM Jay.Orlander@med.va.gov OI Orlander, Jay/0000-0003-0204-8449 NR 3 TC 2 Z9 2 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2007 VL 29 IS 2-3 BP 89 EP 92 DI 10.1080/01421590701287913 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 207QE UT WOS:000249265100004 PM 17701616 ER PT J AU Miller, E Green, AR AF Miller, Elizabeth Green, Alexander R. TI Student reflections on learning cross-cultural skills through a 'cultural competence' OSCE SO MEDICAL TEACHER LA English DT Article ID STRUCTURED CLINICAL EXAMINATION; MEDICAL-STUDENTS; COMMUNICATION-SKILLS; SUBSTANCE-ABUSE; HEALTH-CARE; EDUCATION; RESIDENTS; CURRICULUM; PHYSICIAN; AWARENESS AB Background: Medical schools use OSCEs ( objective structured clinical examinations) to assess students' clinical knowledge and skills, but the use of OSCEs in the teaching and assessment of cross- cultural care has not been well described. Objectives: To examine medical students' reflections on a cultural competence OSCE station as an educational experience. Design and Setting: Students at Harvard Medical School in Boston completed a ' cultural competence' OSCE station ( about a patient with uncontrolled hypertension and medication non- adherence). Individual semi- structured interviews were conducted with a convenience sample of twenty- two second year medical students, which were recorded, transcribed, and analysed. Measurements and Results: Students' reflections on what they learned as the essence of the case encompassed three categories: ( 1) eliciting the patient's perspective on their illness; ( 2) examining how and why patients take their medications and inquiring about alternative therapies; and ( 3) exploring the range of social and cultural factors associated with medication non- adherence. Conclusions: A cultural competence OSCE station that focuses on eliciting patients' perspectives and exploring medication non- adherence can serve as a unique and valuable teaching tool. The cultural competence OSCE station may be one pedagogic method for incorporating cross- cultural care into medical school curricula. C1 Univ Calif Davis, Sch Med, Ctr Reducing Hlth Disparit, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Disparit Solut Ctr, Dept Med, Inst Hlth Policy, Boston, MA 02114 USA. RP Miller, E (reprint author), Univ Calif Davis, Sch Med, Ctr Reducing Hlth Disparit, CRISP 2921,Stockton Blvd,Suite 1400, Sacramento, CA 95817 USA. EM elizabeth.miller@ucdmc.ucdavis.edu RI Miller, Elizabeth/E-7939-2012 NR 39 TC 5 Z9 5 U1 0 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2007 VL 29 IS 4 BP E76 EP E84 DI 10.1080/01421590701266701 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 207XX UT WOS:000249285500032 PM 17786736 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI The von Hippel-Lindau tumor suppressor protein and kidney cancer SO MEDICINA-BUENOS AIRES LA English DT Article; Proceedings Paper CT International Symposium on New Directions in Cancer Management CY JUN 06-08, 2007 CL Acad Nacl Med, Buenos Aires, ARGENTINA SP Weleda, Inst Hischia, Bayer Healthcare AG, Bayer Schering Pharma, Bristol Myer Squibb, Conicet, Fundac Bunge & Born, LKM, Microsules Argentina, Novartis, Novo Nordisk, Pierre Fabre, Raffo, Monteverde, Sidus HO Acad Nacl Med DE renal carcinoma; VHI tumor suppressor gene ID HYPOXIA-INDUCIBLE FACTOR; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; MAMMALIAN TARGET; PROLINE HYDROXYLATION; INTERFERON-ALPHA; GENE-PRODUCT; E-CADHERIN; HIF-ALPHA; CYCLIN D1 AB Inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) plays a causal role in the development of hereditary (von Hippel-Lindau disease) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, is the substrate recognition subunit of a ubiquitin ligase that targets the alpha subunits of the heterodimeric transcription factor HIF (Hypoxia-inducible Factor) for destruction when oxygen is present. Cells lacking functional pVHL, or exposed to low oxygen (hypoxia), accumulate HIF, which activates a suite of genes involved in acute or chronic adaptation to hypoxia. A number of these genes, including VEGF, PDGF B, and TGF?, have been implicated in tumorigenesis. Downregulation of HIF is both necessary and sufficient for pVHL to suppress the growth of VHL-/- tumor cells in animal models, suggesting that drugs that inhibit HIF, or HIF-responsive gene products, might be useful for the treatment of clear cell kidney cancer. Indeed, multiple drugs that inhibit VEGF or its receptor KDR have now demonstrated activity against this disease. The rate of HIF transcription and synthesis is sensitive to changes in the activity of the PI3K-AKT-mTOR pathway. A recent randomized trial showed that patients with kidney cancer benefited from treatment with an mTOR inhibitor. Current studies are aimed at combining VEGF inhibitors with mTOR inhibitors as well as at identifying additional agents that can, at least indirectly, inhibit HIF or cancer-relevant HIF-responsive gene products. C1 Brigham & Womens Hosp, Harvard Med Sch, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 65 TC 0 Z9 0 U1 0 U2 1 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2007 VL 67 BP 6 EP 10 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 211KH UT WOS:000249522200004 ER PT S AU Vosburgh, KG Estepar, RS AF Vosburgh, Kirby G. Estepar, Raul San Jose BE Westwood, JD Haluck, RS Hoffman, HM Mogel, GT Phillips, R Robb, RA Vosburgh, KG TI Natural Orifice Transluminal Endoscopic Surgery (NOTES): An Opportunity for Augmented Reality Guidance SO MEDICINE MEETS VIRTUAL REALITY 15 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 15th Conference on Medicine Meets Virtual Reality CY FEB 06-09, 2007 CL Long Beach, CA DE endoscopy; augmented reality; laparoscopy; image registration; NOTES AB Laparoscopic techniques have gained wide acceptance because they offer a safe and less invasive alternative to open surgery. To further reduce the invasiveness of peritoneal access, the next logical step is to eliminate the incision through the abdominal wall using natural orifices as entry points. This Natural Orifice Transluminal Endoscopic Surgery (NOTES) approach has the potential to replace or augment current techniques. Several research groups have cut through the stomach or colon wall (per-oral transgastric or per-anal transcolonic) to perform organ resections in animal models, and some procedures in humans have been reported anecdotally. Widespread use of these techniques will depend on providing the physician with adequate visual feedback, clear indicators of instrument location and orientation, and support in the recognition of anatomic structures. Compared with laparoscopy, successful endoscopy must accommodate several additional complexities: (1) The flexibility of the endoscope tip complicates the understanding of its distal orientation. Successful navigation inside the stomach and in the abdominal cavity generally requires two years of sub-specialty training. (2) Several surgical targets lie in a retrograde position with respect to an incision in the stomach wall. Efficient and safe access to the pancreas, gall bladder, or the kidneys requires detailed knowledge of the tip placement relative to adjacent anatomic structures. (3) Since there is limited direct access to the abdomen, iatrogenic injuries, such as the accidental cutting of an artery, will be more dangerous and difficult to manage. We present here approaches to resolving these limitations though augmented reality techniques using pre-procedure CT or MRI imaging, real time tracking and reference image registration, and display to the operating physician. As an example, the utility of image registration techniques for orientation for the gastric access puncture is discussed in detail. It is anticipated that such augmentation will make intra-cavitary interventional techniques easier to master and use in practice, and thus more likely to be widely adopted. C1 [Vosburgh, Kirby G.] Massachusetts Gen Hosp, CIMIT, Boston, MA 02114 USA. RP Vosburgh, KG (reprint author), 702,165 Cambridge St, Boston, MA 02114 USA. EM kirby@bwh.harvard.edu; kirby@bwh.harvard.edu FU NHLBI NIH HHS [K25 HL104085] NR 11 TC 33 Z9 35 U1 1 U2 1 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-713-0 J9 ST HEAL T PY 2007 VL 125 BP 485 EP 490 PG 6 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BLN86 UT WOS:000270613800112 PM 17377333 ER PT J AU Ecker, JL AF Ecker, Jeffrey L. TI Evidence and opinion: closing the gap SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02138 USA. RP Ecker, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02138 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2007 VL 14 IS 1 BP 3 EP 4 DI 10.1097/01.gme.0000247018.48630.e4 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 136XG UT WOS:000244256800002 PM 17179792 ER PT J AU Avis, NE Pian-Smith, MCM AF Avis, Nancy E. Pian-Smith, May C. M. TI Acupuncture for hot flashes SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID QUALITY-OF-LIFE; HORMONE REPLACEMENT THERAPY; MENOPAUSE-RELATED SYMPTOMS; ESTROGEN PLUS PROGESTIN; MIDDLE-AGED WOMEN; POSTMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; ALTERNATIVE MEDICINE; PLACEBO NEEDLE; HEALTH C1 Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. RP Avis, NE (reprint author), Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. NR 38 TC 3 Z9 3 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2007 VL 14 IS 1 BP 10 EP 13 DI 10.1097/01.gme.0000252908.72738.9f PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 136XG UT WOS:000244256800005 PM 17179790 ER PT J AU Clermont, AC Bursell, SE AF Clermont, Allen C. Bursell, Sven-Erik TI Retinal blood flow in diabetes SO MICROCIRCULATION LA English DT Article DE diabetes; endothelin; nitric oxide; protein kinase C; retinal blood flow; vitamin E ID PROTEIN-KINASE-C; ENDOTHELIUM-DEPENDENT VASODILATION; VIDEO FLUORESCEIN ANGIOGRAPHY; ANGIOTENSIN-CONVERTING ENZYME; ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE SYNTHESIS; VON-WILLEBRAND-FACTOR; BETA-ISOFORM; VITAMIN-E; IN-VIVO AB Objective: This is a review of work focused on characterizing retinal blood flow in diabetes. The review describes results on validation of the methodology for retinal blood flow measurements, the mechanisms of action of various of factors that contribute to abnormalities if retinal blood flow in diabetic rodent models, and the translation Of these results to clinical studies demonstrating the effectiveness of different different therapeutic agents in normalizing retinal blood flow abnormalities in patients with diabetes. Methods: Retinal blood flow measurements were performed using video fluorescein angiography, a methodology that is based on the measurement of fluorescein dye circulation times through retinal circulation Results: The results of a number of experiments are summarized, detailing the effects of hyperglycemia and the roles of factors such as Protein kinase C activation, endothelin-1 and endothelin-3, angiotensin- II, and nitric oxide in the development of retinal blood flow abnormalities in diabetes. Conclusion: The measurement of retinal blood flow, both in animals and in clinical trials using the same retinal blood flow measurement methodology can provide a valuable method of quantitation allowing characterization of physiological effects and their association with metabolic alterations in diabetes and their effects on the development and incidence of microvasenlar complications. C1 Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Eye Res Sect, Boston, MA USA. RP Bursell, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA USA. NR 70 TC 40 Z9 42 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD JAN PY 2007 VL 14 IS 1 BP 49 EP 61 DI 10.1080/10739680601072164 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 135VN UT WOS:000244182100005 PM 17365661 ER PT B AU Rosowski, JJ Furlong, C Ravicz, ME Rodgers, MT AF Rosowski, J. J. Furlong, C. Ravicz, M. E. Rodgers, M. T. BE Huber, A Eiber, A TI REAL-TIME OPTO-ELECTRONIC HOLOGRAPHIC MEASUREMENTS OF SOUND-INDUCED TYMPANIC MEMBRANE DISPLACEMENTS SO MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY LA English DT Proceedings Paper CT 4th International Symposium on Middle Ear Mechanics in Research and Otology CY JUL 27-30, 2006 CL Univ zurich, Zurich, SWITZERLAND HO Univ zurich ID MIDDLE-EAR; VIBRATIONS; MECHANICS; CAT AB Computer-aided Opto-Electronic Holography (OEH) was used to measure the sound-induced displacement of the tympanic membrane (TM) of cadaver cats and chinchillas. Real-time time-averaged holograms (gathered at video rates) were used to roughly determine the frequency dependence of TM displacements as tone frequency was swept from 0.4 to 20 kHz. Stroboscopic holography was used at selected frequencies to measure the difference in displacement between condensation and rarefaction phase of the pressure stimulus and enable discrimination of inward and outward displacements of the TM surface with nanometer resolution. The time-averaged holographic data demonstrate standing wave patterns on the cat's TM surface, which move from simple uni-modal or bi-modal patterns at low frequencies, through complicated multi-modal patterns above 3 kHz, to highly ordered arrangements of displacement waves with tone frequencies above 15 kHz. The frequency boundaries of the different wave patterns are lower in chinchilla (simple patterns below 0.6 kHz, ordered patterns above 4 kHz) than cat. The stroboscopic holography measurements indicate wave-like motion patterns on the TM surface, where the number of wavelengths captured along a transect of the TM increased with stimulus frequency with as many as 11 wavelengths visible on the chinchilla TM at 16 kHz. Counts of the visible number of wavelengths on TM transects with different sound stimulus frequency provided estimates of wave velocity along the TM surface that ranged from 5 m/s at frequencies below 8 kHz and increased to 25 m/s by 20 kHz. C1 [Rosowski, J. J.; Ravicz, M. E.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-270-737-6 PY 2007 BP 295 EP 305 DI 10.1142/9789812708694_0040 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA BIP97 UT WOS:000261795300040 ER PT J AU Gold, JI Taft, CT Keehn, MG King, DW King, LA Samper, RE AF Gold, Jeffrey I. Taft, Casey T. Keehn, Molly G. King, Daniel W. King, Lynda A. Samper, Rita E. TI PTSD symptom severity and family adjustment among female Vietnam veterans SO MILITARY PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; CHILD-BEHAVIOR; PARTNERS; SCALES AB This study examined relations between posttraumatic stress disorder (PTSD) symptom severity and several family adjustment variables among a sample of 89 female Vietnam veterans and their male relationship partners. Findings revealed associations between PTSD symptom severity and measures of marital adjustment, family adaptability, family cohesion, parenting satisfaction, and psychological abuse. Results suggest that the presence of PTSD symptomatology may have important implications with regard to the family life of female Vietnam veterans. C1 Univ So Calif, Keck Sch Med, Dept Anesthesiol & Pediat, Los Angeles, CA 90089 USA. Childrens Hosp Los Angeles, Dept Anesthesiol Crit Care Med, Los Angeles, CA 90027 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Dept Psychiat & Psychol, Boston, MA 02215 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM caseytaft2003@yahoo.com NR 45 TC 39 Z9 39 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0899-5605 J9 MIL PSYCHOL JI Milit. Psychol. PY 2007 VL 19 IS 2 BP 71 EP 81 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 173RE UT WOS:000246889400001 ER PT J AU Caviness, VS AF Caviness, Verne S. BE Fischer, KW Bernstein, JH ImmordinoYang, MH TI Essay: Brain volume and the acquisition of adaptive capacities SO MIND, BRAIN, AND EDUCATION IN READING DISORDERS SE Cambridge Studies in Cognitive and Perceptual Development LA English DT Article; Book Chapter ID DEVELOPMENTAL DYSLEXIA; INDIVIDUAL VARIABILITY; CORTICAL ORGANIZATION; LANGUAGE-DEVELOPMENT; FUNCTIONAL-ANATOMY; CHILDREN; MRI; PLASTICITY; INJURY; SKILLS C1 [Caviness, Verne S.] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. [Caviness, Verne S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. NR 59 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-85479-5 J9 CAMB STUD COGN PERC PY 2007 IS 11 BP 30 EP 36 PG 7 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA BYF83 UT WOS:000298475000003 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Yamaji, T Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Kirkner, Gregory J. Yamaji, Taiki Loda, Massimo Fuchs, Charles S. TI Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP SO MODERN PATHOLOGY LA English DT Article DE colon cancer; CIMP; p27; p53; cyclin-dependent kinase inhibitor; MSI ID ISLAND METHYLATOR PHENOTYPE; UBIQUITIN-PROTEASOME PATHWAY; KINASE INHIBITOR P27; DNA METHYLATION; PROGNOSTIC-SIGNIFICANCE; DOWN-REGULATION; TUMORS; P53; DEGRADATION; EXPRESSION AB Downregulation of p27 (cyclin-dependent kinase inhibitor-1B, CDKN1B or KIP1) is caused by increased ubiquitin-mediated proteasomal degradation in colorectal cancer, and has been associated with poor prognosis. CpG island methylator phenotype ( CIMP) is a phenotype of colorectal cancer with extensive promoter methylation, and associated with high degree of microsatellite instability (MSI-H) and BRAF mutations. We have recently shown that both CIMP and MSI-H are inversely associated with downregulation of p21 ( CDKN1A or CIP1), another cyclin-dependent kinase inhibitor. However, no study to date has examined relationship between p27 and CIMP status in colorectal cancer. Using MethyLight assays, we measured DNA methylation in five CIMP-specific gene promoters {CACNA1G, CDKN2A (p16), CRABP1, MLH1 and NEUROG1} in 706 colorectal cancer samples obtained from two large prospective cohorts. Among the 706 tumors, 112 (16%) were CIMP-high tumors with >= 4/5 methylated promoters. We assessed p27 and p53 expressions by immunohistochemistry. Loss of nuclear p27 expression {observed in 231 tumors (33%)} was significantly associated with CIMP-high, MSI-H and BRAF mutations, and these associations were much more pronounced among p53-negative tumors than p53-positive tumors. When CIMP-high and non-CIMP-high tumors were stratified by MSI status ( or KRAS and BRAF status), CIMP-high and MSI-H ( but not BRAF mutations) were still significantly associated with nuclear p27 loss. Nuclear p27 loss did not appear to be directly related to CDKN2A ( p16) methylation. We conclude that downregulation of nuclear p27 is associated with CIMP-high and MSI- H in colorectal cancer. These associations are stronger among p53 wild-type tumors, implying important interplay of p27 and p53 functions ( or dysfunctions) in the development of various molecular subtypes of colorectal cancer. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 46 TC 46 Z9 46 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2007 VL 20 IS 1 BP 15 EP 22 DI 10.1038/modpathol.3800709 PG 8 WC Pathology SC Pathology GA 119IC UT WOS:000243005000003 PM 17086168 ER PT J AU Berchtold, CM Wu, ZH Huang, TT Miyamoto, S AF Berchtold, Craig M. Wu, Zhao-Hui Huang, Tony T. Miyamoto, Shigeki TI Calcium-dependent regulation of NEMO nuclear export in response to genotoxic stimuli SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; DNA-DAMAGE; IONIZING-RADIATION; SUBCELLULAR-LOCALIZATION; TOPOISOMERASE INHIBITORS; REACTIVE OXYGEN; GENE-EXPRESSION; PORE COMPLEXES; CANCER-THERAPY; RAN/TC4 GTPASE AB The mechanisms involved in activation of the transcription factor NF-kappa B by genotoxic agents are not well understood. Previously, we provided evidence that a regulatory subunit of the I kappa B kinase (IKK) complex, NF-kappa B essential modulator (NEMO)/IKK gamma, is a component of a nuclear signal that is generated after DNA damage to mediate NF-kappa B activation. Here, we found that etoposide (VP16) and camptothecin induced increases in intracellular free calcium levels at 60 min after stimulation of CEM T leukemic cells. Inhibition of calcium increases by calcium chelators, BAPTA-AM and EGTA-AM, abrogated NF-kappa B activation by these agents in several cell types examined. Conversely, thapsigargin and ionomycin attenuated the BAPTA-AM effects and promoted NF-kappa B activation by the genotoxic stimuli. Analyses of nuclear NEMO levels in VP16-treated cells suggested that calcium was required for nuclear export of NEMO. Inhibition of the nuclear exporter CRM1 by leptomycin B did not interfere with NEMO nuclear export. Similarly, deficiency of a plausible calcium-dependent nuclear export receptor, calreticulin, failed to prevent NF-kappa B activation by VP16. However, temperature inactivation of the Ran guanine nucleotide exchange factor RCC1 in the tsBN2 cell line harboring a temperature-sensitive mutant of RCC1 blocked NF-kappa B activation induced by genotoxic stimuli. Overexpression of Ran in this cell model showed that DNA damage stimuli induced formation of a complex between Ran and NEMO, suggesting that RCC1 regulated NF-kappa B activation through the modulation of RanGTP. Indeed, evidence for VP16-inducible interaction between Ran-GTP and NEMO could be obtained by means of glutathione S-transferase (GST) pull-down assays using GST fused to the Ran binding domain of RanBP2, which specifically interacts with the GTP-bound form of Ran. BAPTA-AM did not alter these interactions, suggesting that calcium is a necessary step beyond the formation of a Ran-GTP-NEMO complex in the nucleus. These results suggest that calcium has a unique role in genotoxic stress-induced NF-kappa B signaling by regulating nuclear export of NEMO subsequent to the formation of a nuclear export complex composed of Ran-GTP, NEMO, and presumably, an undefined nuclear export receptor. C1 Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miyamoto, S (reprint author), Univ Wisconsin, Dept Pharmacol, 301 SMI,1300 Univ Ave, Madison, WI 53706 USA. EM smiyamot@wisc.edu FU NCI NIH HHS [R01 CA077474, R01 CA 77474, R01 CA 81065, R01 CA081065] NR 92 TC 25 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2007 VL 27 IS 2 BP 497 EP 509 DI 10.1128/MCB.01772-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124FR UT WOS:000243353500007 PM 17074802 ER PT J AU Gao, L Wang, JN Wang, YZ Andreadis, A AF Gao, Lei Wang, Junning Wang, Yingzi Andreadis, Athena TI SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID PRE-MESSENGER-RNA; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; EXPRESSION; GENE; ENHANCER; SEQUENCES; LOCALIZATION; DOMAINS; COMPLEX AB The microtubule-associated protein tau is important to normal neuronal function in the mammalian nervous system. Aggregated tau is the major component of neurofibrillary tangles (NFTs), present in several neurodegenerative diseases, including Alzheimer's and frontotemporal dementia with Parkinsonism (FTDP). Splicing misregulation of adult-specific exon 10 results in expression of abnormal ratios of tau isoforms, leading to FTDP. Positions +3 to +16 of the intron downstream of exon 10 define a clustering region for point mutations that are found in FTDP. The serine/arginine-rich (SR) factor 9G8 strongly inhibits inclusion of tau exon 10. In this study, we established that 9G8 binds directly to this clustering region, requires a wild-type residue at position + 14 to inhibit exon inclusion, and RNAi constructs against 9G8 increase exon 10 inclusion. These results indicate that 9G8 plays a key role in regulation of exon 10 splicing and imply a pathogenic role in neurodegenerative diseases. (c) 2006 Elsevier Inc. All rights reserved. C1 UMMS, Shriver Ctr, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. RP Andreadis, A (reprint author), UMMS, Shriver Ctr, 200 Trapelo Rd, Waltham, MA 02452 USA. EM athena.andreadis@umassmed.edu FU NIA NIH HHS [AG018486, R01 AG018486] NR 52 TC 28 Z9 28 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2007 VL 34 IS 1 BP 48 EP 58 DI 10.1016/j.mcn.2006.10.004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 127PG UT WOS:000243598200006 PM 17137791 ER PT J AU Jeon, SJ Oshima, K Heller, S Edge, ASB AF Jeon, Sang-Jun Oshima, Kazuo Heller, Stefan Edge, Albert S. B. TI Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID DEVELOPING NERVOUS-SYSTEM; SENSORY EPITHELIA; STROMAL CELLS; ADULT HUMAN; NULL MICE; SPIRAL GANGLION; DIFFERENTIATION; EXPRESSION; MATH1; NEURONS AB Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. RP Edge, ASB (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@meei.harvard.edu FU NIDCD NIH HHS [F33 DC006789, P30 DC05209, R01 DC007174-01A1, R01 DC007174-02, R33 DC006789, P30 DC005209, R01 DC007174] NR 54 TC 58 Z9 74 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2007 VL 34 IS 1 BP 59 EP 68 DI 10.1016/j.mcn.2006.10.003 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 127PG UT WOS:000243598200007 PM 17113786 ER PT J AU An, JB Rettig, MB AF An, Jiabin Rettig, Matthew B. TI Epidermal growth factor receptor inhibition sensitizes renal cell carcinoma cells to the cytotoxic effects of bortezomib SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NF-KAPPA-B; PHASE-II TRIAL; TUMOR-SUPPRESSOR GENE; CYCLE ARREST; INDUCED APOPTOSIS; CANCER-THERAPY; PROTEASOME; PS-341; ACTIVATION; TRANSCRIPTION AB In renal cell carcinoma (RCC) models, maximal cytotoxicity of the proteasome inhibitor bortezomib is dependent on efficient blockade of constitutive nuclear factor KB (NF-KB) activity. Signaling through the epidermal growth factor receptor (EGFR) has been shown to result in NF-KB activation. Thus, we sought to investigate whether inhibition of the EGFR sensitizes RCC cells to the cytotoxic effects of bortezomib. We first established that constitutive NF-KB activity is dependent on signaling through the EGFR in RCC cells. Indeed, blockade of EGFR signaling with an EGFR tyrosine kinase inhibitor (TKI) resulted in inhibition of NF-KB activity. Using pharmacologic and genetic approaches, we also showed that EGFR-mediated NF-KB activation occurs through the phosphotidylinositol-3-OH kinase/AKT pathway. Combinations of the EGFR-TKI and bortezomib resulted in synergistic cytotoxic effects when RCC cells were pretreated with the EGFR-TKI, but an antagonistic interaction was observed with bortezomib pretreatment. Evaluation of the effects of drug sequencing on inhibition of NF-KB activity revealed that EGFR-TKI pretreatment markedly augmented the NF-KB inhibitory effect of bortezomib, whereas bortezomib preexposure resulted in suboptimal NF-KB blockade and thus provides a biochemical explanation for the drug interaction results. We conclude that the constitutive NF-KB activity observed in RCC cells is mediated, at least in part, through an EGFR/phosphotidylinositol-3-OH kinase/AKT signaling cascade. Pretreatment with an EGFR-TKI sensitizes to bortezomib-mediated cytotoxicity by inhibiting constitutive NF-KB activity. The combination of bortezomib and a currently approved EGFR inhibitor warrants clinical investigation. C1 VA Greater Los Angeles Healthcare Syst W Los Ange, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Rettig, MB (reprint author), VA Greater Los Angeles Healthcare Syst W Los Ange, 11301 Wilshire Blvd,Bldg 304,Room E1-22, Los Angeles, CA 90073 USA. EM matthew.rettig@med.va.gov NR 54 TC 40 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 61 EP 69 DI 10.1158/1535-7163.MCT-06-0255 PG 9 WC Oncology SC Oncology GA 129WC UT WOS:000243759800007 PM 17237266 ER PT J AU Sha, SK Sato, T Kobayashi, H Ishigaki, M Yamamoto, S Sato, H Takada, A Nakajyo, S Mochizuki, Y Friedman, JM Cheng, FC Okura, T Kimura, R Kufe, DW VonHoff, DD Kawabe, T AF Sha, Shi-Ken Sato, Takuji Kobayashi, Hidetaka Ishigaki, Machiyo Yamamoto, Sayaka Sato, Hitoshi Takada, Asako Nakajyo, Sigetosi Mochizuki, Yasuo Friedman, Jonathan M. Cheng, Fong-Chi Okura, Takashi Kimura, Ryohei Kufe, Donald W. VonHoff, Daniel D. Kawabe, Takumi TI Cell cycle phenotype-based optimization of G(2)-abrogating peptides yields CBP501 with a unique mechanism of action at the G(2) checkpoint SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID 14-3-3 PROTEIN-BINDING; DNA-DAMAGE; KINASE; CANCER; CDC25C; TRANSITION; CHK1; ATR AB Cell cycle G(2) checkpoint abrogation is an attractive strategy for sensitizing cancer cells to DNA-damaging anticancer agent without increasing adverse effects on normal cells. However, there is no single proven molecular target for this therapeutic approach. High-throughput screening for molecules inhibiting CHK1, a kinase that is essential for the G(2) checkpoint, has not yet yielded therapeutic G(2) checkpoint inhibitors, and the tumor suppressor phenotypes of ATM and CHK2 suggest they may not be ideal targets. Here, we optimized two G(2) checkpoint-abrogating peptides, TAT-S216 and TAT-S216A, based on their ability to reduce G(2) phase accumulation of DNA-damaged cells without affecting M phase accumulation of cells treated with a microtubule-disrupting compound. This approach yielded a peptide CBP501, which has a unique, focused activity against molecules that phosphorylate Ser(216) of CDC25C, including MAPKAP-K2, C-Talk 1, and CHK1. CBP501 is > 100-fold more potent than TAT-S216A and retains its selectivity for cancer cells. CBP501 is unusually stable, enters cells rapidly, and increases the cytotoxicity of DNA-damaging anticancer drugs against cancer cells without increasing adverse effects. These findings highlight the potency of CBP501 as a G(2)-abrogating drug candidate. This report also shows the usefulness of the cell cycle phenotype-based protocol for identifying G(2) checkpoint-abrogating compounds as well as the potential of peptide-based compounds as focused multitarget inhibitors. C1 CanBas Co Ltd, Numazu 4100891, Japan. Fazix Co, New York, NY USA. MDS Pharma Serv, Taipei, Taiwan. Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. RP Kawabe, T (reprint author), CanBas Co Ltd, Makiya Bldg 5F,9 Tooriyoko Cho, Numazu 4100891, Japan. EM takumi@canbas.co.jp OI friedman, jonathan/0000-0001-6908-5928 NR 29 TC 31 Z9 33 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 147 EP 153 DI 10.1158/1535-7163.MCT-06-0371 PG 7 WC Oncology SC Oncology GA 129WC UT WOS:000243759800016 PM 17237275 ER PT J AU Chaudhuri, D Orsulic, S Ashok, BT AF Chaudhuri, Devyani Orsulic, Sandra Ashok, Badithe T. TI Antiproliferative activity of sulforaphane in Akt-overexpressing ovarian cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SIGNALING PATHWAYS; PROSTATE-CANCER; IN-VIVO; EXPRESSION; ISOTHIOCYANATES; PTEN; GENE; INDOLE-3-CARBINOL; PROGRESSION; INHIBITION AB Epidemiologic studies show a correlation between increased consumption of fruits and vegetables with reduced risk of ovarian cancer. One major bioactive compound found in cruciferous vegetables, particularly broccoli, is sulforaphane, derived from the breakdown of glucoraphanin. We observed potent anti proliferative effects of sulforaphane on human ovarian cancer cell line SKOV3 (IC50 40 mu mol/L) and mouse ovarian cancer cell lines C3 and T3 (IC50 25 mu mol/L each) by cell viability assays. The loss of viability is reflected by a downregulation of cell cycle transition regulators cyclin D1, cyclin-dependent kinase 4 (cdk4), and cdk6. The upstream mediators of sulforaphane effects on the cell cycle in ovarian cancer are still unknown. However, because the Akt signal transduction pathway is overactivated in ovarian cancer, we investigated the effects of sulforaphane on this prosurvival pathway. Both total Akt protein and active phosphorylated levels of Akt (Ser(473)) and phosphoinositide 3-kinase were significantly decreased in sulforaphane-treated SKOV3, C3, and T3 cells with a concomitant inhibition of Akt kinase activity by sulforaphane in SKOV3 and C3 cells. This inhibitory effect of sulforaphane leads to a potent induction of apoptosis in all three cell lines, along with the cleavage of poly(ADP)ribose polymerase. Our study is the first to report the antiproliferative effects of sulforaphane in ovarian cancer and identifying the Akt pathway as a target of sulforaphane, with implications for the inhibition of carcinogenesis by diet-based chemoprevention. C1 New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ashok, BT (reprint author), New York Med Coll, Dept Microbiol & Immunol, Room 331,Basic Sci Bldg,Grasslands Reservat, Valhalla, NY 10595 USA. EM ashok_badithe@nymc.edu FU NCI NIH HHS [R01CA103924, CA29502, P01 CA029502, P30 CA029502, R01 CA103924, R01 CA103924-01, R01 CA103924-02, R01 CA103924-03, R01 CA103924-04, R01 CA103924-05, R01 CA103924-06] NR 35 TC 47 Z9 48 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 334 EP 345 DI 10.1158/1535-7163.MCT-06-0404 PG 12 WC Oncology SC Oncology GA 129WC UT WOS:000243759800037 PM 17237292 ER PT J AU Montet-Abou, K Montet, X Weissleder, R Josephson, L AF Montet-Abou, Karin Montet, Xavier Weissleder, Ralph Josephson, Lee TI Cell internalization of magnetic nanoparticles using transfection agents SO MOLECULAR IMAGING LA English DT Article ID MR CONTRAST AGENTS; IN-VIVO TRACKING; STEM-CELLS; FERUMOXIDES; FERUMOXTRAN; PROTAMINE; PEPTIDE AB Transfection agent (TFA)-induced magnetic cell labeling with Feridex IV is an attractive method of loading cells because it employs a pharmaceutical source of iron oxide. Although attractive, the method has two significant drawbacks. First, it requires mixing positively charged transfection agents and negatively charged magnetic nanoparticles, and the resulting loss of nanoparticle surface charge causes nanoparticle precipitation. Second, it can result in nanoparticle adsorption to the cell surface rather than internalization. Internalization of Feridex (and associated dextran) is important since dextran cell exterior can react with the antidextran antibodies, commonly present in human populations, and trigger an antibody-mediated cytotoxicity. Here we employed three assays for selecting Feridex/TFA mixtures to minimize nanoparticle precipitation and surface adsorption: (1) an assay for precipitation or stability (light scattering), (2) an assay for labeled cells (percentage of cells retained by a magnetic filter), and (3) an antidextran-based assay for nanoparticle internalization. Cells loaded with Feridex/protamine had internalized iron, whereas cells loaded with Feridex/Lipofectamine had surf ace-adsorbed iron. Optimal conditions for loading cells were 10 mu g/Feridex and 3 mu g/mL protamine sulfate. Conditions for loading cells with Feridex and a TFA need to be carefully selected to minimize nanoparticle precipitation and dextran adsorption to the cell surface. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Univ Hosp Geneva, Dept Radiol, Geneva, Switzerland. RP Josephson, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Harvard Med Sch Bldg 149,13th St, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU NIBIB NIH HHS [R01 EB004626, R01-EB00662-A01] NR 22 TC 37 Z9 37 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JAN-FEB PY 2007 VL 6 IS 1 BP 1 EP 9 DI 10.2310/7290.2006.00028 PG 9 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 186NK UT WOS:000247785200001 PM 17311760 ER PT J AU Zhang, M Carroll, MC AF Zhang, Ming Carroll, Michael C. TI Natural antibody mediated innate autoimmune response SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 21st International Complement Workshop CY OCT 22-26, 2006 CL Beijing, PEOPLES R CHINA DE natural antibody; innate immunity; complement; ischemia-reperfusion injury ID ISCHEMIA-REPERFUSION INJURY; MANNAN-BINDING LECTIN; NF-KAPPA-B; COMPLEMENT RECEPTOR TYPE-1; SERINE PROTEASES MASPS; HEAT-SHOCK PROTEINS; RAT SMALL-INTESTINE; MYOCARDIAL-ISCHEMIA; ISCHEMIA/REPERFUSION INJURY; SKELETAL-MUSCLE AB Recent advance in autoimmunity research reveals that the innate immune system is able to recognize self-targets and initiate inflammatory response in a similar way as with pathogens. This review describes one novel example of this innate autoimmunity, ischemia-reperfusion (I/R) injury. Studies of intestinal, skeletal muscle, and heart I/R models showed that reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement system which is activated by natural IgM. The recent identification of a monoclonal natural IgM that initiates I/R led to the identification of non-muscle myosin heavy chain type II A and C as the self-targets in two different tissues. New evidence further suggests that IgM binds initially to ischemic antigen providing a binding site for mannan binding lectin (MBL) which subsequently leads to activation of complement and results in tissue injury. Therefore, natural IgM mediated innate autoimmunity is likely responsible for the detrimental consequences in ischemic diseases. (C) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Suny Downstate Med Ctr, Dept Anesthesiol, Brooklyn, NY 11203 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbrinstitute.org FU NIGMS NIH HHS [P50 GM52585] NR 91 TC 42 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI BP 103 EP 110 DI 10.1016/j.molimm.2006.06.022 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400012 PM 16876247 ER PT J AU Liu, DX Davis, AE AF Liu, Dongxu Davis, Alvin E., III TI Comparison of the binding of C1 inhibitor to gram-negative bacterial lipopolysaccharides SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 20-27, 2006 CL Beijing, PEOPLES R CHINA C1 Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. NR 0 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 136 BP 207 EP 207 DI 10.1016/j.molimm.2006.07.141 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400153 ER PT J AU Liu, DX Davis, AE AF Liu, Dongxu Davis, Alvin E., III TI C1 inhibitor-mediated protection from experimental sepsis SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 20-27, 2006 CL Beijing, PEOPLES R CHINA C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. NR 0 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 135 BP 207 EP 207 DI 10.1016/j.molimm.2006.07.140 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400152 ER PT J AU Wood, A Banda, NK Takahashi, K Ezekowitz, AB Arend, WP Holers, VM AF Wood, Allyson Banda, Nirmal K. Takahashi, Kazue Ezekowitz, Alan B. Arend, William P. Holers, V. Michael TI The lectin pathway of complement activation participates in the passive transfer model of collagen-induced arthritis SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 22-26, 2006 CL Beijing, PEOPLES R CHINA C1 Univ Colorado, Hlth Sci Ctr, Div Rheumatol, Denver, CO 80262 USA. Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. NR 0 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 255 BP 257 EP 258 DI 10.1016/j.molimm.2006.07.260 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400272 ER PT J AU Zhang, M Takahashi, K Alicot, EM Vorup-Jensena, T Kessler, B Thiel, S Jensenius, JC Ezekowitz, RAB Moore, FD Carroll, MC AF Zhang, Ming Takahashi, Kazue Alicot, Elisabeth M. Vorup-Jensena, Thomas Kessler, Benedikt Thiel, Steffen Jensenius, Jens Christian Ezekowitz, R. Alan B. Moore, Francis D. Carroll, Michael C. TI Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 22-26, 2006 CL Beijing, PEOPLES R CHINA C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. DecImmune Therapeut, Boston, MA 02115 USA. Univ Aarhus, Dept Med Microbiol & Immunol, DK-8000 Aarhus C, Denmark. NR 0 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 269 BP 263 EP 264 DI 10.1016/j.molimm.2006.07.274 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400286 ER PT J AU Zhang, C Khandelwal, PJ Chakraborty, R Cuellar, TL Sarangi, S Patel, SA Cosentino, CP O'Connor, M Lee, JC Tanzi, RE Saunders, AJ AF Zhang, Can Khandelwal, Preeti J. Chakraborty, Ranjita Cuellar, Trinna L. Sarangi, Srikant Patel, Shyam A. Cosentino, Christopher P. O'Connor, Michael Lee, Jeremy C. Tanzi, Rudolph E. Saunders, Aleister J. TI An AICD-based functional screen to identify APP metabolism regulators SO MOLECULAR NEURODEGENERATION LA English DT Article AB Background: A central event in Alzheimer's disease (AD) is the regulated intramembraneous proteolysis of the beta-amyloid precursor protein (APP), to generate the beta-amyloid (A beta) peptide and the APP intracellular domain (AICD). A beta is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered. Results: To validate this experimental approach we modulated alpha-, beta-, and gamma-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis. Conclusion: Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y. C1 [Zhang, Can; Khandelwal, Preeti J.; Chakraborty, Ranjita; Cuellar, Trinna L.; Sarangi, Srikant; Patel, Shyam A.; Cosentino, Christopher P.; O'Connor, Michael; Lee, Jeremy C.; Saunders, Aleister J.] Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA. [Tanzi, Rudolph E.] Harvard Univ, Genet & Aging Res Unit, MIND, Massachusetts Gen Hosp,Dept Neurol,Med Sch, Charlestown, MA USA. [Saunders, Aleister J.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. RP Saunders, AJ (reprint author), Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA. EM cz33@drexel.edu; pjk25@drexel.edu; rm3282@drexel.edu; tcuellar@diabetes.ucsf.edu; smg36@drexel.edu; sap42@drexel.edu; nimblejak@aol.com; oconnomp@drexel.edu; jl46@drexel.edu; tanzi@helix.mgh.harvard.edu; Aleister.Saunders@drexel.edu FU NINDS (AJS); Commonwealth of PA; Drexel University FX We would like to thank Dr. Thomas Sudhof and colleagues generously sharing the APP-Gal4, APP*-Gal4 and Gal4-UAS plasmids; Dr Paul Saftig for generously sharing the ADAM10 plasmid; Dr. Carl Blobel for generously sharing ADAM9 and ADAM17 plasmids; and Dr. Mervyn Monteiro for generously sharing the Ubiquilin 1 plasmid. We would also like to thank all the members of the Saunders lab for helpful discussions and technical assistance in the completion of this work. This work was funded by NINDS (AJS), Commonwealth of PA and Drexel University. NR 60 TC 25 Z9 26 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PY 2007 VL 2 AR 15 DI 10.1186/1750-1326-2-15 PG 19 WC Neurosciences SC Neurosciences & Neurology GA V02ET UT WOS:000206907200015 PM 17718916 ER PT J AU Broekman, MLD Baek, RC Comer, LA Fernandez, JL Seyfred, TN Sena-Esteves, M AF Broekman, M. L. D. Baek, R. C. Comer, L. A. Fernandez, J. L. Seyfried, T. N. Sena-Esteves, M. TI Complete correction of enzymatic deficiency and neurochemistry in the GM1-gangliosidosis mouse brain by neonatal adeno-associated virus-mediated gene delivery SO MOLECULAR THERAPY LA English DT Article ID ACID BETA-GALACTOSIDASE; GM1 GANGLIOSIDOSIS MICE; LYSOSOMAL STORAGE; G(M1) GANGLIOSIDOSIS; GENERALIZED GANGLIOSIDOSIS; KNOCKOUT MICE; ANIMAL-MODEL; DISEASE; VECTOR; CHOLESTEROL AB GM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by autosomal recessive deficiency of lysosomal acid beta-galactosidase (beta gal), and characterized by accumulation of GM1-ganglioside and GA1 in the brain. Here we examined the effect of neonatal intracerebroventricular (i.c.v.) injection of an adeno-associated virus (AAV) vector encoding mouse bgal on enzyme activity and brain GSL content in GM1-gangliosidosis (beta gal(-/-)) mice. Histological analysis of bgal distribution in 3-month-old AAV-treated beta gal(-/-) mice showed that enzyme was present at high levels throughout the brain. Biochemical quantification showed that bgal activity in AAV-treated brains was 7- to 65-fold higher than in wild-type controls and that brain GSL levels were normalized. Cerebrosides and sulfatides, which were reduced in untreated beta gal(-/-) mice, were restored to normal levels by AAV treatment. In untreated beta gal(-/-) brains, cholesterol was present at normal levels but showed abnormal cellular distribution consistent with endosomal/lysosomal localization. This feature was also corrected in AAV-treated mice. The biochemical and histological parameters analyzed in this study showed that normal brain neurochemistry was achieved in AAV-treated beta gal(-/-) mice. Therefore we show for the first time that neonatal AAV-mediated gene delivery of lysosomal bgal to the brain may be an effective approach for treatment of GM1-gangliosidosis. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Neurosci, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Pharmacol & Anat, Utrecht, Netherlands. RP Sena-Esteves, M (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Bldg 149,13th St,Room 6309, Charlestown, MA 02129 USA. EM msesteves@partners.org OI Seyfried, Thomas/0000-0003-1491-3989 FU NICHD NIH HHS [HD39722] NR 43 TC 33 Z9 33 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2007 VL 15 IS 1 BP 30 EP 37 DI 10.1038/sj.mt.6300004 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 139AP UT WOS:000244404700011 PM 17164772 ER PT J AU Hallett, PJ Brotchie, JM AF Hallett, Penelope J. Brotchie, J. M. TI Striatal delta opioid receptor binding in experimental models of Parkinson's disease and dyskinesia SO MOVEMENT DISORDERS LA English DT Article DE opioid receptor; MPTP; dyskinesia; macaque; Parkinson's disease ID MESSENGER-RNA EXPRESSION; LEVODOPA-INDUCED DYSKINESIA; LESIONED PRIMATE MODEL; L-DOPA; GLOBUS-PALLIDUS; BASAL GANGLIA; GENE-EXPRESSION; RAT-BRAIN; SUBSTANCE-P; RESERPINE TREATMENT AB Enhanced delta opioid receptor transmission may represent an endogenous compensatory mechanism in parkinsonism to reduce the activity of the indirect striatopallidal pathway following dopamine depletion. Furthermore, increased delta opioid receptor transmission may be causative in the production of dyskinesia following repeated dopaminergic treatment in Parkinson's disease. The present study employed radioligand receptor autoradiography, using [H-3]naltrindole, a ligand selective for the delta opioid receptor, to assess delta opioid receptor binding sites in forebrain regions of reserpine-treated rats, and in parkinsonian nondyskinetic, and dyskinetic MPTP-lesioned macaques. In reserpine-treated animals, specific delta opioid binding was increased in premotor cortex (+30%), sensorimotor striatum (+20%), and associative striatum (+17%) rostrally, but was not changed in caudal forebrain. In contrast, delta opioid receptor binding was not significantly altered at any region analyzed, in either nondyskinetic or dyskinetic, MPTP-lesioned macaques, compared to normal. These results suggest that transient changes in delta opioid receptor binding may occur in motor circuits following acute dopamine depletion. However, in the more chronic MPTP-lesioned macaque model, simple changes in delta opioid receptor number or affinity are unlikely to contribute to mechanisms for abnormal opioid transmission in Parkinson's disease and dyskinesia. (C) 2006 Movement Disorder Society. C1 Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Charlestown, MA USA. Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. RP Hallett, PJ (reprint author), McLean Hosp, MRC1,115 Mill St, Belmont, MA 02478 USA. EM phallett@partners.org OI Hallett, Penelope/0000-0002-8858-9096 NR 65 TC 19 Z9 20 U1 0 U2 1 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 JAN PY 2007 VL 22 IS 1 BP 28 EP 40 DI 10.1002/mds.21163 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 134HF UT WOS:000244073400005 PM 17089424 ER PT J AU Rask-Madsen, C King, GL AF Rask-Madsen, Christian King, George L. TI Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE diabetes mellitus; endothelium; insulin resistance; vascular; vasodilation ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; CARDIOVASCULAR RISK-FACTORS; ISCHEMIC-HEART-DISEASE; SMOOTH-MUSCLE-CELLS; APOE-DEFICIENT MICE; DEPENDENT VASODILATION; OXIDATIVE STRESS; ACCELERATED ATHEROSCLEROSIS; VASCULAR INFLAMMATION AB Endothelial dysfunction is one manifestation of the many changes induced in the arterial wall by the metabolic abnormalities accompanying diabetes and insulin resistance. In type 1 diabetes, endothelial dysfunction is most consistently found in advanced stages of the disease. In other patients, it is associated with nondiabetic insulin resistance and probably precedes type 2 diabetes. In obesity and insulin resistance, increased secretion of proinflammatory cytokines and decreased secretion of adiponectin from adipose tissue, increased circulating levels of free fatty acids, and postprandial hyperglycemia can all alter gene expression and cell signaling in vascular endothelium, cause vascular insulin resistance, and change the release of endothelium-derived factors. In diabetes, sustained hyperglycemia causes increased intracellular concentrations of glucose metabolites in endothelial cells. These changes cause mitochondrial dysfunction, increased oxidative stress, and activation of protein kinase C. Dysfunctional endothelium displays activation of vascular NADPH oxidase, uncoupling of endothelial nitric oxide synthase, increased expression of endothelin 1, a changed balance between the production of vasodilator and vasoconstrictor prostanoids, and induction of adhesion molecules. This review describes how these and other changes influence endothelium-dependent vasodilation in patients with insulin resistance and diabetes. The clinical utility of endothelial function testing and future therapeutic targets is also discussed. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02120 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Room 4304, Boston, MA 02120 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [5 P30 DK36836, DK53105, DK71359] NR 79 TC 249 Z9 266 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JAN PY 2007 VL 3 IS 1 BP 46 EP 56 DI 10.1038/ncpendmet0366 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 117SA UT WOS:000242892100010 PM 17179929 ER PT J AU Hochberg, FH Baehring, JM Hochberg, EP AF Hochberg, Fred H. Baehring, Joachim M. Hochberg, Ephraim P. TI Primary CNS lymphoma SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE intravascular lymphoma; neurolymphomatosis; ocular lymphoma; post-transplant lymphoproliferative disorder; primary CNS lymphoma ID CENTRAL-NERVOUS-SYSTEM; EPSTEIN-BARR-VIRUS; HIGH-DOSE METHOTREXATE; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; ABERRANT SOMATIC HYPERMUTATION; POLYMERASE-CHAIN-REACTION; NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMAS; DEFERRED RADIOTHERAPY; PHASE-II AB Non-Hodgkin's lymphoma invades the brain, the vitreous body and nerves of the eye, the meninges, and the nerve roots of brain and spine, leading to the development of a primary CNS lymphoma. The mechanism of involvement of these locations by malignant B lymphocytes is unknown, but it might involve molecular targeting of lymphoma cells generated at cryptic systemic sites. The diagnosis of primary CNS lymphoma has been facilitated by advances in imaging techniques and the discovery of molecular markers. Methotrexate-based regimens, even when radiation is deferred, prolong overall survival to over 5 years, but relapses eventually occur in most cases. Better tools for earlier diagnosis and monitoring of treatment response will emerge from molecular studies of therapeutic targets. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Yale Brain Tumor Ctr, New Haven, CT USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9010, Boston, MA 02114 USA. EM fhochberg@partners.org NR 76 TC 72 Z9 73 U1 4 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD JAN PY 2007 VL 3 IS 1 BP 24 EP 35 DI 10.1038/ncpneuro0395 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 122WG UT WOS:000243257500010 PM 17205072 ER PT J AU Shipley, WU AF Shipley, William U. TI Radiation-sensitizing chemotherapy after transurethral resection as an alternative treatment for high-risk T1 bladder cancer SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material DE radiation-sensitizing chemotherapy; T1 bladder cancer; transitional cell carcinoma; transurethral resection; treatment ID TRANSITIONAL-CELL CARCINOMA; CYSTECTOMY; PROGRESSION; THERAPY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Shipley, WU (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. EM wshipley@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD JAN PY 2007 VL 4 IS 1 BP 24 EP 25 DI 10.1038/ncpuro0675 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 122XM UT WOS:000243260900010 PM 17211422 ER PT J AU Bertram, L McQueen, MB Mullin, K Blacker, D Tanzi, RE AF Bertram, Lars McQueen, Matthew B. Mullin, Kristina Blacker, Deborah Tanzi, Rudolph E. TI Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database SO NATURE GENETICS LA English DT Article ID POLYMORPHISM; SUSCEPTIBILITY; POPULATION; RISK; BIAS; AGE AB The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses for each polymorphism with available genotype data in at least three case-control samples. In addition to identifying the epsilon 4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11 - 1.38 for risk alleles and 0.92 - 0.67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases. C1 Massachusetts Gen Hosp, Dept Neurol, MIND, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Massachusetts Gen Hosp, Gerontol Res Unit, Dept Psychiat, Charlestown, MA 02129 USA. RP Bertram, L (reprint author), Massachusetts Gen Hosp, Dept Neurol, MIND, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM bertram@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NICHD NIH HHS [R01 HD060726] NR 30 TC 909 Z9 939 U1 6 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2007 VL 39 IS 1 BP 17 EP 23 DI 10.1038/ng1934 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 121CU UT WOS:000243136500012 PM 17192785 ER PT J AU Tomlins, SA Mehra, R Rhodes, DR Cao, XH Wang, L Dhanasekaran, SM Kalyana-Sundaram, S Wei, JT Rubin, MA Pienta, KJ Shah, RB Chinnaiyan, AM AF Tomlins, Scott A. Mehra, Rohit Rhodes, Daniel R. Cao, Xuhong Wang, Lei Dhanasekaran, Saravana M. Kalyana-Sundaram, Shanker Wei, John T. Rubin, Mark A. Pienta, Kenneth J. Shah, Rajal B. Chinnaiyan, Arul M. TI Integrative molecular concept modeling of prostate cancer progression SO NATURE GENETICS LA English DT Article ID GENE-EXPRESSION; HIGH-GRADE; INTRAEPITHELIAL NEOPLASIA; CARCINOMA; TRANSCRIPTOME; PROFILES; MARKERS; CARCINOGENESIS; ADENOCARCINOMA; TMPRSS2 AB Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with the observed histological progression are unclear. Using laser-capture microdissection to isolate 101 cell populations, we have profiled prostate cancer progression from benign epithelium to metastatic disease. By analyzing expression signatures in the context of over 14,000 'molecular concepts', or sets of biologically connected genes, we generated an integrative model of progression. Molecular concepts that demarcate critical transitions in progression include protein biosynthesis, E26 transformation-specific (ETS) family transcriptional targets, androgen signaling and cell proliferation. Of note, relative to low-grade prostate cancer (Gleason pattern 3), high-grade cancer (Gleason pattern 4) shows an attenuated androgen signaling signature, similar to metastatic prostate cancer, which may reflect dedifferentiation and explain the clinical association of grade with prognosis. Taken together, these data show that analyzing gene expression signatures in the context of a compendium of molecular concepts is useful in understanding cancer biology. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Bioinformat Program, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Kalyana-Sundaram, Shanker/F-6860-2012; Wei, John/E-8967-2012; Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [UO1 CA111275-01, 5P30 CA46592, P50CA69568, R01 CA102872]; NIDA NIH HHS [U54 DA021519-01A1] NR 50 TC 482 Z9 494 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2007 VL 39 IS 1 BP 41 EP 51 DI 10.1038/ng1935 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 121CU UT WOS:000243136500016 PM 17173048 ER PT J AU Roberts, AE Araki, T Swanson, KD Montgomery, KT Schiripo, TA Joshi, VA Li, L Yassin, Y Tamburino, AM Neel, BG Kucherlapati, RS AF Roberts, Amy E. Araki, Toshiyuki Swanson, Kenneth D. Montgomery, Kate T. Schiripo, Taryn A. Joshi, Victoria A. Li, Li Yassin, Yosuf Tamburino, Alex M. Neel, Benjamin G. Kucherlapati, Raju S. TI Germline gain-of-function mutations in SOS1 cause Noonan syndrome SO NATURE GENETICS LA English DT Article ID RAS ACTIVATOR SON; FACIO-CUTANEOUS SYNDROME; SEVENLESS; MUTANTS; PATHWAY; DOMAIN; KRAS AB Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition(1). Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause similar to 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation(2), and Noonan syndrome mutants enhance ERK activation ex vivo(3,4) and in mice(5). KRAS mutations account for < 5% of cases of Noonan syndrome(6), but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in similar to 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease ;and providing new insights into RAS-GEF regulation. C1 Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Neel, BG (reprint author), Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. EM bneel@bidmc.harvard.edu FU NCI NIH HHS [R37CA49152]; NCRR NIH HHS [M01-RR02172]; NIDCR NIH HHS [DE16140] NR 23 TC 278 Z9 292 U1 5 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2007 VL 39 IS 1 BP 70 EP 74 DI 10.1038/ng1926 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 121CU UT WOS:000243136500019 PM 17143285 ER PT J AU Kiepiela, P Ngumbela, K Thobakgale, C Ramduth, D Honeyborne, I Moodley, E Reddy, S de Pierres, C Mncube, Z Mkhwanazi, N Bishop, K van der Stok, M Nair, K Khan, N Crawford, H Payne, R Leslie, A Prado, J Prendergast, A Frater, J McCarthy, N Brander, C Learn, GH Nickle, D Rousseau, C Coovadia, H Mullins, JI Heckerman, D Walker, BD Goulder, P AF Kiepiela, Photini Ngumbela, Kholiswa Thobakgale, Christina Ramduth, Dhanwanthie Honeyborne, Isobella Moodley, Eshia Reddy, Shabashini de Pierres, Chantal Mncube, Zenele Mkhwanazi, Nompumelelo Bishop, Karen van der Stok, Mary Nair, Kriebashnie Khan, Nasreen Crawford, Hayley Payne, Rebecca Leslie, Alasdair Prado, Julia Prendergast, Andrew Frater, John McCarthy, Noel Brander, Christian Learn, Gerald H. Nickle, David Rousseau, Christine Coovadia, Hoosen Mullins, James I. Heckerman, David Walker, Bruce D. Goulder, Philip TI CD8(+) T-cell responses to different HIV proteins have discordant associations with viral load SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY INFECTION; ESCAPE VARIANTS; LYMPHOCYTE RESPONSES; ACUTE SEROCONVERSION; IMMUNE-RESPONSES; TYPE-1 INFECTION; AUTOLOGOUS VIRUS; SIV REPLICATION; VACCINE DESIGN AB Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation. C1 Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa. Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. Dept Zool, Oxford OX1 3SY, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Microsoft Res, Redmond, WA 98052 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Goulder, P (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa. EM philip.goulder@paediatrics.ox.ac.uk RI McCarthy, Noel/K-3314-2012; OI Brander, Christian/0000-0002-0548-5778; Bishop, Karen/0000-0003-4935-7708 FU Medical Research Council [G0500384, G108/626]; NIAID NIH HHS [2R01AI46995-06, P30 AI027757, R01AI067073]; PHS HHS [N01-A1-15422]; Wellcome Trust NR 48 TC 654 Z9 675 U1 4 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2007 VL 13 IS 1 BP 46 EP 53 DI 10.1038/nm1520 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 123NE UT WOS:000243301800035 PM 17173051 ER PT J AU Liu, TX Becker, MW Jelinek, J Wu, WS Deng, M Mikhalkevich, N Hsu, K Bloomfield, CD Stone, RM DeAngelo, DJ Galinsky, IA Issa, JP Clarke, MF Look, AT AF Liu, Ting Xi Becker, Michael W. Jelinek, Jaroslav Wu, Wen-Shu Deng, Min Mikhalkevich, Natallia Hsu, Karl Bloomfield, Clara D. Stone, Richard M. DeAngelo, Daniel J. Galinsky, Ilene A. Issa, Jean-Pierre Clarke, Michael F. Look, A. Thomas TI Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation SO NATURE MEDICINE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; MOLECULAR DELINEATION; TUMOR-SUPPRESSOR; STEM-CELLS; REGION; LEUKEMIA; LINE; IDENTIFICATION; DISEASES AB m Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML)(1), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes(2). Although a major commonly deleted region (CDR) has been delineated on chromosome band 5q31.1 (refs.3-7), attempts to identify tumor suppressors within this band have been unsuccessful. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions(8,9), and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region(10,11), showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Lab Dev & Dis, Shanghai 200025, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China. Univ Rochester, Div Hematol Oncol, Rochester, NY 14642 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Chicago, Canc & Leukemia Grp, Chicago, IL 60606 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Stanford Univ, Inst Stem Cell & Regenerat Med, Palo Alto, CA 94304 USA. Stanford Univ, Div Hematol Oncol, Palo Alto, CA 94304 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu RI Jelinek, Jaroslav/A-8476-2008; Wu, Wen-Shu/I-1258-2014; Jelinek, Jaroslav/D-2282-2012; OI Wu, Wen-Shu/0000-0002-0225-2522; Jelinek, Jaroslav/0000-0002-2533-0220; Becker, Michael/0000-0001-9890-8815 FU NCI NIH HHS [CA101140, CA104987, CA108631] NR 27 TC 128 Z9 134 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2007 VL 13 IS 1 BP 78 EP 83 DI 10.1038/nm1512 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 123NE UT WOS:000243301800039 PM 17159988 ER PT J AU Fischer, W Perkins, S Theiler, J Bhattacharya, T Yusim, K Funkhouser, R Kuiken, C Haynes, B Letvin, NL Walker, BD Hahn, BH Korber, BT AF Fischer, Will Perkins, Simon Theiler, James Bhattacharya, Tanmoy Yusim, Karina Funkhouser, Robert Kuiken, Carla Haynes, Barton Letvin, Norman L. Walker, Bruce D. Hahn, Beatrice H. Korber, Bette T. TI Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS-MONKEYS; LYMPHOCYTE ESCAPE; VIRAL ESCAPE; TYPE-1; RESPONSES; INFECTION; IMMUNOGENICITY; ENVELOPE; AIDS AB HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences via a computational optimization method. Mosaic proteins resemble natural proteins, and a mosaic set maximizes the coverage of potential T-cell epitopes (peptides of nine amino acids) for a viral population. We found that coverage of viral diversity using mosaics was greatly increased compared to coverage by natural-sequence vaccine candidates, for both variable and conserved proteins; for conserved HIV-1 proteins, global coverage may be feasible. For example, four mosaic proteins perfectly matched 74% of 9-amino-acid potential epitopes in global Gag sequences; 87% of potential epitopes matched at least 8 of 9 positions. In contrast, a single natural Gag protein covered only 37% (9 of 9) and 67% (8 of 9). Mosaics provide diversity coverage comparable to that afforded by thousands of separate peptides, but, because the fragments of natural proteins are compressed into a small number of native-like proteins, they are tractable for vaccines. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Korber, BT (reprint author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA. EM btk@lanl.gov RI Fischer, Will/B-1323-2013; Bhattacharya, Tanmoy/J-8956-2013; OI Fischer, Will/0000-0003-4579-4062; Bhattacharya, Tanmoy/0000-0002-1060-652X; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [P01 AI061734-01, R21 AI055421-01-A1]; PHS HHS [N01-15442] NR 32 TC 224 Z9 228 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2007 VL 13 IS 1 BP 100 EP 106 DI 10.1038/nm1461 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 123NE UT WOS:000243301800043 PM 17187074 ER PT J AU Leduc, PR Wong, MS Ferreira, PM Groff, RE Haslinger, K Koonce, MP Lee, WY Love, JC McCammon, JA Monteiro-Riviere, NA Rotello, VM Rubloff, GW Westervelt, R Yoda, M AF LeDuc, Philip R. Wong, Michael S. Ferreira, Placid M. Groff, Richard E. Haslinger, Kiryn Koonce, Michael P. Lee, Woo Y. Love, J. Christopher McCammon, J. Andrew Monteiro-Riviere, Nancy A. Rotello, Vincent M. Rubloff, Gary W. Westervelt, Robert Yoda, Minami TI Towards an in vivo biologically inspired nanofactory SO NATURE NANOTECHNOLOGY LA English DT Editorial Material ID TRANSMEMBRANE PORE; NANOTECHNOLOGY; NANOMEDICINE; TRANSPORT; PROSPECTS; VESICLES; DELIVERY; CELLS AB Nanotechnology is having a major impact on medicine and the treatment of disease, notably in imaging and targeted drug delivery. It may, however, be possible to go even further and design 'pseudo-cell' nanofactories that work with molecules already in the body to fight disease. C1 Carnegie Mellon Univ, Dept Mech & Biomed Engn, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77251 USA. Rice Univ, Dept Chem, Houston, TX 77251 USA. Univ Illinois, Dept Mech & Ind Engn, Urbana, IL 61801 USA. Clemson Univ, Dept Elect & Comp Engn, Clemson, SC 29634 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Wadsworth Ctr, Div Mol Med, Albany, NY 12201 USA. Stevens Inst Technol, Dept Chem, Hoboken, NJ 07030 USA. Stevens Inst Technol, Dept Biomed, Hoboken, NJ 07030 USA. Stevens Inst Technol, Dept Mat Engn, Hoboken, NJ 07030 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. N Carolina State Univ, Ctr Chem Toxicol Res & Pharmacokinet, Raleigh, NC 27606 USA. Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA. Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA. Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Georgia Inst Technol, Sch Mech Engn, Atlanta, GA 30332 USA. RP Leduc, PR (reprint author), Carnegie Mellon Univ, Dept Mech & Biomed Engn, Pittsburgh, PA 15213 USA. EM prleduc@cmu.edu; mswong@rice.edu RI ferreira, placid/D-5308-2012; Rubloff, Gary/D-4142-2009; Wong, Michael/F-9286-2010; LeDuc, Philip/M-1103-2014 OI ferreira, placid/0000-0002-5517-6586; Rubloff, Gary/0000-0002-1901-3982; Wong, Michael/0000-0002-3652-3378; LeDuc, Philip/0000-0001-6397-2905 NR 38 TC 83 Z9 83 U1 1 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD JAN PY 2007 VL 2 IS 1 BP 3 EP 7 DI 10.1038/nnano.2006.180 PG 5 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 131WQ UT WOS:000243902900002 PM 18654192 ER PT J AU Glykys, J Peng, ZC Chandra, D Homanics, GE Houser, CR Mody, I AF Glykys, Joseph Peng, Zechun Chandra, Dev Homanics, Gregg E. Houser, Carolyn R. Mody, Istvan TI A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol SO NATURE NEUROSCIENCE LA English DT Article ID CA1 PYRAMIDAL NEURONS; DELTA-SUBUNIT; TONIC INHIBITION; DENTATE GYRUS; GRANULE CELLS; A RECEPTORS; ALPHA-1 SUBUNIT; DEFICIENT MICE; KNOCKOUT MICE; RAT-BRAIN AB According to the rules of GABA(A) receptor (GABA(A)R) subunit assembly, alpha 4 and alpha 6 subunits are considered to be the natural partners of delta subunits. These GABA(A)Rs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: d subunits of hippocampal interneurons are coexpressed and colocalized with alpha 1 subunits, but not with alpha 4, alpha 6 or any other alpha subunits. Ethanol potentiates the tonic inhibition mediated by such native alpha 1/delta GABA(A)Rs in wild-type and in alpha 4 subunit-deficient (Gabra4(-/-)) mice, but not in delta subunit - deficient (Gabrd(-/-)) mice. We also ruled out any compensatory upregulation of alpha 6 subunits that might have accounted for the ethanol effect in Gabra4(-/-) mice. Thus, alpha 1/delta subunit assemblies represent a new neuronal GABA(A)R subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol. C1 Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Mody, I (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA. EM mody@ucla.edu OI Homanics, Gregg/0000-0003-3641-8153 FU BLRD VA [I01 BX000404]; NIAAA NIH HHS [AA14003]; NINDS NIH HHS [NS051311, NS30549, NS35958] NR 52 TC 147 Z9 148 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 40 EP 48 DI 10.1038/nn1813 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100014 PM 17159992 ER PT J AU Sieburth, D Madison, JM Kaplan, JM AF Sieburth, Derek Madison, Jon M. Kaplan, Joshua M. TI PKC-1 regulates secretion of neuropeptides SO NATURE NEUROSCIENCE LA English DT Article ID PROTEIN-KINASE-C; ELEGANS NEUROMUSCULAR-JUNCTION; ADRENAL CHROMAFFIN CELLS; READILY RELEASABLE POOL; DENSE-CORE VESICLES; CAENORHABDITIS-ELEGANS; SYNAPTIC-TRANSMISSION; TRANSMITTER RELEASE; PHORBOL ESTERS; DEPENDENT PHOSPHORYLATION AB The secretion of neurotransmitters and neuropeptides is mediated by distinct organelles-synaptic vesicles (SVs) and dense-core vesicles (DCVs), respectively. Relatively little is known about the factors that differentially regulate SV and DCV secretion. Here we show that protein kinase C-1 (PKC-1), which is most similar to the vertebrate PKC eta and epsilon isoforms, regulates exocytosis of DCVs in Caenorhabditis elegans motor neurons. Mutants lacking PCK-1 activity had delayed paralysis induced by the acetylcholinesterase inhibitor aldicarb, whereas mutants with increased PKC-1 activity had more rapid aldicarb-induced paralysis. Imaging and electrophysiological assays indicated that SV release occurred normally in pkc-1 mutants. By contrast, genetic analysis of aldicarb responses and imaging of fluorescently tagged neuropeptides indicated that mutants lacking PKC-1 had reduced neuropeptide secretion. Similar neuropeptide secretion defects were found in mutants lacking unc-31 ( encoding the protein CAPS) or unc-13 (encoding Munc13). These results suggest that PKC-1 selectively regulates DCV release from neurons. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches 7,185 Cambridge St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NINDS NIH HHS [1F32NS10310] NR 66 TC 111 Z9 129 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 49 EP 57 DI 10.1038/nn1810 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100015 PM 17128266 ER PT J AU Li, J Makrigiorgos, GM AF Li, Jin Makrigiorgos, G. Mike TI Anti-primer quenching-based real-time PCR for simplex or multiplex DNA quantification and single-nucleotide polymorphism genotyping SO NATURE PROTOCOLS LA English DT Article ID AMPLIFICATION; FLUORESCENCE; PROBES; FORMAT AB Nucleic acid amplification and detection plays an increasingly important role in genetic analysis of clinical samples, medical diagnostics and drug discovery. We present a new quantitative PCR method that allows versatile and flexible nucleic acid target quantification. One of the PCR primers is modified by an oligonucleotide "tail'' fluorescently labeled at the 5' end. An oligonucleotide complementary to this tail, carrying a 3'-quencher ("anti-primer''), is included in the PCR along with the two primers. Following primer extension, the reaction temperature is lowered such that the anti-primer hybridizes to and quenches the fluorescence of only the free primer and not the double-stranded PCR product, allowing real-time fluorescent quantification of the latter. This anti-primer-based quantitative real-time PCR (aQRT-PCR) allows simplex or multiplex quantification or single-nucleotide polymorphism genotyping in clinical samples of widely differing quality (e. g., fresh samples, formalin-fixed paraffin-embedded samples and plasma-circulating DNA) and provides a practical alternative to existing, more expensive approaches. The process of aQRT-PCR takes 1.5-2 h. C1 [Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [CA 115439-01, 1 R21 CA111994-01] NR 17 TC 11 Z9 13 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 1 BP 50 EP 58 DI 10.1038/nprot.2007.11 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262GW UT WOS:000253138000009 PM 17401338 ER PT J AU Liang, P Meade, JD Pardee, AB AF Liang, Peng Meade, Jonathan D. Pardee, Arthur B. TI A protocol for differential display of mRNA expression using either fluorescent or radioactive labeling SO NATURE PROTOCOLS LA English DT Article ID GENE-EXPRESSION AB Since its invention in the early 1990s, differential display (DD) has become one of the most commonly used techniques for identifying differentially expressed genes at the mRNA level. Unlike other genomic approaches, such as DNA microarrays, DD systematically detects changes in mRNA profiles among multiple samples being compared without the need of any prior knowledge of genomic information of the living organism being studied. Here, we present an optimized DD protocol with a fluorescent digital readout as well as traditional radioactive labeling. The resulting streamlined fluorescent DD process offers an unprecedented accuracy, sensitivity and throughput in comprehensive and quantitative analysis of eukaryotic gene expression. Results usually can be obtained within days using a limited number of primer combinations, but a comprehensive DD screen may take weeks or months to accomplish, depending on gene coverage required and the number of differentially expressed genes present within a biological system being compared. C1 [Liang, Peng; Meade, Jonathan D.] GenHunter Corp, Nashville, TN 37211 USA. [Liang, Peng] Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Pardee, Arthur B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liang, P (reprint author), GenHunter Corp, 624 Grassmere Pk Dr,Suite 17, Nashville, TN 37211 USA. EM peng.liang@vanderbilt.edu; arthur_pardee@dfci.harvard.edu NR 18 TC 17 Z9 20 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 3 BP 457 EP 470 DI 10.1038/nprot.2007.46 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262GY UT WOS:000253138200001 PM 17406608 ER PT J AU Duda, DG Cohen, KS Scadden, DT Jain, RK AF Duda, Dan G. Cohen, Kenneth S. Scadden, David T. Jain, Rakesh K. TI A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood SO NATURE PROTOCOLS LA English DT Article ID RECTAL-CANCER PATIENTS; ANTIANGIOGENIC THERAPY; BEVACIZUMAB; STEM AB Blood circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells (CPCs) represent two cell populations that are thought to play important roles in tissue vascularization. CECs and CPCs are currently studied as surrogate markers in patients for more than a dozen pathologies, including heart disease and cancer. However, data interpretation has often been difficult because of multiple definitions, methods and protocols used to evaluate and count these cells by different laboratories. Here, we propose a cytometry protocol for phenotypic identification and enumeration of CECs and CPCs in human blood using four surface markers: CD31, CD34, CD133 and CD45. This method allows further phenotypic analyses to explore the biology of these cells. In addition, it offers a platform for longitudinal studies of these cells in patients with different pathologies. The protocol is relatively simple, inexpensive and can be adapted for multiple flow cytometer types or software. The procedure should take 2-2.5 h, and is expected to detect 0.1-6.0% viable CECs and 0.01-0.20% CPCs within blood mononuclear cell population. C1 [Duda, Dan G.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. [Cohen, Kenneth S.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R01 CA115767-03, P01 CA080124, P01 CA080124-08, P01-CA80124, R01 CA115767, R01-CA115767] NR 12 TC 162 Z9 168 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 4 BP 805 EP 810 DI 10.1038/nprot.2007.111 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HC UT WOS:000253138600005 PM 17446880 ER PT J AU Yoo, SD Cho, YH Sheen, J AF Yoo, Sang-Dong Cho, Young-Hee Sheen, Jen TI Arabidopsis mesophyll protoplasts: a versatile cell system for transient gene expression analysis SO NATURE PROTOCOLS LA English DT Article ID VACUOLAR TRAFFICKING; SIGNAL-TRANSDUCTION; AUX/IAA PROTEINS; INNATE IMMUNITY; THALIANA; PLANTS; MAP; IDENTIFICATION; TRANSCRIPTION; ETHYLENE AB The transient gene expression system using Arabidopsis mesophyll protoplasts has proven an important and versatile tool for conducting cell-based experiments using molecular, cellular, biochemical, genetic, genomic and proteomic approaches to analyze the functions of diverse signaling pathways and cellular machineries. A well-established protocol that has been extensively tested and applied in numerous experiments is presented here. The method includes protoplast isolation, PEG-calcium transfection of plasmid DNA and protoplast culture. Physiological responses and high-throughput capability enable facile and cost-effective explorations as well as hypothesis-driven tests. The protoplast isolation and DNA transfection procedures take 6-8 h, and the results can be obtained in 2-24 h. The cell system offers reliable guidelines for further comprehensive analysis of complex regulatory mechanisms in whole-plant physiology, immunity, growth and development. C1 [Yoo, Sang-Dong; Cho, Young-Hee; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yoo, Sang-Dong; Cho, Young-Hee; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Yoo, SD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM yoo@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM060493] NR 30 TC 1165 Z9 1242 U1 46 U2 220 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 7 BP 1565 EP 1572 DI 10.1038/nprot.2007.199 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HI UT WOS:000253139200001 PM 17585298 ER PT J AU Weisbord, SD Fried, LF Unruh, ML Kimmel, PL Switzer, GE Fine, MJ Arnold, RM AF Weisbord, Steven D. Fried, Linda F. Unruh, Mark L. Kimmel, Paul L. Switzer, Galen E. Fine, Michael J. Arnold, Robert M. TI Associations of race with depression and symptoms in patients on maintenance haemodialysis SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE depression; haemodialysis; spirituality; symptoms ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; DIALYSIS PATIENTS; RACIAL-DIFFERENCES; PERCEPTION; BELIEFS; ILLNESS; NEED AB Background. Although studies have shown that African American haemodialysis patients report better overall quality of life than Whites, racial differences in depression and symptom burden remain less well characterized. The aim of this study was to compare these domains between African American and White patients on chronic haemodialysis. Methods. We surveyed African American and White maintenance haemodialysis patients. Depression was assessed using the Beck Depression Inventory (BDI) and Cognitive Depression Index (CDI). Symptoms were evaluated using the Dialysis Symptom Index (DSI). Results. Among the 82 Whites and 78 African Americans enrolled, there were no racial differences in the prevalence of depression (27% in African Americans vs 27% in Whites, P = 1.0), BDI Scores (11.2 vs 10.9, P = 0.6) or CDI scores (6.0 vs 6.0, P = 0.9). Symptom burden was substantial in both African Americans and Whites (median number of symptoms 8.5 and 9.0, respectively) with no racial differences in the overall burden or severity of symptoms. However, based on a single item, African Americans were more likely to describe their religious/spiritual beliefs as 'very important'. Adjustment for demographic and treatment characteristics had no impact on the associations of race with depression or symptoms. Conclusions. Depression and symptoms are highly prevalent in both African American and White haemodialysis patients, without racial differences in these health-related domains. In exploratory analyses, spiritual/religious beliefs appear to be of greater importance to African Americans. The relevance of these observations to the advantages in quality of life and survival among African Americans on haemodialysis warrants further investigation. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, Pittsburgh, PA 15260 USA. George Washington Univ, Sch Med, Div Renal Dis & Hypertens, Washington, DC 20052 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU NCATS NIH HHS [UL1 TR000005]; NIAID NIH HHS [K24 AI 001769] NR 20 TC 25 Z9 28 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JAN PY 2007 VL 22 IS 1 BP 203 EP 208 DI 10.1093/ndt/gfl521 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 126FG UT WOS:000243497200035 PM 16998218 ER PT J AU Bertram, L Hsiao, M McQueen, MB Parkinson, M Mullin, K Blacker, D Tanzi, RE AF Bertram, Lars Hsiao, Monica McQueen, Matthew B. Parkinson, Michele Mullin, Kristina Blacker, Deborah Tanzi, Rudolph E. TI The LDLR locus in alzheimer's disease: A family-based study and meta-analysis of case-control data SO NEUROBIOLOGY OF AGING LA English DT Article DE low density lipoprotein receptor; LDLR; meta-analysis AB Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,MIND,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit,Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bertram, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,MIND,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bertram@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 4 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2007 VL 28 IS 1 BP 18 EP 19 DI 10.1016/j.neurobiolaging.2005.11.005 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 115ND UT WOS:000242740100003 ER PT J AU Zhang, F Wang, SP Cao, GD Gao, YQ Chen, J AF Zhang, Feng Wang, Suping Cao, Guodong Gao, Yanqin Chen, Jun TI Signal transducers and activators of transcription 5 contributes to erythropoietin-mediated neuroprotection against hippocampal neuronal death after transient global cerebral ischemia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE STAT5; CA1; ischemia; EPO ID PHOSPHATIDYLINOSITOL 3-KINASE; NEUROTROPHIC FACTOR; STAT5 ACTIVATION; PROTECTS NEURONS; CELL-LINE; BRAIN; APOPTOSIS; EXPRESSION; PROTEINS; RAT AB The signal transducers and activators of transcription (STAT) proteins are a group of transcriptional factors. Among them, STAT5 initiates a pro-survival signaling cascade. So far, little has been known about the role of STAT5 in cerebral ischemia and reperfusion. This study examines the phosphorylation status of STAT5 in hippocampal CA1 in the early stage after transient global cerebral ischemia in rats. Our data show that the phosphorylation of STAT5 was increased in hippocampal CA1 at 1 h and 3 It ischemia. Taking advantage of the neuroprotective effect of erythropoietin (EPO) in CA1, we further demonstrated that the administration of EPO enhanced the phosphorylation of STAT5, with SATA5a being phosphorylated earlier. The enhanced phosphorylation of STAT5 in the EPO-treated group was accompanied by the upregulation of STAT5 downstream gene products, Bcl-xL and XIAP. Consequently, ischemic CA1 neuronal damage was attenuated by the administration of EPO. Both the enhancement of STAT5 phosphorylation and the neuroprotection rendered by EPO were blocked by Tyrphostin, a selective inhibitor for Janus kinase 2, which is an upstream kinase of STAT5. These findings suggest an association between the activation of STAT5 and CA1 neuronal survival after cerebral ischemia. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai, Peoples R China. Vet Affairs Pittsburg Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU NINDS NIH HHS [NS38560, NS36736, NS43802, NS45048, R01 NS036736, R01 NS043802, R01 NS045048] NR 47 TC 42 Z9 47 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2007 VL 25 IS 1 BP 45 EP 53 DI 10.1016/j.nbd.2006.08.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 114KN UT WOS:000242665200006 PM 17008107 ER PT J AU Outeiro, TF McLean, PJ Hyman, BT AF Outeiro, Tiago Fleming McLean, Pamela J. Hyman, Bradley T. BE Gilman, S TI Protein Aggregation Disorders SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE aggregation; amyloid; conformation; neurodegenerative disease; protein misfolding ID FAMILIAL PARKINSONS-DISEASE; AMYLOID-BETA-PROTEIN; PROTOFIBRILLAR ALPHA-SYNUCLEIN; PHOSPHOLIPASE-D ACTIVATION; ALZHEIMERS-DISEASE; LEWY BODIES; NEURODEGENERATIVE DISEASE; VESICLE PERMEABILIZATION; MEMBRANE INTERACTIONS; MOLECULAR CHAPERONES C1 [Outeiro, Tiago Fleming; McLean, Pamela J.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Outeiro, TF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 101 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 111 EP 123 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000011 ER PT J AU Furie, K AF Furie, Karen BE Gilman, S TI Cardioembolism SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE atrial fibrillation; cardiac; cardioembolic; cerebrovascular; embolic; stroke ID PATENT FORAMEN OVALE; CARDIOGENIC BRAIN EMBOLISM; ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; MYOCARDIAL-INFARCTION; CEREBRAL INFARCTION; PREDICTING STROKE; ENDOCARDITIS; RECURRENCE; LAUSANNE C1 Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Furie, K (reprint author), Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 235 EP 240 DI 10.1016/B978-012088592-3/50024-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000023 ER PT J AU Mrugala, M Newcomer, A Batchelor, T AF Mrugala, Maciej Newcomer, Anne Batchelor, Tracy BE Gilman, S TI Primary Central Nervous System Lymphoma SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE B cell; cancer; central nervous system; human immunodeficiency virus; lymphoma ID PRIMARY CNS LYMPHOMA; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMAS; HIGH-DOSE METHOTREXATE; FOLATE CARRIER GENE; MALIGNANT-LYMPHOMA; PHASE-II; IMMUNOCOMPETENT PATIENTS; DEFERRED RADIOTHERAPY; SALVAGE CHEMOTHERAPY C1 [Mrugala, Maciej; Batchelor, Tracy] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stephen E & Catherine Papp, Boston, MA 02115 USA. RP Mrugala, M (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stephen E & Catherine Papp, Boston, MA 02115 USA. NR 92 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 395 EP 412 DI 10.1016/B978-012088592-3/50038-4 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000037 ER PT J AU Meyer, AC Birbeck, GL AF Meyer, Ana-Claire Birbeck, Gretchen L. BE Gilman, S TI Parasitic Infections SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE Acanthamoeba; amebic brain abscess; Angiostrongylus cantonensis; aseptic meningitis; Balamuthia; Baylisascaris procyonis; bilharzias; cerebral hydatid disease; cerebral malaria; cerebral schistosomiasis; chorioretinitis; Echinococcus; Entamoeba histolytica; eosinophilic meningitis; Gnathostoma spinigerum; granulomatous amebic encephalitis; human African trypanosomiasis; malaria; Naegleria fowleri; neural larva migrans; neurocysticercosis; Plasmodium falciparum; primary amoebic meningoencephalitis; raccoon roundworm; rat lungworm; schistosomiasis; schistosoma mansoni; sleeping sickness; Strongyloides stercoralis; Taenia solium; tick paralysis; Toxocara canis; Toxocara cati; toxoplasmosis; Trichinella spiralis; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; trypanosomiasis; vasculitis ID HUMAN AFRICAN TRYPANOSOMIASIS; CENTRAL-NERVOUS-SYSTEM; FALCIPARUM-MALARIA; CLINICAL-ASPECTS; TOXOPLASMOSIS; DISEASE; HUMANS; MENINGOENCEPHALITIS; NEUROCYSTICERCOSIS; NEUROTRICHINOSIS C1 [Meyer, Ana-Claire] Massachusetts Gen Hosp, Partners Neurol Program, Boston, MA 02114 USA. [Birbeck, Gretchen L.] Michigan State Univ, Int Neuropsychiat Epidemiol Program INPEP, E Lansing, MI 48824 USA. RP Meyer, AC (reprint author), Massachusetts Gen Hosp, Partners Neurol Program, Boston, MA 02114 USA. OI Meyer, Ana-Claire/0000-0002-4906-3059 NR 41 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 453 EP 472 DI 10.1016/B978-012088592-3/50043-8 PG 20 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000042 ER PT J AU Herbert, MR AF Herbert, Martha R. BE Gilman, S TI Autism SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE autism; excitation:inhibition ratio; macrocephaly; neurobehavioral disorder; neuroinflammation; social-emotional impairment; underconnectivity ID FUSIFORM FACE AREA; NEURODEVELOPMENTAL DISORDERS; INTERNEURON DEVELOPMENT; SPECTRUM DISORDERS; MENTAL-RETARDATION; BRAIN; CHILDREN; SEROTONIN; NEUROPEPTIDES; ARCHITECTURE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol,Ctr Morphometr Anal, Charlestown, MA USA. RP Herbert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol,Ctr Morphometr Anal, Charlestown, MA USA. NR 53 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 581 EP 591 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000053 ER PT J AU Pomerantz, SR Lev, MH AF Pomerantz, Stuart R. Lev, Michael H. BE Gilman, S TI Neurovascular Computed Tomography Angiography SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE aneurysm; computed tomography angiography; computed tomography perfusion; computed tomography scanning; multidetector row computed tomography; neurovascular disease; neurovascular imaging; stroke ID ACUTE ISCHEMIC-STROKE; DIGITAL-SUBTRACTION-ANGIOGRAPHY; 3-DIMENSIONAL CT-ANGIOGRAPHY; CAROTID-ARTERY STENOSIS; ANEURYSMAL SUBARACHNOID HEMORRHAGE; MEDIA-INDUCED NEPHROTOXICITY; IODINATED CONTRAST AGENTS; HELICAL CT; CONVENTIONAL ANGIOGRAPHY; INTRACRANIAL ANEURYSMS C1 [Pomerantz, Stuart R.; Lev, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Pomerantz, SR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. NR 98 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 801 EP 819 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000075 ER PT J AU Ramsay, RE Macias, FM Rowan, AJ AF Ramsay, R. Eugene Macias, Flavia M. Rowan, A. James TI Diagnosing epilepsy in the elderly SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; DIFFERENTIAL-DIAGNOSIS; STATUS EPILEPTICUS; CLINICAL CHARACTERISTICS; NONEPILEPTIC SEIZURES; UNPROVOKED SEIZURES; THYROID STORM; DISORDERS; EPIDEMIOLOGY; POPULATION AB Elderly individuals represent the fastest-growing segment of the US population. Seizures are common among elderly persons, and the etiology, clinical presentation, and prognosis of seizure disorders can often between elderly patients and younger individuals. However, published information regarding the diagnosis and management of elipepsy in elderly patients is scarce. Because a number of conditions that are common in elderly patients may resemble epilepsy, diagnosis can be challenging. Cardiovascular conditions, migraines, drug effects, infections, metabolic disturbances, sleep disorders, and psychiatric disorders arc all associated with signs and symptoms that may often mimic epilepsy. New paradigms must be put into practice to establish an accurate diagnosis in the elderly patient; besides an initial evaluation, the patient history and an electroencephalogram should be obtained. Proper diagnosis is essential for proper treatment in the elderly patient. C1 Univ Miami, Sch Med, Dept Neurol, Int Ctr Epilepsy, Miami, FL 33136 USA. Miami VA Med Ctr, Dept Neurol, Miami, FL 33125 USA. Bronx Vet Adm Med Ctr, Dept Neurol, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Ramsay, RE (reprint author), Univ Miami, Sch Med, Dept Neurol, Int Ctr Epilepsy, Miami, FL 33136 USA. RI Ramsay, R. Eugene/D-4491-2011 NR 80 TC 9 Z9 11 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 129 EP + DI 10.1016/S0074-7742(06)81008-1 PG 24 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400008 PM 17433921 ER PT J AU Berlowitz, DR Pugh, MJV AF Berlowitz, Dan R. Pugh, Mary Jo V. TI Pharmacoepidemiology in community-dwelling elderly taking antiepileptic drugs SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID CARBAMAZEPINE; PRIMIDONE; PHENYTOIN AB This study used the national inpatient, outpatient, and pharmacy databases from the US Veterans Health Administration to examine prescribing patterns for older patients with epilepsy and to determine the factors associated with receiving recommended antiepileptic drugs (AEDs) such as lamotrigine, gabapentin, or carbamazepine. Among patients with epilepsy, the AED monotherapy most prescribed was phenytoin (70%), followed by phenobarbital (17%). While the rate of phenytoin, use was similar for both previously and newly diagnosed patients with epilepsy, phenobarbital was less commonly used in newly diagnosed patients. Multivariable analyses suggested that reveiving outpatient neurological Care was the strongest predictor of receipt of recommended AED regimens in newly diagnosed elderly patients with epilepsy. These data suggest that the challenge remains to narrow the gap between expert recommendations and actual practice if patients with epilepsy arc to fully benefit from the tremendous progress that has been made in the pharmacological management of this disease. C1 Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Sci, Boston, MA 02118 USA. S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Berlowitz, DR (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. OI Pugh, Mary Jo/0000-0003-4196-7763 NR 14 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 153 EP 163 DI 10.1016/S0074-7742(06)81009-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400009 PM 17433922 ER PT J AU Pugh, MJV Berlowitz, DR Kazis, L AF Pugh, Mary Jo V. Berlowitz, Dan R. Kazis, Lewis TI The impact of epilepsy on older veterans SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID QUALITY-OF-LIFE; HEALTH-STATUS; PEOPLE AB Despite the fact that old age is the time with highest incidence of epilepsy, little is know specifically about the impact of epilepsy on the daily lives of the elderly. Previous studies have explored the impact of epilepsy on health status in a general population, but typically have not included enough older individuals to adequately describe this population. The study on which this chapter is based used a general survey instrument to begin exploration of this tissue in a population of older veterans with epilepsy. Older patients (>= 65 years of age) were identified who had both International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), codes indicating epilepsy and prescriptions of antiepileptic drugs in national Veterans Affairs (VA) administrative and pharmacy databases during fiscal year 1999. Using these databases, patients were further identified as newly or previously diagnosed. Diagnostic data were then linked with data from the 1999 Large Health Survey of Veteran Enrollees, using encrypted identifiers, and the impact of epilepsy on patients of different ages was assessed using individual scales and component summaries of the Veterans SF-36. Results showed that older individuals with epilepsy had lower scores on measures of both physical and mental health than did their counterparts with no epilepsy. Further, scores associated with mental health functioning were significantly lower with newly diagnosed epilepsy than for those with chronic epilepsy, but differences associated with scores on physical functioning were not significant. Thus, while previous studies suggest that the effects of chronic neurological disorders such as epilepsy are most obvious on measures of mental health, these data suggest that older patients experience difficulties in both physical and mental health. C1 S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02118 USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX 78229 USA. OI Kazis, Lewis/0000-0003-1800-5849; Pugh, Mary Jo/0000-0003-4196-7763 NR 26 TC 5 Z9 5 U1 2 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 221 EP 233 DI 10.1016/S0074-7742(06)81014-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400014 PM 17433927 ER PT J AU Macias, FM Ramsay, RE Rowan, AJ AF Macias, Flavia M. Ramsay, R. Eugene Rowan, A. James TI Recruitment and retention in clinical trials of the elderly SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID OLDER-PEOPLE; STRATEGIES; PREVENTION; PROGRAM AB The recruitment and retention of elderly patients in Clinical trials provide many challenges. Challenges. Factors affecting recruitment, retention, and cost of recruitment are discussed in this chapter. Various methods are described that were used in recruiting and retaining elderly patients in a Veterans Affairs (VA) Administration clinical trial that compared two newer antiepileptic drugs (AEDs), gabapentin and and lamotrigine, to the established standard AED, carbamazepine. Various strategies were utilized in the VA study to improve recruitment, and each strategy's overall effectiveness was monitored. modification of the patient inclusion criteria, by lowering the age of eligibility from 65 to 60 years, added approximately 100 patients to the study. Replacing five trial sites that had poor recruiting records, extending the patient recruitment period by 3 months, and conducting site visits also Improved patient recruitment rates, such that 82.4% of target enrollment (720 patients) was achieved. The main reasons that screened patients were excluded from the study included: lack of seizures during the prior 3 months, unstable medical condition, adequate treatment with an AED, satisfaction with current treatment, and the ability to give informed consent. Retaining patients for 1 year was the primary outcome measure of this trial, with 46.8% of patients completing the year. The most Common reasons for early termination were study drug-related adverse events (43.0%) and lack of seizure control (10.8%). Comorbidities and polypharmacy occurred more frequently in the elderly, and both had a negative influence on recruitment and retention. C1 Miami VA Med Ctr, Dept Neurol, Miami, FL 33125 USA. Univ Miami, Sch Med, Dept Neurol, Int Ctr Epilepsy, Miami, FL 33136 USA. Bronx Vet Adm Med Ctr, Dept Neurol, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Macias, FM (reprint author), Miami VA Med Ctr, Dept Neurol, Miami, FL 33125 USA. RI Ramsay, R. Eugene/D-4491-2011 NR 13 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 265 EP 272 DI 10.1016/S0074-7742(06)81017-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400017 PM 17433930 ER PT J AU Levine, JM Snider, R Finkelstein, D Gurol, ME Chanderraj, R Smith, EE Greenberg, SM Rosand, J AF Levine, Joshua M. Snider, Ryan Finkelstein, David Gurol, Mahmut E. Chanderraj, Rishi Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan TI Early edema in warfarin-related intracerebral hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE intracerebral hemorrhage; cerebral hemorrhage; cerebral edema; warfarin; anticoagulation; mortality ID BRAIN EDEMA; PERIHEMATOMAL EDEMA; THROMBIN GENERATION; DIABETES-MELLITUS; GUSTO-1 TRIAL; STROKE; INTENSITY; ANTICOAGULATION; ACTIVATION; EXPRESSION AB Background and purpose The pathophysiology and clinical significance of perihematomal edema (PHE), a cause of secondary neuronal injury after intracerebral hemorrhage (ICH), is poorly understood. A leading theory proposes that early PHE results from activation of the clotting cascade. We sought to test this theory by examining the relationship between early PHE and warfarin use in ICH patients. Methods ICH and PHE volumes were measured in consecutive patients with warfarin-related ICH and compared to those of controls with non-coagulopathic ICH. Subjects were identified from a prospective database of ICH patients. Clinical and radiological predictors of PHE volume and relative PHE (PHE volume/ICH volume) were identified. The relationship between PHE volume and 90-day mortality was determined. Results For the 49 consecutive warfarin-related ICH patients and 49 matched controls: median INRs (interquartile ranges) were 3.2 (2.3, 4.1) and 1.1 (1.08, 1.2); median hematoma volumes were 3 7.8 cm(3) (6.7,102.9) and 18.1 cm(3) (9, 5 1) (P = 0. 18); median PHE volumes were 12 cm(3) (3.7, 36.7), and 11 cm(3) (4.1, 24) (P = 0.87); and median relative PHE was 0.38 (0.28, 0.52) and 2 (1.37, 3.06), respectively. In multivariable analysis, ICH volume and warfarin use independently predicted PHE volume. There was an association between higher PHE volume and decreased 90-day mortality. Conclusions Warfarin-related ICH is associated with less early relative edema than non-coagulopathic ICH. This is consistent with the theory that coagulation contributes to early edema. Early edema may be associated with improved functional outcome. C1 Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Levine, JM (reprint author), Hosp Univ Penn, Dept Neurol, 3W Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM Joshua.Levine@uphs.upenn.edu RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS42695-01, R01 NS042147-02] NR 39 TC 18 Z9 18 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2007 VL 7 IS 1 BP 58 EP 63 DI 10.1007/s12028-007-0039-3 PG 6 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 200EN UT WOS:000248746800011 PM 17657657 ER PT J AU Nogueira, RG Bodock, MJ Koroshetz, WJ Topcuoglu, MA Carter, BS Ogilvy, CS Pryor, JC Buonanno, FS AF Nogueira, Raul G. Bodock, Michael J. Koroshetz, Walter J. Topcuoglu, Mehmet A. Carter, Bob S. Ogilvy, Christopher S. Pryor, Johnny C. Buonanno, Ferdinando S. TI High-dose bosentan in the prevention and treatment of subarachnoid hemorrhage-induced cerebral vasospasm: An open-label feasibility study SO NEUROCRITICAL CARE LA English DT Article DE bosentan; endothelin; antagonist; subarachnoid hemorrhage; vasospasm ID ENDOTHELIN-RECEPTOR ANTAGONIST; PLASMA ENDOTHELIN; ET(B) RECEPTORS; CEREBROSPINAL-FLUID; DOUBLE-BLIND; ARTERIES; ET(A); HYPERTENSION; EXPRESSION; EFFICACY AB Objective To evaluate the safety of high-dosages of the endothelin ETA/B receptor antagonist bosentan in SAH patients at high-vasospasm risk. Methods Ten Fisher group-3 SAH patients, enrolled within 96 h of ictus, received bosentan in a dose-escalation manner (20, 30, 40 mg/kg/day orally every 4 hours on treatment days 1, 2, and 3 respectively, to a maximum dose of 4000 mg/day), followed by maintenance of the maximum tolerated dose until 14 days post-SAH or vasospasm resolution. Further management followed standard protocols: nimodipine in all patients; daily transcranial Doppler (TCD); "triple-H"/endovascular treatment, as indicated. Results Two of the ten patients never developed any clinical or TCD signs of vasospasm; the other eight patients exhibited some elevation of TCD velocities during the vasospasm watch period. Four of the eight patients remained asymptomatic; of them, one had only mild elevation on peak systolic velocities, thought to represent hyperemia. The other three were further assessed with CT-angiography; this revealed moderate vasospasm (asymptomatic) in only one patient. The remaining four patients developed symptomatic vasospasm requiring endovascular treatment; two developed cerebral infarction; both bad started bosentan relatively later than the other subjects. The most common adverse drug effects were flushing and transient liver enzyme elevations, reversible in all. Two patients had ALT/AST elevations >3x normal limit, requiring bosentan-dose reduction or discontinuation (one case each). Conclusion High-dose bosentan (up to 40 mg/kg/day) appears to be safe in SAH patients at high risk of developing vasospasm. Further studies are required to properly investigate the efficacy of this regimen in the prevention and treatment of SAH-induced vasospasm. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Neurosurg Serv, Boston, MA 02114 USA. MIT, Harvard Med Sch, Dept Neurol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pharm, Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Neurosurg Serv, Boston, MA USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Neurosurg Serv, GRB-2-241,55 Fruit St, Boston, MA 02114 USA. EM rnogueira@partners.org NR 39 TC 6 Z9 6 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2007 VL 7 IS 3 BP 194 EP 202 DI 10.1007/s12028-007-0070-4 PG 9 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 237SO UT WOS:000251396900003 PM 17901934 ER PT J AU Goddeau, RP Silverman, SB Sims, JR AF Goddeau, Richard P., Jr. Silverman, Scott B. Sims, John R. TI Dexmedetomidine for the treatment of paroxysmal autonomic instability with dystonia SO NEUROCRITICAL CARE LA English DT Article DE dexmedetomidine; sympathetic storming; paroxysmal autonomic instability with dystonia; diencephalic seizure; dysautonomia; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; DIENCEPHALIC SEIZURES; SYMPATHETIC STORM; DYSAUTONOMIA; STIMULATION; LABETALOL; INFUSION AB Introduction A 38-year-old man with severe head trauma complicated by paroxysmal severe intracranial pressure elevation associated with tachypnea, tachycardia, diaphoresis, and extensor posturing was diagnosed as suffering from paroxysmal autonomic instability with dystonia (PAID). These events were unresponsive to standard medical therapy, which included morphine, fentanyl, labetalol, lorazepam, metoprolol, and clonidine. Methods A trial treatment with dexmedetomidine dine, a central acting alpha2-agonist, to control symptoms of PAID was initiated 12 days after injury. PAID-related events subsided during the 72-h infusion protocol of 0.2-0.7 mcg/kg/h. No further events were noted after termination of the 72-h infusion. Conclusions Dexmedetomidine may be a novel pharmacologic agent to aid in abrogating PAID. C1 Massachusetts Gen Hosp East, Dept Neurol & Radiol, Div Neurocrit Care & Stroke, Boston, MA 02129 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Div Neucrit Care & Stroke, Boston, MA USA. RP Sims, JR (reprint author), Massachusetts Gen Hosp East, Dept Neurol & Radiol, Div Neurocrit Care & Stroke, CNY149 Rm6403, Boston, MA 02129 USA. EM jsims@partners.org NR 23 TC 18 Z9 18 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2007 VL 7 IS 3 BP 217 EP 220 DI 10.1007/s12028-007-0066-0 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 237SO UT WOS:000251396900006 PM 17603760 ER PT J AU Muehlschlegel, S Dunser, MW Gabrielli, A Wenzel, V Layon, AJ AF Muehlschlegel, Susanne Dunser, Martin W. Gabrielli, Andrea Wenzel, Volker Layon, A. Joseph TI Arginine vasopressin as a supplementary vasopressor in refractory hypertensive, hypervolemic, hemodilutional therapy in subarachnoid hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE arginine vasopressin; brain injury; subarachnoid hemorrhage; hyponatremia; cerebral vasospasm; HHH therapy ID VASODILATORY SEPTIC SHOCK; LOW-DOSE VASOPRESSIN; CEREBRAL-BLOOD-FLOW; BRAIN EDEMA; VASOSPASM; RECEPTOR; RAT; HEMODYNAMICS; ANTAGONIST; ANEURYSMS AB Introduction: Hypertensive, hypervolemic, and hemodilutional (HHH) therapy for vasospasm in subarachnoid hemorrhage (SAH) refractory to phenylephrine requires high doses of catecholamines, leading to adverse adrenergic effects. Arginine vasopressin (AVP) has been shown to stabilize advanced shock states while facilitating reduction of catecholamine doses, but its use has never been reported in SAH. In this retrospective study, we investigated the hemodynamic effects and feasibility of supplementary AVP in refractory HHH therapy in SAH. Methods: Hemodynamic response (mean arterial pressure [MAP], heart rate, central venous pressure, cardiac index, systemic vascular resistance index, and end diastolic volume index) to a supplementary AVP infusion (0.01-0.04 IU/minute) was recorded within the first 24 hours in 22 patients. Secondary endpoints (serum sodium concentration, incidence of vasospasm, and intracranial pressure [ICP]) were compared to controls on HHH therapy with phenylephrine alone. Results: After initiation of AVP, MAP increased significantly compared to baseline. Phenylephrine doses decreased significantly, whereas other hemodynamic parameters remained stable. Serum sodium concentrations decreased similarly in both groups (-5 +/- 7 mmol/L versus -6 +/- 4 mmol/L; p = 0.25). No detrimental effects on vasospasm incidence or ICP and cerebral perfusion pressure were noted. Conclusion: AVP may be considered as an alternative supplementary vasopressor in refractory HHH therapy with phenylephrine in SAH. Although we did not observe any deleterious effect of AVP on cerebral circulation, close observation for development of cerebral vasospasm should be undertaken, until it is clearly demonstrated that AVP has no adverse effects on regional cerebral blood flow and symptomatic cerebral vasospasm. Our limited data suggest that low-dose AVP does not cause brain edema, but further study is merited. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Brigham Womens Hosp, Dept Neurol,Div Vasc Neurol & Neurocrit Care, Boston, MA 02114 USA. Univ Hosp Bern, Dept Intens Care Med, CH-3010 Bern, Switzerland. Univ Florida, Coll Med, Dept Anesthesiol, Div Crit Care Med, Gainesville, FL USA. Univ Florida, Coll Med, Dept Surg, Div Crit Care Med, Gainesville, FL USA. Univ Florida, Coll Med, Dept Med, Div Crit Care Med, Gainesville, FL USA. Innsbruck Med Univ, Dept Anesthesiol & Crit Care Med, Innsbruck, Austria. RP Muehlschlegel, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Brigham Womens Hosp, Dept Neurol,Div Vasc Neurol & Neurocrit Care, 55 Fruit St,Blake 12, Boston, MA 02114 USA. EM smuehlschlegel@partners.org OI Layon, A. Joseph/0000-0002-2226-9516 NR 47 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2007 VL 6 IS 1 BP 3 EP 10 DI 10.1385/Neurocrit.Care2007;06:3-10 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 146QI UT WOS:000244949000002 PM 17356185 ER PT J AU Greer, DM AF Greer, David M. TI Continuous intravenous NSAID administration for fever control SO NEUROCRITICAL CARE LA English DT Editorial Material ID ACUTE BRAIN-INJURY; INTENSIVE-CARE; CARDIAC-ARREST; HYPERTHERMIA; PYREXIA; HYPOTHERMIA; ISCHEMIA; DAMAGE C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greer, DM (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 13 TC 0 Z9 0 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2007 VL 6 IS 2 BP 79 EP 81 DI 10.1007/s12028-007-0021-0 PG 3 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 179DW UT WOS:000247270700001 PM 17522788 ER PT J AU Mollenhauer, B Steinacker, P Bahn, E Bibl, M Brechlin, P Schlossmacher, MG Locascio, JJ Wiltfang, J Kretzschmar, HA Poser, S Trenkwalder, C Otto, M AF Mollenhauer, Brit Steinacker, Petra Bahn, Erik Bibl, Mirko Brechlin, Peter Schlossmacher, Michael G. Locascio, Joseph J. Wiltfang, Jens Kretzschmar, Hans A. Poser, Sigrid Trenkwalder, Claudia Otto, Markus TI Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: Marker candidates for dementia with Lewy bodies SO NEURODEGENERATIVE DISEASES LA English DT Article DE heart-type fatty acid-binding protein; tau protein; Alzheimer's disease; dementia with Lewy bodies; Parkinson disease dementia; cerebrospinal fluid ID ACUTE MYOCARDIAL-INFARCTION; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; BIOLOGICAL MARKERS; CLINICAL-DIAGNOSIS; TASK-FORCE; BRAIN-TYPE; PLASMA; TISSUE AB Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nonclemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of HFABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum HFABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio >= 8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB. Copyright (c) 2007 S. Karger AG, Basel. C1 Harvard Inst Med, Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Memory & Movement Disorder Unit, Boston, MA 02115 USA. Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany. Univ Gottingen, Dept Pathol, D-3400 Gottingen, Germany. Univ Gottingen, Dept Psychiat, D-3400 Gottingen, Germany. Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. Univ Erlangen Nurnberg, Dept Psychiat, Nurnberg, Germany. Univ Munich, Inst Neuropathol, D-8000 Munich, Germany. Univ Gottingen, Paracelsus Elena Klin, Kassel, Germany. RP Mollenhauer, B (reprint author), Harvard Inst Med, Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 77,Ave Louis Pasteur, Boston, MA 02115 USA. EM bmollenhauer@rics.bwh.harvard.edu RI Otto, Markus/F-4304-2015; OI Otto, Markus/0000-0003-4273-4267; Wiltfang, Jens/0000-0003-1492-5330 NR 49 TC 23 Z9 24 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2007 VL 4 IS 5 BP 366 EP 375 DI 10.1159/000105157 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 195BB UT WOS:000248386400002 PM 17622779 ER PT J AU Irizarrya, MC Yao, Y Hyman, BT Growdon, JH Pratico, D AF Irizarrya, M. C. Yao, Y. Hyman, B. T. Growdon, J. H. Pratico, D. TI Plasma F2A lsoprostane levels in Alzheimer's and Parkinson's disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; Parkinson's disease; mild cognitive; impairment; isoprostanes; oxidative stress; biomarkers ID MILD COGNITIVE IMPAIRMENT; PEROXIDATION IN-VIVO; LIPID-PEROXIDATION; OXIDATIVE STRESS; F-2-ISOPROSTANES; DEMENTIA; PREDICTOR; DIAGNOSIS; AGE AB Background: Oxidative damage is implicated in the pathophysiology of Alzheimer's disease (AD). F-2-isoprostane is a marker of lipid peroxidation which is elevated in AD CSF Plasma F-2-isoprostane has been proposed as a diagnostic marker for AD and mild cognitive impairment (MCI). Objective:To determine whether plasma F-2-isoprostane levels differ between nondemented control individuals and patients with AD, MCI, or Parkinson's disease (PD). Methods: We collected plasma from 191 outpatients with a diagnosis of AD (49), MCI (47), nondemented PD (47), and no dementia (48). Plasma levels of the isoprostane iP2 alpha-IV (F2A) were determined by gas chromatography/mass spectroscopy. Results: Mean plasma levels of F2A isoprostane did not differ significantly between the four diagnostic groups. Within the MCI and AD groups, F2A levels did not correlate with duration of memory impairment or with cognitive test scores. F2A levels were marginally lower in users of cholinesterase inhibitors and individuals with an APOE epsilon 4 allele. Conclusions: While CSF isoprostane levels are elevated in AD, plasma isoprostane measures were neither sensitive nor specific for the clinical diagnosis of MCI or AD. Copyright (c) 2007 S. Karger AG, Basel. C1 GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Massachussets Alzheimers Dis Res Ctr, Boston, MA 02114 USA. Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Irizarrya, MC (reprint author), GlaxoSmithKline Inc, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM michael.c.irizarry@gsk.com FU NIA NIH HHS [AG05134]; PHS HHS [IT32N5048005-01] NR 17 TC 36 Z9 38 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2007 VL 4 IS 6 BP 403 EP 405 DI 10.1159/000107699 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221WM UT WOS:000250258100001 PM 17934322 ER PT J AU Schillerstrom, JE Baker, PS Allman, RM Rungruang, B Zamrini, E Royall, DR AF Schillerstrom, Jason E. Baker, Patricia Sawyer Allman, Richard M. Rungruang, Bunja Zamrini, Edward Royall, Donald R. TI Clock drawing phenotypes in community-dwelling African Americans and caucasians: Results from the university of Alabama at Birmingham study of aging SO NEUROEPIDEMIOLOGY LA English DT Article DE aging; executive function; clock drawing task; cognition; African American population; dementia ID EXECUTIVE IMPAIRMENT; COGNITIVE IMPAIRMENT; DEMENTIA PATIENTS; HISPANIC EPESE; PREVALENCE; PATTERNS; SERVICE; HEALTH; CARE AB Background: Two dementia patterns have been described: 'type 1' dementia is characterized by executive function impairment and posterior cortical impairment, and 'type 2' dementia is characterized by executive impairment and relatively preserved posterior cortical function. The Executive Clock Drawing Task ( CLOX) has been used to discriminate between type 1, type 2, and normal cognitive phenotypes. The aim of this study was to describe the prevalence of these phenotypes in community-dwelling African American and Caucasian elders. Methods: 433 African Americans and 477 Caucasians over the age of 65 were recruited. Executive function was assessed using CLOX1, a command-directed clock drawing task. Posterior cortical impairment was assessed using CLOX2, a clock copy task. CLOX scores were combined to estimate the prevalence of type 1 phenotype ( those with poor CLOX1 and CLOX2 performance) versus type 2 phenotype ( those with only poor CLOX1 performance). Results: 351 ( 39%) subjects had poor executive performance. Three hundred ( 33%) subjects had a type 1 phenotype and this pattern was 2.5 times more common among African Americans than Caucasians. One hundred and thirty seven ( 15%) subjects had a type 2 phenotype with no significant difference between African Americans and Caucasians. African American ethnicity was independently associated with poor CLOX1 performance after adjusting for sociodemographic factors, posterior cortical function, and global cognition. CLOX2 performance was not associated with ethnicity. Conclusion: The prevalence of poor executive performance in community-dwelling elders is high. African Americans were more likely to have a type 1 phenotype and these ethnic differences were not explained by sociodemographic variables alone. Copyright (C) 2007 S. Karger AG, Basel. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Alabama, Ctr Aging, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Birmingham Atlant VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Schillerstrom, JE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM schillerstr@uthscsa.edu FU NIA NIH HHS [AG15062, R01 AG015062, AG 16582] NR 23 TC 2 Z9 2 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2007 VL 28 IS 3 BP 175 EP 180 DI 10.1159/000104095 PG 6 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 207BD UT WOS:000249225700007 PM 17579283 ER PT J AU Hachinski, V Skoog, I Scheltens, P Wallin, A Erkinjuntti, T Nagata, K Pasquier, F Breteler, MMB DeCarli, C Kalaria, RN Li Hsian, CC Royall, DR Roman, GC AF Hachinski, Vladimir Skoog, Ingmar Scheltens, Philip Wallin, Anders Erkinjuntti, Timo Nagata, Ken Pasquier, Florence Breteler, Monique M. B. DeCarli, Charles Kalaria, Rajesh N. Li Hsian, Christopher Chen Royall, Donald R. Roman, Gustavo C. TI Declaration of San Antonio, Texas SO NEUROEPIDEMIOLOGY LA English DT Editorial Material C1 Univ Western Ontario, London, ON, Canada. Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. Univ Gothenburg, Gothenburg, Sweden. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. Univ Helsinki, Memory Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Res Inst Brain & Blood Vessels, Akita, Japan. Lille Univ Hosp, Memory Clin, Lille, France. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Neuroepidemiol Sect, Rotterdam, Netherlands. Univ Calif Davis, Imaging Dementia & Aging Lab, Dept Neurol, Sacramento, CA 95817 USA. Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. Newcastle Gen Hosp, Wolfson Res Ctr, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Chair Sci Comm San Antonio, San Antonio, TX USA. Singapore Gen Hosp, Singapore 0316, Singapore. Natl Inst Neurosci, Singapore, Singapore. Vet Adm Hosp, Geriatr Res Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Geriatr Psychiat Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Memory Clin, San Antonio, TX USA. Univ Calif Davis, UC Davis Alzheimers Dis Ctr, Sacramento, CA 95817 USA. RP Hachinski, V (reprint author), Univ Western Ontario, London, ON, Canada. RI DeCarli, Charles/B-5541-2009 NR 0 TC 3 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2007 VL 28 IS 3 BP 191 EP 192 DI 10.1159/000107278 PG 2 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 207BD UT WOS:000249225700010 ER PT J AU Prakash, N Biag, JD Sheth, SA Mitsuyama, S Theriot, J Ramachandra, C Toga, AW AF Prakash, Neal Biag, Jonathan D. Sheth, Sameer A. Mitsuyama, Satoshi Theriot, Jeremy Ramachandra, Chaithanya Toga, Arthur W. TI Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex SO NEUROIMAGE LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; OPTICAL IMAGING SPECTROSCOPY; INTRINSIC SIGNALS; NEURONAL-ACTIVITY; BARREL CORTEX; BLOOD-FLOW; NEURAL ACTIVITY; LAYER-IV; FUNCTIONAL ARCHITECTURE; CEREBRAL-CORTEX AB Background: Mechanisms of neurovascular coupling-the relationship between neuronal chemoelectrical activity and compensatory metabolic and hemodynamic changes-appear to be preserved across species from rats to humans despite differences in scale. However, previous work suggests that the highly cellular dense mouse somatosensory cortex has different functional hemodynamic changes compared to other species. Methods: We developed novel hardware and software for 2-dimensional optical spectroscopy (2DOS). Optical changes at four simultaneously recorded wavelengths were measured in both rat and mouse primary somatosensory cortex (S1) evoked by forepaw stimulation to create four spectral maps. The spectral maps were converted to maps of deoxy-, oxy-, and total-hemoglobin (HbR, HbO, and HbT) concentration changes using the modified Beer-Lambert law and phantom HbR and HbO absorption spectra. Results: Functional hemodynamics were different in mouse versus rat neocortex. On average, hemodynamics were as expected in rat primary somatosensory cortex (S1): the fractional change in the log of HbT concentration increased monophasically 2 s after stimulus, whereas HbO changes mirrored HbR changes, with HbO showing a small initial dip at 0.5 s followed by a large increase 3.0 s post stimulus. In contrast, mouse S1 showed a novel type of stimulus-evoked hemodynamic response, with prolonged, concurrent, monophasic increases in HbR and HbT and a parallel decrease in HbO that all peaked 3.5-4.5 s post stimulus onset. For rats, at any given time point, the average size and shape of HbO and HbR forepaw maps were the same, whereas surface veins distorted the shape of the HbT map. For mice, HbO, HbR, and HbT forepaw maps were generally the same size and shape at any poststimulus time point. Conclusions: 2DOS using image splitting optics is feasible across species for brain mapping and quantifying the map topography of cortical hemodynamics. These results suggest that during physiologic stimulation, different species and/or cortical architecture may give rise to different hemodynamic changes during neurovascular coupling. Published by Elsevier Inc. C1 Univ Calif Los Angeles, David Greffen Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90095 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Prakash, N (reprint author), Univ Calif Los Angeles, Lab Neuro Imaging, 635 Charles E Young Dr S, Suite 225, Los Angeles, CA 90095 USA. EM neal.prakash@gmail.com FU NIMH NIH HHS [MH52083, R01 MH052083, R01 MH052083-07A1] NR 73 TC 20 Z9 20 U1 2 U2 5 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 PY 2007 VL 37 SU 1 BP S27 EP S36 DI 10.1016/j.neuroimage.2007.04.063 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 210CK UT WOS:000249434100003 PM 17574868 ER PT J AU Ganis, G Schendan, HE Kosslyn, SM AF Ganis, Giorgio Schendan, Haline E. Kosslyn, Stephen M. TI Neuroimaging evidence for object model verification theory: Role of prefrontal control in visual object categorization SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY; NEURAL MECHANISMS; HUMAN BRAIN; NEUROPHYSIOLOGICAL EVIDENCE; VISUOSPATIAL ATTENTION; IDENTIFYING OBJECTS; SELECTIVE ATTENTION; CORTEX; RECOGNITION AB Although the visual system rapidly categorizes objects seen under optimal viewing conditions, the categorization of objects seen under impoverished viewing conditions not only requires more time but may also depend more on top-down processing, as hypothesized by object model verification theory. Two studies, one with functional magnetic resonance imaging (fMRI) and one behavioral with the same stimuli, tested this hypothesis. FMRI data were acquired while people categorized more impoverished (MI) and less impoverished (LI) line drawings of objects. FMRI results revealed stronger activation during the MI than LI condition in brain regions involved in top-down control (inferior and medial prefrontal cortex, intraparietal sulcus), and in posterior, object-sensitive brain regions (ventral and dorsal occipito-temporal, and occipitoparietal cortex). The behavioral study indicated that taxing visuospatial working memory, a key component of top-down control processes during visual tasks, interferes more with the categorization of MI stimuli (but not LI stimuli) than does taxing verbal working memory. Together, these findings provide evidence for object model verification theory and implicate greater prefrontal cortex involvement in top-down control of posterior visual processes during the categorization of more impoverished images of objects. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02142 USA. RP Ganis, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Bldg 149, Charlestown, MA 02129 USA. EM ganis@nmr.mgh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIA NIH HHS [5 F32 AG005914, F32 AG005914]; NIEHS NIH HHS [27300C0032]; NIMH NIH HHS [R01 MH060734, 1 R21 MH068610-01A1, 2 R01 MH060734-05A1, R01 MH060734-05A1, R01 MH060734-06, R21 MH068610, R21 MH068610-02] NR 80 TC 29 Z9 33 U1 1 U2 5 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 JAN 1 PY 2007 VL 34 IS 1 BP 384 EP 398 DI 10.1016/j.neuroimage.2006.09.008 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 115LH UT WOS:000242735300038 PM 17071109 ER PT J AU Bortfeld, H Wruck, E Boas, DA AF Bortfeld, Heather Wruck, Eric Boas, David A. TI Assessing infants' cortical response to speech using near-infrared spectroscopy SO NEUROIMAGE LA English DT Article ID CEREBRAL OXYGENATION CHANGES; HUMAN BRAIN; NEWBORN-INFANTS; HEMODYNAMIC-RESPONSES; VISUAL-STIMULATION; OPTICAL TOPOGRAPHY; AWAKE INFANTS; ACTIVATION; PERCEPTION; LANGUAGE AB Sensitivity to spoken language is an integral part of infants' formative development, yet relatively little is known about the neural mechanisms that underlie the emerging ability to perceive and process speech. This is in large part because there are a limited number of non-invasive techniques available to measure brain functioning in human infants. Near-infrared spectroscopy (NIRS), an optical imaging technique that estimates changes in neuronal activity by measuring changes in total hemoglobin concentration and oxygenation, may be a viable procedure for assessing the relation between speech processing and brain function in human infants. While auditory processing data have been gathered from newborn and preterm infants using NIRS, such data have not been collected from older infants. Many behavioral measures used to establish linguistic sensitivity in this population are accompanied by visual stimuli; however, it is unclear how coupling of auditory and visual stimuli influences neural processing. Here we studied cortical activity in infants aged 6-9 months, as measured by NIRS, during exposure to linguistic stimuli paired with visual stimuli and compared this to the activity observed in the same regions during exposure to visual stimuli alone. Results dissociate infants' hemodynamic responses to multimodal and unimodal stimuli, demonstrating the utility of NIRS for studying perceptual development in infants. In particular, these findings support the use of NIRS to study the neurobiology of language development in older infants, a task that is difficult to accomplish without the use of attention-getting visual stimuli. (c) 2006 Elsevier Inc. All rights reserved. C1 Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Bortfeld, H (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU,Coll Stn, College Stn, TX 77843 USA. EM hbortfeld@psych.tamu.edu OI Bortfeld, Heather/0000-0002-3545-5449 FU NCRR NIH HHS [P41-RR14075, P41 RR014075]; NICHD NIH HHS [R03 HD046533, R03-HD046533] NR 52 TC 70 Z9 71 U1 1 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 JAN 1 PY 2007 VL 34 IS 1 BP 407 EP 415 DI 10.1016/j.neuroimage.2006.08.010 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 115LH UT WOS:000242735300040 PM 17045812 ER PT J AU Marcus, DS Olsen, TR Ramaratnam, M Buckner, RL AF Marcus, Daniel S. Olsen, Timothy R. Ramaratnam, Mohana Buckner, Randy L. TI The Extensible Neuroimaging Archive Toolkit - An informatics platform for managing, exploring, and sharing neuroimaging data SO NEUROINFORMATICS LA English DT Article DE data sharing; database; genetics; informatics; metadata; neuroinformatics; open source; quality control; workflow; XML schema ID FUNCTIONAL-DEPENDENCIES; XML; REPRESENTATION; DATABASES; FRAMEWORK; COGNITION; DEMENTIA; VOLUME AB The Extensible Neuroimaging Archive Toolkit (XNAT) is a software platform designed to facilitate common management and productivity tasks for neuroimaging and associated data. In particular, XNAT enables quality-control procedures and provides secure access to and storage of data. XNAT follows a three-tiered architecture that includes a data archive, user interface, and middleware engine. Data can be entered into the archive as XML or through data entry forms. Newly added data are stored in a virtual quarantine until an authorized user has validated it. XNAT subsequently maintains a history profile to track all changes made to the managed data. User access to the archive is provided by a secure web application. The web application provides a number of quality control and productivity features, including data entry forms, data-type-specific searches, searches that combine across data types, detailed reports, and listings of experimental data, upload/download tools, access to standard laboratory workflows, and administration and security tools. XNAT also includes an online image viewer that supports a number of common neuroimaging formats, including DICOM and Analyze. The viewer can be extended to support additional formats and to generate custom displays. By managing data with XNAT, laboratories are prepared to better maintain the long-term integrity of their data, to explore emergent relations across data types, and to share their data with the broader neuroimaging community. C1 Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Marcus, DS (reprint author), Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. EM dmarcus@wustl.edu FU NCRR NIH HHS [U24RR021382] NR 39 TC 148 Z9 149 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PY 2007 VL 5 IS 1 BP 11 EP 33 DI 10.1385/NI:5:1:11 PG 23 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 160HB UT WOS:000245930400003 PM 17426351 ER PT J AU Bryant, M Marta, C Kim, F Haroutunian, V Pfeiffer, SE Bansal, R AF Bryant, M. Marta, C. Kim, F. Haroutunian, V. Pfeiffer, S. E. Bansal, R. TI FGF Receptor-2 in oligodendrocytes and myelin SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Bryant, M.; Marta, C.; Pfeiffer, S. E.; Bansal, R.] Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT USA. [Haroutunian, V.] Bronx Vet Affairs Med Ctr, New York, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S94 EP S94 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800289 ER PT J AU Hickman, S Allison, E Luster, A El Khoury, J AF Hickman, Suzanne Allison, Elizabeth Luster, Andrew El Khoury, Joseph TI Microglia in aged PS1-APP mice exhibit downregulation of A beta clearing genes and upregulation of pro-inflammatory cytokines SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Hickman, Suzanne; Allison, Elizabeth; Luster, Andrew; El Khoury, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S113 EP S114 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800351 ER PT J AU Woolf, CJ AF Woolf, Clifford J. TI The complement cascade in spinal cord microglia contributes to neuropathic pain SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Woolf, Clifford J.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S15 EP S15 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800045 ER PT J AU Mallinckrodt, CH Prakash, A Houston, JP Swindle, R Detke, MJ Fava, M AF Mallinckrodt, Craig H. Prakash, Apurva Houston, John P. Swindle, Ralph Detke, Michael J. Fava, Maurizio TI Differential antidepressant symptom efficacy: Placebo-controlled comparisons of duloxetine and SSRIs (fluoxetine, paroxetine, escitalopram) SO NEUROPSYCHOBIOLOGY LA English DT Article DE duloxetine; selective serotonin reuptake inhibitor; major depressive disorder, symptom severity; antidepressant ID MAJOR DEPRESSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; PAINFUL PHYSICAL SYMPTOMS; RATING-SCALE; DOUBLE-BLIND; CONTROLLED TRIAL; CLINICAL-TRIAL; VENLAFAXINE; SUBSCALES; SAFETY AB Objective: To test the hypothesis that in patients with major depressive disorder ( MDD), the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors (SSRIs) and that patterns of response will differ based on symptom severity at baseline. Method: Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD: 7 randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133) versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80 and 120 mg/ day. SSRI doses were 10 mg/ day (escitalopram) and 20 mg/ day (fluoxetine and paroxetine). Results: Compared to SSRI-treated patients, duloxetine-treated patients had a significantly greater (p <= 0.05) reduction in the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score and HAMD(17) items of work and activities, psychomotor retardation, genital symptoms and hypochondriasis. Differences favoring the SSRIs approached significance for middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine. Similarly, the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms (p = 0.056), with an effect size twice that observed for the SSRIs. The HAMD(17) total score difference was driven mostly by patients with lower baseline MDD severity (HAMD(17) total score <= 19), where the HAMD(17) effect size advantage for duloxetine over combined SSRIs was statistically significant (p = 0.031). Conclusion: Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity, and different HAMD(17) items responded differently to duloxetine compared with SSRIs. Understanding these differences may be useful in tailoring antidepressant therapy for individual patients. Copyright (c) 2007 S. Karger AG, Basel. C1 Indiana Univ, Sch Med, Indianapolis, IN USA. [Mallinckrodt, Craig H.; Prakash, Apurva; Houston, John P.; Swindle, Ralph; Detke, Michael J.] Lilly Res Labs, Indianapolis, IN USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Detke, Michael J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Mallinckrodt, CH (reprint author), Eli Lilly & Co, Lilly Corp Ctr, DC 4103, Indianapolis, IN 46285 USA. EM cmallinc@lilly.com NR 43 TC 30 Z9 34 U1 7 U2 14 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2007 VL 56 IS 2-3 BP 73 EP 85 DI 10.1159/000111537 PG 13 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 260MN UT WOS:000253014500003 PM 18037817 ER PT J AU Papakostas, GI Crawford, CM Scalia, MJ Fava, M AF Papakostas, George I. Crawford, Christine M. Scalia, Margaret J. Fava, Maurizio TI Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder SO NEUROPSYCHOBIOLOGY LA English DT Article DE depression, symptom, resolution; timing, improvement; selective serotonin reuptake inhibitor ID TRUE DRUG RESPONSE; PATTERN-ANALYSIS; FLUOXETINE TREATMENT; DOUBLE-BLIND; PLACEBO; ANTIDEPRESSANT; ONSET; METAANALYSIS; RELAPSE; AMITRIPTYLINE AB Background: Our objective was to assess for the relationship between timing of clinical improvement and resolution of depressive symptoms during the treatment of major depressive disorder (MDD). Thirty-nine MDD outpatients who responded following a 12-week, double-blind study comparing Hypericum perforatum, fluoxetine or placebo were included in the analysis. Methods: Onset of clinical improvement was defined as a 25% decrease in 17-item Hamilton Depression Scale (HDRS-17) scores that was not followed by a subsequent worsening of symptoms. Controlling for baseline symptom severity, we then assessed for the relationship between timing of clinical improvement and depressive symptom severity at endpoint. Results: Among responders, earlier clinical improvement predicted lower HDRS-17 scores at week 12 (p = 0013). This was also true of responders who received active treatment (n = 29, p = 0.0113) but not placebo responders (n = 10; p > 0.05). Finally, patients with an early onset of clinical improvement ( occurring during the first 2 weeks) had lower week 12 HDRS- 17 scores than patients with a late onset of clinical improvement (p = 0.0404). Conclusion: In the present work, earlier as well as early clinical improvement during treatment is predictive of greater symptom resolution at endpoint among responders. This was replicated among patients who received active treatment (either hypericum or fluoxetine) but not placebo. Copyright (c) 2008 S. Karger AG, Basel. C1 [Papakostas, George I.; Crawford, Christine M.; Scalia, Margaret J.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 15 Parkman St,WAC 8120, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 39 TC 15 Z9 15 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2007 VL 56 IS 2-3 BP 132 EP 137 DI 10.1159/000115779 PG 6 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 260MN UT WOS:000253014500012 PM 18259086 ER PT J AU Tamietto, M Adenzato, M Geminiani, G de Gelder, B AF Tamietto, Marco Adenzato, Mauro Geminiani, Giuliano de Gelder, Beatrice TI Fast recognition of social emotions takes the whole brain: Interhemispheric cooperation in the absence of cerebral asymmetry SO NEUROPSYCHOLOGIA LA English DT Review DE social cognition; face perception; hemispheric laterality; redundant target effect; bilateral gain; flirtatiousness; arrogance ID SEPARATE-ACTIVATION MODELS; SPLIT BRAIN; FACIAL EXPRESSIONS; NEURAL SUMMATION; DIVIDED ATTENTION; REDUNDANT SIGNALS; PREFRONTAL CORTEX; ASPERGER-SYNDROME; CORPUS-CALLOSUM; FMRI AB Hemispheric asymmetry in emotional perception has been traditionally studied for basic emotions and very little is known about laterality for more complex social emotions. Here, we used the "redundant target paradigm" to investigate interhemispheric asymmetry and cooperation for two social emotions in healthy subjects. Facial expressions of flirtatiousness or arrogance were briefly presented either unilaterally in the left (LVF) or right visual field (RVF), or simultaneously to both visual fields (BVF) while participants responded to the target expression (flirtatious or arrogant, counterbalanced between blocks). In bilateral conditions the faces could show the same emotion (congruent condition) or two different expressions (incongruent condition). No difference between unilateral presentations was found, suggesting that the perception of social emotions is not hemispherically lateralized. Responses were faster and more accurate in bilateral displays with two emotionally congruent but physically different faces (i.e., a male and a female expressing the same emotion) than in unilateral conditions. This "redundant target effect" was consistent with a neural summation model, thereby showing that interhemispheric cooperation may occur for social emotions despite major perceptual differences between faces posing the same expression. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Turin, Dept Psychol, I-10123 Turin, Italy. Univ Turin, Ctr Cognit Sci, I-10123 Turin, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP Tamietto, M (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy. EM tamietto@psych.unito.it; degelder@nmr.mgh.harvard.edu RI Adenzato, Mauro/I-5127-2012; OI Adenzato, Mauro/0000-0002-6997-9283; Tamietto, Marco/0000-0002-8815-8499 NR 71 TC 34 Z9 35 U1 5 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 4 BP 836 EP 843 DI 10.1016/j.neuropsychologia.2006.08.012 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 143YZ UT WOS:000244763600022 PM 16996092 ER PT J AU Addis, DR Wong, AT Schacter, DL AF Addis, Donna Rose Wong, Alana T. Schacter, Daniel L. TI Remembering the past and imagining the future: Common and distinct neural substrates during event construction and elaboration SO NEUROPSYCHOLOGIA LA English DT Article DE episodic; autobiographical memory; fMRI; hippocampus; frontopolar ID AUTOBIOGRAPHICAL MEMORY RETRIEVAL; POSITRON-EMISSION-TOMOGRAPHY; EPISODIC MEMORY; PREFRONTAL CORTEX; STRATEGIC RETRIEVAL; HIPPOCAMPAL COMPLEX; TEMPORAL-LOBES; FRONTAL LOBES; SELF; ACTIVATION AB People can consciously re-experience past events and pre-experience possible future events. This fMRI study examined the neural regions mediating the construction and elaboration of past and future events. Participants were cued with a noun for 20s and instructed to construct a past or future event within a specified time period (week, year, 5-20 years). Once participants had the event in mind, they made a button press and for the remainder of the 20 s elaborated on the event. Importantly, all events generated were episodic and did not differ on a number of phenomenological qualities (detail, emotionality, personal significance, field/observer perspective). Conjunction analyses indicated the left hippocampus was commonly engaged by past and future event construction, along with posterior visuospatial regions, but considerable neural differentiation was also observed during the construction phase. Future events recruited regions involved in prospective thinking and generation processes, specifically right frontopolar cortex and left ventrolateral prefrontal cortex, respectively. Furthermore, future event construction uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. In contrast to the construction phase, elaboration was characterized by remarkable overlap in regions comprising the autobiographical memory retrieval network, attributable to the common processes engaged during elaboration, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findinas that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Addis, DR (reprint author), Harvard Univ, Dept Psychol, William James Hall,Rm 854,33 Kirkland St, Cambridge, MA 02138 USA. EM daddis@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061; Addis, Donna Rose/0000-0002-6231-1491 FU NIA NIH HHS [AG08441, R01 AG008441, R37 AG008441]; NIMH NIH HHS [MH060941, R01 MH060941] NR 80 TC 700 Z9 714 U1 20 U2 134 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 7 BP 1363 EP 1377 DI 10.1016/j.neuropsychologia.2006.10.016 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 153ZR UT WOS:000245477100001 PM 17126370 ER PT J AU Hwang, DY Gallo, DA Ally, BA Black, PM Schacter, DL Budson, AE AF Hwang, David Y. Gallo, David A. Ally, Brandon A. Black, Peter M. Schacter, Daniel L. Budson, Andrew E. TI Diagnostic retrieval monitoring in patients with frontal lobe lesions: Further exploration of the distinctiveness heuristic SO NEUROPSYCHOLOGIA LA English DT Article DE memory; metacognition; metamemory; frontal lobes; retrieval monitoring; false memory ID REDUCING FALSE MEMORIES; CARD SORTING TEST; COGNITIVE NEUROSCIENCE; EXECUTIVE FUNCTIONS; EPISODIC MEMORY; RECOGNITION; RECOLLECTION; CORTEX; METACOGNITION; DISORDERS AB The distinctiveness heuristic is a diagnostic monitoring strategy whereby a subject expects a vivid recollection if a test item has been seen during the study session; the absence of a vivid recollection suggests the test item is novel. Consistent with the hypothesis that memory monitoring is dependent upon the frontal lobes, previous work using a repetition-tag paradigm found that patients with frontal lobe lesions were unable to use the distinctiveness heuristic. Evidence from recent neuroimaging studies, however, has suggested that use of the distinctiveness heuristic decreases the need for frontal processing. The present study used the criterial recollection task to revisit the question of whether patients with frontal lobe lesions are able to use a distinctiveness heuristic. Subjects studied black words paired with the same word in red font, a corresponding picture of the word, or both. They then took three memory tests designed to elicit false recognition of presented items. Both frontal lesion patients and matched control subjects showed intact ability to use the distinctiveness heuristic to reduce false recognition when tested on whether items were previously presented as pictures compared to red words. This use of the distinctiveness heuristic is evidence that patients with frontal lesions can use certain diagnostic monitoring strategies during recognition memory tasks when given guidance in coordinating their decision-making processes. This result suggests that the frontal lobes are necessary for self-initiation of this strategy during recognition memory tasks. Published by Elsevier Ltd. C1 Edith Nourse Rogers Mem Vet Hosp, Geriatr Res Educ Clin Ctr, Bedford, MA 01730 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Budson, AE (reprint author), Edith Nourse Rogers Mem Vet Hosp, Geriatr Res Educ Clin Ctr, 200 Springs Rd,Bldg 62,Room B30, Bedford, MA 01730 USA. EM abudson@bu.edu OI Schacter, Daniel/0000-0002-2460-6061; Ally, Brandon/0000-0002-6034-7968 FU NIA NIH HHS [AG08441, P30 AG013846, P30 AG13846, R01 AG008441, R01 AG025815, R01 AG025815-04, R37 AG008441] NR 55 TC 6 Z9 6 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 11 BP 2543 EP 2552 DI 10.1016/j.neuropsychologia.2007.03.018 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 187RL UT WOS:000247865800014 PM 17485102 ER PT J AU Kan, IP Giovanello, KS Schnyer, DM Makris, N Verfaellie, M AF Kan, Irene P. Giovanello, Kelly S. Schnyer, David M. Makris, Nikos Verfaellie, Mieke TI Role of the medial temporal lobes in relational memory: Neuropsychological evidence from a cued recognition paradigm SO NEUROPSYCHOLOGIA LA English DT Article DE amnesia; relational memory; cued recognition; medial temporal lobes; hippocampus; recognition memory ID CONFIGURAL ASSOCIATION THEORY; HIPPOCAMPAL-FORMATION; PROCESS DISSOCIATION; ITEM RECOGNITION; AMNESIC PATIENTS; IMPLICIT MEMORY; INFORMATION; SINGLE; FAMILIARITY; RECALL AB In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally. Published by Elsevier Ltd. C1 Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Univ N Carolina, Biomed Res Imaging Ctr, Chapel Hill, NC USA. Univ Texas, Dept Psychol, Austin, TX 78712 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Kan, IP (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 151-A,150 S Huntington Ave, Boston, MA 02130 USA. EM ikan@bu.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [R01 MH057681-10, R01 MH057681, MH57681] NR 49 TC 32 Z9 32 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 11 BP 2589 EP 2597 DI 10.1016/j.neuropsychologia.2007.03.006 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 187RL UT WOS:000247865800019 PM 17433382 ER PT J AU Wehner, DT Ahlfors, SP Mody, M AF Wehner, Daniel T. Ahlfors, Seppo P. Mody, Maria TI Effects of phonological contrast on auditory word discrimination in children with and without reading disability: A magnetoencephalography (MEG) study SO NEUROPSYCHOLOGIA LA English DT Article DE speech perception; developmental dyslexia; MEG; children; phonology ID EVENT-RELATED POTENTIALS; SPEECH-PERCEPTION; DEVELOPMENTAL DYSLEXIA; MISMATCH NEGATIVITY; DISABLED-CHILDREN; POOR READERS; DEFICITS; BRAIN; FMRI; ACTIVATION AB Poor readers perform worse than their normal reading peers on a variety of speech perception tasks, which may be linked to their phonological processing abilities. The purpose of the study was to compare the brain activation patterns of normal and impaired readers on speech perception to better understand the phonological basis in reading disability. Whole-head magnetoencephalography (MEG) was recorded as good and poor readers, 7-13 years of age, performed an auditory word discrimination task. We used an auditory oddball paradigm in which the 'deviant' stimuli (/bat/, /kat/, /rat/) differed in the degree of phonological contrast (one versus three features) from a repeated standard word (/pat/). Both good and poor readers responded more slowly to deviants that were phonologically similar compared to deviants that were phonologically dissimilar to the standard word. Source analysis of the MEG data using minimum, norm estimation (MNE) showed that compared to good readers, poor readers had reduced left-hemisphere activation to the most demanding phonological condition reflecting their difficulties with phonological processing. Furthermore, unlike good readers, poor readers did not show differences in activation as a function of the degree of phonological contrast. These results are consistent with a phonological account of reading disability. (C) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Charlestown, MA 02129 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mody, M (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM maria@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41 RR014075-09, P41RR14075, P41 RR014075]; NIBIB NIH HHS [5T32EB001680, T32 EB001680, T32 EB001680-05]; NICHD NIH HHS [HD056355]; NIDCD NIH HHS [DC 00038, DC00159, K23 DC000159, K23 DC000159-06, T32 DC000038, T32 DC000038-16] NR 80 TC 14 Z9 15 U1 5 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 14 BP 3251 EP 3262 DI 10.1016/j.neuropsychologia.2007.06.018 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 230DG UT WOS:000250855400012 PM 17675109 ER PT J AU Oscar-Berman, M Marinkovic, K AF Oscar-Berman, Marlene Marinkovic, Ksenija BE Kalechstein, A van Gorp, WG TI Alcohol SO NEUROPSYCHOLOGY AND SUBSTANCE USE: STATE-OF-THE-ART AND FUTURE DIRECTIONS SE Studies on Neuropsychology Development and Cognition LA English DT Article; Book Chapter ID EVENT-RELATED POTENTIALS; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; ABSTINENT ALCOHOLICS; CORPUS-CALLOSUM; WHITE-MATTER; FRONTAL-LOBE; BRAIN-DAMAGE; VENTRAL HIPPOCAMPUS C1 [Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. [Marinkovic, Ksenija] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. NR 166 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-83771-9 J9 STUD NEUROPSYCH DEV PY 2007 BP 43 EP 73 PG 31 WC Psychology, Biological; Substance Abuse; Neurosciences; Psychology SC Psychology; Substance Abuse; Neurosciences & Neurology GA BUX53 UT WOS:000290615100003 ER PT B AU Harwood, DG Kalechstein, A Sultzer, DL AF Harwood, Dylan G. Kalechstein, Ari Sultzer, David L. BE Kalechstein, A van Gorp, WG TI Substance use and neuropsychological disorders in aging SO NEUROPSYCHOLOGY AND SUBSTANCE USE: STATE-OF-THE-ART AND FUTURE DIRECTIONS SE Studies on Neuropsychology Development and Cognition LA English DT Article; Book Chapter ID SUBCLINICAL HEPATIC-ENCEPHALOPATHY; ALCOHOL-RELATED DEMENTIA; TERM BENZODIAZEPINE USE; CEREBRAL-BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; WERNICKE-KORSAKOFF-SYNDROME; ISCHEMIC VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; RISK-FACTORS; COGNITIVE PERFORMANCE C1 [Harwood, Dylan G.; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Harwood, DG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. NR 149 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-83771-9; 978-1-84169-457-3 J9 STUD NEUROPSYCH DEV PY 2007 BP 323 EP 348 PG 26 WC Psychology, Biological; Substance Abuse; Neurosciences; Psychology SC Psychology; Substance Abuse; Neurosciences & Neurology GA BUX53 UT WOS:000290615100011 ER PT J AU Watanabe, T Sasaki, Y Tsushima, Y AF Watanabe, Takeo Sasaki, Yuka Tsushima, Yoshiaki TI Effects of "invisible" stimuli on plasticity SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. ERATO Shimojo Implicit Brain Funct Project, Pasadena, CA USA. Boston Univ, Program Neurosci, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S25 EP S25 DI 10.1016/j.neures.2007.06.146 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272800143 ER PT J AU Abbed, KM Coumans, JVCE AF Abbed, Khalid M. Coumans, Jean-Valery C. E. TI Cervical radiculopathy: Pathophysiology, presentation, and clinical evaluation SO NEUROSURGERY LA English DT Article DE cervical spine; cervical spondylosis; nerve root; radiculopathy ID INTERVERTEBRAL-DISK; HERNIATED DISK; DOUBLE-CRUSH; DIAGNOSIS; SPINE; MYELOGRAPHY; SPONDYLOSIS; TOMOGRAPHY; DISEASE; LESIONS AB CERVICAL RADICULOPATHY IS a common condition that usually results from compression and inflammation of cervical nerve root or roots in the region of the neutral foramen. It is frequently caused by cervical disc herniation and cervical spondylosis. The diagnosis can be established by history and physical examination, but care should be taken, as diagnoses can mimic or coexist with cervical radiculopathy, such as entrapment neuropathies. The pathphysiology, presentation, and clinical evaluation of cervical radiculopathy are discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Coumans, JVCE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,WACC 021, Boston, MA 02114 USA. EM jcoumans@partners.org NR 36 TC 34 Z9 34 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2007 VL 60 IS 1 SU S BP 28 EP 34 DI 10.1227/01.NEU.0000249223.51871.C2 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 125DI UT WOS:000243421600011 ER PT J AU Cristofaro, V Peters, CA Yalla, SV Sullivan, MP AF Cristofaro, V. Peters, C. A. Yalla, S. V. Sullivan, M. P. TI Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE bladder; caveolae; smooth muscle ID INTRINSIC NEUROMUSCULAR DEFECTS; GERIATRIC VOIDING DYSFUNCTION; LIPID RAFTS; PLASMALEMMAL CAVEOLAE; NEUROGENIC BLADDER; STRUCTURAL BASIS; URINARY-BLADDER; KNOCKOUT MICE; CELL BIOLOGY; RAT BLADDER AB Aims: Caveolae are cholesterol-rich plasmalemmal microdomains that serve as sites for sequestration of signaling proteins and thus may facilitate, organize, and integrate responses to extraccllular stimuli. While previous studies in the bladder have demonstrated alterations in caveolae with particular physiologic or pathologic conditions, little attention has been focused oil the functional significance of these organelles. Therefore, the purpose of this study Was to investigate the role of caveolae in the modulation of receptor-mediated signal transduction and determine the presence and localization of caveolin proteins in bladder tissue. Methods: Contractile responses to physiologic agonists were measured in rat bladder tissue before and after disruption of caveolae achieved by depleting membrane cholesterol with methyl-beta-cyclodextrin. Stimulation with agonists was repeated after caveolae were restored as a result of cholesterol replenishment. RT-PCR, immmunohistochemistry, and Western blotting were used to determine the expression and localization of caveolin mRNA and proteins. Results: Following caveolae disruption, contractile responses to angiotensin II and serotonin were attenuated, whereas responses to bradykinin and phenylephrine were augmented. Cholesterol replenishment restored responses towards baseline. Carbachol and KCl induced contractions were not affected by caveolae disruption. Ultrastructure analysis confirmed loss of caveolae following cholesterol depletion with cyclodextrin and cavcolae restoration following cholesterol replacement. Gene and protein expression of caveolin-1, -2, and -3 was detected in bladder tissue. Immunoreactivity for all three caveolins was observed in smooth muscle cells throughout the bladder. Conclusions: The functional effects of cholesterol depletion on specific agonist-induced contractile events and the expression of all three caveolins in bladder smooth Muscle Support a central role for cavcolae in regulation of selective G-protein-coupled receptor signaling pathways in bladder smooth muscle. Thus, caveolae serve to differentially regulate bladder smooth muscle by a stimulus-dependent potentiation or inhibition of bladder contraction. Neurourol. Urodynam. 26:71-80, 2007. (c) 2006 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Urol, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Virginia, Sch Med, Div Urol, Charlottesville, VA 22908 USA. RP Sullivan, MP (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Urol, 1400 VFW Pkwy, Boston, MA 02132 USA. EM msullivan@rics.bwh.harvard.edu OI Peters, Craig/0000-0001-7598-0865 FU NIDDK NIH HHS [R01DK55086-01] NR 45 TC 28 Z9 28 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 1 BP 71 EP 80 DI 10.1002/nau.20361 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 126BP UT WOS:000243487500015 PM 17123298 ER PT J AU Mijailovich, SM Sullivan, MP Yalla, SV Venegas, JG AF Mijailovich, Srboljub M. Sullivan, Maryrose P. Yalla, Subbarao V. Venegas, Jose G. TI Effect of urethral compliance on the steady state p-Q relationships assessed with a mechanical analog of the male lower urinary tract SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE collapsible tubes; compliance; critical flow; modeling and experiments; prostate; urodynamics ID RESTING FEMALE URETHRA; PRESSURE-FLOW RELATION; COLLAPSIBLE TUBES; ELASTIC CONSTRICTION; MALE MICTURITION; OUTLET FUNCTION; RESISTANCE; QUANTIFICATION; HYDRODYNAMICS; OBSTRUCTION AB Aims: Using a lumped parameter theoretical model of bladder outlet function, we previously explored the relationship between the tube law of the urethra and the pressure-flow characteristics during micturition [Mijailovich et al., 2004]. To validate this theoretical model, we constructed a mechanical analog of the male lower urinary tract that incorporated elements simulating all relevant parameters of the theoretical model. In addition, we determined the effect of alterations in compliance of the flow-controlling zone on these relationships. Methods: In the mechanical analog, the bladder neck and urethra were represented by a thin-walled conduit made of latex rubber and the prostate with a fluid filled cuff of variable compliance encircling the conduit. We measured in the same system steady-state pressure-flow (p-Q) and pressure-area (p-A) relationships of the flow-controlling zone. The effects of bladder outlet obstruction and prostatic compliance on these relationships were simulated by varying cuff pressure and capacitative coupling of the cuff, respectively. Results: We demonstrated two previously described flow regimes-critical for low Q, and subcritical for higher Q. In the critical flow regime, the cross-sectional area of the collapsible conduit downstream of the cuff became narrow up to a site where the area suddenly expanded (elastic jump). Pressure losses across the cuff region decreased with increasing Q as the elastic jump approached the cuff, and the jump vanished when Q became suberitical. By altering prostatic cuff compliance and cuff pressure, we showed that an increase in opening pressures was associated with a steeper p-Q relationship. Conclusions: Using this mechanical analog, the measurements of p-A and p-Q relationships under various experimental conduit conditions validated our previous theoretical model of the male lower urinary tract. Both the experimental measurements and our previous theoretical model predictions indicate that an increase in opening pressure is associated with an increase in the slope of the p-Q relationship which becomes steeper with decreased cuff compliance. These data are in accordance with urodynamic findings in patients with benign prostatic hypertrophy (BPH) and suggest that a reduction in prostatic compliance exacerbates the severity of obstruction. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, Boston, MA 02115 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mijailovich, SM (reprint author), Harvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, Bldg 1,Room 1306E,665 Huntington Ave, Boston, MA 02115 USA. EM smijailo@hsph.harvard.edu OI Mijailovich, Srboljub/0000-0003-1498-308X FU NHLBI NIH HHS [HL 68011, HL 33009]; NIAMS NIH HHS [AR 048776-03] NR 27 TC 4 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 2 BP 234 EP 246 DI 10.1002/nau.20302 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 155DF UT WOS:000245557300017 PM 17039462 ER PT J AU Burgio, K AF Burgio, K. TI Combining behavior and drug therapy to improve drug withdrawal in the treatment of urge incontinence: A randomized trial SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 37th Annual Meeting of the International-Continence-Society CY AUG 20-24, 2007 CL Rotterdam, NETHERLANDS SP Int Continence Soc ID URINARY-INCONTINENCE C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NIDDKD, NIH, Bethesda, MD USA. NR 3 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 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 5 MA 21 BP 629 EP 630 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 197DM UT WOS:000248534000022 ER PT J AU Nygaard, I Kreder, K Mueller, E Brubaker, L Goode, P Visco, A Weber, AM Cundiff, G Wei, J AF Nygaard, Ingrid Kreder, Karl Mueller, Elizabeth Brubaker, Linda Goode, Patricia Visco, Anthony Weber, Anne M. Cundiff, Geoff Wei, John CA Pelvic Floor Disorders Network TI Does urethral competence affect urodynamic voiding parameters in women with prolapse? SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE obstruction; pelvic organ prolapse; urodynamics; voiding ID PELVIC ORGAN PROLAPSE; VAGINAL VAULT PROLAPSE; UTEROVAGINAL PROLAPSE; URINARY-INCONTINENCE; STRESS-INCONTINENCE; CONTINENT WOMEN; COLPOSUSPENSION; PREVALENCE; REPAIR AB Aims: To (1) compare voiding parameters and (2) correlate symptoms and urodynamic findings in women with pelvic organ prolapse (POP) and varying degrees of urethral competence. Methods: We compared three groups of women with stages II-IV POP. Groups 1 and 2 were symptomatically stress continent women participating in the Colpopexy and Urinary Reduction Efforts (CARE) trial; during prolapse reduction before sacrocolpopexy, Group I (n = 67) did not have and Group 2 (n 84) had urodynamic stress incontinence (USI) during prolapse reduction. Group 3 participants (n = 74), recruited specifically for this study, had stress urinary incontinence (SUI) symptoms and planned sacrocolpopexy. Participants completed standardized uroflowmetry, pressure voiding studies, and validated symptom questionnaires. Results: Subjects' median age was 61 years, median parity 3 and 87% had stage III or IV POP. Four-teen percent of women in Group 3 demonstrated USI without, and 70% with, prolapse reduction. Women in Groups 2 and 3 had more detrusor overactivity (DO) than Group 1 (17 and 24% vs. 6%, P = 0.02) and detrusor overactivity incontinence (DOI) (15 and 8% vs. 0%, P = 0.004). Based on the Blaivis-Groutz nomogram, 60% of all women were obstructed. Post-void residual volume (PVR), peak flow rate, detrusor pressure at peak flow, voiding mechanisms, voiding patterns, obstruction and urinary retention did not differ among groups. Women in Group 3 had higher irritative and obstructive symptom scores than Group 1 or 2; neither score differed by presence of DO nor obstruction, respectively. Conclusion: Women with POP have significant rates of urodynamic obstruction and retention, independent of their continence status. Symptoms of obstruction and retention correlate poorly with urodynamic findings. C1 Univ Utah, Dept Obstet & Gynecol, Coll Med, Salt Lake City, UT 84132 USA. Univ Iowa, Dept Urol, Carver Coll Med, Iowa City, IA USA. Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Alabama, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. NICHHD, Bethesda, MD USA. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V5Z 1M9, Canada. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. RP Nygaard, I (reprint author), Univ Utah, Dept Obstet & Gynecol, Coll Med, 30 North 1900 East,Room 2B 242, Salt Lake City, UT 84132 USA. EM Ingrid.nygaard@hsc.utah.edu OI Mueller, Elizabeth R./0000-0003-3069-4069 FU NICHD NIH HHS [U10 HD41269, U10 HD41248, U10 HD41268, U01 HD41249, U10 HD041261, U10 HD41267, U10 HD41263, U10 HD41250, U10 HD41261] NR 18 TC 5 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 7 BP 1030 EP 1035 DI 10.1002/nau.20436 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 227BV UT WOS:000250633100015 PM 17638306 ER PT J AU Lee, U Daneshgari, F Liu, G Li, M Lin, DL Zaszczurynski, P Pan, HQ Li, T Damaser, MS AF Lee, Una Daneshgari, Firouz Liu, Guiming Li, Mei Lin, Dan Li Zaszczurynski, Paul Pan, Hui Q. Li, Tiansen Damaser, Margot S. TI Urinary incontinence, bladder dysfunction and pelvic organ prolapse in lysyl oxidase like-1 (LOXL1) mutant mice: A complete animal model for female pelvic floor disorders? SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Urodynamics-and-Female-Urology (SUFU) CY FEB 21-24, 2007 CL San Diego, CA SP Soc Urodynam & Female Urol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 7 SU S BP 1088 EP 1088 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 228SW UT WOS:000250753900056 ER PT J AU Depue, JD McCabe, B Kazura, A Becker, B Papandonatos, GD Chun, T Emmons, K AF DePue, Judith D. McCabe, Bhrett Kazura, Alessandra Becker, Bruce Papandonatos, George D. Chun, Thomas Emmons, Karen TI Assessment of parents' smoking behaviors at a pediatric emergency department SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; INTEGRATIVE MODEL; HEALTH-SERVICES; SELF-CHANGE; CHILDREN; INTERVENTION; EXPOSURE; ASTHMA; MAINTENANCE; ATTITUDES AB The pediatric emergency department is an important source of treatment for children with complaints related to environmental tobacco smoke (ETS) and may provide a teachable moment to address parent smoking. Parents who smoke were recruited from a pediatric emergency department waiting room and completed an interview assessment used to develop intervention messages. Of the 715 parents in the final sample, 77% were women, 60% White, and 60% low income (< USS30,000/year); 25% wanted to quit smoking in the next month, 50% wanted to quit within 6 months, and 48.5% "almost always" smoked outside. Parents reporting more frequent ETS protection behaviors had stronger beliefs about harmful effects of ETS and about ETS protection, and more confidence to resist smoking when tempted. Parents more ready to quit smoking were more likely to be men, and were more likely to report more daily hassles, stronger cons of smoking, higher personal vulnerability to smoking effects, and stronger beliefs about ETS protection. Findings showed that most parents in this setting are concerned about limiting their children's ETS exposure. However, this concern alone appeared insufficient to motivate parents to quit smoking. Interventions should encourage parents to limit ETS exposure, while encouraging quitting for optimal protection from effects of cigarette smoke for their children and themselves. C1 Brown Univ, Ctr Behav & Prevent Med, Miriam Hosp, Sch Med, Providence, RI 02903 USA. Brown Univ, Dept Emergency Med, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Brown Univ, Sch Med, Bradley Hasbro Res Ctr, Providence, RI 02912 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Depue, JD (reprint author), Brown Univ, Ctr Behav & Prevent Med, Miriam Hosp, Sch Med, Coro Bldg,Suite 500,1 Hoppin St, Providence, RI 02903 USA. EM jdepue@lifespan.org RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X FU NCI NIH HHS [CA74538] NR 41 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2007 VL 9 IS 1 BP 33 EP 41 DI 10.1080/14622200601078269 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 135GO UT WOS:000244142300004 PM 17365734 ER PT J AU David, SP Strong, DR Munafo, MR Brown, RA Lloyd-Richardson, EE Wileyto, PE Evins, EA Shields, PG Lerman, C Niaura, R AF David, Sean P. Strong, David R. Munafo, Marcus R. Brown, Richard A. Lloyd-Richardson, Elizabeth E. Wileyto, Paul E. Evins, Eden A. Shields, Peter G. Lerman, Caryn Niaura, Raymond TI Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: Analysis of pooled data from two clinical trials SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SUSTAINED-RELEASE BUPROPION; NICOTINE REPLACEMENT THERAPY; TOBACCO DEPENDENCE; GENETIC-VARIATION; RECEPTOR DRD2; SUBUNIT GENE; BEHAVIOR; ASSOCIATION; ADDICTION; CYP2A6 AB We analyzed pooled data from two comparable randomized placebo- controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available. A total of 722 smokers across the two trials were randomized to 10 weeks of sustained- release bupropion hydrochloride or placebo. General estimating equation analysis demonstrated a significant gene x drug interaction ( B=50.87, SE=0.34, p=.009). Smokers with the A2/A2 genotype using bupropion were more than three times as likely, relative to placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; OR=3.25, 95% CI 2.00-5.28) and at 6 months of follow-up (26.7% vs. 12.2%; OR=2.81, 95% CI 1.66-4.77), which was attenuated by 12 months (16.3% vs. 10.7%; OR=1.70, 95% CI 0.95-3.05). We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes. These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype. C1 [David, Sean P.] Brown Univ, Mem Hosp Rhode Isl, Warren Alpert Med Sch,Ctr Primary Care & Prevent, Primary Care Genet & Translat Res Ctr, Pawtucket, RI 02860 USA. [Niaura, Raymond] Brown Univ, Butler Hosp, Warren Alpert Med Sch, Translat Res Ctr, Pawtucket, RI 02860 USA. [Munafo, Marcus R.] Univ Bristol, Dept Expt Psychol, Bristol BS8 1TH, Avon, England. [Lloyd-Richardson, Elizabeth E.] Brown Univ, Warren Alpert Med Sch, Ctr Behav & Prevent Med, Pawtucket, RI 02860 USA. [Wileyto, Paul E.; Lerman, Caryn] Univ Penn, Tobacco Use Res Ctr, Philadelphia, PA 19104 USA. [Evins, Eden A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Shields, Peter G.] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP David, SP (reprint author), Brown Univ, Ctr Primary Care & Prevent, 111 Brewster St, Pawtucket, RI 02860 USA. EM sean_david@brown.edu RI Shields, Peter/I-1644-2012; OI David, Sean/0000-0002-4922-2603; Munafo, Marcus/0000-0002-4049-993X FU NCI NIH HHS [R01 CA063562, CA63562, CA84718, P50 CA084718, P50 CA084719]; NHLBI NIH HHS [HL32318]; NIDA NIH HHS [DA08511, DA14276-04, K08 DA014276, K08 DA014276-01A2, K08 DA014276-02, K08 DA014276-03, K08 DA014276-04, K08 DA014276-05, R01 DA008511, R01 DA008511-08] NR 44 TC 44 Z9 45 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 12 BP 1251 EP 1257 DI 10.1080/14622200701705027 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 245VE UT WOS:000251966100002 PM 18058343 ER PT J AU Fukumura, D Edwin, L AF Fukumura, D. Edwin, L. TI Nitric oxide mediates tumor vessel maturation SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [Fukumura, D.; Edwin, L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. [Fukumura, D.; Edwin, L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S11 EP S11 DI 10.1016/j.niox.2007.09.014 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000010 ER PT J AU Hanser, SB AF Hanser, Suzanne B. TI Receptive methods in music therapy: Techniques and clinical applications for music therapy clinicians, educators and students SO NORDIC JOURNAL OF MUSIC THERAPY LA English DT Book Review C1 [Hanser, Suzanne B.] Berklee Coll Mus, Mus Therapy Dept, Boston, MA 02215 USA. [Hanser, Suzanne B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hanser, SB (reprint author), Berklee Coll Mus, Mus Therapy Dept, Boston, MA 02215 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU GRIEG ACADEMY PI BERGEN PA UNIV BERGEN, DEPT MUSIC, LARS HILLES GATE 3, BERGEN, N-5015, NORWAY SN 0803-9828 J9 NORD J MUSIC THER JI Nord. J. Music Ther. PY 2007 VL 16 IS 2 BP 177 EP 177 PG 1 WC Rehabilitation SC Rehabilitation GA 319WH UT WOS:000257194900011 ER PT J AU Moscato, SR Miller, J Logsdon, K Weinberg, S Chorpenning, L AF Moscato, Susan Randles Miller, Judith Logsdon, Karen Weinberg, Stephen Chorpenning, Lori TI Dedicated education unit: An innovative clinical partner education model SO NURSING OUTLOOK LA English DT Article AB This article describes the implementation and evaluation of the Dedicated Education Unit (DEU) as an innovative model of clinical nursing education. A partnership of nurse executives, staff nurses and faculty transformed patient care units into environments of support for nursing students and staff nurses while continuing the critical work of providing quality care to acutely ill adults. Various methods were used to obtain formative data during the implementation of this model in which staff nurses assumed the role of nursing instructors. Results showed high student and nurse satisfaction and a marked increase in clinical capacity that allowed for increased enrollment. This article reports on a 3-year project to operationalize the DEU concept with 6 nursing units in 3 hospitals. The development of staff nurses as clinical instructors, best practices to teach and evaluate critical thinking in students, and the mix of student learners continue as focus areas. C1 Univ Portland, Sch Nursing, Portland, OR 97203 USA. Duke Univ, Durham, NC 27706 USA. Portland VA Med Ctr, Portland, OR USA. RP Moscato, SR (reprint author), Univ Portland, Sch Nursing, 5000 N Willamette Blvd, Portland, OR 97203 USA. EM moscato@up.edu NR 11 TC 66 Z9 67 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2007 VL 55 IS 1 BP 31 EP 37 DI 10.1016/j.outlook.2006.11.001 PG 7 WC Nursing SC Nursing GA 139UX UT WOS:000244459200007 PM 17289465 ER PT J AU Sato, MK Senesac, PM AF Sato, Marsha K. Senesac, Pamela M. TI Imagining nursing practice: The Roy adaptation model in 2050 SO NURSING SCIENCE QUARTERLY LA English DT Editorial Material C1 Mt St Marys Coll, MSN Program, Los Angeles, CA USA. Massachusetts Gen Hosp, Inst Hlth Prof, Grad Programs Nursing, Boston, MA 02114 USA. RP Sato, MK (reprint author), Mt St Marys Coll, MSN Program, Los Angeles, CA USA. NR 12 TC 1 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD JAN PY 2007 VL 20 IS 1 BP 47 EP 50 DI 10.1177/0894318406296807 PG 4 WC Nursing SC Nursing GA 120RN UT WOS:000243103700014 PM 17354353 ER PT J AU Rich-Edwards, JW Ganmaa, D Pollak, MN Nakamoto, EK Kleinman, K Tserendolgor, U Willett, WC Frazier, AL AF Rich-Edwards, Janet W. Ganmaa, Davaasambuu Pollak, Michael N. Nakamoto, Erika K. Kleinman, Ken Tserendolgor, Uush Willett, Walter C. Frazier, A. Lindsay TI Milk consumption and the prepubertal somatotropic axis SO NUTRITION JOURNAL LA English DT Article AB Background: Nutrients, hormones and growth factors in dairy foods may stimulate growth hormone (GH), insulin-like growth factor 1 (IGF-1), and raise the ratio of IGF-1 to its binding protein, IGFBP-3. We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children. Methods: In Ulaanbaatar, we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10-11 year old schoolchildren. In a randomized cross-over study in Boston, we compared plasma hormone levels of 28 6-8 year old girls after one week of drinking 710 ml lowfat (2%) milk with their hormone levels after one week of consuming a macronutrient substitute for milk. Results: After a month of drinking whole milk, Mongolian children had higher mean plasma levels of IGF-1 (p < 0.0001), IGF-1/IGFBP-3 (p < 0.0001), and 75th percentile of GH levels (p = 0.005). After a week of drinking lowfat milk, Boston girls had small and non-significant increases in IGF-1, IGF-1/IGFBP-3 and GH. Conclusion: Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys. The finding that milk intake may raise GH levels is novel, and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production. C1 [Willett, Walter C.; Frazier, A. Lindsay] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. [Frazier, A. Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rich-Edwards, Janet W.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Rich-Edwards, Janet W.; Nakamoto, Erika K.; Kleinman, Ken] Harvard Pilgrim Hlth Care, Boston, MA USA. [Rich-Edwards, Janet W.; Nakamoto, Erika K.; Kleinman, Ken] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Rich-Edwards, Janet W.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ganmaa, Davaasambuu; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Dept Oncol, Canc Prevent Div, Montreal, PQ, Canada. [Tserendolgor, Uush] Inst Publ Hlth, Ulaanbaatar, Mongol Peo Rep. RP Frazier, AL (reprint author), Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. EM jrichedwards@partners.org; gdavaasa@hsph.harvard.edu; michael.pollak@mcgill.ca; Erika_Nakamoto@harvardpilgrim.org; ken.kleinman@gmail.com; utseren@mongol.net; wwillett@hsph.harvard.edu; Lindsay_frazier@dfci.harvard.org RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU Breast Cancer Research Foundation; National Center for Research Resources, National Institutes of Health [M01-RR02172]; Canadian Breast Cancer Research Alliance FX These projects were funded by the Breast Cancer Research Foundation; grant M01-RR02172 from the National Center for Research Resources, National Institutes of Health to the Children's Hospital Boston General Clinical Research Center; a translational acceleration grant to Dr. Pollak from the Canadian Breast Cancer Research Alliance; and charitable contributions by the Boston office of Deloitte & Touche LLP and the Ames Family Foundation. NR 33 TC 47 Z9 47 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2891 J9 NUTR J JI Nutr. J. PY 2007 VL 6 AR 28 DI 10.1186/1475-2891-6-28 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V21OG UT WOS:000208216300028 PM 17900364 ER PT J AU Bennett, GG Wolin, KY James, SA AF Bennett, Gary G. Wolin, Kathleen Y. James, Sherman A. TI Lifecourse socioeconomic position and weight change among blacks: The Pitt County Study SO OBESITY LA English DT Article DE blacks/African Americans; race/ethnicity; socioeconomic factors; BMI; weight gain ID BODY-MASS INDEX; RISK-FACTORS; UNITED-STATES; OBESITY; WOMEN; ADULTS; HEALTH; OVERWEIGHT; ATTITUDES; EDUCATION AB Objective: The elevated prevalence of obesity among U.S. blacks has been attributed to low socioeconomic position (SEP), despite inconsistent empirical findings. It is unclear whether low SEP at various lifecourse stages differentially influences adulthood BMI and BMI change. Research Methods and Procedures: Among 1167 black adults in the Pitt County Study, we examined independent cross-sectional and longitudinal associations between SEP, measured in childhood and adulthood, and BMI and 13-year BMI change. Low vs. high childhood SEP was measured by parental occupation and childhood household deprivation; low vs. high adulthood SEP was assessed by employment status, education, and occupation. Using childhood and adulthood SEP, four lifecourse SEP categories were created: low-low, low-high, high-low, high-high. Results: We found no consistent associations between SEP and BMI or BMI change among men. Among women, we observed the expected inverse association between SEP and BMI at baseline. In multivariable-adjusted analyses, socio-economically advantaged women demonstrated larger 13-year increases in BMI: skilled vs. unskilled parental occupation (6.1 vs. 4.8 kg/m(2), P = 0.04); college-educated vs. < high school (6.2 vs. 4.5 kg/m(2), p = 0.04); white-collar vs. blue-collar job (5.8 vs. 4.8 kg/m(2), P = 0.05); and high-high vs. low-low lifecourse SEP (6.5 vs. 4.6 kg/m(2), p = 0.02). Discussion:For women in this black cohort, lower SEP predicted earlier onset of obesity; however, low SEP was less predictive of BMI increases over time. Our findings demonstrate complex patterns of association between SEP and BMI change among black women. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Ctr Community Based Res,Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Duke Univ, Terry Sanford Inst Publ Policy, Durham, NC USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Ctr Community Based Res,Dana Farber Canc Inst, 44 Binney St,SM256, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [3 R01 CA098864-02S1, R25 CA100600-01A1]; NHLBI NIH HHS [HL 65645] NR 25 TC 22 Z9 23 U1 3 U2 4 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2007 VL 15 IS 1 BP 172 EP 181 DI 10.1038/oby.2007.522 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OA UT WOS:000249605500022 PM 17228045 ER PT J AU Borrero, S Schwarz, EB Reeves, MF Bost, JE Creinin, MD Ibrahim, SA AF Borrero, Sonya Schwarz, Eleanor B. Reeves, Matthew F. Bost, James E. Creinin, Mitchell D. Ibrahim, Said A. TI Race, insurance status, and tubal sterilization SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID UNITED-STATES; CONTRACEPTIVE STERILIZATION; FEMALE STERILIZATION; WOMEN; HEALTH AB OBJECTIVE: To examine the independent effects of race or ethnicity and insurance status on use of tubal sterilization rates. METHODS: This study used cross-sectional data collected by the 2002 National Survey of Family Growth. The survey is designed to represent women and men aged 15-44 years in the household population of the United States. Our main outcome measure was tubal sterilization at any time before interview. A multivariable logistic regression model was used to estimate the effects of race or ethnicity and insurance status on rates of tubal sterilization after adjusting for important confounders. RESULTS: The sample consisted of 7,643 women: 66% were white, 15% were Hispanic, and 14% were African American; 68% had private insurance and 32% had public or no insurance. After adjusting for age, insurance status, parity, income, education, marital status, and religion, African-American women were more likely than white women to undergo tubal sterilization (adjusted odds ratio 1.43, 95% confidence interval 1.08-1.88). After adjusting for age, race or ethnicity, parity, income, education, marital status, and religion, women with public or no insurance were more likely to undergo sterilization compared with women with private insurance (adjusted odds ratio 1.38, 95% confidence interval 1.09-1.74). CONCLUSION: African-American women and women with no or public insurance were more likely to have undergone! tubal sterilization compared with white women and women with private insurance, respectively. Additional research to identify factors that influence women's decision to undergo sterilization is warranted. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot 151C, Div Gen Internal Med, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Magee Womens Res Inst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Inst Clin Res Educ, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity & Promot, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot 151C, Div Gen Internal Med, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov OI Reeves, Matthew/0000-0001-7749-7447; Schwarz, Eleanor Bimla/0000-0002-9912-8236 NR 19 TC 31 Z9 31 U1 0 U2 2 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 JAN PY 2007 VL 109 IS 1 BP 94 EP 100 DI 10.1097/01.AOG.0000249604.78234.d3 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171YO UT WOS:000246771500014 PM 17197593 ER PT J AU Schaumberg, DA Gulati, A Mathers, WD Clinch, T Lemp, MA Nelson, JD Foulks, GN Dana, R AF Schaumberg, Debra A. Gulati, Abha Mathers, William D. Clinch, Thomas Lemp, Michael A. Nelson, J. Daniel Foulks, Gary N. Dana, Reza TI Development and validation of a short global dry eye symptom index SO OCULAR SURFACE LA English DT Article DE dry eye; dry eye symptoms; epidemiology questionnaires; Symptom Assessment iN Dry Eye (SANDE); visual analog scale ID RELIABILITY; PREVALENCE; REPEATABILITY; AGREEMENT; DISEASE AB We have developed and evaluated the repeatability of a short questionnaire based on a visual analog scale (VAS) to quantify the frequency and severity of symptoms of dry eye syndrome (DES). The "Symptom Assessment iN Dry Eye" (SANDE) questionnaire utilizes a 100 mm horizontal VAS technique to quantify patient symptoms of ocular dryness and/or irritation. Fifty-two subjects with DES were prospectively enrolled and followed-up at 2 and 4 months with repeated administrations of the SANDE questionnaire and clinical ocular surface evaluation. Subjects demonstrated a wide range of symptom scores indicative of the variability of the disease. Analyses comparing the repeatability of SANDE scores from baseline to the 2-month follow-up indicated a significant downward regression of scores toward the mean. In contrast, repeatability measures were consistently good for questionnaires administered within a few days of one another (ICC ranging from 0.53 to 0.76). Bland-Altman analysis demonstrated that 50% of repeated SANDE symptom scores were within 10 mm of each other, 80% were within 20 mm, and 95% were within less than 30 mm. These data describe good repeatability for the SANDE symptom score when repeated assessments are made within a few days. The results are encouraging and suggest that further refinement and testing of the SANDE questionnaire in larger populations may result in a reliable questionnaire to detect change in irritative symptoms over time. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Univ Ophthalmol Consultants Washington, Washington, DC USA. Reg Hosp, Hlth Partners Med Grp, St Paul, MN USA. Univ Louisville, Louisville, KY 40292 USA. RP Schaumberg, DA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E,, Boston, MA 02215 USA. EM dschaumberg@rics.bwh.harvard.edu NR 21 TC 41 Z9 41 U1 1 U2 3 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD JAN PY 2007 VL 5 IS 1 BP 50 EP 57 PG 8 WC Ophthalmology SC Ophthalmology GA 131ZZ UT WOS:000243912800006 PM 17252166 ER PT J AU Walker, SR Nelson, EA Frank, DA AF Walker, S. R. Nelson, E. A. Frank, D. A. TI STAT5 represses BCL6 expression by binding to a regulatory region frequently mutated in lymphomas SO ONCOGENE LA English DT Article DE STAT5; BCL6; transcription; chromatin ID B-CELL LYMPHOMA; AFFECTING BAND 3Q27; CHRONIC MYELOGENOUS LEUKEMIA; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCER; GENE-EXPRESSION; SELF-RENEWAL; DIFFERENTIATION; TRANSLOCATIONS; IDENTIFICATION AB Deregulated expression of BCL6 is a pathogenic event in many lymphomas. BCL6 blocks cellular differentiation by repressing transcription of its target genes, and this may promote tumorigenesis. Conversely, the transcription factor signal transducers and activators of transcription (STAT) 5 promotes differentiation in many systems. STAT5 upregulates a number of genes repressed by BCL6, raising the possibility that STAT5 and BCL6 have opposing roles in transcriptional regulation. Therefore, we sought to determine the effects of STAT5 activation on BCL6 expression and function. We found that activation of STAT5 downregulates BCL6 expression in B-lymphoma cells and other hematopoietic cell lines. We identified two potential STAT-binding regions in the first exon and first intron of BCL6 that fell within regions of high interspecies homology, suggesting conservation of regulatory function. STAT5 can bind inducibly and regulate transcription at one of these regions, identifying BCL6 as a STAT5 target gene. Additionally, STAT5-mediated downregulation of BCL6 results in loss of BCL6 repression of its target genes, confirming that STAT5 is a negative regulator of BCL6 function. The STAT5 responsive region of the BCL6 gene is mutated frequently in B-cell lymphomas, suggesting that loss of the repressive effects of STAT5 on BCL6 might contribute to the pathogenesis of these cancers. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,M522B, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 62 TC 66 Z9 66 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2007 VL 26 IS 2 BP 224 EP 233 DI 10.1038/sj.onc.1209775 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124VM UT WOS:000243398300006 PM 16819511 ER PT J AU Sequist, LV Joshi, VA Janne, PA Muzikansky, A Fidias, P Meyerson, M Haber, DA Kucherlapati, R Johnson, BE Lynch, TJ AF Sequist, Lecia V. Joshi, Victoria A. Janne, Pasi A. Muzikansky, Alona Fidias, Panos Meyerson, Matthew Haber, Daniel A. Kucherlapati, Raju Johnson, Bruce E. Lynch, Thomas J. TI Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing SO ONCOLOGIST LA English DT Article DE lung cancer; EGFR; mutation; genetic screening ID GROWTH-FACTOR-RECEPTOR; GENE-MUTATIONS; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; SMOKING HISTORY; KINASE DOMAIN; ERLOTINIB; CARCINOMA AB Somatic mutations in the epidermal growth factor receptor ( EGFR) gene are associated with clinical response and prolonged survival in patients with non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We began screening patients for somatic EGFR mutations by DNA sequencing as part of clinical care in 2004. We performed a retrospective cohort study of 278 patients with NSCLC referred for EGFR testing over a 10-month period. Tumor samples underwent direct DNA sequence analyses of EGFR exons 18 through 24. We determined the clinical characteristics and EGFR mutation status of the patients and analyzed their response to therapy and survival. EGFR somatic mutations were identified in 68 (24%) of patients. A minimal smoking history was the strongest clinical predictor of harboring a mutation. In multivariable analyses, each pack-year of smoking corresponded to a 5% decreased likelihood of having an EGFR mutation. Among 92 patients with unresectable disease undergoing subsequent systemic therapy, EGFR mutations were associated with an increased response rate to EGFR TKIs (p < .0001) but not chemotherapy. Overall survival was significantly prolonged in EGFR mutation-positive patients (p = .001), with a median survival of 3.1 years compared with 1.6 years in mutation-negative patients, after adjusting for age, gender, and stage at diagnosis. Integrating molecular profiling into clinical care is feasible in NSCLC patients and provides useful clinical information. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St,Yawkey Suite 7B, Boston, MA 02114 USA. EM lvsequist@partners.org RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [T32 CA 09001] NR 45 TC 95 Z9 109 U1 1 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 1 BP 90 EP 98 DI 10.1634/theoncologist.12-1-90 PG 9 WC Oncology SC Oncology GA 127NY UT WOS:000243594600009 PM 17285735 ER PT J AU Gee, DW Rattner, DW AF Gee, Denise W. Rattner, David W. TI Management of gastroesophageal tumors SO ONCOLOGIST LA English DT Article DE esophageal carcinoma; gastric carcinoma; esophagogastrectomy; neoadjuvant therapy; adjuvant therapy ID LYMPH-NODE DISSECTION; SQUAMOUS-CELL CARCINOMA; LONG-TERM SURVIVAL; PROSPECTIVE RANDOMIZED TRIAL; DISEASE-SPECIFIC SURVIVAL; LOCALLY ADVANCED CANCER; GASTRIC-CANCER; ESOPHAGEAL CANCER; ESOPHAGOGASTRIC JUNCTION; NEOADJUVANT CHEMOTHERAPY AB The incidence of adenocarcinomas of the gastroesophageal junction has increased in recent years. These tumors possess distinct pathophysiologic characteristics. Although the consensus is that an R-0 resection (complete microscopic and macroscopic resection) is the goal when operating for curative intent, much controversy remains regarding other aspects of patient management. There is lack of consensus regarding the type of surgery to perform, the role and extent of lymphadenectomy, and the role of neoadjuvant therapy. Utilizing an evidence-based approach, this review article provides an overview of the management of gastroesophageal junction carcinomas with particular emphasis on current areas of controversy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Gen & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 98 TC 19 Z9 30 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 2 BP 175 EP 185 DI 10.1634/theoncologist.12-2-175 PG 11 WC Oncology SC Oncology GA 139BO UT WOS:000244407200007 PM 17296813 ER PT J AU Chabner, BA Roberts, TG AF Chabner, Bruce A. Roberts, Thomas G. TI The FDA in 2006: Reasons for optimism SO ONCOLOGIST LA English DT Editorial Material ID EXPRESSION; INHIBITOR; SAFETY C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 3 BP 247 EP 249 DI 10.1634/theoncologist.12-3-247 PG 3 WC Oncology SC Oncology GA 154YE UT WOS:000245543600002 PM 17405888 ER PT J AU Sequist, LV AF Sequist, Lecia V. TI Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer SO ONCOLOGIST LA English DT Article DE epidermal growth factor receptor; non-small cell lung cancer; tyrosine kinase ID HUMAN COLON-CARCINOMA; ORALLY-ACTIVE INHIBITOR; ACQUIRED-RESISTANCE; PHASE-I; IRREVERSIBLE INHIBITOR; EGF RECEPTOR; ANTITUMOR-ACTIVITY; BREAST-CANCER; GEFITINIB; ERLOTINIB AB Inhibiting epidermal growth factor receptor ( EGFR) signaling has proven to be an effective strategy for treating non-small cell lung cancer (NSCLC) patients and the first generation of agents developed for this purpose, gefitinib and erlotinib, stimulated a unique escalation in both biologic and clinical research within the field. Second-generation EGFR-targeted agents that aim to further improve patient outcomes are now in preclinical and clinical trials. This review discusses four promising agents that are currently being studied in NSCLC: EKB-569, HKI-272, CI-1033, and ZD6474. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St,Yawley Suite 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 53 TC 40 Z9 42 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 3 BP 325 EP 330 DI 10.1634/theoncologist.12-3-325 PG 6 WC Oncology SC Oncology GA 154YE UT WOS:000245543600011 PM 17405897 ER PT J AU Strumberg, D Clark, JW Awada, A Moore, MJ Richly, H Hendlisz, A Hirte, HW Eder, JP Lenz, HJ Schwartz, B AF Strumberg, Dirk Clark, Jeffrey W. Awada, Ahmad Moore, Malcolm J. Richly, Heike Hendlisz, Alain Hirte, Hal W. Eder, Joseph P. Lenz, Heinz-Josef Schwartz, Brian TI Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: A review of four phase I trials in patients with advanced refractory solid tumors SO ONCOLOGIST LA English DT Review DE sorafenib; BAY 43-9006; phase I clinical trials; review ID RENAL-CELL CARCINOMA; RECEPTOR TYROSINE KINASES; GROWTH-FACTOR VEGF; DAYS ON/7 DAYS; BAY 43-9006; RAF KINASE; BRAF MUTATIONS; K-RAS; HEPATOCELLULAR-CARCINOMA; THERAPEUTIC INTERVENTION AB Sorafenib is an oral multikinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases involved in tumor growth and angiogenesis. It has demonstrated preclinical and clinical activity in several tumor types. Sorafenib 400 mg twice daily ( bid) has been approved in several countries worldwide for the treatment of renal cell carcinoma. This review summarizes key safety, pharmacokinetic, and efficacy data from four phase I, single-agent, dose-escalation studies with sorafenib in patients with advanced refractory solid tumors (n = 173). These trials followed different treatment regimens ( 7 days on/7 days off, n = 19; 21 days on/7 days off, n = 44; 28 days on/7 days off, n = 41; or continuous dosing, n = 69) to establish the optimum dosing schedule. Sorafenib was generally well tolerated; most adverse events were mild to moderate in severity up to the defined maximum-tolerated dose of 400 mg twice daily ( bid). The most frequently reported drug-related adverse events at any grade included fatigue (40%), anorexia (35%), diarrhea (34%), rash/desquamation (27%), and hand - foot skin reaction (25%). Sorafenib demonstrated preliminary antitumor activity, particularly among patients with renal cell carcinoma or hepatocellular carcinoma: overall, two of 137 evaluable patients achieved partial responses and 38 (28%) had stable disease. Although there was high interpatient variability in plasma pharmacokinetics across these studies, this was not associated with an increased incidence or severity of toxicity. Preliminary studies suggest that phosphorylated extracellular signal - related kinase in tumor cells or peripheral blood lymphocytes may be a useful biomarker for measuring and, ultimately, predicting the effects of sorafenib. Based on these findings, continuous daily 400 mg bid sorafenib was chosen as the optimal regimen for phase II/III studies. Trials are ongoing in renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer. C1 Univ Med Sch Bochum, Marienhosp Herne, Dept Hematol & Med Oncol, D-44621 Herne, Germany. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Bayer Pharmaceut Corp, West Haven, CT USA. RP Strumberg, D (reprint author), Univ Med Sch Bochum, Marienhosp Herne, Dept Hematol & Med Oncol, Holkeskampring 40, D-44621 Herne, Germany. EM dirk.strumberg@marienhospital-herne.de NR 68 TC 255 Z9 265 U1 2 U2 14 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 4 BP 426 EP 437 DI 10.1634/theoncologist.12-4-426 PG 12 WC Oncology SC Oncology GA 165FT UT WOS:000246290200009 PM 17470685 ER PT J AU Allen, AM Tishler, RB AF Allen, Aaron M. Tishler, Roy B. TI Commentary: IMRT for head and neck cancer: Many chapters left to write SO ONCOLOGIST LA English DT Editorial Material ID MODULATED RADIATION-THERAPY; SQUAMOUS-CELL CARCINOMA; NASOPHARYNGEAL CARCINOMA; CONVENTIONAL FRACTIONATION; ACCELERATED FRACTIONATION; OROPHARYNGEAL CARCINOMA; RANDOMIZED TRIAL; 2ND CANCERS; RADIOTHERAPY; CHEMORADIOTHERAPY C1 Dana Farber Canc Inst, Dept Radiat Oncol, Brigham & Womens Canc Ctr, Boston, MA 02215 USA. RP Allen, AM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Brigham & Womens Canc Ctr, 44 Binney St, Boston, MA 02215 USA. EM AALLEN@LROC.HARVARD.EDU NR 33 TC 3 Z9 3 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 5 BP 565 EP 568 DI 10.1634/theoncologist.12-5-565 PG 4 WC Oncology SC Oncology GA 172JE UT WOS:000246799400010 PM 17522244 ER PT J AU Chen, YB Rahemtullah, A Hochberg, E AF Chen, Yi-Bin Rahemtullah, Aliyah Hochberg, Ephraim TI Primary effusion lymphoma SO ONCOLOGIST LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKIN-LYMPHOMA; EPSTEIN-BARR-VIRUS; STEM-CELL TRANSPLANTATION; GENE-EXPRESSION PROFILE; HIGH-DOSE METHOTREXATE; CAVITY-BASED LYMPHOMAS; HIV-INFECTED PATIENTS AB Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma (NHL) that accounts for approximately 4% of all HIV- associated NHL. PEL has a unique clinical presentation in having a predilection for arising in body cavities such as the pleural space, pericardium, and peritoneum. PEL cells are morphologically variable with a null lymphocyte immunophenotype and evidence of human herpesvirus (HHV)-8 infection. The exact oncogenic mechanisms of HHV-8 have not been clearly defined. Treatment is usually with combination CHOP( cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and antiretroviral therapy ( if HIV positive). The prognosis for PEL is poor, with a median survival time of around 6 months. As the exact molecular steps in HHV-8 driven oncogenesis are unraveled, it is hoped that more specific therapeutic targets will be revealed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hochberg, E (reprint author), Yawkey 7B-7854,MGH,32 Fruit St, Boston, MA 02114 USA. EM ehochberg@partners.org NR 68 TC 96 Z9 96 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 5 BP 569 EP 576 DI 10.1634/theoncologist.12-5-569 PG 8 WC Oncology SC Oncology GA 172JE UT WOS:000246799400011 PM 17522245 ER PT J AU Garcia, JM Polvino, WJ AF Garcia, Jose M. Polvino, William J. TI Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: Results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers SO ONCOLOGIST LA English DT Article ID TUMOR-BEARING RATS; CANCER-PATIENTS; FOOD-INTAKE; CACHEXIA; APPETITE; PEPTIDE; INTERLEUKIN-6; SECRETION; ANOREXIA; RECEPTOR AB Purpose. RC-1291is a novel, oral ghrelin mimetic and growth hormone (GH) secretagogue being developed to increase appetite and lean muscle mass in patients with cancer-associated anorexia/cachexia. This randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation phase I study in healthy volunteers evaluated RC1291 once daily (qd) and twice daily ( bid) for effect on body weight and safety. Methods. The study was conducted with three sequential groups of volunteers. Panel A subjects ( n = 8) received placebo or RC-1291, 25 mg qd, for 5 days. Panel B subjects received RC-1291, 25 mg bid or 50 mg qd, for 6 days then crossed over to the other dosage for 5 days ( n = 12); three subjects received placebo for all 11 doses to maintain double-blinding. Panel C subjects ( n = 9) received placebo or RC-1291, 75 mg qd, for 6 days. Results. Subjects who received RC-1291, 50 or 75 mg, had significant dose-related weight gain after 6 days versus placebo, with the greatest increases seen with daily dosing. The mean increase in weight from baseline after 50 mg qd was 1.25 +/- 0.725 kg ( p =.0022 versus placebo), and after 75 mg qd it was 1.16 +/- 0.651 kg ( p =.0022 versus placebo). One subject in the 50 mg qd group had moderate transient elevation in aspartate aminotransferase and alanine aminotransferase levels. No other laboratory or clinical adverse events of consequence were reported. Conclusions. Results indicate that RC-1291 produces dose-related increases in body weight with no dose-limiting adverse effects, and may be an effective treatment for anorexia/cachexia. C1 Michael E DeBakey Vet Affairs Med Ctr, Div Endocrinol Diabet & Metab, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Sapphire Therapeut Inc, Bridgewater, NJ USA. RP Garcia, JM (reprint author), MEDVA Med Ctr, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Jgarcia1@bcm.tmc.edu NR 33 TC 65 Z9 65 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 5 BP 594 EP 600 DI 10.1634/theoncologist.12-5-594 PG 7 WC Oncology SC Oncology GA 172JE UT WOS:000246799400014 PM 17522248 ER PT J AU Lynch, TJ Kim, ES Eaby, B Garey, J West, DP Lacouture, ME AF Lynch, Thomas J., Jr. Kim, Ed S. Eaby, Beth Garey, Jody West, Dennis P. Lacouture, Mario E. TI Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: An evolving paradigm in clinical management SO ONCOLOGIST LA English DT Article DE EGFR; erlotinib; cetuximab; panitumumab; cutaneous toxicity; pathobiology; forum consensus ID CELL LUNG-CANCER; EGF-RECEPTOR; KINASE INHIBITORS; RANDOMIZED-TRIAL; TYROSINE KINASE; CETUXIMAB; GEFITINIB; SURVIVAL; EFFICACY; THERAPY AB Epidermal growth factor receptor inhibitors (EGFRIs) have demonstrated improved overall survival in patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer; however, their use is associated with dermatologic reactions of varying severity. The similar spectrum of events observed with monoclonal antibodies and tyrosine kinase inhibitors suggests such toxicities are a class effect. While such reactions do not necessarily require any alteration in EGFRI treatment, being best addressed through symptomatic treatment, there is limited evidence on which to base such therapies. In October 2006, at an international and interdisciplinary EGFRI dermatologic toxicity forum, the underlying mechanisms of these toxicities were discussed and commonly used therapeutic interventions were evaluated. Our aim was to reach a current consensus on management strategies. A three-tiered, EGFRI-focused toxicity grading system is suggested for the purposes of therapeutic decision making, and as a framework on which to build a stepwise approach to intervention. This approach to successful management is specifically tailored to accurately categorize dermatologic toxicity associated with EGFRIs, and can be easily applied by all health care professionals. The goal is to maximize quality of life in patients who are being treated with these agents - many of whom will be on these drugs for several months or even years. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW7, Boston, MA 02114 USA. EM tlynch@partners.org OI West, Dennis/0000-0002-9107-6697 NR 58 TC 175 Z9 179 U1 1 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 5 BP 610 EP 621 DI 10.1634/theoncologist.12-5-610 PG 12 WC Oncology SC Oncology GA 172JE UT WOS:000246799400016 PM 17522250 ER PT J AU Richardson, PG Mitsiades, C Schlossman, R Munshi, N Anderson, K AF Richardson, Paul G. Mitsiades, Constantine Schlossman, Robert Munshi, Nikhil Anderson, Kenneth TI New drugs for myeloma SO ONCOLOGIST LA English DT Review DE bortezomib; lenalidomide; multiple myeloma; thalidomide ID REFRACTORY MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; THALIDOMIDE PLUS DEXAMETHASONE; HIGH-DOSE DEXAMETHASONE; COOPERATIVE-ONCOLOGY-GROUP; PHASE-II TRIAL; COMBINATION THERAPY PS-341/BORTEZOMIB; PATIENTS RECEIVING THALIDOMIDE; PREVIOUSLY UNTREATED PATIENTS AB Although multiple myeloma remains incurable with conventional treatments, management of the disease has recently been transformed with the introduction of three novel agents, bortezomib, thalidomide, and lenalidomide. The proteasome inhibitor bortezomib is approved for the treatment of patients who have received one prior therapy; there is a growing body of clinical evidence showing its effectiveness alone and in combination in the frontline setting, with high response rates and consistently high rates of complete response. Thalidomide plus dexamethasone is approved as frontline treatment of multiple myeloma. Other combination regimens including thalidomide have demonstrated substantial activity in both relapsed and frontline settings. Recently, the thalidomide analogue lenalidomide has been approved, in combination with dexamethasone, for the treatment of patients who have received one prior therapy; this regimen has shown promising results in the frontline setting. These agents represent a new generation of treatments for multiple myeloma that affect both specific intracellular signaling pathways and the tumor microenvironment. Other novel, targeted therapies are also being evaluated in preclinical and clinical studies. Regimens incorporating bortezomib, thalidomide, lenalidomide, and other novel agents, together with commonly used conventional drugs, represent a promising future direction in myeloma treatment. At present, further investigation is required to assess the safety and activity of combinations integrating these other novel agents. However, bortezomib, thalidomide, and lenalidomide are now in widespread clinical use. This review therefore focuses on the extensive clinical data available from studies of these drugs in the treatment of newly diagnosed and advanced multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 166 TC 117 Z9 122 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 6 BP 664 EP 689 DI 10.1634/theoncologist.12-6-664 PG 26 WC Oncology SC Oncology GA 186UI UT WOS:000247803400006 PM 17602058 ER PT J AU Posner, M AF Posner, Marshall TI Evolving strategies for combined-modality therapy for locally advanced head and neck cancer SO ONCOLOGIST LA English DT Article DE head and neck cancer; induction therapy; sequential therapy; combined modality; treatment; SCCHN ID PHASE-III TRIAL; SQUAMOUS-CELL CARCINOMA; STAGE OROPHARYNX CARCINOMA; ADVANCED LARYNGEAL-CANCER; INDUCTION CHEMOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; NEOADJUVANT CHEMOTHERAPY; CONCURRENT CHEMOTHERAPY; ORGAN PRESERVATION AB Despite continual advances in the treatment of head and neck cancer, disease-free survival, functional outcome, toxicity of therapy, and overall survival remain less than optimal. While traditional treatment has focused on surgical resection with or without radiation and chemoradiotherapy, newer combined-modality regimens offer patients a better prognosis, organ preservation, and less morbidity. In this paper, single agents and doublet therapy are reviewed, as are emerging data on the utility of induction therapy, chemoradiotherapy, and surgery as a sequential treatment regimen. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Posner, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St,SW430, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu NR 27 TC 16 Z9 18 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 8 BP 967 EP 974 DI 10.1634/theoncologist.12-8-967 PG 8 WC Oncology SC Oncology GA 206QB UT WOS:000249196900009 PM 17766656 ER PT J AU Bunnell, CA Winer, EP AF Bunnell, Craig A. Winer, Eric P. TI Optimizing endocrine therapy for premenopausal and postmenopausal women with breast cancer - The Cianfrocca/Wolff article reviewed SO ONCOLOGY-NEW YORK LA English DT Article ID TAMOXIFEN; RECEPTOR; CHEMOTHERAPY C1 [Bunnell, Craig A.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Bunnell, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2007 VL 21 IS 1 BP 69 EP + PG 2 WC Oncology SC Oncology GA 270QZ UT WOS:000253736600009 ER PT J AU Hoffner, B Hitchcock-Bryan, S Bauer-Wu, S Wolanksi, A Joffe, S AF Hoffner, Brianna Hitchcock-Bryan, Suzanne Bauer-Wu, Susan Wolanksi, Andrew Joffe, Steven TI Recruitment challenges and innovations in conducting social-behavioral research within the context of biomedical clinical trials. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2007 VL 34 IS 1 MA 16 BP 174 EP 174 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000046 ER PT J AU Sarna, L Cooley, M Brown, JK Chernecky, C Elashoff, D AF Sarna, Linda Cooley, Mary Brown, Jean K. Chernecky, Cynthia Elashoff, David TI Symptom patterns after thoracotomy for lung cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Boston, MA USA. SUNY Buffalo, Sch Nursing, Buffalo, NY USA. Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. Sch Nursing, Sch Publ Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 44 BP 185 EP 185 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000074 ER PT J AU McDermott, K Roper, K Coakley, C Boyd, K Cooley, M AF McDermott, Kathleen Roper, Kristin Coakley, Christine Boyd, Kecia Cooley, Mary TI Lessons learned in the recruitment and retention of young adult cancer survivors in a longitudinal clinical trial. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN PY 2007 VL 34 IS 1 MA 48 BP 186 EP 187 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000078 ER PT J AU Cooley, M Powell, M Hoskinson, R AF Cooley, Mary Powell, Mark Hoskinson, Randall TI Age-related differences in smoking relapse among women. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JAN PY 2007 VL 34 IS 1 MA 51 BP 188 EP 188 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000081 ER PT J AU Brown, J Sarna, L Cooley, M Chernecky, C AF Brown, Jean Sarna, Linda Cooley, Mary Chernecky, Cynthia TI Analysis of symptom clusters in women with lung cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 SUNY Buffalo, Sch Nursing, Buffalo, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 63 BP 192 EP 193 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000093 ER PT J AU Nirenberg, A Davis, A Friese, C Gillespie, T Bush, AP Rice, D AF Nirenberg, Anita Davis, Arlene Friese, Christopher Gillespie, Theresa Bush, Annette Parry Rice, David TI ONS neutropenia management state of the knowledge. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Atlanta VA Med Ctr, Decatur, GA USA. Oncol Nursing Soc, Pittsburgh, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 JAN PY 2007 VL 34 IS 1 MA 78 BP 198 EP 199 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000108 ER PT J AU Fonteyn, M Polinski, K Lynch, K McKenna, C Gorman, D Saint-Eloi, S AF Fonteyn, Marsha Polinski, Karen Lynch, Kathleen McKenna, Christin Gorman, Dan Saint-Eloi, Suzelle TI An evidence-based policy to guide nurses in using a power injector to instill contrast media. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JAN PY 2007 VL 34 IS 1 MA 79 BP 199 EP 199 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000109 ER PT J AU Bauer-Wu, S Norris, R Powell, M Healey, M Habin, K Partridge, A Schapira, L AF Bauer-Wu, Susan Norris, Rebecca Powell, Mark Healey, Martha Habin, Karleen Partridge, Ann Schapira, Lidia TI A web-based expressive writing intervention for young women with newly diagnosed breast cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 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 JAN PY 2007 VL 34 IS 1 MA 88 BP 202 EP 202 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000118 ER PT J AU Kreicbergs, U Valdimarsdottir, U Hauksdottir, A Hunt, H Onelov, E Henter, JI Steineck, G AF Kreicbergs, Ulrika Valdimarsdottir, Unnur Hauksdottir, Arna Hunt, Hayley Onelov, Erik Henter, Jan-Inge Steineck, Gunnar TI Parental awareness of their child's impending death due to cancer impacts their long-term psychological morbidity. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN PY 2007 VL 34 IS 1 MA 146 BP 223 EP 224 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000176 ER PT J AU Kreicbergs, U Phil, PLL Onelov, E AF Kreicbergs, UIrika Phil, Patrizia Lannen Lic Onelov, Erik TI Support from healthcare staff can facilitate parental grieving following the loss of a child to cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2007 VL 34 IS 1 MA 147 BP 224 EP 224 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000177 ER PT J AU Cooley, M Xiarhos, B AF Cooley, Mary Xiarhos, Beth TI Smoking cessation interventions in cancer care: Missed opportunities. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 JAN PY 2007 VL 34 IS 1 MA 159 BP 228 EP 229 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000189 ER PT J AU Radwin, L Wilkes, G Curtin, L Hackel, M Saba, C Garvey, J Schrantz, A AF Radwin, Laurel Wilkes, Gail Curtin, Linda Hackel, Mary Saba, Christine Garvey, Joanne Schrantz, Amber TI Cancer patients' trust in oncology nursing care. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Massachusetts, Boston, MA 02125 USA. Boston Med Ctr, Boston, MA USA. Brockton Hosp, Brockton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Falmouth Hosp, Falmouth, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JAN PY 2007 VL 34 IS 1 MA 182 BP 237 EP 237 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000212 ER PT J AU Hitchcock-Bryan, S Bauer-Wu, S Powell, M Hoffner, B Joffe, S Parker, C Wolanski, A AF Hitchcock-Bryan, Suzanne Bauer-Wu, Susan Powell, Mark Hoffner, Brianna Joffe, Steven Parker, Christina Wolanski, Andrew TI Entering a clinical trial: Is it right for you? A randomized study of the clinical trials video and its impact on the informed consent process. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JAN PY 2007 VL 34 IS 1 MA 213 BP 248 EP 248 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000243 ER PT J AU Norden, AD Batchelor, TT AF Norden, Andrew D. Batchelor, Tracy T. TI Reversible posterior leukoencephalopathy syndrome SO ONKOLOGIE LA English DT Editorial Material ID CHEMOTHERAPY C1 Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 18 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2007 VL 30 IS 3 BP 90 EP 91 DI 10.1159/000098642 PG 2 GA 143TC UT WOS:000244746800001 PM 17341892 ER PT J AU Breuer, A Kandel, M Fisseler-Eckhoff, A Sutter, C Schwaab, E Luck, HJ du Bois, A AF Breuer, Annette Kandel, Michaela Fisseler-Eckhoff, Annette Sutter, Christian Schwaab, Eva Lueck, Hans-Joachim du Bois, Andreas TI BRCA1 germline mutation in a woman with metaplastic squamous cell breast cancer SO ONKOLOGIE LA English DT Article DE BRCA1 mutation; squamous cell cancer of the breast; breast cancer, basal-like ID BASAL PHENOTYPE; CARCINOMA; CHEMOTHERAPY; POPULATION AB Background: Breast cancers arising in women with germline BRCA1 mutations are most likely to be estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative (so-called triple negative or basal-like breast cancers). Metaplastic carcinoma with pure squamous differentiation is a very rare histological subtype (0.1% of all breast cancers) and is usually ER, PR, and HER2/neu negative by immunohistochemistry. A BRCA1 germline mutation in squamous cell breast cancer has never been reported. Case Report: A 25-year-old woman was diagnosed with squamous cell cancer of the breast. Three years later, she developed contralateral breast cancer, also of the squamous cell subtype. Both tumors were triple negative. Because of the patient's history and her strong family history, genetic testing was recommended. The patient was found to be carrier of a BRCA1 germline mutation. Conclusion: We report, to our knowledge, the first case of a BRCA1 mutation in a woman with metaplastic squamous cell breast cancer. C1 HSK, Klin Gynakol & Gynakol Onkol, D-65199 Wiesbaden, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. HSK, Inst Pathol & Zytol, D-65199 Wiesbaden, Germany. Univ Heidelberg, Inst Humangenet, D-6900 Heidelberg, Germany. Facharztin Humangenet, Wiesbaden, Germany. RP Breuer, A (reprint author), HSK, Klin Gynakol & Gynakol Onkol, Ludwig Erhard Str 100, D-65199 Wiesbaden, Germany. EM gynecology@web.de NR 29 TC 8 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2007 VL 30 IS 6 BP 316 EP 318 DI 10.1159/000101515 PG 3 GA 175QQ UT WOS:000247028500005 PM 17551255 ER PT J AU Thiagalingam, S Mcgee, TL Weleber, RG Sandberg, MA Trzupek, KM Berson, EL Dryja, TP AF Thiagalingam, Sureka McGee, Terri L. Weleber, Richard G. Sandberg, Michael A. Trzupek, Karmen M. Berson, Eliot L. Dryja, Thaddeus P. TI Novel mutations in the KCNV2 gene in patients with cone dystrophy and a supernormal rod electroretinogram SO OPHTHALMIC GENETICS LA English DT Article DE gene mutation; retinal degeneration; electroretinogram ID RETINAL DEGENERATION; B-WAVES; ERG; DYSFUNCTION; RESPONSES; CHANNEL AB Purpose: To identify mutations in KCNV2 in patients with a form of cone dystrophy characterized by a supernormal rod electroretinogram (ERG). Methods: The 2 exons and flanking intron DNA of KCNV2 from 8 unrelated patients were PCR amplified and sequenced. Results: We found 1 frameshift, 2 nonsense, 1 non-stop, and 6 missense mutations. Every patient had one or two mutations identified. Of the missense mutations, 4 affected residues were in the amino terminal region of the protein, and two in the pore region. Conclusions: KCNV2 mutations account for most if not all cases of cone dystrophy with a supernormal rod ERG. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Sch Med,Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. EM Thaddeus_Dryja@meei.harvard.edu FU NEI NIH HHS [EY014104, EY08683, EY00169] NR 19 TC 20 Z9 20 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1381-6810 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PY 2007 VL 28 IS 3 BP 135 EP 142 DI 10.1080/13816810701503681 PG 8 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA 218JG UT WOS:000250011200004 PM 17896311 ER PT J AU Bailey, K Ng, JD Hwang, PH Saulny, SM Holck, DEE Rubin, PAD AF Bailey, Kristi Ng, John D. Hwang, Peter H. Saulny, Stanley M. Holck, David E. E. Rubin, Peter A. D. TI Infraorbital nerve surgical decompression for chronic infraorbital nerve hyperesthesia SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Purpose: To present three cases of chronic infraorbital nerve hyperesthesia relieved by surgical decompression of the infraorbital nerve. Methods: Retrospective chart review. Results: We identified three cases of chronic hyperesthesia of the infraorbital nerve. Two cases were related to previous blunt orbital trauma, whereas the third was associated with a long-standing anophthalmic socket with numerous previous surgeries. In each case, patients had dramatic relief of infraorbital nerve hyperesthesia and pain after surgical decompression of the infraorbital nerve. Conclusions: Surgical decompression of the infraorbital nerve can provide significant symptomatic improvement in patients with chronic infraorbital nerve hyperesthesia secondary to nerve compression. C1 Oregon Hlth Sci Univ, Oculoplast Dept, Casey Eye Inst, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97239 USA. Wilford Hall USAF Med Ctr, Dept Ophthalmol, San Antonio, TX 78236 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Bailey, K (reprint author), Oregon Hlth Sci Univ, Oculoplast Dept, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM ngj@ohsu.edu NR 5 TC 5 Z9 5 U1 0 U2 1 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 JAN-FEB PY 2007 VL 23 IS 1 BP 49 EP 51 DI 10.1097/IOP.0b013e31802dd3fc PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 132NZ UT WOS:000243950800012 PM 17237691 ER PT S AU Chang, SK Rizvi, I Solban, N Hasan, T AF Chang, Sung K. Rizvi, Imran Solban, Nicolas Hasan, Tayyaba BE Kessel, D TI In vivo, on-line monitoring of molecular response to photodynamic therapy: Molecular imaging of vascular endothelial growth factor - art. no. 64270P SO Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XVI CY JAN 20-21, 2007 CL San Jose, CA DE photodynamic therapy; optical molecular imaging; vascular endothelial growth factor ID PROSTATE-CANCER; RADIATION-THERAPY; BREAST-CANCER; FACTOR VEGF; MODEL; ANGIOGENESIS; METASTASIS; CARCINOMA; STRATEGY AB Cytokines are important messengers in cell-to-cell communications that regulate vital cellular and physiological processes, and play an important role in defining the diagnosis, prognosis and treatment response in various diseases. Although current ex vivo biochemical assays for cytokine quantitation are useful, their capabilities for studying dynamic cytokine expression in living systems are limited. Optical molecular imaging technology can help probe the spatiotemporal dynamics of cytokine expression in vivo and in real-time. We developed an in vivo optical molecular imaging strategy for monitoring one of these cytokines, the vascular endothelial growth factor (VEGF). With the imaging strategy, changes in tumoral VEGF concentration following cobalt chloride treatment and photodynamic therapy (PDT) were monitored. This was the first systematic study to test the feasibility of VEGF-targeted molecular imaging, and can potentially set the basis for online monitoring of cytokines that will help develop effective tools for diagnosis, prognosis, treatment planning and monitoring. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chang, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6540-5 J9 P SOC PHOTO-OPT INS PY 2007 VL 6427 BP P4270 EP P4270 AR 64270P DI 10.1117/12.706605 PG 5 WC Oncology; Engineering, Biomedical; Optics SC Oncology; Engineering; Optics GA BGF70 UT WOS:000246489700017 ER PT S AU Kumar, ATN Raymond, SB Boas, DA Bacskai, BJ AF Kumar, Anand T. N. Raymond, Scott B. Boas, David A. Bacskai, Brian J. BE Chance, B Alfano, RR Tromberg, BJ Tamura, M SevickMuraca, EM TI A direct approach to time domain fluorescence tomography based on asymptotic lifetime analysis - art. no. 64340E SO Optical Tomography and Spectroscopy of Tissue VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue VII CY JAN 21-24, 2007 CL San Jose, CA SP SPIE DE fluorescence imaging; time resolved; lifetime sensing ID DIFFUSE OPTICAL TOMOGRAPHY; SINGULAR-VALUE ANALYSIS; EARLY-ARRIVING PHOTONS; TURBID MEDIUM; RESOLVED FLUORESCENCE; MOLECULAR TOMOGRAPHY; IMAGING MICROSCOPY; MEDIA; TISSUE; OPTIMIZATION AB A theoretical framework is presented that allows a lifetime based analysis of the entire temporal diffuse fluorescence response curve from a turbid medium. Optimization studies using singular value decomposition analysis show that direct time domain fluorescence reconstructions are optimally performed using a few points near the peak and rise portions of the temporal response. It is also shown that the initial portion of the fluorescent response curve offers superior contrast-to-noise performance, while the late decay portions offer minimal cross-talk between multiple lifetime components. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6547-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6434 BP E4340 EP E4340 AR 64340E DI 10.1117/12.699692 PG 9 WC Engineering, Biomedical; Instruments & Instrumentation; Optics; Spectroscopy SC Engineering; Instruments & Instrumentation; Optics; Spectroscopy GA BGA90 UT WOS:000245836000008 ER PT S AU Raymond, SB Kumar, ATN Dunn, AK Boas, DA Bacskai, BJ AF Raymond, Scott B. Kumar, Anand T. N. Dunn, Andrew K. Boas, David A. Bacskai, Brian J. BE Chance, B Alfano, RR Tromberg, BJ Tamura, M SevickMuraca, EM TI Fluorescence tomography in a murine model of Alzheimer's disease - art. no. 64342H SO Optical Tomography and Spectroscopy of Tissue VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue VII CY JAN 21-24, 2007 CL San Jose, CA SP SPIE DE near infrared; molecular imaging; amyloid; biomarker ID OPTICAL-PROPERTIES; BRAIN; TISSUES; RANGE AB Noninvasive molecular imaging of amyloid plaques in murine Alzheimer's disease models would accelerate drug development and basic Alzheimer's research. Amyloid plaques differ from traditional fluorescent targets in size and spatial distribution and therefore present a unique challenge for biomarker development and tomography. To study imaging feasibility and establish biomarker criteria, we developed a digital mouse head model from a 100 mu m-resolution, digital, segmented mouse atlas(1). The cortical region of the brain was filled with a spatially uniform distribution of plaques that had different fluorescent properties from the surrounding brain tissue, similar to current transgenic mouse models of Alzheimer's disease. Fluorescence was simulated with a Monte Carlo algorithm using different plaque densities, detection geometries, and background fluorescence. Our preliminary results demonstrated that shielding effects might require nonlinear reconstruction algorithms and that background fluorescence would seriously hinder quantitative burden estimation. The Monte Carlo based approach presented here offers a powerful way to study the feasibility of non-invasive imaging in murine Alzheimer's models and to optimize experimental conditions. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Charlestown, MA 02129 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6547-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6434 BP H4342 EP H4342 AR 64342H DI 10.1117/12.700199 PG 8 WC Engineering, Biomedical; Instruments & Instrumentation; Optics; Spectroscopy SC Engineering; Instruments & Instrumentation; Optics; Spectroscopy GA BGA90 UT WOS:000245836000048 ER PT J AU Ozcan, A Digonnet, MJF Kino, GS AF Ozcan, Aydogan Digonnet, Michel J. F. Kino, Gordon S. TI Quasi-phase-matched grating characterization using minimum-phase functions SO OPTICS COMMUNICATIONS LA English DT Article ID FOURIER-TRANSFORM TECHNIQUE; 2ND-ORDER NONLINEARITY; PROFILES; SILICA AB Measurement of the second-harmonic power generated by a quasi-phase-matched (QPM) grating as a function of the frequency detuning parameter yields the Fourier transform (FT) magnitude of the complex nonlinear coefficient profile along the QPM device. This FT magnitude can be measured by tuning either the wavelength of the fundamental laser beam or the temperature of the QPM grating. However, the measured magnitude of the FT cannot be unambiguously inverted without the FT phase to uniquely recover the complex nonlinear coefficient profile of the QPM grating. As we demonstrate in this work, this ambiguity can be completely eliminated by placing a stronger and thinner nonlinear sample against the input or output of the QPM device of interest and measuring the detuning curve of this composite structure. By construction, the nonlinear profile of this assembly has a sharp peak due to the thinner sample, followed by the weaker, broader profile of the QPM grating, which essentially constitutes a minimum-phase function. Therefore, its FT phase can be calculated uniquely from its measured FT magnitude, for example by applying to the FT amplitude the logarithmic Hilbert transform or an iterative error-reduction algorithm. This processing then enables the full recovery of the complex nonlinear coefficient profile of the QPM device from its measured detuning curve. In this paper, we demonstrate with numerical examples that this powerful new technique can accurately recover the period, envelope, and chirp parameters of any QPM grating. (c) 2006 Elsevier B.V. All rights reserved. C1 Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. EM aozcan@mgh.harvard.edu RI Ozcan, Aydogan/I-2608-2013 OI Ozcan, Aydogan/0000-0002-0717-683X NR 15 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0030-4018 J9 OPT COMMUN JI Opt. Commun. PD JAN 1 PY 2007 VL 269 IS 1 BP 199 EP 205 DI 10.1016/j.optcom.2006.07.047 PG 7 WC Optics SC Optics GA 114MT UT WOS:000242671000030 ER PT J AU Wang, HB Merchant, SN Sorensen, MS AF Wang, Haobing Merchant, Saumil N. Sorensen, Mads S. TI A downloadable three-dimensional virtual model of the visible ear SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE 3-D reconstruction; human temporal bone; surface rendering ID TEMPORAL BONE DISSECTION; 3-D RECONSTRUCTION; 3D RECONSTRUCTION; TEACHING TOOL AB Purpose: To develop a three-dimensional (3-D) virtual model of a human temporal bone and surrounding structures. Methods: A fresh-frozen human temporal bone was serially sectioned and digital images of the surface of the tissue block were recorded (the 'Visible Ear'). The image stack was resampled at a final resolution of 50 x 50 x 50/100 mu m/voxel, registered in custom software and segmented in PhotoShop (R) 7.0. The segmented image layers were imported into Amira (R) 3.1 to generate smooth polygonal surface models. Results: The 3-D virtual model presents the structures of the middle, inner and outer ears in their surgically relevant surroundings. It is packaged within a cross-platform freeware, which allows for full rotation, visibility and transparency control, as well as the ability to slice the 3-D model open at any section. The appropriate raw image can be superimposed on the cleavage plane. The model can be downloaded at https://research.meei.harvard.edu/Otopathology/3dmodels/ Copyright (c) 2007 S. Karger AG, Basel. C1 Univ Copenhagen, Dept Otolaryngol Head & Neck Surg, Rigshosp, DK-2100 Copenhagen, Denmark. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Sorensen, MS (reprint author), Univ Copenhagen, Dept Otolaryngol Head & Neck Surg, Rigshosp, F 2074, DK-2100 Copenhagen, Denmark. EM ms.sorensen@dadlnet.dk FU NIDCD NIH HHS [P30 DC05209, U24 DC008559, P30 DC005209, U24 DC008559-01] NR 17 TC 22 Z9 23 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2007 VL 69 IS 2 BP 63 EP 67 DI 10.1159/000097369 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 117BO UT WOS:000242847700001 PM 17124433 ER PT J AU Hunter, DJ LaValley, M Li, J Zhang, Y Bauer, D Nevitt, M Guermazi, A DeGroot, J Sakkee, N Gale, D Felson, DT AF Hunter, D. J. LaValley, M. Li, J. Zhang, Y. Bauer, D. Nevitt, M. Guermazi, A. DeGroot, J. Sakkee, N. Gale, D. Felson, D. T. TI Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE pentosidine; cartilage loss; MRI; knee osteoarthritis ID GLYCATION END-PRODUCTS; HUMAN ARTICULAR-CARTILAGE; OLIGOMERIC MATRIX PROTEIN; AGE-RELATED ACCUMULATION; RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID; NONENZYMATIC GLYCATION; EXTRACELLULAR-MATRIX; COLLAGEN TURNOVER; HYALURONIC-ACID AB Objective: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major changes in the extracellular matrix of cartilage is the age-related accumulation of advanced glycation end products (AGEs). Pentosidine, an AGE crosslink, is one of the few characterized AGEs and is considered an adequate marker for the many AGEs that are formed in vivo. We used data from a longitudinal observation study to determine if urinary pentosidine could serve as a marker to predict cartilage loss. Methods: We conducted a prospective analysis of data from the Boston Ostecarthritis of the Knee Study (BOKS); a completed natural history study of knee OA. All subjects in the study met American College of Rheumatology (ACR) criteria for knee OA. Knee magnetic resonance (MR) images were scored for cartilage in 14 plates of the knee using the Whole Organ Magnetic Resonance Imaging Score (WORMS) semi-quantitative grading scheme. Within the BOKS population, a nested sample of 127 subjects (39% of the whole sample) who had both baseline pentosidine and longitudinal magnetic resonance imaging (MRI) measurements (MRIs performed at baseline and 30 months later) was assessed. Urinary pentosidine was assayed and normalized to creatinine to account for differences in urine concentrations. We analyzed the data using three different methods to assess if baseline measures of pentosidine predicted subsequent cartilage loss on MRI. These were (1) analysis 1: logistic regression with the outcome cartilage loss in any plate; (2) analysis 2: proportional odds model where the outcome was defined as 0 = no cartilage loss, 1 = cartilage loss in one plate, 2 cartilage loss in two plates, and 3 = cartilage loss in at least three plates; and (3) analysis 3: Poisson regression with the outcome the number of plates with cartilage loss. All analyses were adjusted for age, sex and Body Mass Index (BMI). Results: At baseline the mean (standard deviation) age was 67 (9) years and 54% were male. The results for the three analytic steps are as follows: Analysis 1: the odds ratio for cartilage loss is 1.01 (95% confidence interval (CI) 0.93-1.09) with 1 unit increase in pentosidine. Analysis 2: the odds ratio for more cartilage loss is 0.99 (95% CI 0.92-1.06) with 1 unit increase in pentosidine. Analysis 3: the relative number of plates with cartilage loss decreased was 1.00 (95% CI 0.95-1.03) with a 1 unit increase in pentosidine. Conclusion: Urinary pentosidine does not predict knee cartilage loss. Previous studies have suggested that local content within cartilage of AGEs is elevated in persons at high risk for progression. Our data suggest that these changes are not measurable systemically. Alternatively, urinary pentosidine levels reflect cartilage degradation in all joints (thus whole body cartilage breakdown) and may therefore not relate to CA severity in a single knee joint. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. UCSF, San Francisco, CA USA. OARG, San Francisco, CA USA. TNO Qual Life, Leiden, Netherlands. VA Boston Healthcare Syst, Dept Radiol, Boston, MA USA. RP Hunter, DJ (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Room A203,715 Albany St, Boston, MA 02118 USA. EM djhunter@bu.edu RI DeGroot, Jeroen/C-4585-2012; Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Zhang, Yuqing/0000-0001-7954-1149; Felson, David/0000-0002-2668-2447; LaValley, Michael/0000-0002-8488-5170 FU NIAMS NIH HHS [AR47785, U01 AR50900] NR 25 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2007 VL 15 IS 1 BP 93 EP 97 DI 10.1016/j.joca.2006.06.011 PG 5 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 135VV UT WOS:000244182900011 PM 16857393 ER PT J AU Kronenberg, HM AF Kronenberg, Henry M. TI PTH regulates the hematopoietic stem cell niche in bone SO OSTEOIMMUNOLOGY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID JANSENS METAPHYSEAL CHONDRODYSPLASIA; PARATHYROID-HORMONE; MARROW NICHE; EXPRESSION; RECEPTORS; PEPTIDE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Enocrine Unit, Boston, MA 02115 USA. RP Kronenberg, HM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Enocrine Unit, Boston, MA 02115 USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 602 BP 57 EP 60 PG 4 WC Immunology; Medicine, Research & Experimental; Orthopedics SC Immunology; Research & Experimental Medicine; Orthopedics GA BGR94 UT WOS:000250200200008 PM 17966388 ER PT S AU McKenna, MJ Kristiansen, AG AF McKenna, Michael J. Kristiansen, Arthur G. BE Arnold, W Hausler, R TI Molecular biology of otosclerosis SO Otosclerosis and Stapes Surgery SE ADVANCES IN OTO-RHINO-LARYNGOLOGY LA English DT Proceedings Paper CT International Symposium on Otosclerosis and Stapes Surgery CY APR, 2004 CL Saas Fee, SWITZERLAND ID IMPERFECTA TYPE-I; COL1A1 NULL ALLELES; OSTEOGENESIS-IMPERFECTA; OSTEOPROTEGERIN LIGAND; CLINICAL OTOSCLEROSIS; ACTIVE OTOSCLEROSIS; PAGETS-DISEASE; TEMPORAL BONE; OTIC CAPSULE; COLLAGEN AB Otosclerosis is a bone disease of the human otic capsule, which is among the most common causes of acquired hearing loss. The pathologic process is characterized by a wave of abnormal bone remodeling in specific sites of predilection within the endochondral layer of the temporal bone. Although the cause of otosclerosis remains uncertain, there is a clear genetic predisposition with half of all cases occurring in families with more than one affected member. There is also compelling evidence that measles virus may play a role in some cases. Ultimately, how genetic factors and viral infection result in otosclerosis must be explained by effects on the molecular factors that control bone remodeling. Copyright (c) 2007 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC03401] NR 48 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-8113-4 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2007 VL 65 BP 68 EP 74 DI 10.1159/000098674 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA BGB51 UT WOS:000245918600011 PM 17245026 ER PT S AU Merchant, SN Rosowski, JJ McKenna, MJ AF Merchant, Saumil N. Rosowski, John J. McKenna, Michael J. BE Arnold, W Hausler, R TI Superior semicircular canal dehiscence mimicking otosclerotic hearing loss SO Otosclerosis and Stapes Surgery SE ADVANCES IN OTO-RHINO-LARYNGOLOGY LA English DT Proceedings Paper CT International Symposium on Otosclerosis and Stapes Surgery CY APR, 2004 CL Saas Fee, SWITZERLAND ID PRESSURE-INDUCED VERTIGO; TYMPANIC MEMBRANE; BONE DEHISCENCE AB A puzzling aspect of middle ear surgery is the presence of an air-bone gap in a small number of cases with no apparent cause. We believe that some of these cases are due to unrecognized superior semicircular canal dehiscence (SSCD). We have now gathered experience from 20 patients with SSCD presenting with apparent conductive hearing loss without vestibular symptoms. All affected cars had SSCD on high-resolution CT scan. The common findings in these patients were: (1) the air-bone gaps occurred in the lower frequencies below 2,000 Hz, and ranged from 10 to 60 dB; (2) bone conduction thresholds below 2,000 Hz were sometimes negative (- 5 dB to - 15 dB); (3) the acoustic (stapedial) reflex was present; (4) measurement of umbo velocity by laser Doppler vibrometry showed slight hypermobility of umbo motion; (5) the vestibular-evoked myogenic potential response was present, with thresholds that were abnormally low, and (6) the middle ear was normal at exploratory tympanotomy, including normal mobility of the ossicles and a patent round window niche. We have investigated the mechanism of the air-bone gap due to SSCD using a theoretical framework, clinical research data and an animal model (chinchilla). Our research supports the hypothesis that SSCD introduces a 'third' window into the inner ear which produces the airbone gap by (1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and (2) increasing the difference in impedance between the scala tympani and scala vestibuli, thus improving thresholds for bone-conducted sound. Copyright (c) 2007 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Merchant, SN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC004798-07, R01 DC004798, R01 DC04798] NR 11 TC 37 Z9 39 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-8113-4 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2007 VL 65 BP 137 EP 145 DI 10.1159/000098790 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA BGB51 UT WOS:000245918600020 PM 17245035 ER PT J AU Shalaby, AA Voigt, A El-Saed, A Mains, M Shusterman, V AF Shalaby, Alaa A. Voigt, Andrew El-Saed, Aiman Mains, Martin Shusterman, Vladimir TI Microvolt T-wave alternans during atrial and ventricular pacing SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 15th World Congress in Cardiac Electrophysiology (CARDIOSTIM 2006) CY JUN 14-17, 2006 CL Nice, FRANCE DE risk stratification; microvolt T-wave alternans; ventricular pacing; atrial pacing ID DEFIBRILLATOR IMPLANTATION; MYOCARDIAL-INFARCTION; ARRHYTHMIAS; BENEFIT AB Introduction: Assessment of microvolt T-wave alternans (MTWA) by the spectral analysis (SA) method requires the heart rate to be stable within a certain range. This can be achieved by ventricular pacing (VP). We compared MTWA during short-term VP versus atrial pacing (AP). Methods: Patients presenting for evaluation of risk of sudden cardiac death underwent an invasive electrophysiologic study. The concordance of results of MTWA-VP with MTWA-AP was evaluated, as well as the specificity, sensitivity, negative, and positive predictive values of MTWA-VP versus MTWA-AP. The maximum recorded amplitude of MTWA (MValt) in concordant positive results, as well as noise levels in all, were compared in both pacing modes. Results: We studied 42 consecutive patients, of whom 31 completed both tests (32 by AP, 40 by VP). Compared to AP, VP-MTWA SA had a sensitivity of 93%, specificity of 71%, negative predictive value of 92%, and positive predictive value of 72%. The results were concordant in 25 patients (80%, kappa = 0.62, P < 0.001). The noise level was significantly higher during VP than AP (1.4 +/- 0.8 vs 1 +/- 0.8, P< 0.01), and there was a trend toward a higher amplitude of TWA by VP (10.7 +/- 5.3 vs 7.8 +/- 3.9, P = 0.058). Conclusions: MTWA SA is m ore likely to be completed during VP than AP. Overall there was concordance between both tests. VP generates higher amplitudes and noise, and a higher percentage of nonnegative results. C1 VA Pittsburgh Healthcare Syst, Div Cardiol, Cardiac Electrophysiol Serv, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Shalaby, AA (reprint author), VA Pittsburgh Healthcare Syst, Div Cardiol, Cardiac Electrophysiol Serv, 111 C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@med.va.gov NR 12 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2007 VL 30 SU 1 BP S178 EP S182 PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 135VI UT WOS:000244181600040 PM 17302700 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. TI ISIS and AAPM: Encouraging best practices in spine treatment SO PAIN MEDICINE LA English DT Editorial Material ID PAIN TREATMENT; OUTCOMES 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 6 TC 0 Z9 0 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 JAN-FEB PY 2007 VL 8 IS 1 BP 4 EP 5 DI 10.1111/j.1526-4637.2007.00266.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138UY UT WOS:000244390000003 ER PT J AU Gallagher, RM Weiz-Bosna, M Gammaitoni, A AF Gallagher, Rollin M. Weiz-Bosna, Maripat Gammaitoni, Arnold TI Assessment of dosing frequency of sustained-release opioid preparations in patients with chronic nonmalignant pain SO PAIN MEDICINE LA English DT Article DE opioid; prospective study; daily dosing; chronic pain; long-acting ID THERAPY AB Objective. Many patients with moderate to severe chronic nonmalignant pain require dosing of long-acting opioids more frequently than recommended by the product's manufacturer. To accurately quantitate opioid dosing in clinical practice, daily dosing was prospectively assessed in pain clinic patients. Design. A single-center, 30-day, prospective, observational cohort study, approved by the hospital IRB. Patients. Forty-one evaluable adult outpatients receiving treatment with long-acting opioids for moderate to severe chronic nonmalignant pain. Outcome Measures. The primary measure was the daily number of consumed doses of prescribed long-acting opioid. Rescue medication use, average daily pain intensity, and patient-reported adverse events were also recorded. Results. The mean daily number of doses was 3.0 for oxycodone controlled release (CR), 2.9 for morphine CR, and 3.7 for methadone. For transdermal fentanyl, 50% of patients required dosing every 24-48 hours. Ninety-one percent of oxycodone CR-treated patients, 86% of morphine CR-treated patients, and 50% of fentanyl patch-treated patients required dosing more frequently than that recommended by the product's manufacturer. Patients who received oxycodone CR, morphine CR, and transdermal fentanyl required a mean of 2.9, 2.9, and 3.7 rescue doses per day, respectively. Conclusions. Many patients taking common long-acting opioids for chronic nonmalignant pain require dosing more frequently than recommended by product labeling, and take an additional 34 daily doses of rescue opioid, yet they continue to report moderate to severe pain. Newer opioid formulations that can provide sustained analgesia with convenient dosing are needed as well as a better understanding of the many additional factors that may influence opioid use patterns in patients with chronic pain. C1 Philadelphia VA Med Ctr, Pain Med Serv, Philadelphia, PA 19104 USA. Univ Penn, Ctr Pain Med Res & Policy, Philadelphia, PA 19104 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. RP Gallagher, RM (reprint author), Philadelphia VA Med Ctr, Pain Med Serv, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM rgallagh@mail.med.upenn.edu NR 8 TC 18 Z9 18 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD JAN-FEB PY 2007 VL 8 IS 1 BP 71 EP 74 DI 10.1111/j.1526-4637.2007.00260.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 138UY UT WOS:000244390000012 PM 17244106 ER PT J AU von Gunten, CF Eappen, S Cleary, JF Taylor, SG Moots, P Regevik, N Cleeland, C Celia, D AF von Gunten, Charles F. Eappen, Sarah Cleary, James Francis Taylor, Samuel G. Moots, Paul Regevik, Nina Cleeland, Charles Celia, David TI Flecainide for the treatment of chronic neuropathic pain: A Phase II trial SO PALLIATIVE MEDICINE LA English DT Article DE neuropathic; pain; cancer; flecainide; AIDS ID INTRAVENOUS LIDOCAINE; MANAGEMENT; OXIDATION; PLACEBO AB Background: Management of neuropathic pain is challenging. Medications that interfere with sodium channel transport, such as lidocaine, mexilitene and flecainide, are promising as analgesics. Objective: In a general population of patients with a working diagnosis of neuropathic pain, whether if flecainide produces enough of an improvement in pain to warrant further clinical study is determined. Design: Phase I/II prospective exploratory clinical trial. Eligible patients were observed for week 1, then 50 mg flecainide was administered twice daily for week 2 and then administered 100 mg twice daily for week 3. Setting/ Subjects: Multi-institutional members of the Eastern Co-operative Oncology Group. Patients had neuropathic pain diagnosed by their oncologists as defined by the International Association for the Study of Pain and a diagnosis of cancer or AIDS. Measurements: The Wisconsin Brief Pain Inventory was used. The primary endpoint was a decrease of 3 points (0-10 numerical scale) or a decrease of 50% in the worst pain rating at either day 15 or day 22 relative to the average of days I and 8 ratings. Results: Nineteen patients were registered for the study. Four patients were ineligible. Of the remaining 15, one was unevaluable due to incomplete pain rating. Four out of 14 patients had an average drop of 5 points or 53% in their worst pain ratings on a 0-10 numerical scale of pain. No patients withdrew from study because of toxicity. There were no life-threatening or lethal toxicities. All patients were alive at the time of the analysis. Conclusions: Flecainide produced a 30% response rate. Response in this study was defined to be highly relevant and clinically significant reduction in pain. The drug merits study in a randomized placebo-controlled trial. C1 [von Gunten, Charles F.] Northwestern Univ, Chicago, IL 60611 USA. [Eappen, Sarah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taylor, Samuel G.] Illinois Masonic Med Ctr, Chicago, IL 60657 USA. [Cleary, James Francis] Univ Wisconsin, Madison, WI USA. [Moots, Paul] Vanderbilt Univ, Nashville, TN USA. [Regevik, Nina] Raritan Bay Med Ctr, Perth Amboy, NJ USA. [Cleeland, Charles] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Celia, David] Evanston NW Healthcare, Evanston, IL USA. RP von Gunten, CF (reprint author), Ctr Palliat Studies, 4311 3rd Ave, San Diego, CA USA. EM cvongunten@sdhospice.org FU NCI NIH HHS [CA21115, CA49883, CA66636, CA49957, CA21076, CA23318] NR 28 TC 6 Z9 6 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2007 VL 21 IS 8 BP 667 EP 672 DI 10.1177/0269216307083031 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 252RC UT WOS:000252463300002 PM 18073252 ER PT J AU Ito, Y Lugea, A Pandol, SJ McCuskey, RS AF Ito, Yoshiya Lugea, Aurelia Pandol, Stephen J. McCuskey, Robert S. TI Substance P mediates cerulein-induced pancreatic microcirculatory dysfunction in mice SO PANCREAS LA English DT Article DE permeability; edema; perfusion; capillary ID NEUTROPHILS; MICROSCOPY; ACTIVATION; EDEMA; RAT; PERMEABILITY; DERANGEMENT; RECEPTOR AB Objectives: The present study was conducted to examine the contribution of substance P to the pancreatic microcirculatory dysfunction during acute pancreatitis. Methods: Pancreatitis was elicited by up to 6 hourly injections of cerulein (50 mu g/kg IP) in male C57B1/6 mice. At 0, 1, 3, and 6 hours after cerulein treatment, the pancreatic microvasculature in anesthetized mice was studied using established high-resolution in vivo microscopic methods. Results: Treatment of mice with cerulein for 6 hours caused a 30% decrease in capillary perfusion and the diameter of the capillaries and an increase in microvascular permeability (20%) and interstitial space (30-fold). The administration of the substance P receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) (2 mg/kg IP) minimized the pancreatic microcirculatory dysfunction 3 hours after cerulein treatment. The superfusion of substance P for 0.5 hours decreased the diameter (by 22%) and increased microvascular permeability (by 23%) along with interstitial space (22-fold increase). Blockade of substance P receptor attenuated substance P-induced pancreatic microcirculatory dysfunction. Conclusions: These results suggest that substance P mediates pancreatic microcirculatory dysfunction during the development of acute pancreatitis. C1 Univ Arizona, Coll Med, Dept Cell Biol & Anat, Tucson, AZ 85724 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP McCuskey, RS (reprint author), Univ Arizona, Coll Med, Dept Cell Biol & Anat, POB 245044, Tucson, AZ 85724 USA. EM mccuskey@email.arizona.edu FU NIAAA NIH HHS [1-U56-AA0114643]; NIDDK NIH HHS [R01 DK-59508]; PHS HHS [P50-A11999] NR 24 TC 7 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 2007 VL 34 IS 1 BP 138 EP 143 DI 10.1097/01.mpa.0000246663.30751.24 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 168CF UT WOS:000246499200018 PM 17198196 ER PT J AU Pandol, SJ Raraty, M AF Pandol, Stephen J. Raraty, Michael TI Pathobiology of alcoholic pancreatitis SO PANCREATOLOGY LA English DT Review DE alcohol; pancreatitis ID KAPPA-B ACTIVATION; ACID ETHYL-ESTER; NONOXIDATIVE ETHANOL METABOLITES; HEPATIC STELLATE CELLS; CERULEIN-INDUCED PANCREATITIS; CYTOSOLIC-FREE CALCIUM; PROTEIN-KINASE-C; ACINAR-CELLS; ANGIOTENSIN-II; TRYPSINOGEN ACTIVATION AB This paper provides a summary of the effects of alcohol abuse on the pathobiologic responses that occur during acute and chronic pancreatitis considering both the human disease and animal/tissue models. The effects are multiple and include ones on cell death leading to necrosis; on inflammation resulting in a sensitized response to pancreatic stress; and fibrosis through effects of ethanol on pancreatic stellate cells and the plasminogen system. Although the effects of alcohol are multiple and complex, it is likely that a combination of a few key effects on these pathobiologic responses drive the increased sensitivity of the pancreas to acute pancreatitis with pancreatic stress and the promotion of chronic pancreatitis with pancreatic injury occurring during acute pancreatitis. Copyright (c) 2007 S. Karger AG, Basel and IAP. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Dept Vet Affairs, Los Angeles, CA USA. Univ Liverpool, Royal Liverpool Univ Hosp, Div Surg & Oncol, Liverpool L69 3BX, Merseyside, England. RP Pandol, SJ (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM stephen.pandol@va.gov RI Raraty, Michael/B-5328-2013 NR 127 TC 44 Z9 45 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2007 VL 7 IS 2-3 BP 105 EP 114 DI 10.1159/000104235 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 192YV UT WOS:000248240900003 PM 17592222 ER PT J AU Gonzalez-Fernandez, MC Lezcano, E Ross, OA Gomez-Esteban, JC Gomez-Busto, F Velasco, F Alvarez-Alvarez, M Rodriguez-Martinez, MB Ciordia, R Zarranz, JJ Farrer, MJ Mata, IF de Pancorbo, MM AF Gonzalez-Fernandez, Maria C. Lezcano, Elena Ross, Owen A. Gomez-Esteban, Juan C. Gomez-Busto, Fernando Velasco, Fernando Alvarez-Alvarez, Maite Rodriguez-Martinez, Maria B. Ciordia, Roberto Zarranz, Juan J. Farrer, Matthew J. Mata, Ignacio F. de Pancorbo, Marian M. TI Lrrk2-associated parkinsonism is a major cause of disease in Northern Spain SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; LRRK2; dardarina; Spain; mutation ID AUTOSOMAL-DOMINANT PARKINSONISM; LRRK2 G2019S; SPANISH PATIENTS; MUTATIONS; COMMON; FAMILIES; FOUNDER; R1441G; GENE AB Herein we describe a comparative clinical and genetic study of Lrrk2-associated parkinsonism in Northern Spain. In our sample from the Basque region, Lrrk2 R1441G and G2019S account for 15 out of 50 kindreds (30%) with familial Parkinson's disease. We observe common founder haplotypes for both R 1441 G and G2019S carriers. Our findings highlight the importance of Lrrk2 parkinsonism in this population and may have important consequences for its extended Diaspora in North, Central and South Americas. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Gonzalez-Fernandez, Maria C.; Alvarez-Alvarez, Maite; Rodriguez-Martinez, Maria B.; de Pancorbo, Marian M.] Univ Basque Country, Dept Biol Celular, Banco de ADN, Serv Gen Invest Genom, Vitoria, Spain. [Gonzalez-Fernandez, Maria C.; Ross, Owen A.; Farrer, Matthew J.; Mata, Ignacio F.] Mayo Clin, Dept Neurosci, Jacksonville, FL USA. [Lezcano, Elena; Gomez-Esteban, Juan C.; Velasco, Fernando; Ciordia, Roberto] Hosp Cruces, Serv Neurol, Baracaldo, Spain. [Gomez-Busto, Fernando] Residencia Tercera Edad San Prudencio Ayuntamient, Serv Geriatr, Vitoria, Spain. [Mata, Ignacio F.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Mata, IF (reprint author), Geriatr Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM nachofm@u.washington.edu RI Zarranz, Juan Jose/E-2955-2012; Gomez, Juan Carlos/E-3020-2012; Ross, Owen/D-7573-2013; OI M. de Pancorbo, Marian/0000-0002-8081-0702; MARTINEZ DE PANCORBO, MARIA DE LOS ANGELES/0000-0002-7408-6068; Fernandez Mata, Ignacio/0000-0003-1198-0633 FU NINDS NIH HHS [P50 #NS40256] NR 20 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2007 VL 13 IS 8 BP 509 EP 515 DI 10.1016/j.parkreldis.2007.04.003 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 242VE UT WOS:000251753500009 PM 17540608 ER PT J AU Perner, S Demichelis, F Beroukhim, R Mosquera, JM Tomlins, SA Kuefer, R Meyerson, ML Lee, C Chinnaiyan, AM Rubin, MA AF Perner, S. Demichelis, F. Beroukhim, R. Mosquera, J.-M. Tomlins, S. A. Kuefer, R. Meyerson, M. L. Lee, C. Chinnaiyan, A. M. Rubin, M. A. TI TMPRSS2-ERG fusion caused by a intronic deletion provides insight into the heterogeneity of prostate cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ulm Klinikum, Inst Pathol, Ulm, Germany. Povo, ITCirst, SRA Div, Bioinformat Grp, Trento, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard & MIT, Broad Inst, Cambridge, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Ulm Klinikum, Urol Klin, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2007 VL 203 IS 5 MA 75 BP 278 EP 278 PG 1 WC Pathology SC Pathology GA 179TF UT WOS:000247312300066 ER PT J AU Perner, S Mosquera, JM Demichelis, F Hofer, MD Paris, PL Chinnaiyan, AM De Marzo, AM Rubin, MA AF Perner, S. Mosquera, J.-M. Demichelis, F. Hofer, M. D. Paris, P. L. Chinnaiyan, A. M. De Marzo, A. M. Rubin, M. A. TI TMPRSS2-ERG fusion prostate cancer: an early molecular event in the development of prostate cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ulm, Ulm, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Baltimore, MD USA. Harvard Univ, MIT, Broad Inst, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2007 VL 203 IS 5 MA 184 BP 319 EP 320 PG 2 WC Pathology SC Pathology GA 179TF UT WOS:000247312300169 ER PT J AU Perner, S Mosquera, JM Demichelis, F Hofer, MD Bismar, TA Chinnaiyan, AM Rubin, MA AF Perner, S. Mosquera, J. M. Demichelis, F. Hofer, M. D. Bismar, T. A. Chinnaiyan, A. M. Rubin, M. A. TI Morphological features of TMPRSS2-ERG fusion prostate cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ulm, Ulm, Germany. Povo, ITCirst, SRA Div, Bioinformat Grp, Trento, Italy. McGill Univ, Montreal, PQ, Canada. Univ Michigan, Ann Arbor, MI 48109 USA. Harvard & MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Ctr Comprehens Canc, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2007 VL 203 IS 5 MA 259 BP 348 EP 348 PG 1 WC Pathology SC Pathology GA 179TF UT WOS:000247312300239 ER PT S AU You, LW Zhang, P Boden, M Brusic, V AF You, Liwen Zhang, Ping Boden, Mikael Brusic, Vladimir BE Rajapakse, JC Schmidt, B Volkert, G TI Understanding prediction systems for HLA-binding peptides and T-Cell epitope identification SO PATTERN RECOGNITION IN BIOINFORMATICS, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 2nd International Workshop on Pattern Recognition in Bioinformatics CY OCT 01-02, 2007 CL Singapore, SINGAPORE SP IAPR ID VECTOR MACHINES; MHC MOLECULES; MODELS; SURVIVIN AB Peptide binding to HLA molecules is a critical step in induction and regulation of T-cell mediated immune responses. Because of combinatorial complexity of immune responses, systematic studies require combination of computational methods and experimentation. Most of available computational predictions are based on discriminating binders from non-binders based on use of suitable prediction thresholds. We compared four state-of-the-art binding affinity prediction models and found that nonlinear models show better performance than linear models. A comprehensive analysis of HLA binders (A*0101, A*0201, A*0301, A*1101, A*2402, B*0702, B*0801 and B*1501) showed that non-linear predictors predict peptide binding affinity with high accuracy. The analysis of known T-cell epitopes of survivin and known HIV T-cell epitopes showed lack of correlation between binding affinity and immunogenicity of HLA-presented peptides. T-cell epitopes, therefore, can not be directly determined from binding affinities by simple selection of the highest affinity binders. C1 [You, Liwen] Halmstad Univ, Sch Informat Sci Comp & Elect Engn, Halmstad, Sweden. [You, Liwen] Lund Univ, Dept Theoret Phys, Lund, Sweden. [You, Liwen; Zhang, Ping; Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld, Australia. [Boden, Mikael] Univ Queensland, Sch Informat Technol & Elect Engn, Brisbane, Qld, Australia. [Brusic, Vladimir] Cancer Vaccine Ctr, Dana Farber Cancer Inst, Boston, MA 02215 USA. RP You, LW (reprint author), Halmstad Univ, Sch Informat Sci Comp & Elect Engn, Halmstad, Sweden. EM liwen@thep.lu.se; p.zhang2@uq.edu.au; m.boden@uq.edu.au; vladimir_brusic@dfci.harvard.edu RI Zhang, Ping/E-5306-2010; Boden, Mikael/A-6030-2010 OI Boden, Mikael/0000-0003-3548-268X FU National Research School in Genomics and Bioinformatics, Sweden; EC [FP6-2004-IST-4, 028069] FX LY was supported by the National Research School in Genomics and Bioinformatics, Sweden. The authors acknowledge the support of the ImmunoGrid project, EC contract FP6-2004-IST-4, No. 028069. NR 26 TC 7 Z9 8 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-75285-1 J9 LECT NOTES COMPUT SC PY 2007 VL 4774 BP 337 EP 348 PG 12 WC Biochemical Research Methods; Computer Science, Artificial Intelligence; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BGY27 UT WOS:000251314800032 ER PT J AU Kearney, SL Nemeth, E Neufeld, EJ Thapa, D Ganz, T Weinstein, DA Cunningham, MJ AF Kearney, Susan L. Nemeth, Elizabeta Neufeld, Ellis J. Thapa, Dharma Ganz, Tomas Weinstein, David A. Cunningham, Melody J. TI Urinary hepcidin in congenital chronic anemias SO PEDIATRIC BLOOD & CANCER LA English DT Article DE ineffective erythropoiesis; iron overload; sickle cell disease; thalassemia ID PEPTIDE HEPCIDIN; CHRONIC DISEASE; IRON OVERLOAD; HEMOCHROMATOSIS; INFLAMMATION; EXPRESSION; PROTEIN; LIVER; GENE; MICE AB Background. Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias. Procedure. Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion. Results. In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P = 0.013 and < 0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count. Conclusions. This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. in thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA. RP Cunningham, MJ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Fegan 703, Boston, MA 02115 USA. EM Melody.Cunningham@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; Thapa, Dharma/C-2854-2012 FU NCRR NIH HHS [RR017560, M01 RR02172]; NHLBI NIH HHS [K24 HL004184, U01 HL065260]; NIDDK NIH HHS [DK065029] NR 16 TC 90 Z9 93 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2007 VL 48 IS 1 BP 57 EP 63 DI 10.1002/pbc.20616 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 111BF UT WOS:000242425000012 PM 16220548 ER PT J AU Mikati, MA Chaaban, HR Karam, PE Krishnamoorthy, KS AF Mikati, Mohamad A. Chaaban, Hala R. Karam, Pascal E. Krishnamoorthy, Kalpathy S. TI Brain malformation and infantile spasms in a SCAD deficiency patient SO PEDIATRIC NEUROLOGY LA English DT Article AB This report presents a case of short-chain acyl-coenzyme A (CoA) dehydrogenase deficiency with a previously unreported presentation with brain malformations and infantile spasms. This female infant developed repeated tonic clonic seizures at the age of 3(1)/(2) months. She subsequently developed West syndrome at the age of 4 months. Her electroencephalogram disclosed hypsarrhythmia, and video-electroencephalographic monitoring confirmed the presence of infantile spasms. Magnetic resonance imaging revealed a small midline frontal meningocele, abnormal cortical gyration, and partial agenesis of the corpus callosum consistent with neuronal migrational disorder. Metabolic evaluation indicated ethylmalonic acidemia. Muscle biopsy with enzymatic assay of short-chain acyl-coenzyme A revealed low enzymatic activity confirming the diagnosis of short-chain acylcoenzyme A dehydrogenase deficiency. To our knowledge, this is the first report of the coexistence of short-chain acyl-coenzyme A dehydrogenase deficiency, infantile spasms, and brain malformation. We conclude that short-chain acyl-coenzyme A dehydrogenase deficiency should be considered in the differential diagnosis of gyral abnormality, corpus callosal hypoplasia, and infantile spasms. (c) 2007 by Elsevier Inc. All rights reserved. C1 Amer Univ Beirut, Dept Pediat, Adult & Pediat Epilepsy Program, Med Ctr, Beirut, Lebanon. Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mikati, MA (reprint author), Amer Univ Beirut, Dept Pediat, Adult & Pediat Epilepsy Program, Med Ctr, Beirut, Lebanon. EM mamikati@aub.edu.lb OI Chaaban, Hala/0000-0002-7112-564X NR 6 TC 8 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 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JAN PY 2007 VL 36 IS 1 BP 48 EP 50 DI 10.1016/j.pediatrneurol.2006.08.008 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 119ZJ UT WOS:000243052700009 PM 17162197 ER PT J AU Freedman, S Laposata, M AF Freedman, Steven Laposata, Michael TI A unifying theory to explain how CFTR leads to the lipid abnormalities in CF and altered inflammatory signaling SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT 21st Annual North American Cystic Fibrosis Conference CY OCT 03-06, 2007 CL Anaheim, CA ID CYSTIC-FIBROSIS C1 [Freedman, Steven] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Med, Boston, MA 02215 USA. [Laposata, Michael] Massachusetts Gen Hosp, Harvard Med Sch, Med Lab, Boston, MA USA. RP Freedman, S (reprint author), Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Med, Boston, MA 02215 USA. NR 4 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 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 BP 184 EP 185 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000064 ER PT J AU Fracchia, MS Kinane, TB Dorkin, H Stuart, L AF Fracchia, M. S. Kinane, T. B. Dorkin, H. Stuart, L. TI Using a Caenorhabditis elegans model of cystic fibrosis to understand the role of the innate immune system in limiting P. aeruginosa and B. cepacia infections SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Fracchia, M. S.; Kinane, T. B.; Dorkin, H.; Stuart, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 156 BP 255 EP 256 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000233 ER PT J AU Hale, JE Parad, RB O'Sullivan, BP Quizon, AL Martin, T Yee, W Dorkin, HL Comeau, AM AF Hale, J. E. Parad, R. B. O'Sullivan, B. P. Quizon, A. L. Martin, T. Yee, W. Dorkin, H. L. Comeau, A. M. TI Quality measures enhanced by short and long-term follow up in a newborn screening program collaborating with multiple centers SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Hale, J. E.; Parad, R. B.; Comeau, A. M.] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica, MA USA. [O'Sullivan, B. P.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Quizon, A. L.] Baystate Med Ctr, Springfield, MA USA. [Yee, W.] Tufts Univ New England Med Ctr, Boston, MA 02111 USA. [Dorkin, H. L.] Massachusetts Gen Hosp, Boston, MA USA. [Parad, R. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Parad, Richard/E-8559-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 212 BP 276 EP 276 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000289 ER PT J AU AL-Turkmani, M Andersson, C Savaille, JE Cluette-Brown, JE Alturkmani, R Freedman, SD Laposata, M AF AL-Turkmani, M. Andersson, C. Savaille, J. E. Cluette-Brown, J. E. Alturkmani, R. Freedman, S. D. Laposata, M. TI Increased metabolism of linoleic acid through the N-6 pathway in cultured cells with a cystic fibrosis phenotype is corrected by docosahexaenoic acid (DHA) supplementation SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [AL-Turkmani, M.; Savaille, J. E.; Cluette-Brown, J. E.; Alturkmani, R.; Laposata, M.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Andersson, C.; Freedman, S. D.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 492 BP 378 EP 379 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000569 ER PT J AU AL-Turkmani, M Freedman, SD Laposata, M AF AL-Turkmani, M. Freedman, S. D. Laposata, M. TI Decreased levels of linoleic acid and docosahexaenoic acid (DHA) are associated with increased cellular uptake and subsequent mobilization in cultured cells with a cystic fibrosis phenotype SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [AL-Turkmani, M.; Laposata, M.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Freedman, S. D.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, 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 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 493 BP 379 EP 379 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000570 ER PT J AU Zaman, MM Andersson, C Cluette-Brown, JE Laposata, M Freedman, SD AF Zaman, M. M. Andersson, C. Cluette-Brown, J. E. Laposata, M. Freedman, S. D. TI Decreased PEMT activity in CF mice is dependent on choline status SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Zaman, M. M.; Andersson, C.; Freedman, S. D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cluette-Brown, J. E.; Laposata, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 495 BP 379 EP 380 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000572 ER PT J AU Habal, H AL-Turkmani, M Freedman, S Laposata, M AF Habal, H. AL-Turkmani, M. Freedman, S. Laposata, M. TI Increased uptake of saturated, monounsaturated, and polyunsaturated fatty acids into cells with a cystic fibrosis phenotype, and its downregulation by docosahexaenoic acid (DHA) supplementation SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Habal, H.; AL-Turkmani, M.; Laposata, M.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Freedman, S.] Harvard Med Sch, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 514 BP 387 EP 387 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000591 ER PT J AU Ollero, M Freedman, S Zaman, MM Blanco, PG Andersson, C Urman, Y Laposata, M AF Ollero, M. Freedman, S. Zaman, M. M. Blanco, P. G. Andersson, C. Urman, Y. Laposata, M. TI DHA increases the localization of 18 : 2n-6 and 18 : 3n-3 into phospholipids in CFTR-/- mice but not in wild-type SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Ollero, M.] INSERM, U845, Paris, France. [Ollero, M.; Freedman, S.; Zaman, M. M.; Blanco, P. G.; Andersson, C.; Urman, Y.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Laposata, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 523 BP 390 EP 391 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000600 ER PT J AU Newburg, DS Walker, WA AF Newburg, David S. Walker, W. Allan TI Protection of the neonate by the innate immune system of developing gut and of human milk SO PEDIATRIC RESEARCH LA English DT Review ID BREAST-FED INFANTS; INTESTINAL HOST-DEFENSE; CELL ALPHA-DEFENSINS; NECROTIZING ENTEROCOLITIS; GASTROINTESTINAL-TRACT; BACTERIAL-COLONIZATION; SHIGELLA-FLEXNERI; GROWTH-FACTOR; STEM-CELLS; IN-VITRO AB The neonatal adaptive immune system, relatively naive to foreign antigens, requires synergy with the innate immune system to protect the intestine. Goblet cells provide mucins, Paneth cells produce antimicrobial peptides, and dendritic cells (DCs) present luminal antigens. Intracellular signaling by Toll-like receptors (TLRs) elicits chemokines and cytokines that modulate inflammation. Enteric neurons and lymphocytes provide paracrine and endocrine signaling. However, full protection requires human milk. Breast-feeding reduces enteric infection and may reduce chronic disease in later life. Although human milk contains significant secretory immunoglobulin A (sIgA), most of its protective factors are constitutively expressed. Multifunctional milk components are nutrients whose partial digestion products inhibit pathogens. Cytokines, cytokine receptors, TLR agonists and antagonists, hormones, anti-inflammatory agents, and nucleotides in milk modulate inflammation. Human milk is rich in glycans (complex carbohydrates): As prebiotics, indigestible glycans stimulate colonization by probiotic organisms, modulating mucosal immunity and protecting against pathogens. Through structural homology to intestinal cell surface receptors, glycans inhibit pathogen binding, the essential first step of pathogenesis. Bioactive milk components comprise an innate immune system of human milk whereby the mother protects her nursing infant. Interactions between human milk glycans, intestinal micro-flora, and intestinal mucosa surface glycans underlie ontogeny of innate mucosal immunity, pathobiology of enteric infection, and inflammatory bowel diseases. C1 Massachusetts Gen Hosp, Program Glycobiol Pediat Gastroenterol & Nutr, Glycobiol & Mucosal Immunol Labs, Pediat Gastroenterol & Nutr Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, Program Glycobiol Pediat Gastroenterol & Nutr, Glycobiol & Mucosal Immunol Labs, Pediat Gastroenterol & Nutr Unit, 114 16th St, Charlestown, MA 02129 USA. EM dnewburg@partners.org FU NICHD NIH HHS [P01-HD13021, R37-HD12437]; NIDDK NIH HHS [P30 DK040561-11, P30 DK040561, P30-DK40561] NR 94 TC 188 Z9 199 U1 7 U2 47 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2007 VL 61 IS 1 BP 2 EP 8 DI 10.1203/01.pdr.0000250274.68571.18 PG 7 WC Pediatrics SC Pediatrics GA 119WS UT WOS:000243045700002 PM 17211132 ER PT J AU Horwitz, SM Kelleher, KJ Stein, REK Storfer-Isser, A Youngstrom, EA Park, ER Heneghan, AM Jensen, PS O'Connor, KG Hoagwood, KE AF McCue Horwitz, Sarah Kelleher, Kelly J. Stein, Ruth E. K. Storfer-Isser, Amy Youngstrom, Eric A. Park, Elyse R. Heneghan, Amy M. Jensen, Peter S. O'Connor, Karen G. Eaton Hoagwood, Kimberly TI Barriers to the identification and management of psychosocial issues in children and maternal depression SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Society/Society-for-Pediatric-Research CY MAY 14-17, 2005 CL Washington, DC SP Pediat Acad Soc, Soc Pediat Res DE barriers; maternal depression; child psychosocial problems; primary care ID CARE PEDIATRICIANS ROLES; RESPONSE RATES; MENTAL-HEALTH; PERCEIVED RESPONSIBILITIES; OFFICE SETTINGS; SERVICE USE; RECOGNITION; DISORDERS; PREVALENCE; COMPONENTS AB CONTEXT. Child psychosocial issues and maternal depression are underidentified and undertreated, but we know surprisingly little about the barriers to identification and treatment of these problems by primary care pediatricians. OBJECTIVES. The purpose of this work was to determine whether (1) perceived barriers to care for children's psychosocial issues and maternal depression aggregate into patient, physician, and organizational domains, (2) barrier domains are distinct for mothers and children, and (3) physician, patient, and practice/organizational characteristics are associated with different barrier domains for children and mothers. METHODS. We conducted a cross-sectional survey of the 50 818 US nonretired members of the American Academy of Pediatrics. Of a random sample of 1600 members, 832 (745 nontrainee members) responded. This was a mailed 8-page survey with no patients and no intervention. We measured physician assessment of barriers to providing psychosocial care for children's psychosocial problems and maternal depression. RESULTS. Pediatricians frequently endorse the lack of time to treat mental health problems ( 77.0%) and long waiting periods to see mental health providers (74.0%) as the most important barriers to the identification and treatment of children's psychosocial problems. For maternal depression, pediatricians most often endorsed lack of training in treatment (74.5%) and lack of time to treat (64.3%) as important barriers. Pediatricians' reports of barriers clustered into physician and organizational domains. Physician domains were distinct for children and mothers, but organizational domains were not. Several physician and practice characteristics are significantly associated with the 4 barrier scales, and different characteristics (eg, sociodemographic, attitudinal, and practice features) were related to each barrier area. CONCLUSIONS. Pediatricians endorse a wide range of barriers with respect to the diagnosis and treatment of children's mental health problems and maternal depression. The specificity of factors relating to various barrier areas suggests that overcoming barriers to the identification and treatment of child mental health problems and maternal depression in primary care pediatrics is likely to require a multifaceted approach that spans organizational, physician, and patient issues. In addition, comprehensive interventions will likely require social marketing approaches designed to engage diverse audiences of clinicians and their patients to participate. C1 Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. Montefiore Med Ctr, Sch Med, New York, NY USA. Ohio State Univ, Coll Med & Publ Hlth, Dept Pediat, Columbus, OH USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Amer Acad Pediat, Dept Res, Elk Grove Village, IL USA. RP Horwitz, SM (reprint author), Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Room W-G 72,10900 Euclid Ave, Cleveland, OH 44106 USA. EM sarah.horwitz@case.edu OI Jensen, Peter/0000-0003-2387-0650 NR 44 TC 83 Z9 83 U1 2 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2007 VL 119 IS 1 BP E208 EP E218 DI 10.1542/peds.2005-1997 PG 11 WC Pediatrics SC Pediatrics GA 121YB UT WOS:000243191800030 PM 17200245 ER PT S AU Kraemer, B Schellenberg, GD AF Kraemer, Brian Schellenberg, Gerard D. BE Dwyer, DS TI Using Caenorhabditis elegans models of neurodegenerative disease to identify neuroprotective strategies SO PHARMACOLOGY OF NEUROGENESIS AND NEUROENHANCEMENT SE International Review of Neurobiology LA English DT Review ID BETA-AMYLOID PEPTIDE; NECROTIC CELL-DEATH; ALZHEIMERS-DISEASE; C-ELEGANS; ALPHA-SYNUCLEIN; NEURONAL DEGENERATION; OXIDATIVE STRESS; PROTEIN AGGREGATION; INVERTEBRATE MODELS; MUTANT C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Kraemer, B (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. NR 65 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-373678-9 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2007 VL 77 BP 219 EP 246 DI 10.1016/S0074-7742(06)77007-6 PG 28 WC Neurosciences SC Neurosciences & Neurology GA BFP47 UT WOS:000243623500007 PM 17178476 ER PT J AU Zickmund, S AF Zickmund, Susan TI Deliberation, phronesis, and authenticity: Heidegger's early conception of rhetoric SO PHILOSOPHY AND RHETORIC LA English DT Article ID ARISTOTLE C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Dept Med Commun, Pittsburgh, PA 15206 USA. RP Zickmund, S (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Dept Med Commun, Pittsburgh, PA 15206 USA. NR 15 TC 3 Z9 4 U1 0 U2 1 PU PENN STATE UNIV PRESS PI UNIVERSITY PK PA 820 NORTH UNIV DRIVE, U S B 1, STE C, UNIVERSITY PK, PA 16802 USA SN 0031-8213 J9 PHILOS RHETORIC JI Philos. Rhetor. PY 2007 VL 40 IS 4 BP 406 EP 415 PG 10 WC Literature; Philosophy SC Literature; Philosophy GA 255FT UT WOS:000252643800005 ER PT J AU Akilov, OE Kosaka, S O'Riordan, K Hasan, T AF Akilov, Oleg E. Kosaka, Sachiko O'Riordan, Katie Hasan, Tayyaba TI Photodynamic therapy for cutaneous leishmaniasis: the effectiveness of topical phenothiaziniums in parasite eradication and Th1 immune response stimulation SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID MICE; PHOTOSENSITIZER; RESISTANCE; EFFICACY; REFUGEE; ACID AB Photodynamic therapy (PDT) is emerging as a therapeutic modality in the clinical management of cutaneous leishmaniasis (CL). The efficacy of PDT against CL has been demonstrated previously with aminolevulinic acid, although the prolonged terms of therapy were less than ideal, and the search for new photosensitizers (PS) is ongoing. However, phenothiaziniums have demonstrated high parasiticidal effects in vitro. The subject of our investigation is the in vivo activity of two PS, 5-ethylamino-9-diethylaminobenzo[a] phenoselenazinium chloride (EtNBSe) and (3,7-Bis(N, N-dibutylamino) phenothiazinium bromide (PPA904). The results of our comparative analysis of the efficacy of these two phenothiazinium analogues demonstrated a high antiparasitic activity of EtNBSe in vitro, and the higher efficacy of PPA904 in a mouse model of CL. The kinetics of photodestruction are different in parasite and mammalian cells, and with both dyes, the macrophages are more susceptible to photodynamic effects than L. major parasites. As the number of parasites in the lesions undergoes a biphasic change, temporarily increasing on days 2-4 and decreasing on days 5-7, more than one treatment is required within an interval of 5 to 7 days. We have also shown that PPA904-PDT can provide an immunomodulating, dose-dependent efflux on IL-12p70 production. This mechanism could be responsible for promoting a more rapid healing in PPA904-PDT treated mice. Our initial data indicate that phenothiaziniums exhibit a high parasiticidal effect in vivo against CL; this finding may be of use in establishing curative PDT regimens for future clinical trials. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. EM thasan@partners.org NR 29 TC 29 Z9 31 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2007 VL 6 IS 10 BP 1067 EP 1075 DI 10.1039/b703521g PG 9 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 217CJ UT WOS:000249925700012 PM 17914480 ER PT J AU O'Riordan, K Akilov, OE Chang, SK Foley, JW Hasan, T AF O'Riordan, Katie Akilov, Oleg E. Chang, Sung K. Foley, James W. Hasan, Tayyaba TI Real-time fluorescence monitoring of phenothiazinium photosensitizers and their anti-mycobacterial photodynamic activity against Mycobacterium bovis BCG in in vitro and in vivo models of localized infection SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID PHOTOBACTERICIDAL ACTIVITY; CUTANEOUS LEISHMANIASIS; STAPHYLOCOCCUS-AUREUS; TOLUIDINE BLUE; THERAPY; TUBERCULOSIS; PHOTOINACTIVATION; PHOTOTOXICITY; THIORIDAZINE; STRAINS AB An objective was to explore the photodynamic activity of two cationic photosensitizers (PS) (benzo[a] phenothiazinium chloride and benzo[a] phenoselenazinium chloride) against Mycobacterium bovis BCG both in vitro and in a murine model of BCG-granuloma. The hypothesis being tested in this study was that cationic molecules could best interact with the negatively charged membrane of BCG as a model for mycobacterial infection. Cells in culture were incubated with various concentrations of PS and subsequently illuminated using a 635 nm diode laser. Dark-and light-induced killing profiles were generated as a function of fluence and dye concentration. In vivo, local injection of the PS into subcutaneous Mycobacterium-induced granuloma sites in murine model was followed by red light illumination of the same area. A special microscope was fabricated for real-time in vivo fluorescent microscopy to monitor EtNBS delivery to subcutaneous murine granulomata. Both PS demonstrated good in vitro antimycobacterial photodynamic activity with varying degrees of toxicity under dark conditions. Real time in vivo monitoring of benzophenothiazine chloride in the mouse model indicated that this fluorescent photosensitizer was delivered rapidly to the subcutaneous granuloma site. In vivo, photosensitizer specific dark-and photo-toxicities depended on the structure, concentration of the photosensitizer and the light dose utilized. Cationic phenothiazine photosensitizers are promising candidates for use in anti-mycobacterial PDT for localized diseases such as cutaneous and pulmonary C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Rowland Inst Harvard, Cambridge, MA USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. EM thasan@partners.org NR 36 TC 13 Z9 14 U1 1 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2007 VL 6 IS 10 BP 1117 EP 1123 DI 10.1039/b707962a PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 217CJ UT WOS:000249925700018 PM 17914486 ER PT J AU Mroz, P Tegos, GP Gali, H Wharton, T Sarna, T Hamblin, MR AF Mroz, Pawel Tegos, George P. Gali, Hariprasad Wharton, Tim Sarna, Tadeusz Hamblin, Michael R. TI Photodynamic therapy with fullerenes SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID MESOSUBSTITUTED CATIONIC PORPHYRINS; GRAM-NEGATIVE BACTERIA; CARCINOMA-CELL LINE; SINGLET OXYGEN; PHOTOINDUCED CYTOTOXICITY; FUNCTIONALIZED FULLERENES; PHOTOSENSITIZED OXIDATION; BIOLOGICAL APPLICATIONS; HUMAN KERATINOCYTES; LIPOPHILIC CATIONS AB Fullerenes are a class of closed- cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended pi-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Lynntech Inc, College Stn, TX USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Jagiellonian Univ, Dept Biophys, Krakow, Poland. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R43 CA103268, R43CA103268]; NIAID NIH HHS [R01 AI050875, R01 AI050875-05A1, R01AI050875, R01CA/AI838801, R44 AI068400, R44AI68400] NR 92 TC 129 Z9 132 U1 2 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2007 VL 6 IS 11 BP 1139 EP 1149 DI 10.1039/b711141j PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 226KY UT WOS:000250589200009 PM 17973044 ER PT J AU Vazquez, A AF Vazquez, Alexel TI Impact of memory on human dynamics SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE human dynamics; memory; activity patterns ID HEAVY TAILS; NETWORKS; BURSTS AB Our experience of web access slowing down is a consequence of the aggregated web access pattern of web users. This is just one example among several human-oriented services which are strongly affected by human activity patterns. Recent empirical evidence is indicating that human activity patterns are characterized by power-law distributions of inter-event times, where large fluctuations rather than regularity is the common case. I show that this temporal heterogeneity can be explained by two mechanisms: (i) humans have some perception of their past activity rate and (ii) based on that they react by accelerating or reducing their activity rate. Using these two mechanisms I explain the inter-event time statistics of Darwin's and Einstein's correspondence and the email activity within an university environment. Moreover, they are typical examples of the accelerating and reducing class, respectively. These results are relevant to the system design of human-oriented services (c) 2006 Elsevier B.V. All rights reserved. C1 Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Complex Networks Res, Notre Dame, IN 46556 USA. RP Vazquez, A (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM avazquel@nd.edu NR 13 TC 60 Z9 68 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JAN 1 PY 2007 VL 373 BP 747 EP 752 DI 10.1016/j.physa.2006.04.060 PG 6 WC Physics, Multidisciplinary SC Physics GA 109NU UT WOS:000242316000064 ER PT J AU Jabre, JF Salzsieder, BT Gnemi, KE AF Jabre, Joe F. Salzsieder, Byron T. Gnemi, Kenneth E. TI Criterion validity of the NC-stat automated nerve conduction measurement instrument SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE EMG; nerve conduction; peroneal; posterior tibial; NC-stat; criterion; validity ID DIABETIC NEUROPATHY; CMAP AMPLITUDE; RELIABILITY; REPRODUCIBILITY; POLYNEUROPATHY; DEVICE; TESTS; ULNAR AB The purpose of this study is to assess the criterion validity of peroneal and posterior tibial nerve conduction measurements obtained with the NC-stat system. Sixty patients referred to the Boston VA EMG laboratory were enrolled. Each subject had a full study of the lower extremity performed using traditional EMG equipment prior to obtaining the NC-stat measurements. These included peroneal and posterior tibial distal motor latency (DML), amplitude (AMP) and F-wave latency (FLAT) measurements. Excellent criterion validity was demonstrated for the peroneal and posterior tibial FLATs and the peroneal AMP. Acceptable criterion validity was identified in the peroneal DML and the posterior tibial AMP. The validity of the posterior tibial DML could not be demonstrated. With the exception of the peroneal DML, criterion validity was maintained in a sub-group analysis of the 50% most abnormal parameter values. The comparability of NCS performed with the NC-stat and in traditional settings has been demonstrated for motor studies of the median and ulnar nerves in previous studies. This study shows that the technology used by the NC-stat for studying the peroneal and posterior tibial nerves compares favorably as well with that obtained with traditional EMG equipment used under neurologist supervision. C1 Boston VA Healthcare Syst, Neurol Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Jabre, JF (reprint author), Boston VA Healthcare Syst, Neurol Serv, Boston, MA USA. EM jfj@bu.edu NR 31 TC 8 Z9 8 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 J9 PHYSIOL MEAS JI Physiol. Meas. PD JAN PY 2007 VL 28 IS 1 BP 95 EP 104 DI 10.1088/0967-3334/28/1/009 PG 10 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA 129SP UT WOS:000243750700009 PM 17151423 ER PT J AU Craff, MN Zeballos, JL Johnson, TS Ranka, MP Howard, R Motarjem, P Randolph, MA Winograd, JM AF Craff, Melody N. Zeballos, Jose L. Johnson, Timothy S. Ranka, Milan P. Howard, Robert Motarjem, Pejman Randolph, Mark A. Winograd, Jonathan M. TI Embryonic stem cell-derived motor neurons preserve muscle after peripheral nerve injury SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Peripheral-Nerve CY JAN 15-16, 2005 CL San Juan, PR SP Amer Soc Peripheral Nerve ID NEUROMUSCULAR-JUNCTION; NCAM; EXPRESSION; IDENTITY; SIGNALS; MICE AB Background: The potential of motor neuron progenitor cell transplants to preserve muscle tissue after denervation was studied in in vivo and in vitro adult mammalian model of peripheral nerve injury. Methods: Embryonic stem cells were differentiated to induce cholinergic motor neuron progenitors. Flourescent-labeled progenitor cells were injected into the gastrocnemius muscle of Sprague-Dawley rats (n = 10) after denervation by ipilateral sciatic nerve transection. Control rats received injections of either a phosphate-buffered saline solution only (n = 12), murine embryonic fibroblast (STO) cells (n = 6), or undifferentiated embryonic stem cells (n = 6). Muscles were weighed and analyzed at 7 and 21 days using histology, histomorphometry, and immunostaining. Results: Seven days after progenitor cell transplant, both muscle mass and myocyte cross-sectional area were preserved, compared with control muscles, which demonstrated muscle mass reduction to 70 percent and reduction of cross-sectional area to 72 percent of normal. Fluorescent microscopy of transplanted muscles confirmed the presence of motor neuron progenitors. Presynaptic neuronal staining of the transplants overlapped with alpha-bungarotoxin-labeled muscle fibers, revealing the presence of new neuromuscular junctions. By 21 days, muscle atrophy in the experimental muscles was equal to that of controls and no transplanted cells were observed. Co-culture of the motor neuron progenitor cells and myocytes also demonstrated new neuromuscular junctions by immunofluorescence. Conclusions: Transplanted motor neuron progenitors prevent muscle atrophy after denervation for a brief time. These progenitor cell transplants appear to form new neuromuscular junctions with denervated muscle fibers in vivo and with myocytes in vitro. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Plast Surg,Plast Surg Res Lab, Boston, MA 02114 USA. RP Winograd, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Plast Surg,Plast Surg Res Lab, WACC 453, Boston, MA 02114 USA. EM Jwinograd@partners.org NR 18 TC 17 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2007 VL 119 IS 1 BP 235 EP 245 DI 10.1097/01.prs.0000244863.71080.f0 PG 11 WC Surgery SC Surgery GA 120OP UT WOS:000243094700032 PM 17255679 ER PT J AU Bergmeier, W Wagner, DD AF Bergmeier, Wolfgang Wagner, Denisa D. BE Michelson, AD TI Inflammation SO PLATELETS, 2ND EDITION LA English DT Article; Book Chapter ID VON-WILLEBRAND-FACTOR; NECROSIS-FACTOR-ALPHA; CIRCULATING ACTIVATED PLATELETS; WEIBEL-PALADE BODIES; SOLUBLE P-SELECTIN; THROMBOTIC THROMBOCYTOPENIC PURPURA; INTERCELLULAR-ADHESION MOLECULE-1; MONOCYTE CHEMOTACTIC PROTEIN-1; ENDOTHELIAL CELL-INTERACTIONS; ACUTE MYOCARDIAL-INFARCTION/ C1 [Bergmeier, Wolfgang; Wagner, Denisa D.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bergmeier, W (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02215 USA. NR 162 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046586-9 PY 2007 BP 713 EP 726 DI 10.1016/B978-012369367-9/50801-6 PG 14 WC Hematology SC Hematology GA BCR96 UT WOS:000311226400041 ER PT J AU Kuter, DJ AF Kuter, David J. BE Michelson, AD TI Platelet Growth Factors SO PLATELETS, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; FACTOR PEG-RHUMGDF; IMMUNE THROMBOCYTOPENIC PURPURA; ACUTE MYELOID-LEUKEMIA; MARROW STROMAL CELLS; MPL-DEFICIENT MICE; PHASE-I TRIAL; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; HUMAN-IMMUNODEFICIENCY-VIRUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA 02215 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA 02215 USA. NR 197 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046586-9 PY 2007 BP 1211 EP 1235 PG 25 WC Hematology SC Hematology GA BCR96 UT WOS:000311226400068 ER PT J AU Lipsitch, M Cohen, T Murray, M Levin, BR AF Lipsitch, Marc Cohen, Ted Murray, Megan Levin, Bruce R. TI Antiviral resistance and the control of pandemic influenza SO PLOS MEDICINE LA English DT Article ID ISONIAZID PREVENTIVE THERAPY; ANTIBIOTIC-RESISTANCE; DRUG-RESISTANCE; MYCOBACTERIUM-TUBERCULOSIS; OSELTAMIVIR RESISTANCE; VIRUSES RESISTANT; UNITED-STATES; A VIRUSES; EMERGENCE; FITNESS AB Background: The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir), combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness). Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans. Methods and Findings: We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing) that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains. Conclusions: The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance should be considered in pandemic planning and monitored closely during a pandemic. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis & Gen Med, Boston, MA 02114 USA. Emory Univ, Dept Biol, Atlanta, GA 30322 USA. RP Lipsitch, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM mlipsitc@hsph.harvard.edu RI Cohen, Ted/G-8101-2011; OI Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [K08 AI055985, K08 AI055985-05, R01 AI040662, R01 AI40662]; NIGMS NIH HHS [5U01GM076497, R01 GM091875, U01 GM076497] NR 42 TC 114 Z9 121 U1 5 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2007 VL 4 IS 1 BP 111 EP 121 AR e15 DI 10.1371/journal.pmed.0040015 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 130ZW UT WOS:000243838500018 PM 17253900 ER PT J AU Lin, HH Ezzati, M Murray, M AF Lin, Hsien-Ho Ezzati, Majid Murray, Megan TI Tobacco smoke, indoor air pollution and tuberculosis: A systematic review and meta-analysis SO PLOS MEDICINE LA English DT Review ID PULMONARY TUBERCULOSIS; RISK-FACTORS; HONG-KONG; CIGARETTE-SMOKING; RESIDENTIAL HOMES; PASSIVE SMOKING; SOUTH-INDIA; SKIN-TEST; PREVALENCE; MORTALITY AB Background Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures and the risk of infection, disease, and death from TB. Methods and Findings We conducted a systematic review and meta-analysis of observational studies reporting effect estimates and 95% confidence intervals on how tobacco smoking, passive smoke exposure, and indoor air pollution are associated with TB. We identified 33 papers on tobacco smoking and TB, five papers on passive smoking and TB, and five on indoor air pollution and TB. We found substantial evidence that tobacco smoking is positively associated with TB, regardless of the specific TB outcomes. Compared with people who do not smoke, smokers have an increased risk of having a positive tuberculin skin test, of having active TB, and of dying from TB. Although we also found evidence that passive smoking and indoor air pollution increased the risk of TB disease, these associations are less strongly supported by the available evidence. Conclusions There is consistent evidence that tobacco smoking is associated with an increased risk of TB. The finding that passive smoking and biomass fuel combustion also increase TB risk should be substantiated with larger studies in future. TB control programs might benefit from a focus on interventions aimed at reducing tobacco and indoor air pollution exposures, especially among those at high risk for exposure to TB. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Murray, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu OI LIN, HSIEN-HO/0000-0002-7481-6016 NR 76 TC 238 Z9 243 U1 4 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2007 VL 4 IS 1 BP 173 EP 189 AR e20 DI 10.1371/journal.pmed.0040020 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 130ZW UT WOS:000243838500024 PM 17227135 ER PT J AU Quinn, LS AF Quinn, L. S. TI Interleukin-15: A cytokine which modulates fat : lean body composition SO POULTRY SCIENCE LA English DT Meeting Abstract DE interleukin-15; muscle; adipose tissue C1 [Quinn, L. S.] Univ Washington, Seattle, WA 98195 USA. [Quinn, L. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2007 VL 86 SU 1 BP 1 EP 1 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 213UM UT WOS:000249692600003 ER PT J AU Purton, LE AF Purton, Louise E. TI Roles of Retinoids and Retinoic Acid Receptors in the Regulation of Hematopoietic Stem Cell Self-Renewal and Differentiation SO PPAR RESEARCH LA English DT Review AB Multipotent hematopoietic stem cells (HSCs) sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self-renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs. Copyright (C) 2007 Louise E. Purton. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Purton, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Harvard Stem Cell Inst, Boston, MA 02114 USA. EM lpurton@partners.org FU National Institute of Health (USA) [DK71773] FX thank Dr. C. Walkley for critical comments. This work was supported by a Grant from the National Institute of Health, DK71773 (USA). NR 51 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2007 AR 87934 DI 10.1155/2007/87934 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V14CC UT WOS:000207711500001 ER PT J AU Hutson, HR Rice, PL Chana, JK Kyriacou, DN Chang, YH Miller, RM AF Hutson, H. Range Rice, Phillip L., Jr. Chana, Jasroop K. Kyriacou, Demetrios N. Chang, Yuchiao Miller, Robert M. TI A review of police pursuit fatalities in the United States from 1982-2004 SO PREHOSPITAL EMERGENCY CARE LA English DT Review DE police pursuits; police pursuit fatalities; police pursuit crashes. AB Background. High-speed police pursuits are common in the United States (US). Most states do not gather statistics on police pursuits, pursuit crashes, injuries or fatalities for annual review. Objective. The objective of this study is to determine the number of pursuit fatalities to officers, those in the chased vehicle, and those uninvolved in pursuits from 1982-2004. Methods. A review of police pursuit fatalities reported to the National Highway Traffic Safety Administration (NHTSA) Fatality Analysis Reporting System (FARS) database from 1982-2004. The data was reviewed for fatalities, demographic data, alcohol involvement, road surface type (rural versus urban) and mechanism of collision leading to a pursuit fatality. Results. From 1982-2004, 881,733 fatal crashes were reported to NHTSA, leading to 987,523 fatalities. Of fatal crashes, 6,336 (0.7%) were secondary to pursuits, leading to 7,430 (0.8%) fatalities, a mean of 323 per year. Among these fatalities, chased vehicle occupants accounted for 5,355 (72%); police for 81 (1%); those uninvolved for 1994 (27%). Of fatalities, 6074 (82%) were male, 2,092 (28%) were children and adolescents. Mean age of death was 24 years. African Americans 1,154 (24%) and Native Americans 101 (2%) died at a higher proportion than their percentage of the US population. Collisions with solid objects accounted for 3,175 (59%) of fatalities in the chased vehicles. Collisions with other moving vehicles accounted for 1,434 (80%) of fatalities of vehicular occupants uninvolved in pursuits. Most fatal crashes, 3,130 (62%), occurred on urban roadways. Alcohol was involved in 4,628 (62%) fatalities. Of police fatalities, 20 (25%) were intoxicated. Conclusions. Police pursuits results in a small yet significant number of fatal motor vehicular crashes and fatalities. All states should record the total number of police pursuits, pursuit crashes, injuries and fatalities for annual review. The findings in this study have important operational implications for EMS care. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. N Hampshire Hosp, Basingstoke, Hants, England. Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. RP Hutson, HR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. EM hhutson@partners.org NR 26 TC 5 Z9 5 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2007 VL 11 IS 3 BP 278 EP 283 DI 10.1080/10903120701385414 PG 6 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 187VJ UT WOS:000247876800003 PM 17613900 ER PT J AU Shewakramani, S Thomas, SH Harrison, TH Gates, JD AF Shewakramani, Sanjay Thomas, Stephen H. Harrison, Tim H. Gates, Jonathan D. TI Air transport of patients with unstable aortic aneurysms directly into operating rooms SO PREHOSPITAL EMERGENCY CARE LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Phys DE aortic aneurysm; interfacility transport; helicopter; EMS ID MYOCARDIAL-INFARCTION; HELICOPTER TRANSPORT; TRAUMA MORTALITY; ANGIOPLASTY; PREDICTORS; TRIAL; DEATH AB Objective. The purpose of this study was to describe an air transport service's protocol for direct transport of patients with abdominal aortic aneurysm leak (AAAL) into receiving hospital operating rooms (ORs). Methods. This retrospective consecutive-case analysis examined AAAL patients undergoing nurse-paramedic Boston MedFlight (BMF) transport during 1999-2004, who were taken directly into ORs at four academic centers. BMF uses a rotating roster system to assign receiving hospitals when referring physicians have no preidentified receiving facility, but this practice may prolong patient transport or be associated with less diagnostic certainty, and thus more delay, at receiving hospitals. Thus, the study compared "Roster" versus "Non-roster" patients' time and outcome end points. Continuous nonparametric data (e.g., time intervals) were described with median and interquartile range (IQR). Chi-square and Kruskal-Wallis tests were used for univariate comparisons; regression analysis assessed dependent variables while adjusting for covariates (e.g., transport mileage). Results. There were 29 direct-to-OR transports, with median distance of 30 miles. All patients had AAAL diagnosis confirmed; 51.7% survived. System performance for end points was similar as assessed between Roster versus Non-roster patients. Conclusions. Interfacility direct-to-OR transport of AAAL patients is feasible. Use of a roster system allows for timely transport facilitation for patients needing specialized care; roster patients achieve similar end points as did patients who had already identified receiving hospitals upon air medical transport request. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston MedFlight, Boston, MA USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Clin Bldg Room 115,55 Fruit St, Boston, MA 02114 USA. EM Thomas.Stephen@MGH.Harvard.edu NR 14 TC 2 Z9 2 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2007 VL 11 IS 3 BP 337 EP 342 DI 10.1080/10903120701348024 PG 6 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 187VJ UT WOS:000247876800013 PM 17613910 ER PT J AU Thomas, SH AF Thomas, Stephen H. TI Helicopter EMS transport outcomes literature: Annotated review of articles published 2004-2006 SO PREHOSPITAL EMERGENCY CARE LA English DT Review DE HEMS; helicopter transport; outcomes; trauma; nontrauma; scene; interfacility ID TRIAGE; CARE AB Helicopter EMS( HEMS) and its possible association with outcomes improvement continues to be a subject of debate. As is the case with other scientific endeavors, debate over HEMS usefulness should be framed around an evidence-based assessment of the relevant literature. In an effort to facilitate the academic pursuit of assessment of HEMS utility, in late 2000 the National Association of EMS Physicians' (NAEMSP) Air Medical Task Force prepared annotated bibliographies of the HEMS-related outcomes literature. As a result of that work, two review articles, one covering HEMS use in nontrauma and the other in trauma, published in 2002 in Prehospital Emergency Care surveyed HEMS outcomes-related literature published between 1980 and mid-2000. The project was extended with a 2004 review that covered the literature published between 2000 and 2003. The current review continues the series, outlining outcomes-associated HEMS literature from 2004 through 2006. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. Boston MedFlight, Boston, MA USA. RP Thomas, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 55 Fruit St,Clin Bldg 115, Boston, MA 02114 USA. EM thomas.stephen@mgh.harvard.edu NR 12 TC 21 Z9 22 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2007 VL 11 IS 4 BP 477 EP 488 DI 10.1080/10903120701537097 PG 12 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 217PA UT WOS:000249958600020 PM 17907037 ER PT B AU Atwood, CW AF Atwood, Charles W., Jr. BE Pagel, JF PandiPerumal, SR TI Obstructive Sleep Apnea Clinical Presentation SO PRIMARY CARE SLEEP MEDICINE SE Current Clinical Practice Series LA English DT Article; Book Chapter ID GENDER-DIFFERENCES; LATENCY TEST; POPULATION; SCALE; PREVALENCE; DIAGNOSIS; IMPACT; SAMPLE; WOMEN; MEN C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Pulm Allergy & Crit Care Med, Sleep Disorders Program,Med Ctr,Sleep Med Ctr, Pittsburgh, PA 15260 USA. RP Atwood, CW (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Pulm Allergy & Crit Care Med, Sleep Disorders Program,Med Ctr,Sleep Med Ctr, Pittsburgh, PA 15260 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-59745-421-6 J9 CURR CLIN PRACT PY 2007 BP 89 EP 95 DI 10.1007/978-1-59745-421-6_8 D2 10.1007/978-1-59745-421-6 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA BNF87 UT WOS:000274465800010 ER PT B AU Atwood, CW AF Atwood, Charles W., Jr. BE Pagel, JF PandiPerumal, SR TI Portable Monitoring SO PRIMARY CARE SLEEP MEDICINE SE Current Clinical Practice Series LA English DT Article; Book Chapter ID SLEEP-APNEA C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Pulm Allergy & Crit Care Med, Sleep Disorders Program,Med Ctr,Sleep Med Ctr, Pittsburgh, PA 15260 USA. RP Atwood, CW (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Pulm Allergy & Crit Care Med, Sleep Disorders Program,Med Ctr,Sleep Med Ctr, Pittsburgh, PA 15260 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-59745-421-6 J9 CURR CLIN PRACT PY 2007 BP 305 EP 309 DI 10.1007/978-1-59745-421-6_28 D2 10.1007/978-1-59745-421-6 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA BNF87 UT WOS:000274465800030 ER PT J AU Vacanti, J Vacanti, CA AF Vacanti, Joseph Vacanti, Charles A. BE Lanza, R Langer, R Vacanti, J TI The History and Scope of Tissue Engineering SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID FUTURE C1 [Vacanti, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Vacanti, Charles A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Vacanti, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 3 EP 6 DI 10.1016/B978-012370615-7/50005-6 PG 4 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100005 ER PT J AU Lanza, R Langer, R Vacanti, J AF Lanza, Robert Langer, Robert Vacanti, Joseph BE Lanza, R Langer, R Vacanti, J TI PRINCIPLES OF TISSUE ENGINEERING Third Edition PREFACE SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02142 USA. [Vacanti, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP XXXI EP XXXI DI 10.1016/B978-012370615-7/50002-0 PG 1 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100002 ER PT J AU Lanza, R Langer, R Vacanti, J AF Lanza, Robert Langer, Robert Vacanti, Joseph BE Lanza, R Langer, R Vacanti, J TI PRINCIPLES OF TISSUE ENGINEERING Third Edition PREFACE TO THE SECOND EDITION SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02142 USA. [Vacanti, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP XXXIII EP XXXIII DI 10.1016/B978-012370615-7/50003-2 PG 1 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100003 ER PT J AU Faustman, DL AF Faustman, Denise L. BE Lanza, R Langer, R Vacanti, J TI Immunomodulation SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID ISLET ALLOGRAFT SURVIVAL; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I ANTIGENS; T-CELL; GENE; GAL-ALPHA(1,3)GAL; INHIBITION; EXPRESSION; ANTIBODIES; ADHESION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Boston, MA 02129 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 389 EP 397 DI 10.1016/B978-012370615-7/50031-7 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100031 ER PT J AU Kunisaki, SM Vacanti, J AF Kunisaki, Shaun M. Vacanti, Joseph BE Lanza, R Langer, R Vacanti, J TI Alimentary Tract SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID ENGINEERED SMALL-INTESTINE; NATIVE SMALL-BOWEL; STEM-CELL TRANSPLANTATION; COLLAGEN SPONGE SCAFFOLD; INTRATHORACIC ESOPHAGEAL REPLACEMENT; BASEMENT-MEMBRANE COMPONENTS; BRUSH-BORDER ENZYMES; SMOOTH-MUSCLE-CELLS; TERM-FOLLOW-UP; ARTIFICIAL ESOPHAGUS C1 [Kunisaki, Shaun M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Vacanti, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kunisaki, SM (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 59 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 681 EP 694 DI 10.1016/B978-012370615-7/50050-0 PG 14 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100050 ER PT J AU Kunisaki, SM Fauza, DO AF Kunisaki, Shaun M. Fauza, Dario O. BE Lanza, R Langer, R Vacanti, J TI Current State of Clinical Application SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; SKELETAL MYOBLAST TRANSPLANTATION; ENGINEERED VASCULAR AUTOGRAFTS; HUMAN SKIN EQUIVALENT; ACUTE LIVER-FAILURE; PARKINSONS-DISEASE; CONTROLLED-TRIAL; BONE-MARROW; MYOCARDIAL-INFARCTION; ISLET TRANSPLANTATION C1 [Kunisaki, Shaun M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Fauza, Dario O.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. RP Kunisaki, SM (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 51 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 1189 EP 1200 DI 10.1016/B978-012370615-7/50082-2 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100082 ER PT J AU Vacanti, J AF Vacanti, Joseph BE Lanza, R Langer, R Vacanti, J TI PRINCIPLES OF TISSUE ENGINEERING Third Edition Epilogue SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Vacanti, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 1289 EP 1289 DI 10.1016/B978-012370615-7/50091-3 PG 1 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100091 ER PT B AU Wan, L Li, GA AF Wan, Lu Li, Guoan GP ASME TI The effect of permeability of cartilage superficial zone on the behavior of stress relaxation and creep of human ankle joint SO PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007 LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 24-28, 2007 CL Keystone, CO SP ASME, Bioengn Div ID ARTICULAR-CARTILAGE C1 [Wan, Lu; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02115 USA. RP Wan, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4798-5 PY 2007 BP 353 EP 354 PG 2 WC Engineering, Biomedical SC Engineering GA BHB85 UT WOS:000252105700177 ER PT B AU Li, G Wan, L Kozanek, M AF Li, Guoan Wan, Lu Kozanek, Michall GP ASME TI Determination of real time in-vivo cartilage contact deformation in the ankle joint SO PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007 LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 24-28, 2007 CL Keystone, CO SP ASME, Bioengn Div C1 [Li, Guoan; Wan, Lu; Kozanek, Michall] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4798-5 PY 2007 BP 541 EP 542 PG 2 WC Engineering, Biomedical SC Engineering GA BHB85 UT WOS:000252105700271 ER PT B AU Suggs, JF Hanson, GR Li, G AF Suggs, Jeremy F. Hanson, George R. Li, Guoan GP ASME TI In-vivo tibiofemoral contact stress in the knee after TKA SO PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007 LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 24-28, 2007 CL Keystone, CO SP ASME, Bioengn Div ID KINEMATICS C1 [Suggs, Jeremy F.; Hanson, George R.; Li, Guoan] Harvard Univ, Sch Med, Bioengn Lab, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Suggs, JF (reprint author), Harvard Univ, Sch Med, Bioengn Lab, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4798-5 PY 2007 BP 661 EP 662 PG 2 WC Engineering, Biomedical SC Engineering GA BHB85 UT WOS:000252105700331 ER PT B AU Ottensmeyer, MP Yip, M Walsh, CJ Kobler, JB Heaton, JT Zeitels, SM AF Ottensmeyer, Mark P. Yip, Michael Walsh, Conor J. Kobler, James B. Heaton, James T. Zeitels, Steven M. GP ASME TI Intra-operative laryngoscopic instrument for characterizing vocal fold viscoelasticity SO Proceedings of the 2nd Frontiers in Biomedical Devices Conference LA English DT Proceedings Paper CT Frontiers in Biomedical Devices Conference CY JUN 07-08, 2007 CL Irvine, CA SP Amer Soc Mech Engineers ID TISSUES C1 Massachusetts Gen Hosp, CIMIT, Simulat Grp, Boston, MA 02114 USA. RP Ottensmeyer, MP (reprint author), Massachusetts Gen Hosp, CIMIT, Simulat Grp, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4266-9 PY 2007 BP 133 EP 134 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BGT86 UT WOS:000250478200057 ER PT S AU Czanner, G Dreyer, AA Eden, UT Wirth, S Lim, HH Suzuki, WA Brown, EN AF Czanner, Gabriela Dreyer, Anna A. Eden, Uri T. Wirth, Sylvia Lim, Hubert H. Suzuki, Wendy A. Brown, Emery N. GP IEEE TI Dynamic models of neural spiking activity SO PROCEEDINGS OF THE 46TH IEEE CONFERENCE ON DECISION AND CONTROL, VOLS 1-14 SE IEEE Conference on Decision and Control LA English DT Proceedings Paper CT 46th IEEE Conference on Decision and Control CY DEC 12-14, 2007 CL New Orleans, LA SP IEEE Control Syst Soc, United Technol, Springer, Wiley Blackwell, Taylor & Francis, Princeton Univ Press, Maplesoft, Siam ID RECEPTIVE-FIELD PLASTICITY; INFERIOR COLLICULUS; SINGLE NEURONS; BEHAVIORAL-EXPERIMENTS; MAXIMUM-LIKELIHOOD; FIRING PATTERNS; POINT-PROCESSES; TRAIN; STIMULATION; HIPPOCAMPUS AB We present a state-space generalized linear model (SS-GLM) for characterizing neural spiking activity in multiple trials. We estimate the model parameters by maximum likelihood using an approximate Expectation-Maximization (EM) algorithm which employs a recursive point process filter, fixed-interval smoothing and state-space covariance algorithms. We assess model goodness-of-fit using the time-rescaling theorem and guide the choice of model order with Akaike's information criterion. We illustrate our approach in two applications. In the analysis of hippocampal neural activity recorded from a monkey performing a location-scene association task, we use the model to quantify the neural changes related to learning. In the analysis of primary auditory cortex responses to different levels of electrical stimulation in the rat midbrain, we use the method to analyze auditory threshold detection. Our findings have important implications for developing theoretically-sound and practical tools to characterize the dynamics of spiking activity. C1 [Czanner, Gabriela; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Dreyer, Anna A.; Brown, Emery N.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Wirth, Sylvia] Ctr Natl Rech Sci, Ctr Neurosci Cognit, F-69675 Bron, France. [Lim, Hubert H.] Hannover Med Sch, Dept Otorhinolaryngol, D-30625 Hannover, Germany. [Suzuki, Wendy A.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Brown, Emery N.] MIT, Harbor Med Sch, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Czanner, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM gabriela@neurostat.mgh.harvard.edu; adreyer@mit.edu; tzvi@bu.edu; swirth@isc.cnrs.fr; Hubertlim@aol.com; wendy@cns.nyu.edu; brown@neurostat.mgh.harvard.edu FU NIH [T32DC000038, MH58847, R01 DA015644, MH59733, P41EB2030, F31DC007009]; McKnight Foundation FX Manuscript received March 6,2007. This work was supported by NIH grant, T32DC000038, MH58847, R01 DA015644, MH59733, P41EB2030, F31DC007009 and the McKnight Foundation. NR 42 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0743-1546 BN 978-1-4244-1497-0 J9 IEEE DECIS CONTR P PY 2007 BP 4173 EP + PG 2 WC Automation & Control Systems; Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Automation & Control Systems; Computer Science; Engineering GA BHP50 UT WOS:000255181702081 ER PT B AU Dunker, AK Yang, JY Oldfield, CJ Obradovic, Z Meng, JW Romero, P Uversky, VN AF Dunker, A. Keith Yang, Jack Y. Oldfield, Christopher J. Obradovic, Zoran Meng, Jingwei Romero, Pedro Uversky, Vladimir N. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI IEEE 7(th) BIBE invited plenary keynote: Intrinsically disordered proteins: Predictions and applications SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc AB About 10 years ago we published our first predictor of intrinsically disordered protein residues in another IEEE journal, the Proceedings of the IEEE International Conference on Neural Networks. Others call such proteins "natively unfolded" and "intrinsically unstructured." Since then, we and others have substantially improved the prediction of intrinsically disordered residues. The prediction of protein intrinsic disorder is similar to the prediction of secondary structure in terms of methodology, but, at the structural level, secondary structure (especially random coil) and intrinsic disorder differ completely in their dynamic motion. First, we will briefly describe the prediction of protein disorder, show the progress from similar to 70% to similar to 85% per residue prediction accuracy, and show that intrinsically disordered proteins are common over the three domains of life, but are especially common among the eukaryotes. Next we will discuss our methods for deducing functions that are associated with disordered rather than structured proteins. In brief, structured proteins have advantages for catalysis while disordered proteins and regions have advantages for the reversible, weak binding often observed in signaling, control, and regulation. After that we will discuss how disorder facilitates binding diversity in protein-protein interaction networks, both for single disordered regions binding to many partners and for many disordered regions with different sequences binding to a common site on the surface of one structured protein. Part three presents data indicating that alternative splicing is more prevalent in regions of RNA that code for disorder than those that code for structure, thus providing a means for evolving tissue-specific signaling networks. Finally, we will present a novel approach to drug discovery based on disordered protein. C1 [Dunker, A. Keith; Oldfield, Christopher J.; Romero, Pedro; Uversky, Vladimir N.] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Yang, Jack Y.] Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. [Obradovic, Zoran] Temple Univ, Ctr Informat Sci & Technol, Philadelphia, PA 19122 USA. [Meng, Jingwei] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Uversky, Vladimir N.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Russia. [Dunker, A. Keith; Oldfield, Christopher J.; Romero, Pedro] Indiana Univ, Ctr Computat Biol & Bioinformat, Sch Informat, Indianapolis, IN 46202 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dunker, AK (reprint author), Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. EM kedunker@iupui.edu; vuversky@iupui.edu RI Meng, Jingwei/K-8880-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 1 EP 1 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200001 ER PT B AU Quackenbush, J AF Quackenbush, John BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI IEEE 7(th) BIBE invited plenary keynote: Stochasticity and networks in genomic data SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man, Cybermet Soc AB Two trends are driving innovation and discovery in biological sciences: technologies that allow holistic surveys of genes, proteins, and metabolites and a realization that biological processes are driven by complex networks of interacting biological molecules. However, there is a gap between the gene lists emerging from genome sequencing projects and the network diagrams that are essential if we are to understand the link between genotype and phenotype. 'Omic technologies such as DNA microarrays were once heralded as providing a window into those networks, but so far their success has been limited. Although many techniques have been developed to deal with microarray data, to date their ability to extract network relationships has been limited. We believed that by imposing constraints on the networks, based on associations reported through articles indexed in PubMed, we could more effectively extract biologically relevant results from microarray data and develop testable hypotheses that could then be validated in the laboratory. Using literature networks as constraints on a Bayesian network analysis of microarray data, we show that we are able to recover evidence for a wide range of known networks and pathways, even in experiments not explicitly designed to probe them. With a putative gene-interaction network, the problem of producing viable models of the cell remains. While systems biology approaches that attempt to develop quantitative, predictive models of cellular processes have received great attention, it is surprising to note that the starting point for all cellular gene expression, the transcription of RNA, has not been described and measured in a population of living cells. To address this problem, we propose a simple (and obvious) model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels. Although what we describe as a microscopic process, occurring at the level of an individual cell, the data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems. Together these two approaches open new avenues of investigation that may help us in our eventual understanding of the function of biological systems, addressing many of the important questions that have arisen in the context of systems biology. Our ultimate goal will be to create predictive models that allow one to examine the current state of a biological system and to estimate the likelihood that, at some later time, the system will have evolved to a new state. Such an approach, if successful, could have a wide range of applications spanning laboratory, clinical, and translational biology. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 2 EP 2 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200002 ER PT B AU Dunker, AK Yang, JY Oldfield, CJ Obradovic, Z Meng, JW Romero, P Uversky, VN AF Dunker, A. Keith Yang, Jack Y. Oldfield, Christopher J. Obradovic, Zoran Meng, Jingwei Romero, Pedro Uversky, Vladimir N. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Intrinsically disordered proteins: An update SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE disorder prediction; cell signaling; regulation and control; protein-protein interactions; alternative splicing; and disorder-based drug discovery ID RNA-BINDING PROTEIN; MOLECULAR RECOGNITION; FUNCTIONAL ANTHOLOGY; INTERACTION NETWORKS; CRYSTAL-STRUCTURES; ALPHA-SYNUCLEIN; SPLICE VARIANTS; UNSTRUCTURED PROTEINS; FUNCTION PREDICTION; ALZHEIMERS-DISEASE AB Just over 10 years ago, in June, 1997, in the Proceedings of the IEEE International Conference on Neural Networks, we published our first predictor of intrinsically disordered protein [1]. Since then, we have substantially improved our predictors, and more than 20 other laboratory groups have joined in efforts to improve the prediction of protein disorder. At the algorithmic level, prediction of protein intrinsic disorder is similar to the prediction of secondary structure, but, at the structural level, secondary structure and intrinsic disorder are entirely different. The secondary structure class called random coil or irregular differs from intrinsic disorder due to very different dynamic properties, with the secondary structure class being much less mobile than the region of disorder. At the biological level, unlike the prediction of secondary structure, the prediction of intrinsic disorder has been revolutionary. That is, for many years, experimentalists have provided evidence that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. Experimentalists further are showing that, for some proteins, functions depended on the unstructured rather than structured state. However, these examples have been mostly ignored. To our knowledge, not one disordered protein or disorder-associated function is discussed in any biochemistry textbook even though such examples began to be discovered more than 50 years ago. Disorder prediction has been important for showing that the few experimentally characterized examples represent a very large cohort that is found all across all three domains of life. We now know that many significant biological functions depend directly on, or are importantly associated with, the unfolded or partially folded state. In this paper, we will briefly review some of the key discoveries that have occurred in the last decade, and, furthermore, will make a few highly speculative projections. C1 [Dunker, A. Keith; Uversky, Vladimir N.] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. [Oldfield, Christopher J.; Romero, Pedro] Indiana Univ, Sch Informat, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Obradovic, Zoran] Temple Univ, Ctr Informat Sci & Technol, Philadelphia, PA 19122 USA. [Meng, Jingwei] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Uversky, Vladimir N.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Russia. RP Dunker, AK (reprint author), Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. EM kedunker@iupui.edu; vuversky@iupui.edu RI Meng, Jingwei/K-8880-2015 FU NIH; NSF; DOE; Indiana Genomics Initiative; Lilly Endowment FX We would like to thank NIH, NSF, DOE, and the Indiana Genomics Initiative (funded in part by the Lilly Endowment) for supporting our work. In addition, we would like to thank the many students, faculty members, and other scientists who have collaborated with us on this work over the past 10 years. NR 128 TC 0 Z9 0 U1 0 U2 6 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 49 EP + PG 4 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200016 ER PT B AU Liang, ZL Karl, WC Do, SH Hoffmann, U Brady, T Pien, H AF Liang, Zhuangli Karl, W. Clem Do, Synho Hoffmann, Udo Brady, Thomas Pien, Homer BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Calcium De-blooming in Coronary CT image SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc ID COMPUTED-TOMOGRAPHY; ANGIOGRAPHY AB Recent development of Multi-detector Computerized Tomography (MDCT) holds the promise of a non-invasive diagnostic method to evaluate coronary artery disease as an alternative to standard angiography. A major impediment preventing its utilization in routine clinical practice is the presence of image "blooming" artifacts due to vascular calcium. For high-risk patients with serious coronary stenosis who often have significant calcified plaque, this problem becomes very acute. In this paper, we examine an approach to ameliorate the degradations due to the presence of calcium and thus increase the applicability of MDCT. We assume the blooming effect is well modeled as a linear convolutional blur. We then use this model as the basis to perform image restoration, thus deblurring the original image. The aim is to produce CT images with reduced calcium artifacts. We evaluate our method on simulated, ex vivo and clinical data and show that this method has the potential to improve coronary CT image and thus improve stenosis diagnosis. C1 [Liang, Zhuangli; Karl, W. Clem] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Do, Synho; Hoffmann, Udo; Brady, Thomas; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Liang, ZL (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. EM sliang@bu.edu; wckarl@bu.edu; sdo@partners.org; uhofftnann@partners.org; tom@nmr.mgh.harvard.edu; hpien@nmr.mgh.harvard.edu FU Department of Defense; NSF; MGH Department of Radiology FX This study was partially supported by the Center for Integration of Medicine and Innovative Technologies (CIMIT) from the Department of Defense, Center for Sensing and Subsurface Imaging Systems (CenSSIS) from NSF, and the MGH Department of Radiology). NR 15 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 257 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200046 ER PT B AU Yang, JY Yang, MQ Niemierko, A Deng, YP AF Yang, Jack Y. Yang, Mary Qu Niemierko, Andrzej Deng, Youping BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Non-monotonic radio-sensitivity over tumor volumes on adjuvant radio therapy SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE radiotherapy; microscopic tumor tissue; Poisson statistics; radio-sensitivity and cell killing; Niemierko's EUD; equivalent radio-sensitivity model AB Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics have been used extensively to validate clinical data. We found that Poisson statistics on RT is actually derived from bacterial cells despite of many validations from clinical data. However cancerous cells do have abnormal cellular communications and use chemical messengers to signal both surrounding normal and cancerous cells to develop new blood vessels and to invade, to metastasis and to overcome intercellular spatial confinements in general. We therefore investigated the cell killing effects on adjuvant RT and found that radio-sensitivity is actually not a monotonic function of volume as it was believed before. We present detailed analysis and explanation to justify above statement. Based on Niemierko's EUD, we present an equivalent radio-sensitivity model. We conclude that radio sensitivity is a sophisticated function over tumor volumes, since tumor responses upon radio therapy also depend on cellular communications. C1 [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Niemierko, Andrzej] Massachusetts Gen Hosp, Div Biomath & Biostat, Boston, MA 02114 USA. [Yang, Mary Qu] NIH, Natl Human Genome Res Inst, US Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Deng, Youping] Univ Southern Mississippi, Dept Biol Sci, Bioinformat & Canc Bio Lab, Hattiesburg, MS 39406 USA. RP Yang, JY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM yang@hadron.mgh.Harvard.edu; yangma@mail.NIH.gov FU NIHWNCI [RO1 CA50628] FX The research was partially supported by NIHWNCI RO1 CA50628 NR 17 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 524 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200083 ER PT J AU Xiao, YF AF Xiao, Yong-Fu TI Cyclic AMP-dependent modulation of cardiac L-type Ca2+ and transient outward K+ channel activities by epoxyeicosatrienoic acids SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE cytochrome P450; arachidonic acid; epoxyeicosatrienoic acid; ion channel; cAMP; protein kinase A ID SPONTANEOUSLY HYPERTENSIVE RATS; ARACHIDONIC-ACID; CYTOCHROME-P450 METABOLITES; HYDROXYLASE INHIBITION; VENTRICULAR MYOCYTES; MOLECULAR-CLONING; HUMAN PLATELETS; HEME OXYGENASE; SMOOTH MUSCLES; PIG-HEART AB The three major enzyme systems, cyclo-oxygenase, lipoxygenase, and cytochrome P450 (P450/CYP), metabolize arachidonic acid (AA) to biologically active compounds. P450 and its associated monooxygenase activities have been identified in mammalian cardiac tissue, including humans. The four regioisomeric eicosanoids, 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) of AA metabolites derived by P450 epoxygenases have shown to possess potent biological effects in numerous tissues. In the coronary circulation the EETs are leading candidates for endothelial-derived hyperpolarizing factors that hyperpolarize vascular smooth muscle cells by opening Ca2+-activated K+ channels. Recently, the effects of the CYP pathways and their metabolites on cardiac ischemia-reperfusion injury have been evaluated in animal models. Some of these AA metabolites are cardioprotective and some are detrimental. However, EETs appear to be cardioprotective in CYP2J2 transgenic mice and in a canine ischemic model. Multiple effects of EETs on cardiac ion channels have been observed, such as activation of ATP-sensitive K+ channels and L-type Ca2+ channels in cardiomyocytes and inhibition of cardiac Na+ channels and L-type Ca2+ channels reconstructed in planar lipid bilayers. This brief review summarizes EET induced modulation of cardiac ion channels. (c) 2006 Elsevier Inc. All rights reserved. C1 Medtronic Inc, Cardiac Rhythm Dis Management, Minneapolis, MN 55432 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02129 USA. RP Xiao, YF (reprint author), Medtronic Inc, Cardiac Rhythm Dis Management, 7000 Cent Ave NE,B252, Minneapolis, MN 55432 USA. EM yong-fu.xiao@medtronic.com NR 51 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 2007 VL 82 IS 1-4 SI SI BP 11 EP 18 DI 10.1016/j.prostaglandins.2006.05.023 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126YY UT WOS:000243552800003 PM 17164128 ER PT J AU Rogers, B Bosker, GW Crawford, RH Faustini, MC Neptune, RR Walden, G Gitter, AJ AF Rogers, Bill Bosker, Gordon W. Crawford, Richard H. Faustini, Mario C. Neptune, Richard R. Walden, Gail Gitter, Andrew J. TI Advanced trans-tibial socket fabrication using selective laser sintering SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Article DE amputees; prosthetics; CAD/CAM ID MANUFACTURE; PROSTHESES AB There have been a variety of efforts demonstrating the use of solid freeform fabrication (SFF) for prosthetic socket fabrication though there has been little effort in leveraging the strengths of the technology. SFF encompasses a class of technologies that can create three dimensional objects directly from a geometric database without specific tooling or human intervention. A real strength of SFF is that cost of fabrication is related to the volume of the part, not the part's complexity. For prosthetic socket fabrication this means that a sophisticated socket can be fabricated at essentially the same cost as a simple socket. Adding new features to a socket design becomes a function of software. The work at The University of Texas Health Science Center at San Antonio (UTHSCSA) and University of Texas at Austin (UTA) has concentrated on developing advanced sockets that incorporate structural features to increase comfort as well as built in fixtures to accommodate industry standard hardware. Selective laser sintering (SLS) was chosen as the SFF technology to use for socket fabrication as it was capable of fabricating sockets using materials appropriate for prosthetics. This paper details the development of SLS prosthetic socket fabrication techniques at UTHSCSA/UTA over a six-year period. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78284 USA. Univ Texas, Dept Mech Engn, Austin, TX 78712 USA. S Texas Vet Healthcare Syst, PM&R Serv, San Antonio, TX USA. RP Rogers, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78284 USA. EM rogers@uthscsa.edu RI Rogers, Bill/F-7689-2010 NR 16 TC 23 Z9 23 U1 2 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0309-3646 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PY 2007 VL 31 IS 1 BP 88 EP 100 DI 10.1080/03093640600983923 PG 13 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 168SY UT WOS:000246545500009 PM 17365888 ER PT J AU Baldessarini, RJ Leahy, L Arcona, S Gause, D Zhang, W Hennen, J AF Baldessarini, Ross J. Leahy, Leslie Arcona, Stephen Gause, Douglas Zhang, Winnie Hennen, John TI Patterns of psychotropic drug prescription for US patients with diagnoses of bipolar disorders SO PSYCHIATRIC SERVICES LA English DT Article ID WEEKLY SYMPTOMATIC STATUS; SUICIDAL-BEHAVIOR; I DISORDER; NATURAL-HISTORY; MOOD DISORDERS; LITHIUM; ANTIDEPRESSANTS; RECURRENCE; PREVENTION; DEPRESSION AB Bipolar disorders are prevalent major illnesses with high rates of morbidity, comorbidity, disability, and mortality. A growing number of psychotropic drugs are used to treat bipolar disorder, often off-label and in untested, complex combinations. Methods: To quantify utilization rates for psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan research databases to identify 7,760 persons with ICD-9 bipolar disorder subtypes. Survival analysis was used to estimate times until initial monotherapies were augmented, changed, or discontinued. Results: The most commonly prescribed first drug class was antidepressants (50% of patients), followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%), sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients were receiving monotherapy. Those receiving monotherapy were ranked by initial drug prescribed and percentage of patients (bipolar I and bipolar 11): antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and 31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to adding another psychotropic was 2.5-times less than median time to changing the initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median weeks until therapy was changed in any way for 25% of patients was as follows: lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13; and sedatives, 9. Conclusions: Antidepressants were the first-choice agent twice as often as mood stabilizers. Lithium was sustained longer than monotherapy with other mood stabilizers. Time to augmentation was much shorter than time to change or discontinuation. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. PE Consulting Inc, Media, PA USA. RP Baldessarini, RJ (reprint author), Massachusetts Gen Hosp, McLean Div, 115 Mill St, Belmont, MA 02478 USA. EM jb@mclean.org NR 40 TC 161 Z9 166 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2007 VL 58 IS 1 BP 85 EP 91 DI 10.1176/appi.ps.58.1.85-a PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 124QE UT WOS:000243384200013 PM 17215417 ER PT J AU Parsons, SK Saiki-Craigill, S Mayer, DK Sullivan, AM Jeruss, S Terrin, N Tighiouart, H Nakagawa, K Iwata, Y Hara, J Grier, HE Block, S AF Parsons, Susan K. Saiki-Craigill, Shigeko Mayer, Deborah K. Sullivan, Amy M. Jeruss, Stefanie Terrin, Norma Tighiouart, Hocine Nakagawa, Kaoru Iwata, Yoko Hara, Junichi Grier, Holcombe E. Block, Susan TI Telling children and adolescents about their cancer diagnosis: Cross-cultural comparisons between pediatric oncologists in the US and Japan SO PSYCHO-ONCOLOGY LA English DT Article; Proceedings Paper CT 7th World Congress of Psycho-Oncology CY AUG 25-28, 2004 CL Copenhagen, DENMARK DE truth disclosure; physician-patient relations; patient advocacy; communication; psychological; child; adolescent; cancer ID COMMUNICATION-SKILLS; INFORMED CONSENT; BAD-NEWS; TRUTH; ATTITUDES; CARE; INFORMATION; LEUKEMIA; BEHAVIOR; MOTHERS AB Purpose: Over the last 50 years, direct communication about cancer with adults has shifted from an approach of not telling to one of telling. Less is known about communication practices with children. The purpose of this study is to (1) describe patterns of communication at diagnosis between pediatric oncologists and children with cancer and (2) compare cultural differences in these practices in the US and Japan. Methods: This 2003 survey, developed in English and translated into Japanese was mailed to members of the American Society of Pediatric Hernatology/Oncology and the two Japanese Societies of Pediatric Hematology and Oncology; there were 350 US and 362 Japanese respondents. Descriptive statistics and logistic regressions were performed. Results: US physicians had a consistent pattern of telling children (65% always told the child; less than 1% rarely or never told). Japanese physicians had greater variability in their patterns of telling (with only 9.5% always telling, 34.5% rarely or never telling). Direct communication with the child was influenced by personal attitudes, patient factors, and work culture in both countries. Many more variables emerged as influencing Japanese physicians' communication practices than for US physicians. US physicians were influenced by their own sense of responsibility for telling, while Japanese physicians were more influenced by personal attitudes, patient factors, and work culture. Conclusions: US and Japanese physicians differed when communicating directly with the child about his or her cancer. The impact of these practices on children and their parents should be explored and the parent and child's perspectives elicited. This information will help facilitate culturally sensitive patient and family centered communication. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 Tufts Univ New England Med Ctr, Ctr Child & Family Outcomes, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tokyo Metropolitan Univ Hlth Sci, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Osaka Univ, Osaka, Japan. RP Parsons, SK (reprint author), Tufts Univ New England Med Ctr, Ctr Child & Family Outcomes, Inst Clin Res & Hlth Policy Studies, 750 Washington St 345, Boston, MA 02111 USA. EM sparsons@tufts-nemc.org NR 44 TC 26 Z9 27 U1 2 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2007 VL 16 IS 1 BP 60 EP 68 DI 10.1002/pon.1048 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 128ZY UT WOS:000243699400006 PM 16874746 ER PT J AU Biederman, J Spencer, TJ Newcorn, JH Gao, H Milton, DR Feldman, PD Witte, MM AF Biederman, Joseph Spencer, Thomas J. Newcorn, Jeffrey H. Gao, Haitao Milton, Denai R. Feldman, Peter D. Witte, Michael M. TI Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data SO PSYCHOPHARMACOLOGY LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; comorbidity; oppositional defiant disorder; pediatric patients ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; EXECUTIVE FUNCTIONING DEFICITS; CONDUCT DISORDER; DOUBLE-BLIND; ADOLESCENTS; METHYLPHENIDATE; ODD; ASSOCIATION AB Rationale Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40-60% of children with ADHD. Objectives This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD. Methods Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6-16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6-8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and Lifetime Versions). Results Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response. Conclusions Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Psychiat & Pediat, New York, NY 10029 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Biederman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,Yawkey Ctr Outpatient Care 6-A, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 41 TC 53 Z9 54 U1 5 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2007 VL 190 IS 1 BP 31 EP 41 DI 10.1007/s00213-006-0565-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 111GQ UT WOS:000242439800004 PM 17093981 ER PT J AU Verrico, CD Miller, GM Madras, BK AF Verrico, Christopher D. Miller, Gregory M. Madras, Bertha K. TI MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Neuroscience CY OCT 23-27, 2004 CL San Diego, CA SP Soc Neurosci DE MDMA; ecstasy; dopamine; serotonin; norepinephrine; transporters; trace amine receptors; monoamines; reuptake inhibitors ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN SLICES; ABUSED DRUG MDMA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONHUMAN-PRIMATES; TRACE AMINES; METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; MONOAMINE TRANSPORTERS; PARA-CHLOROAMPHETAMINE AB Rationale: 3,4-Methylenedioxymethamphetamine (MDMA, designated as "Ecstasy" if illicitly marketed in tablet form) induces significant decrements in neuronal serotonin (5-HT) markers in humans, nonhuman primates, and rats as a function of dosing and dosing regimen. In rats, MDMA-mediated effects are attributed, in part, to selective high-affinity transport of MDMA into 5-HT neurons by the 5-HT transporter (SERT), followed by extensive 5-HT release. Objectives: To clarify whether SERT-selective effects of MDMA at human monoamine transporters can account for the reported MDMA-induced selective toxicity of serotonin neurons in primate brain. Methods: We investigated the interaction of [H-3](+/-, RS)- (+, S)- and (-, R)-MDMA with the human SERT, dopamine (DA) transporter (DAT), and norepinephrine (NE) transporter (NET) in stably transfected human embryo kidney (HEK)-293 cells. Results: The human DAT, NET, and SERT actively transported [H-3]RS (+/-)-MDMA saturably, stereoselectively, and in a temperature-, concentration-, and transporter-dependent manner. MDMA exhibited the highest affinity for the NET >> SERT > DAT, the same rank order for MDMA inhibition of [H-3]DA, [H-3]NE, and [H-3]5-HT transport and stimulated release of the [H-3]monoamines, which differed from reports derived from rodent monoamine transporters. The extent of MDMA-induced release of 5-HT was higher compared with release of DA or NE. Conclusions: The affmity of MDMA for the human SERT in transfected cells does not clarify the apparent selective toxicity of MDMA for serotonin neurons, although conceivably, its higher efficacy for stimulating 5-HT release may be a distinguishing factor. The findings highlight the need to investigate MDMA effects in DAT-, SERT-, and NET-expressing neurons in the primate brain and the therapeutic potential of NET or DAT inhibitors, in addition to SERT-selective inhibitors, for alleviating the pharmacological effects of NMMA. C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurochem,Dept Psychiat, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurochem,Dept Psychiat, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM bertha_madras@hms.harvard.edu RI Verrico, Christopher/I-4552-2013 OI Verrico, Christopher/0000-0002-8272-0778 FU NCRR NIH HHS [RR 00168]; NIDA NIH HHS [DA06303, DA11558, DA15305] NR 92 TC 63 Z9 63 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2007 VL 189 IS 4 BP 489 EP 503 DI 10.1007/s00213-005-0174-5 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 126OM UT WOS:000243523700009 PM 16220332 ER PT J AU Dennehy, EB Bauer, MS Perlis, RH Kogan, JN Sachs, GS AF Dennehy, Ellen B. Bauer, Mark S. Perlis, Roy H. Kogan, Jane N. Sachs, Gary S. TI Concordance with Treatment Guidelines for Bipolar Disorder: Data from the Systematic Treatment Enhancement Program for Bipolar Disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE bipolar disorder; guideline adherence; treatment AB Background: Concordance with evidence-based guidelines in the treatment of chronic mental disorders is typically low. The study assesses the degree of concordance to recommendations of published treatment guidelines for bipolar disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Potential demographic and clinical predictors of adherence were examined. Methods: STEP-BD treating psychiatrists participated in extensive training in evidence-based pharmacological management focusing on published clinical practice guidelines. Recommended medications and dosing for each specific mood episode were extracted from published treatment guidelines and collapsed into a Composite guideline. Prescribed medication information for patients at the first visit in a prospectively observed new-onset mood episode (depressive, mixed, or hypomanic/manic) was then compared with guideline recommendations. Results: The current study included 964 STEP-BD patients, observed over 2 years, who experienced a prospectively observed episode (n = 716 depressive; n = 182 hypomanic/manic; n = 66 mixed). Guideline concordant treatments were prescribed in 81.8% of mixed episodes, 81.9% of hypomanic/manic episodes, and 83.4% of depressive episodes, exceeding rates previously reported in randomized controlled trials of guideline implementation. Younger age of onset and receipt of adequate pharmacotherapy at STEP-BD entry predicted those more likely to receive guideline-concordant care. Conclusions: The reported under naturalistic conditions. We speculate that basic provider education plus a collaborative approach to medication choice may have contributed to the high treatment concordance rates in this large national trial. As in other studies, few patient-specific factors were associated with the likelihood of receiving guideline-concordant care. Psychopharmacology Bulletin. 2007;40(3):72-84. C1 [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Bauer, Mark S.] Brown Univ, Providence Vet Affairs Med Ctr, Providence, RI 02912 USA. [Perlis, Roy H.; Sachs, Gary S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kogan, Jane N.] Outcomes & Res Adm, Pittsburgh, PA USA. [Kogan, Jane N.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Dennehy, EB (reprint author), Purdue Univ, Dept Psychol Sci, 703 3rd St, W Lafayette, IN 47907 USA. EM edennehy@psych.purdue.edu FU National Institute of Mental Health (NIMH), National Institutes of Health [N01MH80001] FX This project has been funded in whole or in part with Federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH80001. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NIMH. This article was approved by the publication committee of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). NR 32 TC 31 Z9 31 U1 0 U2 4 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2007 VL 40 IS 3 BP 72 EP 84 PG 13 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HK UT WOS:000207792900008 PM 18007570 ER PT J AU Ahearn, EP Juergens, T Smith, T Krahn, D Kalin, N AF Ahearn, Eileen P. Juergens, Timothy Smith, Tracey Krahn, Dean Kalin, Ned TI Fear, Anxiety, and the Neuroimaging of PTSD SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE fear; anxiety; neuroimaging; Posttraumatic stress disorder AB The clinical manifestations of Posttraumatic Stress Disorder (PTSD) include both fear and anxiety symptoms. Animal studies provide significant information about the neurobiological pathways involved in fear and anxiety and are relevant to the study of PTSD. These studies are reviewed along with Rauch's proposed neurobiologic model for PTSD. Neuroimaging findings in PTSD are summarized by region. Most neuroimaging studies to date have been provocation studies which present a trauma-related stimulus and measure response. While providing information about PTSD, these complex studies were not designed to target specific emotions. Studies which can specifically elicit fear or anxiety and evaluate associated brain regions, such as the bed nucleus of the stria terminalis (BNST) may provide a clearer understanding of the biologic underpinnings of PTSD and bridge the knowledge between animal neurobiology and human studies. Psychopharmacology Bulletin. 2007;40(3):88-103. C1 [Ahearn, Eileen P.; Juergens, Timothy; Smith, Tracey; Krahn, Dean] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Ahearn, Eileen P.; Juergens, Timothy; Smith, Tracey; Krahn, Dean; Kalin, Ned] Univ Wisconsin, Madison, WI USA. RP Ahearn, EP (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM eileen.ahearn@va.gov RI Smith, Tracey/J-2030-2014 OI Smith, Tracey/0000-0001-5338-9142 NR 90 TC 3 Z9 3 U1 1 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2007 VL 40 IS 3 BP 88 EP 103 PG 16 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HK UT WOS:000207792900009 PM 18007571 ER PT J AU Kilbourne, AM Copeland, LA Zeber, JE Bauer, MS Lasky, E Good, CB AF Kilbourne, Amy M. Copeland, Laurel A. Zeber, John E. Bauer, Mark S. Lasky, Elaine Good, Chester B. TI Determinants of Complementary and Alternative Medicine Use by Patients with Bipolar Disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE mood disorders-bipolar; alternative medicine; utilization; pharmacotherapy; drug-drug interactions AB Objectives: We determined the prevalence and correlates of complementary and alternative medicine (CAM) use among patients with bipolar disorder. Methods: Patients with bipolar disorder recruited from a large urban mental health facility from 2004 to 2006 completed a baseline questionnaire on CAM use, demographics, treatment perspectives, and behaviors. Additional data on current medications and clinical features were ascertained via chart review. Multivariable logistic regression was used to determine the patient sociodemographic, clinical, and treatment factors associated with use of different CAM practices. Results: Of 435 patients, the mean age was 49 years; 77% were white, 13% were black, and 10% other race/ethnicity. Patients reported a wide range of CAM use, including prayer/spiritual healing (54%), meditation (53%), vitamins or herbs (50%), and weight loss supplements (22%). Multivariable analyses controlling for sociodemographic, clinical, and treatment factors revealed that patients of other racial/ethnic groups (other than whites or Blacks), those diagnosed with bipolar spectrum disorders (other than bipolar I disorder), and those prescribed anticonvulsants (eg, valproic acid, carbamazepine), or atypical antipsychotics were most likely to use CAM. Conclusions: A substantial number of patients diagnosed with bipolar disorder is using CAM. CAM use may be popular among patients with this illness because conventional pharmacotherapy for managing bipolar symptoms can also disrupt quality of life. Mental health providers should be aware of CAM use among patients with bipolar disorder and assess the potential impact of CAM use on treatment course. Psychopharmacology Bulletin. 2007;40(3):104-115. C1 [Kilbourne, Amy M.] VA Ann Arbor Natl Serious Mental Illness Treatmen, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Copeland, Laurel A.; Zeber, John E.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Copeland, Laurel A.; Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Brockton, MA USA. [Lasky, Elaine; Good, Chester B.] VA Pittsburgh Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), VA Ann Arbor SMITREC 11H, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 02-283]; Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System; Veterans Evidence-based Research, Dissemination, and Implementation Center (VERDICT); VA Health Services Research and Development program FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 02-283; A. Kilbourne, PI). This work was also completed with the support of the Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System and the Veterans Evidence-based Research, Dissemination, and Implementation Center (VERDICT). Dr. Copeland is funded by the Career Development Award Merit Review Entry Program from the VA Health Services Research and Development program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 23 TC 8 Z9 10 U1 3 U2 9 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2007 VL 40 IS 3 BP 104 EP 115 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HK UT WOS:000207792900010 PM 18007572 ER PT J AU Miklowitz, DJ Otto, MW AF Miklowitz, David J. Otto, Michael W. TI Psychosocial Interventions for Bipolar Disorder: A Review of Literature and Introduction of the Systematic Treatment Enhancement Program SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Review DE bipolar disorder; ethnicity/race; health disparities; illness characteristics ID INPATIENT FAMILY INTERVENTION; RANDOMIZED CLINICAL-TRIAL; LONGITUDINAL FOLLOW-UP; LIFE EVENTS; COGNITIVE THERAPY; METHODOLOGICAL ISSUES; MAINTENANCE TREATMENT; RELAPSE PREVENTION; EXPRESSED EMOTION; MANIA AB What is the evidence that psychosocial treatment adds to the efficacy of pharmacotherapy in forestalling episodes of bipolar disorder (BPD)? This article gives the rationale for including psychosocial intervention in the outpatient maintenance of BPD. Attention is placed on the three psychosocial modalities that have achieved empirical support in randomized trials: family psychoeducational treatment, cognitive-behavioral therapy, and interpersonal and social rhythm therapy. These three treatments a re being contrasted with a psychosocial control condition in the context of the ongoing, multi-center Systematic Treatment Enhancement Pro gram for Bipolar Disorder (STEP-BD). The objectives, de sign, and potential contributions of the STEP-B D study are explained. Future directions for the evaluation and dissemination of manual-based psychosocial interventions are discussed. Psychopharmacology Bulletin. 2007;40(4):116-131. C1 [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Otto, Michael W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Otto, Michael W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Miklowitz, DJ (reprint author), MedWorks Media, 1048 17th St, Santa Monica, CA 90403 USA. EM mthase@medworksmedia.com FU National Institute of Mental Health [R21-MH62555, 98 DS 001]; National Alliance for Research on Schizophrenia and Depression FX This research was supported by grants R21-MH62555 (Dr. Miklowitz) and Contract No. 98 DS 001 (Dr. Gary Sachs) from the National Institute of Mental Health, and a Distinguished Investigator Award to Dr. Miklowitz from the National Alliance for Research on Schizophrenia and Depression. NR 74 TC 19 Z9 20 U1 2 U2 6 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2007 VL 40 IS 4 BP 116 EP 131 PG 16 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15OF UT WOS:000207810600008 PM 18227782 ER PT J AU Metzger, LJ Orr, SP Paige, SR Pitman, RK AF Metzger, Linda J. Orr, Scott P. Paige, Stephen R. Pitman, Roger K. TI Intensity-dependence of the auditory P2 in monozygotic twins discordant for vietnam combat: Associations with PTSD SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 16-21, 2007 CL Savannah, GA DE PTSD; P2 intensity-dependence; twin study C1 Vet Affairs Med Ctr, Manchester, Lancs, England. 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2007 VL 44 SU 1 BP S102 EP S102 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 203VK UT WOS:000249001900464 ER PT J AU Pontoski, KE Bovin, MJ Sloan, DM Marx, BP AF Pontoski, Kristin E. Bovin, Michelle J. Sloan, Denise M. Marx, Brian P. TI Does respiratory sinus arrhythmia predict PTSD symptom severity? SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 16-21, 2007 CL Savannah, GA DE PTSD; respiratory sinus arrhythmia; heart rate C1 Temple Univ, Philadelphia, PA 19122 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2007 VL 44 SU 1 BP S56 EP S57 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 203VK UT WOS:000249001900257 ER PT J AU Santesso, DL Cowman, E Pajtas, P Evans, AE Pizzagalli, DA AF Santesso, Diane L. Cowman, Erika Pajtas, Petra Evans, A. Eden Pizzagalli, Diego A. TI The effects of pramipexole, a D2/D3 agonist, on reward processing: An ERP source localization study SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 16-21, 2007 CL Savannah, GA C1 Harvard Univ, Cambridge, MA 02138 USA. 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2007 VL 44 SU 1 BP S81 EP S81 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 203VK UT WOS:000249001900369 ER PT J AU Labus, JS Mayer, EA Chang, L Bolus, R Naliboff, BD AF Labus, Jennifer S. Mayer, Emeran A. Chang, Ln Bolus, Roger Naliboff, Bruce D. TI The central role of gastrointestinal-specific anxiety in irritable bowel syndrome: Further validation of the visceral sensitivity index SO PSYCHOSOMATIC MEDICINE LA English DT Article DE gastrointestinal; anxiety; assessment; irritable bowel syndrome ID ASIAN-AMERICAN; PAIN ANXIETY; DEPRESSION; SCALE; FEAR; NEUROTICISM; GUIDELINES; EXPERIENCE; REGRESSION; DISORDERS AB Objectives: The Visceral Sensitivity Index (VSI) was developed as the first instrument to assess gastrointestinal-specific anxiety, the cognitive, affective, and behavioral response to fear of gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. The purpose of the current study was to a) replicate the previously reported psychometric properties of the VSI, b) assess the known-groups and concurrent validity of the instrument, and c) test conceptual hypotheses regarding gastrointestinal-specific anxiety in comparison to other general measures of psychological distress as a crucial mechanism (mediator/moderator) underlying irritable bowel syndrome diagnosis and its symptoms. Methods: Two undergraduate student samples (n > 500) were administered the VSI along with measures assessing presence of lower gastrointestinal symptoms, nongastrointestinal pain, health-service utilization, anxiety, depression, vitality, neuroticism, and anxiety sensitivity. Path analyses tested the hypothesis that gastrointestinal-specific anxiety mediates the relationship between affective variables and irritable bowel syndrome diagnosis and symptoms. A 'known-groups' validity approach elucidated the relevance of gastrointestinal-specific anxiety across a spectrum of irritable bowel syndrome patients. Results: Good concurrent, divergent and discriminant validity was demonstrated. Logistic regression revealed that gastrointestinal-specific anxiety is the key explanatory variable of irritable bowel syndrome diagnostic status. Path analysis demonstrated that gastrointestinal-specific anxiety mediates the relationship between general psychological distress measures and gastrointestinal symptom severity. The VSI was related to gastrointestinal, but not nongastrointestinal, symptom severity. Conclusions: Overall, the VSI demonstrated excellent psychometric properties providing further support for its use in mechanistic studies of the role of anxiety in irritable bowel syndrome presentation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Labus, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Peter V Ueberroth Bldg,Rm 2338C2,10946 Le Conte A, Los Angeles, CA 90095 USA. EM jlabus@ucla.edu FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [P50 DK64539]; NINR NIH HHS [NR 04881] NR 47 TC 87 Z9 88 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2007 VL 69 IS 1 BP 89 EP 98 DI 10.1097/PSY.0b013e31802e2f24 PG 10 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 131EX UT WOS:000243852200013 PM 17244851 ER PT J AU Perlis, RH Beasley, CM Wines, JD Tamura, RN Cusin, C Shear, D Amsterdam, J Quitkin, F Strong, RE Rosenbaum, JF Fava, M AF Perlis, Roy H. Beasley, Charles M., Jr. Wines, James D., Jr. Tamura, Roy N. Cusin, Cristina Shear, Deborah Amsterdam, Jay Quitkin, Frederick Strong, Robert E. Rosenbaum, Jerrold F. Fava, Maurizio TI Treatment-associated suicidal ideation and adverse effects in an open, multicenter trial of fluoxetine for major depressive episodes SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE fluoxetine; suicidal ideation ID SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT TREATMENT; PSYCHOMETRIC CHARACTERISTICS; PSYCHIATRIC OUTPATIENTS; RISK; PLACEBO; EMERGENCE; AKATHISIA; SSRIS; RELAPSE AB Background: Some reports suggest that a subset of depressed patients may experience suicidality-that is increase or emergence of suicidal ideation ( SI) or behavior-after initiation of an antidepressant. The time course and clinical correlates of this phenomenon have not been characterized in detail. Method: We conducted a secondary analysis of a multicenter, prospective, open, 12-week trial of fluoxetine 20 mg in outpatients with nonpsychotic major depressive episodes. Adverse effects and other clinical features associated with the emergence of suicidality, defined using item 3 of the Hamilton Depression Rating Scale, were examined using Cox regression models. Results: Among 414 subjects without SI at baseline, 59 (14.3%) reported SI on at least 1 postbaseline visit. In a Cox regression, emergence of activation and worsening of depression severity were independently associated with emergence of SI, along with female gender, younger age and having thoughts that life was not worth living prior to treatment. Treatment response and remission were significantly less likely among subjects who developed SI. Conclusions: New SI was relatively common in this trial of fluoxetine and associated with the emergence of activation and overall symptomatic worsening. Whether prophylaxis against or aggressive treatment of adverse events can decrease emergence of SI merits further study. Copyright (c) 2007 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. Univ Penn, Med Ctr, Depression Res Unit, Philadelphia, PA 19104 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Utah, Salt Lake City, UT USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org FU NIDA NIH HHS [K23 DA-00455]; NIMH NIH HHS [K23 MH-067060] NR 52 TC 48 Z9 51 U1 2 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2007 VL 76 IS 1 BP 40 EP 46 DI 10.1159/000096363 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 116JK UT WOS:000242798400005 PM 17170562 ER PT J AU Ghaemi, SN Baldessarini, RJ AF Ghaemi, S. Nassir Baldessarini, Ross J. TI The manic-depressive spectrum and mood stabilization: Kraepelin's ghost SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Editorial Material ID BIPOLAR-I DISORDER; ANTIDEPRESSANTS; SCHIZOPHRENIA; EVOLUTION; MAINTENANCE; TRANSLATION; FREQUENCY; INSANITY; ILLNESS C1 Emory Univ, Sch Med, Dept Psychiat, Bipolar Disorder Res Program, Atlanta, GA 30322 USA. Harvard Univ, McLean Div, Biopolar Disorder Program, Massachusetts Gen Hosp,Med Sch,Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, McLean Div, Biopolar Disorder Program, Massachusetts Gen Hosp,Med Sch,Neurosci Program, Belmont, MA 02178 USA. RP Ghaemi, SN (reprint author), Cambridge Hlth Alliance, Dept Psychiat, CSHC, 1493 Cambridge St, Cambridge, MA 02139 USA. EM ghaemi@hms.harvard.edu RI Ghaemi, Nassir/J-4934-2013 FU NIMH NIH HHS [MH64189-02] NR 35 TC 24 Z9 24 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2007 VL 76 IS 2 BP 65 EP 69 DI 10.1159/000097964 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 127DJ UT WOS:000243565200001 PM 17230046 ER PT J AU Papakostas, GI Perlis, RH Seifert, C Fava, M AF Papakostas, George I. Perlis, Roy H. Seifert, Cheryl Fava, Maurizio TI Antidepressant dose reduction and the risk of relapse in major depressive disorder SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE antidepressant dose reduction; antidepressants, dosing and relapse; depression; depressive relapse; dose of depressants; major depressive disorder; relapse/recurrence rates ID IMPRESSIONS RATING-SCALE; CLINICAL-TRIALS; RELATIVE SENSITIVITY; RECURRENT DEPRESSION; METAANALYSIS; PREVENTION; CRISIS AB Background: Whether the dose of antidepressants can be reduced following clinical improvement without subsequently increasing the likelihood of depressive relapse has not been established. Thus, the aim of this work was to compare relapse rates among patients with major depressive disorder ( MDD) randomized to either continue receiving the full versus a reduced dose of antidepressants following partial or full improvement of symptoms. Methods: Five double-blind, randomized clinical trials involving 1,009 patients with MDD randomized to either continue receiving the full versus a reduced dose of antidepressants following partial or full improvement of symptoms were pooled using a random-effect meta-analysis model. Results: Patients randomized to continue treatment with lower doses of antidepressants were more likely to experience a depressive relapse than patients who continued treatment with the full dose ( risk ratio 1.62, 95% confidence interval: 1.52-2.80, p = 0.001). Pooled relapse rates were 25.3 and 15.1% for the two treatment groups. Conclusions: Decreasing the antidepressant dose following partial or full symptom improvement is associated with an increased risk of relapse in MDD. Copyright (c) 2007 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Depress Clin & Res Program, Massachusetts Gen Hosp,Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Depress Clin & Res Program, Massachusetts Gen Hosp,Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 19 TC 14 Z9 15 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2007 VL 76 IS 5 BP 266 EP 270 DI 10.1159/000104702 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 201CH UT WOS:000248808600003 PM 17700046 ER PT J AU Harley, RM Baity, MR Blais, MA Jacobo, MC AF Harley, Rebecca M. Baity, Matthew R. Blais, Mark A. Jacobo, Michelle C. TI Use of dialectical behavior therapy skills training for borderline personality disorder in a naturalistic setting SO PSYCHOTHERAPY RESEARCH LA English DT Article ID VALIDATION; FEATURES; EFFICACY; WOMEN AB This nonrandomized, naturalistic study describes a modified outpatient dialectical behavior therapy (DBT) program for borderline personality disorder (BPD) in which some patients receive the comprehensive, empirically supported DBT package and others receive DBT skills group therapy with non-DBT individual therapy. Patients who completed one skills group cycle showed significant improvements in BPD, depression, and suicidal ideation as measured by the Personality Assessment Inventory. Fifty-one percent of patients dropped out of skills group, but patients with in-system individual therapy were significantly more likely to complete group therapy. Although causal conclusions cannot be drawn, this report demonstrates that a modified DBT program can be implemented successfully in settings in which a full DBT package for all patients may not be feasible and suggests that BPD patients receiving non-DBT individual therapy may benefit from DBT skills group. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Harley, RM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rharley@partners.org NR 23 TC 11 Z9 11 U1 2 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PY 2007 VL 17 IS 3 BP 362 EP 370 DI 10.1080/10503300600830710 PG 9 WC Psychology, Clinical SC Psychology GA 168NS UT WOS:000246531900010 ER PT J AU Nelson, KM Starkebaum, GA Reiber, GE AF Nelson, Karin M. Starkebaum, Gordon A. Reiber, Gayle E. TI Veterans using and uninsured veterans not using veterans affairs (VA) Health Care SO PUBLIC HEALTH REPORTS LA English DT Article ID OUTPATIENT CLINICS; MEDICAL-CARE; COVERAGE; SYSTEM; ENROLLEES; ACCESS; ADULTS; COSTS; HMOS AB The objectives of this study were to: (1) examine veteran reliance on health services provided by the Veterans Health Administration (VA), (2) describe the characteristics of veterans who receive VA care, and (3) report rates of uninsurance among veterans and characteristics of uninsured veterans. The authors analyzed data from the 2000 Behavioral Risk Factor Surveillance System. Using bivariate and multivariate analyses, the association of veteran's demographic characteristics, health insurance coverage, and use of VA services were examined. Veterans not reporting VA coverage and having no other source of health insurance were considered uninsured. Among veteran respondents, 6.2% reported receiving all of their health care at the VA, 6.9% reported receiving some of their health care at the VA, and 86.9% did not use VA health care. Poor, less-educated, and minority veterans were more likely to receive all of their health care at the VA. Veterans younger than age 65 who utilized the VA for all of their health care also reported coverage with either private insurance (42.6%) or Medicare (36.3%). Of the veterans younger than age 65, 8.6% (population estimate: 1.3 million individuals) were uninsured. Uninsured veterans were less likely to be able to afford a doctor or see a doctor within the last year. Veterans who utilized the VA for all of their health care were more likely to be from disadvantaged groups. A large number of veterans who could use VA services were uninsured. They should be targeted for VA enrollment given the detrimental clinical effects of being uninsured. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98107 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98107 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way,S-111 GIMC, Seattle, WA 98107 USA. EM Karin.Nelson@va.gov NR 32 TC 37 Z9 37 U1 0 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 JAN-FEB PY 2007 VL 122 IS 1 BP 93 EP 100 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 133JU UT WOS:000244010000013 PM 17236614 ER PT J AU Efimova, O Volokhov, A Hales, CA AF Efimova, Olga Volokhov, Alexel Hales, Charles A. TI Injection of prostaglandin F2 alpha into the bronchial artery in sheep increases the pulmonary vascular permeability to protein SO PULMONARY PHARMACOLOGY & THERAPEUTICS LA English DT Article CT Annual Meeting of the Da-Vinci-Society CY SEP 23-25, 2005 CL Camogli, ITALY SP Da Vinci Soc DE tracheobronchial circulation; lung lymph flow; lung lymph permeability; eicosanoids ID INHALATION INJURY; BLOOD-FLOW; LUNG; CIRCULATION; SMOKE; EXPOSURE; EDEMA; LIGATION; ACROLEIN; TRACHEAL AB Lung injury and oedema following smoke inhalation are associated with eicosanoid release and the injury is heavily influenced by the tracheobronchial circulation. We hypothesized that injection of a vasoactive eicosanoid, prostaglandin F2alpha (PGF2 alpha), into the tracheobronchial circulation would induce a permeability leak in that circulation as measured in lung lymph flow and protein content. PGF2a when injected into the bronchial artery increased lung lymph flow, protein content and lymph protein flux (protein times flow). The increase in lymph to plasma protein concentration after injection of PGF2 alpha is consistent with an increase in vascular protein permeability since an increase in pressure alone would cause an increase in fluid flow in excess of protein with a fall in protein concentration. Ligation of the bronchial artery 3 min after injection of the PGF2 alpha largely prevented the late changes suggesting that the protein leak into the lymph was from the bronchial arteries. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org NR 23 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1094-5539 J9 PULM PHARMACOL THER JI Pulm. Pharmacol. Ther. PY 2007 VL 20 IS 2 BP 167 EP 171 DI 10.1016/j.pupt.2005.12.005 PG 5 WC Pharmacology & Pharmacy; Respiratory System SC Pharmacology & Pharmacy; Respiratory System GA 130FP UT WOS:000243785400014 PM 16979921 ER PT J AU Suit, H Goldberg, S Niemierko, A Ancukiewicz, M Hall, E Goitein, M Wong, W Paganetti, H AF Suit, Herman Goldberg, Saveli Niemierko, Andrzej Ancukiewicz, Marek Hall, Eric Goitein, Michael Wong, Winifred Paganetti, Harald TI Secondary carcinogenesis in patients treated with radiation: A review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects SO RADIATION RESEARCH LA English DT Review ID ATOMIC-BOMB SURVIVORS; 2ND PRIMARY-CANCER; FISSION-SPECTRUM NEUTRONS; IRRADIATED RHESUS-MONKEYS; TRANSFORMATION IN-VITRO; INCREASED TUMOR RATES; STAGE BREAST-CANCER; SOFT-TISSUE SARCOMA; MAMMOGRAPHY X-RAYS; 20-YEAR FOLLOW-UP AB Concern for risk of radiation-induced cancer is growing with the increasing number of cancer patients surviving long term. This study examined data on radiation transformation of mammalian cells in vitro and on the risk of an increased cancer incidence after irradiation of mice, dogs, monkeys, atomic bomb survivors, occupationally exposed persons, and patients treated with radiation. Transformation of cells lines in vitro increased linearly with dose from similar to 1 to similar to 4-5 Gy. At < 0.1 Gy, transformation was not increased in all studies. Dose-response relationships for cancer incidence varied with mouse strain, gender and tissue/organ. Risk of cancer in Macoca mulatta was not raised at 0.25-2.8 Gy. From the atomic bomb survivor study, risk is accepted as increasing linearly to 2 Sv for establishing exposure standards. In irradiated patients, risk of cancer increased significantly from 1 to 45 Gy (a low to a high dose level) for stomach and pancreas, but not for bladder and rectum (1-60 Gy) or kidney (1-15 Gy). Risk for several organs/tissues increased substantially at doses far above 2 Gy. There is great heterogeneity in risk of radiation-associated cancer between species, strains of a species, and organs within a species. At present, the heterogeneity between and within patient populations of virtually every parameter considered in risk estimation results in substantial uncertainty in quantification of a general risk factor. An implication of this review is that reduced risks of secondary cancer should be achieved by any technique that achieved a dose reduction down to -0.1 Gy, i.e. dose to tissues distant from the target. The proportionate gain should be greatest for dose decrement to less than 2 Gy. (c) 2007 by Radiation Research Society. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. RP Suit, H (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Founders Bldg,Room 544, Boston, MA 02114 USA. EM Hsuit@Partners.Org FU NCI NIH HHS [CA50628, CA21239] NR 112 TC 113 Z9 117 U1 0 U2 5 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2007 VL 167 IS 1 BP 12 EP 42 DI 10.1667/RR0527.1 PG 31 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 123HX UT WOS:000243288100002 PM 17214511 ER PT J AU Prabhakar, HB Sahani, DV Fischman, AJ Mueller, PR Blake, MA AF Prabhakar, Hima B. Sahani, Dushyant V. Fischman, Alan J. Mueller, Peter R. Blake, Michael A. TI Bowel hot spots at PET-CT SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID POSITRON-EMISSION-TOMOGRAPHY; GASTROINTESTINAL STROMAL TUMORS; ORAL CONTRAST-MEDIUM; IN-LINE PET/CT; WHOLE-BODY PET; FDG-PET; CLINICAL-SIGNIFICANCE; COLORECTAL-CANCER; DISEASE ACTIVITY; F-18-FDG PET AB Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy- D-glucose (FDG) has been shown to be sensitive in the detection of many bowel malignancies, but its specificity is lower because of various physiologic and pathologic patterns of bowel FDG uptake. PET - computed tomography (CT) can be useful in localizing and characterizing foci of increased FDG uptake within the bowel. As the use of PET-CT in the staging and monitoring of oncologic disease continues to expand, familiarity with these patterns of bowel FDG uptake is essential and can help determine the need for and the relative urgency of further testing. Although a variety of imaging protocols are used for PET-CT, the use of negative oral contrast agent allows improved bowel distention while eliminating potential artifacts caused by high-density oral contrast agents. In addition, correlation with the CT portion of the combined PET-CT examination can sometimes help identify the cause of focal or segmental bowel uptake. The radiologist should be aware of potential pitfalls in the evaluation of FDG-avid foci within the abdomen, including bowel motility and low-attenuation lesions mimicking bowel. Nevertheless, even though the precise role of combined PET-CT for bowel assessment has yet to be determined, the application of sound basic principles of image interpretation will help ensure the accurate interpretation of bowel findings seen with this combined modality. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 39 TC 61 Z9 63 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2007 VL 27 IS 1 BP 145 EP U13 DI 10.1148/rg.271065080 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 127PV UT WOS:000243599700014 PM 17235004 ER PT J AU Weissleder, R Imhof, H AF Weissleder, R. Imhof, H. TI Molecular imaging - a new focal point of radiology SO RADIOLOGE LA German DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Med Univ Wien, Klin Radiodiagnost, Vienna, Austria. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. NR 0 TC 2 Z9 3 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD JAN PY 2007 VL 47 IS 1 BP 6 EP 7 DI 10.1007/s00117-006-1447-7 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 138ZV UT WOS:000244402700002 PM 17136404 ER PT J AU Nahrendorf, M Weissleder, R AF Nahrendorf, M. Weissleder, R. TI Advances in cardiovascular medicine through molecular imaging SO RADIOLOGE LA German DT Article DE molecular imaging; atherosclerosis; VCAM-1; myocardial infarction; healing; apoptosis; factor XIII; stem cells ID MATRIX-METALLOPROTEINASE ACTIVITY; IN-VIVO; MYOCARDIAL-INFARCTION; IRON-OXIDE; ATHEROSCLEROTIC PLAQUE; VISUALIZATION; ACCUMULATION; NANOPARTICLE; INFLAMMATION; MACROPHAGES AB We will witness a change of paradigm in cardiovascular imaging, which is empowered by advances in imaging technology, biochemistry, molecular biology and nanotechnology. Instead of simply following the physical distribution of established contrast agents, we now have the opportunity to noninvasively image biological processes such as enzyme activity, interaction with cell surface markers, gene expression and cell migration. These advancements open up new avenues in basic cardiovascular research and will greatly speed up the pace of discovery. Patient management will profit as well: cardiovascular molecular imaging will strengthen personlized and prophylactic medicine through timely and precise diagnostics. In our review we describe selected molecular imaging strategies in atherosclerosis, myocardial ischemia and healing. C1 Harvard Univ, Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Nahrendorf, M (reprint author), Harvard Univ, Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm,5406,149 31th St, Charlestown, MA 02129 USA. EM MNahrendorf@partners.org NR 30 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD JAN PY 2007 VL 47 IS 1 BP 18 EP 24 DI 10.1007/s00117-006-1450-z PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 138ZV UT WOS:000244402700004 PM 17187263 ER PT J AU Grimm, J Kircher, MF Weissleder, R AF Grimm, J. Kircher, M. F. Weissleder, R. TI Cell tracking. Principles and applications SO RADIOLOGE LA German DT Article DE cell tracking; cell trafficking; marker gene; labeling; stem cells; immunotherapy ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO TRACKING; GENE-EXPRESSION; TAT PEPTIDE; REAL-TIME; NANOPARTICLES; MIGRATION; THERAPY; CANCER AB Cell based therapies such as stem cell therapies or adoptive immunotherapies are currently being explored as a potential treatment for a variety of diseases such as Parkinson's disease, diabetes or cancer. However, quantitative and qualitative evaluation of adoptively transferred cells is indispensable for monitoring the efficiency of the treatment. Current approaches mostly analyze transferred cells from peripheral blood, which cannot assess whether transferred cells actually home to and stay in the targeted tissue. Using cell-labeling methods such as direct labeling or transfection with a marker gene in conjunction with various imaging modalities (MRI, optical or nuclear imaging), labeled cells can be followed in vivo in real-time, and their accumulation as well as function in vivo can be monitored and quantified accurately. This method is usually referred to as "cell tracking" or "cell trafficking" and is also being applied in basic biological sciences, exemplified in the evaluation of genes contributing to metastasis. This review focuses on principles of this promising methodology and explains various approaches by highlighting recent examples. C1 Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA USA. RP Grimm, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. EM grimmj@mskcc.org RI Grimm, Jan/B-1937-2008 NR 32 TC 19 Z9 20 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD JAN PY 2007 VL 47 IS 1 BP 25 EP 33 DI 10.1007/s00117-006-1449-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 138ZV UT WOS:000244402700005 PM 17187264 ER PT J AU Stein, PD Woodard, PK Weg, JG Wakefield, TW Tapson, VF Sostman, HD Sos, TA Quinn, DA Leeper, KV Hull, RD Hales, CA Gottschalk, A Goodman, LR Fowler, SE Buckley, JD AF Stein, Paul D. Woodard, Pamela K. Weg, John G. Wakefield, Thomas W. Tapson, Victor F. Sostman, H. Dirk Sos, Thomas A. Quinn, Deobrah A. Leeper, Kenneth V., Jr. Hull, Russell D. Hales, Charles A. Gottschalk, Alexander Goodman, Lawrence R. Fowler, Sarah E. Buckley, John D. TI Diagnostic pathways in acute pulmonary embolism: Recommendations of the PIOPED II investigators SO RADIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; ACUTE VENOUS THROMBOSIS; SIMPLE CLINICAL-MODEL; D-DIMER; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; CONTRAST-MEDIA; HELICAL CT; ANGIOGRAPHY; NEPHROTOXICITY C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Duke Univ, Dept Med, Durham, NC 27706 USA. Weill Cornell Med Coll, Off Dean, New York, NY USA. Methodist Hosp, Off Execut Vice President, Houston, TX 77030 USA. Weill Cornell Med Coll, Dept Radiol, New York, NY USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Univ Calgary, Dept Med, Calgary, AB, Canada. Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. George Washington Univ, Ctr Biostat, Dept Epidemiol & Biostat, Rockville, MD USA. Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinpo@trinity-health.org FU NHLBI NIH HHS [HL63932, HL63899, HL63928, HL63931, HL63940, HL63941, HL63942, HL63981, HL63982, HL67453] NR 53 TC 121 Z9 132 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2007 VL 242 IS 1 BP 15 EP 21 DI 10.1148/radiol.2421060971 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131BH UT WOS:000243842500005 PM 17185658 ER PT J AU Menezes, NM Connolly, SA Shapiro, F Olear, EA Jimenez, RM Zurakowski, D Jaramillo, D AF Menezes, Nina M. Connolly, Susan A. Shapiro, Frederic Olear, Elizabeth A. Jimenez, Rafael M. Zurakowski, David Jaramillo, Diego TI Early ischemia in growing piglet skeleton: MR diffusion and perfusion imaging SO RADIOLOGY LA English DT Article ID CAPITAL FEMORAL EPIPHYSIS; CALVE-PERTHES-DISEASE; BONE-SCINTIGRAPHY; IMMATURE PIGS; NECROSIS; HEAD; INFARCTION; MORPHOLOGY; CARTILAGE; HIP AB Purpose: To determine whether diffusion changes with ischemia of increasing duration, whether diffusion magnetic resonance (MR) imaging provides different information than does gadolinium-enhanced imaging, and which structural and/or biochemical changes are potentially responsible for any changes in diffusion. Materials and Methods: Ischemia was surgically induced in one hip of each piglet (n = 8) after approval from the Subcommittee on Research Animal Care; the other hip served as a control. Piglets were imaged at approximately 48 hours and 1, 2, 4, and 8 weeks after surgery at 1.5 T by using line-scan diffusion and dynamic gadolinium-enhanced MR imaging. Apparent diffusion coefficients (ADCs) and enhancement ratios (ERs) were calculated. Significant differences in ADC and ER values over time were evaluated by using the Student t test (P < .05). At 8 weeks, piglets were sacrificed for histologic evaluation. Results: MR images of ischemic hips showed esesentially no flow 48 hours after surgery. Spontaneous partial reperfusion was observed 1-4 weeks after surgery (ischemic ER/control ER = 66% +/- 35 [standard deviation]), and the ER of the ischemic hips was well above that of the control hips at 8 weeks. The ADC of ischemic hips was elevated above that of control hips before reperfusion 1 week after surgery by 47% +/- 12 and remained elevated despite flow restoration. Gross structural abnormalities on MR images appeared to coincide with reperfusion. Histologic findings revealed abnormal epiphyseal cartilage thickening, cartilaginous islands within ossified tissue, and less fatty marrow in ischemic hips than in control hips; all of these factors could explain elevated ADC. Conclusion: Diffusion is sensitive to early ischemia and follows a different time course than that of changes observed with gadolinium enhancement. ADC remained elevated in this model of severe, prolonged ischemia despite the spontaneous partial restoration of blood flow seen on gadolinium-enhanced images. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. RP Menezes, NM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM nmenezes@nmr.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR042396-09] NR 26 TC 36 Z9 43 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2007 VL 242 IS 1 BP 129 EP 136 DI 10.1148/radiol.2421050680 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131BH UT WOS:000243842500017 PM 17185664 ER PT B AU Aikawa, E Aikawa, M AF Aikawa, E. Aikawa, M. BE Kimchi, A TI Identification of subclinical cardiovascular inflammation and calcification SO RECENT ADVANCES IN CARDIOVASCULAR DISEASE: PROCEEDINGS OF THE 13TH WORLD CONGRESS HEART DISEASE LA English DT Proceedings Paper CT 13th World Congress on Heart Disease CY JUL 28-31, 2007 CL Vancouver, CANADA ID IN-VIVO; ATHEROSCLEROSIS; DISEASE; PREDICTION; MEDICINE; VALVES AB Atherosclerosis and its complications contribute critically to morbidity and mortality. Macrophages produce various factors that promote inflammatory milieu in arteries and cause plaque destabilization, thrombogenicity and calcification. Emerging molecular imaging approach offers a sensitive diagnostic tool that provides functional information to identify novel mechanisms in various cardiovascular diseases including atherosclerosis and arterial and valvular calcification. Combine use of molecular imaging, novel biomarkers and genetics will identify subclinical inflamed lesions and provide new insight into preventive cardiovascular medicine. Key words: Subclinical lesions, personalized medicine, preventive medicine, risk predictor, clinical trials, precalcification, microcalcification, inflammation, macrophages. C1 [Aikawa, E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Cambridge, MA 02138 USA. RP Aikawa, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Cambridge, MA 02138 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-369-1 PY 2007 BP 1 EP 6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHX88 UT WOS:000257311100001 ER PT J AU Murphy, JM AF Murphy, Jane M. BE Tsuang, MT Stone, WS Lyons, MJ TI Social Environment and Psychiatric Disorders A Historical Review Presented on Receipt of the Paul H. Hoch Award SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Review; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; EPIDEMIOLOGIC CATCHMENT-AREA; NATIONAL-COMORBIDITY-SURVEY; DIAGNOSTIC-INTERVIEW-SCHEDULE; MENTAL-HEALTH; MAJOR DEPRESSION; UNITED-STATES; STIRLING-COUNTY; PREVALENCE; COMMUNITY C1 [Murphy, Jane M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Murphy, Jane M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Murphy, Jane M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Murphy, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 99 TC 0 Z9 0 U1 3 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 53 EP 74 PG 22 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300004 ER PT J AU Breitner, JCS AF Breitner, John C. S. BE Tsuang, MT Stone, WS Lyons, MJ TI Prevention of Alzheimer's Disease Principles and Prospects SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Article; Book Chapter ID MILD COGNITIVE IMPAIRMENT; ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; APOLIPOPROTEIN-E; CACHE COUNTY; DOUBLE-BLIND; RISK C1 [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, Seattle, WA 98195 USA. RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 319 EP 328 PG 10 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300014 ER PT J AU Pitman, RK Delahanty, DL AF Pitman, Roger K. Delahanty, Douglas L. BE Tsuang, MT Stone, WS Lyons, MJ TI Conceptually Driven Pharmacological Approaches to Acute Trauma SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; MOTOR-VEHICLE ACCIDENTS; MEMORY CONSOLIDATION; BASOLATERAL AMYGDALA; EMOTIONAL EVENTS; SEPTIC SHOCK; HEART-RATE; PTSD; SURVIVORS; HYDROCORTISONE C1 [Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [Delahanty, Douglas L.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 72 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 371 EP 387 PG 17 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300017 ER PT J AU Ajar, A Hoeft, M Alsofrom, GF Mukerji, SK Rathmell, JP AF Ajar, Amir Hoeft, Mark Alsofrom, Gary F. Mukerji, Suresh K. Rathmell, James P. TI Review of brachial plexus anatomy as seen on diagnostic imaging: Clinical correlation with computed tomography-guided brachial plexus block SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Editorial Material ID NERVE BLOCK; SURGERY; HAND; CT C1 Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Vermont, Coll Med, Dept Anesthesiol, Burlington, VT USA. Univ Vermont, Coll Med, Dept Radiol, Burlington, VT USA. Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Pain Ctr, Dept Anesthesia & Crit Care, 15 Parkway St,WACC 333, Boston, MA 02114 USA. EM jrathmell@partners.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2007 VL 32 IS 1 BP 79 EP 83 DI 10.1016/j.rapm.2006.09.006 PG 5 WC Anesthesiology SC Anesthesiology GA 123QT UT WOS:000243311100014 PM 17196497 ER PT S AU Gergely, J AF Gergely, John BE Ebashi, S Ohtsuki, I TI Highlights of the history of calcium regulation of striated muscle SO REGULATORY MECHANISMS OF STRIATED MUSCLE CONTRACTION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 33rd Symposium on Regulatory Mechanisms of Striated Muscle Contraction CY OCT 25-28, 2005 CL Okazaki, JAPAN SP Natl Inst Physiol Sci, Jikei Univ Sch Med, Japan Sci & Technol Agcy, Uehara Memorial Fdn Life Sci, Sankyo Life Sci Fdn, Naito Memorial Fdn, Kato Memorial Fund Dis, Zenyaku Kogyo Co Ltd ID THIN FILAMENT PROTEINS; AMINO-ACID-SEQUENCE; TROPONIN-C; SKELETAL-MUSCLE; BINDING-SITES; F-ACTIN; CONFORMATIONAL TRANSITION; BIOLOGICAL-ACTIVITY; STRUCTURAL-CHANGES; TROPOMYOSIN C1 Harvard Univ, Boston Biomed Res Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gergely, J (reprint author), Harvard Univ, Boston Biomed Res Inst, Boston, MA 02115 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-4-431-38451-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 592 BP 11 EP 18 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BFT89 UT WOS:000244562500003 PM 17278352 ER PT J AU Tofovic, SP Salah, EM Jackson, EK Melhem, M AF Tofovic, Stevan P. Salah, Ernan M. Jackson, Edwin K. Melhem, Mona TI Early renal injury induced by caffeine consumption in obese, diabetic ZSF(1) rats SO RENAL FAILURE LA English DT Review DE caffeine; metabolic syndrome; proteinuria; renal failure; tempol ID ADENOSINE RECEPTOR; METABOLIC SYNDROME; RENIN SECRETION; US ADULTS; HYPERTENSION; KIDNEY; TEMPOL; FAILURE; HEALTH; RISK AB Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/ L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2-9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immumohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine-most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine-augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats. C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsurgh Hlth Syst, Pittsburgh, PA USA. RP Tofovic, SP (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, 100 Technol Dr,Suite 450, Pittsburgh, PA 15219 USA. EM tofovic@dom.pitt.edu NR 45 TC 7 Z9 7 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0886-022X J9 RENAL FAILURE JI Ren. Fail. PY 2007 VL 29 IS 7 BP 891 EP 902 DI 10.1080/08860220701569846 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 227EY UT WOS:000250641200017 PM 17994459 ER PT J AU Kong, J Kaptchuk, TJ Polich, G Kirsch, I Gollub, RL AF Kong, Jian Kaptchuk, Ted J. Polich, Ginger Kirsch, Irving Gollub, Randy L. TI Placebo analgesia: Findings from brain Imaging studies and emerging hypotheses SO REVIEWS IN THE NEUROSCIENCES LA English DT Review DE placebo; placebo analgesia; pain; brain imaging; fMRI; PET ID ANTERIOR CINGULATE CORTEX; ORTHOGRADE HORSERADISH-PEROXIDASE; MEDIAL PREFRONTAL CORTEX; TOP-DOWN CONTROL; ORBITOFRONTAL CORTEX; SOMATOSENSORY CORTEX; PERIAQUEDUCTAL GRAY; PAIN INTENSITY; CORTICAL PROJECTIONS; OPIOID ANALGESIA AB Placebo analgesia is one of the most robust and best-studied placebo effects. With the help of brain imaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), our understanding of the brain's role in placebo analgesia has been greatly expanded. Previous studies suggest that multiple mechanisms may underlie the phenomenon of placebo analgesia. This review posits a theoretical framework for interpreting the results of the neuroimaging literature of placebo analgesia. According to this framework, placebo treatment may exert an analgesic effect on at least three stages of pain processing, by 1) influencing pre-stimulus expectation of pain relief, 2) modifying pain perception, and 3) distorting post-stimulus pain rating. Importantly, change in one such stage may hasten change in another, and furthermore, contribution from any or all of the three stages may vary by circumstance, or between individuals. The literature suggests that multiple brain regions, including the anterior cingulate cortex, anterior insula, prefrontal cortex and periaqueductal grey, play a pivotal role in these processes. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Osher Inst, Cambridge, MA 02138 USA. Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England. MIT, MGH, HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. MGH, GCRC Biomed Imaging Core, Charlestown, MA USA. RP Kong, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2661, Charlestown, MA 02129 USA. EM kongj@mnr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCCIH NIH HHS [K01AT003883] NR 122 TC 53 Z9 53 U1 2 U2 16 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2007 VL 18 IS 3-4 BP 173 EP 190 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 225VX UT WOS:000250547400001 PM 18019605 ER PT S AU Piekna-Przybylska, D Liu, B Fournier, MJ AF Piekna-Przybylska, Dorota Liu, Ben Fournier, Maurille J. BE Gott, JM TI The U1 snRNA hairpin II as a RNA affinity tag for selecting snoRNP complexes SO RNA MODIFICATION SE Methods in Enzymology LA English DT Review; Book Chapter ID PRE-RIBOSOMAL-RNA; SMALL-SUBUNIT PROCESSOME; SMALL NUCLEOLAR RNAS; ARCHAEAL BOX C/D; SACCHAROMYCES-CEREVISIAE; IN-VITRO; RIBONUCLEOPROTEIN COMPLEXES; BINDING PROTEIN; PURIFICATION METHOD; SECONDARY STRUCTURE AB 7When isolating ribonucleoprotein (RNP) complexes by an affinity selection approach, tagging the RNA component can prove to be strategically important. This is especially true for purifying single types of snoRNPs, because in most cases the snoRNA is thought to be the only unique component. Here, we present a general strategy for selecting specific snoRNPs that features a high-affinity tag in the snoRNA and another in a snoRNP core protein. The RNA tag (called U1hpll) is a small (26 nt) stem-loop domain from human U1 snRNA. This structure binds with high affinity (K-D = 10(-11) M) to the RRM domain of the snRNP protein U1A. In our approach, the U1A protein contains a unique affinity tag and is coexpressed in vivo with the tagged snoRNA to yield snoRNP-U1A complexes with two unique protein tags-one in the bound U1A protein and the other in the snoRNP core protein. This scheme has been used effectively to select C/D and H/ACA snoRNPs, including both processing and modifying snoRNPs, and the snoRNA and core proteins are highly enriched. Depending on selection stringency other proteins are isolated as well, including an RNA helicase involved in snoRNP release from pre-rRNA and additional proteins that function in ribosome biogenesis. Tagging the snoRNA component alone is also effective when U1A is expressed with a myc-Tev-protein A fusion sequence. Combined with reduced stringency, enrichment of the U14 snoRNP with this latter system revealed potential interactions with two other snoRNPs, including one processing snoRNP involved in the same cleavages of pre-rRNA. C1 Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Piekna-Przybylska, D (reprint author), Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. FU NIGMS NIH HHS [GM 19351] NR 93 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374155-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 425 BP 317 EP 353 DI 10.1016/S0076-6879(07)25014-1 PG 37 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGN29 UT WOS:000248588300014 PM 17673090 ER PT J AU El-Serag, HB Graham, DY Rabeneck, L Avid, A Richardson, P Genta, RM AF El-Serag, Hashem B. Graham, David Y. Rabeneck, Linda Avid, Adjula Richardson, Peter Genta, Robert M. TI Prevalence and determinants of histological abnormalities of the gastric cardia in volunteers SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE carditis; epidemiology; gastritis; GERD; Helicobacter pylori; metaplasia; risk factors ID HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL-REFLUX DISEASE; INTESTINAL METAPLASIA; INFLAMMATION; JUNCTION; ESOPHAGUS; SYMPTOMS; MUCOSA AB Objective. The findings of studies examining the prevalence and major risk factors of histological abnormalities of the gastric cardia have been inconsistent. Selection bias was possible in these studies depending on whether patients were referred for ulcer or gastroesophageal reflux disease ( GERD). There have been no studies on non-patient populations. The aim of this study was to mitigate the potential effects of selection bias. Material and methods. In a study comprising health-care workers, we distributed symptom questionnaires and invitations to undergo upper endoscopy. A single endoscopist performed standard endoscopy and biopsy examinations ( 2 antral, 2 corporal, and 2 cardiac biopsies). Staining was done using triple stain. Two pathologists, who were blinded to the results of the questionnaires and endoscopy, interpreted and recorded the histological findings. Results. A total of 226 participants underwent endoscopy. Gastric cardia, as defined by the presence of mucous glands, was identified in 191 subjects; mean age of the subjects was 45 years, 117 ( 61%) were women, and 49% were black. Active gastritis of the cardia was present in 58 ( 30.4%), chronic gastritis in 133 ( 69.6%), intestinal metaplasia ( IM) in 29 ( 15.2%), and pancreatic metaplasia in 25 ( 13%). Direct ( organisms) or indirect evidence ( active anywhere or chronic gastritis in antrum or corpus) for Helicobacter pylori was present in all participants with active gastritis, 60% of subjects with chronic gastritis, and approximately half of those with IM of the cardia. Approximately 15% with chronic carditis had neither H. pylori nor GERD symptoms. There were also no significant differences in the prevalence of heartburn or acid regurgitation, or the use of histamine-2-receptor antagonists ( H2RAs) or proton-pump inhibitors ( PPIs) between groups with and without active or chronic gastritis, IM, or pancreatic metaplasia, whereas active or chronic gastritis in the antrum or corpus and H. pylori infection were more frequent ( 1.5- to 2-fold) among those with histological abnormalities of the cardia. Conclusions. Active and chronic gastritis as well as intestinal metaplasia of the gastric cardia are relatively common in health-care worker volunteers. Although GERD symptoms are not significantly associated with these abnormalities, H. pylori infection is a strong risk factor. However, a considerable number of participants with chronic gastritis of the cardia have neither H. pylori nor GERD. C1 Houston Dept Vet Affiars Med Ctr 152, Gastroenterol Sect, Houston, TX 77030 USA. Houston Dept Vet Affiars Med Ctr, Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dallas VA Med Ctr, Pathol Sect, Dallas, TX USA. RP El-Serag, HB (reprint author), Houston Dept Vet Affiars Med Ctr 152, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 21 TC 6 Z9 6 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2007 VL 42 IS 10 BP 1158 EP 1166 DI 10.1080/00365520701299915 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 217NZ UT WOS:000249955900003 PM 17852849 ER PT J AU Herrmann, M Selige, J Raffael, S Sachs, G Brambilla, A Klein, T AF Herrmann, Michael Selige, Jens Raffael, Sandra Sachs, George Brambilla, Andrea Klein, Thomas TI Systematic expression profiling of the gastric H+/K+ ATPase in human tissue SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE acid pump antagonist; APA; GERD; H+/ K+ ATPase; K+ -competitive inhibitor; P-CAB; PPI; proton pump inhibitor; reflux disease; TaqMan PCR ID H,K-ATPASE BETA-SUBUNIT; MEDULLARY COLLECTING DUCT; K+-COMPETITIVE INHIBITOR; PROTON PUMP INHIBITORS; ACID-SECRETION; ALPHA-SUBUNIT; FUNCTIONAL-ROLE; H+,K+-ATPASE; NA,K-ATPASE; BINDING AB Objective. The potassium-competitive acid blockers (P-CABs), comprise a new, innovative group of competitive and reversible inhibitors of the gastric H+/K+ ATPase. Our aim was to identify sites of expression of the H+/K+ ATPase that are potential targets of these compounds by examining the expression profile of the gastric H+/K+ ATPase in the human body from a broad range of tissues. Material and methods. Expression profiling was done by quantitative mRNA analysis (TaqMan PCR). Tissues that were mRNA-positive for the alpha subunit were investigated further by Western blot and immunohistochemistry (IHC) for the presence of gastric H+/K+ ATPase protein. Results. In addition to the very high expression levels in the stomach, the adrenal gland, cerebellum and pancreas gave unexpectedly positive mRNA signals for the alpha subunit of gastric H+/K+ ATPase. However, they were negative for mRNA of the beta subunit, and Western blot and IHC were negative for alpha and beta subunit protein. Another group of tissues with low alpha subunit mRNA expression including the frontal cortex, cortex grey matter, testis, thymus and larynx submucosa were also found negative for both alpha and beta subunit protein. In contrast to mouse kidney, no gastric H+/K+ATPase could be detected in human kidney. Conclusions. We therefore conclude that the only organ in humans expressing significant levels of the P-CAB target gastric H+/K+ ATPase is the stomach. C1 ALTANA Pharma AG, Dept Biochem Gastroenterol, D-78467 Constance, Germany. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. AXXAM Srl, Milan, Italy. RP Klein, T (reprint author), ALTANA Pharma AG, Dept Biochem Gastroenterol, Byk Gulden Str 2, D-78467 Constance, Germany. EM thomas.klein@altanapharma.com NR 49 TC 14 Z9 15 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0036-5521 EI 1502-7708 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2007 VL 42 IS 11 BP 1275 EP 1288 DI 10.1080/00365520701405579 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 217OC UT WOS:000249956200002 PM 17852870 ER PT J AU Chan, ED Kaminska, AM Gill, W Chmura, K Feldman, NE Bai, XY Floyd, CM Fulton, KE Huitt, GA Strand, MJ Iseman, MD Shapiro, L AF Chan, Edward D. Kaminska, Aleksandra M. Gill, Wendy Chmura, Kathryn Feldman, Nicole E. Bai, Xiyuan Floyd, Corinne M. Fulton, Kayte E. Huitt, Gwen A. Strand, Matthew J. Iseman, Michael D. Shapiro, Leland TI Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONTUBERCULOUS MYCOBACTERIA; CLINICAL-FEATURES; PULMONARY-DISEASE; DEFICIENCY; EPIDEMIOLOGY AB Rapidly growing mycobacteria (RGM) are ubiquitous in the environment but cause lung disease in only a fraction of exposed individuals. This variable susceptibility to disease implies vulnerability to RGM infection due to weakness in host defense. Since most persons who contract RGM lung disease have no known host defense defect, it is likely that uncharacterized host deficiencies exist that predispose to RGM infection. Alpha-1-antitrypsin (AAT) is a host factor that may protect individuals from respiratory infections. Therefore, we assessed AAT protein anomalies as a risk factor for RGM lung disease. In a cohort of 100 patients with RGM lung disease, Mycobacterium (M.) abscessus was the most prevalent organism, isolated in 64 (64%) subjects. Anomalous AAT proteins were present in 27% of the cohort, which is 1.6 times the estimated prevalence of anomalous AAT proteins in the United States population (p = 0.008). In in vitro studies, both AAT and a synthetic inhibitor of serine proteases suppressed M. abscessus infection of monocyte-derived macrophages by up to 65% (p <0.01). AAT may be an anti-RGM host-defense factor, and anomalous AAT phenotypes or AAT deficiency may constitute risk factors for pulmonary disease due to RGM. C1 Univ Colorado Denver & Hlth Sci Ctr, Dept Med, Div Infect Dis, Denver, CO 80262 USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. Natl Jewish Med & Res Ctr, Program Cell Biol, Denver, CO USA. Natl Jewish Med & Res Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Sch Med, Boulder, CO 80309 USA. RP Shapiro, L (reprint author), Univ Colorado Denver & Hlth Sci Ctr, Dept Med, Div Infect Dis, 4200 E 9th Ave,Box B168, Denver, CO 80262 USA. EM leland.shapiro@uchsc.edu FU NHLBI NIH HHS [R01-HL66112] NR 22 TC 45 Z9 48 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2007 VL 39 IS 8 BP 690 EP 696 DI 10.1080/00365540701225744 PG 7 WC Infectious Diseases SC Infectious Diseases GA 197FY UT WOS:000248541200005 PM 17654345 ER PT J AU Calkins, ME Dobie, DJ Cadenhead, KS Olincy, A Freedman, R Green, MF Greenwood, TA Gur, RE Gur, RC Light, GA Mintz, J Nuechterlein, KH Radant, AD Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Stone, WS Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Calkins, Monica E. Dobie, Dorcas J. Cadenhead, Kristin S. Olincy, Ann Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Light, Gregory A. Mintz, Jim Nuechterlein, Keith H. Radant, Allen D. Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI The consortium on the genetics of endophenotypes in schizophrenia: Model recruitment, assessment, and endophenotyping methods for a multisite collaboration SO SCHIZOPHRENIA BULLETIN LA English DT Article DE neurophysiology; neurocognitive; genes ID CONTINUOUS PERFORMANCE-TEST; SORTING TEST-PERFORMANCE; QUANTITATIVE TRAIT LOCI; WORKING-MEMORY; SUSTAINED ATTENTION; RELATIVES; DEFICITS; PAIRS; RECOGNITION; MECHANISMS AB Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. Methods: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. Results: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). Discussion: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia. C1 Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Calkins, ME (reprint author), Univ Penn, Dept Psychiat, Neuropsychiat Sect, 10 Gates,3400 Spruce St, Philadelphia, PA 19104 USA. EM mcalkins@bbl.med.upenn.edu; DBraff@ucsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016 OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894 FU NIMH NIH HHS [R01-MH65707, MH43518, R01 MH043518, R01 MH065554, R01 MH065558, R01 MH065562, R01 MH065571, R01 MH065578, R01 MH065588, R01 MH065707, R01-MH065554, R01-MH065562, R01-MH065571, R01-MH65558, R01-MH65578, R01-MH65588, R37 MH043518] NR 68 TC 99 Z9 101 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2007 VL 33 IS 1 BP 33 EP 48 DI 10.1093/schbul/sbl044 PG 16 WC Psychiatry SC Psychiatry GA 120FW UT WOS:000243070900007 PM 17035358 ER PT J AU Dickey, CC McCarley, RW Xu, ML Seidman, LJ Voglmaier, MM Niznikiewicz, MA Connor, E Shenton, ME AF Dickey, Chandlee C. McCarley, Robert W. Xu, Mina L. Seidman, Larry J. Voglmaier, Martina M. Niznikiewicz, Margaret A. Connor, Erin Shenton, Martha E. TI MRI abnormalities of the hippocampus and cavum septi pellucidi in females with schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; schizotypal personality disorder; hippocampus; cavum septum pellucidum; delayed alternation task; spatial working memory ID STRUCTURAL BRAIN ABNORMALITIES; WORKING-MEMORY; TEMPORAL-LOBE; NEUROPSYCHOLOGICAL MEASURES; 1ST-EPISODE SCHIZOPHRENIA; MAJOR DEPRESSION; PROFILE ANALYSIS; FORMATION VOLUME; CAUDATE-NUCLEUS; SEX-DIFFERENCES AB Objective: This study examined MRI hippocampal volume and cavum septi pellucidi (CSP) in female subjects with schizotypal personality disorder (SPD) and comparison subjects. Method: MRI was performed on 20 SPD and 29 comparison subjects with delineation of left and right hippocampi. Number of slices containing the CSP was counted. Subjects were given a working memory task, the Delayed Alternation task and other measures of working memory including the Wechsler Memory Test-Revised and the California Verbal Learning Test. Clinical measures were derived from the SCID-II. Results: SPD females evinced bilaterally smaller hippocampal volumes compared with non-psychiatric female subjects (15.1% on left, 15.7% on right). Additionally, SPD subjects showed statistically significantly more slices containing CSP, and a trend level difference when large CSP was defined as four or more slices (20% vs. 6.9%). SPD subjects demonstrated more errors, more perseverations, and a trend toward more failure to maintain set on the Delayed Alternating task, which were associated with smaller left hippocampal volumes. There was no difference between groups in logical memory, verbal learning or semantic clustering nor a significant correlation between these measures and hippocampal volumes. Clinically, in SPD subjects, right hippocampal volumes correlated negatively with odd appearance/behavior and positively with suspiciousness/paranoia, and odd speech was positively correlated with the number of slices containing a CSP in exploratory analyses. Conclusions: Female SPD subjects showed bilaterally smaller hippocampal volumes and larger CSP than comparison subjects, similar to what has been shown in schizophrenia. Moreover, these abnormalities have clinically significant associations which may help to explain some of the manifestations of the disorder. Published by Elsevier B.V. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Lab Neurosci,Clin Neurosci Div, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr Publ Psychiat Div,D, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Cambridge Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Washington Univ, Sch Med, St Louis, MO USA. RP Dickey, CC (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Lab Neurosci,Clin Neurosci Div, Boston, MA USA. EM chandlee_dickey@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH RO1 50740, MH K05 01110, MH RO1 40799, R01 MH050740, R01 MH050740-15] NR 75 TC 31 Z9 31 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2007 VL 89 IS 1-3 BP 49 EP 58 DI 10.1016/j.schres.2006.08.004 PG 10 WC Psychiatry SC Psychiatry GA 128KC UT WOS:000243655600005 PM 17027236 ER PT J AU Thomas, EA Yao, JK AF Thomas, Elizabeth A. Yao, Jeffrey K. TI Clozapine specifically alters the arachidonic acid pathway in mice lacking apolipoprotein D SO SCHIZOPHRENIA RESEARCH LA English DT Article DE apolipoprotein; antipsychotic; clozapine; arachidonic acid; fatty acid; HPLC ID ANTIPSYCHOTIC-DRUG TREATMENT; PSYCHIATRIC-DISORDERS; FATTY-ACID; SCHIZOPHRENIC-PATIENTS; RAT-BRAIN; PATHOPHYSIOLOGY; PHARMACOTHERAPY; PROGESTERONE; METABOLISM; EXPRESSION AB Apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid-binding proteins, exhibits abundant expression within the CNS of many species, including humans; however, its physiological role remains unclear. Treatment with atypical antipsychotic drugs, especially clozapine, results in elevation of apoD expression levels in rodent brain and in human plasma samples. In order to further explore the role of apoD in mechanisms of clozapine function, we have measured a panel of membrane fatty acids and membrane lipids in brain from drug-treated apoD knock-out mice. Mice received clozapine (10 mg/kg/day) in their drinking water for 28 days and forebrain samples were analyzed using high performance liquid chromatography and capillary gas chromatography. We identified significant differences in the levels of membrane fatty acids in response to clozapine treatment specifically in the brains of apoD knock-out mice, but not wild-type (wt) mice. The most striking observations were decreases in the levels of fatty acids related to metabolism of arachidonic acid (AA), which is a known binding partner for apoD. These include the precursor to arachidonic acid, linoleic acid (LA; 18:2n6c), arachidonic acid itself (20:4n6) and the elongation product of arachidonic acid, adrenic acid (22:4n6). We further report increases in LA, eicosadienoic acid and docosahexaenoic acid in apoD knock-out compared to wild-type mice. These findings implicate an important apoD/AA interaction, which may be necessary for clozapine function. (c) 2006 Elsevier B.V. All rights reserved. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. VA Pittsburgy Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA 15206 USA. RP Thomas, EA (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd,MB-10, La Jolla, CA 92037 USA. EM bthomas@scripps.edu FU NIMH NIH HHS [MH58141, MH069696]; NINDS NIH HHS [NS44169] NR 33 TC 14 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2007 VL 89 IS 1-3 BP 147 EP 153 DI 10.1016/j.schres.2006.08.011 PG 7 WC Psychiatry SC Psychiatry GA 128KC UT WOS:000243655600016 PM 17011169 ER PT J AU Hackett, AS Watnick, SG AF Hackett, Amy S. Watnick, Suzanne G. TI Withdrawal from dialysis in end-stage renal disease: Medical, social, and psychological issues SO SEMINARS IN DIALYSIS LA English DT Article ID LIFE-SUPPORT; RISK-FACTORS; OF-LIFE AB Dialysis withdrawal is common, accounting for over 20% of patient deaths. It is the third leading cause of death among patients receiving dialysis, after cardiovascular disease and infectious complications. Here we present a case of a patient with significant comorbid disease who ultimately elected to withdraw from dialysis. The medical, social and psychological issues encountered by caregivers are reviewed. Additionally we discuss the available data on factors affecting the decision to withdraw, current practice guidelines, and efforts to educate nephrology fellows on end-of-life issues. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Div Nephrol & Hypertens, Portland, OR USA. RP Watnick, SG (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Div Nephrol & Hypertens, P3 NEPH,3710 SW US Vet Hosp Rd, Portland, OR USA. EM watnicks@ohsu.edu NR 15 TC 10 Z9 13 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 2007 VL 20 IS 1 BP 86 EP 90 DI 10.1111/j.1525-139X.2007.00249.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 131ZN UT WOS:000243911600018 PM 17244129 ER PT J AU Hong, TS Crowley, EM Killoran, J Mamon, HJ AF Hong, Theodore S. Crowley, Elizabeth M. Killoran, Joseph Mamon, Harvey J. TI Considerations in treatment planning for esophageal cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article DE esophageal cancer; treatment planning; normal tissue tolerance; PET scanning; IMRT ID POSITRON-EMISSION-TOMOGRAPHY; VOLUME HISTOGRAM ANALYSIS; CELL LUNG-CANCER; POSTOPERATIVE PULMONARY COMPLICATIONS; INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; FDG-PET; PREOPERATIVE CHEMOTHERAPY; ESOPHAGOGASTRIC JUNCTION; ENDOSCOPIC ULTRASOUND C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Mamon, HJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM hmamon@partners.org NR 44 TC 13 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2007 VL 17 IS 1 BP 53 EP 61 DI 10.1016/j.semradonc.2006.09.001 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 161EX UT WOS:000245998400008 PM 17185198 ER PT S AU Turner, JN Coaxum, SD Gelasco, AK Garnovskaya, MN Raymond, JR AF Turner, Justin N. Coaxum, Sonya D. Gelasco, Andrew K. Garnovskaya, Maria N. Raymond, John R. BE Chattopadhyay, A TI Calmodulin Is a 5-HT Receptor-Interacting and Regulatory Protein SO SEROTONIN RECEPTORS IN NEUROBIOLOGY SE Frontiers in Neuroscience LA English DT Article; Book Chapter ID 3RD INTRACELLULAR LOOP; INSULIN-STIMULATED PHOSPHORYLATION; CORTICAL PYRAMIDAL NEURONS; CYCLIC-AMP ACCUMULATION; GROWTH-FACTOR-RECEPTOR; KINASE-C; SEROTONIN RECEPTORS; NA+/H+ EXCHANGE; SIGNAL-TRANSDUCTION; RAT HIPPOCAMPUS AB This chapter explores emerging roles for calmodulin as a regulator of 5-HT receptor function and describes recent work suggesting that calmodulin may be a so-called RIP (receptor-interacting protein) that binds to and modifies the functions of G protein-coupled 5-HT receptors. C1 [Turner, Justin N.; Coaxum, Sonya D.; Gelasco, Andrew K.; Garnovskaya, Maria N.; Raymond, John R.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Turner, Justin N.; Coaxum, Sonya D.; Gelasco, Andrew K.; Garnovskaya, Maria N.; Raymond, John R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Turner, JN (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. NR 99 TC 2 Z9 2 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-5723 J9 FRONT NEUROSCI JI Front. Neurosci. PY 2007 BP 61 EP 80 D2 10.1201/9781420005752 PG 20 WC Neurosciences SC Neurosciences & Neurology GA BKV55 UT WOS:000269396700005 ER PT S AU Kronenberg, HM AF Kronenberg, Henry M. BE Zaidi, M TI The role of the perichondrium in fetal bone development SO SKELETAL BIOLOGY AND MEDICINE, PT A: ASPECTS OF BONE MORPHOGENESIS AND REMODELING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE perichondrium; growth plate; cartilage; parathyroid hormone-related protein; Indian hedgehog ID HORMONE-RELATED PEPTIDE; INDIAN HEDGEHOG; CHONDROCYTE DIFFERENTIATION; GROWTH-PLATE; ENDOCHONDRAL SKELETON; OSTEOBLAST LINEAGE; CHONDROGENESIS; PROLIFERATION; OSTEOGENESIS; CARTILAGE AB Most cells in mesenchymal condensations that form endochondral bone become chondrocytes; cells at the outer edges of the condensations, however, become perichondrial cells with distinct properties and functions. Some perichondrial cells become osteoblasts that populate both the future cortical and trabecular bone; others probably become chondrocytes. Perichondrial cells both send signals to the underlying growth cartilage and receive signals from the cartilage. Here I illustrate briefly examples of the complicated interactions between the perichondrium and the underlying growth cartilage. C1 [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kronenberg, Henry M.] Harvard Med Sch, Boston, MA USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM hkronenberg@partners.org NR 17 TC 39 Z9 39 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-684-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1116 BP 59 EP 64 DI 10.1196/annals.1402.059 PG 6 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Orthopedics SC Endocrinology & Metabolism; Science & Technology - Other Topics; Orthopedics GA BHA44 UT WOS:000251898900004 PM 18083921 ER PT S AU Maes, C Kobayashi, T Kronenberg, HM AF Maes, Christa Kobayashi, Tatsuya Kronenberg, Henry M. BE Zaidi, M TI A novel Transgenic mouse model to study the osteoblast lineage in vivo SO SKELETAL BIOLOGY AND MEDICINE, PT A: ASPECTS OF BONE MORPHOGENESIS AND REMODELING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE osteoblast; lineage tracing; inducible Cre; tamoxifen; Cre-ERt; perichondrium; endochondral ossification; bone development; osteoprogenitor; osteoblast differentiation ID SITE-SPECIFIC RECOMBINATION; BONE-FORMATION; CRE RECOMBINASE; INDIAN HEDGEHOG; STEM-CELLS; CHONDROCYTE PROLIFERATION; SKELETAL DEVELOPMENT; ADULT HEMATOPOIESIS; GROWTH-PLATE; SPINAL-CORD AB Over the past few decades, osteoblast differentiation has been studied extensively in a variety of culture systems and findings from these experiments have shaped our understanding of the bone-forming cell lineage. However, in vitro assays are bound by intrinsic limitations and are unable to effectively mirror many aspects related to osteoblasts in vivo, including their origin, destiny, and life span. Therefore, these fundamental questions strongly advocate the need for novel models to characterize the osteoblast lineage in vivo. Here, we developed a transgenic mouse system to study stage-specific subsets of osteoblast lineage cells. We believe that this system will prove to be a helpful tool in deciphering multiple aspects of osteoblast biology in vivo. C1 [Maes, Christa; Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Harvard Med Sch, Boston, MA 02114 USA. RP Maes, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Harvard Med Sch, 50 Blossom St,Thier 1101, Boston, MA 02114 USA. EM cmaes1@partners.org FU NIDDK NIH HHS [DK056246] NR 61 TC 27 Z9 27 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-684-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1116 BP 149 EP 164 DI 10.1196/annals.1402.060 PG 16 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Orthopedics SC Endocrinology & Metabolism; Science & Technology - Other Topics; Orthopedics GA BHA44 UT WOS:000251898900011 PM 18083926 ER PT S AU Provot, S Schipani, E AF Provot, Sylvain Schipani, Ernestina BE Zaidi, M TI Fetal growth plate - A developmental model of cellular adaptation to hypoxia SO SKELETAL BIOLOGY AND MEDICINE, PT B: DISEASE MECHANISMS AND THERAPEUTIC CHALLENGES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE hypoxia; Hif-1 alpha; VHL; VEGF; chondrocytes; mensenchymal cells; joint ID INDUCIBLE FACTOR 1-ALPHA; SYNOVIAL JOINT FORMATION; EPIPHYSEAL CHONDROCYTES; ENDOPLASMIC-RETICULUM; PROLYL HYDROXYLATION; TUMOR-SUPPRESSOR; BONE-DEVELOPMENT; GENE-EXPRESSION; CYCLE ARREST; HIF-ALPHA AB Fetal growth plate chondrocyte is a unique mesenchymal tissue, as it is avascular and hypoxic. Yet, chondrocytes not only survive in this environment, but also undergo all cellular processes (proliferation, growth arrest, differentiation, etc.) required for normal endochondral bone development. A crucial mediator of the adaptive response of cells to hypoxia is a transcription factor named hypoxia-inducible factor lot (Hif-1 alpha). One target of Hif-1 alpha transcriptional activation is the angiogenic factor vascular endothelial growth factor (VEGF), whereas Hif-1 alpha accumulation is controlled by the von Hippel-Lindau (VHL) tumor suppressor, an E3-ubiquitin ligase that induces its degradation by the proteasome. We, and others, demonstrated that each component of this pathway is a critical regulator of endochondral bone development. In particular, we previously established that Hif-1 alpha is a survival factor for hypoxic chondrocytes, and that it also negatively regulates cell proliferation. Interestingly, we also showed that hypoxia increases extracellular matrix accumulation in a Hif-1 alpha-dependent fashion. This suggested that Hif-1 alpha could be critically important not only for cell survival and proliferation but also for cell differentiation. We recently demonstrated that Hif-1 alpha is indeed a differentiation factor since it is required in mesenchymal cells both for early chondrogenesis, and for joint development. C1 [Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Provot, Sylvain] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Schipani, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Thier Res Bldg Room 1101,50 Blossom St, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR048191] NR 62 TC 44 Z9 47 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-728-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1117 BP 26 EP 39 DI 10.1196/annals.1402.076 PG 14 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Pathology; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Pathology; Physiology GA BHD19 UT WOS:000252266600003 PM 18056035 ER PT S AU Potts, JT Gardella, TJ AF Potts, John T. Gardella, Thomas J. BE Zaidi, M TI Progress, paradox, and potential - Parathyroid hormone research over five decades SO SKELETAL BIOLOGY AND MEDICINE, PT B: DISEASE MECHANISMS AND THERAPEUTIC CHALLENGES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE parathyroid hormone; PTH ID AMINO-ACID SEQUENCE; (PTH)/PTH-RELATED PROTEIN-RECEPTOR; BONE; PTH; OSTEOPOROSIS; SELECTIVITY; EXTRACTION; PEPTIDE; CALCIUM; BINDING AB With the advent of advances in chemical and molecular biology, the structure of parathyroid hormone (PTH); the related protein, parathyroid-related protein (PTHrP); and their principal receptor (PTH/PTHrP receptor [PTHR1]) were established over recent decades. Tests with purified hormonal peptide in humans led to the surprising, even paradoxical, finding that PTH can be used pharmacologically to build bone, providing a dramatic therapeutic impact on osteoporosis. These developments plus recent insights into previously unappreciated ligand-receptor conformations that cause prolonged biological activation have stimulated the field of calcium and bone biology and posed new questions about the role of PTH and PTHrP as well as possible new directions in the therapy of osteoporosis and calcium-deficit states. C1 [Potts, John T.; Gardella, Thomas J.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Potts, John T.; Gardella, Thomas J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Potts, JT (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 4013, Charlestown, MA 02129 USA. EM potts.john@mgh.harvard.edu NR 38 TC 65 Z9 65 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-728-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1117 BP 196 EP 208 DI 10.1196/annals.1402.088 PG 13 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Pathology; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Pathology; Physiology GA BHD19 UT WOS:000252266600019 PM 18056044 ER PT J AU Kassarjian, A Llopis, E Palmer, WE AF Kassarjian, Ara Llopis, Eva Palmer, William E. TI Distal clavicular osteolysis: MR evidence for subchondral fracture SO SKELETAL RADIOLOGY LA English DT Article DE MRI; shoulder; clavicle osteolysis; subchondral fracture ID STRESS-INDUCED OSTEOLYSIS; POSTTRAUMATIC OSTEOLYSIS AB Purpose To investigate the association between distal clavicular osteolysis and subchondral fractures of the distal clavicle at MRI. Materials and methods This study was approved by the hospital human research committee, which waived the need for informed consent. Three radiologists retrospectively analyzed 36 shoulder MR examinations in 36 patients with imaging findings of distal clavicular osteolysis. The presence of a subchondral fracture of the distal clavicle, abnormalities of the acromioclavicular joint, rotator cuff tears and labral tears were assessed by MRI. These cases were then compared with 36 age-matched controls. Results At MRI, 31 of 36 patients (86%) had a subchondral line within the distal clavicular edema, consistent with a subchondral fracture. Of the 36 patients, 32 (89%) had fluid in the acromioclavicular joint, while 27 of 36 patients (75%) had cysts or erosions in the distal clavicle. There were 13 patients (36%) with associated labral tears, while eight patients (22%) had partial-thickness rotator cuff tears. In the control group one of 36 (3%) had a subchondral line (P < 0.05), while ten of 36 (28%) had rotator cuff tears and 13 of 36 (36%) had labral tears. These latter two were not statistically significant between the groups. Conclusion A distal clavicular subchondral fracture is a common finding in patients with imaging evidence of distal clavicular osteolysis. These subchondral fractures may be responsible for the propensity of findings occurring on the clavicular side of the acromioclavicular joint. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Yawkey Ctr, Boston, MA 02114 USA. Hosp Ribera, Dept Radiol, Valencia 46600, Spain. RP Kassarjian, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Yawkey Ctr, 6th Floor,55 Fruit St, Boston, MA 02114 USA. EM akassarjian@partners.org NR 13 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JAN PY 2007 VL 36 IS 1 BP 17 EP 22 DI 10.1007/s00256-006-0209-y PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 111GY UT WOS:000242440600003 PM 17021902 ER PT J AU Nakano, K Kiyokane, K Benvenuto-Andrade, C Gonzalez, S AF Nakano, K. Kiyokane, K. Benvenuto-Andrade, C. Gonzalez, S. TI Real-time reflectance confocal microscopy, a noninvasive tool for in vivo quantitative evaluation of comedolysis in the rhino mouse model SO SKIN PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE reflectance confocal microscopy; rhino mouse comedones; all-trans-retinoic acid; all-trans-retinol ID SCANNING LASER MICROSCOPY; TRANS-RETINOIC ACID; HUMAN SKIN; CONTACT-DERMATITIS; ROUTINE HISTOLOGY; FLUORESCENCE; ACNE AB Background: Near-infrared reflectance confocal microscopy (RCM) is a noninvasive tool that provides real-time images of thin virtual horizontal tissue sections. Aims/Methods: We have used a rhino mouse model in combination with topical application of all-trans-retinoic acid and all-transretinol to investigate the usefulness of RCM as a noninvasive imaging tool to evaluate comedolysis in vivo and over time. Optical images were correlated with routine histology. Results: Our results demonstrate that RCM in vivo can visualize the process of transformation of utriculi (pseudocomedones) towards a normal-appearing follicular structure during retinoid treatment. The retinoic acid intervention group showed a dose-related response, while the vehicle-treated group did not show utricular changes. Conclusions: RCM represents a useful tool for in vivo morphological and quantitative evaluation of skin utriculi over time and could be used as an adjunct tool to histopathological techniques for comedolysis studies. Copyright (c) 2007 S. Karger AG, Basel. C1 Mem Sloan Kettering Canc Ctr, Serv Dermatol, New York, NY 10044 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr, Boston, MA USA. Osaka Med Coll, Dept Dermatol, Osaka, Japan. RP Gonzalez, S (reprint author), Mem Sloan Kettering Canc Ctr, Serv Dermatol, 160 E 53rd St,2nd Floor, New York, NY 10044 USA. EM gonzals6@mskcc.org NR 28 TC 12 Z9 15 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-5527 J9 SKIN PHARMACOL PHYS JI Skin Pharmacol. Physiol. PY 2007 VL 20 IS 1 BP 29 EP 36 DI 10.1159/000096169 PG 8 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 117BM UT WOS:000242847500005 PM 17035719 ER PT J AU Astner, S Wu, A Chen, J Philips, N Rius-Diaz, F Parrado, C Mihm, MC Goukassian, DA Pathak, MA Gonzalez, S AF Astner, S. Wu, A. Chen, J. Philips, N. Rius-Diaz, F. Parrado, C. Mihm, M. C. Goukassian, D. A. Pathak, M. A. Gonzalez, S. TI Dietary lutein/zeaxanthin partially reduces photoaging and photocarcinogenesis in chronically UVB-irradiated Skh-1 hairless mice SO SKIN PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE lutein; zeaxanthin; carotenoids; photoaging; photocarcinogenesis ID HIGH-DOSE SUPPLEMENTATION; BETA-CAROTENE; MACULAR PIGMENT; CLINICAL-TRIAL; BREAST-CANCER; SKIN-CANCER; VISION LOSS; MOUSE SKIN; BASAL-CELL; VITAMIN-C AB Lutein and zeaxanthin are xanthophyll carotenoids with potent antioxidant properties protecting the skin from acute photodamage. This study extended the investigation to chronic photodamage and photocarcinogenesis. Mice received either a lutein/zeaxanthin-supplemented diet or a standard nonsupplemented diet. Dorsal skin of female Skh-1 hairless mice was exposed to UVB radiation with a cumulative dose of 16,000 mJ/cm(2) for photoaging and 30,200 mJ/cm(2) for photocarcinogenesis. Clinical evaluations were performed weekly, and the animals were sacrificed 24 h after the last UVB exposure. For photoaging experiments, skin fold thickness, suprapapillary plate thickness, mast cell counts and dermal desmosine content were evaluated. For photocarcinogenesis, samples of tumors larger than 2 mm were analyzed for histological characterization, hyperproliferation index, tumor multiplicity, total tumor volume and tumor-free survival time. Results of the photoaging experiment revealed that skin fold thickness and number of infiltrating mast cells following UVB irradiation were significantly less in lutein/zeaxanthin-treated mice when compared to irradiated animals fed the standard diet. The results of the photocarcinogenesis experiment were increased tumor-free survival time, reduced tumor multiplicity and total tumor volume in lutein/zeaxanthin-treated mice in comparison with control irradiated animals fed the standard diet. These data demonstrate that dietary lutein/zeaxanthin supplementation protects the skin against UVB-induced photoaging and photocarcinogenesis. Copyright (c) 2007 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Fairleigh Dickinson Univ, Sch Nat Sci, Dept Biol Sci, Teaneck, NJ USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10021 USA. Univ Malaga, Fac Med, E-29071 Malaga, Spain. RP Gonzalez, S (reprint author), 160 E 53rd St, New York, NY 10022 USA. EM gonzals6@mskcc.org RI Parrado, Concepcion/K-9270-2014 OI Parrado, Concepcion/0000-0002-7627-4310 NR 50 TC 17 Z9 20 U1 2 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-5527 J9 SKIN PHARMACOL PHYS JI Skin Pharmacol. Physiol. PY 2007 VL 20 IS 6 BP 283 EP 291 DI 10.1159/000107576 PG 9 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 225WV UT WOS:000250549800003 PM 17717424 ER PT J AU Mccoy, JG Tartar, JL Bebis, AC Ward, CP McKenna, JT Baxter, MG McGaughy, J McCarley, RW Strecker, RE AF McCoy, John G. Tartar, Jaime L. Bebis, Alaina C. Ward, Christopher P. McKenna, James T. Baxter, Mark G. McGaughy, Jill McCarley, Robert W. Strecker, Robert E. TI Experimental sleep fragmentation impairs attentional set-shifting in rats SO SLEEP LA English DT Article DE attention; sleep fragmentation; sleep deprivation; sleep apnea syndromes; discrimination learning; executive function; reversal learning; animal model ID MEDIAL FRONTAL-CORTEX; VENTROLATERAL PREOPTIC NEURONS; PREFRONTAL CORTEX; BASAL FOREBRAIN; AGED RATS; ADENOSINE; DEPRIVATION; PERFORMANCE; RECEPTORS; MEMORY AB Study Objective: To evaluate the effect of experimental sleep fragmentation (sleep interruption; SI) on complex learning in an intradimensional-extradimensional (ID/ED) set-shifting task in rats. Design: A sleep fragmentation paradigm of intermittent forced locomotion was validated in adult rats by examining electrographic effects. Discrimination task performances were assessed in rats following sleep fragmentation or 2 control conditions. Participants: 41 young adult male Fischer-Norway rats. Intervention: A treadmill was used to produce 30 awakenings/h for the 24-h period prior to testing. Exercise control rats received an equivalent amount of treadmill-induced locomotion that permitted 30-minute pauses to allow consolidated sleep. Measurement and Results: SI rats were selectively impaired on the extradimensional-shift phase of the task, taking significantly more trials to achieve criterion performance (15.4 +/- 2.0) than either control group (cage control = 10.4 +/- 0.9; exercise control = 6.3 +/- 0.2). The SI schedule reduced the average duration of nonREM sleep (NREMS) episodes to 56 s (baseline = 182 s), while the exercise control group increased average NREMS episode duration to 223 s. Total (24-h) NREMS time declined from 50% during baseline to 33% during SI, whereas rapid eye movement sleep (REMS) was absent in SI animals (7% during baseline and 0% during SI), and time spent awake increased proportionally (from 43% during baseline to 67% during SI). Conclusion: 24-hour SI produced impairment in an attentional set-shifting that is comparable to the executive function and cognitive deficits observed in humans with sleep apnea or after a night of experimental sleep fragmentation. C1 Harvard Univ, Sch Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton, MA USA. Univ So Mississippi, Dept Psychol, Hattiesburg, MS 39406 USA. Stonehill Coll, Dept Psychol, Easton, PA USA. Univ Oxford, Dept Psychol, Oxford, England. Univ New Hampshire, Dept Psychol, Durham, NH 03824 USA. RP Strecker, RE (reprint author), Harvard Univ, Sch Med, 940 Belmont St, Brockton, MA 02301 USA. EM robert_strecker@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 NR 37 TC 34 Z9 37 U1 0 U2 3 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2007 VL 30 IS 1 BP 52 EP 60 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 125QL UT WOS:000243456900007 PM 17310865 ER PT J AU Alessi, C Martin, J Josephson, K Khan-Hudson, A Vandenberg, T Birath, J Martinez, S AF Alessi, C. Martin, J. Josephson, K. Khan-Hudson, A. Vandenberg, T. Birath, J. Martinez, S. TI Sleep disturbance predicts functional impairment among older people in assisted living facilities SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 305 BP A104 EP A105 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900307 ER PT J AU Budhiraja, R Zeater, M Parthasarathy, S Quan, S AF Budhiraja, R. Zeater, M. Parthasarathy, S. Quan, S. TI Factors determining adherence to continuous positive airway pressure (CPAP) therapy in veterans with obstructive sleep apnea (OSA) SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 So Arizona VA Healthcare Syst, Tucson, AZ USA. US Dept Vet Affairs, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. RI Parthasarathy, Sairam/L-1612-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 487 BP A166 EP A166 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900488 ER PT J AU Budhiraja, R Zeater, M Parthasarathy, S Quan, S AF Budhiraja, R. Zeater, M. Parthasarathy, S. Quan, S. TI Comparison of features of central sleep apnea and obstructive sleep apnea SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Arizona, Tucson, AZ USA. US Dept Vet Affairs, Tucson, AZ USA. RI Parthasarathy, Sairam/L-1612-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 463 BP A158 EP A158 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900464 ER PT J AU Chen, L Basheer, R Bolortuya, Y Thakkar, M McCarley, R AF Chen, L. Basheer, R. Bolortuya, Y. Thakkar, M. McCarley, R. TI Using small interfering RNA to knockdown different sleep related genes in rats SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Harvard Med Sch, VA Boston Healthcare Syst, Brockton, MA USA. Harvard Med Sch, VA Boston Healthcare Syst, W Roxbury, MA USA. Univ Missouri, Columbia, MO 65211 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 1061 BP A364 EP A364 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224901062 ER PT J AU Christie, W Chen, L Bolortuya, Y Lee, E McCarley, R Strecker, R AF Christie, W. Chen, L. Bolortuya, Y. Lee, E. McCarley, R. Strecker, R. TI Introduction of the rat-psychomotor vigilance task (RPVT): Vigilance impairments produced by adenosine perfusion in the basal forebrain. SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Harvard Med Sch, VA Boston Healthcare Syst, Brockton, MA USA. SK Corp, Brockton, MA USA. Harvard Med Sch, VA Med Ctr, Brockton, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 1095 BP A376 EP A377 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224901096 ER PT J AU Dzierzewski, J Mccrae, C Marsiske, M Mccoy, K McNamara, J Dautovich, N Ross, A Stripling, A AF Dzierzewski, J. Mccrae, C. Marsiske, M. McCoy, K. McNamara, J. Dautovich, N. Ross, A. Stripling, A. TI Daily variability in objective and subjective sleep and cognition in older adults with insomnia SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Florida, Gainesville, FL USA. Vet Adm, San Antonio, TX USA. Univ Florida, Gainesville, FL 32611 USA. RI Stripling, Ashley/D-8421-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 326 BP A112 EP A112 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900327 ER PT J AU Fava, M Pollack, M Rubens, R Amato, D Kostal, A Hayduk, R McCall, W AF Fava, M. Pollack, M. Rubens, R. Amato, D. Kostal, A. Hayduk, R. McCall, W. TI Evaluation of the Hamilton depression scale following eszopiclone treatment for insomnia in patients with insomnia co-morbid with major depressive disorder or generalized anxiety disorder SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Duke Univ, Durham, NC 27706 USA. Quintiles, San Diego, CA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 964 BP A329 EP A330 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900965 ER PT J AU Hannah, C Imran, A Budhiraja, R Quan, S Parthasarathy, S AF Hannah, C. Imran, A. Budhiraja, R. Quan, S. Parthasarathy, S. TI Alternative management strategies for sleep apnea improve access to care in veterans SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 US Dept Vet Affairs, Tucson, AZ USA. Univ Arizona, Tucson, AZ 85721 USA. RI Parthasarathy, Sairam/L-1612-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 538 BP A182 EP A182 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900539 ER PT J AU Krystal, A Fava, M Pollack, M Rubens, R Schaefer, K Amato, D Roth, T AF Krystal, A. Fava, M. Pollack, M. Rubens, R. Schaefer, K. Amato, D. Roth, T. TI Sleep outcomes following eszopiclone discontinuation in patients with primary insomnia and insomnia co-existing with major depressive disorder or generalized anxiety disorder SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Duke Univ, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 720 BP A245 EP A245 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900721 ER PT J AU Madan, V Brennan, F Ross, R Horbal, A Dunn, G Mann, G Morrison, A AF Madan, V Brennan, F. Ross, R. Horbal, A. Dunn, G. Mann, G. Morrison, A. TI Long-term effects of cued fear conditioning on rem sleep microarchitecture and phasic events in rats SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 12 BP A4 EP A5 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900014 ER PT J AU Martin, J Irwin, M Martinez, S Birath, J Josephson, K Alessi, C AF Martin, J. Irwin, M. Martinez, S. Birath, J. Josephson, k Alessi, C. TI More daytime sleeping is associated with higher proinflammatory cytokine levels in older postacute rehabilitation patients SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 313 BP A107 EP A108 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900315 ER PT J AU McCoy, J Ward, C McKenna, J Connolly, N McCarley, R Strecker, R AF McCoy, J. Ward, C. McKenna, J. Connolly, N. McCarley, R. Strecker, R. TI Effects of experimental sleep fragmentation and intermittent hypoxia on water maze performance in rats SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. Univ Florida, Gainesville, FL USA. Wheaton Coll, Norton, MA 02766 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 602 BP A203 EP A203 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900603 ER PT J AU Methippara, M Kumar, S Noor, AM Szymusiak, R McGinty, D AF Methippara, M. Kumar, S. Noor, Alum M. Szymusiak, R. McGinty, D. TI Lateral ventricular perfusion of salubrinal, which arrests protein translation, promotes SWS in rats SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Vet Adm Greater Los Angeles HealthCare Syst, North Hills, CA USA. Univ Patna, Patna 800005, Bihar, India. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 1054 BP A362 EP A362 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224901055 ER PT J AU Parthasarathy, S Lowman, X Kuo, M Quan, S AF Parthasarathy, S. Lowman, X. Kuo, M. Quan, S. TI Preferred tidal volume setting for non-invasive ventilation is different for sleep and wakefulness SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 US Dept Vet Affairs, Tucson, AZ USA. Univ Arizona, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 535 BP A181 EP A181 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900536 ER PT J AU Parthasarathy, S Fitzgerald, M Goodwin, J Budhiraja, R Resnick, H Quan, S AF Parthasarathy, S. Fitzgerald, M. Goodwin, J. Budhiraja, R. Resnick, H. Quan, S. TI Nocturia and sleep-disordered breathing in the sleep heart health cohort SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 US Dept Vet Affairs, Tucson, AZ USA. Loyola Univ, Chicago, IL 60611 USA. Univ Arizona, Tucson, AZ 85721 USA. RI Parthasarathy, Sairam/L-1612-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 530 BP A180 EP A180 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900531 ER PT J AU Pollack, M Rubens, R Amato, D Schaefer, K Pfleeger, K Hayduk, R Roth, T AF Pollack, M. Rubens, R. Amato, D. Schaefer, K. Pfleeger, K. Hayduk, R. Roth, T. TI Effects of eszopiclone co-therapy with escitalopram on measures of anxiety and mood outcomes in patients with insomnia and comorbid generalized anxiety disorder SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Henry Ford Hlth Syst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 965 BP A330 EP A330 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900966 ER PT J AU Scheer, F Hilton, M Benjamin, T Barb, D Mantzoros, C Shea, S AF Scheer, F. Hilton, M. Benjamin, T. Barb, D. Mantzoros, C. Shea, S. TI Desynchrony between sleep-wake cycle and circadian cycle leads to suppressed plasma leptin; potential relevance for shift workers SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med,Med Chronobiol Program, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 178 BP A61 EP A61 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900180 ER PT S AU Strehler, EE Caride, AJ Filoteo, AG Xiong, YN Penniston, JT Enyedi, A AF Strehler, Emanuel E. Caride, Ariel J. Filoteo, Adelaida G. Xiong, Yuning Penniston, John T. Enyedi, Agnes BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE calcium homeostasis; calcium pump; calcium signaling; PMCA; splice variant ID PROTEIN-KINASE-C; CALMODULIN-BINDING DOMAIN; NITRIC-OXIDE SYNTHASE; CA2+-ATPASE ISOFORM 2; SPERM MOTILITY; MALE-FERTILITY; PUMP; 4B; EXPRESSION; INTERACTS AB Plasma membrane Ca2+ ATPases (PMCAs) are essential components of the cellular toolkit to regulate and fine-tune cytosolic Ca2+ concentrations. Historically, the PMCAs have been assigned a housekeeping role in the maintenance of intracellular Ca2+ homeostasis. More recent work has revealed a perplexing multitude of PMCA isoforms and alternative splice variants, raising questions about their specific role in Ca2+ handling under conditions of varying Ca2+ loads. Studies on the kinetics of individual isoforms, combined with expression and localization studies suggest that PMCAs are optimized to function in Ca2+ regulation according to tissue- and cell-specific demands. Different PMCA isoforms help control slow, tonic Ca2+ signals in some cells and rapid, efficient Ca2+ extrusion in others. Localized Ca2+ handling requires targeting of the pumps to specialized cellular locales, such as the apical membrane of cochlear hair cells or the basolateral membrane of kidney epithelial cells. Recent studies suggest that alternatively spliced regions in the PMCAs are responsible for their unique targeting, membrane localization, and signaling cross-talk. The regulated deployment and retrieval of PMCAs from specific membranes provide a dynamic system for a cell to respond to changing needs of Ca2+ regulation. C1 Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. Natl Med Ctr, H-1113 Budapest, Hungary. RP Strehler, EE (reprint author), Mayo Clin, Coll Med, Dept Biochem & Mol Biol, 200 1st St SW, Rochester, MN 55905 USA. EM strehler.emanuel@mayo.edu RI Enyedi, Agnes/N-9742-2013 OI Enyedi, Agnes/0000-0002-7366-9376 FU NIGMS NIH HHS [R01 GM028835, GM28835] NR 39 TC 68 Z9 68 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 226 EP 236 DI 10.1196/annals.1387.023 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300027 PM 17446463 ER PT S AU Paszty, K Antalffy, G Hegedus, L Padanyi, R Penheiter, AR Filoteo, AG Penniston, JT Enyedi, A AF Paszty, Katalin Antalffy, Geza Hegedus, Luca Padanyi, Rita Penheiter, Alan R. Filoteo, Adelaida G. Penniston, John T. Enyedi, Agnes BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI Cleavage of the plasma membrane Ca(2+) ATPase during apoptosis SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE plasma membrane Ca(2+) ATPase; calmodulin; apoptosis; caspase-3; activation; localization; truncated mutant; structure function ID CALMODULIN-BINDING DOMAIN; CALCIUM-PUMP; CELL-DEATH; ISOFORM 4B; PROTEINS; NECROSIS; DEFICIENCY; MODULATION; MECHANISMS; INTERACTS AB Maintenance of Ca(2+) homeostasis is essential for normal cellular function and survival. Recent evidences suggest that Ca(2+) is also an important player of apoptosis. We demonstrated that the plasma membrane Ca(2+) ATPase (PMCA) isoform 4b, a key element of cellular Ca(2+) homeostasis, was cleaved by caspase-3 during the course of apoptosis. This cleavage of PMCA removed the entire regulatory region from the C terminus, leaving behind a 120-kDa catalytic fragment. Since loss of PMCA activity could lead to intracellular Ca(2+) overload and consequently necrotic cell death, an important question is whether the apoptotic fragment of PMCA retains full activity or it is inactivated. To address this question, we constructed a C-terminally truncated mutant that corresponded to the caspase-3 fragment of PMCA4b and showed that it was fully and constitutively active. This mutant was targeted properly to the plasma membrane when it was expressed stably or transiently in several different cell lines. We followed truncation of PMCA during apoptosis induced by mitochondrial or receptor-mediated pathways and found that a similar fragment of 120 kDa was formed and remained intact for several hours after treatment. We have also demonstrated that the caspase-3 cleavage site is an important structural element of PMCA and found that the accessibility of the caspase-3 site depended strongly on the conformational state of the protein. C1 Natl Med Ctr, H-1113 Budapest, Hungary. Hungarian Acad Sci, Membrane Res Grp, H-1051 Budapest, Hungary. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Neurosci Ctr, Boston, MA 02114 USA. RP Enyedi, A (reprint author), Natl Med Ctr, Dioszegi Ut 64, H-1113 Budapest, Hungary. EM enyedi@biomembrane.hu RI Enyedi, Agnes/N-9742-2013; OI Enyedi, Agnes/0000-0002-7366-9376; Paszty, Katalin/0000-0003-2457-8555 FU NIGMS NIH HHS [GM28835] NR 45 TC 11 Z9 13 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 440 EP 450 DI 10.1196/annals.1387.003 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300049 PM 17446484 ER PT J AU Goldstein, G Allen, DN Haas, GL AF Goldstein, Gerald Allen, Daniel N. Haas, Gretchen L. BE Fujii, D Ahmed, I TI Schizophrenia SO SPECTRUM OF PSYCHOTIC DISORDERS: NEUROBIOLOGY, ETIOLOGY, AND PATHOGENESIS LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; LATE-ONSET SCHIZOPHRENIA; DENDRITIC SPINE DENSITY; CEREBRAL-BLOOD-FLOW; PREMORBID ADJUSTMENT; PREFRONTAL CORTEX; FOLLOW-UP; 1ST-EPISODE SCHIZOPHRENIA; FAMILY INTERVENTION C1 [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Allen, Daniel N.] Univ Nevada, Las Vegas, NV 89154 USA. [Haas, Gretchen L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 93 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-85056-8 PY 2007 BP 15 EP 38 D2 10.2277/ 0521850568 PG 24 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BYQ38 UT WOS:000299729200003 ER PT J AU Takeshita, J Thompson, D Nicolson, SE AF Takeshita, Junji Thompson, Diane Nicolson, Stephen E. BE Fujii, D Ahmed, I TI Medication-induced psychosis SO SPECTRUM OF PSYCHOTIC DISORDERS: NEUROBIOLOGY, ETIOLOGY, AND PATHOGENESIS LA English DT Article; Book Chapter ID CENTRAL ANTICHOLINERGIC SYNDROME; SEROTONIN REUPTAKE INHIBITORS; DRUG-INDUCED PSYCHOSIS; VISUAL HALLUCINATIONS; INTERFERON-ALPHA; CANCER-PATIENTS; AUDITORY HALLUCINATIONS; NEUROPSYCHIATRIC COMPLICATIONS; MUSICAL HALLUCINATIONS; PARKINSONS-DISEASE C1 [Takeshita, Junji] Univ Hawaii, Honolulu, HI 96822 USA. [Nicolson, Stephen E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Takeshita, J (reprint author), Univ Hawaii, Honolulu, HI 96822 USA. NR 145 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-85056-8 PY 2007 BP 406 EP 451 D2 10.2277/ 0521850568 PG 46 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BYQ38 UT WOS:000299729200023 ER PT J AU Ericksen, S Tsuang, D AF Ericksen, Sasha Tsuang, Debby BE Fujii, D Ahmed, I TI Dementia with lewy bodies SO SPECTRUM OF PSYCHOTIC DISORDERS: NEUROBIOLOGY, ETIOLOGY, AND PATHOGENESIS LA English DT Article; Book Chapter ID AUTOSOMAL-DOMINANT PARKINSONISM; CLINICAL DIAGNOSTIC-ACCURACY; SLEEP BEHAVIOR DISORDER; TEMPORAL-LOBE ATROPHY; ALPHA-SYNUCLEIN GENE; ALZHEIMERS-DISEASE; BODY DISEASE; NEURODEGENERATIVE DISEASES; INTERNATIONAL WORKSHOP; VISUAL HALLUCINATIONS C1 [Ericksen, Sasha; Tsuang, Debby] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Tsuang, Debby] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Ericksen, S (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 88 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-85056-8 PY 2007 BP 472 EP 489 D2 10.2277/ 0521850568 PG 18 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BYQ38 UT WOS:000299729200025 ER PT J AU Polyak, K AF Polyak, Kornelia TI Breast cancer stem cells: A case of mistaken identity? SO STEM CELL REVIEWS LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM komelia_polyak@dfci.harvard.edu NR 10 TC 23 Z9 23 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2007 VL 3 IS 2 BP 107 EP 109 DI 10.1007/s12015-007-0020-8 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 208SX UT WOS:000249340600002 PM 17873341 ER PT J AU Polyak, K AF Polyak, Kornelia TI Breast cancer stem cells: Reply SO STEM CELL REVIEWS LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM komelia_polyak@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PY 2007 VL 3 IS 2 BP 113 EP 113 DI 10.1007/s12015-007-0021-7 PG 1 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 208SX UT WOS:000249340600004 ER PT J AU Michor, F AF Michor, Franziska TI Chronic myeloid leukemia blast crisis arises from progenitors SO STEM CELLS LA English DT Article DE chronic myeloid leukemia; hematopoietic stem cells; hematopoietic progenitor cells; differentiation ID CHRONIC MYELOGENOUS LEUKEMIA; KINASE INHIBITOR STI571; HEMATOPOIETIC STEM-CELLS; ALPHA PLUS CYTARABINE; CHRONIC-PHASE; IMATINIB MESYLATE; SELF-RENEWAL; RESISTANCE; GENE; MECHANISMS AB Chronic myeloid leukemia (CML) progresses through three distinct clinical stages: chronic phase, accelerated phase, and blast crisis. The progression to accelerated phase and blast crisis is driven by activation of oncogenes, inactivation of tumor suppressor genes, and/or amplification of the BCR-ABL fusion gene, which causes the chronic phase of the disease. The cell of origin of blast crisis is a subject of speculation. Here, I develop a simple mathematical model of CML blast crisis to investigate whether blasts arise from leukemic stem cells or more differentiated leukemic cells. I use data of patients treated with imatinib and previous agents to estimate the effects of therapy on the rate of progression. Imatinib reduces the progression rate 10-fold as compared with previous (ineffective) therapies. If blasts were produced by leukemic stem cells, there would be no difference in the rate of progression between patients treated with imatinib and previous therapies, because imatinib seems to be incapable of depleting leukemic stem cells. Imatinib does, however, deplete leukemic progenitors. Therefore, CML blasts are likely to arise from leukemic progenitors. C1 Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Michor, F (reprint author), Harvard Univ, Soc Fellows, 78 Mt Auburn St, Cambridge, MA 02138 USA. EM michor@fas.harvard.edu NR 45 TC 29 Z9 30 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 5 BP 1114 EP 1118 DI 10.1634/stemcells.2006-0638 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 165GR UT WOS:000246292700004 PM 17218393 ER PT J AU Szotek, PP Chang, HL Zhang, LH Preffer, F Dombkowski, D Donahoe, PK Teixeira, J AF Szotek, Paul P. Chang, Henry L. Zhang, LiHua Preffer, Frederic Dombkowski, David Donahoe, Patricia K. Teixeira, Jose TI Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation SO STEM CELLS LA English DT Article DE mouse myometrium; stem cell niche; label-retaining cells; mesenchymal stem cell; myometrial stem cell ID INTESTINAL STEM-CELLS; MULLERIAN-INHIBITING SUBSTANCE; GLAND SIDE POPULATION; MAMMARY-GLAND; SKELETAL-MUSCLE; CANCER-CELLS; SELF-RENEWAL; BETA-CATENIN; IN-VITRO; NICHE AB Conditional deletion of beta-catenin in the Mullerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in beta-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5- bromo-2'-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with alpha- smooth muscle actin, estrogen receptor-alpha, and beta-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing '' side population '' that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Mullerian duct mesenchyme. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Flow Cytometry Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Thier 913,55 Fruit St, Boston, MA 02114 USA. OI Teixeira, Jose/0000-0002-6438-5064 FU NCI NIH HHS [T32CA071345, CA17393]; NICHD NIH HHS [HD32112] NR 54 TC 54 Z9 63 U1 1 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 5 BP 1317 EP 1325 DI 10.1634/stemcells.2006-0204 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 165GR UT WOS:000246292700026 PM 17289934 ER PT J AU Gale, JT Amirnovin, R Eskandar, EN AF Gale, J. T. Amirnovin, R. Eskandar, E. N. TI Subthalamic oscillations and movement SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2007 VL 85 IS 1 BP 25 EP 26 PG 2 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 113SE UT WOS:000242616800019 ER PT J AU Jain, FA Eskandar, EN AF Jain, F. A. Eskandar, E. N. TI Single neuron activity during movement: Comparison of Parkinson's patients and normal primates SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Neurodegenerat & Repair, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2007 VL 85 IS 1 BP 26 EP 26 PG 1 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 113SE UT WOS:000242616800020 ER PT J AU Williams, ZM Curry, WT Eskandar, EN Barker, FG AF Williams, Z. M. Curry, W. T. Eskandar, E. N. Barker, F. G. TI Racial and socioeconomic disparities in surgical treatment for Parkinson disease in the United States, 1997-2003 SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2007 VL 85 IS 1 BP 26 EP 27 PG 2 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 113SE UT WOS:000242616800022 ER PT J AU Williams, ZM Amirnovin, R Lee, KH Eskandar, EN AF Williams, Z. M. Amirnovin, R. Lee, K. H. Eskandar, E. N. TI A highly selective dopamine-dependent mechanism for learning enhancement SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2007 VL 85 IS 1 BP 41 EP 42 PG 2 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 113SE UT WOS:000242616800060 ER PT J AU Eskandar, EN Williams, ZM Amirnovin, R Lee, KH Blaha, CD AF Eskandar, E. N. Williams, Z. M. Amirnovin, R. Lee, K. H. Blaha, C. D. TI Striatal stimulation as a prosthesis to enhance learning SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2007 VL 85 IS 1 BP 50 EP 50 PG 1 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 113SE UT WOS:000242616800079 ER PT S AU Yehuda, R Bierer, LM AF Yehuda, Rachel Bierer, Linda M. BE DeKloet, ER Vermetten, E TI Transgenerational transmission of cortisol and PTSD risk SO STRESS HORMONES AND POST TRAUMATIC STRESS DISORDER: BASIC STUDIES AND CLINICAL PERSPECTIVES SE Progress in Brain Research LA English DT Review CT Colloquium on Stress Hormones and Post Traumatic Stress Disorder - Basic Studies and Clinical Perspectives CY AUG 28-30, 2006 CL Amsterdam, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Minist Defence Netherlands DE posttraurnatic stress disorder; glucocorticoid programming; epigenetics; cortisol; intergenerational effects; risk factors ID POSTTRAUMATIC-STRESS-DISORDER; HOLOCAUST SURVIVORS; TRAUMA EXPOSURE; GENE-EXPRESSION; PARENTAL PTSD; MATERNAL-CARE; RESPONSES; VULNERABILITY; VETERANS; TWIN AB Parental posttraumatic stress disorder (PTSD) appears to be a relevant risk factor for the development of PTSD, as evidenced by a greater prevalence of PTSD, but not trauma exposure, in adult offspring of Holocaust survivors with PTSD, compared to children of Holocaust-exposed parents without PTSD. This paper summarizes recent neuroendocrine studies in offspring of parents with PTSD. Offspring of trauma survivors with PTSD show significantly lower 24-h mean urinary cortisol excretion and salivary cortisol levels as well as enhanced plasma cortisol suppression in response to low dose dexamethasone administration than offspring of survivors without PTSD. In all cases, neuroendocrine measures were negatively correlated with severity of parental PTSD symptoms, even after controlling for PTSD and even other symptoms in offspring. Though the majority of our work has focused on adult offspring of Holocaust survivors, recent observations in infants born to mothers who were pregnant on 9/11 demonstrate that low cortisol in relation to parental PTSD appears to be present early in the course of development and may be influenced by in utero factors such as glucocorticoid programming. Since low cortisol levels are particularly associated with the presence of maternal PTSD the findings suggest the involvement of epigenetic mechanisms. C1 [Yehuda, Rachel; Bierer, Linda M.] Mt Sinai Sch Med & Bronx Vet Affairs, Dept Psychiat, Traumat Stress Studies Program, James J Peters VAMC, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med & Bronx Vet Affairs, Dept Psychiat, Traumat Stress Studies Program, James J Peters VAMC, 116-A,OOMH-PTSD,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.yehuda@va.gov NR 55 TC 10 Z9 10 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53140-7 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 167 BP 121 EP 135 DI 10.1016/S0079-6123(07)67009-5 PG 15 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences; Psychiatry; Psychology SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry; Psychology GA BHE65 UT WOS:000252487200009 ER PT S AU Pitman, RK AF Pitman, R. K. BE DeKloet, ER Vermetten, E TI Commentary: synthesis and perspectives SO STRESS HORMONES AND POST TRAUMATIC STRESS DISORDER: BASIC STUDIES AND CLINICAL PERSPECTIVES SE Progress in Brain Research LA English DT Review CT Colloquium on Stress Hormones and Post Traumatic Stress Disorder - Basic Studies and Clinical Perspectives CY AUG 28-30, 2006 CL Amsterdam, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Minist Defence Netherlands DE stress disorders; post-traumatic; hormones; memory; conditioning ID BASOLATERAL AMYGDALA; MEMORY; BRAIN; RATS C1 Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp East, Room 2616 Bldg 149,13th St, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53140-7 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 167 BP 249 EP + DI 10.1016/S0079-6123(07)67018-6 PG 5 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences; Psychiatry; Psychology SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry; Psychology GA BHE65 UT WOS:000252487200018 ER PT S AU Calderwood, SK Mambula, SS Gray, PJ AF Calderwood, Stuart K. Mambula, Salamatu S. Gray, Phillip J., Jr. BE Csermely, P Korcsmaros, T Sulyok, K TI Extracellular heat shock proteins in cell signaling and immunity SO STRESS RESPONSES IN BIOLOGY AND MEDICINE: STRESS OF LIFE IN MOLECULES, CELLS, ORGANISMS, AND PSYCHOSOCIAL COMMUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd World Conference on Stress CY AUG 23-26, 2007 CL Budapest, HUNGARY DE extracellular; heat; shock; protein; secretion; receptor ID ANTIGEN-PRESENTING CELLS; RECEPTOR-MEDIATED ENDOCYTOSIS; SCAVENGER RECEPTORS; HEAT-SHOCK-PROTEIN-70 PEPTIDE; MOLECULAR CHAPERONES; CHRONIC INFLAMMATION; CROSS-PRESENTATION; DENDRITIC CELLS; STRESS PROTEINS; HSP70 AB Extracellular stress proteins including heat shock proteins (Hsps) and glucose-regulated proteins (Grps) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological "danger signals." Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis. After release into the extracellular fluid, Hsp or Grp may then bind to the surfaces of adjacent cells and initiate signal transduction cascades as well as the transport of cargo molecules, such as antigenic peptides. In addition, Hsp60 and Hsp70 are able to enter the bloodstream and may possess the ability to act at distant sites in the body. Many of the effects of extracellular stress proteins are mediated through cell-surface receptors. Such receptors include toll-like receptors (TLRs) 2 and 4, CD40, CD91, CCR5, and members of the scavenger receptor family, such as LOX-1 and SREC-1. The possession of a wide range of receptors for the Hsp and Grp family permits binding to a diverse range of cells and the performance of complex multicellular functions particularly in immune cells and neurons. C1 Harvard Univ, Sch Med, BIDMC, Dept Radiat Oncol, Boston, MA 02215 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, BIDMC, Dept Radiat Oncol, Rm553B,21-27 Burlington Ave, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu FU NCI NIH HHS [5R01CA047407, 3R01CA094397] NR 64 TC 132 Z9 137 U1 2 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-675-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1113 BP 28 EP 39 DI 10.1196/annals.1391.019 PG 12 WC Psychology, Biological; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences; Psychology, Social SC Psychology; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGX56 UT WOS:000251158200003 PM 17978280 ER PT J AU Voetsch, B Jin, RC Bierl, C Benke, KS Kenet, G Simioni, P Ottaviano, F Damasceno, BP Annichino-Bizacchi, JM Handy, DE Loscalzo, J AF Voetsch, Barbara Jin, Richard C. Bierl, Charlene Benke, Kelly S. Kenet, Gili Simioni, Paolo Ottaviano, Filomena Damasceno, Benito P. Annichino-Bizacchi, Joyce M. Handy, Diane E. Loscalzo, Joseph TI Promoter polymorphisms peroxidase in the plasma glutathione (GPx-3) gene - A novel risk factor for arterial ischemic stroke among young adults and children SO STROKE LA English DT Article DE oxidative stress; platelets; thrombosis ID NITRIC-OXIDE; HUMAN GENOME; EXPRESSION; PLATELET; DISEASE; PURIFICATION; INHIBITION; DEFICIENCY; FIBRINOGEN; INFARCTION AB Background and Purpose-Plasma glutathione peroxidase (GPx-3)-deficiency increases extracellular oxidant stress, decreases bioavailable nitric oxide, and promotes platelet activation. The aim of this study is to identify polymorphisms in the GPx-3 gene, examine their relationship to arterial ischemic stroke (AIS) in a large series of children and young adults, and determine their functional molecular consequences. Methods-We studied the GPx-3 gene promoter from 123 young adults with idiopathic AIS and 123 age- and gender-matched controls by single-stranded conformational polymorphism and sequencing analysis. A second, independent population with childhood stroke was used for a replication study. We identified 8 novel, strongly linked polymorphisms in the GPx-3 gene promoter that formed 2 main haplotypes (H1 and H2). The transcriptional activity of the 2 most prevalent haplotypes was studied with luciferase reporter gene constructs. Results-The H2 haplotype was over-represented in both patient populations and associated with an independent increase in the risk of AIS in young adults (odds ratio=2.07, 95% CI= 1.03 to 4.47; P=0.034) and children (odds ratio=2.13. 95% CI=1.23 to 4.90; P=0.027). In adults' simultaneously exposed to vascular risk factors, the risk of AIS approximately doubled (odds ratio=5.18, 95% CI=1.82 to 15.03; P < 0.001). Transcriptional activity of the H2 haplotype was lower than that of the H1 haplotype, especially after upregulation by hypoxia (normalized relative luminescence: 3.54 +/- 0.32 versus 2.47 +/- 0.26; P=0.0083). Conclusion-These findings indicate that a novel GPx-3 promoter haplotype is an independent risk factor for AIS in children and young adults. This haplotype reduces the gene's transcriptional activity, thereby compromising gene expression and plasma antioxidant and antithrombotic activities. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Univ Estadual Campinas, Dept Neurol, Campinas, SP, Brazil. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Padua, Dept Med & Surg Sci, Padua, Italy. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. RP Loscalzo, J (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB,Rm 630, Boston, MA 02115 USA. EM jloscalzo@partners.org FU NHLBI NIH HHS [HL55993, HL58976, HL61795, HL81587, HV28718, N01 HV028178, P01 HL081587, P50 HL055993, R01 HL058976, R01 HL061795, R37 HL061795] NR 37 TC 76 Z9 80 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2007 VL 38 IS 1 BP 41 EP 49 DI 10.1161/01.STR.0000252027.53766.2b PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124HP UT WOS:000243359200015 PM 17122425 ER PT J AU Liu, YR D'Arceuil, HE Westmoreland, S He, JL Duggan, M Gonzalez, RG Pryor, J de Crespigny, AJ AF Liu, Yutong D'Arceuil, Helen E. Westmoreland, Susan He, Julian Duggan, Michael Gonzalez, R. Gilberto Pryor, Johnny de Crespigny, Alex J. TI Serial diffusion tensor MRI after transient and permanent cerebral ischemia in nonhuman primates SO STROKE LA English DT Article DE brain imaging; diffusion tensor imaging; diffusion-weighted imaging; experimental; focal ischemia; interventional neuroradiology; magnetic resonance; MRI; neuroradiology; pathology ischemia; stroke ID WATER DIFFUSION; TIME-COURSE; TEMPORAL EVOLUTION; EARLY REPERFUSION; ACUTE STROKE; COEFFICIENT; PERFUSION; INFARCTION; ANISOTROPY; INJURY AB Background and Purpose-We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point. Methods-Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, n=4 or permanent occlusion, n=3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis. Results-Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes. Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling. Conclusions-Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Martinos Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neuroradiol Sect, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. RP de Crespigny, AJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Martinos Ctr, Rm 2301,Bldg 149,13th St, Boston, MA 02129 USA. EM alexdec@nmr.mgh.harvard.edu FU NINDS NIH HHS [1R01-NS41285] NR 32 TC 55 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2007 VL 38 IS 1 BP 138 EP 145 DI 10.1161/01.STR.0000252127.07428.9c PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124HP UT WOS:000243359200031 PM 17122422 ER PT J AU Menezes, NM Ay, H Zhu, MW Lopez, CJ Singhal, AB Karonen, JO Aronen, HJ Liu, YW Nuutinen, J Koroshetz, WJ Sorensen, AG AF Menezes, Nina M. Ay, Hakan Zhu, Ming Wang Lopez, Chloe J. Singhal, Aneesh B. Karonen, Jari O. Aronen, Hannu J. Liu, Yawu Nuutinen, Juho Koroshetz, Walter J. Sorensen, A. Gregory TI The real estate factor - Quantifying the impact of infarct location on stroke severity SO STROKE LA English DT Article DE infarcts; magnetic resonance imaging; models; outcome; statistical; stroke ID ISCHEMIC-STROKE; SCALE; HEMISPHERE; VOLUME AB Background and Purpose-The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. Methods-We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. Results-Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). Conclusions-The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Kuopio Univ Hosp, Dept Clin Radiol, SF-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. Helsinki Brain Res Ctr, Funct Brain Imaging Unit, Helsinki, Finland. Finnish Def Forces, Ctr Mil Med, Helsinki, Finland. Univ Turku, Dept Diagnost Radiol, Turku, Finland. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu FU AHRQ HHS [R01HS011392]; NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [R01NS38477] NR 7 TC 60 Z9 62 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2007 VL 38 IS 1 BP 194 EP 197 DI 10.1161/01.STR.0000251792.76080.45 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124HP UT WOS:000243359200040 PM 17122428 ER PT J AU Shetty, SK Lev, MH AF Shetty, Sanjay K. Lev, Michael H. BA Torbey, MT Selim, MH BF Torbey, MT Selim, MH TI Computed tomography in acute stroke SO STROKE BOOK LA English DT Article; Book Chapter ID ACUTE ISCHEMIC-STROKE; APPARENT DIFFUSION-COEFFICIENT; 3-DIMENSIONAL FUNCTIONAL CT; ANGIOGRAPHY SOURCE IMAGES; CEREBRAL-BLOOD-FLOW; HYPERACUTE STROKE; INTRAARTERIAL THROMBOLYSIS; PERFUSION; PENUMBRA; ACCURACY C1 [Shetty, Sanjay K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Lev, Michael H.] Massachusetts Gen Hosp, CT & Neurovasc Lab, Boston, MA 02114 USA. RP Shetty, SK (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-67160-6 PY 2007 BP 95 EP 114 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA BAC61 UT WOS:000303805600009 ER PT J AU Krakauer, EL AF Krakauer, Eric L. BE Good, B Biehl, J kleinman, A TI "To Be Freed from the Infirmity of (the) Age" Subjectivity, Life-Sustaining Treatment, and Palliative Medicine SO SUBJECTIVITY: ETHNOGRAPHIC INVESTIGATIONS SE Ethnographic Studies in Subjectivity LA English DT Article; Book Chapter ID CARDIAC MASSAGE; CRITICALLY-ILL; WITHDRAWAL; NUTRITION; SUPPORT C1 [Krakauer, Eric L.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Krakauer, EL (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 38 TC 3 Z9 5 U1 0 U2 0 PU UNIV CALIFORNIA PRESS PI BERKELEY PA 2120 BERKELEY WAY, BERKELEY, CA 94720 USA BN 978-0-52093-963-9 J9 ETHNOG STUD SUBJ PY 2007 VL 7 BP 381 EP 396 D2 10.1525/california/9780520247925.001.0001 PG 16 WC Anthropology SC Anthropology GA BXF70 UT WOS:000295972600018 ER PT J AU Huckans, MS Loftis, JM Blackwell, AD Linke, A Hauser, P AF Huckans, Marilyn S. Loftis, Jennifer M. Blackwell, Aaron D. Linke, Alex Hauser, Peter TI Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article ID ILLICIT-DRUG-USERS; VIRUS-INFECTION; PLUS RIBAVIRIN; MANAGEMENT; VETERANS; MULTICENTER; POPULATION; PREVALENCE; DRINKERS; BARRIERS AB Background: Individuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group). Results: Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%). Conclusion: Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy. C1 [Huckans, Marilyn S.; Loftis, Jennifer M.; Blackwell, Aaron D.; Linke, Alex; Hauser, Peter] Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97201 USA. [Huckans, Marilyn S.; Loftis, Jennifer M.; Blackwell, Aaron D.; Linke, Alex; Hauser, Peter] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Huckans, Marilyn S.; Loftis, Jennifer M.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Loftis, Jennifer M.; Hauser, Peter] Portland VA Med Ctr, JENS Lab, Portland, OR USA. [Blackwell, Aaron D.] Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA. RP Huckans, MS (reprint author), Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97201 USA. EM marilyn.huckans@va.gov; loftisj@ohsu.edu; ablackwe@uoregon.edu; alex.linke@va.gov; peter.hauser2@va.gov RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 38 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PY 2007 VL 2 AR 4 DI 10.1186/1747-597X-2-4 PG 8 WC Substance Abuse SC Substance Abuse GA V00DD UT WOS:000206768100004 PM 17222348 ER PT J AU Yamamoto, RT Karlsgodt, KH Rott, D Lukas, SE Elman, I AF Yamamoto, Rinah T. Karlsgodt, Katherine H. Rott, David Lukas, Scott E. Elman, Igor TI Effects of perceived cocaine availability on subjective and objective responses to the drug SO SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY LA English DT Article AB Rationale: Several lines of evidence suggest that cocaine expectancy and craving are two related phenomena. The present study assessed this potential link by contrasting reactions to varying degrees of the drug's perceived availability. Method: Non-treatment seeking individuals with cocaine dependence were administered an intravenous bolus of cocaine (0.2 mg/kg) under 100% ('unblinded'; N = 33) and 33% ('blinded'; N = 12) probability conditions for the delivery of drug. Subjective ratings of craving, high, rush and low along with heart rate and blood pressure measurements were collected at baseline and every minute for 20 minutes following the infusions. Results: Compared to the 'blinded' subjects, their 'unblinded' counterparts had similar craving scores on a multidimensional assessment several hours before the infusion, but reported higher craving levels on a more proximal evaluation, immediately prior to the receipt of cocaine. Furthermore, the 'unblinded' subjects displayed a more rapid onset of high and rush cocaine responses along with significantly higher cocaine-induced heart rate elevations. Conclusion: These results support the hypothesis that cocaine expectancy modulates subjective and objective responses to the drug. Provided the important public health policy implications of heavy cocaine use, health policy makers and clinicians alike may favor cocaine craving assessments performed in the settings with access to the drug rather than in more neutral environments as a more meaningful marker of disease staging and assignment to the proper level of care. C1 [Yamamoto, Rinah T.; Lukas, Scott E.; Elman, Igor] Harvard Univ, McLean Hosp, Sch Med, Behav Psychopharmacol Res Lab, Belmont, MA 02178 USA. [Karlsgodt, Katherine H.; Elman, Igor] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Addict Res Program, Belmont, MA 02178 USA. [Rott, David] Hadassah Hebrew Univ, Med Ctr, Dept Med, Jerusalem, Israel. [Karlsgodt, Katherine H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Yamamoto, RT (reprint author), Harvard Univ, McLean Hosp, Sch Med, Behav Psychopharmacol Res Lab, 115 Mill St, Belmont, MA 02178 USA. EM yamamoto@mclean.harvard.edu; karlsgodt@psych.ucla.edu; drott@012.net.il; lukas@mclean.harvard.edu; ielman@partners.org RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 FU NIDA NIH HHS [DA017959, DA015036, DA014410, K23 DA014410, R01 DA017959, T32 DA015036] NR 64 TC 13 Z9 13 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-597X J9 SUBST ABUSE TREAT PR JI Subst/ Abus. Treatment Prev. Pol. PY 2007 VL 2 AR 30 DI 10.1186/1747-597X-2-30 PG 8 WC Substance Abuse SC Substance Abuse GA V00DD UT WOS:000206768100030 PM 17931408 ER PT J AU Regillo, CD D'Amico, DJ Mieler, WF Schneebaum, C Beasley, CH Sullins, GT AF Regillo, Carl D. D'Amico, Donald J. Mieler, William F. Schneebaum, Cary Beasley, Cliff H. Sullins, Gregory T. TI Clinical safety profile of posterior juxtascleral depot administration of anecortave acetate 15 mg suspension as primary therapy or adjunctive therapy with photodynamic therapy for treatment of wet age-related macular degeneration SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE AMD; anecortave acetate; posterior juxtascleral depot administration; safety ID ANGIOSTATIC ACTIVITY; CHICK-EMBRYO; NEOVASCULARIZATION; STEROIDS; CAM AB Objectives: Safety data for anecortave acetate 15 mg suspension (Retaane 15 mg, Alcon Research, Ltd., Ft. Worth, TX 76134) as primary or adjunctive therapy with photodynamic therapy are available for 358 patients with age-related macular degeneration who received this novel cortisene during clinical trials in which the drug was administered Via posterior juxtascleral depot every 6 months for 2 years. Methods: Detailed ophthalmic examinations, physical examinations, and adverse event reporting were used to characterize the clinical safety of anecortave acetate 15 mg and were monitored by an Independent Safety Committee. Results: Anecortave acetate 15 mg was safe and well tolerated in the overall patient population. No serious, treatment-related deaths were reported. Ocular adverse events assessed as related to anecortave acetate 15 mg were non-serious with one exception (retinal detachment), mild to moderate in intensity with one exception, generally resolved with or without treatment, and did not interrupt patient participation in the studies with two exceptions. Conclusions: Anecortave acetate 15 mg is safe and well-tolerated when administered as a posterior juxtascleral depot at 6-month intervals for use as primary therapy or as adjunctive therapy with PDT. C1 Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA. Alcon Res Ltd, Med Monitor, Ft Worth, TX USA. Alcon Res Ltd, Invest Prod Safety, Ft Worth, TX USA. RP Regillo, CD (reprint author), Wills Eye Hosp & Res Inst, Retina Serv, 840 Walnut St,Suite 1020, Philadelphia, PA 19107 USA. NR 10 TC 5 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 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JAN PY 2007 VL 52 SU 1 BP S70 EP S78 DI 10.1016/j.survophthal.2006.11.001 PG 9 WC Ophthalmology SC Ophthalmology GA 135KZ UT WOS:000244153800009 PM 17240259 ER PT J AU Chandra, D Gupta, S Reddy, RM Gregoric, ID Kar, B AF Chandra, Divay Gupta, Sachin Reddy, Raghu M. Gregoric, Igor D. Kar, Biswajit TI Gastric volvulus after ventricular assist device explantation and cardiac transplantation SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE cardiac transplantation; device removal; stomach volvulus; heart assist devices/adverse effects; hernia, diaphragmatic/ diagnosis/etiology/surgery; postoperative complications ID HEART-TRANSPLANTATION; LVAD AB Diaphragmatic herniation has been recognized as a complication of unrepaired diaphragmatic defects after left ventricular assist device explantation and cardiac transplantation. We believe this to be the 1st report of diaphragmatic herniation that resulted in gastric volvulus in a cardiac transplant recipient. The presentation, diagnosis, and treatment of this potentially fatal condition are discussed herein. Nine months after removal of a Thoratec HeartMate (R) II left ventricular assist device and orthotopic cardiac transplantation, the patient presented with intermittent upper abdominal and lower chest discomfort of 3 weeks' duration. Physical examination was notable for fullness in the upper abdomen. Plain radiographs and computed tomographic scans of the chest and abdomen without contrast were unexceptional. Two weeks later, the patient's pain began to worsen rapidly, and an upper gastrointestinal barium study revealed partial herniation of the stomach into the chest and omento-axial gastric volvulus without luminal obstruction. The patient underwent uncomplicated laparotomy for repair of the diaphragmatic defect and reduction of the herniated stomach. This case highlights the need for increased awareness of diaphragmatic herniation as a complication of unrepaired diaphragmatic defects so that diagnosis is not delayed, and underscores the importance of primary repair of all such defects to prevent future complications. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Div Pulm & Crit Care Med, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiothorac Surg & Mech Circulatory Support, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Div Cardiol, Houston, TX 77030 USA. RP Chandra, D (reprint author), Baylor Coll Med, Dept Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM divaychandra@gmail.com NR 11 TC 4 Z9 4 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 2007 VL 34 IS 1 BP 112 EP 114 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 152EO UT WOS:000245344000026 PM 17420807 ER PT J AU Guiot, C Delsanto, PP Deisboeck, TS AF Guiot, Caterina Delsanto, Pier P. Deisboeck, Thomas S. TI Morphological instability and cancer invasion: a 'splashing water drop' analogy SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Article AB Background: Tissue invasion, one of the hallmarks of cancer, is a major clinical problem. Recent studies suggest that the process of invasion is driven at least in part by a set of physical forces that may be susceptible to mathematical modelling which could have practical clinical value. Model and conclusion: We present an analogy between two unrelated instabilities. One is caused by the impact of a drop of water on a solid surface while the other concerns a tumor that develops invasive cellular branches into the surrounding host tissue. In spite of the apparent abstractness of the idea, it yields a very practical result, i.e. an index that predicts tumor invasion based on a few measurable parameters. We discuss its application in the context of experimental data and suggest potential clinical implications. C1 [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. [Guiot, Caterina] Univ Turin, Dip Neurosci, I-10124 Turin, Italy. [Guiot, Caterina] Univ Turin, CNISM, I-10124 Turin, Italy. [Delsanto, Pier P.] Politecn Torino, Dip Fis, Turin, Italy. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. EM caterina.guiot@unito.it; pier.delsanto@polito.it; deisboec@helix.mgh.harvard.edu RI guiot, caterina/C-6708-2009; OI guiot, caterina/0000-0001-8529-1625 FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. NR 34 TC 8 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PY 2007 VL 4 AR 4 DI 10.1186/1742-4682-4-4 PG 6 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V19EE UT WOS:000208054900004 PM 17254360 ER PT J AU Wang, ZH Zhang, L Sagotsky, J Deisboeck, TS AF Wang, Zhihui Zhang, Le Sagotsky, Jonathan Deisboeck, Thomas S. TI Simulating non-small cell lung cancer with a multiscale agent-based model SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Article AB Background: The epidermal growth factor receptor (EGFR) is frequently overexpressed in many cancers, including non-small cell lung cancer (NSCLC). In silico modeling is considered to be an increasingly promising tool to add useful insights into the dynamics of the EGFR signal transduction pathway. However, most of the previous modeling work focused on the molecular or the cellular level only, neglecting the crucial feedback between these scales as well as the interaction with the heterogeneous biochemical microenvironment. Results: We developed a multiscale model for investigating expansion dynamics of NSCLC within a two-dimensional in silico microenvironment. At the molecular level, a specific EGFR-ERK intracellular signal transduction pathway was implemented. Dynamical alterations of these molecules were used to trigger phenotypic changes at the cellular level. Examining the relationship between extrinsic ligand concentrations, intrinsic molecular profiles and microscopic patterns, the results confirmed that increasing the amount of available growth factor leads to a spatially more aggressive cancer system. Moreover, for the cell closest to nutrient abundance, a phase-transition emerges where a minimal increase in extrinsic ligand abolishes the proliferative phenotype altogether. Conclusion: Our in silico results indicate that in NSCLC, in the presence of a strong extrinsic chemotactic stimulus (and depending on the cell's location) downstream EGFR-ERK signaling may be processed more efficiently, thereby yielding a migration-dominant cell phenotype and overall, an accelerated spatio-temporal expansion rate. C1 [Wang, Zhihui; Zhang, Le; Sagotsky, Jonathan; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. EM billwang@nmr.mgh.harvard.edu; adamzhan@nmr.mgh.harvard.edu; sagotsky@nmr.mgh.harvard.edu; deisboec@helix.mgh.harvard.edu FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by NIH grant CA 113004 (The Center for the Development of a Virtual Tumor, CViT [71]) and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. We would like to acknowledge helpful discussions with Drs. Raju Kucherlapati, Victoria Joshi and David Sarracino from the Harvard-Partners Center for Genetics and Genomics (HPCGG). NR 72 TC 41 Z9 42 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PY 2007 VL 4 AR 50 DI 10.1186/1742-4682-4-50 PG 14 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V19EE UT WOS:000208054900050 PM 18154660 ER PT J AU Kim, ND Luster, AD AF Kim, Nancy D. Luster, Andrew D. TI Regulation of immune cells by eicosanoid receptors SO THESCIENTIFICWORLDJOURNAL LA English DT Review DE prostaglandin D-2; DP1; DP2; CRTH2; leukotriene B-4; BLT1; BLT2; cysteinyl leukotriene; CysLT(1); CysLT(2) ID LEUKOTRIENE B-4 RECEPTOR; HUMAN MAST-CELLS; PLATELET-ACTIVATING FACTOR; D-PROSTANOID RECEPTOR-1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INFL AMMATORY ARTHRITIS; HUMAN DENDRITIC CELLS; CYSTEINYL LEUKOTRIENES; PROSTAGLANDIN D-2; MOLECULAR-CLONING AB Eicosanoids are potent, bioactive, lipid mediators that regulate important components of the immune response, including defense against infection, ischemia, and injury, as well as instigating and perpetuating autoimmune and inflammatory conditions. Although these lipids have numerous effects on diverse cell types and organs, a greater understanding of their specific effects on key players of the immune system has been gained in recent years through the characterization of individual eicosanoid receptors, the identification and development of specific receptor agonists and inhibitors, and the generation of mice genetically deficient in various eicosanoid receptors. In this review, we will focus on the receptors for prostaglandin D-2, DP1 and DP2/CRTH2; the receptors for leukotriene B-4, BLT1 and BLT2; and the receptors for the cysteinyl leukotrienes, CysLT(1) and CysLT(2), by examining their specific effects on leukocyte subpopulations, and how they may act in concert towards the development of immune and inflammatory responses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol,Ctr Immunol & Inflammat Dis, Boston, MA USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol,Ctr Immunol & Inflammat Dis, Boston, MA USA. EM luster.andrew@mgh.harvard.edu NR 143 TC 43 Z9 45 U1 2 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 PY 2007 VL 7 BP 1307 EP 1328 DI 10.1100/tsw.2007.181 PG 22 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 210BY UT WOS:000249432900004 PM 17767352 ER PT J AU Vianello, F Poznansky, MC Furlan, A Piccioti, A Prandoni, P AF Vianello, F. Poznansky, M. C. Furlan, A. Piccioti, A. Prandoni, P. TI Low-molecular weight heparin antagonizes the CXCL12-driven migration of chronic lymphocytic leukemia B cells SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Thrombosis and Hemostasis Issues in Cancer CY OCT 26-28, 2007 CL Bergamo, ITALY C1 [Vianello, F.; Furlan, A.; Piccioti, A.; Prandoni, P.] Univ Padua Hosp, Padua, Italy. [Poznansky, M. C.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RI Vianello, Fabrizio/M-5211-2016 OI Vianello, Fabrizio/0000-0002-7174-4651 NR 0 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 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2007 VL 120 SU 2 BP S163 EP S164 DI 10.1016/S0049-3848(07)70211-6 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248IT UT WOS:000252147500090 ER PT S AU Levine, RA Nam, EC Oron, Y Melcher, JR AF Levine, R. A. Nam, E. C. Oron, Y. Melcher, J. R. BE Langguth, B Hajak, G Kleinjung, T Cacace, A Moller, AR TI Evidence for a tinnitus subgroup responsive to somatosensory based treatment modalities SO TINNITUS: PATHOPHYSIOLOGY AND TREATMENT SE Progress in Brain Research LA English DT Review; Book Chapter DE acupuncture; trigger point injections; temporomandibular; dorsal cochlear nucleus; electrical ID DORSAL COCHLEAR NUCLEUS; PAIN-DYSFUNCTION SYNDROME; DOUBLE-BLIND CROSSOVER; TEMPOROMANDIBULAR DISORDER; ELECTRICAL-STIMULATION; MUSCLE-CONTRACTIONS; SPINAL MANIPULATION; LATERALIZATION; ACUPUNCTURE; THERAPY AB Studies have established that the somatosensory system of the upper cervical region and head can be intimately involved in tinnitus. Tinnitus can arise directly from a disorder of the head and upper neck through activation of the somatosensory system. "Somatic testing" (a series of strong muscle contractions of the head and neck) can (1) modulate the tinnitus percept of similar to 80% of people with ongoing tinnitus, and (2) elicit a sound percept in similar to 50% of people with no tinnitus. These somatic phenomena are equally prevalent among people with or without functioning cochlea. Likely neural pathways underlying both the induction and modulation of tinnitus have been revealed in animal studies. Because somatic influences are fundamental to the operation of the auditory system, in general, and to tinnitus, in particular, somatic testing should be incorporated into all evaluations of tinnitus (1) to improve understanding of the role of the somatosensory system in any individual and (2) to identify subgroups of tinnitus patients who may respond to a particular treatment modality (as has already been shown for the tinnitus associated with temporomandibular disorder). Our clinical experience and review of reports of treatment modalities directed toward the somatosensory system supports the hypothesis that these modalities can benefit individuals with symmetric hearing thresholds but asymmetric widely fluctuating tinnitus. Treatment modalities involving the somatosensory system should be re-assessed by targeting this tinnitus subgroup. C1 [Levine, R. A.; Nam, E. C.; Melcher, J. R.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Nam, E. C.] Kangwon Natl Univ, Coll Med, Dept Otolaryngol, Chunchon, South Korea. [Oron, Y.] Wolfson Med Ctr, Dept Otolaryngol, Holon, Israel. RP Levine, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM ObbyLevine@yahoo.com NR 40 TC 34 Z9 35 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53167-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 166 BP 195 EP 207 DI 10.1016/S0079-6123(07)66017-8 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA BQC09 UT WOS:000280613600019 PM 17956783 ER PT S AU Langguth, B Goodey, R Azevedo, A Bjorne, A Cacace, A Crocetti, A Del Bo, L De Ridder, D Diges, I Elbert, T Flor, H Herraiz, C Sanchez, TG Eichhammer, P Figueiredo, R Hajak, G Kleinjung, T Landgrebe, M Londero, A Lainez, MJA Mazzoli, M Meikle, MB Melcher, J Rauschecker, JP Sand, PG Struve, M Van de Heyning, P Van Dijk, P Vergara, R AF Langguth, B. Goodey, R. Azevedo, A. Bjorne, A. Cacace, A. Crocetti, A. Del Bo, L. De Ridder, D. Diges, I. Elbert, T. Flor, H. Herraiz, C. Ganz Sanchez, T. Eichhammer, P. Figueiredo, R. Hajak, G. Kleinjung, T. Landgrebe, M. Londero, A. Lainez, M. J. A. Mazzoli, M. Meikle, M. B. Melcher, J. Rauschecker, J. P. Sand, P. G. Struve, M. Van de Heyning, P. Van Dijk, P. Vergara, R. BE Langguth, B Hajak, G Kleinjung, T Cacace, A Moller, AR TI Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, July 2006 SO TINNITUS: PATHOPHYSIOLOGY AND TREATMENT SE Progress in Brain Research LA English DT Review; Book Chapter DE tinnitus; standards; assessment; questionnaires; treatment; outcome; case history ID PSYCHOMETRIC PROPERTIES; QUESTIONNAIRE; INVENTORY AB There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies. C1 [Langguth, B.; Eichhammer, P.; Hajak, G.; Landgrebe, M.; Sand, P. G.] Univ Regensburg, Dept Psychiat, D-93053 Regensburg, Germany. [Goodey, R.] Univ Auckland, Dept Surg, Auckland 1, New Zealand. [Azevedo, A.; Figueiredo, R.] Otosul Otorrinolaringol, Dept Otolaryngol, Volta Redonda, Brazil. [Bjorne, A.] Ystad Hosp, Vertigo Tinnitus & Pain Unit, SE-27131 Ystad, Sweden. [Cacace, A.] Inst Neurosci, Dept Neurol, Albany, NY USA. [Cacace, A.] Adv Imaging Res Ctr, Albany, NY USA. [Crocetti, A.; Del Bo, L.] Fdn Ascolta & Vivi, Milan, Italy. [De Ridder, D.] Univ Antwerp Hosp, Dept Neurosurg, Antwerp, Belgium. [Diges, I.; Herraiz, C.] Fdn Hosp Alcorcon, Tinnitus Clin Dept Otorhinolaryngol, Madrid 28922, Spain. [Elbert, T.] Univ Konstanz, Dept Clin & Neuropsychol, D-78457 Constance, Germany. [Flor, H.; Struve, M.] Univ Heidelberg, Inst Clin & Cognit Neurosci, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. [Ganz Sanchez, T.] Univ Sao Paulo, Sch Med, Dept Otolaryngol, Sao Paulo, Brazil. [Kleinjung, T.] Univ Regensburg, Dept Otorhinolaryngol, Regensburg, Germany. [Londero, A.] Hop Europeen Georges Pompidou, Consultat Acouphenes Serv ORL, Paris, France. [Lainez, M. J. A.] Univ Valencia, Dept Neurol, Valencia 46010, Spain. [Mazzoli, M.] UOC ORL OTOCHIRURG, Padua, Italy. [Meikle, M. B.] Oregon Hearing Res Ctr, Dept Otolaryngol, Portland, OR USA. [Melcher, J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Rauschecker, J. P.] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. [Van de Heyning, P.] Univ Antwerp Hosp, Dept Otolaryngol, Antwerp, Belgium. [Van Dijk, P.] Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol, NL-9713 AV Groningen, Netherlands. [Vergara, R.] Fdn Ciencia & Tecnol, Bogota, Colombia. RP Langguth, B (reprint author), Univ Regensburg, Dept Psychiat, Univ Str 84, D-93053 Regensburg, Germany. EM Berthold.Langguth@medbo.de; Berthold.Langguth@medbo.de RI Van Dijk, Pim/E-8019-2010; Sand, Philipp/C-1924-2009; Elbert, Thomas/C-8556-2009; Rauschecker, Josef/A-4120-2013 OI Flor, Herta/0000-0003-4809-5398; Van Dijk, Pim/0000-0002-8023-7571; Sand, Philipp/0000-0001-5806-5841; FU NIDCD NIH HHS [R01 DC003489, R01 DC003489-05, RC1 DC010720] NR 15 TC 113 Z9 117 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53167-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 166 BP 525 EP 536 DI 10.1016/S0079-6123(07)66050-6 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA BQC09 UT WOS:000280613600052 PM 17956816 ER PT J AU Chan, BP Hui, TY Chan, OCM So, KF Lu, W Cheung, KMC Salomatina, E Yaroslavsky, A AF Chan, B. P. Hui, T. Y. Chan, O. C. M. So, K. -F. Lu, W. Cheung, K. M. C. Salomatina, E. Yaroslavsky, A. TI Photochemical cross-linking for collagen-based scaffolds: A study on optical properties, mechanical properties, stability, and hematocompatibility SO TISSUE ENGINEERING LA English DT Article ID INTEGRATING-SPHERE MEASUREMENTS; PHOTODYNAMIC THERAPY; PHYSICAL-PROPERTIES; SINGLET OXYGEN; TISSUE; REPAIR; BLOOD; GRAFT AB Collagen presents an attractive biomaterial for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. However, some intrinsic features related to the mechanical stability and thrombogenicity limit its applications in orthopedic and vascular tissue engineering. Photochemical crosslinking is an emerging technique able to stabilize tissue grafts and improve the physicochemical properties of collagen-based structures. However, other important properties of collagen-based structures and the effect of processing parameters on these properties have not been explored. In this study, we aim to investigate the dose dependence of tensile and swelling properties on two parameters, namely, laser energy fluence and rose Bengal photosensitizer concentration. We also study the compression properties using cyclic compression test, long-term stability using subcutaneous implantation, and hematocompatibility using platelets adhesion test, of cross-linked collagen structures. Moreover, because limited optical penetration in turbid media is the major obstacle for light-based techniques, we also characterize the optical properties, which partially determine the effective optical penetration depth in collagen gel samples, during photochemical cross-linking. Laser energy fluence and rose Bengal concentration are important parameters affecting the cross-linking efficiency, which was characterized as the mechanical and the swelling properties, in a dose-dependent manner. Under the experimental conditions in this study, the peak fluence was 12.5J/cm(2) and the minimal rose Bengal concentration for effective cross-linking was > 0.00008 % (0.786 mu mol). Photochemical cross-linking also enhanced the compression strength and long-term stability of collagen structures without compromising the tissue compatibility. Furthermore, photochemical cross-linking reduced platelet adhesion and abolished fibrin mesh formation, thereby improving the hematocompatibility of collagen structures. These results suggest the feasibility of using the photochemically cross-linked collagen structures for orthopedic and vascular tissue engineering. Finally, the effective optical penetration depth in collagen gel samples is wavelength and rose Bengal concentration dependent, and was similar to 12 mm at 514 nm at 0.001 % (9.825 mu mol), the rose Bengal concentration mostly used in this study. C1 Univ Hong Kong, Med Engn Program, Dept Mech Engn, Hong Kong, Peoples R China. Univ Hong Kong, Dept Anat, Hong Kong, Peoples R China. Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Chan, BP (reprint author), Univ Hong Kong, Med Engn Program, Dept Mech Engn, Room 711,Haking Wong Bldg,Pokfulam Rd, Hong Kong, Peoples R China. EM bpchan@hkucc.hku.hk RI Chan, BP/C-1886-2009; So, Kwok Fai/C-4399-2009 NR 51 TC 29 Z9 30 U1 2 U2 13 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 JAN PY 2007 VL 13 IS 1 BP 73 EP 85 DI 10.1089/ten.2006.004 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 130PU UT WOS:000243812300008 PM 17518582 ER PT J AU Hannouche, D Terai, H Fuchs, JR Terada, S Zand, S Nasseri, BA Petite, H Sedel, L Vacanti, JP AF Hannouche, D. Terai, H. Fuchs, J. R. Terada, S. Zand, S. Nasseri, B. A. Petite, H. Sedel, L. Vacanti, J. P. TI Engineering of implantable cartilaginous structures from bone marrow-derived mesenchymal stem cells SO TISSUE ENGINEERING LA English DT Article ID IN-VITRO CHONDROGENESIS; PROGENITOR CELLS; ENDOTHELIAL-CELLS; ALGINATE BEADS; STROMAL CELLS; TISSUE; DIFFERENTIATION; SCAFFOLD; COLLAGEN; GROWTH AB Fabrication of implantable cartilaginous structures that could be secured in the joint defect could provide an alternative therapeutic approach to prosthetic joint replacement. Herein we explored the possibility of using biodegradable hydrogels in combination with a polyglycolic acid (PGA) scaffold to provide an environment propitious to mesenchymal stem cells (MSCs) chondrogenic differentiation. We examined the influence of type I collagen gel and alginate combined with PGA meshes on the extracellular matrix composition of tissue-engineered transplants. MSCs were isolated from young rabbits, expanded in monolayers, suspended in each hydrogel, and loaded on PGA scaffolds. All constructs (n = 48) were cultured in serum-free medium containing transforming growth factor beta-1, under dynamic conditions in specially designed bioreactors for 3-6 weeks. All cell-polymer constructs had a white, shiny aspect, and retained their initial size and shape over the culture period. Their thickness increased substantially over time, and no shrinkage was observed. All specimens developed a hyalin-like extracellular matrix containing glycosaminoglycans (GAGS) and type II collagen, but significant differences were observed among the three different groups. In PGA/MSCs and collagen-PGA/MSCs constructs, the cell growth phase and the chondrogenic differentiation phase of MSCs occurred during the first 3 weeks. In alginate-PGA/MSCs constructs, cells remained round in the hydrogel and cartilage extracellular matrix deposition was delayed. However, at 6 weeks, alginate-PGA/MSCs constructs exhibited higher contents of GAGS and lower contents of type I collagen. These results suggest that the implied time for the transplantation of in vitro engineered constructs depends, among other factors, on the nature of the scaffold envisioned. In this study, we demonstrated that the use of a composite hydrogel-PGA scaffold supported the in vitro growth of implantable cartilaginous structures cultured in a bioreactor system. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Univ Paris, Fac Med Lariboisiere St Louis, Lab Rech Orthoped, F-75252 Paris, France. RP Vacanti, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Warren 11-1157,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org RI Petite, Herve/E-3478-2016 OI Petite, Herve/0000-0003-1694-5060 NR 53 TC 52 Z9 55 U1 1 U2 9 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 JAN PY 2007 VL 13 IS 1 BP 87 EP 99 DI 10.1089/ten.2006.0067 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 130PU UT WOS:000243812300009 PM 17518583 ER PT S AU Nahmias, Y Berthiaume, F Yarmush, ML AF Nahmias, Yaakov Berthiaume, Francois Yarmush, Martin L. BE Lee, K Kaplan, D TI Integration of technologies for hepatic tissue engineering SO TISSUE ENGINEERING II: BASICS OF TISSUE ENGINEERING AND TISSUE APPLICATIONS SE Advances in Biochemical Engineering-Biotechnology LA English DT Article; Book Chapter ID PERFUSED-RAT-LIVER; CELL-CELL INTERACTIONS; LONG-TERM CULTURE; OF-THE-ART; IN-VITRO; NONPARENCHYMAL CELLS; BIOARTIFICIAL LIVER; EXTRACELLULAR-MATRIX; HEPATOCYTE FUNCTION; GENE-EXPRESSION AB The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25 000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen "sandwich" and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burn Hosp,Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burn Hosp,Ctr Engn Med,Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU NIBIB NIH HHS [P41 EB002503]; NIDDK NIH HHS [R01DK43371] NR 133 TC 90 Z9 96 U1 7 U2 30 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0724-6145 BN 3-540-36185-5 J9 ADV BIOCHEM ENG BIOT JI Adv. Biochem. Eng. Biotechnol. PY 2007 VL 103 BP 309 EP 329 DI 10.1007/10_029 PG 21 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BFN17 UT WOS:000243222900008 PM 17195468 ER PT J AU Li, YF Wheeler, DL Ananthaswamy, HN Verma, AK Oberley, TD AF Li, Yafan Wheeler, Deric L. Ananthaswamy, Honnavara N. Verma, Ajit K. Oberley, Terry D. TI Differential tumor biology effects of double-initiation in a mouse skin chemical carcinogenesis model comparing wild type versus protein kinase Cepsilon overexpression mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE protein kinase Cepsilon; cell death; papilloma; squamous cell carcinoma ID SQUAMOUS-CELL CARCINOMA; TRANSGENIC MICE; C-EPSILON; IN-SITU; ACTIVATION; EPIDERMIS; PAPILLOMAS AB Our previous studies showed that protein kinase Cepsilon (PKC epsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol- 13-acetate (TPA)-promotion in the absence of preceding papilloma formation as is typically observed in wild type mice. The present study demonstrates that double-DMBA initiation modulates tumor incidence, multiplicity, and latency period in both wild type and PKC epsilon overexpression transgenic (PKC epsilon-Tg) mice. After 17 weeks (wks) of tumor promotion, a reduction in papilloma multiplicity was observed in double- versus single-DMBA initiated wild type mice. Papilloma multiplicity was inversely correlated with cell death indices of interfollicular keratinocytes, indicating decreased papilloma formation was caused by increased cell death and suggesting the origin of papillomas is in interfollicular epidermis. Double-initiated PKC epsilon-Tg mice had accelerated carcinoma formation and cancer incidence in comparison to single-initiated PKC epsilon-Tg mice. Morphologic analysis of mouse skin following double initiation and tumor promotion showed a similar if not identical series of events to those previously observed following single initiation and tumor promotion: putative preneoplastic cells were observed arising from hyperplastic hair follicles (HF's) with subsequent cancer cell infiltration into the dermis. Single-initiated PKC epsilon-Tg mice exhibited increased mitosis in epidermal cells of HFs during tumor promotion. C1 [Li, Yafan] Univ New Mexico, Hlth Sci Ctr, Coll Pharm, Program Toxicol & Pharmacol, Albuquerque, NM 87131 USA. [Wheeler, Deric L.; Verma, Ajit K.] Univ New Mexico, Sch Med & Publ Hlth, Dept Human Oncol, Albuquerque, NM 87131 USA. [Ananthaswamy, Honnavara N.] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Oberley, Terry D.] VA Hosp, Pathol & Lab Med Serv, Madison, WI USA. [Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Oberley, TD (reprint author), Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu RI Wheeler, Deric/B-7175-2013 OI Wheeler, Deric/0000-0001-5915-3675 FU NCI NIH HHS [CA35368] NR 14 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 7 BP 942 EP 951 DI 10.1080/01926230701748164 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 243JO UT WOS:000251792800010 PM 18098040 ER PT J AU Baronas, ET Lee, JW Alden, C Hsieh, FY AF Baronas, Elizabeth Tengstrand Lee, Ju-Whei Alden, Carl Hsieh, Frank Y. TI Biomarkers to monitor drug-induced phospholipidosis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE drug-induced phospholipidosis; amiodarone; azithromycin; gentamicin; mass spectrometry; biomarker; phospholipids; cationic amphiphilic drugs ID AMIODARONE-INDUCED PHOSPHOLIPIDOSIS; RAT RENAL-CORTEX; BIS(MONOACYLGLYCEROL) PHOSPHATE; LYSOSOMAL PHOSPHOLIPIDOSIS; MACROLIDE AZITHROMYCIN; TREATED RATS; ACID; AMINOGLYCOSIDES; GENTAMICIN; NEPHROTOXICITY AB Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) was identified as a promising phospholipidosis (PL) biomarker in rats treated with either amiodarone, gentamicin, or azithromycin. Sprague-Dawley rats received either antiodarone (150 mg/kg), gentarnicin (100 mg/kg) or azithromycin (30 mg/kg) once daily for ten consecutive days. Histopathological examination of tissues by transmission electron microscopy (TEM) indicated different degrees of accumulation of phospholipidosis in liver, lung, mesenteric lymph node, and kidney of drug-treated rats but not controls. Liquid chromatography coupled to mass spectrometry (LC/MS) was used to identify levels of endogenous biochemical profiles in rat urine. Urinary levels of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) correlated with induction of phospholipidosis for amiodarone, gentamicin and azithromycin. Rats treated with gentarnicin also had increased urinary levels of several phosphatidylinositol, (PI), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) species. (c) 2006 Elsevier Inc. All rights reserved. C1 Nextecea Inc, Lexington, MA 02421 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Drug Safety & Disposit, Cambridge, MA 02139 USA. RP Hsieh, FY (reprint author), Nextecea Inc, 3 Goffe Rd, Lexington, MA 02421 USA. EM frank.hsieh@nextcea.com NR 37 TC 48 Z9 51 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 1 PY 2007 VL 218 IS 1 BP 72 EP 78 DI 10.1016/j.taap.2006.10.015 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 129MQ UT WOS:000243734000009 PM 17156806 ER PT J AU Saito, Y AF Saito, Yoriko TI Making a stealth organ by RNA inhibition: will it fly? SO TRANSFUSION LA English DT Editorial Material ID TRANSGENE EXPRESSION; LENTIVIRAL VECTORS; STEM-CELLS; INTERFERENCE; INFECTION; KNOCKDOWN; DELIVERY; THERAPY C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Saito, Y (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM ysaito@partners.org NR 14 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 JAN PY 2007 VL 47 IS 1 BP 4 EP 5 DI 10.1111/j.1537-2995.2007.01086.x PG 2 WC Hematology SC Hematology GA 118SX UT WOS:000242963100003 PM 17207222 ER PT J AU Duke-Cohan, JS Khwaja, FH van Meir, EG AF Duke-Cohan, Jonathan S. Khwaja, Fatima H. van Meir, Erwin G. TI Attractin, neurodegeneration and glioma development SO TUMOR BIOLOGY LA English DT Meeting Abstract CT 35th Meeting of the International-Society-for-Oncodevelopmental-Biology-and-Medicine CY SEP 15-19, 2007 CL Prague, CZECH REPUBLIC SP Int Soc Oncodev Bio & Med, Roche, Abbot Lab, Beckman Coulter, Inc, Olympus, Novartis, Ceska Sporitelna, Bayer Health Care, Siemens Med Solutions Diagnostics, Bio-Rad, Bio-Consult, CEZ, AstraZeneca, Immunotech, Zentiva, Biovica, DiaSorin, FUJIREBIO, BRAHMS, IDL Inc, LACOMED, Liga proti rakovine Praha C1 [Duke-Cohan, Jonathan S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Duke-Cohan, Jonathan S.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Khwaja, Fatima H.; van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2007 VL 28 SU 1 BP 3 EP 3 PG 1 WC Oncology SC Oncology GA 237TK UT WOS:000251399100005 ER PT J AU Kawase, Y Suzuki, Y Ikeno, F Yoneyama, R Hoshino, K Ly, HQ Lau, GT Hayase, M Yeung, AC Hajjar, RJ Jang, IK AF Kawase, Yoshiaki Suzuki, Yoriyasu Ikeno, Fumiaki Yoneyama, Ryuichi Hoshino, Kozo Ly, Hung Q. Lau, George T. Hayase, Motoya Yeung, Alan C. Hajjar, Roger J. Jang, Ik-Kyung TI Comparison of nonuniform rotational distortion between mechanical IVUS and OCT using a phantom model SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE optical coherence tomography; mechanical intravascular ultrasound; nonuniform rotational distortion ID OPTICAL-COHERENCE-TOMOGRAPHY; PACLITAXEL-ELUTING STENTS; CORONARY-ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; CATHETER; PLAQUE; INTERVENTIONS; TRIALS AB Optical coherence tomography (OCT) is an optical analog of mechanical intravascular ultrasound (M-IVUS) with much higher spatial resolution. However, no data exist regarding the nonuniform rotational distortion (NURD) with OCT. The aim of the study was to investigate whether OCT generates less NURD relative to M-IVUS. A coronary artery phantom model was constructed with a rubber ring (3.68 mm in diameter), located at the distal end of the phantom. This model was also composed of eight equally spaced steel wires and an additional marker-wire. Two types of vascular phantoms were used, mild curve (90 degrees) and acute curve (near 180 degrees). Subsequent M-IVUS (n = 6) and OCT (n = 6) imaging was performed. Eight angles between eight wires, except the marker-wire, were measured from each image. These angles, measured with M-IVUS and OCT, were compared with those of high-resolution optical photography as a gold standard. The average in angle differences was significantly smaller in OCT compared with M-IVUS in the mild curve model (3.2 +/- 1.0 degrees vs, 6.9 +/- 2.11 degrees, p < 0.01). Compared with the latter model, the average in angle differences was exaggerated in the acute curve model with M-IVUS (9.1 +/- 0.9 degrees vs. 6.9 +/- 2.1 degrees p < 0.05) but not with OCT (3.5 +/- 0.8 degrees vs. 3.2 +/- 1.0 degrees, p = not significant). OCT generates significantly less NURD compared with M-IVUS, especially in tortuous situation. (E-mail: ijang@partners.org) (c) 2006 World Federation for Ultrasound in Medicine & Biology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. Stanford Med Ctr, Div Cardiovasc Med, Stanford, CA USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Lab Integrat Physiol & Imaging, 55 Fruit St,Bulfinch 161, Boston, MA 02114 USA. EM ijang@partners.org NR 23 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JAN PY 2007 VL 33 IS 1 BP 67 EP 73 DI 10.1016/j.ultrasmedbio.2006.07.020 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 122RH UT WOS:000243243700008 PM 17189048 ER PT J AU Quirk, GJ Milad, MR Santini, E Lebron, K AF Quirk, Gregory J. Milad, Mohammed R. Santini, Edwin Lebron, Kelimer BE Kirmayer, LJ Lemelson, R Barad, M TI Learning Not to Fear: A Neural Systems Approach SO UNDERSTANDING TRAUMA: INTEGRATING BIOLOGICAL, CLINICAL, AND CULTURAL PERSPECTIVES LA English DT Article; Book Chapter ID MEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL-BLOOD-FLOW; CONDITIONED FEAR; POTENTIATED STARTLE; PROTEIN-SYNTHESIS; SPONTANEOUS-RECOVERY; SYNAPTIC PLASTICITY; LATERAL NUCLEUS; EXTINCTION C1 [Quirk, Gregory J.] Ponce Sch Med, Dept Physiol, Ponce, PR 00716 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Santini, Edwin] Ponce Sch Med, Dept Pharmacol, Ponce, PR USA. [Milad, Mohammed R.; Lebron, Kelimer] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Quirk, GJ (reprint author), Ponce Sch Med, Dept Physiol, Ponce, PR 00716 USA. NR 81 TC 3 Z9 3 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-85428-3 PY 2007 BP 60 EP 77 DI 10.1017/CBO9780511500008.007 PG 18 WC Psychology, Clinical SC Psychology GA BYX93 UT WOS:000300698700007 ER PT J AU Coen, JJ Zietman, AL Kaufman, DS Shipley, WU AF Coen, John J. Zietman, Anthony L. Kaufman, Donald S. Shipley, William U. TI Benchmarks achieved in the delivery of radiation therapy for muscle-invasive bladder cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE bladder cancers; radiation therapy; combined modality therapy; bladder preservation ID PAINFUL BONE METASTASES; PROSPECTIVE RANDOMIZED TRIAL; QUALITY-OF-LIFE; RADICAL CYSTECTOMY; ONCOLOGY-GROUP; PREOPERATIVE RADIOTHERAPY; NEOADJUVANT CHEMOTHERAPY; PALLIATIVE RADIOTHERAPY; TRANSURETHRAL RESECTION; ORGAN PRESERVATION AB Radiation therapy has a multifaceted role in the treatment of muscle-invasive bladder cancer, from being a component of bladder sparing regimens to adjuvant therapy for patients after partial cystectomy, to palliative treatment in patients with metastatic disease. Here, we review the techniques currently used and the settings in which these techniques are applied. Advances in imaging and radiation delivery have allowed for definition of more precise treatment volumes, permitting the delivery of higher tumor doses and lesser doses to critical targets. Better tumor control, fewer therapeutic complications, and better quality of life outcomes are anticipated. In the United States, the most rapidly growing use of radiation in the treatment of bladder cancer is as a component of selective bladder conservation. It uses trimodality therapy, consisting of a maximal transurethral resection followed by concurrent chemotherapy and radiation. Careful cystoscopic surveillance by an experienced urologist ensures a prompt cystectomy at the fist sign of treatment failure. The majority of patients retain a well-functioning bladder with no survival decrement. Radiation therapy is also used as adjuvant therapy after partial cystectomy in select patients. In this setting, it decreases the risk of local or incisional recurrence. It is also used in patients with pelvic recurrences after cystectomy, often combined with concurrent chemotherapy. Radiation is a very effective palliative agent for patients with locally advanced or metastatic disease. It can palliate bleeding and pain for patients with local progression or alleviate pain from bony metastases. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jcoen@partners.org NR 36 TC 15 Z9 15 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN-FEB PY 2007 VL 25 IS 1 BP 76 EP 84 DI 10.1016/j.urolonc.2006.05.012 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 129AY UT WOS:000243702000013 PM 17208144 ER PT J AU Milosevic, M Gospodarowicz, M Zietman, A Abbas, F Haustermans, K Moonen, L Rodel, C Schoenberg, M Shipley, W AF Milosevic, Michael Gospodarowicz, Mary Zietman, Anthony Abbas, Farhat Haustermans, Karin Moonen, Luc Rodel, Claus Schoenberg, Mark Shipley, William TI Radiotherapy for bladder cancer SO UROLOGY LA English DT Review ID TRANSITIONAL-CELL-CARCINOMA; CHEMOTHERAPY FOLLOWING CYSTECTOMY; PREOPERATIVE RADIATION-THERAPY; SELECTIVE ORGAN PRESERVATION; EXTERNAL-BEAM RADIOTHERAPY; FULL-DOSE IRRADIATION; SALVAGE CYSTECTOMY; PROGNOSTIC-FACTORS; RADICAL RADIOTHERAPY; ADJUVANT CHEMOTHERAPY AB The radiotherapy panel met to develop international consensus about the optimal use of radiotherapy, alone or in combination with surgery and chemotherapy, in the radical treatment of patients with bladder cancer. A consensus meeting of experts in the treatment of bladder cancer was convened by the Societe Internationale d'Urologie (SIU). The radiotherapy committee, which had international representation from 6 countries, performed a critical review of the English-language literature and developed evidence-based guidelines for the use of radiotherapy in the treatment of patients with bladder cancer. The strength of the evidence supporting each recommendation was ranked according to a 4-point scale. Consensus statements were developed that address (1) the effectiveness of radiotherapy in the treatment of bladder cancer, (2) the most appropriate patients for curative treatment with radiotherapy, (3) the optimal method of delivery of radiotherapy, (4) the best radiation prescription for treating bladder cancer, and (5) optimal management of the patient's condition after radiotherapy has been provided. Radiotherapy is effective treatment for selected patients with bladder cancer; it produces long-term disease control with preservation of normal bladder function. Modern radiotherapy treatment techniques offer the potential to improve cure rates and reduce adverse effects. All patients in whom the condition is newly diagnosed should be assessed in a multidisciplinary setting, where the relative merits of surgery, radiotherapy, and chemotherapy can be considered on an individual basis with the aim of optimizing overall outcomes. C1 Princess Margaret Hosp, Radiat Med Program, Toronto, ON M5G 2M9, Canada. Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Aga Khan Univ Hosp, Dept Urol, Karachi, Pakistan. Univ Hosp Gasthuisberg, Dept Radiat Oncol, B-3000 Louvain, Belgium. Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands. Univ Erlangen Nurnberg, Dept Radiat Therapy, Erlangen, Germany. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. RP Milosevic, M (reprint author), Princess Margaret Hosp, Radiat Med Program, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM mike.milosevic@rmp.uhn.on.ca NR 102 TC 33 Z9 33 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2007 VL 69 SU 1A BP 80 EP 92 DI 10.1016/j.urology.2006.05.060 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 136UK UT WOS:000244249400006 PM 17280910 ER PT J AU Scranton, RE Bozeman, SR Burton, TM Hoaglin, DC Sirko, S Hollenbeak, CS Wilson, PWF AF Scranton, Richard E. Bozeman, Samuel R. Burton, Tanya M. Hoaglin, David C. Sirko, Steven Hollenbeak, Christopher S. Wilson, Peter W. F. TI Simple demographic model to predict multiple cardiometabolic risk factors in two well-known observational cohorts SO VALUE IN HEALTH LA English DT Article DE Atherosclerosis Risk in Communities Study; body mass index; diabetes; dyslipidemia; Framingham Offspring Study; glucose; metabolic syndrome; obesity; prediction model ID CORONARY-HEART-DISEASE; INCIDENT CARDIOVASCULAR-DISEASE; NUTRITION EXAMINATION SURVEY; METABOLIC SYNDROME; NATIONAL-HEALTH; UNITED-STATES; PREVALENCE; MORTALITY; ADULTS; ASSOCIATION AB Objectives: Determining the prevalence of multiple cardiometabolic risk (CMR) factors requires clinical and laboratory data not readily available to most health-care plans. We evaluated the ability of a simple model derived from the National Health and Nutrition Examination Survey (NHANES) using commonly available demographic information to predict prevalence of multiple CMR factors. Methods: We defined CMR factors according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP 111) and International Diabetes Federation (IDF) guidelines for metabolic syndrome classification in both the Atherosclerosis Risk in Communities (ARIC) and the Framingham Offspring Study (FOS) cohorts. Using NHANES data, a simple demographic model consisting of sex, race and ethnicity, smoking status, and the natural logarithm of age, generated the coefficients used to predict the prevalence of multiple CMR factors in ARIC and FOS. Predicted prevalences were compared with the observed prevalences in both cohorts. Results: The ARIC and FOS cohorts consisted of 11,596 and 3532 subjects with a mean age of 62.6 and 58.8 years, respectively. The observed proportion of participants with metabolic syndrome in ARIC was 52.1% and 58.8%) according to the NCEP and IDF definitions, respectively. In FOS the observed prevalence was 41.4% and 45.8% using the NCEP and IDF definitions. Predicted prevalences of metabolic syndrome for the NCEP and IDF definitions, respectively, were 51.3% and 53.5% in ARIC, and 48.2% and 51.4% in FOS. Differences between the observed and predicted prevalences for three of four additional risk factor sets, including abdominal obesity (AO) alone, AO plus diabetes, and AO plus diabetes plus dyslipidemia, were small (between 1 to 7 percentage points) in both cohorts. The model poorly predicted the prevalence of AO plus dyslipidemia. Conclusion: A simple demographic model adequately predicted the prevalence of CMR factors. The model should help health-care plans lacking clinical and laboratory data to estimate prevalence of CMR factors in their populations. Future studies need to evaluate the influence of race, sex, and ethnicity on prevalence of these risk factors in various settings. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Boston VA Healthcare Syst, Boston, MA 02121 USA. ABT Associates Inc, Bridgewater, NJ USA. Sanofi Aventis, Bridgewater, NJ USA. Penn State Univ, Coll Med, State Coll, PA 16804 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Scranton, RE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Boston VA Healthcare Syst, 1620 Tremont St, Boston, MA 02121 USA. EM richardscrantonmd@rcn.com NR 25 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JAN-FEB PY 2007 VL 10 SU 1 BP S37 EP S44 DI 10.1111/j.1524-4733.2006.00153.x PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 135VJ UT WOS:000244181700007 ER PT J AU Zhou, W Choi, L Lin, PH Dardik, A Eraso, A Lumsden, AB AF Zhou, Wei Choi, Lorraine Lin, Peter H. Dardik, Alan Eraso, Andrea Lumsden, Alan B. TI Percutaneous transhepatic thrombectomy and pharmacologic thrombolysis of mesenteric venous thrombosis SO VASCULAR LA English DT Article DE endovascular; mesenteric venous thrombosis; oral contraceptives; pancreatitis; percutaneous thrombectomy; transhepatic ID PORTAL-VEIN THROMBOSIS; LIVER-TRANSPLANTATION; MANAGEMENT; STENT AB Mesenteric venous occlusion is a rare yet highly morbid condition that is traditionally treated with anticoagulation while surgery serves as the last resort. Percutaneous intervention provides an effective option with relatively low mortality and morbidity. We herein describe use of transhepatic percutaneous thrombectomy and pharmacologic thrombolysis in treating two cases of symptomatic mesenteric venous thrombosis. These cases underscore the fact that transhepatic thrombectomy and thrombolysis are a highly effective strategy for treating acute symptomatic mesenteric venous thrombosis. Several percutaneous techniques are also reviewed. C1 Baylor Coll Med, Michael E DeBakey Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Surg, VA Connecticut Healthcare Syst, New Haven, CT USA. Michael E DeBakey Med Ctr, Div Radiol, Houston, TX USA. RP Zhou, W (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg, 1709 Dryden St,Suite 1500, Houston, TX 77030 USA. EM wzhou1@bcm.edu NR 20 TC 17 Z9 22 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1708-5381 J9 VASCULAR JI Vascular PD JAN-FEB PY 2007 VL 15 IS 1 BP 41 EP 45 DI 10.2310/6670.2007.00013 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 191OX UT WOS:000248141900009 PM 17382054 ER PT J AU Jaff, M Campbell, LA Constant, J Hiatt, W Sternlicht, A AF Jaff, Michael Campbell, Lee Anne Constant, John Hiatt, William Sternlicht, Andrew TI Increased seroprevalence of elevated IgG antibodies to C. pneumoniae in PAD vs CAD patients in a phase III trial SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. PRA Int, Ottawa, ON, Canada. Colorado Prevent Ctr, Denver, CO USA. ActivBiotics Inc, Lexington, 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 1358-863X J9 VASC MED JI Vasc. Med. PY 2007 VL 12 IS 2 MA 5 BP 140 EP 140 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 181XT UT WOS:000247470400012 ER PT J AU Maree, AO Islam, MA Snuderl, M Lamuraglia, GM Stone, JR Olmsted, K Rosenfield, KA Jaff, MR AF Maree, Andrew O. Islam, M. Ashequl Snuderl, Matija Lamuraglia, Glenn M. Stone, James R. Olmsted, Kari Rosenfield, Kenneth A. Jaff, Michael R. TI External iliac artery endofibrosis in an amateur runner: hemodynamic, angiographic, histopathological evaluation and percutaneous revascularization SO VASCULAR MEDICINE LA English DT Article DE amateur runner; Doppler; endofibrosis; iliac artery; intimal hyperplasia ID CYCLISTS AB We describe a case of external iliac artery endofibrosis in an amateur competitive runner. The diagnosis was made by a combination of hemodynamic, angiographic and histopathological assessment and percutaneous revascularization was performed using a balloon expandable stent. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Vasc Med Sect,Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Gen Vasc Serv, Boston, MA 02115 USA. RP Jaff, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Vasc Med Sect,Div Cardiol, Boston, MA 02115 USA. EM mjaff@partners.org OI Snuderl, Matija/0000-0003-0752-0917 NR 8 TC 17 Z9 17 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2007 VL 12 IS 3 BP 203 EP 206 DI 10.1177/1358863x07080844 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225YT UT WOS:000250554900006 PM 17848477 ER PT J AU Bhatti, S Hakeem, A Ahmad, U Malik, M Kosolcharoen, P Chang, SM AF Bhatti, Sabha Hakeem, Abdul Ahmad, Usman Malik, Maher Kosolcharoen, Peter Chang, Su Min TI Persistent left superior vena cava (PLSVC) with anomalous left hepatic vein drainage into the right atrium: role of imaging and clinical relevance SO VASCULAR MEDICINE LA English DT Article DE anomalous left hepatic vein; central venous access; left superior vena cava; thoracic veins ID PARKINSON-WHITE-SYNDROME; CENTRAL VENOUS CATHETER; CORONARY-SINUS; EXPERIENCE; CLOSURE AB Persistent left superior vena cava (PLSVC) is a very rare and yet the most commonly described thoracic venous anomaly in medical literature. It has a 10-fold higher incidence with congenital heart disease. PLSVC often becomes apparent when an unknown PLSVC is incidentally discovered during central venous line placement, intracardiac electrode/pacemaker placement or cardiopulmonary bypass, where it may cause technical difficulties and life-threatening complications. PLSVC is also associated with disturbances of cardiac impulse formation and conduction including varying degrees of heart blocks, supraventricular arrhythmias and Wolff Parkinson White syndrome. We describe the case of an 86-year-old male with a history of coronary artery disease and chronic atrial fibrillation who presented with worsening dyspnea and syncopal episodes. An ECG was consistent with complete heart block. During lead placement for the pacemaker, a left subclavian approach was unsuccessful. A left venogram was performed through the brachial vein that demonstrated a left superior vena cava. The diagnosis was confirmed with echocardiography using a bubble study and also a chest CT. The anatomy was unique as there was anomalous left hepatic vein drainage into the right atrium. The case provides insight into the diagnostic modalities and clinical considerations of this unusual thoracic venous anomaly. C1 [Bhatti, Sabha; Hakeem, Abdul; Malik, Maher; Kosolcharoen, Peter; Chang, Su Min] Univ Wisconsin Hosp & Clin, Dept Cardiovasc Med, Madison, WI 53792 USA. [Bhatti, Sabha; Hakeem, Abdul; Malik, Maher; Kosolcharoen, Peter; Chang, Su Min] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Ahmad, Usman] Yale Univ, Sch Med, New Haven, CT USA. RP Hakeem, A (reprint author), 2705 Univ Ave 11, Madison, WI 53705 USA. EM a.hakeem@hosp.wisc.edu NR 31 TC 13 Z9 16 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2007 VL 12 IS 4 BP 319 EP 324 DI 10.1177/1358863x07084859 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 248VR UT WOS:000252185700007 PM 18048468 ER PT J AU Jaff, MR AF Jaff, Michael R. BE Rooke, TW TI Vascular Medicine and Endovascular Interventions Preface SO VASCULAR MEDICINE AND ENDOVASCULAR INTERVENTIONS LA English DT Editorial Material; Book Chapter C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69235-6 PY 2007 BP XI EP XI D2 10.1002/9780470692356 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BCJ48 UT WOS:000310287100001 ER PT B AU Jaff, MR AF Jaff, Michael R. BE Rooke, TW TI Carotid Artery Disease and Stroke SO VASCULAR MEDICINE AND ENDOVASCULAR INTERVENTIONS LA English DT Article; Book Chapter ID HIGH-GRADE; ENDARTERECTOMY; TRIAL; STENOSIS; RISK; MORTALITY C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69235-6; 978-1-4051-5827-5 PY 2007 BP 212 EP 220 D2 10.1002/9780470692356 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BCJ48 UT WOS:000310287100020 ER PT J AU Longacre, TA Oliva, E Soslow, RA AF Longacre, Teri A. Oliva, Esther Soslow, Robert A. CA Assoc Directors Anatomic Surgical TI Recommendations for the reporting of fallopian tube neoplasms SO VIRCHOWS ARCHIV LA English DT Article ID OVARIAN-CANCER; RISK; OOPHORECTOMY; CARCINOMA; LIGATION; CARRIERS C1 Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Longacre, TA (reprint author), Stanford Univ, Dept Pathol, 300 Pasteur Dr, Stanford, CA 94305 USA. EM longacre@stanford.edu OI Soslow, Robert/0000-0002-7269-5898 NR 10 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD JAN PY 2007 VL 450 IS 1 BP 25 EP 29 DI 10.1007/s00428-006-0303-5 PG 5 WC Pathology SC Pathology GA 136HQ UT WOS:000244213600003 PM 17334802 ER PT J AU Roehrl, MHA Selig, MK Nielsen, GP Dal Cin, P Oliva, E AF Roehrl, Michael H. A. Selig, Martin K. Nielsen, G. Petur Dal Cin, Paola Oliva, Esther TI A renal cell carcinoma with components of both chromophobe and papillary carcinoma SO VIRCHOWS ARCHIV LA English DT Article DE renal cell carcinoma; chromophobe; papillary; case report; immunohistochemistry; electron microscopy; fluorescene in-situ hybridization; histogenesis ID COMPARATIVE GENOMIC HYBRIDIZATION; COLLECTING DUCT CARCINOMA; STEM-CELLS; EPITHELIAL NEOPLASMS; HISTOLOGIC SUBTYPES; BREAST-CANCER; TUMORS; KIDNEY; CLASSIFICATION; IDENTIFICATION AB We report a case of a morphologically unusual renal cell carcinoma with features of both chromophobe and papillary carcinoma. Immunohistochemical analysis of high molecular weight cytokeratins (HMWCK), cytokeratin 7 (CK7), cytokeratin 19 (CK19), c-Kit, and alpha-methylacyl-CoA racemase (AMACR) demonstrated differential profiles for the two components of the tumor, consistent with the respective patterns commonly observed for pure chromophobe and papillary renal cell carcinomas. Specifically, the chromophobe tumor cells expressed CK7 and c-Kit weakly, while HMWCK, CK19, and AMACR were not detectable. In contrast, the papillary tumor cells expressed uniformly HMWCK, CK7, and c-Kit and focally CK19 and AMACR. Fluorescence in situ hybridization analysis of nuclei isolated from paraffin-embedded tumor tissue detected monosomy 1, disomy 7, and monosomy 17, a common and characteristic finding in chromophobe carcinomas, in a majority of, but not all tumor cells, whereas a population characterized by disomy 1, trisomy 7, and trisomy 17, a frequent finding in papillary carcinoma, was not identifiable. Electron microscopic analysis revealed numerous characteristic small cytoplasmic vesicles in the chromophobe areas, which were absent in the papillary component. This case illustrates the rare coexistence of two distinct and admixed histologic types of renal cell carcinoma. C1 Massachusetts Gen Hosp, Dept Pathol & Lab Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Roehrl, MHA (reprint author), Massachusetts Gen Hosp, Dept Pathol & Lab Med, James Homer Wright Pathol Labs, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM michael_roehrl@hms.harvard.edu NR 45 TC 8 Z9 10 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD JAN PY 2007 VL 450 IS 1 BP 93 EP 101 DI 10.1007/s00428-006-0331-1 PG 9 WC Pathology SC Pathology GA 136HQ UT WOS:000244213600011 PM 17124599 ER PT S AU Seco, J Gierga, D Sharp, G Turcotte, J Paganetti, H AF Seco, J. Gierga, D. Sharp, G. Turcotte, J. Paganetti, H. BE Kim, SI Suh, TS TI Effects of intra-fraction motion on IMRT treatments with low monitor unit segments SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING 2006, VOL 14, PTS 1-6 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY AUG 27-SEP 01, 2006 CL Seoul, SOUTH KOREA SP IUPSEM, IFMBE, IOMP, KSMP, KSMBE, AAPM, AFOMP, BMES, EFOMP, IAEA, AIMBE, IEEE EMB, WHO, SIEMENS, TomoTherapy, Philips, iba, Varian, CIVCO, Elekta, Samsung DE Intra-fraction Motion; IMRT; few monitor unit segments ID ORGAN MOTION; RADIOTHERAPY; DELIVERY; LUNG AB Purpose: Intra-fraction motion can affect the delivered dose distribution in radiotherapy. This is a concern in intensity-modulated radiotherapy (IMRT) because of potential interplay between the delivered fluence pattern and the patient's breathing pattern. In the present study we assess if breathing compromises the radiotherapy treatment with IMRT segments delivering only few monitor units, where the delivery time of the segments will be of the order of the breathing period. An in-house made motor driven platform, which moves sinusoidally with a user-specified amplitude and a period of 4-5s for tumor motion was used. The measurements were performed for motion amplitude of 4 cm in 4x4cm(2)-10x10cm(2) open fields and dose-rate of 500MUmin(-1). The monitor units (MUs) delivered were 4, 8, 17, 25, 33, 42, 50, 67, 83, 100, 133 and 150 MUs, corresponding to delivery times of 0.5s, 1s, 2s, 3s, 4s, 5s, 6s, 8s, 10s, 12s, 16s and 18s. The measurements were repeated for ten different initial phases. Results: The delivered dose to a moving target varies with initial phase and with segment delivery time. For very long segment times the delivered dose has a 3% spread with the initial phase. Therefore, over 30 fractions, the average dose delivered to the moving tumor will converge to the mean dose delivered over the breathing-period. However, for short delivery times, the delivered dose varies significantly with the initial phase. These differences occur because the dose delivered to the tumor becomes dependent on non-uniform dose and penumbra effects. Conclusions: For IMRT treatment with only a few segments and a segment delivery time (4-12s) in the order of the breathing period (3-5s), interplay between organ and leaf motion can significantly influence the delivered dose. Since there are interplay effects for segments with only a few MU, the delivered dose depends strongly on the initial phase. Therefore, there could be cases where organ motion cannot be modeled as a probability density function in IMRT optimization. C1 [Seco, J.; Gierga, D.; Sharp, G.; Turcotte, J.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Seco, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU National Cancer Institute, DHHS [R01-CA111590] FX This work was supported by grant R01-CA111590 from the National Cancer Institute, DHHS. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1680-0737 BN 978-3-540-36839-7 J9 IFMBE PROC PY 2007 VL 14 BP 1763 EP + PN 1-6 PG 2 WC Engineering, Biomedical; Physics, Applied; Imaging Science & Photographic Technology SC Engineering; Physics; Imaging Science & Photographic Technology GA BIM52 UT WOS:000260855900424 ER PT S AU Paganetti, H AF Paganetti, H. BE Kim, SI Suh, TS TI Treatment planning in 3 and 4 dimensions and the role of Monte Carlo techniques SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING 2006, VOL 14, PTS 1-6 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY AUG 27-SEP 01, 2006 CL Seoul, SOUTH KOREA SP IUPSEM, IFMBE, IOMP, KSMP, KSMBE, AAPM, AFOMP, BMES, EFOMP, IAEA, AIMBE, IEEE EMB, WHO, SIEMENS, TomoTherapy, Philips, iba, Varian, CIVCO, elekta, Samsung DE Monte Carlo; Proton Therapy; 4D planning ID TIME-DEPENDENT GEOMETRIES; SIMULATIONS; MOTION AB Purpose: Monte Carlo dose calculation is considered to be the most accurate method to simulate doses delivered in radiation therapy. It is rarely used in clinical routine because of usually long computing times. Given the fact that dose distributions are more conformal in proton therapy than with conventional modalities, the potential impact of Monte Carlo dose calculation is presumably bigger in proton therapy. The goal of this work was to facilitate the clinical use of Monte Carlo dose calculation to support routine treatment planning and delivery at the Francis H Burr Proton Therapy Center at Massachusetts General Hospital (NIGH). Further, we aimed at incorporating time-dependent patient information, as obtained from 4D CT data, into the dose calculation process. Results: Proton Monte Carlo dose calculation is clinically implemented at NIGH. To do so, the treatment head and patient geometries had to be modeled in detail, the beam had to be well characterized and the dose engine had to be linked to patient database and hardware control parameters. So far, dose calculations have been done for many cases in radiosurgery and for breast, prostate, nasopharynx, paranasal sinus, paraspinal, and lung malignancies. Differences to the commercial pencil-beam algorithm could be identified in cases of frequent soft-tissue/bone/air interfaces and in particular for patient with metallic implants. The resulting Monte Carlo dose distributions can be imported into the planning system for analysis. Based on a simulation of the ionization chamber in the treatment head, the Monte Carlo generated doses are given in absolute units (Gy per proton fluence). To incorporate motion information for thoracic tumors we developed a fourdimensional Monte Carlo dose calculation technique, which allows the consideration of 4D CT data sets. Conclusions: Proton Monte Carlo dose calculation can be done efficiently for treatment planning support. Many steps on the Monte Carlo dose calculation level as well as in linking the dose engine to the patient database and the hardware control system were required to accomplish this. C1 [Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1680-0737 BN 978-3-540-36839-7 J9 IFMBE PROC PY 2007 VL 14 BP 2203 EP 2206 PN 1-6 PG 4 WC Engineering, Biomedical; Physics, Applied; Imaging Science & Photographic Technology SC Engineering; Physics; Imaging Science & Photographic Technology GA BIM52 UT WOS:000260855901039 ER PT S AU Lu, H Brett, R Sharp, G Safai, S Jiang, S Madden, T Flanz, J Chen, G Kooy, H AF Lu, H. Brett, R. Sharp, G. Safai, S. Jiang, S. Madden, T. Flanz, J. Chen, G. Kooy, H. BE Kim, SI Suh, TS TI The development and commissioning of a respiratory-gated treatment system for proton therapy SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING 2006, VOL 14, PTS 1-6 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY AUG 27-SEP 01, 2006 CL Seoul, SOUTH KOREA SP IUPSEM, IFMBE, IOMP, KSMP, KSMBE, AAPM, AFOMP, BMES, EFOMP, IAEA, AIMBE, IEEE EMB, WHO, SIEMENS, TomoTherapy, Philips, iba, Varian, CIVCO, elekta, Samsung DE proton therapy; respiratory gating; time delay AB Proton therapy offers excellent dose conformality and reduction in integral dose. The superior dose distribution is, however, much more sensitive to changes in radiological depths along the beam path than for photon fields. Respiratory motion can cause such changes for treatments sites like lung, liver, and mediastinum structures, and thus affect the proton dose distribution significantly. We have developed and commissioned a respiratory-gated beam control system for our range-modulated treatment beam. A Real-time Position Management (RPM, Varian Inc, Palo Alto, CA) system was used to monitor the patient's breathing cycle and to provide the gating signal, which is combined with the range modulation signal to generate the required gating control of the cyclotron beam current. The gating circuit has been designed to ensure the full modulation cycle is completed so that for any beam-on segment, the delivered dose has the exact planned SOBP distribution. This inevitably introduces a delay of the beam on/off up to the length of the modulation cycle of 100 ms. Using a motion phantom and time resolved measurement, we have measured the response delay of the cyclotron beam control relative to the RPM gating signal, as well as the delay of the RPM system itself relative to the actual mechanical motion of the phantom. It was found that while the cyclotron beam current response delay is less than 5 ms (the lower limit of the our measurement capability), the RPM system poses a delay of 60-90ms with an average of 75 ms. The total gating delay of the beam is thus in the range of 65 to 195 ms. Film test using a motion phantom was conducted to verify the overall gating results. C1 [Lu, H.] Massachusetts Gen Hosp, Boston, MA 02214 USA. RP Lu, H (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02214 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1680-0737 BN 978-3-540-36839-7 J9 IFMBE PROC PY 2007 VL 14 BP 2215 EP 2218 PN 1-6 PG 4 WC Engineering, Biomedical; Physics, Applied; Imaging Science & Photographic Technology SC Engineering; Physics; Imaging Science & Photographic Technology GA BIM52 UT WOS:000260855901042 ER PT S AU Paganetti, H Parodi, K Jiang, H Adams, JA Kooy, HM AF Paganetti, H. Parodi, K. Jiang, H. Adams, J. A. Kooy, H. M. BE Kim, SI Suh, TS TI Comparison of pencil-beam and Monte Carlo calculated dose distributions for proton therapy of skull-base and para-spinal tumors SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING 2006, VOL 14, PTS 1-6 SE IFMBE Proceedings LA English DT Proceedings Paper CT World Congress on Medical Physics and Biomedical Engineering CY AUG 27-SEP 01, 2006 CL Seoul, SOUTH KOREA SP IUPSEM, IFMBE, IOMP, KSMP, KSMBE, AAPM, AFOMP, BMES, EFOMP, IAEA, AIMBE, IEEE EMB, WHO, SIEMENS, TomoTherapy, Philips, iba, Varian, CIVCO, elekta, Samsung DE Monte Carlo; Proton Therapy AB Purpose: Pencil beam algorithms rely on kernels to model proton range in density-scaled water equivalent material. Monte Carlo dose calculation methods are more accurate by design. This study addresses the issue of clinical significance of potential differences between a commercial pencil-beam algorithm and Monte Carlo dose calculation. Skull-base or paraspinal tumors are challenging for dose calculations due to interfaces between high and low density areas in the irradiated volume. In addition, in particular for para-spinal cases, there are often metallic implants that not only distort the CT image but also affect the accuracy of dose calculations. Methods: Proton treatment planning is done at our institution by using FOCUS/XiO (Computerized Medical Systems Inc.). To do full Monte Carlo based dose calculation the treatment head was modeled including a simulation of the modulator wheel rotation as well as aperture and compensator. The capability to import patient CT data was implemented in the Monte Carlo code. The patient CT data information was converted into materials with explicit element composition and density. All secondary particles were tracked. Treatment plans designed with the treatment planning program were recalculated with the Monte Carlo code and compared by analyzing dose distributions and dose volume histograms. Results: The agreement between our Monte Carlo dose calculation and pencil-beam algorithm is generally quite good. For some tumors in the head and neck region and near the spine, Monte Carlo based dose calculation can show significant differences compared to a pencil-beam algorithm. C1 [Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1680-0737 BN 978-3-540-36839-7 J9 IFMBE PROC PY 2007 VL 14 BP 2219 EP 2222 PN 1-6 PG 4 WC Engineering, Biomedical; Physics, Applied; Imaging Science & Photographic Technology SC Engineering; Physics; Imaging Science & Photographic Technology GA BIM52 UT WOS:000260855901043 ER PT J AU Murali, MR Kratz, A Finberg, KE Hopkins, CM Wakem, C AF Murali, Mandakolathur R. Kratz, Alexander Finberg, Karin E. Hopkins, Carolyn M. Wakem, Christopher TI A man with anemia and a low level of HDL cholesterol - Lymphoplasmacytic lymphoma with Waldenstrom's macroglobulinemia and biclonal gammopathy. Falsely low serum HDL cholesterol test result due to the presence of the paraprotein SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MONOCLONAL IMMUNOGLOBULINS; INTERFERENCE; HEPCIDIN C1 Massachusetts Gen Hosp, Div Clin Immunol & Allergy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Murali, MR (reprint author), Massachusetts Gen Hosp, Div Clin Immunol & Allergy, Boston, MA 02114 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 28 PY 2006 VL 355 IS 26 BP 2772 EP 2779 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 120UA UT WOS:000243110500012 PM 17192544 ER PT J AU Sang, SM Ju, JY Lambert, JD Lin, Y Hong, JG Bose, M Wang, S Bai, NS He, K Reddy, BS Ho, CT Li, F Yang, CS AF Sang, Shengmin Ju, Jihyeung Lambert, Joshua D. Lin, Yong Hong, Jungil Bose, Mousumi Wang, Steven Bai, Naisheng He, Kan Reddy, Bandaru S. Ho, Chi-Tang Li, Frederick Yang, Chung S. TI Wheat bran oil and its fractions inhibit human colon cancer cell growth and intestinal tumorigenesis in Apc(min/+) mice SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE wheat bran oil; colon cancer; Apc(min/+) mice; phytochemicals; nonpolar lipids ID DEHYDRATED CITRUS FIBER; DIETARY FIBER; COLORECTAL-CANCER; CORN BRAN; CARCINOGENESIS; MODEL; CHEMOPREVENTION; EPIDEMIOLOGY; PREVENTION; PROTECTION AB This study was designed to investigate the cancer preventive activities of wheat bran (WB) oil. We studied the colon cancer preventive effects of WB oil and its subfractions in the Apc(min/+) mouse model, a recognized mouse model for human colorectal cancer, and used human colon cancer cell lines (HCT-116 and HT-29) to identify possible active fractions in WB oil. Our results showed that the oil fraction of WB was more active than the water fraction against the growth of human colon cancer cell lines and that 2% WB oil significantly inhibited the overall tumorigenesis by 35.7% (p < 0.0001) in the Apc(min/+) mouse model. The WB oil was further fractioned into nonpolar lipids and phytochemicals and the phytochemical fraction was fractionated into phytosterols and phytosterol ferulates, 5-alk(en)ylresorcinols, and unidentified constituents by normal phase silica gel column chromatography. Results on cell culture showed that the phytochemical fraction had a higher inhibitory effect on HCT-116 human colon cancer cells than that of WB oil, whereas the nonpolar lipid fraction had less growth inhibitory effectiveness. However, neither fractions showed a stronger inhibition than WB oil in the Apc(min/+) mouse model. The current results demonstrate, for the first time, the intestinal cancer preventive activity of WB oil. The active ingredients, however, remain to be identified. C1 Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Piscataway, NJ 08854 USA. Canc Inst New Jersey, New Brunswick, NJ 08903 USA. Pure World Bot, S Hackensack, NJ 07606 USA. Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA. Harvard Univ, Dana Farber Canc Inst, Dept Epidemiol, Boston, MA 02115 USA. RP Yang, CS (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM csyang@rci.rutgers.edu NR 31 TC 22 Z9 22 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC 27 PY 2006 VL 54 IS 26 BP 9792 EP 9797 DI 10.1021/jf0620665 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 118KR UT WOS:000242941700024 PM 17177503 ER PT J AU Xiao, DQ Bastia, E Xu, YH Benn, CL Cha, JHJ Peterson, TS Chen, JF Schwarzschild, MA AF Xiao, Danqing Bastia, Elena Xu, Yue-Hang Benn, Caroline L. Cha, Jang-Ho J. Peterson, Tracy S. Chen, Jiang-Fan Schwarzschild, Michael A. TI Forebrain adenosine A(2A) receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 6-hydroxydopamine; Parkinson's disease; basal ganglia; conditional A(2A) knock-out; KW-6002; A(2A) receptor antagonist ID LEVODOPA-INDUCED DYSKINESIAS; DOPA-INDUCED DYSKINESIA; MPTP-TREATED MONKEYS; C-FOS EXPRESSION; PARKINSONS-DISEASE; 6-HYDROXYDOPAMINE-LESIONED RATS; MESSENGER-RNA; NIGROSTRIATAL FUNCTION; CELLULAR-PARAMETERS; ANTAGONIST KW-6002 AB AdenosineA(2A) receptor antagonists provide a promising nondopaminergic approach to the treatment of Parkinson's disease (PD). Initial clinical trials of A(2A) antagonists targeted PD patients who had already developed treatment complications known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia ( LID) in an effort to improve symptoms while reducing existing LID. The goal of this study is to explore the effect of A(2A) antagonists and targeted A(2A) receptor depletion on the actual development of sensitized responses to L-DOPAin mouse models of LID in PD. Hemiparkinsonian mice (unilaterally lesioned with 6-OHDA) were treated daily for 3 weeks with a low dose of L-DOPA ( 2 mg/kg) preceded by a low dose of selective A2A antagonist (KW-6002 [(E)-1,3-diethyl- 8-(3,4-dimethoxystyryl)-7- methyl-3,7-dihydro-1H-purine-2,6-dione] at 0.03 or 0.3 mg/kg, or SCH58261 [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[ 1,5-c] pyrimidine] at 0.03 mg/kg) or vehicle intraperitoneally. In control mice, contralateral rotational responses to daily L-DOPA gradually increased over the initial week before reaching a persistent maximum. Both A(2A) antagonists inhibited the development of sensitized contralateral turning, with KW-6002 pretreatment reducing the sensitized rotational responses by up to threefold. The development of abnormal involuntary movements ( a measure of LID) as well as rotational responses was attenuated by the postnatal depletion of forebrain A(2A) receptors in conditional (Cre/loxP system) knock-out mice. These pharmacological and genetic data provide evidence that striatal A(2A) receptors play an important role in the neuroplasticity underlying behavioral sensitization to L-DOPA, supporting consideration of early adjunctive therapy with an A2A antagonist to reduce the risk of LID in PD. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM MichaelS@helix.mgh.harvard.edu FU NIDA NIH HHS [DA013508]; NINDS NIH HHS [NS045242, NS038106, NS054978, NS41083] NR 51 TC 67 Z9 67 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 27 PY 2006 VL 26 IS 52 BP 13548 EP 13555 DI 10.1523/JNEUROSCI.3554-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 123DZ UT WOS:000243277800016 PM 17192438 ER PT J AU Cosimi, AB AF Cosimi, A. Benedict TI Nobel prizes in medicine in the field of transplantation SO TRANSPLANTATION LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, 55 Fruit St, Boston, MA 02114 USA. EM cpadyk@partners.org NR 15 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2006 VL 82 IS 12 BP 1558 EP 1562 DI 10.1097/01.tp.0000249567.11794.c7 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 121SV UT WOS:000243178200002 PM 17198231 ER PT J AU Wilk, JB Tobin, JE Suchowersky, O Shill, HA Klein, C Wooten, GF Lew, MF Mark, MH Guttman, M Watts, RL Singer, C Growdon, JH Latourelle, JC Saint-Hilaire, MH DeStefano, AL Prakash, R Williamson, S Berg, CJ Sun, M Goldwurm, S Pezzoli, G Racette, BA Perlmutter, JS Parsian, A Baker, KB Giroux, ML Litvan, I Pramstaller, PP Nicholson, G Burn, DJ Chinnery, PF Vieregge, P Slevin, JT Cambi, F MacDonald, ME Gusella, JF Myers, RH Golbe, LI AF Wilk, J. B. Tobin, J. E. Suchowersky, O. Shill, H. A. Klein, C. Wooten, G. F. Lew, M. F. Mark, M. H. Guttman, M. Watts, R. L. Singer, C. Growdon, J. H. Latourelle, J. C. Saint-Hilaire, M. H. DeStefano, A. L. Prakash, R. Williamson, S. Berg, C. J. Sun, M. Goldwurm, S. Pezzoli, G. Racette, B. A. Perlmutter, J. S. Parsian, A. Baker, K. B. Giroux, M. L. Litvan, I. Pramstaller, P. P. Nicholson, G. Burn, D. J. Chinnery, P. F. Vieregge, P. Slevin, J. T. Cambi, F. MacDonald, M. E. Gusella, J. F. Myers, R. H. Golbe, L. I. TI Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age - The GenePD study SO NEUROLOGY LA English DT Article ID RISK-FACTORS; DISEASE; POLYMORPHISMS; TRANSFERASES; PESTICIDES; GENOME; T1; P1 AB Background: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides. Methods: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses. Results: Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group. Conclusions: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada. Barrow Neurol Inst, Muahammad Ali Parkinson Ctr, Phoenix, AZ 85013 USA. Univ Lubeck, Dept Neurol, Lubeck, Germany. Univ Virginia, Hlth Syst, Dept Neurol, Charlottesville, VA 22903 USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Mol Neurogenet Unit, Cambridge, MA 02138 USA. Parkinson Inst, Milan, Italy. Inst Clin Perfezionamento, Milan, Italy. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63130 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA. Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. Univ Sydney, Dept Neurol, ANZAC Res Inst, Concord Hosp, Sydney, NSW 2006, Australia. Newcastle Gen Hosp, Reg Neurosci Ctr, Newcastle Upon Tyne, Tyne & Wear, England. Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 40506 USA. Klinikum Lippe Lemgo, Neurol Klin, Lemgo, Germany. Vet Affairs Med Ctr, Lexington, KY USA. RP Wilk, JB (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 albany St,E-338, Boston, MA 02118 USA. EM jwilk@bu.edu RI Pramstaller, Peter/C-2357-2008; Goldwurm, Stefano/Q-8978-2016; OI Goldwurm, Stefano/0000-0002-1651-567X; Litvan, Irene/0000-0002-3485-3445 FU NCRR NIH HHS [1S10RR163736-01A1]; NINDS NIH HHS [R01 NS036711, R01 NS036711-06, R01 NS36711-05]; Telethon [GTF04007] NR 25 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 26 PY 2006 VL 67 IS 12 BP 2206 EP 2210 DI 10.1212/01.wnl.0000249149.22407.d1 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 120RB UT WOS:000243101500021 PM 17190945 ER PT J AU Nishida, N Walz, T Springer, TA AF Nishida, Noritaka Walz, Thomas Springer, Timothy A. TI Structural transitions of complement component C3 and its activation products SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE electron microscopy; proteolytic; thioester ID CONFORMATIONAL-CHANGES; FUNCTIONAL-PROPERTIES; MONOCLONAL-ANTIBODY; INTERNAL THIOESTER; CRYSTAL-STRUCTURE; C-3; RECEPTORS; INSIGHTS; SYSTEM; PHAGOCYTOSIS AB Complement sensitizes pathogens for phagocytosis and lysis. We use electron microscopy to examine the structural transitions in the activation of the pivotal protein in the complement pathway, C3. In the cleavage product C3b, the position of the thioester domain moves approximate to 100 angstrom, which becomes covalently coupled to antigenic surfaces. In the iC3b fragment, cleavage in an intervening domain creates a long flexible linker between the thioester domain and the macroglobulin domain ring of C3. Studies on two products of nucleophile addition to C3 reveal a structural intermediate in activation, and a final product, in which the anaphylatoxin domain has undergone a remarkable movement through the macroglobulin ring. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, 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 Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Nishida, Noritaka/E-7087-2010 FU NIAID NIH HHS [AI72765, R01 AI072765, R01 AI072765-26A1]; NIGMS NIH HHS [GM62580, P01 GM062580] NR 32 TC 63 Z9 63 U1 1 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 DEC 26 PY 2006 VL 103 IS 52 BP 19737 EP 19742 DI 10.1073/pnas.0609791104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500025 PM 17172439 ER PT J AU Seimon, TA Obstfeld, A Moore, KJ Golenbock, DT Tabas, I AF Seimon, Tracie A. Obstfeld, Amrom Moore, Kathryn J. Golenbock, Douglas T. Tabas, Ira TI Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; atherosclerosis; scavenger receptor; Toll-like receptor; innate immunity ID CHOLESTEROL-LOADED MACROPHAGES; LOW-DENSITY-LIPOPROTEIN; A SCAVENGER RECEPTOR; KINASE-C-DELTA; ENDOPLASMIC-RETICULUM; ATHEROSCLEROTIC LESIONS; APOLIPOPROTEIN-E; INNATE IMMUNITY; SR-A; APOPTOSIS AB Macrophage pattern recognition receptors (PRRs) play key roles in innate immunity, but they also may contribute to disease processes under certain pathological conditions. We recently showed that engagement of the type A scavenger receptor (SRA), a PRR, triggers JNK-dependent apoptosis in endoplasmic reticullum (ER)-stressed macrophages. In advanced atherosclerotic lesions, the SRA, activated JNK, and ER stress are observed in macrophages, and macrophage death in advanced atheromata leads to plaque necrosis. Herein, we show that SRA ligands trigger apoptosis in ER-stressed macrophages by cooperating with another PRR, Toll-like receptor 4 (TLR4), to redirect TLR4 signaling from prosurvival to proapoptotic. Common SRA ligands activate both TLR4 signaling and engage the SRA. The TLR4 effect results in activation of the proapoptotic MyD88-JNK branch of TLR4, whereas the SRA effect silences the prosurvival IRF-3-IFN-beta branch of TLR4. The normal cell-survival effect of LPS-induced TLR4 activation is converted into an apoptosis response by immunoneutralization of IFN-beta, and the apoptosis effect of SRA ligands is converted into a cell-survival response by reconstitution with IFNI-P. Thus, combinatorial signaling between two distinct PRRs results in a functional outcome-macrophage apoptosis that does not occur with either PRR alone. PRR-induced macrophage death may play important roles in advanced atherosclerosis and in other innate immunity-related processes in which the balance between macrophage survival and death is critical. C1 Columbia Univ, Dept Anat & Cell Biol & Physiol & Cellular Biophy, New York, NY 10032 USA. Columbia Univ, Dept Med, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. RP Tabas, I (reprint author), Columbia Univ, Dept Anat & Cell Biol & Physiol & Cellular Biophy, New York, NY 10032 USA. EM iat1@columbia.edu OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [F32 HL079801, F32 HL079801-01, F32 HL079801-02, HL57560, HL75662, HL79801, R01 HL057560, R01 HL075662]; NIGMS NIH HHS [GM54060, R01 GM054060, R37 GM054060] NR 51 TC 126 Z9 136 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 DEC 26 PY 2006 VL 103 IS 52 BP 19794 EP 19799 DI 10.1073/pnas.0609671104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500035 PM 17167049 ER PT J AU Mahoney, ZX Sammut, B Xavier, RJ Cunningham, J Go, G Brim, KL Stappenbeck, TS Miner, JH Swat, W AF Mahoney, Zhen X. Sammut, Benedicte Xavier, Ramnik J. Cunningham, Jeanette Go, Gloriosa Brim, Karry L. Stappenbeck, Thaddeus S. Miner, Jeffrey H. Swat, Wojciech TI Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SAP97; kidney; postsynaptic density-95/discs-large/zonula occludens-1; urogenital; sonic hedgehog ID TUMOR-SUPPRESSOR GENE; DROSOPHILA EPITHELIA; URINARY-TRACT; HUMAN HOMOLOG; JUNCTIONS; KIDNEY; CELLS; DIFFERENTIATION; MESENCHYME; PROTEIN AB Discs-large homolog 1 (DLGH1) is a mouse ortholog of the Drosophila discs-large (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein families. DLG proteins play important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function. Here, we generated a null allele of Dlgh1 and studied its role in urogenital development. Dlg1(-/-) mice developed severe urinary tract abnormalities, including congenital hydronephrosis, which is the leading cause of renal failure in infants and children. DLGH1 is expressed in the developing ureter; in its absence, the stromal cells that normally lie between the urothelial and smooth muscle layers were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle cells were misaligned in a longitudinal orientation. These abnormalities in the ureter led to severely impaired ureteric peristalsis. Similar smooth muscle defects are observed frequently in patients with ureteropelvic junction obstruction, a common form of hydronephrosis. Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis. C1 Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02115 USA. RP Miner, JH (reprint author), Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA. EM minerj@wustl.edu; swat@wustl.edu FU NIAID NIH HHS [R01 AI061077, R01AI061077, R21 AI063024, R21AI063024]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01 DK064687, R01DK064687] NR 34 TC 63 Z9 64 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 DEC 26 PY 2006 VL 103 IS 52 BP 19872 EP 19877 DI 10.1073/pnas.0609326103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500048 PM 17172448 ER PT J AU Ko, V Tambouret, RH Kuebler, DL Black-Schaffer, WS Wilbur, DC AF Ko, Vincent Tambouret, Rosemary H. Kuebler, Diane L. Black-Schaffer, W. Stephen Wilbur, David C. TI Human papillomavirus testing using Hybrid Capture II with SurePath collection - Initial evaluation and longitudinal data provide clinical validation for this method SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE cervical cytology; human papillomavirus testing; SurePath; Hybrid Capture II ID ATYPICAL SQUAMOUS CELLS; UNDETERMINED SIGNIFICANCE; CERVICAL NEOPLASIA; MANAGEMENT; STRATEGIES; TRIAGE AB BACKGROUND. Testing for human papillomavirus (HPV) is an integral part of equivocal cervical cytology triage. Clinical validation of non-FDA (Food and Drug Administration)-approved methods is therefore important because of the high volume of such tests and the implications for missed high-grade lesions if test performance is not optimal. METHODS. A preinitiation study and 17 months of follow-up data using Hybrid Capture II (HC II) HPV detection with SurePath (SP) sample collection were analyzed. Results of HPV tests on abnormal cytology samples were collected and compared with follow-up results. HPV-positive rates were determined in cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL), and follow-up rates of cervical intraepithelial neoplasia (CIN) were determined in HPV-positive and -negative cases of atypical squamous cells of unknown significance (ASC-US). Rates were compared with published data using FDA-validated methods. RESULTS. The preinitiation study showed the test method to be 100% sensitive for the detection of LSIL (20 cases) and HSIL (8). The ASC-US follow-up study (2319 cases with 625 having biopsy results) showed that the rate of CIN III+ in HPV +/- cases was 7.8%/1.4%, and of CIN II+ was 17.5%/4.3%, respectively. The positive predictive values/negative predictive values (PPV/NPVs) (CIN II+) for the test were 17.5%/95.7%, respectively. CONCLUSIONS. Published FDA-validated HPV testing follow-up data show that the expected rates of CIN III+ and CIN II+ in the HPV-negative ASC-US population are 1.4% and 5%, respectively, with PPV/NPVs (CIN II+) of 20%/99%, respectively. By comparison, the present data using HC II with SP show strong similarity, indicating clinical validity for the use of this method. C1 Massachusetts Gen Hosp, Dept Pathol, Div Cytopathol, Boston, MA 02114 USA. RP Ko, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Cytopathol, 55 Fruit St, Boston, MA 02114 USA. EM vko@partners.org NR 11 TC 22 Z9 22 U1 0 U2 0 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 DEC 25 PY 2006 VL 108 IS 6 BP 468 EP 474 DI 10.1002/cncr.22285 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 117MU UT WOS:000242878100004 PM 17091508 ER PT J AU Lim, H Mujat, M Kerbage, C Lee, ECW Chen, Y Chen, TC de Boer, JF AF Lim, H. Mujat, M. Kerbage, C. Lee, E. C. W. Chen, Y. Chen, Teresa C. de Boer, J. F. TI High-speed imaging of human retina in vivo with swept-source optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID ULTRAHIGH-RESOLUTION; ADAPTIVE-OPTICS; LASER; WAVELENGTH; RANGE AB We present the first demonstration of human retinal imaging in vivo using optical frequency domain imaging (OFDI) in the 800-nm range. With 460-mu W incident power on the eye, the sensitivity is 91 dB at maximum and >85 dB over 2-mm depth range. The axial resolution is 13 mu m in air. We acquired images of retina at 43,200 depth profiles per second and a continuous acquisition speed of 84 frames/s ( 512 A-lines per frame) could be maintained over more than 2 seconds. (c) 2006 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP de Boer, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 27 TC 45 Z9 45 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 25 PY 2006 VL 14 IS 26 BP 12902 EP 12908 DI 10.1364/OE.14.012902 PG 7 WC Optics SC Optics GA 121FX UT WOS:000243144600037 PM 19532183 ER PT J AU Wang, HM Kubica, N Ellisen, LW Jefferson, LS Kimball, SR AF Wang, Hongmei Kubica, Neil Ellisen, Leif W. Jefferson, Leonard S. Kimball, Scot R. TI Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CCAAT/ENHANCER-BINDING-PROTEIN; STRESS-RESPONSE GENE; RAT SKELETAL-MUSCLE; TUBEROUS SCLEROSIS; TRANSLATION INITIATION; S6 KINASE; RHEB BINDS; IN-VITRO; PHOSPHORYLATION; GROWTH AB The mammalian target of rapamycin ( mTOR), a critical modulator of cell growth, acts to integrate signals from hormones, nutrients, and growth-promoting stimuli to downstream effector mechanisms involved in the regulation of protein synthesis. Dexamethasone, a synthetic glucocorticoid that represses protein synthesis, acts to inhibit mTOR signaling as assessed by reduced phosphorylation of the downstream targets S6K1 and 4E-BP1. Dexamethasone has also been shown in one study to up-regulate the expression of REDD1 ( also referred to RTP801, a novel stress-induced gene linked to repression of mTOR signaling) in lymphoid, but not nonlymphoid, cells. In contrast to the findings of that study, here we demonstrate that REDD1, but not REDD2, mRNA expression is dramatically induced following acute dexamethasone treatment both in rat skeletal muscle in vivo and in L6 myoblasts in culture. In L6 myoblasts, the effect of the drug on mTOR signaling is efficiently blunted in the presence of REDD1 RNA interference oligonucleotides. Moreover, the dexamethasone-induced assembly of the mTOR regulatory complex Tuberin center dot Hamartin is disrupted in L6 myoblasts following small interfering RNA-mediated repression of REDD1 expression. Finally, overexpression of Rheb, a downstream target of Tuberin function and a positive upstream effector of mTOR, reverses the effect of dexamethasone on phosphorylation of mTOR substrates. Overall, the data support the conclusion that REDD1 functions upstream of Tuberin and Rheb to down-regulate mTOR signaling in response to dexamethasone. C1 Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02116 USA. RP Kimball, SR (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, H166,500 Univ Dr, Hershey, PA 17033 USA. EM skimball@psu.edu FU NIDDK NIH HHS [DK-15658] NR 47 TC 123 Z9 127 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 2006 VL 281 IS 51 BP 39128 EP 39134 DI 10.1074/jbc.M610023200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117UL UT WOS:000242898700020 PM 17074751 ER PT J AU Wang, TJ Gona, P Larson, MG Tofler, GH Levy, D Newton-Cheh, C Jacques, PF Rifai, N Selhub, J Robins, SJ Benjamin, EJ D'Agostino, RB Vasan, RS AF Wang, Thomas J. Gona, Philimon Larson, Martin G. Tofler, Geoffrey H. Levy, Daniel Newton-Cheh, Christopher Jacques, Paul F. Rifai, Nader Selhub, Jacob Robins, Sander J. Benjamin, Emelia J. D'Agostino, Ralph B. Vasan, Ramachandran S. TI Multiple biomarkers for the prediction of first major cardiovascular events and death SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; PLASMINOGEN-ACTIVATOR INHIBITOR; DENSITY-LIPOPROTEIN CHOLESTEROL; BRAIN NATRIURETIC PEPTIDE; CONVENTIONAL RISK-FACTORS; MYOCARDIAL-INFARCTION; PHOSPHOLIPASE A(2); ARTERY DISEASE; FOLLOW-UP AB BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, d-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with ``multimarker'' scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. NHLBI, Bethesda, MD 20892 USA. Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer Dept Agr, Boston, MA 02111 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Div Endocrinol Nutr & Diabet, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [R01-HL-48157, 2K24-HL-04334, K23-HL-074077, N01-HC-25195, R01-HL-076784] NR 40 TC 745 Z9 768 U1 7 U2 46 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 2006 VL 355 IS 25 BP 2631 EP 2639 DI 10.1056/NEJMoa055373 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200004 PM 17182988 ER PT J AU Itani, KMF Wilson, SE Awad, SS Jensen, EH Finn, TS Abramson, MA AF Itani, Kamal M. F. Wilson, Samuel E. Awad, Samir S. Jensen, Erin H. Finn, Tyler S. Abramson, Murray A. TI Ertapenem versus cefotetan prophylaxis in elective colorectal surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SURGICAL SITE INFECTION; COMPLICATED INTRAABDOMINAL INFECTIONS; ANTIMICROBIAL PROPHYLAXIS; PLUS METRONIDAZOLE; COMPARE CEFOTETAN; DOUBLE-BLIND; MULTICENTER; PREVENTION; RESECTION AB BACKGROUND: Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan. METHODS: In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis. RESULTS: Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22). CONCLUSIONS: Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. C1 Vet Affairs Boston Healthcare Syst, W Roxbury, MA 02132 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Calif Irvine, Sch Med, Orange, CA 92668 USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Helathcare Syst, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Merck Res Labs, Upper Gwynedd, PA USA. RP Itani, KMF (reprint author), Vet Affairs Boston Healthcare Syst, 1400 VFW Pkwy,112A, W Roxbury, MA 02132 USA. EM kitani@med.va.gov NR 28 TC 139 Z9 144 U1 1 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 DEC 21 PY 2006 VL 355 IS 25 BP 2640 EP 2651 DI 10.1056/NEJMoa054408 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200005 PM 17182989 ER PT J AU Finkelberg, DL Sahani, D Deshpande, V Brugge, WR AF Finkelberg, Dnitry L. Sahani, Dushyant Deshpande, Vikrarn Brugge, William R. TI Current concepts - Autoimmune pancreatitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; IDIOPATHIC CHRONIC-PANCREATITIS; CARBONIC-ANHYDRASE-II; STEROID-THERAPY; DUCT; FEATURES; AUTOANTIBODIES; INFILTRATION; CHOLANGITIS; LACTOFERRIN C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 42 TC 236 Z9 273 U1 1 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 2006 VL 355 IS 25 BP 2670 EP 2676 DI 10.1056/NEJMra061200 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200008 PM 17182992 ER PT J AU Cha, JHJ Furie, K Kay, J Walensky, RP Mullins, ME Hedley-Whyte, ET Chou, S AF Cha, Jang-Ho J. Furie, Karen Kay, Jonathan Walensky, Rochelle P. Mullins, Mark E. Hedley-Whyte, E. Tessa Chou, Sherry TI Case 39-2006: A 24-year-old woman with systemic lupus erythematosus, seizures, and right arm weakness - Granulomatous amebic encephalitis due to acanthamoeba species SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; CLINICAL SYNDROMES; PATIENT; INFECTIONS; DISEASE; MENINGOENCEPHALITIS; NEUROCYSTICERCOSIS; TOXOPLASMOSIS; ANTIBODIES; MORTALITY C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med & Infect Dis, 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 Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 35 TC 15 Z9 16 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 DEC 21 PY 2006 VL 355 IS 25 BP 2678 EP 2689 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200011 PM 17182994 ER PT J AU Zuniga, J Ilzarbe, M Acunha-Alonzo, V Rosetti, F Herbert, Z Romero, V Almeciga, I Clavijo, O Stern, JNH Granados, J Fridkis-Hareli, M Morrison, P Azocar, J Yunis, EJ AF Zuniga, J. Ilzarbe, M. Acunha-Alonzo, V. Rosetti, F. Herbert, Z. Romero, V. Almeciga, I. Clavijo, O. Stern, J. N. H. Granados, J. Fridkis-Hareli, M. Morrison, P. Azocar, J. Yunis, E. J. TI Allele frequencies for 15 autosomal STR loci and admixture estimates in Puerto Rican Americans SO FORENSIC SCIENCE INTERNATIONAL LA English DT Editorial Material DE short tandem repeat; STR; allelic frequencies; Puerto Rican; AmpFl STR (R) Identifiler (TM) ID POPULATION; POLYMORPHISMS; PROPORTIONS; DNA AB Allelic frequencies of 15 short tandem repeats (STR) markers (CSF1PO, FGA, TH01 TPOX, VWA, D3S11358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, D19S433 and D2S1338) were determined using the AmpFl STR (R) Identifiler (TM) PCR Amplification Kit in Puerto Rican American individuals (N = 205) from Massachusetts. The FGA, D18S51 and D2S1338 loci had a high power of discrimination (PD) with values of 0.967, 0.965 and 0.961, respectively. Significant deviations from the Hardy-Weinberg (HW) equilibrium were not detected. An important genetic contribution of Caucasian European (76.4%) was detected in Puerto Rican Americans. However, comparative analysis between Puerto Rican American and other neighboring populations from United States mainly with African and Caucasian Americans, revealed significant differences in the distribution of STR markers. Our results are important for future comparative genetic studies of different American ethnic groups, in particular a cultural group called Hispanic-Americans and should be helpful for forensic and paternity testing. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Nacl Enfernedades Resp, Mexico City, DF, Mexico. Harvard Univ, Sch Med, Mol Biol Core Facil, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Nacl Antropol & Hist, Escuela Nacl Antropol & Hist, Mexico City, DF, Mexico. Northgate Med Ctr, Springfield, MA USA. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. RP Zuniga, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Joaquin_zuniga@dfci.harvard.edu; jazocar@comcast.net; edmond_yunis@dfci.harvard.edu RI Acuna Alonzo, Victor/E-2312-2013; OI Acuna Alonzo, Victor/0000-0003-2205-7625; Stern, Joel N.H./0000-0002-1259-2256 FU NHLBI NIH HHS [HL29583, HL59838] NR 12 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD DEC 20 PY 2006 VL 164 IS 2-3 BP 266 EP 270 DI 10.1016/j.forsciint.2005.11.022 PG 5 WC Medicine, Legal SC Legal Medicine GA 112QV UT WOS:000242542700029 PM 16426785 ER PT J AU Chan, JA Meyerhardt, JA Chan, AT Giovannucci, EL Colditz, GA Fuchs, CS AF Chan, Jennifer A. Meyerhardt, Jeffrey A. Chan, Andrew T. Giovannucci, Edward L. Colditz, Graham A. Fuchs, Charles S. TI Hormone replacement therapy and survival after colorectal cancer diagnosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LARGE-BOWEL-CANCER; COLON-CANCER; POSTMENOPAUSAL WOMEN; UNITED-STATES; REPRODUCTIVE HISTORY; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; STEROID-HORMONES; RISK; ESTROGEN AB Purpose Postmenopausal estrogen use has been shown to decrease the incidence of colorectal cancer, but there is limited information regarding the effect of estrogen use on survival after diagnosis of colorectal cancer. Participants and Methods We examined the influence of postmenopausal estrogen use on mortality among 834 women participating in the Nurses' Health Study who were diagnosed with colorectal cancer between 1976 and 2000 and observed until death or June 2004, whichever came first. Colorectal cancer-specific mortality and overall mortality according to categories of hormone use were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors for cancer survival. Results Postmenopausal estrogen use before diagnosis of colorectal cancer was associated with significant reduction in mortality. Compared with women with no prior estrogen use, those reporting current use before diagnosis had an adjusted HR of 0.64 (95% CI, 0.47 to 0.88) for colorectal cancer-specific mortality and 0.74 (95% CI, 0.56 to 0.97) for overall mortality. This inverse association between hormone use and mortality was most evident among women whose duration of use was less than 5 years. Longer durations and past use were not associated with significant survival benefit. Assessment of estrogen use after diagnosis demonstrated similar findings. Conclusion Current postmenopausal estrogen use before diagnosis of colorectal cancer was associated with improved colorectal cancer-specific and overall mortality. This benefit was principally limited to women who initiated estrogens within 5 years of diagnosis. Additional efforts to understand mechanisms through which estrogens influence colorectal carcinogenesis and cancer progression seem warranted. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dana 1220,44 Binney St, Boston, MA 02115 USA. EM jang@partners.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [P01CA087969, T32 CA 09001] NR 28 TC 35 Z9 37 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2006 VL 24 IS 36 BP 5680 EP 5686 DI 10.1200/JCO.2006.08.0580 PG 7 WC Oncology SC Oncology GA 119EG UT WOS:000242994400011 PM 17179103 ER PT J AU Pentz, RD Joffe, S Emanuel, EJ Schnipper, LE Haskell, CM Tannock, IF AF Pentz, Rebecca D. Joffe, Steven Emanuel, Ezekiel J. Schnipper, Lowell E. Haskell, Charles M. Tannock, Ian F. TI ASCO core values SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Pentz, RD (reprint author), Emory Univ, Winship Canc Inst, 1365 C Clifton Rd NE,Rm C 3008, Atlanta, GA 30322 USA. EM rebecca.pentz@emoryhealthcare.org OI Joffe, Steven/0000-0002-0667-7384 NR 9 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2006 VL 24 IS 36 BP 5780 EP 5782 DI 10.1200/JCO.2006.08.5068 PG 3 WC Oncology SC Oncology GA 119EG UT WOS:000242994400023 PM 17179111 ER PT J AU Park, MA Moore, SC Limpa-Amara, N Kang, Z Makrigiorgos, GM AF Park, Mi-Ae Moore, Stephen C. Limpa-Amara, Naengnoi Kang, Zhuang Makrigiorgos, G. Mike TI Performance of a coumarin-based liquid dosimeter for phantom evaluations of internal dosimetry SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT 3rd International Conference on Imaging Technologies in Biomedical Sciences CY SEP 25-29, 2005 CL Milos, GREECE DE yttrium-90; internal dosimetry; targeted radionuclide therapy; coumarin; DOSXYZnrc ID S-VALUES; RADIOIMMUNOTHERAPY AB Targeted radionuclide therapy (TRT) requires accurate absorbed dose estimation in individual patients. It has been shown that a coumarin-based liquid dosimeter is useful for various phantom geometries of relevance to patient-specific internal dosimetry. The purpose of this study was to refine the performance limits of the coumarin-3-carboxylic acid (CCA) dosimeter using the high-energy beta-emitter, Y-90, by measuring the dosimeter's dependence on dose rate, by finding the maximum dose limit, and by comparing measured dose values to those from Monte Carlo (MC) simulation. Non-fluorescent CCA is converted to highly fluorescent 7-hydroxyl-coumarin-3-carboxylic acid (7-OH-CCA) upon irradiation. We measured the Y-90-induced fluorescence from 7-OH-CCA tinder different conditions. Fluorescence was measured using activity concentrations from 1.1 to 181 MBq/cc, providing initial dose rates from 0.7 to 117 cGy/min. To determine the maximum dose limit, fluorescence was measured for different elapsed times from 4 to 150h, using a fixed activity concentration, 3.7MBq/cc. A Cs-137 irradiator was used for calibration, to convert fluorescence measurements to absorbed dose. We calculated absorbed dose using the DOSXYZnre MC program. We modeled the geometry of cuvettes realistically, including plastic walls, surrounding air, and Y-90 in liquid. S-values of Y-90 in water were calculated using 1-mm cubic voxels. A linear dependence of fluorescence on dose rate was observed up to 80 cGy/min, and the dependence on total dose was lineal up to similar to 20 Gy The average difference between calculated and measured dose values over 9 samples was 3.6 +/- 2 %. For our geometry, the dose based on voxel S-values was within 1 % of that calculated using MC simulation of the phantom. We refined the performance limits of a CCA-based dosimeter for phantom studies of TRT using Y-90, and confirmed a close agreement between measured and calculated dose values. CCA dosimetry is a promising technique for phantom validation studies of TRT. (c) 2006 Elsevier B.V. All rights reserved. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Faber Brigham & Womens Canc Ctr, Boston, MA 01225 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. RP Park, MA (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM miaepark@bwh.Harvard.edu; scmoore@bwh.harvard.edu NR 9 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD DEC 20 PY 2006 VL 569 IS 2 SI SI BP 543 EP 547 DI 10.1016/j.nima.2006.08.090 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 122QK UT WOS:000243241300086 ER PT J AU Nahrendorf, M Weissleder, R Ertl, G AF Nahrendorf, Matthias Weissleder, Ralph Ertl, Georg TI Does FXIII Deficiency Impair Wound Healing after Myocardial Infarction? SO PLOS ONE LA English DT Article AB Inadequate healing of myocardial infarction may contribute to local expansion of the infarct, frequently leading to chamber dilation, heart failure, or myocardial rupture. Experimental evidence in mouse models suggests that Factor XIII might play a key role in wound healing, and low persistent values lead to increased incidence of cardiac rupture following myocardial infarction. Here we would like to share our initial clinical experiences with strikingly similar observations in patients with this grave disease, and compare these observations to experimental findings. C1 [Nahrendorf, Matthias; Ertl, Georg] Univ Wurzburg, Med Klin & Poliklin 1, Wurzburg, Germany. [Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Ertl, G (reprint author), Univ Wurzburg, Med Klin & Poliklin 1, Wurzburg, Germany. EM Ertl_G@medizin.uni-wuerzburg.de NR 3 TC 9 Z9 9 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2006 VL 1 IS 1 AR e48 DI 10.1371/journal.pone.0000048 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DB UT WOS:000207443600048 PM 17183677 ER PT J AU Yu, LL Tucci, V Kishi, S Zhdanova, IV AF Yu, Lili Tucci, Valter Kishi, Shuji Zhdanova, Irina V. TI Cognitive Aging in Zebrafish SO PLOS ONE LA English DT Article AB Background. Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. Methodology/Principal Findings. Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. Conclusions/Significance. These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline. C1 [Yu, Lili; Tucci, Valter; Zhdanova, Irina V.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Kishi, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Zhdanova, IV (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. EM zhdanova@bu.edu FU NIH [MH065528, AG02264]; Chaikin-Wile foundation; Ellison Medical Foundation FX This work was supported by the grants awarded by NIH (MH065528; to IZ), (AG02264, to SK), Chaikin-Wile foundation (IZ), and Ellison Medical Foundation (SK). NR 33 TC 54 Z9 55 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2006 VL 1 IS 1 AR e14 DI 10.1371/journal.pone.0000014 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DB UT WOS:000207443600014 PM 17183640 ER PT J AU Astrof, NS Salas, A Shimaoka, M Chen, JF Springer, TA AF Astrof, Nathan S. Salas, Azucena Shimaoka, Motomu Chen, JianFeng Springer, Timothy A. TI Importance of force linkage in mechanochemistry of adhesion receptors SO BIOCHEMISTRY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; I-DOMAIN; FIRM ADHESION; P-SELECTIN; HYDRODYNAMIC FLOW; LIGAND-BINDING; DISULFIDE BOND; INTEGRIN; PROTEIN; SHEAR AB The alpha subunit-inserted ( I) domain of integrin alpha(L)beta(2) [ lymphocyte function- associated antigen-1 ( LFA-1)] binds to intercellular adhesion molecule-1 ( ICAM-1). The C- and N-termini of the alpha I domain are near one another on the "lower" face, opposite the metal ion-dependent adhesion site ( MIDAS) on the "upper face". In conversion to the open alpha I domain conformation, alpha 7 angstrom downward, axial displacement of C- terminal helix alpha 7 is allosterically linked to rearrangement of the MIDAS into its high-affinity conformation. Here, we test the hypothesis that when an applied force is appropriately linked to conformational change, the conformational change can stabilize adhesive interactions that resist the applied force. Integrin alpha I domains were anchored to the cell surface through their C- or N-termini using type I or II transmembrane domains, respectively. C- terminal but not N-terminal anchorage robustly supported cell rolling on ICAM-1 substrates in shear flow. In contrast, when the alpha(L) I domain was mutationally stabilized in the open conformation with a disulfide bond, it mediated comparable levels of firm adhesion with type I and type II membrane anchors. To exclude other effects as the source of differential adhesion, these results were replicated using alpha I domains conjugated through the N- or C- terminus to polystyrene microspheres. Our results demonstrate a mechanical feedback system for regulating the strength of an adhesive bond. A review of crystal structures of integrin alpha and beta subunit I domains and selectins in high- and low-affinity conformations demonstrates a common mechanochemical design in which biologically applied tensile force stabilizes the more extended, high- affinity conformation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Anesthesia, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu OI Salas, Azucena/0000-0003-4572-2907 FU NHLBI NIH HHS [P01 HL048675, HL48675] NR 43 TC 85 Z9 85 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 19 PY 2006 VL 45 IS 50 BP 15020 EP 15028 DI 10.1021/bi061566o PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115YZ UT WOS:000242771000015 PM 17154539 ER PT J AU Ongusaha, PP Kim, HG Boswell, SA Ridley, AJ Der, CJ Dotto, GP Kim, YB Aaronson, SA Lee, SW AF Ongusaha, Pat P. Kim, Hyung-Gu Boswell, Sarah A. Ridley, Anne J. Der, Channing J. Dotto, G. Paolo Kim, Young-Bum Aaronson, Stuart A. Lee, Sam W. TI RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress SO CURRENT BIOLOGY LA English DT Article ID GTPASES; CANCER; ACTIVATION; PHOSPHORYLATION; CONTRACTION; SUPPRESSION; PROGRESSION; EXPRESSION; PROTEINS; CLEAVAGE AB The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton [1-6]. The majority of the Rho family proteins function as molecular switches cycling between the active, GTP-bound and the inactive, GDP-bound conformations [1-6]. Unlike typical Rho-family proteins, the Rnd subfamily members, including Rnd1, Rnd2, RhoE (also known as Rnd3), and RhoH, are GTPase deficient and are thus expected to be constitutively active [7-10]. Here, we identify an unexpected role for RhoE/Rnd3 in the regulation of the p53-mediated stress response. We show that RhoE is a transcriptional p53 target gene and that genotoxic stress triggers actin depolymerization, resulting in actin-stress-fiber disassembly through p53-dependent RhoE induction. Silencing of RhoE induction in response to genotoxic stress maintains stress fiber formation and strikingly increases apoptosis, implying an antagonistic role for RhoE in p53-dependent apoptosis. We found that RhoE inhibits ROCK I (Rho-associated kinase 1) activity during genotoxic stress and thereby suppresses apoptosis. We demonstrate that the p53-mediated induction of RhoE in response to DNA damage favors cell survival partly through inhibition of ROCK I-mediated apoptosis. Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. UCL Royal Free & Univ Coll Sch Med, Ludwig Inst Canc Res, London W1W 7BS, England. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. CUNY Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu OI Boswell, Sarah/0000-0002-3118-3378; Ridley, Anne/0000-0001-8186-5708 FU NCI NIH HHS [P01 CA080058, R01 CA127247, R01 CA097216-04, R01 CA097216-03, CA127247, R01 CA097216, CA097216, CA80058]; NIAMS NIH HHS [TG-AR007098-31, T32 AR007098] NR 28 TC 65 Z9 72 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 19 PY 2006 VL 16 IS 24 BP 2466 EP 2472 DI 10.1016/j.cub.2006.10.056 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119UP UT WOS:000243039800031 PM 17174923 ER PT J AU Dec, GW AF Dec, G. William TI Anemia in heart failure - Time to rethink its etiology and treatment? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ERYTHROPOIETIN; PREVALENCE; MORTALITY; COMMON C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,Mailstop 817,55 Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 14 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 19 PY 2006 VL 48 IS 12 BP 2490 EP 2492 DI 10.1016/j.jacc.2006.09.017 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 118BD UT WOS:000242916100012 PM 17174187 ER PT J AU Podar, K Tonon, G Sattler, M Tai, YT LeGouill, S Yasui, H Ishitsuka, K Kumar, S Kumar, R Pandite, LN Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Tonon, Giovanni Sattler, Martin Tai, Yu-Tzu LeGouill, Steven Yasui, Hiroshi Ishitsuka, Kenji Kumar, Shaji Kumar, Rakesh Pandite, Lini N. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis; xenograft mouse model ID OVERCOMES DRUG-RESISTANCE; THERAPEUTIC IMPLICATIONS; MICROARRAY DATA; C-MYC; ANGIOGENESIS; GROWTH; CANCER; PROGRESSION; ANTIANGIOGENESIS; CHEMOTHERAPY AB A critical role for vascular enclothelial factor (VEGF) has been demonstrated in multiple myelorna (IMM) pathogenesis. Here, we characterized the effect of the small-molecule VEGF receptor inhibitor pazopanib on MM cells in the bone marrow milieu. Pazopanib inhibits VEGF-triggered signaling pathways in both tumor and enclothelial cells, thereby blocking in vitro MM cell growth, survival, and migration, and inhibits VEGF-induced up-regulation of adhesion molecules on both enclothelial and tumor cells, thereby abrogating enclothelial cell-MM cell binding and associated cell proliferation. We show that pazopanib is the first-in-class VEGF receptor inhibitor to inhibit in vivo tumor cell growth associated with increased MM cell apoptosis, decreased angiogenesis, and prolonged survival in a mouse xenograft model of human MM. Low-dose pazopanib demonstrates synergistic cytotoxicity with conventional (melphalan) and novel (bortezomib and immunomodulatory drugs) therapies. Finally, gene expression and signaling network analysis show transcriptional changes of several cancer-related genes, in particular c-Myc. Using siRNA, we confirm the role of c-Myc in VEGF production and secretion, as well as angiogenesis. These preclinical studies provide the rationale for clinical evaluation of pazopanib, alone and in combination with conventional and novel therapies, to increase efficacy, overcome drug resistance, reduce toxicity, and improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Nantes, Hotel Dieu Ctr Hosp, Inst Biol, INSERM,U0601, F-44093 Nantes, France. Univ Nantes, Hotel Dieu Ctr Hosp, Serv Hematol Clin, F-44093 Nantes, France. Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU NCI NIH HHS [P01 CA78378, P01 CA078378, P50 CA100707, R01 CA050947, R01 CA50947] NR 38 TC 128 Z9 132 U1 2 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19478 EP 19483 DI 10.1073/pnas.0609329103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600047 PM 17164332 ER PT J AU Odden, MC Chertow, GM Fried, LF Newman, AB Connelly, S Angleman, S Harris, TB Simonsick, EM Shlipak, MG AF Odden, Michelle C. Chertow, Glenn M. Fried, Linda F. Newman, Anne B. Connelly, Stephanie Angleman, Sara Harris, Tamara B. Simonsick, Eleanor M. Shlipak, Michael G. CA HABC Study TI Cystatin C and measures of physical function in elderly adults - The health, aging, and body composition (HABC) study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; cystatin C; exercise tolerance; kidney diseases; muscle weakness; walking ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; EXERCISE CAPACITY; HEMODIALYSIS-PATIENTS; SERUM CREATININE; OLDER-ADULTS; DIALYSIS; RISK AB Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m(2). In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function. C1 Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Nephrol, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Odden, MC (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL073208-01]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [R01 DK 066488] NR 42 TC 56 Z9 57 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2006 VL 164 IS 12 BP 1180 EP 1189 DI 10.1093/aje/kwj333 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 115DK UT WOS:000242714800006 PM 17035344 ER PT J AU Kahn, KL MacLean, CH Liu, H Rubenstein, LZ Wong, AL Harker, JO Chen, WP Fitzpatrick, DM Bulpitt, KJ Traina, SB Mittman, BS Hahn, BH Paulus, HE AF Kahn, K. L. MacLean, C. H. Liu, H. Rubenstein, L. Z. Wong, A. L. Harker, J. O. Chen, W. P. Fitzpatrick, D. M. Bulpitt, K. J. Traina, S. B. Mittman, B. S. Hahn, B. H. Paulus, H. E. TI Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE rheumatoid arthritis; DMARDs; quality of care ID HEALTH ASSESSMENT QUESTIONNAIRE; MODIFYING ANTIRHEUMATIC DRUGS; DISEASE-ACTIVITY INDEX; MEASURING QUALITY; THERAPY; GUIDELINES; CANCER; RELIABILITY; MANAGEMENT; VALIDITY AB Objective. To construct quality measures with measurement validity and meaning for clinicians. Methods. We conducted a prospective cohort study of rates of change in disease-modifying antirheumatic drug (DMARD) and/or systemic corticosteroid drug or dose for 568 patients with rheumatoid arthritis (RA) across 6,159 clinical encounters within 12 months to examine how changes in clinical specifications change adherence. Results. Rates of DMARD change were sensitive to specifications regarding the intensity of disease activity (severe or moderate), duration of specified disease activity, and length of the observation period. Over 12 months, the proportions of 377 patients with severe disease activity observed for 1-month, 2-month, and 3-month time blocks who had a change in DMARD drug or dose were 36%, 57%, and 74%, respectively. Over 12 months, a change in DMARD drug or dose was observed for 44%, 50%, and 68% of 377 patients with severe disease within 3 months, 6 months, and 12 months, respectively, of the patient meeting criteria for severe disease activity. A change in DMARD drug or dose was observed for 21%, 23%, and 34% of 149 patients with moderate disease activity within 3, 6, and 12 months, respectively, of the patient meeting criteria for moderate disease activity. Conclusion. Rates of pharmacologic interventions for patients with moderate and severe RA disease activity vary substantially by intensity and duration of disease activity and by duration of period for observing change. Lack of precision in explicit process criteria could substantially mislead comparisons of quality of care across comparison groups. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RAND, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Kaiser Permanente, W Los Angeles Med Ctr, Los Angeles, CA USA. RP Kahn, KL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Pl,Box 951736, Los Angeles, CA 90095 USA. EM kkahn@mednet.ucla.edu FU NIAMS NIH HHS [5 P60-AR-36834] NR 32 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2006 VL 55 IS 6 BP 884 EP 891 DI 10.1002/art.22361 PG 8 WC Rheumatology SC Rheumatology GA 117SD UT WOS:000242892400009 PM 17139665 ER PT J AU Taylor, CE Fang, MA AF Taylor, Connie E. Fang, Meika A. TI Septic arthritis caused by Abiotrophia defectiva SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; GRANULICATELLA; ENDOCARDITIS; INFECTIONS; DIAGNOSIS; ADIACENS; THERAPY; DISEASE C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90733 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Fang, MA (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11G,11301 Wilshire Blvd, Los Angeles, CA 90733 USA. EM meika.fang@med.va.gov NR 14 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2006 VL 55 IS 6 BP 976 EP 977 DI 10.1002/art.22348 PG 2 WC Rheumatology SC Rheumatology GA 117SD UT WOS:000242892400022 PM 17139646 ER PT J AU Meyers, BS English, J Gabriele, M Peasley-Miklus, C Heo, M Flint, AJ Mulsant, BH Rothschild, AJ AF Meyers, Barnett S. English, Judith Gabriele, Michelle Peasley-Miklus, Catherine Heo, Moonseong Flint, Alastair J. Mulsant, Benoit H. Rothschild, Anthony J. CA STOP-PD Study Group TI A delusion assessment scale for psychotic major depression: Reliability, validity, and utility SO BIOLOGICAL PSYCHIATRY LA English DT Article DE delusions; depression; impact; conviction; bizarreness; disorganization ID BETA-HYDROXYLASE ACTIVITY; PSYCHIATRIC RATING-SCALE; CLINICAL-FEATURES; SCHIZOPHRENIA; DIMENSIONS; EXPERIENCE; HALLUCINATIONS; METAANALYSIS; DISORDERS; BELIEFS AB Background: Although delusions are the hallmark of major depression with psychotic features, a scale to measure the intensify of beliefs across multiple delusional domains in this condition has been unavailable. The development and assessment of the Delusional Assessment Scale (DAS) are described. Methods: Scale items were selected initially based on previous studies of delusional ideation in schizophrenia. A three-point item to assess mood congruence was added. A 15-item scale was assessed in 92 subjects participating in the four-site collaborative study of the pharmacotherapy of major depression with psychotic features. Maximum likelihood method was used to determine scale factors, The internal consistency of these factors was determined. Comparisons between scale scores and ratings from the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) were used to assess convergent and discriminant validity. Results: The data were fit by a five-factor model (impact, conviction, disorganization, bizarreness, and extension). Inter-rater reliability of the five factors ranged from. 77 for conviction and .74 for impact to .37 for disorganization. Internal consistency for each of the five factors was >= .72. Scores on specific domains were signficantly correlated with the BPRS unusual thought content item and positive symptom subscale scores. Conclusions: The DAS is a reliable measure of 5 delusional domains. C1 Cornell Univ, Weill Coll Med, Dept Psychiat, White Plains, NY 10605 USA. New York Presbyterian Hosp, Westchester Div, W Chester, NY USA. Univ Toronto, Univ Hlth Network, Dept Psychiat, Toronto, ON, Canada. Toronto Rehabil Inst, Geriatr Program & Res Inst, Toronto, ON, Canada. VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. Univ Massachusetts Mem Hlth Care, Worcester, MA USA. RP Meyers, BS (reprint author), Cornell Univ, Weill Coll Med, Dept Psychiat, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM bmeyers@med.cornell.edu FU NIMH NIH HHS [MH48512, MH62624, MH62446, MH069430, MH30915, MH62565, MH625518] NR 43 TC 25 Z9 25 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2006 VL 60 IS 12 BP 1336 EP 1342 DI 10.1016/j.biopsych.2006.05.033 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115LL UT WOS:000242735700010 PM 17046724 ER PT J AU Papakostas, GI Nutt, DJ Hallett, LA Tucker, VL Krishen, A Fava, M AF Papakostas, George I. Nutt, David J. Hallett, Lindsay A. Tucker, Vivian L. Krishen, Alok Fava, Maurizio TI Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuntake inhibitors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE sleepiness; fatigue; bupropion; SSRIs; MDD; treatment ID SUSTAINED-RELEASE; DOUBLE-BLIND; ANTIDEPRESSANT TREATMENT; RESIDUAL SYMPTOMS; PRIMARY-CARE; FLUOXETINE; SERTRALINE; ESCITALOPRAM; PAROXETINE; OUTPATIENTS AB Background: The purpose of this study was to examine whether the treatment of major depressive disorder (MDD) with the norepinephrine-dopamine reuptake inhibitor (NDRI) bupropion results in a greater resolution of sleepiness and fatigue than with the selective serotonin reuptake inhibitors (SSRIs). Methods: Six double-blind, randomized clinical trials comparing bupropion (n = 662) with an SSRI (n = 655)for the treatment of MDD were pooled. Hypersomnia scores were defined as the sum of scores of the Hamilton Depression Rating Scale (HDRS) items #22, 23, and 24. Fatigue scores were defined as the score of HDRS item #13. Results. There was a greater improvement in hypersomnia scores among bupropion-treated than SSRI-treated (p < .0001) or placebo-treated patients (p = .0008). There was also a greater improvement in fatigue scores among bupropion-treated (p < .0001) and SSRI-treated (p = .0005) than placebo-treated patients as well as a greater improvement in fatigue scores among bupropion-treated than SSRI-treated patients (p = .0078). Fewer bupropion-remitters than SSRI-remitters experienced residual hypersomnia (20.5% vs. 32.1%; p = .0014) or residualfiatigue (19.5% vs. 30.2%; p = .0020). Conclusion: Treatment of MDD with the NDRI bupropion resulted in a greater resolution of sleepiness and fatigue than SSRIs treatment. Although preliminary, these results warrant prospectively designed studies examining potential differences between bupropion and the SSRIs on these specific depressive symptoms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. Univ Bristol, Psychopharmacol Unit, Bristol, Avon, England. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 42 TC 67 Z9 70 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2006 VL 60 IS 12 BP 1350 EP 1355 DI 10.1016/j.biopsych.2006.06.015 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115LL UT WOS:000242735700012 PM 16934768 ER PT J AU Fan, XD Anderson, EJ Copeland, PM Borba, CP Nguyen, DD Freudenreich, O Goff, DC Henderson, DC AF Fan, Xiaoduo Anderson, Ellen J. Copeland, Paul M. Borba, Christina P. Nguyen, Dana D. Freudenreich, Oliver Goff, Donald C. Henderson, David C. TI Higher fasting serum insulin is associated with increased resting energy expenditure in nondiabetic schizophrenia patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE insulin; fat-free mass; metabolism; resting energy expenditure (REE); schizophrenia ID CENTRAL-NERVOUS-SYSTEM; INDUCED WEIGHT-GAIN; DENSITY-LIPOPROTEIN CHOLESTEROL; FAT-FREE MASS; BODY-COMPOSITION; METABOLIC-RATE; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; FOOD-INTAKE; OLANZAPINE AB Background: Insulin has emerged as an important determinant of food intake, energy expenditure, and weight control. This study examined the relationship between fasting serum insulin level and resting energy expenditure (REE) in a cross-sectional sample of nondiabetic schizophrenia patients. Methods: Subjects were recruited from an urban community mental health clinic. Each subject underwent a series of anthropometric measures and an indirect calorimetry measure. A fasting blood sample was taken for plasma glucose, serum insulin, and lipid profile. Results: Seventy-one subjects (54 male, 17 female) were included in the study. There was a significant positive relationship between REE and fasting serum insulin level (r =.39, P = .001). Stepwise multiple regression analysis was performed with various characteristics such as age, race, antipsychotic agent used, fat-free mass, BMI, waist circumference, waist- hip ratio, physical activity level, and fasting serum insulin as candidate predictors for REE. Only fat-free mass and insulin were able to enter into the regression model, which indicates that higher fat-free mass and higher fasting serum insulin level predict increased PEE. Conclusions: A higher fasting serum insulin level is associated with an increased PEE, which may prevent further weight gain in nondiabetic patients with schizophrenia. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mallininckrodt Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fan, XD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org FU NCRR NIH HHS [5M01RR01066-24] NR 59 TC 9 Z9 9 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2006 VL 60 IS 12 BP 1372 EP 1377 DI 10.1016/j.biopsych.2006.05.006 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115LL UT WOS:000242735700015 PM 16920075 ER PT J AU Joffe, H Cohen, LS Suppes, T Hwang, CH Molay, F Adams, JM Sachs, GS Hall, JE AF Joffe, Hadine Cohen, Lee S. Suppes, Trisha Hwang, Cindy H. Molay, Francine Adams, Judith M. Sachs, Gary S. Hall, Janet E. TI Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the Endocrine-Society CY JUN 04-07, 2005 CL San Diego, CA SP Endocrine Soc DE women; bipolar disorder; PCOS; polycystic ovarian syndrome; valproate; longitudinal ID WEIGHT-GAIN; WOMEN; PREVALENCE; EPILEPSY; LAMOTRIGINE; CONSENSUS; GLUCOSE; HEALTH; RISKS AB Background: In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. Methods. Women with valproate-associated PCOS and those at risk for PCOS (valproate use <= 6 months) were re-evaluated for PCOS. Results: Follow-up (mean 17 months) assessments were completed in 14 women (5 with treatment-emergent PCOS, 9 on valproate <= 6-month). of seven women who developed valproate-associated PCOS, PCOS reproductive features remitted in three of four discontinuing valproate and persisted in all 3 continuing valproate. Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS features remitted (p = 0.01). There was a trend toward lower serum testosterone (p = 0.06). Body-weight and polycystic ovarian morphology did not change. Conclusions. In the first longitudinal bipolar-disorder study of valproate-associated PCOS, most valproate-discontinuers bad improved reproductive features of PCOS despite static body-weight. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Res Program, 185 Cambridge St,Suite 2296, Boston, MA 02114 USA. EM hjoffe@partners.org FU NIMH NIH HHS [N01MH60012, N01MH60014, N01MH60006, N01MH60011, N01MH60013] NR 22 TC 38 Z9 38 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2006 VL 60 IS 12 BP 1378 EP 1381 DI 10.1016/j.biopsych.2006.05.027 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115LL UT WOS:000242735700016 PM 16950230 ER PT J AU Zebrack, B Bleyer, A Albritton, K Medearis, S Tang, J AF Zebrack, Brad Bleyer, Archie Albritton, Karen Medearis, Sandra Tang, Julia TI Assessing the health care needs of adolescent and young adult cancer patients and survivors SO CANCER LA English DT Article DE young adult; adolescent; health care; needs assessment; survivors ID INFORMATIONAL NEEDS; PROSTATE-CANCER; INSTRUMENT; MEN AB BACKGROUND. Improvements in cancer outcomes observed for the United States population as a whole are not experienced as such by adolescent and young adult (AYA) patients. The objective of this study was to identify important health and supportive care needs for AYA patients and survivors. METHODS. Forty oncology health professionals and 37 young adults (ages 18 years to 44 years; diagnosed between ages 15 years and 39 years) participated on a modified Delphi panel. Over 3 iterative rounds of mailed surveys, participants identified, rank ordered, and rated the importance of various items. RESULTS. Overall, there was general agreement among health care providers and young adult survivors, with some notable exceptions. Providers and young adult survivors agreed on the relative importance of having adequate health insurance and oncology care that addresses the unique developmental characteristics of this population. Compared with health professionals, young adults ranked the importance of opportunities to meet other young adult survivors at a relatively higher level, and they also ranked those opportunities higher than the importance of support from family and friends. CONCLUSIONS. These findings provide oncology professionals and young adults with insight into the others' values and perspectives. These findings also suggest areas in which to target investments of resources to promote quality health care and appropriate informational and supportive care services and to overcome the deficit in survival improvement that has occurred in young adults and older adolescents with cancer. C1 Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. St Charles Hosp, Dept Radiat Med, Bend, OR USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Zebrack, B (reprint author), Univ So Calif, Sch Social Work, 669 W 34th St, Los Angeles, CA 90089 USA. EM zebrack@usc.edu NR 24 TC 102 Z9 102 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2006 VL 107 IS 12 BP 2915 EP 2923 DI 10.1002/cncr.22338 PG 9 WC Oncology SC Oncology GA 116YB UT WOS:000242838600022 PM 17103383 ER PT J AU Yang, CW Trent, S Ionescu-Tiba, V Lan, L Shioda, T Sgroi, D Schmidt, EV AF Yang, Chuanwei Trent, Sally Ionescu-Tiba, Viviana Lan, Lan Shioda, Toshi Sgroi, Dennis Schmidt, Emmett V. TI Identification of cyclin D1-and estrogen-regulated genes contributing to breast carcinogenesis and progression SO CANCER RESEARCH LA English DT Article ID CANCER CELLS; PROGNOSTIC VALUE; TRANSGENIC MICE; D1 EXPRESSION; RECEPTOR; PROTEIN; OVEREXPRESSION; PROLIFERATION; ACTIVATION; CARCINOMA AB Tumors can become lethal when they progress from preinvasive lesions to invasive carcinomas. Here, we identify candidate tumor progression genes using gene array analysis of preinvasive and invasive tumors from mice, which were then evaluated in human cancers. Immediate early response protein IEX-1, small stress protein 1 (HSPB8), and tumor necrosis factor-associated factor-interacting protein mRNAs displayed higher expression levels in invasive lesions than in preinvasive lesions using samples obtained by laser capture microdissection (LCM) from transgenic erbB2, ras, and cyclin D1 mice. LCM-isolated tissues from patient-matched normal, ductal carcinoma in situ, and invasive ductal carcinoma revealed similar increased expression in invasive human cancers compared with preinvasive and normal samples. These genes induced anchorage independence, increased cell proliferation, and protected against apoptosis, singly or in collaboration with erbB2. Surprisingly. they were all up-regulated by 17 beta-estradiol and cyclin D1, and cyclin D1 overexpression increased P300/CBP binding to their promoters, supporting the model that cyclin D1-estrogen receptor (ER) coactivator interactions may be important to its role in ER-positive breast cancer. Additionally, an irreversible dual kinase inhibitor of ErbB signaling inhibited expression of the same genes. The up-regulation of genes contributing to increased invasiveness of ER-positive cancers offers a novel explanation for the contribution of cyclin D1 to a worse prognosis in ER-positive cancers. As targets of estrogen, cyclin D1, and erbB2 signaling, these candidates offer insights into the nature of the second events involved in breast cancer progression, regulatory events contributing to invasion, and potential targets of combined inhibition of hormone and growth factor signaling pathways. C1 Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Family Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Royal Marsden Hosp, Dept Radiotherapy, London SW3 6JJ, England. Massachusetts Gen Hosp E, Mol Pathol Unit, Charlestown, MA USA. RP Schmidt, EV (reprint author), Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Canc Res Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA69069, P50 CA89393] NR 49 TC 51 Z9 54 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 11649 EP 11658 DI 10.1158/0008-5472.CAN-06-1645 PG 10 WC Oncology SC Oncology GA 118AY UT WOS:000242915600019 PM 17178859 ER PT J AU Setiawan, VW Cheng, IN Stram, DO Giorgi, E Pike, MC Van Den Berg, D Pooler, L Burtt, NP Le Marchand, L Altshuler, D Hirschhorn, J Henderson, BE Haiman, CA AF Setiawan, Veronica Wendy Cheng, Iona Stram, Daniel O. Giorgi, Elena Pike, Malcolm C. Van Den Berg, David Pooler, Loreall Burtt, Noel P. Le Marchand, Loic Altshuler, David Hirschhorn, Joel Henderson, Brian E. Haiman, Christopher A. TI A systematic assessment of common genetic variation in CYP11A and risk of breast cancer SO CANCER RESEARCH LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; MULTIETHNIC COHORT; MICROSATELLITE POLYMORPHISM; PROSTATE-CANCER; HUMAN GENOME; ASSOCIATION; POPULATION; TRAITS AB CYP11A catalyzes the rate-limiting step in the biosynthesis of sex-steroid hormones. In this study, we employed a systematic approach that involved gene resequencing and a haplotype-based analysis to investigate the relationship between common variation in CYP11A and breast cancer risk among African-Americans, Latinas, Japanese-Americans, Native Hawaiians, and Whites in the Multiethnic Cohort Study. Resequencing in a multiethnic panel of 95 advanced breast cancer cases revealed no common missense variant (>= 5% frequency). Common haplotype patterns were assessed by genotyping 36 densely spaced single nucleotide polymorphisms (SNPs) spanning 67 kb of the CYP11A locus in a multiethnic panel of subjects (n = 349; 1 SNP/1.86 kb on average). We identified one to two regions of strong linkage disequilibrium in these populations. Twelve tagging SNPs were selected to predict the common haplotypes (>= 5% frequency) in these regions with high probability (average R-h(2) = 0.94) and were examined in a breast cancer case-control study in the Multiethnic Cohort Study (1,615 cases and 1,962 controls). A global test for differences in risk according to common haplotypes over the locus was statistically significant (P = 0.006), as were associations with haplotypes in each block (block 1 global test, P = 0.008; haplotype 1D, effect per haplotype copy, odds ratios, 1.23; 95% confidence interval, 1.03-1.48) and block 2 (global test, P = 0.016; haplotype 2F odds ratios, 1.52; 95% confidence interval, 1.15-2.01). These haplotypes were most common in Japanese-Americans and Native Hawaiians, followed by Whites then Latinas, and were rare in African-Americans (< 5% frequency); the haplotype effects on risk across each group were homogeneous. Based on these findings, CIP11A deserves further consideration as a candidate breast cancer susceptibility gene. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Dept Urol, Keck Sch Med, Los Angeles, CA 90033 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA. MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Dept Pediat, Boston, MA USA. Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. RP Setiawan, VW (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, 1441 E Lake Ave,Room 4425, Los Angeles, CA 90033 USA. EM vsetiawa@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA63464, CA116543, CA54281] NR 23 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 12019 EP 12025 DI 10.1158/0008-5472.CAN-06-1101 PG 7 WC Oncology SC Oncology GA 118AY UT WOS:000242915600061 PM 17178901 ER PT J AU Wu, SM Fujiwara, Y Cibulsky, SM Clapham, DE Lien, CL Schultheiss, TM Orkin, SH AF Wu, Sean M. Fujiwara, Yuko Cibulsky, Susan M. Clapham, David E. Lien, Ching-ling Schultheiss, Thomas M. Orkin, Stuart H. TI Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart SO CELL LA English DT Article ID CARDIAC NEURAL CREST; CARDIOVASCULAR-SYSTEM; PROGENITOR CELLS; OUTFLOW TRACT; STEM-CELLS; NKX2-5; DIFFERENTIATION; TRANSCRIPTION; EXPRESSION; EMBRYOS AB Despite recent advances in delineating the mechanisms involved in cardiogenesis, cellular lineage specification remains incompletely understood. To explore the relationship between developmental fate and potential, we isolated a cardiac-specific Nkx2.5(+) cell population from the developing mouse embryo. The majority of these cells differentiated into cardiomyocytes and conduction system cells. Some, surprisingly, adopted a smooth muscle fate. To address the clonal origin of these lineages, we isolated Nkx2.5+ cells from in vitro differentiated murine embryonic stem cells and found similar to 28% of these cells expressed c-kit. These c-kit(+) cells possessed the capacity for long-term in vitro expansion and differentiation into both cardiomyocytes and smooth muscle cells from a single cell. We confirmed these findings by isolating c-kit(+)Nkx2.5(+) cells from mouse embryos and demonstrated their capacity for bipotential differentiation in vivo. Taken together, these results support the existence of a common precursor for cardiovascular lineages in the mammalian heart. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Childrens Hosp Los Angeles, Saban Res Inst, Dept Cardiothorac Surg, Los Angeles, CA 90027 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. Beth Israel Deaconess Med Ctr, Dept Mol & Vasc Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu FU NHLBI NIH HHS [K08 HL081086, T32 HL002807] NR 39 TC 305 Z9 320 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 15 PY 2006 VL 127 IS 6 BP 1137 EP 1150 DI 10.1016/j.cell.2006.10.028 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119CY UT WOS:000242991000013 PM 17123591 ER PT J AU Moretti, A Caron, L Nakano, A Lam, JT Bernshausen, A Chen, YH Qyang, YB Bu, L Sasaki, M Martin-Puig, S Sun, YF Evans, SM Laugwitz, KL Chien, KR AF Moretti, Alessandra Caron, Leslie Nakano, Atsushi Lam, Jason T. Bernshausen, Alexandra Chen, Yinhong Qyang, Yibing Bu, Lei Sasaki, Mika Martin-Puig, Silvia Sun, Yunfu Evans, Sylvia M. Laugwitz, Karl-Ludwig Chien, Kenneth R. TI Multipotent embryonic Isl1(+) progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification SO CELL LA English DT Article ID CONGENITAL HEART-DISEASE; STEM-CELLS; SECONDARY HEART; HEMATOPOIETIC STEM; MYOCARDIAL-CELLS; PROTEIN ISL-1; ARTERIAL POLE; CLONAL ORIGIN; NEURAL CREST; FIELD AB Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1(+) precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1(+) cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1(+)/Nkx2.5(+)/flk1(+) defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1(+) cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Tech Univ Munich, Klinikum Rechts Isar, Med Klin 1, D-81675 Munich, Germany. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Skaggs Sch Pharm, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Pl CPZN 3208,185 Cambridge St, Boston, MA 02114 USA. EM kchien@partners.org RI Bu, Lei/F-4461-2011; Evans, Sylvia/G-1980-2015; Moretti, Alessandra/O-9271-2015; OI Martin-Puig, Silvia/0000-0003-3048-6729 NR 49 TC 571 Z9 600 U1 5 U2 46 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 15 PY 2006 VL 127 IS 6 BP 1151 EP 1165 DI 10.1016/j.cell.2006.10.029 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119CY UT WOS:000242991000014 PM 17123592 ER PT J AU Sharma, SV Settleman, J AF Sharma, Sreenath V. Settleman, Jeffrey TI Oncogenic shock - Turning an activated kinase against the tumor cell SO CELL CYCLE LA English DT Article DE oncogene addiction; kinase inhibitors; cancer therapeutics; oncogenic shock; signal transduction; tyrosine kinases ID HER2-POSITIVE BREAST-CANCER; PHASE-III TRIAL; LUNG-CANCER; BCR-ABL; ADJUVANT CHEMOTHERAPY; TYROSINE KINASE; EGFR MUTATIONS; C-MYC; GEFITINIB; PROTEIN AB Accumulating evidence indicates that mutationally activated kinases are especially good targets for anti-cancer drugs. It has been suggested that this reflects a state of "oncogene addiction" of tumor cells. We recently reported experimental studies that may provide a molecular mechanism to explain such apparent dependency. We find that oncogenic kinases produce both pro-survival and pro-apoptotic signals that decay at different rates upon oncogene inactivation. Pro-survival signals are rapidly attenuated, whereas pro-apoptotic signals are relatively longer-lived. This differential signal decay creates a temporal window during which pro-apoptotic outputs from the oncogenic kinase predominate to actively promote tumor cell death upon kinase inhibition. We refer to this mechanism as "oncogenic shock", and suggest that it has significant implications for the optimal therapeutic use of targeted kinase inhibitors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Mol Therapeut, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 33 TC 21 Z9 23 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2006 VL 5 IS 24 BP 2878 EP 2880 DI 10.4161/cc.5.24.3598 PG 3 WC Cell Biology SC Cell Biology GA 117UF UT WOS:000242898100010 PM 17218790 ER PT J AU Hill, DR Ericsson, CD Pearson, RD Keystone, JS Freedman, DO Kozarsky, PE DuPont, HL Bia, FJ Fischer, PR Ryan, ET AF Hill, David R. Ericsson, Charles D. Pearson, Richard D. Keystone, Jay S. Freedman, David O. Kozarsky, Phyllis E. DuPont, Herbert L. Bia, Frank J. Fischer, Philip R. Ryan, Edward T. TI The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PLACEBO-CONTROLLED TRIAL; ACUTE MOUNTAIN-SICKNESS; HEPATITIS-A VACCINE; IRRITABLE-BOWEL-SYNDROME; PLASMODIUM-FALCIPARUM MALARIA; HIGH-ALTITUDE ILLNESS; YELLOW-FEVER VACCINE; ENTEROTOXIGENIC ESCHERICHIA-COLI; JAPANESE ENCEPHALITIS VACCINE; ANOPHELES-GAMBIAE COMPLEX C1 Univ London London Sch Hyg & Trop Med, Natl Travel Hlth Network & Ctr, London WC1E 7HT, England. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. Univ Toronto, Dept Med, Toronto, ON, Canada. Toronto Gen Hosp, Ctr Travel & Trop Med, Toronto, ON, Canada. Univ Texas, Sch Med, Dept Internal Med, Houston, TX USA. Univ Texas, Sch Publ Hlth, St Lukes Hosp, Dept Internal Med, Houston, TX USA. Univ Texas, Sch Publ Hlth, Ctr Infect Dis, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Virginia, Sch Med, Div Infect Dis & Int Hlth, Dept Med, Charlottesville, VA 22903 USA. Univ Virginia, Sch Med, Div Infect Dis & Int Hlth, Dept Pathol, Charlottesville, VA 22903 USA. Univ Alabama, Dept Med, Div Geog Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Div Geog Med, Birmingham, AL 35294 USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA. Mayo Clin, Coll Med, Dept Pediat, Div Gen Pediat & Adolescent Med, Rochester, MN USA. Mayo Eugenio Litta Childrens Hosp, Mayo Clin, Rochester, MN USA. Harvard Univ, Sch Med, Div Infect Dis, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. RP Hill, DR (reprint author), Hosp Trop Dis, Natl Travel Hlth Network & Ctr, Mortimer Market Ctr, Capper St, London WC1E 6AU, England. EM david.hill@uclh.org NR 377 TC 110 Z9 116 U1 0 U2 11 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2006 VL 43 IS 12 BP 1499 EP 1539 DI 10.1086/508782 PG 41 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 106UD UT WOS:000242126300001 PM 17109284 ER PT J AU Carrieri, MP Amass, L Lucas, GM Vlahov, D Wodak, A Woody, GE AF Carrieri, Maria Patrizia Amass, Leslie Lucas, Gregory M. Vlahov, David Wodak, Alex Woody, George E. TI Buprenorphine use: The international experience SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Forum for Collaborative HIV Research CY JUN 03-04, 2004 CL Washington, DC ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; INJECTING DRUG-USERS; HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-DOSE BUPRENORPHINE; METHADONE-MAINTENANCE TREATMENT; HIGH-DOSAGE BUPRENORPHINE; 2-YEAR FOLLOW-UP; FRENCH GENERAL-PRACTITIONERS; RANDOMIZED CONTROLLED TRIAL/ AB The confluence of the heroin injection epidemic and the human immunodeficiency virus (HIV) infection epidemic has increased the call for expanded access to effective treatments for both conditions. Buprenorphine and methadone are now listed on the World Health Organization's Model Essential Drugs List. In France, which has the most extensive experience, buprenorphine has been associated with a dramatic decrease in deaths due to overdose, and buprenorphine diversion appears to be associated with inadequate dosage, social vulnerability, and prescriptions from multiple providers. Other treatment models (in the United States, Australia, Germany, and Italy) and buprenorphine use in specific populations are also reviewed in the present article. In countries experiencing a dual epidemic of heroin use and HIV infection, such as former states of the Soviet Union and other eastern European and Asian countries, access to buprenorphine and methadone may be one potential tool for reducing the spread of HIV infection among injection drug users and for better engaging them in medical care. C1 INSERM, U379, F-13006 Marseille, France. Friends Res Inst, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. Univ Penn, Sch Med, Treatment Res Inst, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. St Vincents Hosp, Alcohol & Drug Serv, Sydney, NSW 2010, Australia. RP Carrieri, MP (reprint author), INSERM, U379, 23 Rue S Torrents, F-13006 Marseille, France. EM Pmcarrieri@aol.com RI Lucas, Gregory/B-9225-2009 FU NIDA NIH HHS [DA15616]; PHS HHS [H97HA03794] NR 185 TC 68 Z9 69 U1 5 U2 11 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2006 VL 43 SU 4 BP S197 EP S215 DI 10.1086/508184 PG 19 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 106UB UT WOS:000242126100006 PM 17109307 ER PT J AU Goetz, MB Ferguson, MR Han, XL McMillan, G Clair, MS Pappa, KA McClernon, DR O'Brien, WA AF Goetz, Matthew Bidwell Ferguson, Monique R. Han, Xueliang McMillan, Greg Clair, Marty St. Pappa, Keith A. McClernon, Daniel R. O'Brien, William A. TI Evolution of HIV resistance mutations in patients maintained on a stable treatment regimen after virologic failure SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV resistance; protease inhibitors; resistance mutations; reverse transcriptase inhibitors ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; THYMIDINE ANALOG MUTATIONS; COMBINATION THERAPY; HIV-1-INFECTED PATIENTS; DRUG-RESISTANCE; NAIVE PATIENTS; RANDOMIZED-TRIAL; TREATMENT INTERRUPTION; INFECTED PATIENTS AB Objective: We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. Design: Follow-up genotypic resistance testing was done using archived 1 plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. Results: The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4(+) cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used. Conclusions: Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Texas, Med Branch, Dept Med, Galveston, TX 77550 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77550 USA. RP Goetz, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU NIAID NIH HHS [R21 AI058194] NR 48 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2006 VL 43 IS 5 BP 541 EP 549 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 116HR UT WOS:000242793600007 PM 17075391 ER PT J AU Almeciga, I Wang, ZGC Zuniga, J Fernandez-Vina, M Clavijo, O Araujo, H Romero, V Henry, J Ferrone, S Yunis, EJ AF Almeciga, Ingrid Wang, Zhigang Charles Zuniga, Joaquin Fernandez-Vina, Marcelo Clavijo, Olga Araujo, Hugo Romero, Viviana Henry, John Ferrone, Soldano Yunis, Edmond J. TI Allorecognition of an HLA-A*01 aberrant allele by an HLA identical family member carrying the HLA-A*0101 allele SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; HISTOCOMPATIBILITY ANTIGEN; PROTEASOMAL CLEAVAGES; BLANK ALLELES; CHAINS; PREDICTION; ALGORITHM; REJECTION; COMPLEX; EPITOPE AB We identified and characterized an HLA-A1 aberrant allele (A*0118N) resulting from a novel molecular mechanism; this allele was present in an unusually informative family with a near identical parental HLA haplotype (c d) differing only by one nucleotide substitution in one HLA-A allele, A*0118N, of the maternal HLA haplotype (c) and not of the paternal HLA haplotype (a). Although serologic HLA typing showed a "blank," DNA molecular HLA typing detected a HLA-A*0118N allele. Sequence based typing identified the substitution of guanine by cytosine at the nucleotide position 215, which resulted in the replacement of arginine by proline at position 48 of the HLA-A1 H chain. The loss of surface protein expression was also found by FACS analysis. Isoelectric-focusing analysis detected a HLA-A H chain with a unique isoelectric-focusing pattern, which does not associate with the L chain (beta(2)-microglobulin). These results suggest that the residue 48-containing interaction site on the alpha(1) domain plays a critical role in the association between HLA class I H chain and beta(2)-microglobulin. Functional studies showed that the T cells of the propositus (HLA haplotypes c d) carrying this null allele recognized its wild-type counterpart, HLA-A*010101, in her HLA-identical son that carries the HLA-A*0101 heterodimer. This is the first example of the generation of cytotoxic T cells in the absence of proliferation of CD4(+) T cells (mixed lymphocyte culture) and the description of an aberrant aliele, A*0118N, that may behave as a minor histocompatibility Ag, with implications in allorecognition by cytolytic T cells in solid organ and stem cell transplantation. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. Georgetown Univ, CW Bill Young Dept, Defense Marrow Donor Program, Kensington, MD 20895, Australia. SUNY Upstat, Dept Pathol, Syracuse, NY 13210 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. Univ Texas, AMD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM mfernand@mdanderson.org; edmond_yunis@dfci.harvard.edu FU NCI NIH HHS [CA 67108]; NHLBI NIH HHS [HL 29583, HL 59838] NR 32 TC 2 Z9 4 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 DEC 15 PY 2006 VL 177 IS 12 BP 8643 EP 8649 PG 7 WC Immunology SC Immunology GA 125BP UT WOS:000243416800043 PM 17142764 ER PT J AU Eisenberger, NI Jarcho, JM Lieberman, MD Naliboff, BD AF Eisenberger, Naomi I. Jarcho, Johanna M. Lieberman, Matthew D. Naliboff, Bruce D. TI An experimental study of shared sensitivity to physical pain and social rejection SO PAIN LA English DT Article DE pain sensitivity; social exclusion; social pain; dorsal anterior cingulate cortex; social rejection; pain threshold; pain unpleasantness ID SUPPORT; EXCLUSION; RECOVERY; SURGERY; HURT AB Recent evidence points to a possible overlap in the neural systems underlying the distressing experience that accompanies physical pain and social rejection (Eisenberger et al., 2003). The present study tested two hypotheses that stem from this suggested overlap, namely: (1) that baseline sensitivity to physical pain will predict sensitivity to social rejection and (2) that experiences that heighten social distress will heighten sensitivity to physical pain as well. In the current study, participants' baseline cutaneous heat pain unpleasantness thresholds were assessed prior to the completion of a task that manipulated feelings of social distress. During this task, participants played a virtual ball-tossing game, allegedly with two other individuals, in which they were either continuously included (social inclusion condition) or they were left out of the game by either never being included or by being overtly excluded (social rejection conditions). At the end of the game, three pain stimuli were delivered and participants rated the unpleasantness of each. Results indicated that greater baseline sensitivity to pain (lower pain unpleasantness thresholds) was associated with greater self-reported social distress in response to the social rejection conditions. Additionally, for those in the social rejection conditions, greater reports of social distress were associated with greater reports of pain unpleasantness to the thermal stimuli delivered at the end of the game. These results provide additional support for the hypothesis that pain distress and social distress share neurocognitive substrates. Implications for clinical Populations are discussed. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Davis Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Eisenberger, NI (reprint author), Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. EM neisenbe@ucla.edu; jjarcho@psych.ucla.edu OI Jarcho, Johanna/0000-0001-9075-6968 FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [P50 DK64539]; NIMH NIH HHS [T32 MH019925, MH15750]; NINR NIH HHS [NR04881] NR 24 TC 89 Z9 93 U1 1 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 15 PY 2006 VL 126 IS 1-3 BP 132 EP 138 DI 10.1016/j.pain.2006.06.024 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 119KW UT WOS:000243012200017 PM 16890354 ER PT J AU Tsushima, Y Sasaki, Y Watanabe, T AF Tsushima, Yoshiaki Sasaki, Yuka Watanabe, Takeo TI Greater disruption due to failure of inhibitory control on an ambiguous distractor SO SCIENCE LA English DT Article ID PRIMARY VISUAL-CORTEX; PREFRONTAL CORTEX; BINOCULAR-RIVALRY; MOTION BLINDNESS; PERCEPTION; ATTENTION; DISSOCIATION; SUPPRESSION AB Considerable evidence indicates that a stimulus that is subthreshold, and thus consciously invisible, influences brain activity and behavioral performance. However, it is not clear how subthreshold stimuli are processed in the brain. We found that a task-irrelevant subthreshold coherent motion led to a stronger disturbance in task performance than did suprathreshold motion. With the subthreshold motion, activity in the visual cortex measured by functional magnetic resonance imaging was higher, but activity in the lateral prefrontal cortex was lower, than with suprathreshold motion. These results suggest that subthreshold irrelevant signals are not subject to effective inhibitory control. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. CALTECH, ERATO, Shimojo Implicit Brain Funct Project, Pasadena, CA 91125 USA. RP Watanabe, T (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. EM takeo@bu.edu FU NCRR NIH HHS [P41RR14075]; NEI NIH HHS [R01 EY015980, R21 EY017737] NR 30 TC 88 Z9 88 U1 1 U2 18 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 DEC 15 PY 2006 VL 314 IS 5806 BP 1786 EP 1788 DI 10.1126/science.1133197 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116WD UT WOS:000242833600062 PM 17170308 ER PT J AU Atlas, SJ Chang, YC Keller, RB Singer, DE Wu, YA Deyo, RA AF Atlas, Steven J. Chang, Yuchiao Keller, Robert B. Singer, Daniel E. Wu, Yen A. Deyo, Richard A. TI The impact of disability compensation on long-term treatment outcomes of patients with sciatica due to a lumbar disc herniation SO SPINE LA English DT Article DE workers' compensation; disability; employment; lumbar disc herniation; sciatica; cohort study; outcomes research; lumbar disc surgery; natural history ID LOW-BACK-PAIN; RETURN-TO-WORK; NONSURGICAL MANAGEMENT; SPINAL-DISORDERS; RISK-FACTORS; DETERMINANTS; POPULATION; STENOSIS; DURATION; QUALITY AB Study Design. Prospective, observational study. Objective. To compare long-term disability and health-related quality of life outcomes of individuals receiving or not receiving workers' compensation at baseline evaluation. Summary of Background Data. Disability compensation has long been associated with poor clinical outcomes. However, most studies have assessed outcomes over short time periods using unvalidated measures without controlling for potential confounders. Method. Patients with sciatica due to a herniated lumbar disc were treated by physicians in community based orthopedic, neurosurgical, and occupational medicine practices throughout Maine. Outcomes assessed included disability compensation and work status, and health-related quality of life, controlling for initial treatment received and factors predicting initial workers' compensation status. Results. Among 440 eligible patients, 172 (86%) receiving workers' compensation and 222 (92%) not receiving workers' compensation at baseline evaluation completed at least one follow-up between 5 and 10 years (80% completed 10-year). Baseline demographics, past back history, imaging findings, symptoms, functional status, and expectations significantly differed according to the patient's baseline workers' compensation status. After 5-10 years, most patients, regardless of baseline workers' compensation status (yes or no), were not receiving disability compensation (83% vs. 96%, respectively) and were employed (78% for both groups). However, workers' compensation patients were significantly more likely to be receiving disability compensation and had worse symptoms, functional status, and satisfaction outcomes. Outcome differences diminished in magnitude after controlling for baseline differences among patients receiving workers' compensation or not but continued to favor those not initially receiving workers' compensation. Initial treatment received, either surgical or nonsurgical, did not influence these findings. Conclusions. Long-term employment and disability outcomes were favorable for most patients with a disc herniation, regardless of initial workers' compensation status. However, individuals initially receiving workers' compensation had worse disability and quality of life outcomes compared to individuals not receiving workers' compensation. Despite these differences, long-term work outcomes were, similarly favorable. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Gen Med Div, Boston, MA USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org NR 34 TC 40 Z9 41 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 2006 VL 31 IS 26 BP 3061 EP 3069 DI 10.1097/01.brs.0000250325.87083.8d PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 117TG UT WOS:000242895600012 PM 17173004 ER PT J AU Kahn, SE Hull, RL Utzschneider, KM AF Kahn, Steven E. Hull, Rebecca L. Utzschneider, Kristina M. TI Mechanisms linking obesity to insulin resistance and type 2 diabetes SO NATURE LA English DT Article ID BETA-CELL FUNCTION; IMPAIRED GLUCOSE-TOLERANCE; HUMAN ADIPOSE-TISSUE; FATTY-ACID CYCLE; NONDIABETIC SUBJECTS; SECRETORY CAPACITY; METABOLIC SYNDROME; INCRETIN HORMONES; HIGH-RISK; MELLITUS AB Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, proinflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 NR 83 TC 1538 Z9 1597 U1 49 U2 390 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 14 PY 2006 VL 444 IS 7121 BP 840 EP 846 DI 10.1038/nature05482 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116LW UT WOS:000242805400040 PM 17167471 ER PT J AU Rosen, ED Spiegelman, BM AF Rosen, Evan D. Spiegelman, Bruce M. TI Adipocytes as regulators of energy balance and glucose homeostasis SO NATURE LA English DT Review ID INDUCED INSULIN-RESISTANCE; FATTY-ACID OXIDATION; ACTIVATED PROTEIN-KINASE; BROWN ADIPOSE-TISSUE; TOTAL-BODY FAT; PPAR-GAMMA; IN-VITRO; CHEMOATTRACTANT PROTEIN-1; ADIPONECTIN RECEPTORS; TRANSCRIPTION FACTOR AB Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 111 TC 893 Z9 930 U1 24 U2 141 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 14 PY 2006 VL 444 IS 7121 BP 847 EP 853 DI 10.1038/nature05483 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116LW UT WOS:000242805400041 PM 17167472 ER PT J AU Sandler, A Gray, R Perry, MC Brahmer, J Schiller, JH Dowlati, A Lilenbaum, R Johnson, DH AF Sandler, Alan Gray, Robert Perry, Michael C. Brahmer, Julie Schiller, Joan H. Dowlati, Afshin Lilenbaum, Rogerio Johnson, David H. TI Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; BREAST-CANCER; MICROVESSEL DENSITY; EXPRESSION; ANGIOGENESIS; RECEPTORS; VEGF; ANTIBODY; THERAPY AB BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has been shown to benefit patients with a variety of cancers. METHODS: Between July 2001 and April 2004, the Eastern Cooperative Oncology Group (ECOG) conducted a randomized study in which 878 patients with recurrent or advanced non-small-cell lung cancer (stage IIIB or IV) were assigned to chemotherapy with paclitaxel and carboplatin alone (444) or paclitaxel and carboplatin plus bevacizumab (434). Chemotherapy was administered every 3 weeks for six cycles, and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable. Patients with squamous-cell tumors, brain metastases, clinically significant hemoptysis, or inadequate organ function or performance status (ECOG performance status, >1) were excluded. The primary end point was overall survival. RESULTS: The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab, as compared with 10.3 months in the chemotherapy-alone group (hazard ratio for death, 0.79; P=0.003). The median progression-free survival in the two groups was 6.2 and 4.5 months, respectively (hazard ratio for disease progression, 0.66; P<0.001), with corresponding response rates of 35% and 15% (P<0.001). Rates of clinically significant bleeding were 4.4% and 0.7%, respectively (P<0.001). There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group, including 5 from pulmonary hemorrhage. CONCLUSIONS: The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths. C1 Vanderbilt Univ, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Wisconsin, Madison, WI USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Mt Sinai Hosp, Miami, FL USA. RP Sandler, A (reprint author), Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave, Nashville, TN 37232 USA. EM alan.sandler@vanderbilt.edu RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA14548, CA12046, CA16116, CA21076, CA21115, CA23318, CA31946, CA49957, CA66636] NR 25 TC 3339 Z9 3477 U1 34 U2 237 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 14 PY 2006 VL 355 IS 24 BP 2542 EP 2550 DI 10.1056/NEJMoa061884 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 116BZ UT WOS:000242778800006 PM 17167137 ER PT J AU Caviness, VS Sagar, P Israel, EJ Mackool, BT Grabowski, EF Frosch, MP Zanger, K Mackool, BT Harris, NL AF Caviness, Verne S., Jr. Sagar, Pallavi Israel, Esther J. Mackool, Bonnie T. Grabowski, Eric F. Frosch, Matthew P. Zanger, Kirsten Mackool, Bonnie T. Harris, Nancy Lee TI A boy with headache and abdominal pain - Degos's disease, involving the brain, gastrointestinal tract, and skin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MALIGNANT ATROPHIC PAPULOSIS; CENTRAL NERVOUS SYSTEM; KOHLMEIER-DEGOS; VASCULOPATHY; INVOLVEMENT C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Med Sch, Dept Neurol, Boston, MA USA. Harvard Med Sch, Dept Radiol, Boston, MA USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. Harvard Med Sch, Dept Dermatol, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 31 TC 12 Z9 12 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 14 PY 2006 VL 355 IS 24 BP 2575 EP 2584 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 116BZ UT WOS:000242778800011 PM 17167141 ER PT J AU Lieberman, D AF Lieberman, David TI A call to action - Measuring the quality of colonoscopy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; PREVENTION; ADENOMAS; SURVEILLANCE; POLYPECTOMY; RECURRENCE; CELECOXIB C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol, Portland, OR 97201 USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol, Portland, OR 97201 USA. NR 20 TC 54 Z9 55 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 14 PY 2006 VL 355 IS 24 BP 2588 EP 2589 DI 10.1056/NEJMe068254 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 116BZ UT WOS:000242778800013 PM 17167143 ER PT J AU Pekary, AE Stevens, SA Sattin, A AF Pekary, Albert Eugene Stevens, Schetema A. Sattin, Albert TI Circadian rhythms of TRH-like peptide levels in rat brain SO BRAIN RESEARCH LA English DT Article DE thyrotropin-releasing hormone; limbic system; mood regulation ID THYROTROPIN-RELEASING-HORMONE; RAPID MODULATION; CEREBELLUM; TISSUES AB This is the first report of diurnal variations in the levels of thyrotropin-releasing hormone-like peptides (pGlu-X-Pro-NH2, where "X" can be any amino acid residue) in brain regions involved in mood regulation. These peptides have neuroprotective and antidepressant-like properties that may help stabilize chronobiologic systems that are often abnormal in neuropsychiatric disease. We hypothesized that diurnal fluctuations in the levels of these neuropeptides are components of the chronobiologic regulation of autonomic, behavioral and emotional states. Optimal use of these potentially therapeutic agents will benefit from an understanding of their response to, and effect on, normal vegetative, activity and sleep patterns, and the corresponding disordered patterns of mental illness. For these reasons, 16 male, 200 g, Sprague-Dawley rats were maintained for 4 weeks in a stable 12 h lights on, 12 h lights off photoperiod. Levels of TRH and TRH-like peptides were measured at 3.0 h, 10.5 h, 13.5 h and 21.0 h, where the subjective midnight was 0.0 h, by a combination of HPLC and RIA. Highly significant changes in TRH-like peptide levels were observed in the striatum, posterior cingulate, cerebellum, pyriform cortex, nucleus accumbens and medulla oblongata. TRH-like peptide levels, in general, were highly correlated with changes in TRH concentration, within and between brain regions, and may be colocalized in large glutamatergic neurons innervating the rat limbic system. We conclude that TRH-like peptides may be important components of chronobiologic systems involved in maintaining autonomic, behavioral and mood equilibria. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, 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, Inst Brain Res, Los Angeles, CA 90073 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@va.gov NR 31 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 13 PY 2006 VL 1125 BP 67 EP 76 DI 10.1016/j.brainres.2006.10.003 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 122TZ UT WOS:000243251200009 PM 17113044 ER PT J AU Zhang, Y Leavitt, BR van Raamsdonk, JM Dragatsis, I Goldowitz, D MacDonald, ME Hayden, MR Friedlander, RM AF Zhang, Yu Leavitt, Blair R. van Raamsdonk, Jeremy M. Dragatsis, Ioannis Goldowitz, Dan MacDonald, Marcy E. Hayden, Michael R. Friedlander, Robert M. TI Huntingtin inhibits caspase-3 activation SO EMBO JOURNAL LA English DT Article DE caspases-3; huntingtin; Huntington's ID WILD-TYPE HUNTINGTIN; DISEASE GENE HOMOLOG; MOUSE MODEL; EMBRYONIC LETHALITY; LACKING HUNTINGTIN; BINDING PROTEIN; APOPTOSIS; NEURONS; BRAIN; INACTIVATION AB Huntington's disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear. To probe the prosurvival function of huntingtin, we modulate levels of wild-type huntingtin in a number of cellular and in vivo models. Huntingtin depletion resulted in caspase-3 activation, and overexpression of huntingtin resulted in caspase-3 inhibition. Additionally, we demonstrate that huntingtin physically interacts with active caspase-3. Interestingly, mutant huntingtin binds active caspase-3 with a lower affinity and lower inhibitory effect on active caspase-3 than does wild-type huntingtin. Although reduction of huntingtin levels resulted in caspase-3 activation in all conditions examined, the cellular response was cell-type specific. Depletion of huntingtin resulted in either overt cell death, or in increased vulnerability to cell death. These data demonstrate that huntingtin inhibits caspase-3 activity, suggesting a mechanism whereby caspase-mediated huntingtin depletion results in a detrimental amplification cascade leading to further caspase-3 activation, resulting in cell dysfunction and cell death. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Neuroapoptosis Lab, Boston, MA 02115 USA. Univ British Columbia, Womens & Childrens Hosp, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Womens & Childrens Hosp, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA USA. RP Friedlander, RM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Neuroapoptosis Lab, 75 Francis St, Boston, MA 02115 USA. EM rfriedlander@rics.bwh.harvard.edu RI Hayden, Michael/D-8581-2011; Leavitt, Blair/G-1934-2012; Friedlander, Robert/A-2845-2016 OI Hayden, Michael/0000-0001-5159-1419; Friedlander, Robert/0000-0003-4423-9219 FU NINDS NIH HHS [NS 16367, NS 32765, P50 NS016367, R01 NS032765] NR 36 TC 43 Z9 43 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 13 PY 2006 VL 25 IS 24 BP 5896 EP 5906 DI 10.1038/sj.emboj.7601445 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117RR UT WOS:000242891100025 PM 17124493 ER PT J AU Werner, RM Bradlow, ET AF Werner, Rachel M. Bradlow, Eric T. TI Relationship between medicare's hospital compare performance measures and mortality rates SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-CARE; COMMUNITY-ACQUIRED PNEUMONIA; CONGESTIVE-HEART-FAILURE; HEALTH-CARE; MYOCARDIAL-INFARCTION; COMORBIDITY MEASURES; ADMINISTRATIVE DATA; US HOSPITALS; SURVIVAL; THERAPY AB Context In response to concerns about the quality of care in US hospitals, the Centers for Medicare & Medicaid Services began measuring hospital performance and reporting this performance on their Web site, Hospital Compare. It is unknown whether these process performance measures are related to hospital-level outcomes. Objective To determine whether quality measured with the process measures used in Hospital Compare are correlated with and predictive of hospitals' risk-adjusted mortality rates. Design, Setting, and Participants Cross-sectional study of hospital care between January 1 and December 31, 2004, for acute myocardial infarction, heart failure, and pneumonia at acute care hospitals in the United States included on the Hospital Compare Web site. Ten process performance measures included in Hospital Compare were compared with hospital risk-adjusted mortality rates, which were measured using Medicare Part A claims data. Main Outcome Measures Condition-specific inpatient, 30-day, and 1-year risk-adjusted mortality rates. Results A total of 3657 acute care hospitals were included in the study based on their performance as reported in Hospital Compare. Across all acute myocardial infarction performance measures, the absolute reduction in risk-adjusted mortality rates between hospitals performing in the 25th percentile vs those performing in the 75th percentile was 0.005 for inpatient mortality, 0.006 for 30-day mortality, and 0.012 for 1-year mortality ( P <. 001 for each comparison). For the heart failure performance measures, the absolute mortality reduction was smaller, ranging from 0.001 for inpatient mortality ( P=. 03) to 0.002 for 1-year mortality ( P=. 08). For the pneumonia performance measures, the absolute reduction in mortality ranged from 0.001 for 30-day mortality ( P=. 05) to 0.005 for inpatient mortality ( P <. 001). Differences in mortality rates for hospitals performing in the 75th percentile on all measures within a condition vs those performing lower than the 25th percentile on all reported measures for acute myocardial infarction ranged between 0.008 ( P=. 06) and 0.018 ( P=. 008). For pneumonia, the effects ranged between 0.003 ( P=. 09) and 0.014 ( P <. 001); for heart failure, the effects ranged between - 0.013 ( P=. 06) and - 0.038 ( P=. 45). Conclusions Hospital performance measures predict small differences in hospital risk-adjusted mortality rates. Efforts should be made to develop performance measures that are tightly linked to patient outcomes. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equit Res & Promot, Philadelphia, PA USA. Univ Penn, Dept Mkt, Philadelphia, PA 19104 USA. Univ Penn, Dept Stat, Philadelphia, PA 19104 USA. Univ Penn, Dept Educ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu NR 62 TC 311 Z9 314 U1 4 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 13 PY 2006 VL 296 IS 22 BP 2694 EP 2702 DI 10.1001/jama.296.22.2694 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 115WY UT WOS:000242765700024 PM 17164455 ER PT J AU Amaya, F Wang, HB Costigan, M Allchorne, AJ Hatcher, JP Egerton, J Stean, T Morisset, V Grose, D Gunthorpe, MJ Chessell, IP Tate, S Green, PJ Woolf, CJ AF Amaya, Fumimasa Wang, Haibin Costigan, Michael Allchorne, Andrew J. Hatcher, Jon P. Egerton, Julie Stean, Tania Morisset, Valerie Grose, David Gunthorpe, Martin J. Chessell, Iain P. Tate, Simon Green, Paula J. Woolf, Clifford J. TI The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sensory neuron; peripheral sensitization; inflammation; nociceptor; pain; sodium channel ID PRIMARY SENSORY NEURONS; RESISTANT NA+ CURRENT; DORSAL-ROOT GANGLIA; PROTEIN-KINASE-C; TETRODOTOXIN-RESISTANT; NEUROPATHIC PAIN; DRG NEURONS; ION CHANNELS; CAPSAICIN-RECEPTOR; RAT AB We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A ( sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Nav1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B-2, and purinergic P2X(3) receptors. In Na(v)1.9(-/-) mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Nav1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E-2, bradykinin, interleukin-1 beta, capsaicin, and P2X(3) and P2Y receptor agonists, but not NGF, is either reduced or absent in Nav1.9(-/-) mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9(-/-) mice. Nav1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. GlaxoSmithKline Inc, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England. GlaxoSmithKline Inc, Discovery Res, Stevenage SG1 2NY, Herts, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St, Charlestown, MA 02129 USA. EM cwoolf@partners.org FU NINDS NIH HHS [NS039518, NS38253] NR 52 TC 158 Z9 167 U1 4 U2 21 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 13 PY 2006 VL 26 IS 50 BP 12852 EP 12860 DI 10.1523/JNEUROSCI.4015-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 119EV UT WOS:000242996200002 PM 17167076 ER PT J AU Friedman, J Hyland, K Blau, N MacCollin, M AF Friedman, Jennifer Hyland, Keith Blau, Nenad MacCollin, Mia TI Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency SO NEUROLOGY LA English DT Article ID DYSTONIA; HYPERPHENYLALANINEMIA; MOTOR AB Sepiapterin reductase deficiency (SRD) is a rare, treatable disorder of monoamine metabolism with cognitive delay and L-dopa responsive movement disorder. We describe a patient with SRD and distinctive phenotypic feature of marked hypersomnolence. Our patient showed improvement with therapies directed at both serotonergic and dopaminergic deficiencies. This case illustrates symptoms that characterize the SRD phenotype and demonstrates the importance of systematic treatment trials addressing the various biochemical abnormalities present. C1 Rady Childrens Hosp San Diego, Dept Neurol, San Diego, CA 92123 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Horizon Mol Med, Atlanta, GA USA. Univ Zurich, Childrens Hosp, Div Clin Chem & Biochem, Zurich, Switzerland. RP Friedman, J (reprint author), Rady Childrens Hosp San Diego, Dept Neurol, 8010 Frost St, San Diego, CA 92123 USA. EM jrfriedman@chsd.org NR 9 TC 28 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 12 PY 2006 VL 67 IS 11 BP 2032 EP 2035 DI 10.1212/01.wnl.0000247274.21261.b4 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000242750900024 PM 17159114 ER PT J AU Gleason, CE Schmitz, TW Hess, T Koscik, RL Trivedi, MA Ries, ML Carlsson, CM Sager, MA Asthana, S Johnson, SC AF Gleason, C. E. Schmitz, T. W. Hess, T. Koscik, R. L. Trivedi, M. A. Ries, M. L. Carlsson, C. M. Sager, M. A. Asthana, S. Johnson, S. C. TI Hormone effects on fMRI and cognitive measures of encoding: Importance of hormone preparation SO NEUROLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; ACTIVATION; IMPAIRMENT; DISEASE AB We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects. These preliminary findings emphasize the need to characterize differential neural effects of various HTs. C1 Univ Wisconsin, Dept Med, Sect Geriatr & Gerontol, Madison, WI 53705 USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Gleason, CE (reprint author), Univ Wisconsin, Dept Med, Sect Geriatr, 2870 Univ Ave,Suite 106, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU NIA NIH HHS [R01 AG021155-01A2, K23 AG024302, K23 AG024302-01, K23 AG024302-02, K23 AG024302-03, K23 AG024302-04, K23 AG024302-05, R01 AG021155, R01 AG021155-02, R01 AG021155-03, R01 AG021155-04, R01 AG021155-05, R01 AG21155] NR 9 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 12 PY 2006 VL 67 IS 11 BP 2039 EP 2041 DI 10.1212/01.wnl.0000247277.81400.43 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000242750900026 PM 17159116 ER PT J AU Timmons, M Tsokos, M Abu Asab, M Seminara, SB Zirzow, GC Kaneski, CR Heiss, JD van der Knaap, MS Vanier, MT Schiffmann, R Wong, K AF Timmons, M. Tsokos, M. Abu Asab, M. Seminara, S. B. Zirzow, G. C. Kaneski, C. R. Heiss, J. D. van der Knaap, M. S. Vanier, M. T. Schiffmann, R. Wong, K. TI Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia SO NEUROLOGY LA English DT Article ID SCHWANN-CELLS; ATAXIA AB We identified four unrelated patients (three female, one male) aged 20 to 30 years with hypomyelination, pituitary hypogonadotropic hypogonadism, and hypodontia. Electron microscopy and myelin protein immunohistochemistry of sural nerves showed granular debris-lined clefts, expanded abaxonal space, outpocketing with vacuolar disruption, and loss of normal myelin periodicity. Reduced galactocerebroside, sphingomyelin, and GM1-N-acetylglucosamine and increased esterified cholesterol were found. This is a clinically homogeneous progressive hypomyelinating disorder. The term 4H syndrome is suggested. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vrije Univ Amsterdam, Dept Child Neurol, Med Ctr, NL-1081 HV Amsterdam, Netherlands. Lyon Sud Univ Hosp, Lyon Sud Med Sch, Pierre Benite, France. Lyon Sud Univ Hosp, Fdn Gillet Merieux, Pierre Benite, France. Wilford Hall USAF Med Ctr, Div Neuropathol, San Antonio, TX 78236 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rs4e@nih.gov OI Kaneski, Christine/0000-0003-1453-2502 FU Intramural NIH HHS [Z01 NS002984-09]; NICHD NIH HHS [R01 HD043341]; NINDS NIH HHS [Z01 NS002984] NR 10 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 12 PY 2006 VL 67 IS 11 BP 2066 EP 2069 DI 10.1212/01.wnl.0000247666.28904.35 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000242750900035 PM 17159124 ER PT J AU Hartwell, KA Muir, B Reinhardt, F Carpenter, AE Sgroi, DC Weinberg, RA AF Hartwell, Kimberly A. Muir, Beth Reinhardt, Ferenc Carpenter, Anne E. Sgroi, Dennis C. Weinberg, Robert A. TI The Spemann organizer gene, Goosecoid, promotes tumor metastasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epithelial-mesenchymal transition ID EPITHELIAL-MESENCHYMAL TRANSITIONS; HUMAN-BREAST; NEOPLASTIC TRANSFORMATION; MOLECULAR-MECHANISMS; CANCER PROGRESSION; BETA-CATENIN; XENOPUS; EXPRESSION; TRANSCRIPTION; CARCINOMA AB The process of invasion and metastasis during tumor progression is often reminiscent of cell migration events occurring during embryonic development. We hypothesized that genes controlling cellular changes in the Spemann organizer at gastrulation might be reactivated in tumors. The Goosecoid homeobox transcription factor is a known executer of cell migration from the Spemann organizer. We found that indeed Goosecoid is overexpressed in a majority of human breast tumors. Ectopic expression of Goosecoid in human breast cells generated invasion-associated cellular changes, including an epithelial-mesenchymal transition. TGF-beta signaling, known to promote metastasis, induced Goosecoid expression in human breast cells. Moreover, Goosecoid significantly enhanced the ability of breast cancer cells to form pulmonary metastases in mice. These results demonstrate that Goosecoid promotes tumor cell malignancy and suggest that other conserved organizer genes may function similarly in human cancer. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu RI Carpenter, Anne/C-4982-2008 OI Carpenter, Anne/0000-0003-1555-8261 FU NCI NIH HHS [R01 CA078461, R01 CA 078461]; NIGMS NIH HHS [R01 GM089652] NR 38 TC 108 Z9 115 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 DEC 12 PY 2006 VL 103 IS 50 BP 18969 EP 18974 DI 10.1073/pnas.0608636103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117PC UT WOS:000242884200019 PM 17142318 ER PT J AU Nobori, S Shimizu, A Okumi, M Samelson-Jones, E Griesemer, A Hiralkata, A Sachs, DH Yamada, K AF Nobori, Shuji Shimizu, Akira Okumi, Masayoshi Samelson-Jones, Emma Griesemer, Adam Hiralkata, Atsushi Sachs, David H. Yamada, Kazuhiko TI Thymic rejuvenation and the induction of tolerance by adult thymic grafts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; miniature swine; thymus ID MISMATCHED RENAL-ALLOGRAFTS; BONE-MARROW CHIMERAS; ACTIVATED T-CELLS; MINIATURE SWINE; CLASS-I; TRANSPLANTATION TOLERANCE; LOBE TRANSPLANTATION; STABLE INDUCTION; DONOR ANTIGEN; AGE AB The thymus, the site of origin of T cell immunity, shapes the repertoire of T cell reactivity through positive selection of developing T cells and prevents autoimmunity through negative selection of autoreactive T cells. Previous studies have demonstrated an important role for the thymus not only in central deletional tolerance, but also in the induction of peripheral tolerance by vascularized renal allografts in juvenile miniature swine recipients. The same protocol did not induce tolerance in thymectomized recipients nor in recipients beyond the age of thymic involution. We subsequently reported that vascularized thymic lobe grafts from juvenile donors were capable of inducing tolerance in thymectomized juvenile hosts. However, the important question remained whether aged, involuted thymus could also induce tolerance if transplanted into thymectomized hosts, which, if true, would imply that thymic involution is not an intrinsic property of thymic tissue but is rather determined by host factors extrinsic to the thymus. We report here that aged, involuted thymus transplanted as a vascularized graft into juvenile recipients leads to rejuvenation of both thymic structure and function, suggesting that factors extrinsic to the thymus are capable of restoring juvenile thymic function to aged recipients. We show furthermore that rejuvenated aged thymus has the ability to induce transplant tolerance across class I MHC barriers. These findings indicate that it may be possible to manipulate thymic function in adults to induce transplantation tolerance after the age of thymic involution. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIAID NIH HHS [5P01 AI 45897, 5P01 AI 39755] NR 33 TC 28 Z9 30 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 12 PY 2006 VL 103 IS 50 BP 19081 EP 19086 DI 10.1073/pnas.0605159103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117PC UT WOS:000242884200038 PM 17148614 ER PT J AU Zamborlini, A Usami, Y Radoshitzky, SR Popova, E Palu, G Gottlinger, H AF Zamborlini, Alessia Usami, Yoshiko Radoshitzky, Sheli R. Popova, Elena Palu, Giorgio Gottlinger, Heinrich TI Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMSH; endosomal sorting machinery; viral budding ID IMMUNODEFICIENCY-VIRUS TYPE-1; N-TERMINAL DOMAIN; T-SNARE SSO1P; MULTIVESICULAR-BODY; DEUBIQUITINATING ENZYME; UBIQUITIN ISOPEPTIDASE; PARTICLE-PRODUCTION; BINDING PARTNER; PROTEIN; COMPLEX AB The endosomal sorting complex ESCRT-III, which is formed by the structurally related CHMP proteins, is engaged by HIV-1 to promote viral budding. Here we show that progressive truncations into the C-terminal acidic domains of CHMP proteins trigger an increasingly robust anti-HIV budding activity. Together with biochemical evidence for specific intramolecular interactions between the basic and acidic halves of CHMP3 and CHMP4B, these results suggest that the acidic domains are autoinhibitory. The acidic half of CHMP3 also interacts with the endosome-associated ubiquitin isopeptidase AMSH, and the coexpression of AMSH or its CHMP3-binding domain converts wild-type CHMP3 into a potent inhibitor of HIV-1 release. Point mutations in CHMP3 that prevent binding to AMSH abrogate this effect, suggesting that binding to AMSH relieves the autoinhibition of CHMP3. Collectively, our results indicate that CHMP proteins are regulated through an autoinhibitory switch mechanism that allows tight control of ESCRT-III assembly. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Program Mol Med, Worcester, MA 01605 USA. Univ Padua, Sch Med, Dept Histol Microbiol & Med Biotechnol, I-35122 Padua, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gottlinger, H (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Program Mol Med, Worcester, MA 01605 USA. EM heinrich.gottlinger@umassmed.edu FU NIAID NIH HHS [AI 29873, AI 50466, R01 AI029873, R01 AI050466, R37 AI029873] NR 45 TC 113 Z9 119 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 DEC 12 PY 2006 VL 103 IS 50 BP 19140 EP 19145 DI 10.1073/pnas.0603788103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117PC UT WOS:000242884200048 PM 17146056 ER PT J AU Jia, XQ Yeo, Y Clifton, RJ Jiao, T Kohane, DS Kobler, JB Zeitels, SM Langer, R AF Jia, Xinqiao Yeo, Yoon Clifton, Rodney J. Jiao, Tong Kohane, Daniel S. Kobler, James B. Zeitels, Steven M. Langer, Robert TI Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration SO BIOMACROMOLECULES LA English DT Article ID VISCOELASTIC SHEAR PROPERTIES; INJECTION AUGMENTATION; LAMINA PROPRIA; HYDROGELS; MICROSPHERES; BIOMECHANICS; DELIVERY; GLYCOPROTEIN; METHODOLOGY; MUCOSA AB Vocal fold scarring disrupts the viscoelastic properties of the lamina propria that are critical for normal phonation. There is a clinical need for the development of advanced biomaterials that approximate the mechanical properties of the lamina propria for in vivo vocal fold regeneration. We have developed hyaluronic acid (HA)-based microgels and cross-linked microgel networks with tunable degradation and mechanical properties. HA microgels were prepared by cross-linking HA derivatives carrying hydrazide (HAADH) and aldehyde (HAALD) functionalities within the inverse emulsion droplets. Alternatively, poly(ethylene glycol) dialdehyde ( PEGDiALD) was employed in place of HAALD. Microgels based on HAADH/HAALD are more resistant to enzymatic degradation than those generated from HAADH/PEGDiALD. In vitro cytotoxicity studies using vocal fold fibroblasts indicate that microgels synthesized from HAADH/HAALD are essentially nontoxic, whereas microgels derived from HAADH/PEGDiALD exhibit certain adverse effects on the cultured cells at high concentration (>= 2 mg/mL). These microgels exhibit residual functional groups that can be used as reactive handles for covalent conjugation of therapeutic molecules. The presence of residual functional groups also allows for subsequent cross-linking of the microgels with other reactive polymers, giving rise to doubly cross-linked networks (DXNs) with tunable viscoelasticity. Mechanical measurements using a torsional wave apparatus indicate that HA-based DXNs exhibit elastic moduli that are similar to those of vocal fold lamina propria at frequencies close to the range of human phonation. These HA-based microgel systems are promising candidates for the treatment of vocal fold scarring, not just as biocompatible filler materials, but as smart entities that can repair focal defects, smooth the vocal fold margin, and potentially soften and dissolve scar tissue. C1 Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Brown Univ, Div Engn, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Jia, XQ (reprint author), Univ Delaware, Dept Mat Sci & Engn, 201 DuPont Hall, Newark, DE 19716 USA. EM xjia@udel.edu NR 44 TC 135 Z9 137 U1 3 U2 60 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD DEC 11 PY 2006 VL 7 IS 12 BP 3336 EP 3344 DI 10.1021/bm0604956 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 114YM UT WOS:000242701600009 PM 17154461 ER PT J AU Kumar, ATN Raymond, SB Boverman, G Boas, DA Bacskai, BJ AF Kumar, Anand T. N. Raymond, Scott B. Boverman, Gregory Boas, David A. Bacskai, Brian J. TI Time resolved fluorescence tomography of turbid media based on lifetime contrast SO OPTICS EXPRESS LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; SINGULAR-VALUE ANALYSIS; EARLY-ARRIVING PHOTONS; MOLECULAR TOMOGRAPHY; IMAGING MICROSCOPY; TISSUE; OPTIMIZATION; RESOLUTION; SYSTEM; PROBE AB A general linear model for time domain (TD) fluorescence tomography is presented that allows a lifetime-based analysis of the entire temporal fluorescence response from a turbid medium. Simulations are used to show that TD fluorescence tomography is optimally performed using two complementary approaches: A direct TD analysis of a few time points near the peak of the temporal response, which provides superior resolution; and an asymptotic multi-exponential analysis based tomography of the decay portion of the temporal response, which provides accurate localization of yield distributions for various lifetime components present in the imaging medium. These results indicate the potential of TD technology for biomedical imaging with lifetime sensitive targeted probes, and provide useful guidelines for an optimal approach to fluorescence tomography with TD data. (c) 2006 Optical Society of America C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075]; NIA NIH HHS [R01 AG026240, R01 AG026240-03]; NIBIB NIH HHS [R01 EB000768] NR 30 TC 68 Z9 68 U1 1 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 11 PY 2006 VL 14 IS 25 BP 12255 EP 12270 DI 10.1364/OE.14.012255 PG 16 WC Optics SC Optics GA 118TJ UT WOS:000242964300040 PM 19529654 ER PT J AU Boucrot, E Saffarian, S Massol, R Kirchhausen, T Ehrlich, M AF Boucrot, Emmanuel Saffarian, Saveez Massol, Ramiro Kirchhausen, Tomas Ehrlich, Marcelo TI Role of lipids and actin in the formation of clathrin-coated pits SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE endocytosis; clathrin; 1-butanol; live-cell imaging; actin; phosphoinositides ID RECEPTOR-MEDIATED ENDOCYTOSIS; PHOSPHOLIPASE-D ACTIVITY; PLASMA-MEMBRANE; MAMMALIAN-CELLS; LIVING CELLS; RECRUITMENT; CYTOSKELETON; DYNAMICS; INVAGINATION; ACTIVATION AB Assembly of clathrin-coated pits and their maturation into coated vesicles requires coordinated interactions between specific lipids and several structural and regulatory proteins. In the presence of primary alcohols, phospholipase D generates phosphatidylalcohols instead of PA, reducing stimulation of phosphatidyl inositol 5-kinase (PI5K) and hence decreasing formation of phosphoinositide-4,5-biphosphate (PIP2). Using live-cell imaging, we have shown that acute treatment of cells with 1-butanol or other small primary alcohols induces rapid disassembly of coated pits at the plasma membrane and blocks appearance of new ones. Addition of exogenous PIP2 reverses this effect. Coated pits and vesicles reappear synchronously upon removal of 1-butanol; we have used this synchrony to assess the role of actin in coated vesicle assembly. Prolonged inhibition of actin polymerization by latrunculin A or cytochalasin D reduced by similar to 50% the frequency of coated pit formation without affecting maturation into coated vesicles. As in control cells, removal of 1-butanol in the continued presence of an actin depolymerizer led to synchronous appearance of new pits, which matured normally. Thus, remodeling of the actin cytoskeleton is not essential for clathrin-coated vesicle assembly but may indirectly affect the nucleation of clathrin-coated pits. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. RP Ehrlich, M (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM marceloe@tauex.tau.ac.il FU NIGMS NIH HHS [GM 075252, GM62566, R01 GM075252, P01 GM062566] NR 43 TC 83 Z9 83 U1 0 U2 6 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 10 PY 2006 VL 312 IS 20 BP 4036 EP 4048 DI 10.1016/j.yexcr.2006.09.025 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 116XW UT WOS:000242838100007 PM 17097636 ER PT J AU Iliopoulos, O AF Iliopoulos, Othon TI Molecular biology of renal cell cancer and the identification of therapeutic targets SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID LINDAU TUMOR-SUPPRESSOR; HEPATOCYTE GROWTH-FACTOR; HOGG-DUBE-SYNDROME; HYPOXIA-INDUCIBLE FACTOR; HUMAN MET PROTOONCOGENE; RNA-POLYMERASE-II; FUMARATE-HYDRATASE; UTERINE LEIOMYOMAS; INVASIVE GROWTH; HIF-ALPHA AB Renal cell cancer (RCC) is a heterogeneous disease consisting of different histologic types. Major advances have been accomplished during the last 15 years in our understanding of the genetic events that initiate RCC. These advances were greatly facilitated by meticulous clinical description and registration of patients with familial predisposition to RCC. The cloning of the susceptibility genes that underline familial predisposition to RCC has offered entry points into the signaling pathways that are also deregulated in sporadic RCC. Biochemical studies of these signaling pathways and target validation experiments have already culminated in the discovery and clinical application of small molecules with promising activity in RCC. In this article, we highlight the molecular genetic features of RCC that are more directly related to identification and validation of promising targets for molecular therapy. C1 Massachusetts Gen Hosp, Ctr Canc, Dana Farber Harvard Canc Ctr Renal Canc Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Genet Program, Boston, MA 02114 USA. RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dana Farber Harvard Canc Ctr Renal Canc Program, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM oiliopoulos@partners.org NR 109 TC 31 Z9 32 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 DEC 10 PY 2006 VL 24 IS 35 BP 5593 EP 5600 DI 10.1200/JCO.2006.08.8948 PG 8 WC Oncology SC Oncology GA 118AL UT WOS:000242914300014 PM 17158545 ER PT J AU Lin, B Masland, RH AF Bin Lin Masland, Richard H. TI Populations of wide-field amacrine cells in the mouse retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE retina; mouse; wide-field; axonless; axon-bearing; amacrine cells ID MACAQUE MONKEY RETINA; RABBIT RETINA; ACCUMULATING NEURONS; GANGLION-CELLS; CAT RETINA; SALAMANDER RETINA; RECEPTIVE-FIELDS; PA1 CELLS; MORPHOLOGY; PHYSIOLOGY AB We surveyed wide-field amacrine cells in the mouse, using a large series of retinas from a transgenic strain that expresses the green fluorescent protein (GFP) in isolated retinal cells. Wide-field cells were present in surprising diversity and number. They formed groups that could be defined by arbor depth, arbor size, and soma size. By conventional criteria, these populations of cells make up 11 amacrine cell "types." Five additional types have been reported by others in the mouse. Roughly two-thirds of the wide-field amacrine cells are axon-bearing cells, which have separate dendritic and axonal arbors. The axonal arbor of a single cell sometimes covers the majority of the retinal surface. The axon-bearing cells appear to be centrifugally conducting neurons similar to those studied electrophysiologically in some other species. Although they are classified as independent morphological types, it seems likely that their physiological functions represent variations on a single organizational plan. These cells are present at every level of the inner plexiform layer, which suggests that they affect most of the mouse retina's final outputs to the brain and, by implication, almost all visual function. 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, Wellman 429, Boston, MA 02114 USA. EM masland@helix.mgh.harvard.edu RI Lin, Bin/E-9871-2010 NR 44 TC 48 Z9 48 U1 1 U2 3 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 DEC 10 PY 2006 VL 499 IS 5 BP 797 EP 809 DI 10.1002/cne.21126 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 104EC UT WOS:000241938200007 PM 17048228 ER PT J AU Heine, RJ Diamant, M Mbanya, JC Nathan, DM AF Heine, R. J. Diamant, M. Mbanya, J-C Nathan, D. M. TI Management of hyperglycaemia in type 2 diabetes SO BRITISH MEDICAL JOURNAL LA English DT Review ID BLOOD-GLUCOSE CONTROL; MICROVASCULAR COMPLICATIONS; INSULIN GLARGINE; CONTROLLED-TRIAL; GLYCEMIC CONTROL; THERAPY; METFORMIN; SULFONYLUREAS; MELLITUS; ASSOCIATION C1 VU Univ Med Ctr Amsterdam, Dept Endocrinol, Ctr Diabet, Amsterdam, Netherlands. Univ Yaounde, Dept Internal Med & Specialties, Diabet & Endocrine Unit, Yaounde, Cameroon. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Diabet, Boston, MA USA. RP Heine, RJ (reprint author), VU Univ Med Ctr Amsterdam, Dept Endocrinol, Ctr Diabet, De Boelelaan 1117, Amsterdam, Netherlands. EM RJ.Heine@vumc.nl NR 30 TC 40 Z9 42 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD DEC 9 PY 2006 VL 333 IS 7580 BP 1200 EP 1204A DI 10.1136/bmj.39022.462546.80 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 119JW UT WOS:000243009600016 PM 17158386 ER PT J AU Chen, CC Motegi, A Hasegawa, Y Myung, K Kolodner, R D'Andrea, A AF Chen, Clark C. Motegi, Akira Hasegawa, Yuko Myung, Kyungjae Kolodner, Richard D'Andrea, Alan TI Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164SUMOylation and ubiquitination SO DNA REPAIR LA English DT Article DE ionizing radiation; translesion synthesis; SUMOylation; ubiquitination; mutagenesis; PCNA; DNA repair; homologous recombination; non-homologous end joining; nuclotide excision repair; REV3; REV7; REV1; RAD30; polymerase zeta; polymerase eta; deoxycytidyl transferase ID CELL NUCLEAR ANTIGEN; GAMMA-RAY MUTAGENESIS; STRAND-BREAK REPAIR; NUCLEOTIDE EXCISION-REPAIR; ARRESTED YEAST-CELLS; DNA-POLYMERASE-ZETA; FRAMESHIFT MUTATIONS; CHROMOSOMAL REARRANGEMENTS; SEQUENCE-ANALYSIS; MISMATCH REPAIR AB Ionizing radiation-induced mutagenesis (IR-IM) underlies a basis for radiation associated carcinogenesis as well as resistance to radiation therapy. This process was examined in Saccharomyces cerevisiae using an array of isogenic DNA repair deficient mutants. Mutations inactivating homologous recombination (rad51, 52, 54) or nucleotide excision repair (rad1, radio, rad4) caused elevated IR-IM whereas inactivation of TransLesion Synthesis (TLS: rad6) caused severely defective IR-IM. Of the mutations inactivating TLS polymerases, rev3 and rev1 caused equally severe defects in IR-IM whereas rad30 did not significantly affect the process. The effects of the rev3, rev1, and rad6 mutations on IR-IM were epistatic, suggesting the requirement of both polymerase zeta and Rev1p in IR-IM related TLS. Although PCNA K164 SUMOylation/ubiquitination is a proposed prerequisite for TLS, the IR-IM defect of a rev3 or a rad6 mutant was worse than and epistatic to the pol30K164R mutant, a mutant in which the PCNA had been mutated to abolish such modifications. These results suggested that IR-IM related TLS occurs in the absence of PCNA K164 modification. Further analysis of a mutant simultaneously defective in SUMOylation and mono-ubiquitination (rad18 siz1) revealed that these modifications redundantly affected TLS as well as NHEJ. A genetic model based on these observations is proposed. (c) 2006 Elsevier B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP D'Andrea, A (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Mayer 642, Boston, MA 02114 USA. EM alan-dandrea@dfci.harvard.edu RI Chen, Clark/C-8714-2013 OI Chen, Clark/0000-0001-6258-9277 FU Intramural NIH HHS; NHLBI NIH HHS [R01HL52725]; NIDDK NIH HHS [R01DK43889]; NIGMS NIH HHS [R01GM26017] NR 72 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 9 PY 2006 VL 5 IS 12 BP 1475 EP 1488 DI 10.1016/j.dnarep.2006.07.007 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 114KT UT WOS:000242665800007 PM 16990054 ER PT J AU Scremin, OU Li, MGG Roch, M Booth, R Jenden, DJ AF Scremin, Oscar U. Li, Mingen Grace Roch, Margareth Booth, Ruth Jenden, Donald J. TI Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury SO BRAIN RESEARCH LA English DT Article DE brain injury; acetylcholine; choline ID MAGNETIC-RESONANCE SPECTROSCOPY; TIME-DEPENDENT CHANGES; CEREBRAL-CORTEX; BLOOD-FLOW; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; MEMORY DEFICITS; WORKING MEMORY; RAT-BRAIN; ISCHEMIA AB We assessed acetylcholine (ACh) and choline (Ch) dynamics 2.5 h, 1, 4 and 14 days after cerebral cortex impact injury or craniotomy only in adult male Sprague-Dawley rats. Cortical endogenous ACh (D0ACh), endogenous free Ch (D0Ch), deuterium-labeled Ch (D4Ch), and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry after intravenous injection of D4Ch followed in 1 min by microwave fixation of the brain. D0Ch increased in and around the impact up to 700% of control within 1 day after trauma. Smaller D0Ch increases were found in the cortex contralateral to the impact and in both hemispheres after craniotomy only. D4Ch contents increased to 200% in the impact and surrounding regions 4-14 days post-trauma, with lower increases 2.5 h post-trauma. DOACh decreased at all times post-trauma in the impact center, and initially in the periphery and adjacent regions with a recovery at 14 days. Similar DOACh decreases, although of lesser extent and magnitude were present in the craniotomy only group. D4ACh showed a peak at one day post-trauma in all regions studied in the impact and craniotomy groups. In conclusion, D0Ch tissue level was an early marker of trauma, while 14 days after trauma Ch uptake from blood was enhanced in and around the traumatized cortex. Craniotomy by itself induced a generalized increase in ACh turnover 1 day after this minimal trauma. Choline acetyltransferase activity was reduced in the impact center region but not affected in the adjacent and contralateral regions or by cramotomy. (c) 2006 Elsevier B.V. All rights reserved. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Scremin, OU (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Bldg 115,Room 319, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu NR 53 TC 16 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 8 PY 2006 VL 1124 BP 155 EP 166 DI 10.1016/j.brainres.2006.09.062 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 119MQ UT WOS:000243016800018 PM 17084821 ER PT J AU Li, Q Montalbetti, N Wu, YL Ramos, A Raychowdhury, MK Chen, XZ Cantiello, HF AF Li, Qiang Montalbetti, Nicolas Wu, Yuliang Ramos, Arnolt Raychowdhury, Malay K. Chen, Xing-Zhen Cantiello, Horacio F. TI Polycystin-2 cation channel function is under the control of microtubular structures in primary cilia of renal epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIGHT AXIS DETERMINATION; LEFT-RIGHT ASYMMETRY; KIDNEY-DISEASE; PKD2 INTERACTS; TROPONIN-I; PROTEIN; MICE; CYTOSKELETON; GENE; DEPOLYMERIZATION AB Mutations in the gene encoding polycystin-2 (PC2) result in autosomal dominant polycystic kidney disease and defects in left-right asymmetry during embryogenesis. PC2 is a TRP-type Ca2+-permeable non-selective cation channel, which is expressed in kidney and other organs. PC2 is present and functional in microtubule-containing primary cilia of renal epithelial cells. However, no information is yet available as to whether PC2 interacts with microtubules. Here, we assessed the role of microtubular dynamics in regulating PC2 channel function in primary cilia. Isolated ciliary membranes from LLC-PK1 epithelial cells were reconstituted in a lipid bilayer system. The acute addition of the microtubular disrupter colchicine ( 15 mu M) rapidly abolished, whereas the addition of the microtubular stabilizer paclitaxel (taxol, 15 mu M) increased ciliary PC2 channel activity. The further addition of alpha-tubulin plus GTP also stimulated PC2 channel activity in ciliary membranes. However, alpha-tubulin and GTP had no effect on in vitro translated PC2. Using the yeast two-hybrid assay, we found that PC2 interacts with the microtubule-dependent motor kinesin-2 subunit KIF3A, a protein involved in polycystic kidney disease. The interaction occurred through the carboxyl termini domain of both proteins, which was further confirmed by in vitro glutathione S-transferase pull-down and dot blot overlay assays. Co-immunoprecipitation experiments showed that PC2 and KIF3A are in the same complex in native HEK293, Madin-Darby canine kidney cells (MDCK), and LLC-PK1 cells. Immunofluorescent staining also showed substantial PC2 and KIF3A co-localization in primary cilia of renal epithelial cells. The data indicate that microtubular organization regulates PC2 function, which may explain, among others, the regulatory role of PC2 in the sensory function of primary cilia. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2H7, Canada. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisioquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. RP Chen, XZ (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, 149 13th St, Charlestown, MA 02129 USA. EM xzchen@ualberta.ca OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 38 TC 47 Z9 49 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 2006 VL 281 IS 49 BP 37566 EP 37575 DI 10.1074/jbc.M603643200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100033 PM 16950792 ER PT J AU Sumathipala, R Xu, CS Seago, J Mould, AP Humphries, MJ Craig, SE Patel, Y Wijelath, ES Sobel, M Rahman, S AF Sumathipala, Rushika Xu, Cunshuan Seago, Julian Mould, A. Paul Humphries, Martin J. Craig, Sue E. Patel, Yatin Wijelath, Errol S. Sobel, Michael Rahman, Salman TI The "linker" region (amino acids 38-47) of the disintegrin elegantin is a novel inhibitory domain of integrin alpha(5)beta(1)-dependent cell adhesion on fibronectin - Evidence for the negative regulation of fibronectin synergy site biological activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; SNAKE-VENOM PROTEINS; RGD SEQUENCE MOTIFS; HETERODIMERIC DISINTEGRIN; DIRECTED MUTAGENESIS; LIGAND RECOGNITION; 10TH-FIII DOMAINS; BINDING-SITES; COMPLEX; FIBRINOGEN AB Disintegrins are a family of potent inhibitors of cell-cell and cell-matrix adhesion. In this study we have identified a region of the disintegrin elegantin, termed the "linker domain" (amino acids 38-47), with inhibitory activity toward alpha(5)beta(1)-mediated cell adhesion on fibronectin (Fn). Using a chimeric structure-function approach in which sequences of the functionally distinct disintegrin kistrin were introduced into the elegantin template at targeted sites, a loss of inhibitory function toward alpha(5)beta(1)-mediated adhesion on Fn was observed when the elegantin linker domain was substituted. Subsequent analysis comparing the inhibitory efficacies of the panel of elegantin-kistrin chimeras toward CHO alpha(5) cell adhesion on recombinant Fn III6-10 fragments showed that the loss of inhibitory activity associated with the disruption of the elegantin linker domain was dependent upon the presence of a functional Fn III9 synergy site within the Fn III6-10 substrate. This suggested that the elegantin linker domain inhibits primarily the activity of the Fn synergy domain in promoting alpha(5)beta(1) integrin-mediated cell adhesion. Construction of a cyclic peptide corresponding to the entire region of the elegantin linker domain showed that this domain has intrinsic alpha(5)beta(1) inhibitory activity comparable with the activity of the RGDS peptide. These data demonstrate a novel biological function for a disintegrin domain that antagonizes integrin-mediated cell adhesion. C1 Kings Coll London, Sch Med, St Thomas Hosp, Div Cardiovasc Med,Lab Thrombosis & Vasc Remodell, London SE1 7EH, England. Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. Univ Washington, Sch Med, Div Vasc Surg, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Rahman, S (reprint author), Kings Coll London, Sch Med, St Thomas Hosp, Div Cardiovasc Med,Lab Thrombosis & Vasc Remodell, London SE1 7EH, England. EM salman.rahman@kcl.ac.uk OI Humphries, Martin/0000-0002-4331-6967 NR 37 TC 2 Z9 2 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 DEC 8 PY 2006 VL 281 IS 49 BP 37686 EP 37696 DI 10.1074/jbc.M603943200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100046 PM 16982624 ER PT J AU Eeckhoute, J Briche, I Kurowska, M Formstecher, P Laine, B AF Eeckhoute, J. Briche, I. Kurowska, M. Formstecher, P. Laine, B. TI Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HNF4; islet-1; endocrine pancreas; transcriptional synergy; isoforms ID HEPATOCYTE NUCLEAR FACTOR-4; HEPATIC GENE-EXPRESSION; OVALBUMIN UPSTREAM PROMOTER; FACTOR 4-ALPHA; BETA-CELLS; PROTEIN INTERACTIONS; INSULIN-SECRETION; COACTIVATOR; ACTIVATION; HNF4-ALPHA AB The orphan nuclear receptor HNF4 alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. HNF4 alpha activates numerous genes and mutations in its gene are associated with maturity onset diabetes of the young. Cofactors and transcription factors that interact with HNF4 alpha are crucial to modulate its transcriptional activity, since the latter is not regulated by conventional ligands. These transcriptional partners interact mainly through the HNF4 alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. Here, we showed that Isl1 could enhance the HNF4 alpha-mediated activation of transcription of the HNF1 alpha, PPAR alpha and insulin I promoters. Isl1 interacted with the HNF4 alpha AF-2 but also required the HNF4a carboxy-terminal F domain for optimal interaction and transcriptional synergy. More specifically, we found that naturally occurring HNF4 alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4 alpha F domain. HNF4 alpha interacted with both the homeodomain and the first LIM domain of Isl1. We found that the transcriptional synergy between HNF4 alpha and Isl1 involved an increase in HNF4 alpha loading on promoter. The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4 alpha and Isl1 than on the human HNF1 alpha promoter lacking an Isl1 binding site. Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1 alpha promoter activity. (c) 2006 Elsevier Ltd. All rights reserved. C1 INSERM, U459, F-59045 Lille, France. Univ Lille 2, Fac Med H Warembourg, Lille, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Eeckhoute, J (reprint author), INSERM, U459, F-59045 Lille, France. EM jerome_eeckhoute@dfci.harvard.edu OI Eeckhoute, Jerome/0000-0002-7222-9264 NR 61 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 8 PY 2006 VL 364 IS 4 BP 567 EP 581 DI 10.1016/j.jmb.2006.07.096 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NZ UT WOS:000242674200003 PM 17022998 ER PT J AU Druker, BJ Guilhot, F O'Brien, SG Gathmann, I Kantarjian, H Gattermann, N Deininger, MWN Silver, RT Goldman, JM Stone, RM Cervantes, F Hochhaus, A Powell, BL Gabrilove, JL Rousselot, P Reiffers, J Cornelissen, JJ Hughes, T Agis, H Fischer, T Verhoef, G Shepherd, J Saglio, G Gratwohl, A Nielsen, JL Radich, JP Simonsson, B Taylor, K Baccarani, M So, C Letvak, L Larson, RA AF Druker, Brian J. Guilhot, Francois O'Brien, Stephen G. Gathmann, Insa Kantarjian, Hagop Gattermann, Norbert Deininger, Michael W. N. Silver, Richard T. Goldman, John M. Stone, Richard M. Cervantes, Francisco Hochhaus, Andreas Powell, Bayard L. Gabrilove, Janice L. Rousselot, Philippe Reiffers, Josy Cornelissen, Jan J. Hughes, Timothy Agis, Hermine Fischer, Thomas Verhoef, Gregor Shepherd, John Saglio, Giuseppe Gratwohl, Alois Nielsen, Johan L. Radich, Jerald P. Simonsson, Bengt Taylor, Kerry Baccarani, Michele So, Charlene Letvak, Laurie Larson, Richard A. CA IRIS Investigators TI Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; COMPLETE CYTOGENETIC REMISSION; CHRONIC GRANULOCYTIC-LEUKEMIA; ALPHA PLUS CYTARABINE; PHILADELPHIA-CHROMOSOME; INTERFERON-ALPHA; CHRONIC-PHASE; BLAST CRISIS; CELLS AB BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97239 USA. CHU, Poitiers, France. Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. Novartis, Basel, Switzerland. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Univ Leipzig, D-7010 Leipzig, Germany. Weill Cornell Med Ctr, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Clin Barcelona, Barcelona, Spain. Univ Heidelberg, D-6800 Mannheim, Germany. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Mt Sinai Sch Med, New York, NY USA. Hop St Louis, Paris, France. CHU Bordeaux, Pessac, France. Erasmus MC, Rotterdam, Netherlands. Royal Adelaide Hosp, Adelaide, SA 5000, Australia. Univ Vienna, Innere Med Klin 1, Vienna, Austria. Univ Mainz, D-6500 Mainz, Germany. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Vancover Hosp, Vancouver, BC, Canada. Azienda Osped S Luigi Gonzaga, Orbassano, Italy. Univ Basel Hosp, CH-4031 Basel, Switzerland. Aarhus Kommune Hosp, DK-8000 Aarhus, Denmark. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Akad Sjukhuset, Uppsala, Sweden. Mater Hosp, Brisbane, Qld, Australia. Policlin O Orsola Malpighi, Bologna, Italy. Novarits, Florham Pk, NJ USA. Univ Chicago, Chicago, IL 60637 USA. RP Druker, BJ (reprint author), Oregon Hlth Sci Univ, Inst Canc, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM drukerb@ohsu.edu OI Larson, Richard/0000-0001-9168-3203; Hochhaus, Andreas/0000-0003-0626-0834 NR 36 TC 1847 Z9 1953 U1 15 U2 119 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 2006 VL 355 IS 23 BP 2408 EP 2417 DI 10.1056/NEJMoa062867 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400005 PM 17151364 ER PT J AU Kahn, SE Haffner, SM Heise, MA Herman, WH Holman, RR Jones, NP Kravitz, BG Lachin, JM O'Neill, MC Zinman, B Viberti, G AF Kahn, Steven E. Haffner, Steven M. Heise, Mark A. Herman, William H. Holman, Rury R. Jones, Nigel P. Kravitz, Barbara G. Lachin, John M. O'Neill, M. Colleen Zinman, Bernard Viberti, Giancarlo CA ADOPT Study Grp TI Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; BETA-CELL FUNCTION; RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE CONTROL; INSULIN-RESISTANCE; CONSENSUS STATEMENT; COMPLICATIONS; RISK; SULFONYLUREA; ASSOCIATION AB BACKGROUND: The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known. METHODS: We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter (10.0 mmol per liter), for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin, insulin sensitivity, and (beta)-cell function. RESULTS: Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide (P<0.001 for all comparisons). CONCLUSIONS: The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. GlaxoSmithKline Inc, Harlow, Essex, England. Univ Michigan, Ann Arbor, MI 48109 USA. Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. George Washington Univ, Ctr Biostat, Rockville, MD USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. Univ London, Kings Coll London Sch Med, London WC1E 7HU, England. RP Kahn, SE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 NR 35 TC 1509 Z9 1584 U1 11 U2 66 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 2006 VL 355 IS 23 BP 2427 EP 2443 DI 10.1056/NEJMoa066224 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400007 PM 17145742 ER PT J AU Nathan, DM AF Nathan, David M. TI Thiazolidinediones for initial treatment of type 2 diabetes? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; LONG-TERM COMPLICATIONS; PROGRESSION; MELLITUS; THERAPY; GLUCOSE C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NR 13 TC 37 Z9 39 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 2006 VL 355 IS 23 BP 2477 EP 2480 DI 10.1056/NEJMe068264 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400013 PM 17145743 ER PT J AU Hirshfeld-Becker, DR Biederman, J Henin, A Faraone, SV Dowd, ST De Petrillo, LA Markowitz, SM Rosenbaum, JF AF Hirshfeld-Becker, Dina R. Biederman, Joseph Henin, Aude Faraone, Stephen V. Dowd, Stephanie T. De Petrillo, Lillian A. Markowitz, Sarah M. Rosenbaum, Jerrold F. TI Psychopathology in the young offspring of parents with bipolar disorder: A controlled pilot study SO PSYCHIATRY RESEARCH LA English DT Article DE mood disorders; behavior disorders; children ID POPULATION-ASCERTAINED SUBSAMPLES; TREATMENT ENHANCEMENT PROGRAM; HIGH-RISK CHILDREN; PANIC DISORDER; BEHAVIORAL-INHIBITION; MENTAL-DISORDERS; FOLLOW-UP; STEP-BD; ANXIETY DISORDERS; AFFECTIVE-ILLNESS AB Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a preexisting sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n = 34), of parents with panic or major depression (n = 179), and of parents with neither mood or anxiety disorder (n = 95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-47077-11] NR 92 TC 45 Z9 46 U1 4 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 7 PY 2006 VL 145 IS 2-3 BP 155 EP 167 DI 10.1016/j.psychres.2005.08.026 PG 13 WC Psychiatry SC Psychiatry GA 118AX UT WOS:000242915500008 PM 17083985 ER PT J AU Mark, GP Kinney, AE Grubb, MC Zhu, XM Finn, DA Mader, SL Berger, SP Bechtholt, AJ AF Mark, Gregory P. Kinney, Anthony E. Grubb, Michele C. Zhu, Xiaoman Finn, Deborah A. Mader, Sarah L. Berger, S. Paul Bechtholt, Anita J. TI Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats SO BRAIN RESEARCH LA English DT Article DE muscarinic receptor; mesolimbic dopamine system; progressive ratio; addiction; cholinergic system; acetylcholine; pirenzepine ID MEDIAL PREFRONTAL CORTEX; MUSCARINIC RECEPTORS; CHOLINERGIC MODULATION; PHOSPHOINOSITIDE BREAKDOWN; NICOTINE ADDICTION; DOPAMINE RELEASE; SEEKING BEHAVIOR; ACETYLCHOLINE; NEURONS; BRAIN AB Mesencephalic dopamine neurons form synapses with acetylcholine (ACh)-containing interneurons in the nucleus accumbens (NAcc). Although their involvement in drug reward has not been systematically investigated, these large aspiny interneurons may serve an important integrative function. We previously found that repeated activation of nicotinic cholinergic receptors enhanced cocaine intake in rats but the role of muscarinic receptors in drug reward is less clear. Here we examined the impact of local changes in muscarinic receptor activation within the NAcc on cocaine and food self-administration in rats trained on a progressive ratio (PR) schedule of reinforcement. Animals were given a minimum of 9 continuous days of drug access before testing in order to establish a stable breaking point (BP) for intravenous cocaine infusions (0.75 mg/kg/infusion). Rats in the food group acquired stable responding on the PR schedule within 7 days. On the test day, rats were bilaterally infused in the NAcc with the muscarinic receptor agonist oxotremorine methiodide (OXO: 0.1, 0.3 or 1 nmol/side), OXO plus the M, selective antagonist pirenzepine (PIRENZ; 0.3 nmol/side) or aCSF 15 min before cocaine or food access. OXO dose dependently reduced BP values for cocaine reinforcement (-17%, -44% [p < 0.05] and -91% [p < 0.0001] for 0.1, 0.3 and 1.0 nmol, respectively) and these reductions dissipated by the following session. Pretreatment with PIRENZ blocked the BP-reducing effect of 0.3 nmol OXO. Notably, OXO (0.1, 0.3 and 1.0 nmol/side) injection in the NAcc did not affect BP for food reward. The results suggest that muscarinic ACh receptors in the caudomedial NAcc may play a role in mediating the behavior reinforcing effects of cocaine. (c) 2006 Elsevier B.V. All rights reserved. C1 Oregon Hlth Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Mark, GP (reprint author), Oregon Hlth Sci Univ, Sch Med, Dept Behav Neurosci, L-470,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM markg@ohsu.edu FU NIDA NIH HHS [R29 DA011203, R01 DA014639, F32 DA005965, DA14639, T32 DA07262, T32 DA007262, DA11203, F32 DA05965] NR 61 TC 19 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 6 PY 2006 VL 1123 BP 51 EP 59 DI 10.1016/j.brainres.2006.09.029 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 120BQ UT WOS:000243058900007 PM 17045970 ER PT J AU Lim, J Lim, G Sung, B Wang, SX Mao, JR AF Lim, Jeongae Lim, Grewo Sung, Backil Wang, Shuxing Mao, Jianren TI Intrathecal midazolam regulates spinal AMPA receptor expression and function after nerve injury in rats SO BRAIN RESEARCH LA English DT Article DE AMPA receptor; GABA receptor; midazolam; nerve injury; neuropathic pain; intrathecal ID DORSAL-HORN NEURONS; NEUROPATHIC PAIN; GLUTAMATE-RECEPTOR; PERIPHERAL MONONEUROPATHY; THERMAL NOCICEPTION; MORPHINE-TOLERANCE; TACTILE ALLODYNIA; DOWN-REGULATION; SCIATIC-NERVE; AMINO-ACIDS AB Spinal gamma-aminobutyric acid (GABA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been implicated in the mechanisms of neuropathic pain after nerve injury; however, how these two receptors interact at the spinal level remains unclear. Here we show that intrathecal midazolam through activation of spinal GABAA receptors attenuated the expression and function of spinal AMPA receptors in rats following peripheral nerve injury. Thermal hyperalgesia and mechanical allodynia induced by chronic constriction nerve injury (CCI) in rats were attenuated by the short-acting benzodiazepine midazolam (20=10 > 5 mu g > vehicle) administered intrathecally once daily for 7 postoperative days. CCI-induced upregulation of AMPA receptors within the spinal cord dorsal horn was also significantly reduced by the intrathecal midazolam (10, 20 mu g) treatment. The inhibitory effects of midazolam (10, 20 mu g) on neuropathic pain behaviors and AMPA receptor expression were prevented by co-administration of midazolam with the GABAA receptor antagonist bicuculline (3 mu g), whereas intrathecal treatment with bicuculline (1 or 3 mu g) alone in naive rats induced the upregulation of spinal AMPA receptor expression and nociceptive responses, indicating a tonic regulatory effect from endogenous GABAergic activity on the AMPA receptor expression and spinal nociceptive processing. These results indicate that modulation of spinal AMPA receptor expression and function by the GABAergic activity may serve as a mechanism contributory to the spinal nociceptive processing. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Res Grp,Dept Anesthesia & Crit Care,Div Pain, Boston, MA 02114 USA. Konkuk Univ, Dept Anesthesia & Pain Med, Seoul, South Korea. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Res Grp,Dept Anesthesia & Crit Care,Div Pain, WACC 324, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA008835, R01 DA08835]; NINDS NIH HHS [R01 NS042661, R01 NS42661, R01 NS042661-04, R01 NS045681, R01 NS045681-03, R01 NS45681] NR 50 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 6 PY 2006 VL 1123 BP 80 EP 88 DI 10.1016/j.brainres.2006.09.059 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 120BQ UT WOS:000243058900010 PM 17049496 ER PT J AU Nakazawa, T Nakazawa, C Matsubara, A Noda, K Hisatomi, T She, HC Michaud, N Hafezi-Moghadam, A Miller, JW Benowitz, LI AF Nakazawa, Toru Nakazawa, Chifuyu Matsubara, Akihisa Noda, Kousuke Hisatomi, Toshio She, Haicheng Michaud, Norman Hafezi-Moghadam, Ali Miller, Joan W. Benowitz, Larry I. TI Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glaucoma; retinal ganglion cell; optic nerve; cytokines; oligodendrocyte; microglia ID ELEVATED INTRAOCULAR-PRESSURE; OPTIC-NERVE HEAD; OPEN-ANGLE GLAUCOMA; PERIVENTRICULAR LEUKOMALACIA; GLIAL-CELLS; IN-VIVO; TNF; RECEPTORS; APOPTOSIS; EXPRESSION C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Neurobiol Program, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Benowitz, LI (reprint author), Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. EM Joan_Miller@meei.harvard.edu; larry.benowitz@childrens.harvard.edu OI Hisatomi, Toshio/0000-0003-2552-9595; Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [EY014104, EY05690]; NIAID NIH HHS [K08AI50775] NR 57 TC 209 Z9 219 U1 1 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 DEC 6 PY 2006 VL 26 IS 49 BP 12633 EP 12641 DI 10.1523/JNEUROSCI.2801-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 113VM UT WOS:000242626100002 PM 17151265 ER PT J AU Mick, E Biederman, J Spencer, T Faraone, SV Sklar, P AF Mick, Eric Biederman, Joseph Spencer, Thomas Faraone, Stephen V. Sklar, Pamela TI Absence of association with DAT1 polymorphism and response to methylphenidate in a sample of adults with ADHD SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dopamine transporter (DAT1); methylphenidate; attention-deficit hyperactivity disorder (ADHD); medication response; adults ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; CHILDREN; TRIAL AB A polymorphism in the dopamine transporter gene (DAT1) has been previously associated with ADHD and methylphenidate has been hypothesized to block the dopamine transporter. The goal of this study was to examine whether a 40-bp variable number of tandem repeats (VNTR) of DAT1. moderate response and adverse effects associated with methylphenidate treatment of adults with ADHD. Subjects were 106 adults with ADHD enrolled in 6-week randomized placebo-controlled parallel design trials of methylphenidate (OROS and immediate release preparations). There was no evidence of an association between DAT1 VNTR and response to methylphenidate (F(2,100) = 0.04, P = 0.9). Similarly, there was no pattern of statistically significant association with DAT1 VNTR and cardiovascular or spontaneously reported adverse effects. We failed to identify an association with DAT1 and the response or tolerability of methylphenidate in adults with ADHD. (c) 2006 Wiley-Liss, Inc. C1 Harvard Univ, Pediat Psychopharmacol Res Unit, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Med Genet, Syracuse, NY USA. RP Mick, E (reprint author), Harvard Univ, Pediat Psychopharmacol Res Unit, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM emick1@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [5R29MH057511, 5K01MH065523, K01 MH065523, R29 MH057511, R29 MH057511-05] NR 20 TC 36 Z9 36 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2006 VL 141B IS 8 BP 890 EP 894 DI 10.1002/ajmg.b.30376 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 112SD UT WOS:000242546400010 PM 16917950 ER PT J AU Hopfer, CJ Young, SE Purcell, S Crowley, TJ Stallings, MC Corley, RP Rhee, SH Smolen, A Krauter, K Hewitt, JK Ehringer, MA AF Hopfer, Christian J. Young, Susan E. Purcell, Shaun Crowley, Thomas J. Stallings, Michael C. Corley, Robin P. Rhee, Soo Hyun Smolen, Andrew Krauter, Ken Hewitt, John K. Ehringer, Marissa A. TI Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE cannabis; adolescence; genetics; CNR1 ID POPULATION-BASED SAMPLE; GENE CNR1; MARIJUANA USE; DRUG-DEPENDENCE; SUBSTANCE USE; MALE TWINS; ABUSE; GENOME; VULNERABILITIES; RECONSTRUCTION AB Cannabis is a major substance of abuse, and the gene encoding for the central cannabinoid receptor (CNR1) is a logical candidate gene for vulnerability toward developing symptoms of cannabis dependence. We studied four single-nucleotide polymorphisms (SNPs) in the CNR1 gene for association with having one or more symptoms of cannabis dependence in 541 adolescent subjects who had all tried cannabis five or more times. Cases (327) were defined as those who had tried marijuana and developed one or more symptoms, and controls (214) as those who had tried marijuana but developed no dependence symptoms. Cannabis dependence symptoms were assessed in these youth when they were 17 or older with the Composite International Diagnostic Interview-Substance Abuse Module. Univariate (single-marker) association tests demonstrated that SNP rs806380, located in intron 2 of the CNR1 gene, was significantly associated with developing one or more cannabis dependence symptoms, with the G allele having a protective effect (P < 0.02). This was consistent with the results of the global haplotype test (P < 0.01). One of the common haplotypes examined (present in 21% of the subjects) was significantly associated with a lower rate of having one or more cannabis dependence symptoms. Our findings provide evidence suggesting that a common CNR1 haplotype is associated with developing fewer cannabis dependence symptoms among adolescents who have experimented with cannabis. (c) 2006 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Dept Mol Cellular & Dev Biol, Boulder, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. RP Hopfer, CJ (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave,Box C-268-35, Denver, CO 80262 USA. EM Christian.Hopfer@uchsc.edu FU NIDA NIH HHS [DA012845, DA015522, DA11015, P60 DA011015, P60 DA011015-10, R01 DA012845] NR 36 TC 40 Z9 43 U1 3 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2006 VL 141B IS 8 BP 895 EP 901 DI 10.1002/ajmg.b.30378 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 112SD UT WOS:000242546400011 PM 16917946 ER PT J AU Paltiel, AD Walensky, RP Schackman, BR Seage, GR Mercincavage, LM Weinstein, MC Freedberg, KA AF Paltiel, A. David Walensky, Rochelle P. Schackman, Bruce R. Seage, George R., III Mercincavage, Lauren M. Weinstein, Milton C. Freedberg, Kenneth A. TI Expanded HIV screening in the United States: Effect on clinical outcomes, HIV transmission, and costs SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PREVENTION PROGRAMS; RISK BEHAVIORS; VIRAL LOAD; INFECTION; DISEASE; TRIALS; ADULTS; HEALTH AB Background: An extensive literature supports expanded HIV screening in the United States. However, the question of whom to test and how frequently remains controversial. Objective: To inform the design of HIV screening programs by identifying combinations of screening frequency and HIV prevalence and incidence at which screening is cost-effective. Design: Cost-effectiveness analysis linking simulation models of HIV screening to published reports of HIV transmission risk, with and without antiretroviral therapy. Data Sources: Published randomized trials, observational cohorts, national cost and service utilization surveys, the Red Book, and previous modeling results. Target Population: U.S. communities with low to moderate HIV prevalence (0.05% to 1.0%) and annual incidence (0.0084% to 0.12%). Time Horizon: Lifetime. Perspective: Societal. Interventions: One-time and increasingly frequent voluntary HIV screening of all adults using a same-day rapid test. Outcome Measures: HIV infections detected, secondary transmissions averted, quality-adjusted survival, lifetime medical costs, and societal cost-effectiveness, reported in discounted 2004 dollars per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Under moderately favorable assumptions regarding the effect of HIV patient care on secondary transmission, routine HIV screening in a population with HIV prevalence of 1.0% and annual incidence of 0.12% had incremental cost-effectiveness ratios of $30800/QALY (one-time screening), $32300/QALY (screening every 5 years), and $55500/QALY (screening every 3 years). In settings with HIV prevalence of 0.10% and annual incidence of 0.014%, one-time screening produced cost-effectiveness ratios of $60700/QALY. Results of Sensitivity Analysis: The cost-effectiveness of screening policies varied within a narrow range as assumptions about the effect of screening on secondary transmission varied from favorable to unfavorable. Assuming moderately favorable effects of antiretroviral therapy on transmission, cost-effectiveness ratios remained below $50000/QALY in settings with HIV prevalence as low as 0.20% for routine HIV screening on a one-time basis and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years. Limitations: This analysis does not address the difficulty of determining the prevalence and incidence of undetected HIV infection in a given patient population. Conclusions: Routine, rapid HIV testing is recommended for all adults except in settings where there is evidence that the prevalence of undiagnosed HIV infection is below 0.2%. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP Paltiel, AD (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM david.paltiel@yale.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K24 AI062476, R01AI42006, R01 AI042006, P30AI42851, K24AI062476, K23AI01794, K23 AI001794, P30 AI042851]; NIDA NIH HHS [K01DA0717179, R01DA015612, R01 DA015612, K01 DA017179]; NIMH NIH HHS [R01 MH065869, R01MH65869]; PHS HHS [S1396-20/21] NR 72 TC 138 Z9 142 U1 9 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 5 PY 2006 VL 145 IS 11 BP 797 EP 806 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 114PE UT WOS:000242677300001 PM 17146064 ER PT J AU d'Avila, A Rabischoffsky, A Saad, E AF d'Avila, Andre Rabischoffsky, Arnaldo Saad, Eduardo TI Reverse Bernheim phenomenon as a cause of exercise-induced syncope SO CIRCULATION LA English DT Editorial Material C1 Hosp Pro Cardiaco, Rio De Janeiro, Brazil. RP d'Avila, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Druit St,GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 NR 2 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 5 PY 2006 VL 114 IS 23 BP E618 EP E620 DI 10.1161/CIRCULATIONAHA.106.621144 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XT UT WOS:000243477500018 PM 17145996 ER PT J AU Everett, BM Kurth, T Buring, JE Ridker, PM AF Everett, Brendan M. Kurth, Tobias Buring, Julie E. Ridker, Paul M. TI The relative strength of C-reactive protein and lipid levels as determinants of ischemic stroke compared with coronary heart disease in women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; MIDDLE-AGED MEN; POSTMENOPAUSAL HORMONE-THERAPY; APOLIPOPROTEIN-A-I; RISK-FACTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; SERUM-CHOLESTEROL; PLASMA-CONCENTRATION AB OBJECTIVES We sought to determine the relative strength of high-sensitivity C-reactive protein (hs-CRP) and lipid levels as markers for future ischemic stroke compared with coronary heart disease (CHD) in women. BACKGROUND Although hs-CRP and lipid levels are established risk determinants for vascular disease, the relative strength of these biomarkers for ischemic stroke compared with CHD is uncertain. METHODS Among 15,632 initially healthy women who were followed for a 10-year period, we compared hs-CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDLC), apolipoproteins A-I and B100, and lipid ratios as determinants of ischemic stroke compared with CHD. RESULTS After adjustment for age, smoking status, blood pressure, diabetes, and obesity, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the third versus the first tertile for future ischemic stroke compared with CHD were, respectively, 1.91 (95% CI 1.13 to 3.21) and 2.26 (95% CI 1.64 to 3.12) for TC, 1.29 (95% CI 0.83 to 2.02) and 2.09 (95% CI 1.53 to 2.85) for LDL-C, 0.57 (95% CI 0.36 to 0.92) and 0.38 (95% CI 0.27 to 0.52) for HDL-C, 1.72 (95% CI 1.03 to 2.86) and 2.93 (95% CI 2.04 to 4.21) for non-HDL-C, and 2.76 (95% CI 1.51 to 5.05) and 1.66 (95% CI 1.17 to 2.34) for hs-CRP. Of the lipid ratios, that of TC to HDL-C had the largest HR for both future ischemic stroke and CHD (HR 1.95 [95% CI 1.16 to 3.26] and 4.20 [95% CI 2.79 to 6.32], respectively). CONCLUSIONS In this large prospective cohort of initially healthy women, lipid levels are significant risk determinants for ischemic stroke, but with a magnitude of effect smaller than that observed for CHD. High-sensitiviy CRP associates more closely with ischemic stroke than with CHD. Concomitant evaluation of lipid levels and hs-CRP may improve risk assessment for stroke as well as CHD. C1 Harvard Univ, Ctr Cardiovasc Dis Prevent, Dept Med, Brigham & Womens Hosp,Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Brigham & Womens Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02215 USA. RP Everett, BM (reprint author), Harvard Univ, Ctr Cardiovasc Dis Prevent, Dept Med, Brigham & Womens Hosp,Sch Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM beverett@partners.org RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA-47988, R01 CA047988, R01 CA047988-13]; NHLBI NIH HHS [R01 HL080467, R01 HL043851, R01 HL043851-09, R01 HL043851-10, R01 HL080467-01, R01 HL080467-02, R01 HL080467-03, T32 HL007575, T32 HL007575-23] NR 45 TC 78 Z9 84 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 5 PY 2006 VL 48 IS 11 BP 2235 EP 2242 DI 10.1016/j.jacc.2006.09.030 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 112JD UT WOS:000242520900014 PM 17161253 ER PT J AU Rivolta, C Berson, E Dryja, T AF Rivolta, Carlo Berson, Eliot L. Dryja, Thaddeus P. TI Mutation screening of the peropsin gene, a retinal pigment epithelium specific rhodopsin homolog, in patients with retinitis pigmentosa and allied diseases SO MOLECULAR VISION LA English DT Article ID PROTEIN-COUPLED RECEPTOR; OPSIN; REGENERATION; RGR AB PURPOSE: To investigate the peropsin gene (RRH), encoding a retinal pigment epithelium homolog of the rod-expressed opsin (rhodopsin), for the presence of pathogenic mutations causing retinitis pigmentosa (RP) or other retinal degenerations. METHODS: All seven exons composing the RRH open reading frame and the immediate intron sequences were analyzed by direct nucleotide sequencing of 613 patients with forms of retinal degeneration. RESULTS: One patient with retinitis punctata albescens was a heterozygote with the missense change Cys98Tyr (TGT > TAT, c.293G > A). This change affects the homologous residue that is the target of the rhodopsin mutation Cys110Tyr, a reported cause of dominant RP. Unfortunately, none of the patient's relatives were available for a segregation analysis to determine if this change is unambiguously associated with disease. No definite pathogenic mutation was found in any of the other 612 patients who were evaluated. CONCLUSIONS: The Cys98Tyr is a possible cause of retinitis punctata albescens, although this conclusion is tentative because the change was found in only one patient. Our results indicate that the peropsin gene is not a common cause of RP or some related retinal degenerations, at least in the set of patients we analyzed. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Oculat Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Bermann Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Rivolta, C (reprint author), Univ Lausanne, Dept Med Genet, Rue Bugnon 27, CH-1005 Lausanne, Switzerland. EM carlo.rivolta@unil.ch FU NEI NIH HHS [EY08683, EY00169, EY14104] NR 18 TC 0 Z9 0 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 5 PY 2006 VL 12 IS 172-76 BP 1511 EP 1515 PG 5 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 121AS UT WOS:000243129400002 PM 17167409 ER PT J AU Turk, DC Dworkin, RH Burke, LB Gershon, R Rothman, M Scott, J Allen, RR Atkinson, JH Chandler, J Cleeland, C Cowan, P Dimitrova, R Dionne, R Farrar, JT Haythornthwaite, JA Hertz, S Jadad, AR Jensen, MP Kellstein, D Kerns, RD Manning, DC Martin, S Max, MB McDermott, MP McGrath, P Moulin, DE Nurmikko, T Quessy, S Raja, S Rappaport, BA Rauschkolb, C Robinson, JP Royal, MA Simon, L Stauffer, JW Stucki, G Tollett, J von Stein, T Wallace, MS Wernicke, J White, RE Williams, AC Witter, J Wyrwich, KW AF Turk, Dennis C. Dworkin, Robert H. Burke, Laurie B. Gershon, Richard Rothman, Margaret Scott, Jane Allen, Robert R. Atkinson, J. Hampton Chandler, Julie Cleeland, Charles Cowan, Penny Dimitrova, Rozalina Dionne, Raymond Farrar, John T. Haythornthwaite, Jennifer A. Hertz, Sharon Jadad, Alejandro R. Jensen, Mark P. Kellstein, David Kerns, Robert D. Manning, Donald C. Martin, Susan Max, Mitchell B. McDermott, Michael P. McGrath, Patrick Moulin, Dwight E. Nurmikko, Turo Quessy, Steve Raja, Srinivasa Rappaport, Bob A. Rauschkolb, Christine Robinson, James P. Royal, Mike A. Simon, Lee Stauffer, Joseph W. Stucki, Gerold Tollett, Jane von Stein, Thorsten Wallace, Mark S. Wernicke, Joachim White, Richard E. Williams, Amanda C. Witter, James Wyrwich, Kathleen W. TI Developing patient-reported outcome measures for pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID PATIENTS PERSPECTIVE; END-POINTS; PERCEPTIONS; ASSESSMENTS C1 Univ Washington, Seattle, WA 98195 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. US FDA, Rockville, MD 20857 USA. Northwestern Univ, Chicago, IL 60611 USA. Johnson & Johnson, Raritan, NY USA. AstraZeneca, Wilmington, DE USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Merck & Co Inc, Blue Bell, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Amer Chron Pain Assoc, Rocklin, CA USA. Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Novartis Pharmaceut, E Hanover, NJ USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, New Haven, CT 06520 USA. Celgene Corp, Warren, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. Dalhousie Univ, Halifax, NS, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Johnson & Johnson, Raritan, NJ USA. Alpharma, Elizabeth, NJ USA. Harvard Univ, Sch Med, Boston, MA USA. Alpharma, Piscataway, NJ USA. Univ Munich, Munich, Germany. US Dept Vet Affairs, Washington, DC USA. NeurogesX Inc, San Carlos, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. St Thomas Hosp, London, England. St Louis Univ, St Louis, MO 63103 USA. RP Turk, DC (reprint author), Univ Washington, Seattle, WA 98195 USA. EM Turkdc@u.washington.edu RI Williams, Amanda/C-7816-2009; Farrar, John/A-1037-2007; OI Farrar, John/0000-0001-8656-5157; Yang, Shuman/0000-0002-9638-0890; Williams, Amanda/0000-0003-3761-8704; McGrath, Patrick/0000-0002-9568-2571 NR 23 TC 129 Z9 132 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2006 VL 125 IS 3 BP 208 EP 215 DI 10.1016/j.pain.2006.09.028 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 114NO UT WOS:000242673100005 PM 17069973 ER PT J AU Sabbagh, L Srokowski, CC Pulle, G Snell, LM Sedgmen, BJ Liu, YQ Tsitsikov, EN Watts, TH AF Sabbagh, Laurent Srokowski, Cathy C. Pulle, Gayle Snell, Laura M. Sedgmen, Bradley J. Liu, Yuanqing Tsitsikov, Erdyni N. Watts, Tania H. TI A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Bcl-2 family; influenza virus; knockout/transgenic mice ID NF-KAPPA-B; FAMILY-MEMBER BIM; BCL-2 FAMILY; INDUCED APOPTOSIS; FACTOR (TRAF)-1; 4-1BB LIGAND; IN-VIVO; ACTIVATION; TRAF1; ANTIGEN AB The mechanisms that allow the maintenance of immunological memory remain incompletely defined. Here we report that tumor necrosis factor receptor (TNFR)-associated factor(TRAF) 1, a protein recruited in response to several costimulatory TNFR family members, is required for maximal CD8 T cell responses to influenza virus in mice. Decreased recovery of CD8 T cells in vivo occurred under conditions where cell division was unimpaired. In vitro, TRAF1-deficient, antigen-activated T cells accumulated higher levels of the proapoptotic BH3-only family member Bim, particularly the most toxic isoform, Bim(s). In the presence of excess IL-15, memory phenotype T cells with similar surface phenotype and comparable levels of Bcl-2 family members could be generated from WT or TRAF1-deficient T cell receptor transgenic OT-1 T cells. However, when the memory CD8 T cells were allowed to compete for survival signals in the absence of antigen in vivo, the TRAF1-deficient T cells showed decreased recovery compared with TRAF1-sufficient T cells. This defect in T cell recovery in vivo was alleviated by introduction of siRNA to down-modulate Bim in TRAF1-deficient memory T cells. These studies identify the TRAF1 signaling axis and Bim down-regulation as critical for CD8 memory T cell survival in vivo. C1 Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02468 USA. RP Watts, TH (reprint author), Univ Toronto, Dept Immunol, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM tania.watts@utoronto.ca FU NCI NIH HHS [CA 095127, R01 CA095127] NR 36 TC 49 Z9 49 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 DEC 5 PY 2006 VL 103 IS 49 BP 18703 EP 18708 DI 10.1073/pnas.0602919103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 114TZ UT WOS:000242689800058 PM 17116875 ER PT J AU Mylvaganam, GH McGee, TL Berson, EL Dryja, TP AF Mylvaganam, Geetha H. McGee, Terri L. Berson, Eliot L. Dryja, Thaddeus P. TI A screen for mutations in the transducin gene GNB1 in patients with autosomal dominant retinitis pigmentosa SO MOLECULAR VISION LA English DT Article ID ALPHA-SUBUNIT; RETINOBLASTOMA; DELETIONS AB PURPOSE: To search for mutations in the GNB1 gene (coding for the transducin beta 1-subunit protein) in patients with autosomal dominant retinitis pigmentosa. METHODS: We screened 185 unrelated patients with autosomal dominant retinitis pigmentosa (ADRP) using direct genomic sequencing of the three non-coding exons and 9 coding exons, along with immediately flanking intron DNA. RESULTS: We found 2 polymorphisms, one in intron 1 with a minor allele frequency of 24%, and one in intron 6 with a minor allele frequency of 12% among the 185 patients. Two rare variants (minor allele frequency < 1%) were found in the 3' untranslated region of exon 12. No changes were found in the open reading frame (exons 3-11) or in the noncoding exons 1 and 2. CONCLUSIONS: No likely pathogenic GNB1 mutations have been found in any of 185 unrelated patients with ADRP. This result would be expected if hemizygosity for GNB1 does not result in ADRP or is a rare cause of ADRP. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oculat Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oculat Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. EM thaddeus_dryja@meei.harvard.edu FU NEI NIH HHS [EY08683, EY00169, P30 EY014104] NR 12 TC 3 Z9 3 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 4 PY 2006 VL 12 IS 168-71 BP 1496 EP 1498 PG 3 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 121AR UT WOS:000243129300003 PM 17167406 ER PT J AU Harisinghani, MG AF Harisinghani, M. G. TI Feature section, lymph node assessment in abdominal cancer - Guest editor's introduction SO ABDOMINAL IMAGING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM MHARISINGHANI@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD DEC PY 2006 VL 31 IS 6 BP 631 EP 631 DI 10.1007/s00261-006-9015-1 PG 1 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 151LF UT WOS:000245291100001 ER PT J AU Saksena, MA Kim, JY Harisinghani, MG AF Saksena, M. A. Kim, J. Y. Harisinghani, M. G. TI Nodal staging in genitourinary cancers SO ABDOMINAL IMAGING LA English DT Article DE nodes; staging; genitourinary cancers ID POSITRON-EMISSION-TOMOGRAPHY; GYNECOLOGIC ONCOLOGY GROUP; UTERINE CERVICAL-CARCINOMA; I TESTICULAR TERATOMA; PELVIC LYMPH-NODES; PROSTATE-CANCER; COMPUTED-TOMOGRAPHY; MR LYMPHANGIOGRAPHY; METASTASES; CT AB In patients with genitourinary cancers nodal staging is an integral part of the pretreatment evaluation. The presence of nodal metastatic disease plays an important role in predicting prognosis and treatment planning. Although some nodal groups can be evaluated clinically, most patients undergo various imaging studies for nodal staging. Each modality has its own unique attributes and applications. This article reviews various imaging modalities, namely, contrast enhanced computerized tomography, magnetic resonance imaging (MRI), and positron emission tomography, used for nodal staging in patients with genitourinary cancers and highlights their strengths and weaknesses. Emerging novel techniques such as lymphotropic nanoparticle enhanced MRI are also highlighted. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Saksena, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mansisaksena@gmail.com NR 40 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD DEC PY 2006 VL 31 IS 6 BP 644 EP 651 DI 10.1007/s00261-006-9020-4 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 151LF UT WOS:000245291100003 PM 16967256 ER PT J AU Saokar, A Braschi, M Harisinghani, M AF Saokar, A. Braschi, M. Harisinghani, M. TI Lymphotrophic nanoparticle enhanced MR imaging (LNMRI) for lymph node imaging SO ABDOMINAL IMAGING LA English DT Article DE nodes; staging; iron oxide; magnetic resonance imaging ID SUPERPARAMAGNETIC IRON-OXIDE; UTERINE CERVICAL-CARCINOMA; INITIAL CLINICAL-EXPERIENCE; PROSTATE-CANCER; BREAST-CANCER; NONINVASIVE DETECTION; CONTRAST AGENTS; METASTASES; NECK; HEAD AB Nodal staging is an integral part of the pretreatment staging of any patient with malignancy and has therapeutic and prognostic implications. Currently used imaging techniques used for nodal evaluation are limited in accuracy because they rely on size criteria for the detection of metastases. This has led to the emergence of lymphotropic nanoparticle enhanced magnetic resonance imaging as a promising tool for nodal characterization. This article reviews the properties of lymphotropic iron oxide nanoparticles and the technique, image interpretation, and initial clinical experience with lymphotropic nanoparticle enhanced magnetic resonance imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging & Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, M (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging & Res, White 270,55 Fruit St, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 35 TC 17 Z9 17 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD DEC PY 2006 VL 31 IS 6 BP 660 EP 667 DI 10.1007/s00261-006-9006-2 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 151LF UT WOS:000245291100005 PM 16680506 ER PT J AU Myers, JS Bellini, LM Morris, JB Graham, D Katz, J Potts, JR Weiner, C Volpp, KG AF Myers, Jennifer S. Bellini, Lisa M. Morris, Jon B. Graham, Debra Katz, Joel Potts, John R. Weiner, Charles Volpp, Kevin G. TI Internal medicine and general surgery residents' attitudes about the ACGME duty hours regulations: A multicenter study SO ACADEMIC MEDICINE LA English DT Article ID WORK HOURS; PATIENT SAFETY; SLEEP; CARE; REQUIREMENTS; PERCEPTIONS; PERFORMANCE; PHYSICIAN; EDUCATION; OUTCOMES AB Purpose To assess internal medicine and general surgery residents' attitudes about the effects of the Accreditation Council for Graduate Medical Education duty hours regulations on medical errors, quality of patient care, and residency experiences. Method In 2005, the authors surveyed 200 residents who trained both before and after duty hours reform at six residency programs (three internal medicine, three general surgery) at five academic medical centers in the United States. Residents' attitudes about the effects of the duty hours regulations on the quality of patient care, residency education, and quality of life were measured using a survey instrument containing 19 Likert scale questions on a scale of 1 to 5. Survey responses were compared using the Student's t-test. Results The response rate was 80% (159 residents). Residents reported that whereas fatigue-related errors decreased slightly, errors related to reduced continuity of care significantly increased. Additionally, duty hours regulations somewhat decreased opportunities for formal education, bedside learning, and procedures, but there was no consensus that graduates would be less well trained after duty hours reform. Residents, particularly surgical trainees, reported improvements in quality of life and reduced burnout. Conclusions Residents in medicine and surgery had similar opinions about the effects of duty hours reform, including improved quality of life. However, resident opinions suggest that reduced fatigue-related errors have been offset by errors related to decreased continuity of care and that the quality of the educational experience may have declined. Quantifying the degree to which regulating duty hours affected errors related to discontinuity of care should be a focus of future research. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Dept Surg, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Texas, Dept Surg, Houston, TX USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Policy, Philadelphia, PA USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. RP Myers, JS (reprint author), Hosp Univ Penn, Div Gen Internal Med, 3400 Spruce St,Penn Tower Suite 2009, Philadelphia, PA 19104 USA. EM jennifer.myers@uphs.upenn.edu NR 32 TC 61 Z9 61 U1 2 U2 8 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 DEC PY 2006 VL 81 IS 12 BP 1052 EP 1058 DI 10.1097/01.ACM.0000246687.03462.59 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 112RE UT WOS:000242543800011 PM 17122468 ER PT J AU Jagsi, R Shapiro, J Weissman, JS Dorer, DJ Weinstein, DF AF Jagsi, Reshma Shapiro, Jo Weissman, Joel S. Dorer, David J. Weinstein, Debra F. TI The educational impact of ACGME limits on resident and fellow duty hours: A pre-post survey study SO ACADEMIC MEDICINE LA English DT Article ID INTERNS WORK HOURS; PATIENT-CARE; RESTRICTIONS; PERCEPTIONS; PHYSICIANS; ATTITUDES; SURGERY; REQUIREMENTS; LIMITATIONS; OUTCOMES AB Purpose To assess the educational impact of Accreditation Council for Graduate Medical Education resident work-hour limits implemented in July 2003. Method All trainees in all 76 accredited programs at two large teaching hospitals were surveyed between May and June 2003 (before work-hour reductions) and then between May and June 2004 (after work-hour reductions) about hours, education, and fatigue. Based on changes in weekly duty hours, 13 programs experiencing substantial reduction in hours were classified into a reduced-hours group, Differences in assessments of educational endpoints before and after policy implementation by trainees in the reduced-hours group were compared with those in other programs to control for potential temporal trends, using two-way ANOVA with interaction. Results The number of respondents was 1,770 (60% response rate). The reduced-hours group reported a significant decrease in time spent directly caring for patients (from 48.5 to 42.3 mean h/wk, P = 0.03), but the volume of important clinical experiences, including procedures, was preserved, as was the sense of clinical preparedness. On 22 questions related to educational quality and adequacy, only three differences in differences were significant, with the reduced-hours group reporting a relative increase in opportunities for research, decrease in quality of faculty teaching, and decrease in educational satisfaction. The percentage of trainees reporting frequent negative effects of fatigue dropped more in the reduced-hours programs than in the other programs (P < 0.05). Conclusion This study shows that it may be possible to reduce residents' hours-and the perceived adverse impact of fatigue-while generally preserving the self-assessed quality, quantity, and outcomes of graduate medical education. C1 Massachusetts Gen Hosp, Off Grad Med Educ, Boston, MA 02114 USA. Partners Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Weinstein, DF (reprint author), 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 37 TC 49 Z9 50 U1 1 U2 2 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 DEC PY 2006 VL 81 IS 12 BP 1059 EP 1068 DI 10.1097/01.ACM.0000246685.96372.5e PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 112RE UT WOS:000242543800013 PM 17122470 ER PT J AU Donovan, DM Kivlahan, DR Doyle, SR Longabaugh, R Greenfield, SF AF Donovan, Dennis M. Kivlahan, Daniel R. Doyle, Suzanne R. Longabaugh, Richard Greenfield, Shelly F. TI Concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and AUDIT zones in defining levels of severity among out-patients with alcohol dependence in the COMBINE study SO ADDICTION LA English DT Article DE alcohol dependence; Alcohol Use Disorders Identification Test; assessment; AUDIT zones; AUDIT; screening; severity of dependence ID COMPULSIVE DRINKING SCALE; PRIMARY-CARE; DSM-IV; COMBINED PHARMACOTHERAPIES; BEHAVIORAL INTERVENTIONS; ABUSE; CONSUMPTION; INSTRUMENT; WITHDRAWAL; DIAGNOSIS AB Aims To examine among alcohol-dependent out-patient clients the concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) total score and 'zones' suggested by the World Health Organization for defining levels of severity of alcohol use problems. Design Participants were classified into AUDIT zones (AUDIT total score = 8-15, 16-19, 20-40) and compared on measures of demographics, treatment goals, alcohol consumption, alcohol-related consequences, severity of dependence, physiological dependence, tolerance, withdrawal and biomarkers of alcohol use. Setting Eleven out-patient academic clinical research centers across the United States. Participants Alcohol dependent individuals (n = 1335) entering out-patient treatment in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) study. Measurements The AUDIT was administered as part of an initial screening. Baseline measures used for concurrent validation included the Structured Clinical Interview for Diagnostic and Statistical Manual, 4th edition (DSM-IV) Disorders, the Alcohol Dependence Scale, the Drinker Inventory of Consequences, the Obsessive-Compulsive Drinking Scale, the University of Rhode Island Change Assessment, the Thoughts about Abstinence Scale, the Form-90, %carbohydrate-deficient transferrin and gamma-glutamyl transferase. Findings Indicators of severity of dependence and alcohol-related problems increased linearly with total score and differed significantly across AUDIT zones. The highest zone, with scores of 20 and above, was markedly different with respect to severity from the other two zones and members of this group endorsed an abstinence goal more strongly. Conclusions The AUDIT total score is a brief measure that appears to provide an index of severity of dependence in a sample of alcohol-dependent individuals seeking out-patient treatment, extending its potential utility beyond its more traditional role as a screening instrument in general populations. C1 Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Treatment Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Donovan, DM (reprint author), Univ Washington, Inst Alcohol & Drug Abuse, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM ddonovan@u.washington.edu FU NIAAA NIH HHS [U10AA11773, U10AA11715, U10AA11716, U10AA11721, U10AA11727, U10AA11756, U10AA11768, U10AA11776, U10AA11777, U10AA11783, U10AA11787, U10AA11799] NR 46 TC 64 Z9 67 U1 4 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 2006 VL 101 IS 12 BP 1696 EP 1704 DI 10.1111/j.1360-0443.2006.01606.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 110IU UT WOS:000242372700008 PM 17156168 ER PT J AU Andziak, B O'Connor, TP Qi, WB DeWaal, EM Pierce, A Chaudhuri, AR Van Remmen, H Buffenstein, R AF Andziak, Blazej O'Connor, Timothy P. Qi, Wenbo DeWaal, Eric M. Pierce, Anson Chaudhuri, Asish R. Van Remmen, Holly Buffenstein, Rochelle TI High oxidative damage levels in the longest-living rodent, the naked mole-rat SO AGING CELL LA English DT Article DE DNA damage; glutathione; longevity; maximum lifespan; naked mole-rats; oxidative stress ID DNA-DAMAGE; TRIOSEPHOSPHATE ISOMERASE; LIPID-PEROXIDATION; MITOCHONDRIAL-DNA; STRESS; LONGEVITY; PROTEIN; 8-HYDROXY-2'-DEOXYGUANOSINE; F-2-ISOPROSTANES; ANTIOXIDANTS AB Oxidative stress is reputed to be a significant contributor to the aging process and a key factor affecting species longevity. The tremendous natural variation in maximum species lifespan may be due to interspecific differences in reactive oxygen species generation, antioxidant defenses and/or levels of accrued oxidative damage to cellular macromolecules (such as DNA, lipids and proteins). The present study tests if the exceptional longevity of the longest living (> 28.3 years) rodent species known, the naked mole-rat (NMR, Heterocephalus glaber), is associated with attenuated levels of oxidative stress. We compare antioxidant defenses (reduced glutathione, GSH), redox status (GSH/GSSG), as well as lipid (malondialdehyde and isoprostanes), DNA (8-OHdG), and protein (carbonyls) oxidation levels in urine and various tissues from both mole-rats and similar-sized mice. Significantly lower GSH and GSH/GSSG in mole-rats indicate poorer antioxidant capacity and a surprisingly more pro-oxidative cellular environment, manifested by 10-fold higher levels of in vivo lipid peroxidation. Furthermore, mole-rats exhibit greater levels of accrued oxidative damage to lipids (twofold), DNA (similar to two to eight times) and proteins (1.5 to 2-fold) than physiologically age-matched mice, and equal to that of same-aged mice. Given that NMRs live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress explain the impressive longevity of this species. C1 CUNY City Coll, Dept Biol, New York, NY 10031 USA. Cornell Univ, Weill Med Coll, Dept Med Genet, New York, NY 10021 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Buffenstein, R (reprint author), CUNY City Coll, Dept Biol, New York, NY 10031 USA. EM rbuffen@sci.ccny.cuny.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU NIA NIH HHS [AG 022891, AG 13319]; NIGMS NIH HHS [GM 08168-25] NR 41 TC 169 Z9 171 U1 7 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD DEC PY 2006 VL 5 IS 6 BP 463 EP 471 DI 10.1111/j.1474-9726.2006.00237.x PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 107VI UT WOS:000242198700003 PM 17054663 ER PT J AU Salem, RO Laposata, M AF Salem, Raneem O. Laposata, Michael TI Activation and impairment of platelet function in vitro by fatty acid ethyl ester, a nonoxidative ethanol metabolite: Effect of fatty acid ethyl esters on human platelets SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; arachidonic acid release; cAMP; ethanol; fatty acid ethyl esters; platelet aggregation; lipid ID PROTEIN-KINASE-C; ALCOHOL-CONSUMPTION; ARACHIDONIC-ACID; HEART-DISEASE; CARDIOPULMONARY BYPASS; BLOOD; MARKERS; CELLS; INGESTION; STROKE AB Background: The goal of this study was to investigate the effect of fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, on platelet function. We hypothesized that FAEE increase the risk of bleeding by producing an alteration in platelet membrane structure or function. Methods: Isolated human platelets incubated with FAEE were prepared and multiple assays for platelet activation were performed; beta-thromboglobulin release from platelet granules, platelet aggregation, arachidonate release from phospholipids, and intracellular cyclic AMP (cAMP) levels. We examined also the combined effect of epinephrine and FAEE on platelet aggregation. Results: FAEE induced platelet shape change, release of alpha granules and release of arachidonate from phospholipids without an increase in eicosanoid production and decreased cAMP levels. The platelets did not aggregate in response to FAEE alone, but did shorten the time to maximum aggregation with epinephrine. Conclusion: These studies show that FAEE potentiate platelet activation but do not induce aggregation, presumably because they do not stimulate thromboxane A(2) production. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 54 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2006 VL 30 IS 12 BP 2079 EP 2088 DI 10.1111/j.1530-0277.2006.00256.x PG 10 WC Substance Abuse SC Substance Abuse GA 105OQ UT WOS:000242041800015 PM 17117973 ER PT J AU Kaunitz, JD Akiba, Y AF Kaunitz, J. D. Akiba, Y. TI Review article: duodenal bicarbonate - mucosal protection, luminal chemosensing and acid-base balance SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 11th Taishotoyama International Symposium on Gastroenterology CY APR 22-23, 2005 CL Shimoda, JAPAN ID GENE-RELATED PEPTIDE; RAT GASTRIC-MUCOSA; CYSTIC-FIBROSIS; INTRACELLULAR PH; BLOOD-FLOW; ALKALINE SECRETION; EPITHELIAL-CELLS; SENSING PATHWAYS; HCO3-SECRETION; ANTRAL MUCOSA AB The duodenum serves as a buffer zone between the stomach and the jejunum. Over a length of only 25 cm, large volumes of strong acid secreted by the stomach must be converted to the neutral-alkaline chyme of the hindgut lumen, generating large volumes of CO2. The duodenal mucosa consists of epithelial cells connected by low-resistance tight junctions, forming a leaky epithelial barrier. Despite this permeability, the epithelial cells, under intense stress from luminal mineral acid and highly elevated Pco(2), maintain normal functioning. Bicarbonate ion uniquely protects the duodenal epithelial cells from acid-related injury. The specific protective mechanisms likely involve luminal bicarbonate secretion, intracellular pH buffering and interstitial buffering. Furthermore, the duodenum plays an active role in foregut acid-base homeostasis, absorbing large amounts of H+ and CO2. We have studied mucosal protection and acid-base balance using live-animal fluorescence ratio microimaging and by performing H+ and CO2 balance studies on duodenal perfusates. On the basis of these data, we have formulated novel hypotheses with regard to mucosal protection. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [P30 DK0413, R01 DK 54221] NR 66 TC 21 Z9 21 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD DEC PY 2006 VL 24 SU 4 BP 169 EP 176 DI 10.1111/j1365-2036.2006.00041.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 123PE UT WOS:000243307000025 PM 17209861 ER PT J AU Wood, CG Wei, SJ Hampshire, MK Devine, PA Metz, JM AF Wood, Charles G. Wei, S. Jack Hampshire, Margaret K. Devine, Pamela A. Metz, James M. TI The influence of race on the attitudes of radiation oncology patients towards clinical trial enrollment SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE population groups; clinical trials; attitude; neoplasms; radiation ID CANCER-TREATMENT TRIALS; AFRICAN-AMERICANS; INFORMED-CONSENT; TUSKEGEE SYPHILIS; PROSTATE-CANCER; BREAST-CANCER; INTERNET USE; PARTICIPATION; INFORMATION; RECRUITMENT AB Objectives: Enrollment of adult cancer patients in clinical trials remains low, particularly in the minority population. Understanding patient attitudes towards clinical trials during the recruitment process may enhance accrual. Unfortunately, data describing patient attitudes towards clinical trials are limited, particularly in the radiation oncology clinic setting. Methods: A piloted questionnaire assessing basic demographics and attitudes toward clinical trials was offered in 2 radiation oncology clinics between April 2003 and October 2003. The questionnaire was completed by 166 patients. The mean age of the patients completing the questionnaire was 56 years (range, 15-84 years). Of the 166 patients included in the analysis, 108 (65%) were White. The most common cancer diagnoses included prostate (19%), head and neck (16%), and breast (14%). Results: There was no statistical difference between Whites and non-Whites regarding their interest in learning about clinical trials (84.3% versus 84.9%, P = 0.92); nor was there a significant difference in the rate of previous or current trial enrollment (21.3% versus 34.0%, P = 0.08). White patients were more likely to gather information about clinical trials from the Internet (30.6% versus 11.3%, P = 0.007), and they were more likely to use physicians as a source of this information (50.0% versus 34.0%, P = 0.05). Non-White patients were more likely to obtain information about clinical trials from other patients (24.5% versus 12.0%, P = 0.04). In addition, more non-White patients believed they had been treated on clinical trials without their knowledge (21.6% versus 9.3%, P = 0.032). Patients differed somewhat in their expectations of clinical trials. More non-Whites indicated that they would need a > 50% chance of benefiting from a trial (64.4% versus 45.0%, P = 0.03) to enroll on that trial, though there were no statistical differences in outlook towards potential toxicities associated with treatment on a clinical trial. Conclusions: Minority patients historically enroll in clinical trials at a significantly lower rate. Our study of radiation oncology patients documents significant differences in attitudes towards clinical trials between Whites and non-Whites. Understanding the differences in attitudes may allow physicians to overcome barriers that would otherwise hinder the enrollment of non-White patients into clinical trials. C1 Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA USA. RP Wood, CG (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 2 Donner Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM wood@xrt.upenn.edu NR 58 TC 18 Z9 18 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 DEC PY 2006 VL 29 IS 6 BP 593 EP 599 DI 10.1097/01.coc.0000236213.61427.84 PG 7 WC Oncology SC Oncology GA 114QW UT WOS:000242681700013 PM 17148997 ER PT J AU Melanson, SEF Green, SM Wood, MJ Neilan, TG Lewandrowski, EL AF Melanson, Stacy E. F. Green, Sandy M. Wood, Malissa J. Neilan, Thomas G. Lewandrowski, Elizabeth Lee TI Elevation of myeloperoxidase in conjunction with cardiac-specific markers after marathon running SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE myeloperoxidase; endurance exercise; marathon; troponin T; NT-proBNP ID NATRIURETIC PEPTIDE; TROPONIN-T; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; STRENUOUS EXERCISE; PHYSICAL-ACTIVITY; EUROPEAN-SOCIETY; SUDDEN-DEATH; RUNNERS AB Cardiac-related death has been reported following strenuous exercise, and biochemical markers predicting adverse outcomes would be useful. Despite the fact the myeloperoxidase (MPO) release may precede myocardial injury and identify at-risk patients earlier than traditional markers, information on the effects of marathon running on MPO levels is lacking. We measured MPO in conjunction with the creatine kinase MB fraction (CK-MB), myoglobin, troponin T (TnT), and N-terminal B-type natriuretic peptide (NT-proBNP) in 24 athletes before and after a marathon race. Of the 24 athletes, 22 (92%) had an increased MPO level, and the mean MPO level increased from 281.44 pmol/L to 785.21 pmol/L (P <. 0001). Results for 14 (58%) of the athletes reached or exceeded the manufacturer's recommended clinical threshold. The increases in CK-MB, myoglobin, TnT, and NT-proBNP also reached statistical significance. Although the elevation in MPO most likely represents a systemic inflammatory response, the concurrent elevations in TnT and NT-proBNP suggest that myocardial injury cannot be excluded. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Clin Labs, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lewandrowski, EL (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. NR 38 TC 24 Z9 25 U1 0 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2006 VL 126 IS 6 BP 888 EP 893 DI 10.1309/1D62H6KRFTVQRJ0A PG 6 WC Pathology SC Pathology GA 109OY UT WOS:000242319100010 PM 17074690 ER PT J AU Hull, MJ Griggs, D Knoepp, SM Smogorzewska, A Nixon, A Flood, JG AF Hull, Mindy J. Griggs, David Knoepp, Stewart M. Smogorzewska, Agata Nixon, Andrea Flood, James G. TI Postmortem urine immunoassay showing false-positive phencyclidine reactivity in a case of fatal tramadol overdose SO AMERICAN JOURNAL OF FORENSIC MEDICINE AND PATHOLOGY LA English DT Article DE phencyclidine; tramadol; immunoassay; EMIT; urine; toxicology; false positive ID TOXICOLOGY; DRUGS; ABUSE; COMBINATION; VENLAFAXINE; DEPENDENCE; SEROTONIN AB This is a report of postmortem false-positive reactivity using an enzyme-multiplied urine phencyclidine (PCP) immunoassay (EMIT II+) due to a single-agent fatal tramadol overdose. An autopsy of a 42-year-old male who died alone at home revealed no identifiable lethal anatomic abnormalities, thus leading to toxicologic analysis. Femoral blood was obtained for drug testing by high-performance liquid chromatography (HPLC) and showed a tramadol level of 14.0 mg/L, 2 orders of magnitude greater than the therapeutic range (0.1 to 0.3 mg/L). Urine was also obtained and EMIT II+ immunoassay revealed positivity for PCP at 88 MAU/min. However, confirmatory testing by HPLC failed to identify PCP in either the urine or serum. To verify the suspicion that this was a false-positive PCP result, stock solutions of tramadol and its major metabolite (O-desmethyltramadol) at concentrations of 100 mg/L in 10% methanol/H2O were compared with a blank solution (10% methanol/H2O) for EMIT II+ PCP reactivity and demonstrated reactivities of 44 mAU/min and 27 mAU/min, respectively. While these individual results were below the cutoff reactivity for a positive EMIT II+ PCP result (ca. 85 mAU/min), they were much more reactive than the blank calibrator (set at 0 mAU/min). Therefore, we conclude that the immunoreactivity of tramadol and its metabolites in aggregate is responsible for the PCP immunoassay interference and false-positive result. C1 Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. RP Flood, JG (reprint author), Massachusetts Gen Hosp, Dept Pathol & Lab Med, 55 Fruit St,Gray Bigelow 5, Boston, MA 02114 USA. EM jflood@partners.org RI Smogorzewska, Agata/B-8891-2011 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 0195-7910 J9 AM J FOREN MED PATH JI Am. J. Forensic Med. Pathol. PD DEC PY 2006 VL 27 IS 4 BP 359 EP 362 DI 10.1097/01.paf.0000233534.59330.c2 PG 4 WC Medicine, Legal; Pathology SC Legal Medicine; Pathology GA 112LD UT WOS:000242526500020 PM 17133040 ER PT J AU Jobe, BA Hunter, JG Chang, EY Kim, CY Eisen, GM Robinson, JD Diggs, BS O'Rourke, RW Rader, AE Schipper, P Sauer, DA Peters, JH Lieberman, DA Morris, CD AF Jobe, Blair A. Hunter, John G. Chang, Eugene Y. Kim, Charles Y. Eisen, Glenn M. Robinson, Jedediah D. Diggs, Brian S. O'Rourke, Robert W. Rader, Anne E. Schipper, Paul Sauer, David A. Peters, Jeffrey H. Lieberman, David A. Morris, Cynthia D. TI Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett's esophagus: A randomized and blinded comparison SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HIGH-GRADE DYSPLASIA; LOS-ANGELES CLASSIFICATION; ESOPHAGOGASTRODUODENOSCOPY EGD; TRANSNASAL ESOPHAGOGASTRODUODENOSCOPY; GASTROINTESTINAL ENDOSCOPY; UNITED-STATES; ADENOCARCINOMA; DIAGNOSIS; CANCER; TRIAL AB OBJECTIVES: A major limitation to screening and surveillance of Barrett's esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative. METHODS: Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barrett's esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barrett's esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures. RESULTS: The prevalence of Barrett's esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy (P= 0.503). The level of agreement between the two approaches was "moderate" (kappa= 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy (P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy. CONCLUSIONS: Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application. C1 Portland VA Med Ctr, Surg Serv, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Portland VA Med Ctr, Pathol Serv, Portland, OR USA. Univ Rochester, Dept Surg, Rochester, NY USA. Oregon Hlth Sci Univ, Dept Epidemiol & Outcomes Res, Portland, OR 97201 USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv, P3GS,POB 1034, Portland, OR 97207 USA. OI Diggs, Brian/0000-0003-3586-3757 FU NCI NIH HHS [R03 CA105959-01]; NCRR NIH HHS [5 M01 RR000334]; NIDDK NIH HHS [2U01DK057132-06A1, K23 DK066165-01] NR 37 TC 59 Z9 60 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2006 VL 101 IS 12 BP 2693 EP 2703 DI 10.1111/j.1572-0241.2006.00890.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 110IV UT WOS:000242372800006 PM 17227516 ER PT J AU Okereke, O Kang, JH Gaziano, JM Ma, J Stampfer, MJ Grodstein, F AF Okereke, Olivia Kang, Jae H. Gaziano, J. Michael Ma, Jing Stampfer, Meir J. Grodstein, Francine TI Plasma C-peptide and cognitive performance in older men without diabetes SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE insulin; C-peptide; diabetes; cognition; aging ID INSULIN-DEGRADING ENZYME; ALZHEIMER-DISEASE; PHYSICIANS HEALTH; RANDOMIZED-TRIAL; RISK; MELLITUS; POPULATION; IMPAIRMENT; DEMENTIA; DECLINE AB Background: Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels. Objective: The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes. Setting: The study setting was the Physicians' Health Study-U.S. male physicians. Participants: Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years). Measurements: The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors. Results: On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant Conclusion: Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. VA Boston Healthcare Syst, Jamaica Plain, MA USA. RP Okereke, O (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM ookereke@partners.org RI Okereke, Olivia/R-9934-2016 FU NCI NIH HHS [CA42182, CA97193, R01 CA097193]; NIA NIH HHS [AG15933, AG24215, R01 AG24215]; NIMHD NIH HHS [L32 MD000994, L32 MD000994-01] NR 44 TC 10 Z9 10 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2006 VL 14 IS 12 BP 1041 EP 1050 DI 10.1097/01.JGP.0000240983.25359.00 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 115FA UT WOS:000242719000007 PM 17138810 ER PT J AU Heuser, A Plovie, ER Ellinor, PT Grossmann, KS Shin, JT Wichter, T Basson, CT Lerman, BB Sasse-Klaassen, S Thierfelder, L MacRae, CA Gerull, B AF Heuser, Arnd Plovie, Eva R. Ellinor, Patrick T. Grossmann, Katja S. Shin, Jordan T. Wichter, Thomas Basson, Craig T. Lerman, Bruce B. Sasse-Klaassen, Sabine Thierfelder, Ludwig MacRae, Calum A. Gerull, Brenda TI Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CELL-CELL ADHESION; DESMOSOMAL CADHERINS; PALMOPLANTAR KERATODERMA; PLAKOPHILIN-2 MUTATIONS; WOOLLY HAIR; PLAKOGLOBIN; GENE; DYSPLASIA/CARDIOMYOPATHY; DESMOPLAKIN; DYSPLASIA AB Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor-site mutation in intron 5 (c.631-2A -> G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and the creation of a downstream premature termination codon. Quantitative analysis of cardiac DSC2 expression in patient specimens revealed a marked reduction in the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electron-dense midlines, and associated myocardial contractility defects. These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function. C1 Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. Humboldt Univ, Charite, HELIOS Clin GmbH, Franz Volhard Clin,Dept Clin & Mol Cardiol, D-1086 Berlin, Germany. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Univ Hosp Munster, Dept Cardiol & Angiol, Munster, Germany. Univ Munster, Inst Arteriosclerosis Res, D-4400 Munster, Germany. Cornell Univ, Weill Med Coll, Dept Med, Greenberg Cardiol Div, Ithaca, NY 14853 USA. RP Gerull, B (reprint author), Max Delbruck Ctr Mol Med, Robert Roessle Str 10, D-13092 Berlin, Germany. EM b.gerull@mdc-berlin.de NR 35 TC 122 Z9 128 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2006 VL 79 IS 6 BP 1081 EP 1088 DI 10.1086/509044 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 106WB UT WOS:000242131600009 PM 17186466 ER PT J AU Gazda, HT Grabowska, A Merida-Long, LB Latawiec, E Schneider, HE Lipton, JM Vlachos, A Atsidaftos, E Ball, SE Orfali, KA Niewiadomska, E Da Costa, L Tchernia, G Niemeyer, C Meerpohl, JJ Stahl, J Schratt, G Glader, B Backer, K Wong, C Nathan, DG Beggs, AH Sieff, CA AF Gazda, Hanna T. Grabowska, Agnieszka Merida-Long, Lilia B. Latawiec, Elzbieta Schneider, Hal E. Lipton, Jeffrey M. Vlachos, Adrianna Atsidaftos, Eva Ball, Sarah E. Orfali, Karen A. Niewiadomska, Edyta Da Costa, Lydie Tchernia, Gil Niemeyer, Charlotte Meerpohl, Joerg J. Stahl, Joachim Schratt, Gerhard Glader, Bertil Backer, Karen Wong, Carolyn Nathan, David G. Beggs, Alan H. Sieff, Colin A. TI Ribosomal protein S24 gene is mutated in diamond-blackfan anemia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SPLICED MESSENGER-RNAS; EXPRESSION; REGISTRY; TRANSLATION; MUTATIONS; YEAST; S19; UK AB Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in similar to 25% of probands. We report identification of de novo nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22-q23]) in similar to 2% of RPS19 mutation-negative probands. This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Neurol Program, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Schneider Childrens Hosp, Albert Einstein Coll Med, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY 11042 USA. Univ London St Georges Hosp, Dept Cellular & Mol Med, London, England. Univ Warsaw, Sch Med, Dept Paediat Haematol Oncol, PL-00325 Warsaw, Poland. Univ Paris 11, Inst Gustave Roussy, INSERM U790, Villejuif, France. Hop Bicetre, Le Kremlin Bicetre, France. Univ Freiburg, Dept Paediat, Div Paediat Hematol & Oncol, D-7800 Freiburg, Germany. Max Delbruck Ctr Mol Med, Berlin, Germany. Univ Heidelberg, Interdisciplinary Res Neurosci, D-6900 Heidelberg, Germany. Stanford Univ, Sch Med, Div Pediat Hematol Oncol, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Clin Labs, Stanford, CA 94305 USA. RP Gazda, HT (reprint author), Childrens Hosp, Div Genet, Enders 6,Room 650,300 Longwood Ave, Boston, MA 02115 USA. EM hanna.gazda@childrens.harvard.edu RI Meerpohl, Joerg/J-4224-2013; OI Meerpohl, Joerg/0000-0002-1333-5403; Beggs, Alan/0000-0001-8818-0568 FU NCRR NIH HHS [M01 RR018535]; NHLBI NIH HHS [R01 HL079571-03, 1R01HL07956501, R01 HL079571, R01HL079571]; NIAMS NIH HHS [R01 AR044345, R01AR044345]; NICHD NIH HHS [P30 HD018655, P30 HD18655] NR 24 TC 165 Z9 168 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2006 VL 79 IS 6 BP 1110 EP 1118 DI 10.1086/510020 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 106WB UT WOS:000242131600013 PM 17186470 ER PT J AU Oliver, LC Miracle-McMahill, H AF Oliver, L. Christine Miracle-McMahill, Heidi TI Airway disease in highway and tunnel construction workers exposed to silica SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE tunnel jacking; respirable crystalline silica; concrete dust; slurry wall; asthma; carpenters; tunnel workers; healthy worker effect; OSHA ID OCCUPATIONAL RESPIRATORY-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION; CRYSTALLINE SILICA; DIESEL EXHAUST; INCREASED RISK; ASTHMA; CEMENT; DUST; HEALTH AB Background Construction workers employed in a unique type of tunnel construction known as tunnel jacking were exposed over an 18-month period to respirable crystalline silica at concentrations that exceeded the OSHA permissible exposure limit. The present study examines workplace exposures and occurrence of airway disease in these workers. Methods Medical and occupational histories and chest radiographs were obtained on 343 active construction workers who had worked on the site during the period in question. Chest radiographs were interpreted according to the ILO-1980 system of classification. Standardized questions were used to develop an algorithm to define symptoms consistent with asthma (SCA) and to determine these respiratory outcomes: chronic bronchitis, shortness of breath (SOB), and physician-diagnosed asthma (current vs. not current). Relationships with each of three work activities were examined: slurry wall breakthrough (SWB), chipping caisson overpour, and tunneling/mining. Results Participants included laborers, carpenters, tunnel workers, ironworkers, operating engineers, and electricians. No cases of silicosis were found on chest X-ray. Overall prevalence of chronic bronchitis, SCA, SOB, and physician-diagnosed asthma was 10.7%, 25%, 29%, and 66%, respectively. Odds ratios (OR) for carpenters compared to laborers were significantly elevated for chronic bronchitis, SCA, and SOB. SWB was associated with chronic bronchitis and SCA (OR 4.93, 95% CI = 1.01, 24.17; OR 3.32, 95% CI = 1.25, 8.84, respectively). The interaction between SWB, SCA, and trade was significant for carpenters (OR 687, 95% CI = 1.66, 28.39). Inverse trends were observed for months on the site and chronic bronchitis, SCA, and SOB (P = 0.0374, 0.0006, and 0.0307, respectively). Conclusions Tunnel construction workers exposed to respirable crystalline silica and cement dust are at increased risk for airway disease. Extent of risk varies by trade and work activity. Our data indicate the importance of bystander exposures and suggest that tunnel jacking may be associated with greater risk compared to more traditional methods of tunnel construction. A healthy worker effect is suggested. C1 Occupat Hlth Initiat, Brookline, MA 02446 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Oliver, LC (reprint author), Occupat Hlth Initiat, 1101 Beacon St,4 W, Brookline, MA 02446 USA. EM coliver@ohiinc.com RI Miracle, Maria /G-3482-2016 NR 41 TC 18 Z9 19 U1 1 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2006 VL 49 IS 12 BP 983 EP 996 DI 10.1002/ajim.20406 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108ZN UT WOS:000242277800001 PM 17099903 ER PT J AU Jain, NB Hart, JE Smith, TJ Garshick, E Laden, F AF Jain, Nitin B. Hart, Jaime E. Smith, Thomas J. Garshick, Eric Laden, Francine TI Smoking behavior in trucking industry workers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE smoking; occupational health; industry ID CURRENT POPULATION SURVEY; CIGARETTE-SMOKING; TOBACCO USE; OCCUPATION; CANCER; COHORT; PREVALENCE; EXPOSURE; HABITS; TRENDS AB Background In retrospective occupational studies, the degree of confounding by smoking depends on variation in smoking among job-related exposure groups. We assessed the relationship between job title and smoking behavior as part of a study on occupational exposures and lung cancer Methods A questionnaire on smoking was mailed to a sample of 11,986 trucking industry workers. Company records were used to gather other relevant information. Results The response rate was 40.5%. Among white males, the age-adjusted prevalence of ever smoking was highest among longhaul truck drivers (67%) and lowest among clerks (44%). Smoking rates among workers with other job titles were similar Conclusions Our results will be used to adjust for the differences in smoking among job-related exposure groups when assessing the association between particulate matter exposure and lung cancer mortality. Our study also suggests that an assessment of methods to control for smoking should be considered in the design of retrospective occupational health studies. C1 Channing Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Boston Healthcare Syst, Res Serv, W Roxbury, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. VA Boston Healthcare, Med Serv, Pulm & Crit Care Med Sect, W Roxbury, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Laden, F (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM Francine.Laden@channing.harvard.edu FU NCI NIH HHS [R01 CA090792, R01 CA90792] NR 31 TC 17 Z9 17 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2006 VL 49 IS 12 BP 1013 EP 1020 DI 10.1002/ajim.20399 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108ZN UT WOS:000242277800004 PM 17096359 ER PT J AU Avila, JR Jezewski, PA Vieira, AR Orioli, IM Castilla, EE Christensen, K Daack-Hirsch, S Romitti, PA Murray, JC AF Avila, Joseph R. Jezewski, Peter A. Vieira, Alexandre R. Orioli, Ieda M. Castilla, Eduardo E. Christensen, Kaare Daack-Hirsch, Sandra Romitti, Paul A. Murray, Jeffrey C. TI PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE PVRL1 variants; non-syndromic cleft lip; cleft palate ID ECTODERMAL DYSPLASIA; V-DOMAIN; HUMAN GENOME; CELL; NECTIN; MUTATIONS; MSX1; GENE; AFADIN; DNA AB Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common non-sense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations. Multiple rare and common variants from all three splice isoforms were initially ascertained by sequencing 92 Iowan and 86 Filipino cases and CEPH controls. Using a family-based analysis to examine these variants, the common glycine allele of the G361V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P=0.005). This represented G361V genotyping from over 800 Iowan, Danish, and Filipino families. Among four rare amino acid changes found within the V1 and C1 domains, S112T and T131A were found adjacent to critical amino acid positions within the VI variable domain, regions previously shown to mediate cell-to-cell and cell-to-virus adhesion. The T131A variant was not found in over 1,300 non-affected control samples although the alanine is found in other species. The serine of the S112T variant position is conserved across all known PVRL1 sequences. Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face. (c) 2006 Wiley-Liss, Inc. C1 Univ Iowa, Dept Epidemiol, Iowa City, IA 52246 USA. Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Univ Fed Rio de Janeiro, Dept Genet, ECLAMC, Oswaldo Cruz Inst, Rio De Janeiro, RJ, Brazil. CEMIC, Buenos Aires, DF, Argentina. Univ So Denmark, Ctr Prevent Congenital Malformat, Odense, Denmark. RP Murray, JC (reprint author), Univ Iowa, Dept Epidemiol, 2182 Med Labs, Iowa City, IA 52246 USA. EM jeff-murray@uiowa.edu RI Christensen, Kaare/C-2360-2009 OI Christensen, Kaare/0000-0002-5429-5292 FU FIC NIH HHS [D43 TW005503, TW 05503]; NIDCR NIH HHS [DE08559, DE9160, P50 DE016215, P50 DE16215, R01 DE008559, R01 DE011948, R01 DE11948, R37 DE008559] NR 47 TC 48 Z9 53 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2006 VL 140A IS 23 BP 2562 EP 2570 DI 10.1002/ajmg.a.31367 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 111PQ UT WOS:000242466100010 PM 17089422 ER PT J AU Bent, S Padula, A Moore, D Patterson, M Mehling, W AF Bent, Stephen Padula, Amy Moore, Dan Patterson, Michael Mehling, Woff TI Vaterian for steep: A systematic re view and meta-anatysis SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE herb; alternative medicine; insomnia; sleep; meta-analysis; systematic review ID SLEEP QUALITY; VALERIAN EXTRACT; CHRONIC INSOMNIA; CONTROLLED TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; PLACEBO; METAANALYSIS; VOLUNTEERS; INSTRUMENT AB Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety. (c) 2006 Elsevier Inc. All rights reserved. C1 San Francisco VAMC, Gen Internal Med Sect, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Bent, S (reprint author), San Francisco VAMC, Gen Internal Med Sect, Dept Med, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM stephen.bent@ucsf.edu FU NCCIH NIH HHS [K08 AT001338]; PHS HHS [1 K08 ATO1338-01] NR 39 TC 94 Z9 96 U1 3 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2006 VL 119 IS 12 BP 1005 EP 1012 DI 10.1016/j.amjmed.2006.02.026 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 111XI UT WOS:000242488800003 PM 17145239 ER PT J AU Stein, PD Woodard, PK Weg, JG Wakefield, TW Tapson, VF Sostman, HD Sos, TA Quinn, DA Leeper, KV Hull, RD Hales, CA Gottschalk, A Goodman, LR Fowler, SE Buckley, JD AF Stein, Paul D. Woodard, Pamela K. Weg, John G. Wakefield, Thomas W. Tapson, Victor F. Sostman, H. Dirk Sos, Thomas A. Quinn, Deborah A. Leeper, Kenneth V., Jr. Hull, Russell D. Hales, Charles A. Gottschalk, Alexander Goodman, Lawrence R. Fowler, Sarah E. Buckley, John D. TI Diagnostic pathways in acute pulmonary embolism: Recommendations of the PIOPED II investigators SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE pulmonary embolism; venous thromboembolism; computed tomographic angiography; D-dimer; pulmonary scintigraphy; clinical assessment ID MAGNETIC-RESONANCE ANGIOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; ACUTE VENOUS THROMBOSIS; SIMPLE CLINICAL-MODEL; D-DIMER; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; THROMBOEMBOLIC DISEASE; CONTRAST-MEDIA; HELICAL CT AB PURPOSE: To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials. METHODS: Diagnostic management recommendations were formulated based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) and outcome studies. RESULTS: The PIOPED II investigators recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D-dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast-enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary. CONCLUSION: The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances. (c) 2006 Elsevier Inc. All rights reserved. C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Duke Univ, Dept Med, Durham, NC 27706 USA. Weill Cornell Med Coll, Off Dean, New York, NY USA. Methodist Hosp, Off Execut Vice President, Houston, TX 77030 USA. Weill Cornell Med Coll, Dept Radiol, New York, NY USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. George Washington Univ, Ctr Biostat, Dept Epidemiol & Biostat, Rockville, MD USA. Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [HL063932, HL63899, HL63928, HL63931, HL63940, HL63941, HL63942, HL63981, HL63982, HL67453] NR 53 TC 121 Z9 125 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2006 VL 119 IS 12 BP 1048 EP 1055 DI 10.1016/j.amjmed.2006.05.060 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 111XI UT WOS:000242488800013 PM 17145249 ER PT J AU Rigotti, NA Thorndike, AN Regan, S McKool, K Pasternak, RC Chang, YC Swartz, S Torres-Finnerty, N Emmons, KM Singer, DE AF Rigotti, Nancy A. Thorndike, Anne N. Regan, Susan McKool, Kathleen Pasternak, Richard C. Chang, Yuchiao Swartz, Susan Torres-Finnerty, Nancy Emmons, Karen M. Singer, Daniel E. TI Bupropion for smokers hospitalized with acute cardiovascutar disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE smoking cessation; cardiovascular disease; bupropion; randomized controlled trial ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; SMOKING-CESSATION; MYOCARDIAL-INFARCTION; TRANSDERMAL NICOTINE; DEPRESSED-PATIENTS; INTERVENTION; DEPENDENCE; PROGNOSIS; MORTALITY AB PURPOSE: Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown. METHODS: A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year. RESULTS: Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P = .08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P = .49) at I year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P = .03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69). CONCLUSIONS: Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease. (c) 2006 Elsevier Inc. All fights reserved. C1 Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Maine Med Ctr, Portland, ME 04102 USA. Boston Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org FU NCRR NIH HHS [M01-RR-01066]; NHLBI NIH HHS [K24-HL04440, R01 HL 61779] NR 37 TC 72 Z9 74 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2006 VL 119 IS 12 BP 1080 EP 1087 DI 10.1016/j.amjmed.2006.04.024 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 111XI UT WOS:000242488800017 PM 17145253 ER PT J AU Rana, S Karumanchi, A Thadhani, R AF Rana, Sarosh Karumanchi, Ananth Thadhani, Ravi TI Postpartum adiponectin in women with preeclampsia: Implications for future cardiovascular disease SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal-Fetal Med C1 Brown Univ, Women & Infants Hosp, Providence, RI USA. Beth Israel Deaconess Med Ctr, Dept Med, Ctr Vascular Biol, Div Nephrol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 414 BP S131 EP S131 DI 10.1016/j.ajog.2006.10.452 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500414 ER PT J AU Rana, S Karumanchi, A Levine, R Thadhani, R AF Rana, Sarosh Karumanchi, Ananth Levine, Richard Thadhani, Ravi TI Sequential changes in angiogenic factors in early pregnancy and risk of developing preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Brown Univ, Women & Infants Hosp, Providence, RI USA. Beth Israel Deaconess Med Ctr, Dept Med, Ctr Vascular Biol, Div Nephrol, Boston, MA 02215 USA. Natl Inst Hlth, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 413 BP S131 EP S131 DI 10.1016/j.ajog.2006.10.451 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500413 ER PT J AU Stuebe, A Zera, C Ecker, J McElrath, T AF Stuebe, Alison Zera, Chloe Ecker, Jeffrey McElrath, Thomas TI A prospective assessment of metabolic function, compliance with gestational weight gain guidelines, and associated pregnancy outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Brigham & Womens Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 239 BP S82 EP S82 DI 10.1016/j.ajog.2006.10.262 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500239 ER PT J AU Tobaigy, FM Ghanem, RC Sayegh, RR Hallak, JA Azar, DT AF Tobaigy, Faisal M. Ghanem, Ramon C. Sayegh, Rony R. Hallak, Joelle A. Azar, Dimitri T. TI A control-matched comparison of laser epithelial keratomileusis and laser in situ keratomileusis for low to moderate myopia SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ASSISTED SUBEPITHELIAL KERATECTOMY; PHOTOREFRACTIVE KERATECTOMY; EXCIMER-LASER; BILATERAL KERATECTASIA; ASTIGMATISM; EFFICACY; DIOPTERS; SAFETY; LASIK AB center dot PURPOSE: To compare the visual and refractive out, comes of laser epithelial keratomileusis (LASEK) and laser in situ keratomileusis (LASIK) for the treatment of low to moderate myopia. center dot DESIGN: Retrospective, nonrandomized, control-matched study. center dot METHODS: The charts of 2257 eyes that underwent LASEK or LASIK treatment were reviewed. Patients who were 21 years of age or older having between -0.75 and - 6.00 diopters (D) of myopia with up to - 2.25 D of astigmatism were included. One hundred twenty,two LASEK-treated eyes were matched with 122 LASIK-treated eyes having preoperative spheres, cylinders, and spherical equivalent (SE) within +/- 0.50 D. Both groups had similar preoperative best spectacle,corrected visual acuity (BSCVA), laser platform, and follow,up durations. Outcome measures were visual and refractive results. center dot RESULTS: Preoperatively, the mean SE was -3.50 +/- 1.40 D for LASEK and -3.50 +/- 1.42 D for LASIK (P =.59). Postoperatively, the mean logarithm of mini, mum angle of resolution (logNIAR) uncorrected visual acuity (UCVA) was 0.01 +/- 0.08 (20/21) for LASEK and 0.06 +/- 0.12 (20/23) for LASIK; the mean SE was - 0.15 +/- 0.40 D for LASEK and - 0.37 +/- 0.45 D for LASIK; and the mean logMAR of BSCVA was -0.03 +/- 0.06 (20/19) for LASEK and -0.02 +/- 0.05 (20/19) for LASIK. No eye lost 2 or more lines of BSCVA in both groups. center dot CONCLUSIONS: Slight differences in the visual and refractive results between LASEK and LASIK were observed, despite the use of the same nomogram. Both procedures were safe, effective, and predictable. Nomogram adjustment may be necessary for LASIK surgeons adopting surface ablation. C1 Univ Illinois, Dept Ophthalmol & Visual Sci, Illinois Eye & Ear Infirm, Chicago, IL 60612 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, Illinois Eye & Ear Infirm, Suite 2-50,1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 NR 26 TC 17 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2006 VL 142 IS 6 BP 901 EP 908 DI 10.1016/j.ajo.2006.08.001 PG 8 WC Ophthalmology SC Ophthalmology GA 114MU UT WOS:000242671100001 PM 17157575 ER PT J AU Fang, PK Solomon, KR Zhuang, LY Qi, MS Mckee, M Freeman, MR Yelick, PC AF Fang, Ping-Ke Solomon, Keith R. Zhuang, Liyan Qi, Maosong McKee, Mary Freeman, Michael R. Yelick, Pamela C. TI Caveolin-1 alpha and -1 beta perform nonredundant roles in early vertebrate development SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HINDBRAIN BOUNDARY DEVELOPMENT; DISTINCT MESSENGER-RNAS; MEMBRANE DOMAINS; LIPID RAFTS; MUTATIONAL ANALYSIS; ACTIN CYTOSKELETON; KNOCKOUT MICE; CELL-SURFACE; GENE FAMILY; NULL-MICE AB Caveolins are integral membrane proteins that localize predominantly to lipid rafts, where they oligomerize to form flask-shaped organelles termed caveolae and play important roles in membrane trafficking, signal transduction, and other cellular processes. To investigate potential roles for caveolin-1 (cav-1) in development, cav-1 alpha and -1 beta cDNAs were functionally characterized in the zebrafish. Cav-1 alpha and -1 beta mRNAs exhibited overlapping but distinct expression patterns throughout embryogenesis. Targeted depletion of either Cav-1 isoform, using antisense morpholino, oligomers, resulted in a substantial loss of caveolae and dramatic neural, eye, and somite defects by 12 hours after fertilization, the time at which mRNA levels of both isoforms substantially increased in wildtype animals. Morphant phenotypes were rescued by injection of homotypic (cav-1 alpha/cav-1 beta) but not heterotypic (cav-1 alpha/cav-1 beta) zebrafish and human cav-1 cRNAs, revealing nonredundant and evolutionarily conserved functions for the individual Cav-1 alpha isoforms. Mutation of a known Cav-1 phosphorylation site unique to Cav-1 alpha (Y14 -> F) resulted in a failure to rescue the cav-1 a morphant phenotype, verifying an essential role for Cav-1 beta specifically and implicating this residue in early developmental functions. Cav-1 alpha and -1 beta morphants also exhibited disruption in the actin cytoskeleton. These results support important and previously unanticipated roles for the Caveolin-1 isoforms in vertebrate organogenesis. C1 Harvard Univ, Sch Med, Urol Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Childrens Hosp Boston, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. RP Freeman, MR (reprint author), Tufts Univ, Div Craniofacial & Mol Genet, 136 Harrison Ave,M824, Boston, MA 02111 USA. EM michael.freeman@childrens.harvard.edu; pamela.yelick@tufts.edu FU NCI NIH HHS [R01 CA112303, R01 CA101046]; NIDCR NIH HHS [R01 DE01613]; NIDDK NIH HHS [P50 DK065298, P50 DK65298, R37 DK047556, R37DK47556] NR 69 TC 32 Z9 37 U1 1 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2006 VL 169 IS 6 BP 2209 EP 2222 DI 10.2353/ajpath.2006.060562 PG 14 WC Pathology SC Pathology GA 109PD UT WOS:000242319700028 PM 17148682 ER PT J AU Feng, SJ Lu, X Resendiz, JC Kroll, MH AF Feng, Shuju Lu, Xin Resendiz, Julio C. Kroll, Michael H. TI Pathological shear stress directly regulates platelet alpha(IIb)beta(3) signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE platelets; mechanoreceptor; integrin; shear stress; signal transduction ID VON-WILLEBRAND-FACTOR; BETA(3) CYTOPLASMIC DOMAIN; PROTEIN-TYROSINE KINASES; INTEGRIN ALPHA(IIB)BETA(3); ACTIN CYTOSKELETON; THROMBUS FORMATION; FACTOR BINDING; ACTIVATION; PHOSPHORYLATION; ADHESION AB Integrin mechano-transduction is a ubiquitous biological process. Mechanical forces are transduced transmembranously by an integrin's ligand-bound extracellular domain through its beta-subunit's cytoplasmic domain connected to the cytoskeleton. This often culminates in the activation of tyrosine kinases directing cell responses. The delicate balance between hemostasis and thrombosis requires exquisitely fine-tuned integrin function, and balance is maintained in vivo despite that the major platelet integrin alpha(IIb)beta(3) is continuously subjected to frictional or shearing forces generated by laminar blood flow. To test the hypothesis that platelet function is regulated by the direct effects of mechanical forces on alpha(IIb)beta(3), we examined alpha(IIb)beta(3)/cytoskeletal interactions in human platelets exposed to shear stress in a cone-plate viscometer. We observed that alpha-actinin, myosin heavy chain, and Syk coimmunoprecipitate with alpha(IIb)beta(3) in resting platelets and that 120 dyn/cm(2) shear stress leads to their disassociation from alpha(IIb)beta(3). Shear-induced disassociation of alpha-actinin and myosin heavy chain from the beta(3) tail is unaffected by blocking von Willebrand factor (VWF) binding to glycoprotein (Gp) Ib-IX-V but abolished by blocking VWF binding to alpha(IIb)beta(3). Syk's disassociation from alpha(IIb)beta(3) is inhibited when VWF binding to either GpIb-IX-V or alpha(IIb)beta(3) is blocked. Shear stress-induced phosphorylation of SLP-76 and its association with tyrosine-phosphorylated adhesion and degranulation-promoting adapter protein are inhibited by blocking ligand binding to alpha(IIb)beta(3) but not by blocking ligand binding to GpIb-IX-V. Chinese hamster ovary cells expressing alpha(IIb)beta(3) with beta(3) truncated of its cytoskeletal binding domains demonstrate diminished shear-dependent adhesion and cohesion. These results support the hypothesis that shear stress directly modulates alpha(IIb)beta(3) function and suggest that shear-induced alpha(IIb)beta(3) mediated signaling contributes to the regulation of platelet aggregation by directing the release of constraining cytoskeletal elements from the beta(3)-tail. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. Wihuri Res Inst, SF-00140 Helsinki, Finland. RP Kroll, MH (reprint author), VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mkroll@bcm.tmc.edu NR 52 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 2006 VL 291 IS 6 BP C1346 EP C1354 DI 10.1152/ajpcell.00559.2005 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 104WT UT WOS:000241992000028 PM 16822941 ER PT J AU Payet, MD Goodfriend, TL Bilodeau, L Mackendale, C Chouinard, L Gallo-Payet, N AF Payet, Marcel D. Goodfriend, Theodore L. Bilodeau, Lyne Mackendale, Cherilu Chouinard, Lucie Gallo-Payet, Nicole TI An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE intracellular calcium ion concentration ID ATRIAL-NATRIURETIC-PEPTIDE; ALDOSTERONE SECRETION; ANGIOTENSIN-II; CA2+ CHANNELS; MEMBRANE PHOSPHOINOSITIDES; CYCLOPIAZONIC ACID; CYTOSOLIC CALCIUM; SMOOTH-MUSCLE; POTASSIUM; ENTRY AB EKODE, an epoxy-keto derivative of linoleic acid, was previously shown to stimulate aldosterone secretion in rat adrenal glomerulosa cells (15). In the present study, we investigated the effect of exogenous EKODE on cytosolic [Ca2+] increase and aimed to elucidate the mechanism involved in this process. Through the use of the fluorescent Ca2+-sensitive dye Fluo-4, EKODE was shown to rapidly increase intracellular [Ca2+] ([Ca2+](i)) along a bell-shaped dose-response relationship with a maximum peak at 5 mu M. Experiments performed in the presence or absence of Ca2+ revealed that this increase in [Ca2+](i) originated exclusively from intracellular pools. EKODE-induced [Ca2+](i) increase was blunted by prior application of angiotensin II, Xestospongin C, and cyclopiazonic acid, indicating that inositol trisphosphate (InsP(3))-sensitive Ca2+ stores can be mobilized by EKODE despite the absence of InsP(3) production. Accordingly, EKODE response was not sensitive to the phospholipase C inhibitor U-73122. EKODE mobilized a Ca2+ store included in the thapsigargin (TG)-sensitive stores, although the interaction between EKODE and TG appears complex, since EKODE added at the plateau response of TG induced a rapid drop in [Ca2+](i). 9-Oxo-octadecadienoic acid, another oxidized derivative of linoleic acid, also increases [Ca2+](i), with a dose-response curve similar to EKODE. However, arachidonic and linoleic acids at 10 mu M failed to increase [Ca2+](i) but did reduce the amplitude of the response to EKODE. It is concluded that EKODE mobilizes Ca2+ from an InsP(3)-sensitive store and that this [Ca2+](i) increase is responsible for aldosterone secretion by glomerulosa cells. Similar bell-shaped dose-response curves for aldosterone and [Ca2+](i) increases reinforce this hypothesis. C1 Univ Sherbrooke, Fac Med, Dept Physiol & Biophys, Sherbrooke, PQ J1H 5N4, Canada. Univ Sherbrooke, Fac Med, Serv Endocrinol, Dept Med, Sherbrooke, PQ J1H 5N4, Canada. Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Pharmacol, Madison, WI USA. RP Payet, MD (reprint author), Univ Sherbrooke, Fac Med, Dept Physiol & Biophys, 3001-12 Ave Nord, Sherbrooke, PQ J1H 5N4, Canada. EM marcel.payet@usherbrooke.ca NR 43 TC 7 Z9 7 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2006 VL 291 IS 6 BP E1160 EP E1167 DI 10.1152/ajpendo.00108.2006 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 106XN UT WOS:000242135400004 PM 16822961 ER PT J AU Giraud, GD Faber, JJ Jonker, SS Davis, L Anderson, DF AF Giraud, George D. Faber, J. Job Jonker, Sonnet S. Davis, Lowell Anderson, Debra F. TI Effects of intravascular infusions of plasma on placental and systemic blood flow in fetal sheep SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE fetal sheep; blood pressure; placental flow; systemic flow; placental resistance; systemic resistance ID ARTERIAL-PRESSURE; HYPERTENSION; ANGIOTENSIN; CIRCULATION; REDUCTIONS; RESPONSES; VOLUME; OUTPUT; LAMBS AB Six singleton fetal sheep of 118 - 122 days gestational age were instrumented with flow sensors on the brachiocephalic artery, the postductal aorta, and the common umbilical artery and with arterial and venous intravascular catheters. At 125 - 131 days of gestation, we started week-long continuous recordings of flows and pressures. After control measures had been obtained, the fetuses were given continuous intravenous infusions of adult sheep plasma at an initial rate of 229 ml/day. After 1 wk of infusion, fetal plasma protein concentrations had increased from 34 to 78 g/l, arterial and venous pressures had increased from 42 to 64 and from 2.7 to 3.7 mmHg, and systemic resistance ( exclusive of the coronary bed) had increased from 0.047 to 0.075 mmHg center dot min(-1)center dot ml(-1), whereas placental resistance had increased from 0.065 to 0.111 mmHg center dot min(-1)center dot ml(-1). Fetal plasma renin activities fell as early as 1 day after the start of infusion and remained below control (all changes P < 0.05). All flows decreased slightly although these decreases were not statistically significant. Thus the increase in arterial pressure was entirely due to an increase in systemic and placental resistances. C1 Oregon Hlth Sci Univ, Heart Res Ctr L464, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Giraud, GD (reprint author), Oregon Hlth Sci Univ, Heart Res Ctr L464, Dept Physiol & Pharmacol, Portland, OR 97239 USA. EM giraudg@ohsu.edu OI Jonker, Sonnet/0000-0002-1097-2562 FU NHLBI NIH HHS [R01-HL-45043]; NICHD NIH HHS [5P01-HD-34430, R01-HD-37376] NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2006 VL 291 IS 6 BP H2884 EP H2888 DI 10.1152/ajpheart.00428.2006 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 103AO UT WOS:000241855900042 PM 16905601 ER PT J AU Frank, JA Wray, CM McAuley, DF Schwendener, R Matthay, MA AF Frank, James A. Wray, Charlie M. McAuley, Danny F. Schwendener, Reto Matthay, Michael A. TI Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE alveolar epithelial barrier function; ventilator-associated lung injury; acute lung injury; acute respiratory distress syndrome ID RESPIRATORY-DISTRESS-SYNDROME; ISCHEMIA-REPERFUSION INJURY; TIDAL VOLUME VENTILATION; MECHANICAL VENTILATION; IN-VITRO; ENDOTHELIAL INJURY; EPITHELIAL-CELLS; II CELLS; INFLAMMATION; ACTIVATION AB Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 291: L1191-L1198, 2006. First published July 28, 2006; doi:10.1152/ajplung.00055.2006.-In patients requiring mechanical ventilation for acute lung injury or acute respiratory distress syndrome ( ARDS), tidal volume reduction decreases mortality, but the mechanisms of the protective effect have not been fully explored. To test the hypothesis that alveolar macrophage activation is an early and critical event in the initiation of ventilator-induced lung injury (VILI), rats were ventilated with high tidal volume (HVT) for 10 min to 4 h. Alveolar macrophage counts in bronchoalveolar lavage (BAL) fluid decreased 45% by 20 min of HVT (P < 0.05) consistent with activation-associated adhesion. Depletion of alveolar macrophages in vivo with liposomal clodronate significantly decreased permeability and pulmonary edema following 4 h of HVT (P < 0.05). BAL fluid from rats exposed to 20 min of HVT increased nitric oxide synthase activity nearly threefold in naive primary alveolar macrophages (P < 0.05) indicating that soluble factors present in the air spaces contribute to macrophage activation in VILI. Media from cocultures of alveolar epithelial cell monolayers and alveolar macrophages exposed to 30 min of stretch in vitro also significantly increased nitrite production in naive macrophages (P < 0.05), but media from stretched alveolar epithelial cells or primary alveolar macrophages alone did not, suggesting alveolar epithelial cell- macrophage interaction was required for the subsequent macrophage activation observed. These data demonstrate that injurious mechanical ventilation rapidly activates alveolar macrophages and that alveolar macrophages play an important role in the initial pathogenesis of VILI. C1 Univ Calif San Francisco, Dept Med, Cardiovasc Res Inst, Duv Pulm & Crit Care,Med ICU,San Francisco Med C, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Anesthesia, Inst Cardiovasc Res, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Paul Scherrer Inst, Villigen, Switzerland. RP Frank, JA (reprint author), Univ Calif San Francisco, Dept Med, Cardiovasc Res Inst, Duv Pulm & Crit Care,Med ICU,San Francisco Med C, Box 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu FU NHLBI NIH HHS [HL-51854, HL-69900, K08 HL069900, K08 HL069900-05, R56 HL088440] NR 42 TC 85 Z9 94 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 2006 VL 291 IS 6 BP L1191 EP L1198 DI 10.1152/ajplung.00055.2006 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 103AM UT WOS:000241855600010 PM 16877636 ER PT J AU Schwamm, L Reeves, MJ Frankel, M AF Schwamm, Lee Reeves, Mathew J. Frankel, Michael TI Designing a sustainable national registry for stroke quality improvement SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HEALTH-CARE PROFESSIONALS; TRANSIENT ISCHEMIC ATTACK; OF-NEUROLOGY AFFIRMS; CARDIOVASCULAR RADIOLOGY; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; ASSOCIATION COUNCIL; AMERICAN-COLLEGE; PRACTICE GAP; GUIDELINES AB Several studies have shown wide variations in the delivery of hospital-based care to patients with acute ischemic stroke. The findings of these studies suggest that recommendations drawn from published evidence-based or consensus-based guidelines are implemented inconsistently. Although rates of adherence to stroke quality indicators can be increased through the use of targeted quality improvement (QI) efforts, stroke QI programs are still in their infancy. Current stroke QI programs are often highly variable and poorly coordinated, rely on differing definitions of key data elements and/or indicators, and are challenging to implement and sustain in resource-constrained healthcare environments. Key barriers to long-term success of these programs include inadequate funding at the local and national level, lack of infrastructure to support electronic data capture for QI as part of the process of patient care, lack of a single clearinghouse for uniform data definitions and performance indicator descriptions, competing survey instruments to monitor hospitalized stroke care, and constraints on inpatient and post-discharge data collection imposed by the new Federal Health Insurance Portability and Accountability Act Privacy Rule. In addition, the competing needs of registry activities (e.g., complete case ascertainment) versus QI efforts (e.g., incremental tests of change) must be balanced. Potential solutions include: (1) financial incentives to healthcare providers and institutions for participation in QI initiatives; (2) financial incentives to healthcare providers and institutions for measurable improvements in care; (3) mandatory data reporting on key measures of stroke care; and (4) promotion of active and sustainable collaborations among key stakeholders including healthcare providers (e.g., physicians, nurses), healthcare organizations (e.g., hospitals, physicians' groups), quality improvement organizations, health payers and insurers, public health departments, and state and federal health agencies to create a single national stroke registry for stroke QI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. Emory Univ, Grady Hosp, Dept Neurol, Atlanta, GA 30322 USA. RP Schwamm, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, VBK-915,55 Fruit St, Boston, MA 02114 USA. EM Lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU PHS HHS [U50/CCU120238-1, U50/CCU520272-01, U50/CCU420275-01] NR 32 TC 19 Z9 19 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2006 VL 31 IS 6 SU 2 BP S251 EP S257 DI 10.1016/j.amepre.2006.08.013 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 122AC UT WOS:000243197100014 PM 17178314 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Attention deficit hyperactivity disorder and substance use disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; ORAL METHYLPHENIDATE; YOUNG-ADULTS; SMOKING; ADHD; COMORBIDITY; PREVALENCE; DEPENDENCE; INCREASES; DOPAMINE C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 32 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [K24-DA016264, R01-DA14419] NR 23 TC 30 Z9 31 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2059 EP 2063 DI 10.1176/appi.ajp.163.12.2059 PG 5 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000009 PM 17151154 ER PT J AU Yaeger, D Smith, HG Altshuler, LL AF Yaeger, Deborah Smith, Healy G. Altshuler, Lori L. TI Atypical antipsychotics in the treatment of schizophrenia during pregnancy and the postpartum SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID BODY-MASS INDEX; MATERNAL OBESITY; PSYCHOTIC DISORDERS; MENTAL-ILLNESS; BREAST-MILK; WOMEN; RISPERIDONE; CHILDREN; MOTHERS; RISK C1 W Los Angeles VA Healthcare Ctr, WC, OOAC, Womens Comprehens Healthcare Ctr,Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Yaeger, D (reprint author), W Los Angeles VA Healthcare Ctr, WC, OOAC, Womens Comprehens Healthcare Ctr,Dept Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Deborah.Yaeger@va.gov NR 39 TC 25 Z9 29 U1 3 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2064 EP 2070 DI 10.1176/appi.ajp.163.12.2064 PG 7 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000010 PM 17151155 ER PT J AU Essock, SM Covell, NH Davis, SM Stroup, TS Rosenheck, RA Lieberman, JA AF Essock, Susan M. Covell, Nancy H. Davis, Sonia M. Stroup, T. Scott Rosenheck, Robert A. Lieberman, Jeffrey A. TI Effectiveness of switching antipsychotic medications SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHRONIC-SCHIZOPHRENIA; PRESCRIBING PRACTICES; RISPERIDONE; OLANZAPINE; QUETIAPINE; TRIAL; DRUGS AB Objective: Changing antipsychotics is common despite the dearth of information on risks and benefits associated with medication changes. The authors examined phase 1 findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study to explore whether it was more advantageous to continue taking the medication being received at baseline or to switch to a different antipsychotic. Method: First, for patients randomly assigned to treatment with olanzapine (N = 314) or risperidone (N = 321), the authors assessed the impact of being assigned to stay with the medication they were receiving at entry into the study versus being assigned to switch to these medications from a different antipsychotic. Second, for patients whose baseline antipsychotic was olanzapine (N = 319), risperidone (N = 271), or quetiapine (N = 94), the authors examined the impact of being randomly assigned to stay with the same antipsychotic versus switch. Finally, the authors assessed the impact of removing the data of 209 patients whose random assignment was to stay with their baseline antipsychotic. The authors followed analysis strategies for CATIE; primary outcome was time until all-cause treatment discontinuation. Results: Individuals randomly assigned to olanzapine and risperidone who were continuing with their baseline medication had significantly longer times until discontinuation than did those assigned to switch antipsychotics. When these "stayers" were removed, differences seen in the original CATIE phase 1 analyses were attenuated, although the original pattern of results remained. Conclusions: Comparisons of medication effectiveness should take into account whether medications being compared were each newly initiated. Further, unless the clinical situation requires a medication change, prescribers may want to take steps to optimize current medication regimens (e. g., dosage adjustments, behavioral or psychosocial interventions) before switching medications. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY 10029 USA. James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Quintiles Inc, Res Triangle Pk, NC USA. Univ N Carolina, Chapel Hill, NC USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. VA New England Mental Illness Res & Educ Ctr, West Haven, CT USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Essock, SM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM susan.essock@mssm.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH90001, R01 MH59312, R03 MH 071663] NR 11 TC 114 Z9 116 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2090 EP 2095 DI 10.1176/appi.ajp.163.12.2090 PG 6 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000014 PM 17151159 ER PT J AU Kilbourne, AM Switzer, G Hyman, K Crowley-Matoka, M Fine, MJ AF Kilbourne, Amy M. Switzer, Galen Hyman, Kelly Crowley-Matoka, Megan Fine, Michael J. TI Advancing health disparities research within the health care system: A conceptual framework SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FEE-FOR-SERVICE; MEDICAL OUTCOMES; RACIAL-DIFFERENCES; LUNG-CANCER; BEHAVIORAL-MODEL; CONTROLLED-TRIAL; CLINICAL-TRIALS; QUALITY; RACE/ETHNICITY; INTERVENTIONS AB We provide a frannework for health services-related researchers, practitioners, and policy makers to guide future health disparities research in areas ranging from detecting differences in health and health care to understanding the determinants that underlie disparities to ultimately designing interventions that reduce and eliminate these disparities. To do this, we identified potential selection biases and definitions of vulnerable groups when detecting disparities. The key factors to understanding disparities were multilevel determinants of health disparities, including individual beliefs and preferences, effective patient-provider communication; and the organizational culture of the health care system. We encourage interventions that yield generalizable data on their effectiveness and that promote further engagement of communities, providers, and policymakers to ultimately enhance the application and the impact of health disparities research. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot 151CU, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Anthropol, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot 151CU, Univ Dr C, Pittsburgh, PA 15240 USA. EM amy.kilbourne@va.gov FU NIAID NIH HHS [K24 AI001769, 5K24-AI01769-05]; NIMHD NIH HHS [P60 MD000207, 1P60-MD00207] NR 51 TC 143 Z9 144 U1 5 U2 22 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2006 VL 96 IS 12 BP 2113 EP 2121 DI 10.2105/AJPH.077628 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 111SJ UT WOS:000242474500008 PM 17077411 ER PT J AU Bredella, MA Steinbach, LS Morgan, S Ward, M Davis, JC AF Bredella, Miriam A. Steinbach, Lynne S. Morgan, Stephanie Ward, Michael Davis, John C. TI MRI of the sacroiliac joints in patients with moderate to severe ankylosing spondylitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ankylosing spondylitis; bone; joint; MRI; musculoskeletal imaging; sacroiliac joints; sacroiliitis ID RESONANCE-IMAGING EXAMINATIONS; DISEASE-ACTIVITY; INFLIXIMAB; PATHOLOGY; THERAPY; PROTEIN; SPINE AB OBJECTIVE. The objectives of our study were to evaluate whether MRI findings of the sacroiliac joints are able to distinguish between active and inactive disease in patients with established ankylosing spondylitis and to determine whether these findings correlate with markers of clinical activity, disease duration, severity, and degree of radiographic damage. MATERIALS AND METHODS. Eighteen patients with symptomatic moderate to severe ankylosing spondylitis were evaluated. MRI of the sacroiliac joint (1.5 T) was performed using fat-saturated T2-weighted, T1-weighted, STIR, and fat-saturated contrast-enhanced T1-weighted sequences. The sacroiliac joints were evaluated by two radiologists for enhancement, subchondral bone marrow edema, erosions, and subchondral fatty marrow infiltration. Findings on MRI were analyzed for correlation with multiple clinical characteristics and measures of disease activity, including radiographic scoring. RESULTS. In 17 patients, MRI showed abnormal findings of the sacroiliac joint. Ten patients showed active disease on MRI as measured by abnormal enhancement and subchondral bone marrow edema. Disease activity detected using MRI correlated in a positive fashion with only C-reactive protein (CRP) level. There was no correlation with the other measures of disease activity or with disease duration. In 14 patients, fatty subchondral bone marrow was detected on MRI. These changes were seen in patients with active and chronic disease and correlated with higher radiographic scores but not with disease duration or markers of disease activity. CONCLUSION. Contrast-enhanced MRI of the sacroiliac joint is sensitive in depicting sacroiliitis in patients with established ankylosing spondylitis. Subchondral edema and enhancement correlate with high CRP levels. Subchondral fatty bone marrow changes were seen in both active and chronic sacroiliitis and are correlated with higher radiographic scores; these changes may be a marker of more advanced disease. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Internal Med, Div Rheumatol, San Francisco, CA 94143 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Yawkey Bldg,6400 6E, Boston, MA 02114 USA. EM mbredella@partners.org NR 18 TC 54 Z9 59 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2006 VL 187 IS 6 BP 1420 EP 1426 DI 10.2214/AJR.05.1423 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109DX UT WOS:000242289200006 PM 17114530 ER PT J AU Singh, AK Gervais, DA Alhilali, LM Hahn, PF Mueller, PR AF Singh, Ajay K. Gervais, Debra A. Alhilali, Lea M. Hahn, Peter F. Mueller, Peter R. TI Imaging-guided of abdominal catheter drainage collections with fistulous pancreaticobiliary communication SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE biliary system; catheters; drainage; gallbladder; interventional radiology ID LAPAROSCOPIC CHOLECYSTECTOMY; FLUID COLLECTIONS; ABSCESS; PSEUDOCYSTS; LEAKS AB OBJECTIVE. Our aim was to study the success of percutaneous imaging-guided catheter drainage of abdominal collections with documented fistulous pancreaticobiliary communication. MATERIALS AND METHODS. Fifty-seven patients (age range, 23-88 years) with abdominal collections who underwent imaging-guided catheter drainage were included in this retrospective study. These collections showed communication with either the pancreatic duct (n = 15) or the biliary duct (n = 42) on imaging. The imaging guidance included CT (n = 40), sonography (n = 17), and fluoroscopy (n = 4), either alone or in combination. The success of catheter drainage was described as resolution of the collection on follow-up imaging and clinical improvement. Other treatments directed toward management of leaks or collections were also recorded. RESULTS. The success rates of catheter drainage for abdominal collections with biliary and pancreatic ductal communication were 93% (39/42) and 67% (10/15), respectively. The difference was statistically significant (p = 0.01). The three complications seen in this study were pneumothorax in one patient, bowel perforation in one, and death in one. The drainage catheter was upsized in five patients and an additional catheter was needed in nine patients. CONCLUSION. Imaging-guided catheter drainage is a clinically useful option for drainage of abdominal collections that have pancreaticobiliary communications. The success rate is significantly better for collections with biliary communication than for those with pancreatic communication. C1 Univ Massachusetts, Mem Med Ctr, Div Abdominal Imaging, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Univ Massachusetts, Mem Med Ctr, Div Abdominal Imaging, 55 Lake Ave N, Worcester, MA 01655 USA. NR 16 TC 2 Z9 2 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2006 VL 187 IS 6 BP 1591 EP 1596 DI 10.2214/AJR.04.1948 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109DX UT WOS:000242289200031 PM 17114555 ER PT J AU Wittram, C Jones, SE Scott, JA AF Wittram, Conrad Jones, Stephen E. Scott, James A. TI 99(m)Tc sestamibi uptake by acute pulmonary embolism SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest; CT angiography; embolism; nuclear medicine C1 Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Div Thorac Radiol, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. EM cwittram@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2006 VL 187 IS 6 BP 1611 EP 1613 DI 10.2214/AJR.05.0476 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109DX UT WOS:000242289200034 PM 17114558 ER PT J AU Deshpande, V Chiocca, S Finkelberg, D Selig, MK Mino-Kenudson, M Brugge, WR Colvin, RB Lauwers, GY AF Deshpande, Vikram Chiocca, Sonia Finkelberg, Dmitry Selig, Martin K. Mino-Kenudson, Mari Brugge, William R. Colvin, Robert B. Lauwers, Gregory Y. TI Autoimmune pancreatitis: A systemic immune complex mediated disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE autoimmume pancreatitis; pancreatitis; IgG4; ultrastructure ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; IDIOPATHIC CHRONIC-PANCREATITIS; HEPATIC INFLAMMATORY PSEUDOTUMOR; PLASMA-CELL GRANULOMA; CARBONIC-ANHYDRASE; SJOGRENS-SYNDROME; IGG4 LEVELS; CHOLANGITIS; FEATURES; RELEVANCE AB Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n = 3), salivary glands (n = 3), lung (n = 2), gallbladder (n = 11), and kidney (n = 4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n = 19) and chronic pancreatitisnot otherwise specified (NOS) (n = 14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P = 0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P = 0.02). Additionally, clinical and radiologic differences emerged between the 2 groups. Ultrastructurally, electron dense deposits of immune complexes were identified in the basement membranes of 7 of the 9 AIP cases and in 3 of the 4 renal biopsies evaluated. AIP represents the pancreatic manifestation of a systemic autoimmune disease. Clinical and immunologic findings justify the recognition of pancreatic lobulocentric and ductocentric subtypes. Documentation of increased numbers of tissue IgG4 positive plasma cells, although not an entirely specific marker for AIP, may provide ancillary evidence for the diagnosis of a IgG4-related systemic disease. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, WRN 2,55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 32 TC 185 Z9 207 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2006 VL 30 IS 12 BP 1537 EP 1545 DI 10.1097/01.pas.0000213331.09864.2c PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 109EC UT WOS:000242289700006 PM 17122509 ER PT J AU Ban, S Naitoh, Y Mino-Kenudson, M Sakurai, T Kuroda, M Koyama, I Lauwers, GY Shimizu, M AF Ban, Shinichi Naitoh, Yoshihisa Mino-Kenudson, Mari Sakurai, Takaki Kuroda, Makoto Koyama, Isamu Lauwers, Gregory Y. Shimizu, Michio TI Intracluctal papillary mucinous neoplasm (IPMN) of the pancreas: Its histopathologic difference between 2 major types SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2005 CL San Antonio, TX SP US & Canadian Acad Pathol DE pancreas; intraductal papillary mucinous neoplasm (IPMN); gastric type; intestinal type; mucin ID K-RAS MUTATIONS; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; ORGANOID DIFFERENTIATION; GASTROINTESTINAL-TRACT; ABERRANT METHYLATION; CARCINOMA SEQUENCE; GENE-EXPRESSION; DISTINCT TYPES; IN-SITU AB Intraductal papillary mucinous neoplasm (IPMN) is a unique pancreatic neoplasm developing in the ductal system. Two major histologic subtypes have been reported, that is the gastric type and the intestinal type. However, their histopathologic features, especially those of the gastric type, have not been fully described. To evaluate the features of these two types and refine their differences, we analyzed 80 IPMNs including 50 cases of the gastric type and 30 cases of the intestinal type with mucin immunohistochemistry. By defining a main duct-type lesion as predominantly involving the main pancreatic duct with or without branch ducts, and a branch duct-type lesion as exclusively centered on branch ducts or consisting of a collection of small cystic lesions, gastric-type IPMNs were mostly branch duct-type lesions (98%), whereas the intestinal-type IPMNs were usually main duct type (73%). The histologic grade of the intestinal type was generally higher than that of the gastric type. The intestinal type was also characterized by frequent intraluminal nodular growth, and severe atrophy and fibrosis of the surrounding parenchyma with mucous lake formation. In contrast, pyloric glandlike structures at the base of the papillae and pancreatic intraepithelial neoplasia (PanIN)-like complexes were more frequently observed in the gastric type. A significant difference was observed between the gastric type and the intestinal type with regard to all the above features (P < 0.05). Seven cases (23%) of the intestinal type were associated with an invasive adenocarcinoma (6 mucinous and 1 ductal), versus only 1 case (2%) of the gastric type (invasive ductal carcinoma). All cases of both gastric and intestinal types expressed MUC5AC; however, high immunolabeling scores for MUC2 were mostly observed in the intestinal type (P < 0.05). In conclusion, gastric and intestinal types of IPMNs have distinct histopathologic features and mucin profiles, suggesting that they may follow different biologic pathways. C1 Saitama Med Sch, Dept Pathol, Moroyama, Saitama 3500495, Japan. Saitama Med Sch, Dept Surg, Moroyama, Saitama 3500495, Japan. Kyoto Univ Hosp, Dept Pathol, Kyoto 606, Japan. Fujita Hlth Univ, Dept Pathol, Sch Mecicine, Aichi, Japan. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shimizu, M (reprint author), Saitama Med Sch, Dept Pathol, 38 Morohongo, Moroyama, Saitama 3500495, Japan. EM shimizu@saitama-med.ac.jp NR 48 TC 87 Z9 91 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2006 VL 30 IS 12 BP 1561 EP 1569 DI 10.1097/01.pas.0000213305.98187.d4 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 109EC UT WOS:000242289700009 PM 17122512 ER PT J AU Santagata, S Hornick, JL Ligon, KL AF Santagata, Sandro Hornick, Jason L. Ligon, Keith L. TI Comparative analysis of germ cell transcription factors in CNS germinoma reveals diagnostic utility of NANOG SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE germinoma; NANOG; OCT3/4 (POU5FI); SOX2; stem cell; germ cell; brain ID EMBRYONIC STEM-CELLS; PLACENTAL ALKALINE-PHOSPHATASE; CARCINOMA IN-SITU; TESTICULAR-TUMORS; ES CELLS; PLURIPOTENCY; OCT4; EXPRESSION; DIFFERENTIATION; PATTERNS AB The homeodomain transcription factor, NANOG, along with OCT3/4 (POU5F1) and SOX2, is part of the core set of transcription factors that maintain embryonic stem cell self-renewal and pluripotency. Expression of NANOG has been detected in fetal germ cells and in gonadal germ cell tumors. To assess the diagnostic utility of NANOG in central nervous system (CNS) germ cell tumors, we analyzed its expression by immunohistochemistry in a series of 12 CNS germinomas and compared its expression with other stem cell markers. Strong nuclear expression of NANOG was demonstrated in > 90% of the tumor cells in all cases. In contrast, expression of OCT3/4 and placental alkaline phosphatase was inconsistent and SOX2 was expressed in only rare cells. NANOG was not detected in tumor types frequently considered in the differential diagnosis of CNS germinoma: pineoblastoma, primitive neuroectodermal tumors, medulloblastoma, lymphoma, pituitary adenoma, atypical teratoid/rhabdoid tumor, Langerhans cell histiocytosis, and gliomas. These findings demonstrate that NANOG is a sensitive and specific marker of CNS germinoma. Compared with other currently used markers, NANOG may have superior diagnostic characteristics and can facilitate identification of germinomas in minute surgical biopsies commonly obtained from these tumors. These findings also suggest a potential biologic role for NANOG in maintenance of CNS germinoma. C1 Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ligon, KL (reprint author), Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM kligon@partners.org RI Santagata, Sandro/A-7714-2009 FU NINDS NIH HHS [NS047213] NR 26 TC 28 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2006 VL 30 IS 12 BP 1613 EP 1618 DI 10.1097/01.pas.0000213320.04919.1a PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 109EC UT WOS:000242289700016 PM 17122519 ER PT J AU Horner, BM Cina, RA Wikiel, KJ Lima, B Ghazi, A Lo, DP Yamada, K Sachs, DH Huang, CA AF Horner, B. M. Cina, R. A. Wikiel, K. J. Lima, B. Ghazi, A. Lo, D. P. Yamada, K. Sachs, D. H. Huang, C. A. TI Predictors of organ allograft tolerance following hematopoietic cell transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE chimerism; heart transplant; hematopoietic; kidney transplant; predictor; tolerance ID LARGE-ANIMAL-MODEL; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; RENAL-ALLOGRAFTS; MIXED CHIMERISM; T-CELLS; INDUCTION; MICROCHIMERISM; RESPONSES; MARKER AB Using the miniature swine large animal model we have attempted to determine the relationship between tolerance and the presence of donor cells in the bone marrow, thymus and lineages of peripheral blood in a series of hematopoietic cell transplant recipients receiving delayed donor allografts without immunosuppression. Twenty-two animals receiving hematopoietic cell transplantation and a delayed organ allograft were analyzed. Assays for presence of donor CFUs in bone marrow (by PCR), thymic chimerism (by FACS and PCR/Southern Blot), peripheral blood chimerism (by FACS), and in vitro responsiveness to donor MHC were performed. Presence of donor BM CFUs, thymic chimerism and multilineage peripheral blood chimerism at the time of organ transplantation all correlated precisely with subsequent allograft tolerance (p < 0.001, p < 0.001, p < 0.005 respectively). These parameters were therefore accurate predictors (Positive Predictive Value (PPV) = 100% in all) of tolerance. In vitro assays of responsiveness were also highly associated (p < 0.002, p < 0.002 respectively), but were not as accurate predictors of subsequent organ tolerance (CML PPV = 80%). Engraftment, as indicated by the presence of donor derived CFU in the bone marrow, detectable thymic chimerism and multilineage peripheral blood chimerism are reliable predictors of subsequent donor allograft acceptance in hematopoietic cell transplant recipients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. UCL, Royal Free Hosp, Dept Plast Surg, London WC1E 6BT, England. RP Horner, BM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM ben.horner@tbrc.mgh.harvard.edu NR 32 TC 28 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2006 VL 6 IS 12 BP 2894 EP 2902 DI 10.1111/j.1600-6143.2006.01563.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 106NC UT WOS:000242106500010 PM 17294522 ER PT J AU Kerr, SF Emmons, LH Melby, PC Liu, C Perez, LE Villegas, M Miranda, R AF Kerr, Sara F. Emmons, Louise H. Melby, Peter C. Liu, Chang Perez, Luis E. Villegas, Maria Miranda, Robert TI Leishmania amazonensis infections in Oryzomys acritus and Oryzomys nitidus from Bolivia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CUTANEOUS LEISHMANIASIS; PALEARCTIC ORIGIN; BRAZIL; FOCUS; EPIDEMIOLOGY; VECTOR; STATE AB Three of thirteen Oryzomys acritus, Emmons and Patton 2005 (Rodentia: Muridae: Sigmodontinae) and 3 of 17 Oryzomys nitidus, Thomas 1884, collected from Noel Kempff National Park, Bolivia, from 2002 to 2005, tested positive for Leishmania (Leishmania) amazonensis or L. (L.) mexicana and negative for Leishmania (Viannia) spp. using the polymerase chain reaction (PCR). Based on previous records of L. (L.) amazonensis in humans, rodents, and sand flies from Bolivia, and the geographic distributions of L. (L.) amazonensis and L. (L.) mexicana, it was concluded that the Orvzomys were infected with L. (L.) amazonensis. These results identify two additional species of Oryzomys as hosts of L. (L.) amazonensis, and identify an ecological region of Bolivia where L. (L.) amazonensis is enzootic. C1 Univ Incarnate Word, Dept Biol, San Antonio, TX 78209 USA. Smithsonian Inst, Div Mammals, Washington, DC 20013 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kerr, SF (reprint author), Univ Incarnate Word, Dept Biol, 4301 Broadway, San Antonio, TX 78209 USA. EM kerr@uiwtx.edu FU NIGMS NIH HHS [GM55337]; PHS HHS [H75/CCH615041] NR 24 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2006 VL 75 IS 6 BP 1069 EP 1073 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 117OC UT WOS:000242881600008 PM 17172367 ER PT J AU Sullivan, AF Richman, IB Ahn, CJ Auerbach, BS Pallin, DJ Schafermeyer, RW Clark, S Camargo, CA AF Sullivan, Ashley F. Richman, Ilana B. Ahn, Christina J. Auerbach, Bruce S. Pallin, Daniel J. Schafermeyer, Robert W. Clark, Sunday Camargo, Carlos A., Jr. TI A profile of US emergency departments in 2001 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 17, 2004 CL Orlando, FL SP Soc Acad Emergency Med ID CATEGORIZATION; MEDICINE AB Study objective: Emergency departments (EDs) provide round-the-clock emergency care but also serve as a health care "safety net." We seek to determine the number, distribution, and characteristics of US EDs, with a long-term goal of improving access to emergency care. Methods: We created an inventory of nonfederal nonspecialty US hospitals using 2001 data from 2 independent sources. Hospitals that did not report ED visit data, or with large changes in visit volume by 2003, were contacted to obtain or verify visit volume (n=437; 9% of all hospitals). EDs were divided into 2 groups: those with at least 1 patient per hour, 24 hours per day, 7 days per week (>= 8,760 visits/year) and those with fewer visits. Results: Of 4,917 hospitals, 4,862 (99%) reported an ED. These EDs collectively received 101.6 million visits. One in 3 EDs (n=1,535) received less than 8,760 visits per year; the national median was 15,711 visits per year. Excluding the low-volume EDs, the remaining 3,327 reported 95.2 million annual visits. The typical higher-volume ED received approximately 28,000 visits per year; 28% (n=922) were in a nonurban setting. Among all EDs, per-capita visits varied by state, with the highest ED visit rates in Washington, DC; West Virginia; and Mississippi. Conclusion: Significant variation exists in the distribution and use of US EDs. One third of EDs have an annual visit volume less than 8,760 and, together, they account for 6% of all visits. The United States should consider classifying EDs, as it does trauma centers, to clarify the type of care available in this heterogeneous clinical setting and the distribution of different types of EDs. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Sturdy Mem Hosp, Dept Emergency Med, Attleboro, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU AHRQ HHS [R01 HS13099] NR 32 TC 46 Z9 46 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD DEC PY 2006 VL 48 IS 6 BP 694 EP 701 DI 10.1016/j.annemergmed.2006.08.020 PG 8 WC Emergency Medicine SC Emergency Medicine GA 109LX UT WOS:000242310700008 PM 17067721 ER PT J AU Velicer, CM Dublin, S White, E AF Velicer, Christine M. Dublin, Sascha White, Emily TI Cimetidine use and the risk for prostate cancer: Results from the VITAL cohort study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cimetidine; histamine-2 (H-2) blocker; prostate cancer ID PROLACTIN; ANTAGONISTS; BREAST; ZINC; RATS AB PURPOSE: The histamine-2 (H-2) blocker cimetidine may alter androgen, zinc, and prolactin levels, which could alter prostate cancer risk. Increased risk for men filling more than 20 cimetidine prescriptions was reported previously. We examined the association between cimetidine use and prostate cancer risk in a cohort in western Washington State. METHODS: Participants were 33,506 men, 50 to 76 years old, enrolled in the VITamins And Lifestyle cohort (VITAL). H-2-blocker use during the prior 10 years was self-reported through baseline questionnaire between October 2000 and December 2002. Men were followed up for subsequent prostate cancer by linkage to the Surveillance, Epidemiology and End Results cancer registry. We identified 548 incident invasive prostate cancer cases diagnosed from baseline to December 31, 2003. RESULTS: Overall, no association between ever use of cimetidine or years of cimetidine use and prostate cancer risk was observed. However, daily cimetidine use for 10 years was associated with increased risk (relative risk, 2.35; 95% confidence interval, 1.05-5.26) compared with nonuse of any H-2 blockers. Use of other H-2 blockers was not associated with prostate cancer. CONCLUSIONS: Additional studies are needed to determine whether long-term daily cimetidine use is associated with increased prostate cancer risk in other populations, and if so, the reason for this association. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. RP Velicer, CM (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. EM cvelicer@u.washington.edu FU NCI NIH HHS [CA74846, T32CA09168] NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2006 VL 16 IS 12 BP 895 EP 900 DI 10.1016/j.annepidem.2006.03.003 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120LK UT WOS:000243086000006 PM 16843010 ER PT J AU Ng, AK Mauch, PM AF Ng, A. K. Mauch, P. M. TI The impact of treatment on the risk of second malignancy after Hodgkin's disease SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID INVOLVED-FIELD RADIOTHERAPY; RADIATION-THERAPY; CLINICAL-TRIAL; STAGE-II; CHEMOTHERAPY; ABVD; LYMPHOMA; TUMORS; VINBLASTINE; DOXORUBICIN C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 26 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2006 VL 17 IS 12 BP 1727 EP 1729 DI 10.1093/annonc/mdl433 PG 3 WC Oncology SC Oncology GA 115DM UT WOS:000242715000001 PM 17151000 ER PT J AU Goldhirsch, A Coates, AS Gelber, RD Glick, JH Thurlimann, B Senn, HJ AF Goldhirsch, A. Coates, A. S. Gelber, R. D. Glick, J. H. Thuerlimann, B. Senn, H. -J. CA St Gallen Expert Panel Members TI First-select the target: better choice of adjuvant treatments for breast cancer patients SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; breast cancer; endocrine responsiveness; tailored therapies ID INTERNATIONAL EXPERT CONSENSUS; TRIAL COMPARING DOXORUBICIN; ESTROGEN-RECEPTOR STATUS; ENDOCRINE THERAPY; PHASE-III; 4 CYCLES; CHEMOTHERAPY; TRASTUZUMAB; CYCLOPHOSPHAMIDE; WOMEN AB St Gallen Expert Consensus meetings update evidence on treatment of early breast cancer every 2 years and interpret its significance for treatment of individual patients. Such interpretation is controversial. Clinical decisions cannot, however, be postponed, and the harms of failing to tailor treatment must be balanced against those of overinterpretation. Since the ninth meeting in January 2005, an extraordinary year of progress has significantly changed the landscape in breast cancer therapy. The panel in January recommended a fundamental change in selection of adjuvant systemic therapy, giving prime attention to endocrine responsiveness. Primarily, three categories were acknowledged: endocrine responsive in which the primary treatment should be endocrine, endocrine non-responsive in which endocrine therapy should not be used, and an intermediate group for which both endocrine and other therapies should be offered. Secondarily, three risk groups were defined: low, intermediate, and high, slightly modifying the previous classification. In June 2005, three trials, supported in December by a fourth, demonstrated the additional contribution of targeted therapy with trastuzumab in appropriately selected patients. Reports from several trials strengthened the evidence supporting the inclusion of taxanes, though controversy persists concerning their use in endocrine-responsive disease. This commentary midway between St Gallen meetings, therefore, emphasizes how new information influences algorithms for selecting adjuvant therapy in a rapidly changing environment. C1 European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. Oncol Inst So Switzerland, Int Breast Canc Study Grp, Bellinzona, Switzerland. FRACP AStat, Int Breast Canc Study Grp, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Kantonsspital, Senol Ctr Eastern Switzerland, Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org FU NCI NIH HHS [CA-75362] NR 28 TC 64 Z9 65 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2006 VL 17 IS 12 BP 1772 EP 1776 DI 10.1093/annonc/mdl398 PG 5 WC Oncology SC Oncology GA 115DM UT WOS:000242715000008 PM 17071934 ER PT J AU Leining, MG Gelber, S Rosenberg, R Przypyszny, M Winer, EP Partridge, AH AF Leining, M. G. Gelber, S. Rosenberg, R. Przypyszny, M. Winer, E. P. Partridge, A. H. TI Menopausal-type symptoms in young breast cancer survivors SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; menopausal symptoms; quality of life; young women ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; WOMEN; THERAPY; PREVENTION AB Background: There has been little previous information available about menopausal-type symptoms in very young breast cancer survivors. Methods: In collaboration with the Young Survival Coalition, we conducted an Internet-based survey of women with a history of breast cancer diagnosed at age 40 years or younger using items derived from the Breast Cancer Prevention Trial symptom checklist. Results: A total of 371 respondents were eligible for analysis. Mean age at diagnosis was 32.8 years and mean age at follow-up 36.2 years; 89% of women received chemotherapy, 49% tamoxifen, 15% ovarian suppression, 4% aromatase inhibitors. At the time of survey, 37% were taking tamoxifen and 9% ovarian suppression. Excluding women on ovarian suppression, 77% of women were premenopausal at follow-up. Many women reported bothersome menopausal-type symptoms. In particular, 46% of women reported hot flashes and 39% reported dyspareunia. In a linear regression model of symptom scores, current ovarian suppression, postmenopausal status, baseline anxiety before the diagnosis, pregnancy after the diagnosis, prior chemotherapy, and lower perceived financial status were associated with more bothersome symptoms. Conclusion: A substantial number of young breast cancer survivors experience bothersome menopausal symptoms. While the women who responded to our survey may represent a select group of survivors, these findings may have important implications for treatment decision making and long-term quality of life of young women with breast cancer. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Young Survival Coalit, New York, NY USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 18 TC 49 Z9 49 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2006 VL 17 IS 12 BP 1777 EP 1782 DI 10.1093/annonc/mdl299 PG 6 WC Oncology SC Oncology GA 115DM UT WOS:000242715000009 PM 16971671 ER PT J AU Zeitels, SM Burns, JA Akst, LM Hillman, RE Broadhurst, MS Anderson, RR AF Zeitels, Steven M. Burns, James A. Akst, Lee M. Hillman, Robert E. Broadhurst, Matthew S. Anderson, R. Rox TI Office-based and microlaryngeal applications of a fiber-based thulium laser SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cancer; glottis; laryngoscopy; larynx; papillomatosis; thulium laser; vocal cord; vocal fold ID VOCAL CORDS; SURGERY; CO2-LASER; PAPILLOMATOSIS; CARCINOMA AB Objectives: The carbon dioxide (CO2) laser is the premier dissecting instrument for hemostatic cutting and ablation during endolaryngeal surgery. However, microlaryngeal tangential dissection and office-based photoablation have been limited by the lack of a fiber-based delivery system. To address this limitation, a new laser was designed, which is a diode-pumped solid-state laser with a thulium-doped yttrium-aluminum-garnet laser rod. It produces a continuous-wave beam with a wavelength of 2,013 nm and a target chromophore of water. This new laser functions similarly to a CO2 laser with the benefit of being delivered through a small glass fiber (0.365 to 0.550 mm). Methods: A prospective pilot trial was done in 74 cases to explore applications of the new thulium laser. Thirty-two procedures were done with the laser used as an ablating instrument and topical anesthesia through a flexible laryngoscope (papillomatosis, 20; microinvasive carcinoma, 6; benign supraglottic lesions, 3; edema, 2; granuloma, 1). Forty-two procedures were done with the laser used as a cutting or ablating instrument for microlaryngeal dissection and general anesthesia. These included 27 partial laryngeal resections (supraglottis, 15; glottis, 10; subglottis, 2) and 8 posterior glottic laryngoplasties. The laser was also used as an ablative instrument during microlaryngoscopy in 7 cases. Results: The thulium laser was used effectively in all cases, under both local and general anesthesia. In microlaryngeal dissection, electrocautery was not needed to control bleeding, even during cutting in the highly vascular paraglottic space. No complications related to the use of the thulium laser were experienced in any case. Conclusions: Because of the fiber-based delivery system, the 2,013-nm continuous-wave thulium laser shows substantial promise for tangential dissection during microlaryngoscopy and soft tissue photoablation during office-based flexible laryngoscopy. Hemostasis was judged to be superior to experiences with the CO2 laser. In this pilot study, performing en bloc laryngeal cancer resection procedures was facilitated by use of the thulium laser. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 29 TC 36 Z9 38 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2006 VL 115 IS 12 BP 891 EP 896 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 120LE UT WOS:000243085400006 PM 17214262 ER PT J AU Lanuti, M de Delva, PE Maher, A Wright, CD Gaissert, HA Wain, JC Donahue, DM Mathisen, DJ AF Lanuti, Michael de Delva, Pierre E. Maher, Abdulrahman Wright, Cameron D. Gaissert, Henning A. Wain, John C. Donahue, Dean M. Mathisen, Douglas J. TI Feasibility and outcomes of an early extubation policy after esophagectomy SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 01, 2006 CL Chicago, IL SP Soc Thorac Surg ID MANAGEMENT; CARCINOMA; MORTALITY; CANCER; ANALGESIA; MORBIDITY; RESECTION; VOLUME AB Background. Although early extubation of esophagectomy patients has been found to be feasible, safe, and associated with low morbidity, there is no uniform standard of care among high volume centers. Our objective is to examine a contemporary series of esophagectomies and identify the feasibility and outcome of an early extubation policy. Methods. This study is a retrospective review of all patients who underwent esophagectomy between January 2003 and December 2004 at the Massachusetts General Hospital. One hundred and two patients were analyzed from 129 consecutive patients who underwent esophagectomy and subsequently divided in two groups: The early extubation group was extubated in the operating room and the late extubation group was extubated in the intensive care unit (ICU). Results. Ninety percent were extubated early. Although most patients underwent a transthoracic or thoracoabdominal esophagectomy, the operative approach did not influence failure to extubate. Neoadjuvant therapy was not predictive of extubation failure. Most patients age 70 or greater (86%) were extubated early. There were three nonelective reintubations in the early extubation group secondary to acute respiratory distress syndrome. The median length of stay was 11 days and median ICU stay was one day. The 30-day mortality was 1.9% and the median survival was 28 months. Conclusions. Attention to restricted intraoperative fluid balance, limited blood loss, anesthetic technique, and epidural use permit most patients undergoing esophageal resection to be safely extubated immediately postresection in the operating room. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@partners.org NR 19 TC 19 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2006 VL 82 IS 6 BP 2037 EP 2041 DI 10.1016/j.athoracsur.2006.07.024 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 109GX UT WOS:000242297200013 PM 17126107 ER PT J AU Deliolanis, NC Vanidhis, ED Vainos, NA AF Deliolanis, N. C. Vanidhis, E. D. Vainos, N. A. TI Dispersion of electrogyration in sillenite crystals SO APPLIED PHYSICS B-LASERS AND OPTICS LA English DT Article ID BISMUTH GERMANIUM OXIDE; DIELECTRIC CRYSTALS; OPTICAL-ACTIVITY; SILICON-OXIDE; BI12TIO20; PHOTOACTIVITY; COEFFICIENT; BI12SIO20; GROWTH AB In this paper we report on the dispersion of the electrogyration of the sillenite crystals Bi12SiO20, Bi12GeO20, and Bi12TiO20 over the visible spectrum. We measure the electrogyration coefficient from the rotation of the polarization plane of the transmitted beam due to the externally applied electric field. Both light transmission and electric field direction are parallel to the [111] crystallographic direction in which the influence of the electrooptic effect is diminished. In all cases the electrogyratory coefficient is found to be between 0.5-3.75x10(-13) m/V and has the same dispersion pattern like optical activity and refractive index. C1 Aristotle Univ Thessaloniki, Dept Phys, Solid State Phys Sect, Thessaloniki 54124, Greece. Univ Patras, Dept Mat Sci, Patras 26504, Greece. TPCI, Natl Hellen Res Fdn, Athens 11635, Greece. RP Deliolanis, NC (reprint author), Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Room 5406,149 13th St, Charlestown, MA 02129 USA. EM ndeli@physics.auth.gr RI nhrf, tpci/M-8699-2013; OI Deliolanis, Nikolaos/0000-0002-6392-3035 NR 34 TC 4 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2171 J9 APPL PHYS B-LASERS O JI Appl. Phys. B-Lasers Opt. PD DEC PY 2006 VL 85 IS 4 BP 591 EP 596 DI 10.1007/s00340-006-2437-1 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA 105EW UT WOS:000242013800019 ER PT J AU Magee, KH Pollack, BP Raugi, GJ AF Magee, Kristin H. Pollack, Brian P. Raugi, Gregory J. TI Pustule-studded plaques after abrasion injury - Blastomycosis-like pyoderma. SO ARCHIVES OF DERMATOLOGY LA English DT Article ID VEGETANS; THERAPY C1 Emory Univ, Atlanta, GA 30322 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Magee, KH (reprint author), Emory Univ, Atlanta, GA 30322 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2006 VL 142 IS 12 BP 1643 EP + DI 10.1001/archderm.142.12.1643-a PG 2 WC Dermatology SC Dermatology GA 116LC UT WOS:000242803400018 PM 17178997 ER PT J AU Andreoli, CM Husain, D Davis, TS Loewenstein, JI AF Andreoli, Christopher M. Husain, Deeba Davis, Thomas S. Loewenstein, John I. TI Chorioretinal changes heralding metastatic malignancy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LYMPHOMAS; AIDS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM john_loewenstein@meei.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2006 VL 124 IS 12 BP 1790 EP 1792 DI 10.1001/archopht.124.12.1790 PG 4 WC Ophthalmology SC Ophthalmology GA 115LE UT WOS:000242735000023 PM 17159048 ER PT J AU Mehta, RP Faquin, WC Franco, RA AF Mehta, Ritvik P. Faquin, William C. Franco, Ramon A. TI Pathology quiz case 1 - Osteoma of the larynx SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mehta, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD DEC PY 2006 VL 132 IS 12 BP 1390 EP + DI 10.1001/archotol.132.12.1390 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 115YO UT WOS:000242769900019 PM 17178955 ER PT J AU Renshaw, AA Hughes, JH Wang, E Haja, J Wilbur, D Henry, MR Moriarty, AT AF Renshaw, Andrew A. Hughes, Jonathan H. Wang, Edward Haja, Jennifer Wilbur, David Henry, Michael R. Moriarty, Ann T. CA Cytopathology Resource Committee TI Leukemia/lymphoma in cerebrospinal fluid - Distinguishing between cases that performed well and poorly in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FLOW-CYTOMETRY AB Context.-Although the cytologic features of leukemia/ lymphoma in cerebrospinal fluid specimens are well known, the correlation of these features with the ability f cytologists to identify this tumor have not been well studied. Objective.-To identify the morphologic features of leukemia/lymphoma in cerebrospinal fluid that are associated with good performance and poor performance in an educational interlaboratory comparison program; and to identify the morphologic features associated with how well a slide performs with regard to its reference diagnosis. Design.-The performance of 147 cases of leukemia/ lymphoma in the College of American Pathologists Interlaboratory Comparison Program in Non-gynecologic Cytology was analyzed. The cytologic features of a subset of 31 cases composed of relatively equal numbers of Romanowsky-stained and Papanicolaou-stained specimens were further evaluated, and those that performed poorly (n=12) were compared with those that performed extremely well (n=19). Results.-For all cases of leukemia/lymphoma in the program, the rate of misclassification as benign for cases with Papanicolaou stain was significantly higher than for those with Romanowsky stain (9.5% vs 2.6%, P <.001). Compared with cases that performed well, slides that performed poorly were more likely to have less than 200 abnormal cells (42% vs 5%, P=.02). The size of the tumor cells and preservation were not significant. Conclusion.-Cases of specimens of leukemia/lymphoma in cerebrospinal fluid are more likely to be misdiagnosed as benign if they are Papanicolaou-stained or have 200 abnormal cells. C1 AmeriPath Indiana, Indianapolis, IN 46219 USA. Cleveland Clin, Dept Pathol, Naples, FL USA. Massachusetts Gen Hosp, Cytol Dept, Boston, MA 02114 USA. Coll Maer Pathologists Staff, Surveys Dept, Northfield, IL USA. Univ Illinois, Coll Hlth Sci, Dept Stat, Chicago, IL USA. Lab Med Consultants Ltd, Dept Pathol, Las Vegas, NV USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Moriarty, AT (reprint author), AmeriPath Indiana, 2560 N Shadeland Ave,Suite A, Indianapolis, IN 46219 USA. EM amoriarty@ameripath.com NR 12 TC 4 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2006 VL 130 IS 12 BP 1762 EP 1765 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 114CT UT WOS:000242645000010 PM 17149947 ER PT J AU Young, NA Moriarty, AT Haja, JC Wilbur, DC AF Young, Nancy A. Moriarty, Ann T. Haja, Jennifer C. Wilbur, David C. TI Fine-needle aspiration biopsy of lymphoproliferative disorders- Interpretations based on morphologic criteria alone - Results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FLOW-CYTOMETRY; RECURRENT LYMPHOMA; DIAGNOSIS; SUBCLASSIFICATION; CLASSIFICATION; CYTOLOGY AB Context.-Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. Objective.-To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. Design.-Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. Results.-Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. Conclusions.-The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies. C1 Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. AmeriPath Indiana, Dept Pathol, Indianapolis, IN USA. Coll Amer Pathologists, Cytopathol Comm, Northfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Young, NA (reprint author), Fox Chase Canc Ctr, Dept Pathol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM na_young@fccc.edu NR 12 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2006 VL 130 IS 12 BP 1766 EP 1771 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 114CT UT WOS:000242645000011 PM 17149948 ER PT J AU Melanson, SEF Lee-Lewandrowski, E Griggs, DA Long, WH Flood, JG AF Melanson, Stacy E. F. Lee-Lewandrowski, Elizabeth Griggs, David A. Long, William H. Flood, James G. TI Reduced interference by phenothiazines in amphetamine drug of abuse immunoassays SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID URINE; PROMETHAZINE; METABOLITES; ASSAY AB Context.-Emergency department physicians frequently request urine drug screens, but many are unaware of their limitations, including the potential for false-positive results. Promethazine, a phenothiazine derivative, is used for the treatment of allergies, agitation, nausea, and vomiting. Many patients taking promethazine are subject to urine drug screens and any potential interferences are important to recognize. Design.-During an 11-month period, all patients presenting to the Massachusetts General Hospital emergency department who had a finding of promethazine in their serum drug screen, and who also had a urine drug screen performed, were selected for inclusion in the study. The urine drug screen results (n=22 patients/samples) were then studied. Objective.-To determine if promethazine use can cause false-positive urine amphetamine results in widely used drug of abuse immunoassays. Results.-Thirty-six percent of patients taking promethazine had false-positive test results for urine amphetamines using the EMIT 11 Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Sixty-four percent of patients showed cross-reactivity greater than 20% higher than the blank calibrator rate. In a separate, related study, no promethazine-induced false-positive results were seen with the EMIT 11 Plus, Triage, and TesTcard 9 amphetamine assays, or the Triage methamphetamine assay. Reduced chlorpromazine interference was also seen with these other assays. Conclusions.-False-positive urine amphetamine results can be obtained in patients taking promethazine. Promethazine metabolite(s), and not the parent compound, are the likely cause of these urine false-positive results obtained with EMIT 11 Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Immunoassays from different manufacturers can have very different "interference" profiles, which the pathologist and laboratory scientist must understand and relay to clinicians. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. RP Flood, JG (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM jflood@partners.org NR 12 TC 12 Z9 13 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2006 VL 130 IS 12 BP 1834 EP 1838 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 114CT UT WOS:000242645000022 PM 17149959 ER PT J AU Wellman, RJ Sugarman, DB DiFranza, JR Winickoff, JP AF Wellman, Robert J. Sugarman, David B. DiFranza, Joseph R. Winickoff, Jonathan P. TI The extent to which tobacco marketing and tobacco use in films contribute to children's use of tobacco - A meta-analysis SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Review ID JUNIOR-HIGH-SCHOOL; ADOLESCENT SMOKING; CIGARETTE ADVERTISEMENTS; PSYCHOSOCIAL FACTORS; YOUNG ADOLESCENTS; PUBLICATION BIAS; START SMOKING; YOUTH SMOKING; PRO-TOBACCO; MOVIE STARS AB Objective: To quantify the effect of exposure on initiation of tobacco use among adolescents. Data Sources: Asystematic literature search of MEDLINE, PsychINFO, ABI/INFORM, and Business Source Premier through October/November 2005 was conducted. Unpublished studies were solicited from researchers. Study Selection: Of 401 citations initially identified, 51 (n = 141949 participants) met the inclusion criteria: reporting on exposure and tobacco use outcomes and participants younger than 18 years. Included studies reported 146 effects; 89 were conceptually independent effects. Data were extracted independently by 3 of us using a standardized tool. Weighted averages were calculated using a linear mixed-effects model. Heterogeneity and publication bias were assessed. Main Exposures: Exposures (tobacco advertising, promotions, and samples and pro-tobacco depictions in films, television, and videos) were categorized as low or high engagement based on the degree of psychological involvement required. Main Outcome Measures: Outcomes were categorized as cognitive (attitudes or intentions) or behavioral (initiation, tobacco use status, or progression of use). Results: Exposure to pro-tobacco marketing and media increases the odds of youth holding positive attitudes toward tobacco use (odds ratio, 1.51; 95% confidence interval, 1.08-2.13) and more than doubles the odds of initiating tobacco use (odds ratio, 2.23; 95% confidence interval, 1.79-2.77). Highly engaging marketing and media are more effective at promoting use (odds ratio, 2.67; 95% confidence interval, 2.19-3.25). These effects are observed across time, in different countries, with different study designs and measures of exposure and outcome. Conclusions: Pro-tobacco marketing and media stimulate tobacco use among youth. A ban on all tobacco promotions is warranted to protect children. C1 Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA. Fitchburg State Coll, Dept Behav Sci, Fitchburg, MA USA. Rhode Isl Coll, Dept Psychol, Providence, RI 02908 USA. Massachusetts Gen Hosp, Ctr Child & Adolesent Hlth Policy, Boston, MA 02114 USA. RP Wellman, RJ (reprint author), Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, 55 Lake Ave N, Worcester, MA 01655 USA. EM Robert.Wellman@umassmed.edu OI Wellman, Robert/0000-0003-3653-9545 NR 132 TC 86 Z9 88 U1 5 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 2006 VL 160 IS 12 BP 1285 EP 1296 DI 10.1001/archpedi.160.12.1285 PG 12 WC Pediatrics SC Pediatrics GA 111YW UT WOS:000242492800012 PM 17146027 ER PT J AU Strangman, G Goldstein, R Rauch, SL Stein, J AF Strangman, Gary Goldstein, Richard Rauch, Scott L. Stein, Joel TI Near-infrared spectroscopy and imaging for investigating stroke rehabilitation: Test-retest reliability and review of the literature SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE hemodynamics; motor skills; oxyhemoglobins; rehabilitation; spectroscopy; near infrared ID POSITRON-EMISSION-TOMOGRAPHY; MOTOR RECOVERY; FUNCTIONAL MRI; HEMODYNAMIC-RESPONSE; HEMIPARETIC STROKE; HEMIPLEGIC STROKE; PREMOTOR CORTEX; ACTIVATION; REORGANIZATION; INFARCTION AB Objectives: To review the use of near-infrared spectroscopy (NIRS) in stroke rehabilitation and to evaluate NIRS test-retest reliability within-session on a motor control task commonly used in neuroimaging of stroke recovery. Design: Cohort study. Setting: Hospital-based research laboratory. Participants: Nineteen healthy control subjects (age range, 22-55y). Interventions: Subjects performed 2 experimental runs of a finger-opposition task in a block-design paradigm (finger opposition alternated with a fixation rest period) while undergoing multichannel NIRS and physiologic monitoring. Main Outcome Measure: Reliability coefficients (Pearson r) for oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb) correlated amplitude modulations across measurement channels during individual blocks and block averages. Results: Correlations between single blocks (ie, 16-s slices of data) exhibited a correlation intercept of 33 +/- .09 for O(2)Hb. This value was minimally decreased by increasing lag between compared blocks (slope, -.012; P=.019) but was substantially enhanced by averaging across blocks (within-run slope, 11: between-run slope, .044). Correlations using 64 seconds of data reached 0.6. Results for HHb were virtually identical. Conclusions: NIRS modulations were repeatable even when comparing very short segments of data. When averaging longer data segments, the test-retest correspondences compared favorably to neuroimaging using other modalities. This suggests that NIRS is a reliable tool for longitudinal stroke rehabilitation and recovery studies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Psychiat Neurosci,Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Div Behav & Mental Hlth, Boston, MA USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. RP Strangman, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Psychiat Neurosci,Neural Syst Grp, 149 13th St,Rm 2651, Charlestown, MA 02129 USA. EM strang@nmr.mgh.harvard.edu FU NINDS NIH HHS [K25-NS046554] NR 47 TC 16 Z9 17 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2006 VL 87 IS 12 SU 2 BP S12 EP S19 DI 10.1016/j.apmr.2006.07.269 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 115ZV UT WOS:000242773200003 PM 17140875 ER PT J AU Schulze, PC Liu, HL Choe, E Yoshioka, J Shalev, A Bloch, KD Lee, RT AF Schulze, P. Christian Liu, Heling Choe, Elizabeth Yoshioka, Jun Shalev, Anath Bloch, Kenneth D. Lee, Richard T. TI Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; diabetes mellitus; nitric oxide; oxidative stress; thioredoxin ID UP-REGULATED PROTEIN-1; MUSCLE-CELL-PROLIFERATION; NF-KAPPA-B; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; REDOX REGULATION; S-NITROSYLATION; HELA-CELLS; GENE; ACTIVATION AB Objective - Cellular redox balance is regulated by enzymatic and nonenzymatic systems and freely diffusible nitric oxide ( NO) promotes antioxidative mechanisms. We show the NO-dependent transcriptional regulation of the antioxidative thioredoxin system. Methods and Results - Incubation of rat pulmonary artery smooth muscle cells (RPaSMC) with the NO donor compound S-nitroso-glutathione (GSNO, 100 mu mol/L) suppressed thioredoxin-interacting protein (Txnip), an inhibitor of thioredoxin function, by 71 +/- 18% and enhanced thioredoxin reductase 2.7 +/- 0.2 fold (n = 6; both P < 0.001 versus control). GSNO increased thioredoxin activity (1.9 +/- 0.5-fold after 4 hours; P < 0.05 versus control). Promoter deletion analysis revealed that NO suppression of Txnip transcription is mediated by cis-regulatory elements between -1777 and -1127 bp upstream of the start codon. Hyperglycemia induced Txnip promoter activity (3.9 +/- 0.2-fold; P < 0.001) and abolished NO effects (-37.4 +/- 1.0% at 5.6 mmol/L glucose versus 12.4 +/- 2.1% at 22.4 mmol/L glucose; P < 0.05). Immunoprecipitation experiments demonstrated that GSNO stimulation and mutation of thioredoxin at Cys69, a site of nitrosylation, had no effect on the Txnip/thioredoxin interaction. Conclusions - NO can regulate cellular redox state by changing expression of Txnip and thioredoxin reductase. This represents a novel antioxidative mechanism of NO independent of posttranslational protein S-nitrosylation of thioredoxin. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Schulze, PC (reprint author), Boston Univ, Med Ctr, Dept Med, 80 E Concord St,Evans 124, Boston, MA 02115 USA. EM christian.schulze@bmc.org FU NHLBI NIH HHS [P01 HL64858] NR 33 TC 46 Z9 49 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2006 VL 26 IS 12 BP 2666 EP 2672 DI 10.1161/01.ATV.0000248914.21018.f1 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 127DS UT WOS:000243566100014 PM 17023680 ER PT J AU O'Donnell, CJ Shea, MK Price, PA Gagnon, DR Wilson, PWF Larson, MG Kiel, DP Hoffmann, U Ferencik, M Clouse, ME Williamson, MK Cupples, LA Dawson-Hughes, B Booth, SL AF O'Donnell, Christopher J. Shea, M. Kyla Price, Paul A. Gagnon, David R. Wilson, Peter W. F. Larson, Martin G. Kiel, Douglas P. Hoffmann, Udo Ferencik, Maros Clouse, Melvin E. Williamson, Matthew K. Cupples, L. Adrienne Dawson-Hughes, Bess Booth, Sarah L. TI Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; coronary artery calcification; coronary risk factors; matrix Gla protein ID BEAM COMPUTED-TOMOGRAPHY; VASCULAR CALCIFICATION; HEART-DISEASE; REGULATING PROTEINS; QUANTIFICATION; MINERALIZATION; EXPRESSION; SERUM; RAT AB Objectives - Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP and its associations with CHD risk factors or with CAC in humans. Methods and Results - Serum MGP concentrations were determined in 2 independent populations of men and women free of clinically apparent cardiovascular disease: study A, n = 316, mean age 58 years, and study B, n = 452, mean age 68 years. CAC was determined by computed tomography. Mean MGP concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women, in study A and study B, respectively. In both cohorts, MGP levels were higher with increasing age. In age-adjusted analyses, there was an association of circulating MGP with increasing Framingham CHD risk score (in study A, P = 0.003 in men and P = 0.016 in women, respectively; in study B, a nonsignificant increase in men and P = 0.05 in women, respectively). Significant associations of circulating MGP with high-density lipoprotein and other individual CHD risk factors were also noted in both cohorts. There were no consistent associations between MGP and CAC after adjustment for CHD risk score in the 2 cohorts. Conclusions - MGP is associated with individual CHD risk factors and the Framingham CHD risk score in men and women free of clinically apparent CHD. The relation of MGP with CAC deserves further study in larger populations. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov OI Gagnon, David/0000-0002-6367-3179; Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [HL58090, HL69272, N01-HC-38038, R01 HL058090, R01 HL069272, T32 HL069772]; NIA NIH HHS [R01 AG019147-05, AG14759, AG19147, R01 AG019147, R01 AG019147-01, R01 AG019147-02, R01 AG019147-03, R01 AG019147-04] NR 27 TC 39 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2006 VL 26 IS 12 BP 2769 EP 2774 DI 10.1161/01.ATV.0000245793.83158.06 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 127DS UT WOS:000243566100029 PM 16973975 ER PT J AU Visvanathan, S Rojas, J Wagner, C Kay, J Dasgupta, B Matteson, EL Mack, M Gathany, T Baker, DG Rahman, MU AF Visvanathan, S. Rojas, J. Wagner, C. Kay, J. Dasgupta, B. Matteson, E. L. Mack, M. Gathany, T. Baker, D. G. Rahman, M. U. TI Decreases in E-selectin, IL-18, SAA, and MMP-9 levels may predict clinical response to golimumab plus methottexate therapy in rheumatoid arthritis patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Cent Res & Dev, Malvern, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Southend Hosp, Westcliff South East, England. Mayo Coll Med, Rochester, MN USA. NR 0 TC 1 Z9 1 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 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4038 EP 4039 PG 2 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700063 ER PT J AU Kay, J Todd, DJ Kagan, A Chibnik, LB AF Kay, Jonathan Todd, Derrick J. Kagan, Anna Chibnik, Lori B. TI Nephrogenic fibrosing dermopathy in patients receiving hemodialysis is associated with gadolinium exposure and results in increased early mortality. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4040 EP 4040 PG 1 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700067 ER PT J AU Graham, RR Kyogoku, C Vaslova, I Davies, L Criswell, L Vyse, T Baechler, E Daly, M Moser, K Bojhanen, P Gaffney, P Altshuler, D Behrens, T AF Graham, Robert R. Kyogoku, Chieko Vaslova, Irina Davies, Leela Criswell, Lindsey Vyse, Timothy Baechler, Emily Daly, Mark Moser, Kathy Bojhanen, Paul Gaffney, Patrick Altshuler, David Behrens, Timothy TI Epistasis between three functional variants of IRF5 define risk and protective haplotypes for human lupus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ London Imperial Coll Sci & Technol, London, England. RI Vyse, Tim/G-3887-2011; Altshuler, David/A-4476-2009; Gillespie, Emily/N-1265-2013 OI Altshuler, David/0000-0002-7250-4107; Gillespie, Emily/0000-0001-5261-3931 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4044 EP 4044 PG 1 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700074 ER PT J AU Laine, L Curtis, SP Bombardier, C Weinblatt, ME Kaur, A Cannon, CP AF Laine, Loren Curtis, Sean P. Bombardier, Claire Weinblatt, Michael E. Kaur, Amarjot Cannon, Christopher P. TI Clinical outcomes following long-term treatment with etoricoxib vs. diclofenac in 34,701 patients with osteoarthritis (OA) or rheumatoid arthritis (RA): primary results of the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) program. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ So Calif, Los Angeles, CA USA. Merck & Co Inc, Rahway, NJ USA. Univ Toronto, Toronto, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, Boston, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4051 EP 4052 PG 2 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700088 ER PT J AU Sogg, S Mahaney, P Blackwood, H Blackwood, HS Krukowski, R Friedman, KE AF Sogg, Stephanie Mahaney, Patrick Blackwood, Hilary Blackwood, Hilary S. Krukowski, Rebecca Friedman, Kelli E. TI Clinical Q & A SO BARIATRIC NURSING AND SURGICAL PATIENT CARE LA English DT Editorial Material C1 [Blackwood, Hilary; Blackwood, Hilary S.] Duke Weight Loss Surg Ctr, Durham, NC 27704 USA. [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Mahaney, Patrick; Blackwood, Hilary S.] Duke Hlth Syst, Duke Weight Loss Surg Program, Durham, NC USA. [Krukowski, Rebecca] Duke Univ, Med Ctr, Med Psychol Intern, Durham, NC 27706 USA. RP Blackwood, HS (reprint author), Duke Weight Loss Surg Ctr, 3116 N Duke St, Durham, NC 27704 USA. EM Black124@mc.duke.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1557-1459 J9 BARIAT NURS SURG PAT JI Bariatr. Nurs. Surg. Patient Care PD DEC PY 2006 VL 1 IS 4 BP 293 EP 297 PG 5 WC Nursing SC Nursing GA V78AD UT WOS:000205273100012 ER PT J AU Milad, MR Goldstein, JM Orr, SP Wedig, MM Klibanski, A Pitman, RK Rauch, SL AF Milad, Mohammed R. Goldstein, Jill M. Orr, Scott P. Wedig, Michelle M. Klibanski, Anne Pitman, Roger K. Rauch, Scott L. TI Fear conditioning and extinction: Influence of sex and menstrual cycle in healthy humans SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE learning and memory; estrogen; anxiety; follicular phase; skin conductance response ID MEDIAL PREFRONTAL CORTEX; LONG-TERM POTENTIATION; HIPPOCAMPAL INACTIVATION DISRUPTS; POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHIATRIC DISORDERS; FACIAL EXPRESSIONS; ANXIETY DISORDERS; MEMORY; ESTROGEN; RATS AB Although sex differences have been demonstrated in behavioral paradigms of fear conditioning, the findings have been inconsistent, and fear extinction has been little studied. The present study investigated the influence of sex and menstrual cycle phase on the recall of fear extinction. Three groups of healthy adult participants were studied: women at 2 different phases of the menstrual cycle (early follicular [early cycle] and late follicular [midcycle]) and men. Participants underwent a 2-day fear conditioning and extinction protocol. The paradigm entailed habituation, fear conditioning, and extinction learning on Day I and extinction recall and fear renewal on Day 2. Skin conductance served as the dependent variable. During fear acquisition on Day 1, men showed significantly larger conditioned responses relative to women; early cycle and midcycle women did not differ. No significant group differences were found during extinction learning. On Day 2, men and early cycle women expressed greater extinction memory than midcycle women. These data confirm sex differences in conditioned fear acquisition and suggest that midcycle hormones attenuate extinction recall. C1 Harvard Univ, Psychiat Neurosci Div, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat & Med,Div Womens Hlth, Charlestown, MA 02129 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. RP Rauch, SL (reprint author), Harvard Univ, Psychiat Neurosci Div, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Bldg 149,2nd Floor,13th St, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu NR 63 TC 83 Z9 85 U1 3 U2 15 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD DEC PY 2006 VL 120 IS 6 BP 1196 EP 1203 DI 10.1037/0735-7044.120.5.1196 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 116SM UT WOS:000242822600002 PM 17201462 ER PT J AU Pollock, RA Carter, AS Amir, N Marks, LE AF Pollock, R. A. Carter, A. S. Amir, N. Marks, L. E. TI Anxiety sensitivity and auditory perception of heartbeat SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE anxiety; anxiety sensitivity; panic disorder; heartbeat perception ID PANIC DISORDER; THEORETICAL PERSPECTIVES; ATTENTIONAL BIAS; THREAT CUES; ATTACKS; AWARENESS; MEMORY; PATHOGENESIS; INFORMATION; IMPLICIT AB Anxiety sensitivity (AS) is the fear of sensations associated with autonomic arousal. AS has been associated with the development and maintenance of panic disorder. Given that panic patients often rate cardiac symptoms as the most fear-provoking feature of a panic attack, AS individuals may be especially responsive to cardiac stimuli. Consequently, we developed a signal-in-white-noise detection paradigm to examine the strategies that high and low AS individuals use to detect and discriminate normal and abnormal heartbeat sounds. Compared to low AS individuals, high AS individuals demonstrated a greater propensity to report the presence of normal, but not abnormal, heartbeat sounds. High and low AS individuals did not differ in their ability to perceive normal heartbeat sounds against a background of white noise; however, high AS individuals consistently demonstrated lower ability to discriminate abnormal heartbeats from background noise and between abnormal and normal heartbeats. AS was characterized by an elevated false alarm rate across all tasks. These results suggest that heartbeat sounds may be fear-relevant cues for AS individuals, and may affect their attention and perception in tasks involving threat signals. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Human Genet, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Univ Georgia, Dept Psychol, Athens, GA 30602 USA. John B Pierce Fdn Lab, New Haven, CT 06519 USA. Yale Univ, Dept Epidemiol, New Haven, CT USA. Yale Univ, Dept Psychol, New Haven, CT USA. RP Pollock, RA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Psychiat & Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rpollock@partners.org FU NIDCD NIH HHS [DC00271] NR 53 TC 17 Z9 18 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD DEC PY 2006 VL 44 IS 12 BP 1739 EP 1756 DI 10.1016/j.brat.2005.12.013 PG 18 WC Psychology, Clinical SC Psychology GA 108HC UT WOS:000242229900004 PM 16513082 ER PT J AU Goss, P AF Goss, Paul TI Update on the MA. 17 extended adjuvant trial SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE letrozole; adjuvant therapy; aromatase inhibitor; MA.17; extended adjuvant; disease-free survival; breast cancer ID ADVANCED BREAST-CANCER; ORAL AROMATASE INHIBITOR; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; PRIMARY THERAPY; PHASE-III; TAMOXIFEN; LETROZOLE; RECURRENCE; ANASTROZOLE AB For women with early breast cancer, a substantial risk of relapse remains after surgical resection of the primary tumor, despite adjuvant therapy. Adjuvant endocrine therapy with tamoxifen has been used for many years in the treatment of hormone-receptor-positive (HR+) disease, but exposure to the agent is limited to 5 years due to an unfavorable risk:benefit profile in later years. Despite the beneficial carry-over effects of tamoxifen, the majority of breast cancer recurrences and deaths occur after completion of adjuvant tamoxifen, that is, more than 5 years after initial diagnosis. Hence, additional endocrine therapy could greatly improve outcomes for women with HR+ early breast cancer, but until recently, no agent had been shown to provide a significant benefit over no further treatment. The first interim analysis of the NCIC CTG MA.17 trial showed that the third-generation aromatase inhibitor, letrozole, significantly reduced the risk of relapse, including distant metastases, compared with placebo in women who remained disease-free for up to 3 months after completion of standard adjuvant tamoxifen. On the basis of these results, the trial was stopped and unblinded. Final analysis confirmed these findings and also showed that letrozole significantly improved overall survival in patients with node-positive disease at. diagnosis. Retrospective analysis of MA.17 data has shown that the benefit achieved with letrozole increases with the duration of therapy, at least up to 48 months, raising important questions regarding the optimal duration of extended adjuvant letrozole. Additional retrospective analyses investigating the impact of estrogen- and progesterone-receptor status on response to therapy, and whether letrozole is effective following a prolonged treatment-free interval after stopping tamoxifen, are ongoing, and will help to optimize the use of letrozole in women who have completed tamoxifen. C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Breast Canc, Boston, MA 02114 USA. RP Goss, P (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Breast Canc, Cox Bldg,Suite 640,55 Fruit St,YAW 9A, Boston, MA 02114 USA. EM pgoss@partners.org NR 31 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD DEC PY 2006 VL 20 SU 1 BP S5 EP S13 DI 10.1016/j.beem.2006.10.002 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 126KU UT WOS:000243512600002 ER PT J AU Witczak, CA Hirshman, MF Jessen, N Fujii, N Seifert, MM Brandauer, J Hotamisligil, GS Goodyear, LJ AF Witczak, C. A. Hirshman, M. F. Jessen, N. Fujii, N. Seifert, M. M. Brandauer, J. Hotamisligil, G. S. Goodyear, L. J. TI JNK1 deficiency does not enhance muscle glucose metabolism in lean mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE knockout; mouse; glucose uptake; c-jun-NH2-terminal kinase; glycogen ID ACTIVATED PROTEIN-KINASE; MOUSE SKELETAL-MUSCLE; INSULIN-RESISTANCE; GLOBULAR ADIPONECTIN; STRESS; RAT; INFLAMMATION; OBESITY; ALPHA; PHOSPHORYLATION AB Mice deficient in c-jun-NH2-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction-induced muscle [H-3]2-deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct alterations in muscle. In vivo muscle [3H]2-deoxyglucose uptake in response to a glucose injection was also not enhanced by JNK1 deficiency, demonstrating that a circulating factor was not required to observe altered muscle glucose uptake in the knockout mice. JNK1 deficiency did not affect muscle glycogen levels or the protein expression of key molecules involved in glucose metabolism. This study is the first to directly demonstrate that enhanced skeletal muscle glucose metabolism does not underlie the beneficial effects of JNK1 deficiency in lean mice. (c) 2006 Elsevier lnc. All rights reserved. C1 Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274 FU NIAMS NIH HHS [R01 AR045670-08, F32 AR051663, F32 AR051663-02, F32AR051663, R01 AR042238, R01 AR042238-13, R01 AR045670, R01AR42238, R01AR45670]; NIDDK NIH HHS [DK36836, P30 DK036836, P30 DK036836-19, T32 DK007260, T32 DK007260-26, T32DK07260] NR 28 TC 15 Z9 15 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 1 PY 2006 VL 350 IS 4 BP 1063 EP 1068 DI 10.1016/j.bbrc.2006.09.158 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 100TD UT WOS:000241690800040 PM 17045576 ER PT J AU Niquet, J Seo, DW Wasterlain, CG AF Niquet, J. Seo, D. -W. Wasterlain, C. G. TI Mitochondrial pathways of neuronal necrosis SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology CY JUL 23-27, 2006 CL Swansea Med Sch, Swansea, WALES HO Swansea Med Sch ID APOPTOSIS-INDUCING FACTOR; TRANSIENT CEREBRAL-ISCHEMIA; OXYGEN-GLUCOSE DEPRIVATION; CELL-DEATH; STATUS EPILEPTICUS; INDUCED SEIZURES; GLOBAL-ISCHEMIA; HIPPOCAMPUS; ACTIVATION; MECHANISMS AB We examined the mechanism of neuronal necrosis induced by hypoxia, excitotoxicity or non-excitotoxic hypoxia. our observations showed that neuronal necrosis can be an active process starting with early mitochondrial swelling, followed by cytochrome c release and caspase cascade. Energy failure and/or calcium overloading of mitochondria may trigger this sequence of events. We called this form of necrosis 'programmed necrosis'. We discuss in this paper the contribution of another mitochondrial death factor, apoptosis-inducing factor. C1 Vet Affairs Greater Los Angeles Healthcare Syst 1, Neurol Serv, Epilepsy Res Labs, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Sungkyunkwan Univ, Samsung Med Ctr, Seoul 135710, South Korea. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wasterlain, CG (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst 1, Neurol Serv, Epilepsy Res Labs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU NINDS NIH HHS [R01 NS13515] NR 23 TC 15 Z9 18 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2006 VL 34 BP 1347 EP 1351 PN 6 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119LJ UT WOS:000243013500081 PM 17073816 ER PT J AU Taha, TA Mullen, TD Obeid, LM AF Taha, Tarek A. Mullen, Thomas D. Obeid, Lina M. TI A house divided: Ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE programmed cell death; ceramide; sphingosine; sphingosine-1-phosphate (S1P); sphingolipid; apoptosis ID PROTEIN-KINASE-C; TUMOR-NECROSIS-FACTOR; RADIATION-INDUCED APOPTOSIS; JURKAT T-CELLS; ACID SPHINGOMYELINASE; CYTOCHROME-C; GLIOMA-CELLS; CANCER-CELLS; HL-60 CELLS; CATHEPSIN-D AB Programmed cell death is an important physiological response to many forms of cellular stress. The signaling cascades that result in programmed cell death are as elaborate as those that promote cell survival, and it is clear that coordination of both protein- and lipid-mediated signals is crucial for proper cell execution. Sphingolipids are a large class of lipids whose diverse members share the common feature of a long-chain sphingoid base, e.g., sphingosine. Many sphingolipids have been shown to play essential roles in both death signaling and survival. Ceramide, an N-acylsphingosine, has been implicated in cell death following a myriad of cellular stresses. Sphingosine itself can induce cell death but via pathways both similar and dissimilar to those of ceramide. Sphingosine-1-phosphate, on the other hand, is an anti-apoptotic molecule that mediates a host of cellular effects antagonistic to those of its pro-apoptotic sphingolipid siblings. Extraordinarily, these lipid mediators are metabolically juxtaposed, suggesting that the regulation of their metabolism is of the utmost importance in determining cell fate. In this review, we briefly examine the role of ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death and highlight the potential roles that these lipids play in the pathway to apoptosis. (c) 2006 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132]; NIA NIH HHS [R01 AG016583]; NIGMS NIH HHS [R01 GM062887] NR 129 TC 162 Z9 167 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD DEC PY 2006 VL 1758 IS 12 BP 2027 EP 2036 DI 10.1016/j.bbamem.2006.10.018 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 122IZ UT WOS:000243220800012 PM 17161984 ER PT J AU Yip, KY Yu, HY Kim, PM Schultz, M Gerstein, M AF Yip, Kevin Y. Yu, Haiyuan Kim, Philip M. Schultz, Martin Gerstein, Mark TI The tYNA platform for comparative interactomics: a web tool for managing, comparing and mining multiple networks SO BIOINFORMATICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN INTERACTIONS; DATABASE; MODULARITY; MACHINERY; MOTIFS AB Biological processes involve complex networks of interactions between molecules. Various large-scale experiments and curation efforts have led to preliminary versions of complete cellular networks for a number of organisms. To grapple with these networks, we developed TopNet-like Yale Network Analyzer (tYNA), a Web system for managing, comparing and mining multiple networks, both directed and undirected. tYNA efficiently implements methods that have proven useful in network analysis, including identifying defective cliques, finding small network motifs (such as feed-forward loops), calculating global statistics (such as the clustering coefficient and eccentricity), and identifying hubs and bottlenecks. It also allows one to manage a large number of private and public networks using a flexible tagging system, to filter them based on a variety of criteria, and to visualize them through an interactive graphical interface. A number of commonly used biological datasets have been pre-loaded into tYNA, standardized and grouped into different categories. C1 Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. RP Gerstein, M (reprint author), Yale Univ, Dept Comp Sci, 51 Prospect St, New Haven, CT 06511 USA. EM mark.gerstein@yale.edu NR 20 TC 38 Z9 41 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC 1 PY 2006 VL 22 IS 23 BP 2968 EP 2970 DI 10.1093/bioinformatics/btl488 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 108NK UT WOS:000242246300026 PM 17021160 ER PT J AU Weiss, AP Goff, D Schacter, DL Ditman, T Freudenreich, O Henderson, D Heckers, S AF Weiss, Anthony P. Goff, Donald Schacter, Daniel L. Ditman, Tali Freudenreich, Oliver Henderson, David Heckers, Stephan TI Fronto-hippocampal function during temporal context monitoring in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; hippocampus; frontal lobe; memory; source monitoring; fMRI ID LONG-TERM-MEMORY; RECOGNITION MEMORY; PREFRONTAL CORTEX; 1ST-EPISODE SCHIZOPHRENIA; EPISODIC MEMORY; CONSCIOUS RECOLLECTION; FALSE RECOGNITION; HUMAN HIPPOCAMPUS; NAIVE PATIENTS; FOLLOW-UP AB Background. Patients with schizophrenia have difficulty using contextual information to recall the source of information. Given the importance of the hippocampus and prefrontal cortex (PFC) in this type of memory, we hypothesized that this cognitive deficit stemmed from aberrant fronto-hippocampal activation during memory retrieval. Methods: Patients with schizophrenia (n = 16) and age-matched comparison subjects (n = 16) underwent functional magnetic resonance imaging while performing a verbal memory task that requires intact use of temporal context. Blood oxygen-level dependent (BOLD) signal during correct memory decisions was compared between the two groups with statistical parametric mapping. Results: Contrary to our hypotheses, patients with schizophrenia demonstrated nearly identical memory performance to that of the differences, including a pattern of task-dependent comparison subjects. Despite this, there were significant between-group BOLD signal hypofrontality or hyperfrontality. In addition, whereas the highest-performing subset of the comparison group demonstrated robust modulation of hippocampal activity, this pattern was not seen in the highest-performing patients with schizophrenia. Conclusions: Despite memory performance similar to that of comparison subjects, patients with schizophrenia activated different neural pathways to achieve this success. This might reflect underlying neuropathology in fronto-hippocampal circuitry, the use of an alternate cognitive strategy to accomplish task performance, or both. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Bldg 149,Room 2606,13th St, Charlestown, MA 02129 USA. EM aweiss@partners.org RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [P41RR14075]; NIA NIH HHS [AG08441]; NIMH NIH HHS [MH06019, MH070560, MH60941] NR 69 TC 30 Z9 31 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2006 VL 60 IS 11 BP 1268 EP 1277 DI 10.1016/j.biopsych.2006.06.025 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 108ZW UT WOS:000242278700013 PM 17020747 ER PT J AU Cohen, G Carter, SL Weinberg, KI Masinsin, B Guinan, E Kurtzberg, J Wagner, JE Kernan, NA Parkman, R AF Cohen, Geoff Carter, Shelly L. Weinberg, Kenneth I. Masinsin, Bernadette Guinan, Eva Kurtzberg, Joanne Wagner, John E. Kernan, Nancy A. Parkman, Robertson TI Antigen-specific T-lymphocyte function after cord blood transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE immune reconstitution; antigen-specific immune function; cord blood transplantation ID BONE-MARROW-TRANSPLANTATION; IMMUNE RECONSTITUTION; CELLS; INFECTIONS; RESPONSES; RECOVERY; DISEASE; HUMANS AB It has not been possible to determine the singular contribution of naive T lymphocytes to antigen-specific immunity after hematopoietic stem cell transplantation (HSCT), because of the confounding effects of donor-derived antigen-specific T lymphocytes present in most hematopoietic stem cell (HSC) products. Because umbilical cord blood contains only naive T lymphocytes, we longitudinally evaluated the recipients of unrelated cord blood transplantation (UCBT) for the presence of T lymphocytes with specificity for herpesviruses, to determine the contribution of the naive T lymphocytes to antigen-specific immune reconstitution after HSCT. Antigen-specific T lymphocytes were detected early after UCBT (herpes simplex virus on day 29; cytomegalovirus on day 44; varicella zoster virus on day 94). Overall, 66 of 153 UCBT recipients developed antigen-specific T lymphocytes to I or more herpesviruses during the evaluation period. The likelihood of developing antigen-specific T lymphocyte function was not associated with immunophenotypic T lymphocyte reconstitution, transplant cell dose, primary disease, or acute and chronic graft-versus-host disease. These results indicate that naive T lymphocytes present in the HSC inoculum can contribute to the generation of antigen-specific T-lymphocyte immunity early after transplantation. (C) 2006 American Society fir Blood and Marrow Transplantation. C1 Childrens Hosp Los Angeles, Saban Res Inst, Dept Pediat, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90027 USA. EMMES Corp, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Parkman, R (reprint author), Childrens Hosp Los Angeles, Saban Res Inst, Dept Pediat, Div Res Immunol Bone Marrow Transplantat, 4650 Sunset Blvd,Mail Stop 62, Los Angeles, CA 90027 USA. EM rparkman@chla.usc.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NCI NIH HHS [P01-CA100265, P01 CA100265]; NHLBI NIH HHS [N01HB67132, N01-HB-67132, N01-HB-67113, N01HB67135, N01-HB-67139, N01-HB-67135, N01HB67138, N01-HB-67138, N01HB67139] NR 22 TC 43 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2006 VL 12 IS 12 BP 1335 EP 1342 DI 10.1016/j.bbmt.2006.08.036 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 119KZ UT WOS:000243012500012 PM 17162216 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Science in the blood SO BIOTECHNIQUES LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2006 VL 41 IS 6 BP 659 EP 659 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115LZ UT WOS:000242737100005 ER PT J AU Shivdasani, RA AF Shivdasani, Ramesh A. TI MicroRNAs: regulators of gene expression and cell differentiation SO BLOOD LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BINDING PROTEIN ALPHA; RNAI ENZYME COMPLEX; MESSENGER-RNAS; COMPUTATIONAL IDENTIFICATION; CAENORHABDITIS-ELEGANS/; HEMATOPOIETIC SYSTEM; ANIMAL MICRORNAS; NUCLEAR EXPORT; ZEBRAFISH AB The existence and roles of a class of abundant regulatory RNA molecules have recently come into sharp focus. Micro-RNAs (miRNAs) are small (approximately 22 bases), non-protein-coding RNAs that recognize target sequences of imperfect complementarity in cognate mRNAs and either destabilize them or inhibit protein translation. Although mechanisms of miRNA biogenesis have been elucidated in some detail, there is limited appreciation of their biological functions. Reported examples typically focus on miRNA regulation of a single tissue-restricted transcript, often one encoding a transcription factor, that controls a specific aspect of development, cell differentiation, or physiology. However, computational algorithms predict up to hundreds of putative targets for individual miRNAs, single transcripts may be regulated by multiple miRNAs, and miRNAs may either eliminate target gene expression or serve to fine-tune transcript and protein levels. Theoretical considerations and early experimental results hence suggest diverse roles for miRNAs as a class. One appealing possibility, that miRNAs eliminate low-level expression of unwanted genes and hence refine unilineage gene expression, may be especially amenable to evaluation in models of hematopoiesis. This review summarizes current understanding of miRNA mechanisms, outlines some of the important outstanding questions, and describes studies that attempt to define miRNA functions in hematopoiesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Biney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu NR 67 TC 186 Z9 218 U1 1 U2 26 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3646 EP 3653 DI 10.1182/blood-2006-01-030015 PG 8 WC Hematology SC Hematology GA 109LO UT WOS:000242309800012 PM 16882713 ER PT J AU DeAngelo, DJ Stone, RM Heaney, ML Nimer, SD Paquette, RL Klisovic, RB Caligiuri, MA Cooper, MR Lecerf, JM Karol, MD Sheng, SH Holford, N T Curtin, P Druker, BJ Heinrich, MC AF DeAngelo, Daniel J. Stone, Richard M. Heaney, Mark L. Nimer, Stephen D. Paquette, Ronald L. Klisovic, Rebecca B. Caligiuri, Michael A. Cooper, Michael R. Lecerf, Jean-Michel Karol, Michael D. Sheng, Shihong Holford, Nick T Curtin, Peter Druker, Brian J. Heinrich, Michael C. TI Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; CYTOGENETIC RESPONSES; ACTIVATING MUTATION; LOOP MUTATIONS; IMATINIB; AML; PROGNOSIS; IDENTIFICATION AB Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FILT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FILT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patients with either AML or high-risk myelodysplastic syndrome (MDS). Tandutinib was given orally in doses ranging from 50 mg to 700 mg twice daily The principal dose-limiting toxicity (DLT) of tandutinib was reversible generalized muscular weakness, fatigue, or both, occurring at doses of 525 mg and 700 mg twice daily. Tandutinib's pharmacokinetics were characterized by slow elimination, with achievement of steady-state plasma concentrations requiring greater than 1 week of dosing. Western blotting showed that tandutinib inhibited phosphorylation of FLT3 in circulating leukemic blasts. Eight patients had FLT3-ITD mutations; 5 of these were evaluable for assessment of tandutinib's antileukemic effect. Two of the 5 patients, treated at 525 mg and 700 mg twice daily, showed evidence of antileukemic activity, with decreases in both peripheral and bone marrow blasts. Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Millennium Pharmaceut, Cambridge, MA USA. Univ Auckland, Auckland 1, New Zealand. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland Vet Adm VA Med Ctr, Portland, OR USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ddeangelo@partners.org RI Klisovic, Rebecca/E-3401-2011; OI Holford, Nick/0000-0002-4031-2514 FU NCI NIH HHS [P01 CA066996, P01 CA66996-06A1] NR 26 TC 152 Z9 157 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3674 EP 3681 DI 10.1182/blood-2006-02-005702 PG 8 WC Hematology SC Hematology GA 109LO UT WOS:000242309800016 PM 16902153 ER PT J AU Zirlik, KM Zahrieh, D Neuberg, D Gribben, JG AF Zirlik, Katja Mauerer Zahrieh, David Neuberg, Donna Gribben, John G. TI Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CLASS-I MOLECULES; COMPLEX CLASS-I; NORMAL B-CELLS; ADOPTIVE IMMUNOTHERAPY; DNA IMMUNIZATION; IMMUNE-RESPONSE; REACTIVE CTL; IMMUNOGLOBULIN; IMMUNOGENICITY AB Heteroclitic peptide modifications increase immunogenicity, allowing generation of cytotoxic T lymphocytes (CTLs) against weakly immunogenic tumor-associated antigens (TAAs). A critical issue is whether T cells generated against heteroclitic peptides; retain the ability to recognize and kill tumor cells expressing the original weak TAAs, and whether there is a lower threshold of binding affinity of the native peptides, below which such CTLs can still kill primary tumor cells. To examine this we used a model examining the ability of native and heteroclitic immunoglobulin (Ig)-derived peptides to generate CTLs that can kill chronic lymphocytic leukemia (CLL) cells. We demonstrate that CTLs generated against heteroclitic peptides have enhanced killing of CD40-activated B cells pulsed with either heteroclitic (P <.001) or native peptide (P=.04) and primary CLL cells (P=.01). The novel finding reported here is that the rate-limiting factor appears to be the ability to generate CTLs and that once generated, CTL lysis of primary tumor cells is independent of the binding affinity of the native peptide. These findings have implications for vaccination strategies in malignancies and are currently being further examined in vivo in murine models. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol & Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Comp Biol, Cambridge, MA 02138 USA. Univ Freiburg, Med Ctr, Dept Hematol Oncol, D-7800 Freiburg, Germany. RP Gribben, JG (reprint author), Barts & London Sch Med, Inst Canc, London, England. EM john.gribben@cancer.org.uk FU NCI NIH HHS [P01 CA081534, CA81534] NR 60 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3865 EP 3870 DI 10.1182/blood/2006-04-014415 PG 6 WC Hematology SC Hematology GA 109LO UT WOS:000242309800042 PM 16902144 ER PT J AU Bliziotes, M Eshleman, A Burt-Pichat, B Zhang, XW Hashimoto, J Wiren, K Chenu, C AF Bliziotes, M. Eshleman, A. Burt-Pichat, B. Zhang, X. -W. Hashimoto, J. Wiren, K. Chenu, C. TI Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells SO BONE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TX SP Amer Soc Bone & Mineral Res DE bone; neurotransmitter; transporter; osteoblast; osteocyte ID MESSENGER-RNA EXPRESSION; TRYPTOPHAN-HYDROXYLASE; BONE-FORMATION; ANTIPEPTIDE ANTIBODIES; IMMUNOREACTIVE NERVES; GLUTAMATE RECEPTORS; 5-HT1A RECEPTOR; LONG BONES; FLUID-FLOW; IN-VITRO AB Neurotransmitter regulation of bone metabolism has been a subject of increasing interest and investigation. We reported previously that osteoblastic cells express a functional scrotonin (5-HT) signal transduction system, with mechanisms for responding to and regulating uptake of 5-HT. The clonal murine osteocytic cell line, MLO-Y4, demonstrates expression of the serotonin transporter (5-HTT), and the 5-HT1A, and 5-HT2A receptors by real-time RT-PCR and immunoblot analysis. Immunohistochemistry using antibodies for the 5-HTT, and the 5-HT1A and 5-HT,, receptors reveals expression of all three proteins in both osteoblasts and osteocytes in rat tibia. 5-HTT binding sites were demonstrated in the MLO-Y4 cells with nanomolar affinity for the stable cocaine analog [I-125]RTI-55. Imipramine and fluoxetine, antagonists with specificity for 5-HTT, show the highest potency to antagonize [I-125]RTI-55 binding in the MLO-Y4 cells. GBR-12935, a relatively selective dopamine transporter antagonist, had a much lower potency, as did desipramine, a selective norepinephrine transporter antagonist. The maximal [H-3]5-HT uptake rate in MLO-Y4 cells was 2.85 pmol/15 min/well, with a K-m value of 290 nM. Imipramine and fluoxetine inhibited specific [H-3]5-HT uptake with IC50 values in the nanomolar range. 5-HT rapidly stimulated PGE(2) release from MLO-Y4 cells; the EC50 for 5-HT was 0.1 mu M, with a 3-fold increase seen at 60 min. The rate-limiting enzyme for serotonin synthesis, tryptophan hydroxylase, is expressed in MLO-Y4 cells as well as osteoblastic MC3T3-E1 cells. Thus, osteocytes, as well as osteoblasts, are capable of 5-HT synthesis, and express functional receptor and transporter components of the 5-HT signal transduction system. (c) 2006 Elsevier Inc. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. Hop Edouard Herriot, INSERM Unit 403, Lyon, France. RP Bliziotes, M (reprint author), Portland VA Med Ctr, P3 ENDO, Portland, OR 97239 USA. EM bliziote@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU NIAMS NIH HHS [R01 AR052018-02, R01 AR052018-01A1]; NIDDK NIH HHS [DK54415] NR 50 TC 60 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD DEC PY 2006 VL 39 IS 6 BP 1313 EP 1321 DI 10.1016/j.bone.2006.06.009 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 119KT UT WOS:000243011900019 PM 16884969 ER PT J AU Moore, CW Rauch, PK AF Moore, C. W. Rauch, P. K. TI Addressing parenting concerns of bone marrow transplant patients: opening (and closing) Pandora's box SO BONE MARROW TRANSPLANTATION LA English DT Review DE parental illness; children's coping; family communication ID QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BREAST-CANCER; PSYCHOLOGICAL DISTRESS; ADJUVANT CHEMOTHERAPY; ADOLESCENT CHILDREN; ADJUSTMENT; ILLNESS; FAMILY AB Although a significant number of adults undergoing stem cell transplant (SCT) or bone marrow transplantation (BMT) care for dependent children, and these treatments pose significant challenges for families, research has virtually ignored the impact of parenting on patients' quality of life during BMT/SCT and children's responses to having a parent undergo these treatments. Physicians rarely inquire about parenting concerns related to the extended hospitalizations necessitated by these treatments, yet clinical experience suggests that addressing patient concerns about children's reactions to cancer and BMT/SCT can improve the experience of the patient and the patient's family, and help the medical team respond effectively to sources of patients' distress. Parents frequently want to know what reactions to expect from children, thus general developmental information is reviewed, and recommendations given for when professional help for children is warranted. A key way for parents to support their children is with open, honest communication; however, parents often find it extremely difficult to talk about cancer and BMT/SCT with their children. The medical team can assist patients' efforts to communicate with and support their children by asking about a patient's children, providing some targeted information, and discussing the potential impact of treatments on parenting capacity. Inquiring about and addressing parenting concerns may initially seem difficult, but can ultimately facilitate stronger doctor-patient alliances, and more compassionate care. C1 Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Dept Psychiat, Boston, MA 02114 USA. RP Moore, CW (reprint author), Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Dept Psychiat, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. EM cmoore8@partners.org NR 59 TC 9 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2006 VL 38 IS 12 BP 775 EP 782 DI 10.1038/sj.bmt.1705522 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 110JZ UT WOS:000242376000002 PM 17041607 ER PT J AU Vucic, S Tian, D Chong, PST Cudkowicz, ME Hedley-Whyte, ET Cros, D AF Vucic, S. Tian, D. Chong, P. Siao Tick Cudkowicz, M. E. Hedley-Whyte, E. T. Cros, D. TI Facial onset sensory and motor neuronopathy (FOSMN syndrome): a novel syndrome in neurology SO BRAIN LA English DT Article DE FOSMN syndrome; syringomyelia; motoneuron disease; sensory neuropathy ID SARCOID PERIPHERAL NEUROPATHY; AMYOTROPHIC-LATERAL-SCLEROSIS; SYRINGOMYELIA-LIKE SYNDROME; BULBAR MUSCULAR-ATROPHY; TANGIER-DISEASE; SJOGRENS-SYNDROME; ROOT STIMULATION; NERVE; GENE; MUTATION AB A 'syringomyelia-like' syndrome has been infrequently reported in neurological disorders such as Tangiers disease and lepromatous leprosy. This study reports a novel 'syringomyelia-like' syndrome in four adult male patients, which we have termed facial onset sensory and motor neuronopathy, or FOSMN syndrome, that appears to have a neurodegenerative aetiology. Clinical, neurophysiological and pathological data of four patients were reviewed, including the autopsy in one patient. Four male patients (mean age at onset 43), initially developed paraesthesiae and numbness in a trigeminal nerve distribution, which slowly progressed to involve the scalp, neck, upper trunk and upper limbs in sequential order. Motor manifestations, including cramps, fasciculations, dysphagia, dysarthria, muscle weakness and atrophy developed later in the course of the illness. Neurophysiological findings revealed a generalized sensory motor neuronopathy of caudally decreasing severity in all four patients. Autopsy in one patient disclosed loss of motoneurons in the hypoglossal nucleus and cervical anterior horns, along with loss of sensory neurons in the main trigeminal sensory nucleus and dorsal root ganglia. FOSMN syndrome appears to be a slowly progressive neurodegenerative disorder, whose pathogenesis remains to be determined. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol,Dept Pathol, Boston, MA 02114 USA. Prince Wales Med Res Inst, Randwick, NSW, Australia. RP Cros, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM dcros@partners.org NR 35 TC 22 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 2006 VL 129 BP 3384 EP 3390 DI 10.1093/brain/awl258 PN 12 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 111RE UT WOS:000242471100029 PM 17012296 ER PT J AU Rincon, M Broadwater, G Harris, L Crocker, A Weaver, D Dressler, L Berry, D Sutton, L Michaelson, R Messino, M Kirshner, J Fleming, G Winer, E Hudis, C Appel, S Norton, L Muss, H AF Rincon, Mercedes Broadwater, Gloria Harris, Lyndsay Crocker, Abigail Weaver, Donald Dressler, Lynn Berry, Donald Sutton, Linda Michaelson, Richard Messino, Michael Kirshner, Jeffrey Fleming, Gini Winer, Eric Hudis, Clifford Appel, Stacy Norton, Larry Muss, Hyman CA Canc Leukemia Grp B TI Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Metastases; IL-6; PGP; Paclitaxel response ID SERUM-LEVELS; OVARIAN-CANCER; CHEMOTHERAPY; TUMORS AB Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer. C1 Univ Vermont, Vermont Reg Canc Ctr, Burlington, VT 05401 USA. Duke Univ, CALGB Stat Ctr, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Mt Sinai Sch Med, New York, NY USA. SE Canc Control Consortium Inc, CCOP, Goldsboro, NC USA. SUNY Upstate Med Univ, Syracuse, NY USA. Univ Chicago, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Muss, H (reprint author), Univ Vermont, Vermont Reg Canc Ctr, 1 S Prospect St,UHC Campus,St Joseph 3400, Burlington, VT 05401 USA. EM hyman.muss@uvm.edu OI Norton, Larry/0000-0003-3701-9250 NR 23 TC 17 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2006 VL 100 IS 3 BP 301 EP 308 DI 10.1007/s10549-006-9251-7 PG 8 WC Oncology SC Oncology GA 103MG UT WOS:000241889200008 PM 16773437 ER PT J AU Min, W Geoffrey, B Adrian, C Lyne, B Sylvie, V Andrea, R Ronald, DA Murray, R AF Min, Wu Geoffrey, Boynton Adrian, Cooper Lyne, Breault Sylvie, Vincent Andrea, Richardson Ronald, Depinho A. Murray, Robinson TI Genetically engineered human breast tumors in mice SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas San Antonio, Hlth Sci Ctr C1 AVEO Pharmaceut Inc, Cambridge, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2006 VL 100 IS 3 BP 341 EP 341 PG 1 WC Oncology SC Oncology GA 103MG UT WOS:000241889200018 ER PT J AU Frackelton, AR Hafer, LJ Lis, R Lyle, S Hsieh, CC Liu, Q Bhat, G Sgroi, D Turbin, D Huntsman, DJ AF Frackelton, A. R., Jr. Hafer, L. J. Lis, R. Lyle, S. Hsieh, C.-C. Liu, Q. Bhat, G. Sgroi, D. Turbin, D. Huntsman, D. J. TI Shc proteins in primary breast tumors predict outcome in treatment naive, tamoxifen-treated and chemotherapy-treated patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas San Antonio, Hlth Sci Ctr C1 Roger Williams Canc Med Ctr, Providence, RI USA. Catalyst Oncol, Worcester, MA USA. UMass, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. British Columbia Canc Agcy, GPEC, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2006 VL 100 IS 3 BP 343 EP 343 PG 1 WC Oncology SC Oncology GA 103MG UT WOS:000241889200022 ER PT J AU Stepans, MBF Wilhelm, SL Hertzog, M Rodehorst, TKC Blaney, S Clemens, B Polak, JJ Newburg, DS AF Stepans, Mary Beth Flanders Wilhelm, Susan L. Hertzog, Melody Rodehorst, T. Kim Callahan Blaney, Susan Clemens, Beth Polak, Josef J., III Newburg, David S. TI Early Consumption of Human Milk Oligosaccharides Is Inversely Related to Subsequent Risk of Respiratory and Enteric Disease in Infants SO BREASTFEEDING MEDICINE LA English DT Article AB A pilot study tested the relationship between human milk oligosaccharide consumption, oligosaccharide content of feces, and subsequent disease in breastfed infants. Forty-nine (49) mother-infant pairs provided milk and fecal samples 2 weeks postpartum; infant health was assessed through 2, 6, 12, and 24 weeks. LNF-II (lacto-N-fucopentaose II), a major human milk oligosaccharide, was measured to represent levels of total oligosaccharides consumed in milk and remaining in feces. LNF-II levels in milk at 2 weeks postpartum were associated with fewer infant respiratory problems by 6 weeks (p = 0.010), as were LNF-II levels in infant feces (p = 0.003). LNF-II levels in milk at 2 weeks were also associated with fewer respiratory problems by 12 weeks (p = 0.038), and fewer enteric problems by 6 weeks (p = 0.004) and 12 weeks (p = 0.045). Thus, consumption of human milk oligosaccharides through breastfeeding, represented by LNF-II, was associated with less reported respiratory and gastrointestinal illness in infants. C1 [Polak, Josef J., III; Newburg, David S.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Stepans, Mary Beth Flanders] Univ Wyoming, Sch Nursing, Laramie, WY 82071 USA. [Wilhelm, Susan L.; Rodehorst, T. Kim Callahan; Blaney, Susan; Clemens, Beth] Univ Nebraska Med Ctr, Coll Nursing, Scottsbluff, NE USA. [Hertzog, Melody] Univ Nebraska Med Ctr, Coll Nursing, Lincoln, NE USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM dnewburg@partners.org FU NIH [HD13021, DK40561]; University of Wyoming Northern Rockies [BRIN RR 16474] FX Support for this research was granted by the NIH: HD13021; DK40561; University of Wyoming Northern Rockies BRIN RR 16474. Valuable contributions to this research were made by Mary Jacewicz, David Ma, and Deborah Newburg. D. S. N. owns shares of Glycosyn, Inc.; potential conflicts of interest have been disclosed and are being managed by Massachusetts General Hospital. NR 38 TC 32 Z9 35 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD WIN PY 2006 VL 1 IS 4 BP 207 EP 215 DI 10.1089/bfm.2006.1.207 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA V11LR UT WOS:000207533600002 PM 17661601 ER PT J AU Tohen, M Bowden, CL Calabrese, JR Lin, D Forrester, TD Sachs, GS Koukopoulos, A Yatham, L Grunze, H AF Tohen, Mauricio Bowden, Charles L. Calabrese, Joseph R. Lin, Daniel Forrester, Tammy D. Sachs, Gary S. Koukopoulos, Athanasios Yatham, Lakshmi Grunze, Heinz TI Influence of sub-syndromal symptoms after remission from manic or mixed episodes SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; BIPOLAR-I DISORDER; SUBSYNDROMAL SYMPTOMS; DOUBLE-BLIND; LITHIUM; RECOVERY; IMPAIRMENT; RECURRENCE; OLANZAPINE; MORBIDITY AB Background Sub-syndromal symptoms in bipolar disorder impair functioning and diminish quality of life. Aims To examine factors associated with time spent with sub-syndromal symptoms and to characterise how these symptoms influence outcomes. Method In a double-blind randomised maintenance trial, patients received either olanzapine or lithium monotherapy for 1 year. Stepwise logistic regression models were used to identify factors that were significant predictors of percentage time spent with sub-syndromal symptoms. The presence of sub-syndrornal symptoms during the first 8 weeks was examined as a predictor of subsequent relapse. Results Presence of sub-syndromal depressive symptoms during the first 8 weeks significantly increased the likelihood of depressive relapse (relative risk 4.67, P < 0.001). Patients with psychotic features and those with a greater number of previous depressive episodes were more likely to experience sub-syndromal depressive symptoms (RR=2.51, P < 0.001 and RR=2.35, P=0.03 respectively). Conclusions These findings help to identify patients at increased risk of affective relapse and suggest that appropriate therapeutic interventions should be considered even when syndromal-level symptoms are absent Declaration of interest Sponsorship from Lilly Research Laboratories. C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Lucio Bini, Rome, Italy. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Munich, Dept Psychiat, D-80539 Munich, Germany. RP Tohen, M (reprint author), Lilly Res Labs, Indianapolis, IN 46285 USA. EM m.tohen@lilly.com OI Grunze, Heinz/0000-0003-4712-8979 NR 26 TC 48 Z9 49 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD DEC PY 2006 VL 189 BP 515 EP 519 DI 10.1192/bjp.bp.105.020321 PG 5 WC Psychiatry SC Psychiatry GA 114QH UT WOS:000242680200007 PM 17139035 ER PT J AU Murie, JA Sarr, MG Warshaw, AL AF Murie, J. A. Sarr, M. G. Warshaw, A. L. TI A tale of three papers SO BRITISH JOURNAL OF SURGERY LA English DT Editorial Material ID BILE-DUCT; CHOLECYSTECTOMY; INJURIES C1 Royal Infirm, Dept Vasc Surg, Edinburgh, Midlothian, Scotland. Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Murie, JA (reprint author), Royal Infirm, Dept Vasc Surg, Edinburgh, Midlothian, Scotland. EM bjs@wiley.co.uk NR 6 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD DEC PY 2006 VL 93 IS 12 BP 1560 EP 1562 DI 10.1002/bjs.5642 PG 3 WC Surgery SC Surgery GA 118RY UT WOS:000242960600020 PM 17115395 ER PT J AU Tsai, HK Chen, MH McLeod, DG Carroll, PR Richie, JP D'Amico, AV AF Tsai, Henry K. Chen, Ming-Hui McLeod, David G. Carroll, Peter R. Richie, Jerome P. D'Amico, Anthony V. TI Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer SO CANCER LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol DE prostate carcinoma; radiotherapy; radical prostatectomy; outcome; mortality ID DOSE-ESCALATION; COMPETING RISK; ANTIGEN ERA; MITOXANTRONE; PREDNISONE; RECURRENCE; DOCETAXEL; SURVIVAL; FAILURE; CAPSURE AB BACKGROUND. The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS. The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] > 10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS. Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P-Gray = .0051) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P-Gray < -001]) when compared with men with any I or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS. Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP. C1 Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tsai, HK (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, 375 Longwood Ave, Boston, MA 02115 USA. EM htsai@partners.org NR 24 TC 21 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2006 VL 107 IS 11 BP 2597 EP 2603 DI 10.1002/cncr.22279 PG 7 WC Oncology SC Oncology GA 108UG UT WOS:000242264100011 PM 17039498 ER PT J AU Ryan, DR O'Neil, BH Supko, JG Lima, CMR Dees, EC Appleman, LJ Clark, J Fidias, P Orlowski, RZ Kashala, O Eder, JR Cusack, JC AF Ryan, David R. O'Neil, Bell H. Supko, Jeffrey G. Lima, Carlo M. Rocha Dees, E. Claire Appleman, Leonard J. Clark, Jeffrey Fidias, Phinos Orlowski, Robert Z. Kashala, Oscar Eder, Joseph R. Cusack, James C., Jr. TI A phase I study of bortezomib plus irinotecan in patients with advanced solid tumors SO CANCER 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 DE bortezomib; colorectal cancer; irinotecan; proteasome inhibitor; solid tumors ID PROTEASOME INHIBITOR PS-341; MULTIPLE-MYELOMA CELLS; TOPOISOMERASE-I; REFRACTORY MYELOMA; RESISTANCE; CANCER; TRIAL; APOPTOSIS; MECHANISMS; CHEMOTHERAPY AB BACKGROUND. The authors conducted a Phase I dose-finding trial to study the use of combined bortezomib plus irinotecan in patients with advanced solid tumors. METHODS. Patients who had received >= 1 prior chemotherapy regimen were eligible. Patients received bortezomib (1.0 mg/m(2), 1.3 mg/m(2), or 1.5 mg/m2) on Days 1, 4, 8, and 11 and received irinotecan (from 50 mg/m(2) to 125 mg/m(2)) on Days 1 and 8 of each 21-day cycle for a maximum of 8 cycles. Bortezomib followed irinotecan on coadministration days in Cycle 1 and Cycles 3 through 8 but preceded irinotecan in Cycle 2 to assess the effect of administration sequence on bortezomib pharmacodynamics. RESULTS. Fifty-one enrolled patients with malignancies, including colorectal cancer (n = 23 patients), lung cancer (n 6 patients), gastroesophageal cancer (n = 6 patients), and pancreatic cancer (n 3 patients), received >= 1 dose of study drug. Nausea, vomiting, and diarrhea were the principal dose-limiting toxicities and led to the maximum tolerated doses of 1.3 mg/m(2) bortezomib and 125 mg/m(2) irinotecan. The most common grade >= 3 bortezomib-related nonhematologic adverse events were fatigue (n = 5 episodes), diarrhea (n = 4 episodes), and nausea (n = 4 episodes). grade >= 3 bortezomib-related hematologic adverse events included neutropenia (n = 6 episodes) and thrombocytopenia (n = 4 episodes) and rarely were dose limiting. Of 34 evaluable patients, no objective responses according to the Response Evaluation Criteria in Solid Tumors were seen; 10 patients achieved stable disease. The degree of proteasome inhibition in whole blood indicated that the biologic activity of bortezomib was unaffected by irinotecan coadministration. CONCLUSIONS. The results of this Phase I study in patients with solid tumors indicated that bortezomib at a dose of 1.3 mg/m(2) on Days 1, 4, 8, and 11 plus irinotecan at a dose of 125 mg/m(2) on Days I and 8 every 21 days were the recommended Phase 11 doses. Cancer 2006;107:2688-97. @ 2006 American Cancer Society. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Miami, Miami, FL 33152 USA. Sylvester Canc Ctr, Miami, FL 33152 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Ryan, DR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 100 Blossom St,COX640, Boston, MA 02114 USA. EM dpryan@partners.org OI Appleman, Leonard/0000-0003-4951-7388 NR 30 TC 47 Z9 47 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 DEC 1 PY 2006 VL 107 IS 11 BP 2688 EP 2697 DI 10.1002/cncr.22280 PG 10 WC Oncology SC Oncology GA 108UG UT WOS:000242264100023 PM 17075878 ER PT J AU Kornblith, AB Dowell, JM Herndon, JE Engelman, BJ Bauer-Wu, S Small, EJ Morrison, VA Atkins, J Cohen, HJ Holland, JC AF Kornblith, Alice B. Dowell, Jeannette M. Herndon, James E., II Engelman, Beverly J. Bauer-Wu, Susan Small, Eric J. Morrison, Vicki A. Atkins, James Cohen, Harvey Jay Holland, Jimmie C. TI Telephone monitoring of distress in patients aged 65 years or older with advanced stage cancer - A cancer and leukemia group 8 study SO CANCER LA English DT Article DE adaptation; psychosocial; quality of life; aged ID QUALITY-OF-LIFE; SOCIAL SUPPORT; BREAST-CANCER; DEPRESSION; VALIDATION; ONCOLOGY; ANXIETY; DISEASE; BURDEN; IMPACT AB BACKGROUND. Significant barriers to cancer patients receiving mental health treatment for distress have been reported in the literature. The objective of the current study was to determine whether distress in older patients (aged 65 years and older) would be reduced with educational materials (EM) supplemented by monthly telephone monitoring (TM) (TM + EM) compared with the use of EM alone because of more timely referrals to appropriate health professionals. METHODS. One hundred ninety-two older patients with breast, prostate, and colorectal cancers who had advanced disease and currently were receiving treatment were randomized to receive either TM + EM or EM alone. One hundred thirty-one patients were evaluated by telephone interview for psychologic and physical distress and for social support at baseline and at 6 months using the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 quality-of-life questionnaire, and the Medical Outcomes Study (MOS) Social Support Survey. Patients who in the TM + EM group were called monthly for 6 months to monitor their distress using the HADS and EORTC physical symptom items and the MOS Social Support Survey items, with cutoff levels were established to indicate which patients were in greater distress. Those patients who scored above the cutoff levels were referred to their oncology nurse for referral to the appropriate professional. Patients in the EM group received written materials regarding cancer-related psychosocial issues and available resources. RESULTS. At 6 months, patients in the TM + EM group reported significantly less anxiety (HADS; P <.0001), depression (HADS; P =.0004), and overall distress (HADS; P <.0001) compared with patients in the EM group. CONCLUSIONS. Monthly monitoring of older patients' distress with TM and EM along with referral for appropriate help was found to be an efficient means of reducing patients' anxiety and depression compared with patients who received only EM. C1 Dana Farber Canc Inst, Breast Oncol Program, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B, Statist Ctr, Durham, NC 27706 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. Univ Calif San Francisco, Comprehens Care Ctr, Dept Med & Oncol, San Francisco, CA 94143 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Sect Hemtol Oncol & Infect Dis 3 E, Minneapolis, MN 55417 USA. SE Canc Control Consortium, Winston Salem, NC USA. Duke Univ, Ctr Aging, Durham, NC 27706 USA. Vet Affairs Med Ctr, Durham, NC 27706 USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Breast Oncol Program, Mayer 2,RM 221,44 Binney St, Boston, MA 02115 USA. EM alice_kornblith@dfci.harvard.edu FU NCI NIH HHS [CA47559, CA02599, CA03927, CA04326, CA07968, CA11789, CA12046, CA16450, CA21060, CA26806, CA31946, CA32291, CA33601, CA41287, CA45418, CA45808, CA47577, CA60138, CA74811, CA77406, CA77440, CA77651, CA77658]; PHS HHS [C31946] NR 36 TC 29 Z9 29 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2006 VL 107 IS 11 BP 2706 EP 2714 DI 10.1002/cncr.22296 PG 9 WC Oncology SC Oncology GA 108UG UT WOS:000242264100025 PM 17078057 ER EF