FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chen, YL Yock, T Butler, W Adams, J Fullerton, B Tarbell, N AF Chen, YL Yock, T Butler, W Adams, J Fullerton, B Tarbell, N TI Reduction of cochlear dose using proton boost for pediatric medulloblastoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN 13-16, 2004 CL Boston, MA C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2004 VL 6 IS 4 BP 450 EP 451 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400532 ER PT J AU Sternini, C Patierno, S Selmer, IS Kirchgessner, A AF Sternini, C Patierno, S Selmer, IS Kirchgessner, A TI The opioid system in the gastrointestinal tract SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE ascending excitatory neurones; descending inhibitory neurones; G-protein-coupled receptors; interneurones; receptor endocytosis ID GUINEA-PIG ILEUM; MYENTERIC PLEXUS PREPARATION; ENTERIC NERVOUS-SYSTEM; MU-OPIATE RECEPTOR; POSTOPERATIVE ILEUS; CIRCULAR MUSCLE; SMALL-INTESTINE; ENDOGENOUS OPIOIDS; PORCINE ILEUM; CHOLINERGIC TRANSMISSION AB mu-, delta- and kappa-opioid receptors (ORs) mediate the effects of endogenous opioids and opiate drugs. Here we report (1) the distribution of muOR in the guinea-pig and human gastrointestinal tract in relation to endogenous ligands, to functionally distinct structures in the gut and to deltaOR and kappaOR; and (2) the ligand-induced muOR endocytosis in enteric neurones using in vitro and in vivo models. In the guinea pig, muOR immunoreactivity is confined mainly to the myenteric plexus. muOR myenteric neurones are most numerous in the small intestine, followed by the stomach and the proximal colon. muOR immunoreactive fibres are dense in the muscle layer and the deep muscular plexus, where they are in close association with interstitial cells of Cajal. This distribution closely matches the pattern of enkephalin. muOR enteric neurones comprise functionally distinct populations of neurones of the ascending and descending pathways of the peristaltic reflex. In human gut, muOR immunoreactivity is localized to myenteric and submucosal neurones and to immune cells of the lamina propria. deltaOR immunoreactivity is located in both plexuses where it is predominantly in varicose fibres in the plexuses, muscle and mucosa, whereas kappaOR immunoreactivity appears to be confined to the myenteric plexus and to bundles of fibres in the muscle. muOR undergoes endocytosis in a concentration-dependent manner, in vitro and in vivo. Pronounced muOR endocytosis is observed in neurones from animals that underwent abdominal surgery that has been shown to induce delay in gastrointestinal transit. We can conclude that all three ORs are localized to the enteric nervous system with differences among species, and that muOR endocytosis can be utilized as a means to visualize enteric neurones activated by opioids and sites of opioid release. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol,Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA USA. GlaxoSmithKline, Neurol & GI Ctr Excellence Drug Discovery, Harlow, Essex, England. RP Sternini, C (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Bldg 115,Room 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM csternin@ucla.edu FU NIDDK NIH HHS [DK 41301, DK 54155] NR 89 TC 96 Z9 100 U1 0 U2 13 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD OCT PY 2004 VL 16 SU 2 BP 3 EP 16 DI 10.1111/j.1743-3150.2004.00553.x PG 14 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 852MT UT WOS:000223760100002 PM 15357847 ER PT J AU Long, C Brown, EN Manoach, D Solo, V AF Long, C Brown, EN Manoach, D Solo, V TI Spatiotemporal wavelet analysis for functional MRI SO NEUROIMAGE LA English DT Article DE spatiotemporal; functional MRI; wavelets ID TIME-SERIES ANALYSIS; WORKING-MEMORY; SIGNIFICANT ACTIVATION; STATISTICAL-ANALYSIS; SENSORY STIMULATION; RESAMPLING METHODS; PREFRONTAL CORTEX; SIGNAL CHANGES; FMRI; NOISE AB Characterizing the spatiotemporal behavior of the BOLD signal in functional Magnetic Resonance Imaging (fMRI) is a central issue in understanding brain function. While the nature of functional activation clusters is fundamentally heterogeneous, many current analysis approaches use spatially invariant models that can degrade anatomic boundaries and distort the underlying spatiotemporal signal. Furthermore, few analysis approaches use true spatiotemporal continuity in their statistical formulations. To address these issues, we present a novel spatiotemporal wavelet procedure that uses a stimulus-convolved hemodynamic signal plus correlated noise model. The wavelet fits, computed by spatially constrained maximum-likelihood estimation, provide efficient multiscale representations of heterogeneous brain structures and give well-identified, parsimonious spatial activation estimates that are modulated by the temporal fMRI dynamics. In a study of both simulated data and actual fMRI memory task experiments, our new method gave lower mean-squared error and seemed to result in more localized fMRI activation maps compared to models using standard wavelet or smoothing techniques. Our spatiotemporal wavelet framework suggests a useful tool for the analysis of fMRI studies. (C) 2004 Elsevier Inc. All rights reserved. C1 MGH Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Michigan, Dept Elect Engn, Ann Arbor, MI 48109 USA. RP Long, C (reprint author), Massachusetts Gen Hosp East, Dept Radiol, 13th St,Bldg 149,Charlestown Navy Yard, Charlestown, MA 02129 USA. EM cjl@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR14705]; NIBIB NIH HHS [R01 EB0522]; NIMH NIH HHS [K02 MH61637] NR 49 TC 22 Z9 23 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2004 VL 23 IS 2 BP 500 EP 516 DI 10.1016/j.neuroimage.2004.04.017 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 867BM UT WOS:000224817100006 PM 15488399 ER PT J AU Brambilla, P Stanley, JA Sassi, RB Nicoletti, MA Mallinger, AG Keshavan, MS Soares, JC AF Brambilla, P Stanley, JA Sassi, RB Nicoletti, MA Mallinger, AG Keshavan, MS Soares, JC TI H-1 MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE proton magnetic resonance spectroscopy; lithium; healthy individuals; glutamate; N-acetyl aspartate; prefrontal cortex ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYL-ASPARTATE; HUMAN BRAIN; BIPOLAR DISORDER; IN-VIVO; TEMPORAL-LOBE; PROTEIN BCL-2; P-31 MRS; CREATINE; SCHIZOPHRENIA AB The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo H-1 MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time H-1-MRS measurements of 8 cm(3) single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals ( mean age +/- SD = 25.0 +/- 9.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine ( or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC ( paired t-tests, p>0.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Udine, Sch Med, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, MC 7792,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 01736, MH 30915] NR 42 TC 46 Z9 46 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2004 VL 29 IS 10 BP 1918 EP 1924 DI 10.1038/sj.npp.1300520 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 855TY UT WOS:000223998700016 PM 15257303 ER PT J AU Hoh, BL Topcuoglu, MA Singhal, AB Pryor, JC Rabinov, JD Rordorf, GA Carter, BS Ogilvy, CS AF Hoh, BL Topcuoglu, MA Singhal, AB Pryor, JC Rabinov, JD Rordorf, GA Carter, BS Ogilvy, CS TI Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage SO NEUROSURGERY LA English DT Article DE cerebral aneurysm; clinical outcome; clipping; coiling; craniotomy; subarachnoid hemorrhage; vasospasm ID RUPTURED INTRACRANIAL ANEURYSMS; COMBINED NEUROVASCULAR TEAM; ENDOVASCULAR TREATMENT; SYMPTOMATIC VASOSPASM; SURGICAL-MANAGEMENT; RISK; OCCLUSION; REPAIR; BLOOD AB OBJECTIVE: Although several recent studies have suggested that the incidence of vasospasm after aneurysmal subarachnoid hemorrhage is lower in patients undergoing aneurysmal coiling as compared with clipping, other studies have had conflicting results. We reviewed our experience over 8 years and assessed whether clipping, craniotomy, or coiling affects patient outcomes or the risk for vasospasm. METHODS: We included 515 patients with aneurysmal subarachnoid hemorrhage, identified prospectively from November 2000 to February 2003 (243 patients) and retrospectively from November 1995 to October 2000 (272 patients), by using International Classification of Diseases, 9th Revision, codes for subarachnoid hemorrhage. We classified patients as follows: clipping (413 patients), coiling (79 patients), and craniotomy (436 patients, including all 413 patients who underwent clipping plus 23 who underwent coiling as well as craniotomy for various reasons). We studied four outcome measures: total vasospasm, symptomatic vasospasm, poor outcome (modified Rankin score 3-6), and in-hospital mortality. To assess the risk of total vasospasm and symptomatic vasospasm, we performed multivariate regression analyses adjusting for age, Fisher grade, Hunt and Hess grade, aneurysm location (anterior versus posterior circulation), and aneurysm treatment modality. To assess the risk for poor outcome and in-hospital mortality, we adjusted for all the above variables as well as for total and symptomatic vasospasm. RESULTS: In the clipping group there was 63% total vasospasm and 28% symptomatic vasospasm; in the coiling group there was 54% total vasospasm and 33% symptomatic vasospasm; and in the craniotomy group there was 64% total vasospasm and 28% symptomatic vasospasm. In the multivariate analysis, age <50 years (P = 0.0099) and Fisher Grade 3 (P < 0.00001) predicted total vasospasm, and Fisher Grade 3 (P < 0.000001) and Hunt and Hess Grade IV or V (P = 0.018) predicted symptomatic vasospasm. Predictors of poor outcome were age &GE;50 years (P < 0.0001), Fisher Grade 3 (P = 0.0072), Hunt and Hess Grade IV or V (P < 0.00001), symptomatic vasospasm (P < 0.0001), and coiling (P = 0.0314 versus clipping and P = 0.045 versus craniotomy). Predictors of in-hospital mortality were age ! 50 years (P = 0.0030), Hunt and Hess Grade IV or V (P = 0.0001), symptomatic vasospasm (P < 0.00001), and coiling (P = 0.008 versus clipping and P = 0.0013 versus craniotomy). There was no significant difference in total vasospasm or symptomatic vasospasm when patients who underwent clipping or craniotomy were compared with patients who underwent coiling. In patients with Hunt and Hess Grade I to III ("good grade"), clipping and craniotomy were associated with better outcome and less in-hospital mortality, but there was no difference in total vasospasm or symptomatic vasospasm versus coiling. In patients with Hunt and Hess Grade IV or V ("poor grade"), there was no difference in any outcome measure among the treatment groups. CONCLUSION: In a single-center, retrospective, nonrandomized study, performance of clipping and/or craniotomy had significantly better outcome and lower mortality at discharge than coiling in good-grade patients but had no effect on total vasospasm or symptomatic vasospasm in good- or poor-grade patients. C1 Harvard Univ, Brain Aneurysm AVM Ctr, Neurosurg Serv, Sch Med, Boston, MA 02114 USA. Harvard Univ, Stroke Serv, Dept Neurol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Ogilvy, CS (reprint author), Harvard Univ, Brain Aneurysm AVM Ctr, Neurosurg Serv, Sch Med, VBK 710,55 Fruit St, Boston, MA 02114 USA. EM cogilvy@partners.org NR 29 TC 70 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2004 VL 55 IS 4 BP 779 EP 786 DI 10.1227/01.NEU.0000137628.51839.D5 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 860AI UT WOS:000224309100013 PM 15458586 ER PT J AU Sun, YP Mulkern, RV Schmidt, K Doshi, S Albert, MS Schmidt, NO Ziu, M Black, P Carrol, R Kieran, MW AF Sun, YP Mulkern, RV Schmidt, K Doshi, S Albert, MS Schmidt, NO Ziu, M Black, P Carrol, R Kieran, MW TI Quantification of water diffusion and relaxation times of human U87 tumors in a mouse model SO NMR IN BIOMEDICINE LA English DT Article DE diffusion; T-1; T-2; U87 tumor; brain; MRI; mouse model ID NUCLEAR-MAGNETIC-RESONANCE; EXPERIMENTAL BRAIN-TUMORS; IN-VIVO; MOLECULAR-DIFFUSION; TREATMENT RESPONSE; FIELD GRADIENT; MRI; SPECTROSCOPY; SYSTEM; CANCER AB Assessing the potential of anti-cancer agents can be greatly facilitated by applying MRI methods to investigations with animal models. Quantitative diffusion imaging, T-1, and T-2 measurements may offer valuable information for understanding properties of the tumor and for evaluating new therapeutic approaches. The human U87 high-grade glial tumor is widely used for cancer investigations in orthotopic murine models. The physiological features of this model at the cellular and sub-cellular level have not, however, been well characterized by MRI. In this study, we measured the diffusion, T-1 and T-2 characteristics of water in the human U87 tumor at 8.5 T in an orthotopic murine model in vivo and analyzed their detailed changes in the transition from the tumor core through the tumor periphery, and out to surrounding tissue using custom developed radial profile analysis software. For the tumor bearing mice (n=10), the mean average apparent diffusion coefficient (ADC) of the tumor core was 1.03+/-0.02 (x 10(-3) in mm(2)/s), while in the contralateral normal brain it was 0.73+/-0.03 (x 10(-3) mm(2)/s). The mean T-1 in tumor was 2.03+/-0.08 s and in normal brain tissue was 1.64+/-0.06 s. The mean T-2 in tumor was 0.062+/-0.002 s and in normal brain tissue was 0.048+/-0.001 s. The mean ADC, T-1 and T-2 of the tumor compared to normal tissue were significantly different (p<0.005). Copyright (C) 2004 John Wiley & Sons. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol, Boston, MA 02115 USA. RP Sun, YP (reprint author), Brigham & Womens Hosp, Dept Radiol, 221 Longwood Ave, Boston, MA 02115 USA. EM ysun@bwh.harvard.edu RI Schmidt, Nils Ole/D-5696-2014; OI Ziu, Mateo/0000-0002-3671-2638; Kieran, Mark/0000-0003-2184-7692 NR 35 TC 18 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD OCT PY 2004 VL 17 IS 6 BP 399 EP 404 DI 10.1002/nbm.894 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 860AJ UT WOS:000224309200004 PM 15386627 ER PT J AU Roffman, JL Stern, TA AF Roffman, JL Stern, TA TI Delirium in palliative care - The Friedlander/Brayman/Breitbart article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 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 OCT PY 2004 VL 18 IS 12 SI SI BP 1551 EP 1552 PG 2 WC Oncology SC Oncology GA 052DU UT WOS:000238212200012 ER PT J AU Hollmann, JL Dunn, AK DiMarzio, CA AF Hollmann, JL Dunn, AK DiMarzio, CA TI Computational microscopy in embryo imaging SO OPTICS LETTERS LA English DT Article AB The growth of computing power has greatly improved our ability to extract quantitative information about complicated three-dimensional structures from microscope images. New hardware techniques are also being developed to provide suitable images for these tasks. However, a need exists for synthetic data to test these new developments. The work reported here was motivated by studies of embryo health, but similar needs exist across the field of microscopy. We report a rigorous computer model, based on Maxwell's equations, that can produce the required synthetic images for bright-field, differential interference contrast, interferometric imaging, and polarimetric imaging. After a description of the algorithm, sample results are presented, followed by a discussion of future plans and applications. (C) 2004 Optical Society of America. C1 Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Hollmann, JL (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM dimarzio@ece.neu.edu RI Dunn, Andrew/I-9527-2014 NR 8 TC 12 Z9 12 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2004 VL 29 IS 19 BP 2267 EP 2269 DI 10.1364/OL.29.002267 PG 3 WC Optics SC Optics GA 858LO UT WOS:000224193500019 PM 15524376 ER PT J AU Castro, GF Souza, IPR Lopes, S Stashenko, P Teles, RP AF Castro, GF Souza, IPR Lopes, S Stashenko, P Teles, RP TI Salivary IgA to cariogenic bacteria in HIV-positive children and its correlation with caries prevalence and levels of cariogenic microorganisms SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE dental caries; HIV infection; secretory IgA ID INFECTED PATIENTS; IMMUNOGLOBULIN-A; CANDIDA-ALBICANS; MUCOSAL IMMUNITY; ORAL CANDIDIASIS; PAROTID-SALIVA; AIDS PATIENTS; SERUM; SUBCLASSES; DISEASE AB The interrelationship of HIV infection, dental caries and mucosal immune responses remains controversial. In our study population of 40 HIV-infected and 40 healthy control children (ages 2-5 years) there was a significantly higher prevalence of dental caries in HIV-infected children (P<0.05). The extent of caries correlated with the severity of HIV disease. To determine whether the immunosuppression that ensues after HIV infection could contribute to the increased caries prevalence, the concentrations of total IgA and IgA specific to cariogenic bacteria (Streptococcus mutans, Streptococcus sobrinus and Lactobacillus acidophilus) were determined in whole saliva by enzyme-linked immunosorbent assay . Levels of the same bacteria were also quantified in saliva using checkerboard DNA-DNA hybridization. A significantly increased level of total salivary IgA was found in the HIV-positive population (P < 0.05), but there were comparable titers of specific IgA to cariogenic bacteria in HIV-positive and healthy controls. The microbiological assessment also demonstrated similar levels of cariogenic microorganisms in both groups. We conclude that HIV-positive children appear to maintain the capacity to mount a mucosal immune response to cariogenic microorganisms, at least until late stages of disease. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Univ Fed Rio de Janeiro, Dept Pediat Dent, Rio De Janeiro, Brazil. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM rteles@forsyth.org RI Souza, Ivete/F-1094-2015 FU NIDCR NIH HHS [DE-11664] NR 48 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 2004 VL 19 IS 5 BP 281 EP 288 DI 10.1111/j.1399-302x.2004.00152.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 849JK UT WOS:000223534500001 PM 15327638 ER PT J AU Rauch, SD AF Rauch, SD TI Intratympanic steroids for sensorineural hearing loss SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID DOUBLE-BLIND; SUDDEN DEAFNESS; THERAPY; PLACEBO; TRIAL; PENTOXIFYLLINE; PATHOLOGY; CARBOGEN; DISEASE AB Corticosteroids are standard treatment for a number of inflammatory and immune-mediated inner ear diseases. In recent years there has been growing interest in intratympanic administration of steroids as a means of achieving high inner ear drug concentration and low risk of systemic side effects. Idiopathic sudden sensorineural hearing loss seems to be the condition with the greatest potential for both study and clinical use of intratympanic steroid treatment. Despite promising preliminary observations, there remain many unanswered questions about this treatment modality. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM sdr@epl.meei.harvard.edu NR 43 TC 46 Z9 60 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2004 VL 37 IS 5 BP 1061 EP + DI 10.1016/j.otc.2004.04.004 PG 15 WC Otorhinolaryngology SC Otorhinolaryngology GA 865OV UT WOS:000224713300009 PM 15474111 ER PT J AU Obel, O Mansour, M Picard, M Ruskin, J Keane, D AF Obel, O Mansour, M Picard, M Ruskin, J Keane, D TI Persistence of septal defects after transeptal puncture for pulmonary vein isolation procedures SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ablation; transeptal puncture; septal defects ID PATENT FORAMEN OVALE; ATRIAL-FIBRILLATION; CATHETER; ABLATION; ANATOMY; STROKE AB Pulmonary vein isolation (PVI) is widely practiced as a means of potentially curing atrial fibrillation (AF). Transeptal puncture is performed for PVI procedures, often two such punctures are performed. We sought to examine the prevalence of medium- to long- term iatrogenic septal defects after such procedures. Thirty-one patients who were undergoing their second PVI procedure were studied with transesophageal echocardiography (TEE) with two-dimensional imaging and color Doppler, examining the fossa ovalis for defects. Mean time from the original PVI to the time of TEE was 35 weeks. Two patients were discovered to have iatrogenic septal defects. The interval between the first PVI procedure and the TEE showing a septal defect was 33.7 weeks in one patient and 14.3 weeks in the other. latrogenic septal defects mail, occur in the medium- to long-term in patients undergoing PVI procedures for AF. The clinical implications of such defects are unknown. C1 Massachusetts Gen Hosp, Cardiac Electrophysiol Lab, Boston, MA 02130 USA. RP Obel, O (reprint author), Massachusetts Gen Hosp, Cardiac Electrophysiol Lab, Gray Bigelow 109,55 Fruit St, Boston, MA 02130 USA. EM oobel@hotmail.com OI Picard, Michael/0000-0002-9264-3243 NR 13 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD OCT PY 2004 VL 27 IS 10 BP 1411 EP 1414 DI 10.1111/j.1540-8159.2004.00646.x PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 868OU UT WOS:000224923700013 PM 15511251 ER PT J AU Cottee, PA Nisbet, AJ Boag, PR Larsen, M Gasser, RB AF Cottee, PA Nisbet, AJ Boag, PR Larsen, M Gasser, RB TI Characterization of major sperm protein genes and their expression in Oesophagostomum dentatum (Nematoda : Strongylida) SO PARASITOLOGY LA English DT Article DE major sperm protein (MSP); Oesophagostomum dentatum; Nematoda (Strongylida); gene expression; male-specific ID AMEBOID CELL MOTILITY; FEMALE SCHISTOSOMA-MANSONI; OOCYTE MEIOTIC MATURATION; CAENORHABDITIS-ELEGANS; ASCARIS-SUUM; DICTYOCAULUS-VIVIPARUS; PARASITIC NEMATODES; ONCHOCERCA-VOLVULUS; MSP CYTOSKELETON; VIT-2 PROMOTER AB Major sperm protein (msp) genes were isolated from complementary (cDNA) and genomic DNA libraries prepared from the parasitic nematode, Oesophagostomum dentatum, characterized at the nucleotide and amino acid (aa) levels, and their expression was investigated. Three different msp cDNA and 2 genomic sequences were determined(+)(+), each with an open reading frame (ORF) of 381 nucleotides. Nucleotide variation was detected at 30 positions in the ORF among all 5 sequences. Conceptual translation of the full-length msp sequences inferred 4 different MSPs each of 126 aa. These predicted MSPs differed at aa positions 15 (serine < - > threonine), 101 (alanine < - > glycine), 103 (glutamine < - > leucine) and 126 (proline < - > leucine). Southern blot analysis of O. dentatum genomic DNA, digested separately with various restriction endonucleases, displayed multiple (n = 7-13) bands for each enzyme, providing support for a multigene family. Also, at the genomic level, sequence tracts consistent with a 'substitute' TATA box sequence motif were identified within a region (- 1 to - 123 nt) preceding the 2 msp genes. In contrast to other species of nematode investigated to date, no GATA transcription factor binding motif was detected immediately upstream of the msp coding region. Real-time PCR analysis demonstrated that msp mRNA was expressed exclusively in the males of both fourth-stage larvae (L4s) and adults of O. dentatum (raised in pigs after intragastric inoculation). The magnitude of expression in male O. dentatum raised in pigs in the presence of female worms was the same as in males in the absence of females. Comparative analyses showed aa sequence conservation among MSPs from various nematodes, suggesting similar functional roles for these proteins. C1 Univ Melbourne, Dept Vet Sci, Werribee, Vic 3030, Australia. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Royal Vet & Agr Univ, Danish Ctr Expt Parasitol, DK-1870 Frederiksberg, Denmark. RP Univ Melbourne, Dept Vet Sci, 250 Princes Highway, Werribee, Vic 3030, Australia. EM robinbg@unimelb.edu.au OI Nisbet, Alasdair/0000-0002-4965-5396 NR 57 TC 24 Z9 25 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0031-1820 EI 1469-8161 J9 PARASITOLOGY JI Parasitology PD OCT PY 2004 VL 129 BP 479 EP 490 DI 10.1017/S003118200400561X PN 4 PG 12 WC Parasitology SC Parasitology GA 861DJ UT WOS:000224396000010 PM 15521637 ER PT J AU Karel, MJ Powell, J Cantor, MD AF Karel, MJ Powell, J Cantor, MD TI Using a Values Discussion Guide to facilitate communication in advance care planning SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE advance care planning; values; patient-surrogate communication ID SERIOUSLY ILL PATIENTS; DECISION-MAKING; SUBSTITUTED JUDGMENT; LIFE; END; SUPPORT; DIRECTIVES; FAMILY; INTERVENTION; DISCUSSIONS AB The utility of values clarification tools for advance care planning needs further study. This descriptive, qualitative study aimed to describe patients' and surrogates' experiences using a Values Discussion Guide (VDG), both with and without a professional facilitator. Ten male Veterans Health Administration outpatients over age 50 and their health care agents completed audio-taped discussions, both without and with a facilitator, and responded to structured feedback interviews. Most participants found a discussion using the VDG to be helpful and reassuring. Discussions varied in quantity and quality, and participants varied in preferring self-guided versus professionally facilitated discussions. The best interchanges were elicited by questions about prior experience with medical decisions, for oneself or others, and trusted versus non-trusted others to help with decision-making. A VDG appears a useful tool in a repertoire of advance care planning tools, which need to be geared towards the needs and abilities of particular patients and families. Published by Elsevier Ireland Ltd. C1 Harvard Univ, Sch Med, VA Med Ctr, VA Boston Healthcare Syst, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. GRECC, Boston, MA USA. RP Karel, MJ (reprint author), Harvard Univ, Sch Med, VA Med Ctr, VA Boston Healthcare Syst, 3-5-C,940 Belmont St, Brockton, MA 02301 USA. EM michele.karel@med.va.gov NR 36 TC 16 Z9 16 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2004 VL 55 IS 1 BP 22 EP 31 DI 10.1016/s0738-3991(03)00246-5 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 868HB UT WOS:000224903600004 PM 15476986 ER PT J AU Moran, S Wechsler, H Rigotti, NA AF Moran, S Wechsler, H Rigotti, NA TI Social smoking among US college students SO PEDIATRICS LA English DT Article DE tobacco; smoking; young adults; patterns of use ID YOUNG-ADULTS; OCCASIONAL SMOKING; TOBACCO PROMOTIONS; NATIONAL-SURVEY; BINGE-DRINKING; CIGARETTE USE; PREDICTORS; HABITS; HEALTH; WOMEN AB Objective. Young smokers commonly identify themselves as "social smokers," a pattern of smoking behavior that is poorly understood. We assessed the prevalence and correlates of social smoking among US college students. Methods. Cross-sectional survey of a random sample of 10 904 students enrolled at 119 nationally representative US colleges in 2001. Results. A total of 51% of 2401 current (past 30-day) smokers were social smokers. (To assess social smoking, students were asked, " In the past 30 days, do you smoke mainly when you are with people, mainly when you are alone, or do you smoke as often by yourself as with others?" Students who stated that they smoked mainly with others rather than alone or equally by themselves and others were defined as social smokers for this analysis.) Social smoking was independently associated with a lower frequency and intensity of tobacco use, less nicotine dependence, less intention to quit, and fewer recent quit attempts. Conclusions. Social smoking is a distinct pattern of tobacco use that is common among college students and may represent a stage in the uptake of smoking. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Bulfinch Med Grp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Moran, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Bulfinch Med Grp, Founders 3, Boston, MA 02114 USA. EM smoran1@partners.org FU NHLBI NIH HHS [K24-HL04440] NR 37 TC 130 Z9 131 U1 3 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2004 VL 114 IS 4 BP 1028 EP 1034 DI 10.1542/peds.2003-0558-L PG 7 WC Pediatrics SC Pediatrics GA 859DI UT WOS:000224242200039 PM 15466101 ER PT J AU Martinez, V Wang, LX Million, M Rivier, J Tache, Y AF Martinez, V Wang, LX Million, M Rivier, J Tache, Y TI Urocortins and the regulation of gastrointestinal motor function and visceral pain SO PEPTIDES LA English DT Review DE urocortin 1; urocortin 2; urocortin 3; CRF; stresscopin; stresscopin-related peptide; urotensin-I; CRF receptors; CRF receptor antagonists ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; STRESS-RELATED ALTERATIONS; MESSENGER-RNA EXPRESSION; STIMULATED GASTRIC CONTRACTILITY; FACTOR-RECEPTOR EXPRESSION; EDINGER-WESTPHAL NUCLEUS; IRRITABLE-BOWEL-SYNDROME; ANXIETY-LIKE BEHAVIOR; TYPE-2 CRF RECEPTORS AB Urocortin (Ucn) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related peptides recently characterized in mammals. Urocortin I binds with high affinity to CRF type 1 (CRF1) and type 2 (CRF2) receptors while Ucn 2 and Ucn 3 are selective CRF2 ligands. They also have a distinct pattern of distribution, both in the brain and the gastrointestinal tract, compatible with a role mediating, with CRF, the response to stress. In rats and mice, Ucn 1 injected centrally or peripherally inhibited gastric emptying and stimulated colonic propulsive motor function, mimicking the effects of stress or exogenous CRF. Centrally administered Ucn 2 inhibited gastric emptying with similar potency as CRF, while Ucn 1 and Ucn 3 were less potent. However, after peripheral administration, Ucn I and Ucn 2 were more potent than CRF. In mice, centrally administered Ucn 1 and 2 stimulated colonic motility with lower potency than CRF, and Ucn 3 was inactive. Studies with selective CRF1 and CRF2 antagonists demonstrated that the gastric-inhibitory and colonic-stimulatory effects of exogenously administered Ucns are mediated through CRF2 and CRF1 receptors, respectively. In addition, Ucn 2 showed visceral anti-nociceptive activity associated with the selective activation of CRF2 receptors. These observations suggest that, acting centrally and peripherally, Ucns might play a significant role in the modulation of gastrointestinal motor and pain responses during stress and stress-related pathophysiological conditions. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med,CURE,Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth,Div Digest Di, Los Angeles, CA 90073 USA. AstraZeneca R&D Molndal, Integrat Pharmacol, Gastrointestinal Biol, SE-43183 Molndal, Sweden. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med,CURE,Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth,Div Digest Di, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIAMS NIH HHS [P50 AR049550]; NIDDK NIH HHS [DK-57238-01A1S1, R01 DK-26741, P01 DK-57328, DK-41301, R01-DK-30110] NR 113 TC 67 Z9 67 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD OCT PY 2004 VL 25 IS 10 BP 1733 EP 1744 DI 10.1016/j.peptides.2004.05.025 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 865TX UT WOS:000224727200018 PM 15476940 ER PT J AU Jacobus, S Schneeweiss, S Chan, KA AF Jacobus, S Schneeweiss, S Chan, KA TI Exposure misclassification as a result of free sample drug utilization in automated claims databases and its effect on a pharmacoepidemiology study of selective COX-2 inhibitors SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE exposure misclassification; drug exposure; claims databases; selective COX-2 inhibitors; bias; epidemiologic methods ID ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; EPIDEMIOLOGIC RESEARCH; RISK; NAPROXEN; RECORDS AB Purpose Free drug samples are widely used in clinical practice. We were concerned about free sample drug utilization as a source of misclassification in pharmacoepidemiology research using claims data that may result in biased effect estimates. Methods We investigated the magnitude of potential bias with sensitivity analyses based on a published study that examined cardiovascular risk associated with selective cyclooxygenase 2 (COX-2) inhibitors. We derived an estimate of free sample drug utilization with market data for rofexcoxib and calculated sensitivity of the exposure ascertainment method using claims data. We corrected the incidence rate ratio assuming the observed unexposed incidence rate was actually a weighted average rate of the truly unexposed and free sample drug users. The impact of exposure misclassification measured as the percentage change from a corrected to the reported crude incidence rate ratio was examined under a range of free sample drug utilization proportions and unexposed cohort sizes. Results The proportion of free sample drug utilization of all rofecoxib use in our base case scenario was 15.48%, resulting in sensitivity of 84.52% for exposure ascertainment. The magnitude of bias was an underestimation of the unadjusted incidence rate ratio by 0.03%. With a free sample drug utilization proportion of 1.48% and the same unexposed cohort size of 237 975 person-years, the underestimation was 0.003%. If the unexposed cohort were 975 person-years given a 15.48% proportion, the underestimation was 8.82%. Conclusions In the pharmacoepiderniology study, we examined that uses claims data to ascertain drug exposure, our results suggest that adjustment for free sample drug utilization is probably not warranted. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmaecon, Boston, MA 02115 USA. RP Jacobus, S (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. EM jacobus@jimmy.harvard.edu RI Schneeweiss, Sebastian/C-2125-2013; OI Chan, Kinwei/0000-0001-8161-1986 NR 22 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2004 VL 13 IS 10 BP 695 EP 702 DI 10.1002/pds.981 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 862GO UT WOS:000224478800004 PM 15386727 ER PT J AU Bertram, L Tanzi, RE AF Bertram, L Tanzi, RE TI The current status of Alzheimer's disease genetics: what do we tell the patients? SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Alzheimer's genetics; linkage; association; candidate genes ID INSULIN-DEGRADING ENZYME; AMYLOID BETA-PROTEIN; APOLIPOPROTEIN-E; ALPHA-2-MACROGLOBULIN GENE; LINKAGE DISEQUILIBRIUM; MISSENSE MUTATIONS; GENOME SCREEN; APOE GENOTYPE; IN-VIVO; ONSET AB Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. Fully penetrant (causal) mutations leading to predominantly early-onset familial AD have been identified in three genes (APP, PSEN1, PSEN2), while for the more common late-onset form of the disease, only one partially penetrant genetic risk factor (APOE) has been established to date. Several lines of evidence suggest that additional susceptibility genes exist for both early- and late-onset AD, however, none of the more than three dozen putative AD loci proposed to date have been consistently replicated in follow-up analyses. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk profiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. This review focuses on the analytic tools used to identify genes in complex diseases, and then provides a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on several chromosomes. (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 81 TC 75 Z9 81 U1 2 U2 12 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD OCT PY 2004 VL 50 IS 4 BP 385 EP 396 DI 10.1016/j.phrs.2003.11.018 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 851FM UT WOS:000223671000002 PM 15304236 ER PT J AU Marceille, JR Goins, JA Soni, R Biery, JC Lee, TA AF Marceille, JR Goins, JA Soni, R Biery, JC Lee, TA TI Chronic heart failure-related interventions after starting rosiglitazone in patients receiving insulin SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 32nd Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL Atlanta, GA SP Amer Coll Clin Pharmacy DE rosiglitazone; insulin; chronic heart failure ID FLUID RETENTION; THERAPY AB Study Objective. To determine whether rosiglitazone is associated with the onset or worsening of chronic heart failure (CHF) when administered to patients with type 2 diabetes mellitus who receive insulin. Design. Retrospective cohort analysis. Setting. Veterans Affairs medical center. Subjects. One hundred thirty-nine patients who received insulin for treatment of type 2 diabetes mellitus and had rosiglitazone added to their drug regimens. Intervention. Medical records were reviewed for 6 months before and 6 months after each patient's first rosiglitazone prescription. Records were assessed for the diagnosis of CHF and documented patient complaints of CHF symptoms requiring a medical intervention (unscheduled primary care or emergency room visit, start or dosage adjustment of CHF pharmaco therapy, or hospitalization). Measurements and Main Results. A diagnosis of CHF was documented in Thirty-five (25%) patients in the preindex period (before receiving rosiglitazone) versus 42 (30%) in the postindex period (after receiving rosiglitazone). Fifty (36%) patients received a medical intervention for CHF signs or symptoms in the postindex period compared with only 20 (14%) in the preindex period (p<0.0001). Of the 50 patients requiring a medical intervention in the postindex period, 33 (66%) had not required an intervention in the preindex period. The most common symptom was lower extremity edema; this occurred in 25 (18%) patients in the preindex period and 50 (36%) patients in the postindex period (p<0.0001). Conclusion. More patients were diagnosed with CHF during the 6 months after rosiglitazone was added to their drug regimens than in the previous 6 months, when these patients received insulin but not rosiglitazone. In addition, more medical interventions related to CHF occurred after administration of rosightazone. Data from this study appear to support the Food and Drug Administration's warning of an increased risk of cardiac failure in patients receiving concurrent treatment with rosiglitazone and insulin. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Marceille, JR (reprint author), Edward Hines Vet Adm Med Ctr, Serv Pharm, M-C 119K,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. NR 12 TC 17 Z9 18 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2004 VL 24 IS 10 BP 1317 EP 1322 DI 10.1592/phco.24.14.1317.43155 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858HG UT WOS:000224182300004 PM 15628829 ER PT J AU Dergalust, S Licht, E Ferrer, C Baumhefner, AR Lee, WT Sayers, JF AF Dergalust, S Licht, E Ferrer, C Baumhefner, AR Lee, WT Sayers, JF TI Is occurrence of an antiepileptic drug related adverse drug reaction related to an active or prior history of neoplasm? SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 24-27, 2004 CL Dallas, TX SP Amer Coll Clin Pharm C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2004 VL 24 IS 10 MA 11 BP 1421 EP 1422 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858HG UT WOS:000224182300024 ER PT J AU Kelliher, AE Henault, RG Alexis, G AF Kelliher, AE Henault, RG Alexis, G TI Cost-effectiveness of FEIBA vs NovoSeven as initial therapy for the treatment of mild-to-moderate bleeds in hemophilia patients with inhibitors. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 24-27, 2004 CL Dallas, TX SP Amer Coll Clin Pharm C1 VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2004 VL 24 IS 10 MA 115 BP 1438 EP 1439 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858HG UT WOS:000224182300111 ER PT J AU Miller, CD Echevarria, K Summers, KK AF Miller, CD Echevarria, K Summers, KK TI Inaccurate susceptibility results with VITEK 1 may impair proper empiric antimicrobial selection for Pseudomonas aeruginosa infection SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 24-27, 2004 CL Dallas, TX SP Amer Coll Clin Pharm C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2004 VL 24 IS 10 MA 124 BP 1440 EP 1440 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858HG UT WOS:000224182300118 ER PT J AU Wagner, CA Finberg, KE Breton, S Marshansky, V Brown, D Geibel, JP AF Wagner, CA Finberg, KE Breton, S Marshansky, V Brown, D Geibel, JP TI Renal vacuolar H+-ATPase SO PHYSIOLOGICAL REVIEWS LA English DT Review ID MEDULLARY COLLECTING DUCT; PROTON-TRANSLOCATING ATPASE; YEAST V-ATPASE; TRANSMEMBRANE CONDUCTANCE REGULATOR; CHRONIC METABOLIC-ACIDOSIS; CLATHRIN-COATED VESICLES; BORDER MEMBRANE-VESICLES; BETA-INTERCALATED CELLS; MALE REPRODUCTIVE-TRACT; RECEPTOR-MEDIATED ENDOCYTOSIS AB Vacuolar H+-ATPases are ubiquitous multisubunit complexes mediating the ATP-dependent transport of protons. In addition to their role in acidifying the lumen of various intracellular organelles, vacuolar H+-ATPases fulfill special tasks in the kidney. Vacuolar H+-ATPases are expressed in the plasma membrane in the kidney almost along the entire length of the nephron with apical and/or basolateral localization patterns. In the proximal tubule, a high number of vacuolar H+-ATPases are also found in endosomes, which are acidified by the pump. In addition, vacuolar H+-ATPases contribute to proximal tubular bicarbonate reabsorption. The importance in final urinary acidification along the collecting system is highlighted by monogenic defects in two subunits (ATP6V0A4, ATP6V1B1) of the vacuolar H+-ATPase in patients with distal renal tubular acidosis. The activity of vacuolar H+-ATPases is tightly regulated by a variety of factors such as the acid-base or electrolyte status. This regulation is at least in part mediated by various hormones and protein-protein interactions between regulatory proteins and multiple subunits of the pump. C1 Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Boston, MA 02115 USA. RP Wagner, CA (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM Wagnerca@access.unizh.ch; john.geibel@yale.edu FU NICHD NIH HHS [HD 40793]; NIDDK NIH HHS [DK 17433, DK 32573, DK 38452, DK 42595, DK 50230] NR 595 TC 251 Z9 261 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 2004 VL 84 IS 4 BP 1263 EP 1314 DI 10.1152/physrev.00045.2003 PG 52 WC Physiology SC Physiology GA 857CT UT WOS:000224094500005 PM 15383652 ER PT J AU Saxena, V Hwang, CW Huang, S Eichbaum, Q Ingber, D Orgill, DP AF Saxena, V Hwang, CW Huang, S Eichbaum, Q Ingber, D Orgill, DP TI Vacuum-assisted closure: Micro deformations of wounds and cell proliferation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ENDOTHELIAL-CELLS; SHEAR-STRESS; GROWTH; SHAPE; TENSION; CYCLE; DISTRACTION; FIBRONECTIN; EXPERIENCE; ACTIVATION AB The mechanism of action Of the Vacuum Assisted Closure Therapy (VAC; KCl, San Antonio, Texas), a recent novel innovation in the care of wounds, remains unknown. In vitro studies have revealed that cells allowed to stretch tend to divide and proliferate in the presence of soluble mitogens, whereas retracted cells remain quiescent. The authors hypothesize that application of micro-mechanical forces to wounds in vivo can promote wound healing through this cell shape-dependent, mechanical control mechanism. The authors created a computer model (finite element) of a wound and simulated VAC application. Finite element modeling is coin in only used to engineer complex systems by breaking them down into simple discrete elements. In this model, the authors altered the pressure, pore diameter, and pore volume fraction to study the effects of vacuum-induced material deformations. The authors compared the morphology of deformation of this wound model with histologic sections of wounds treated with the VAC The finite element model showed that most elements stretched by VAC application experienced deformations of 5 to 20 percent strain, which are similar to in vitro strain levels shown to promote cellular proliferation. Importantly, the deformation predicted by the model also was similar in morphology to the surface undulations observed in histologic cross-sections of the wounds. The authors hypothesize that this tissue deformation stretches individual cells, thereby promoting proliferation in the wound microenvironment. The application of micromechanical forces may be a useful method with which to stimulate wound healing through promotion of cell division, angiogenesis, and local elaboration of growth factors. Finite element modeling of the VAC device is consistent with this mechanism of action. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Saxena, V (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. OI Orgill, Dennis/0000-0002-8279-7310 FU NCI NIH HHS [CA 45548] NR 25 TC 314 Z9 355 U1 3 U2 19 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 OCT PY 2004 VL 114 IS 5 BP 1086 EP 1096 DI 10.1097/01.prs.0000135330.51408.97 PG 11 WC Surgery SC Surgery GA 861DQ UT WOS:000224396700009 PM 15457017 ER PT J AU Mason, SD Howlett, RA Kim, MJ Olfert, IM Hogan, MC McNulty, W Hickey, RP Wagner, PD Kahn, CR Giordano, FJ Johnson, RS AF Mason, SD Howlett, RA Kim, MJ Olfert, IM Hogan, MC McNulty, W Hickey, RP Wagner, PD Kahn, CR Giordano, FJ Johnson, RS TI Loss of skeletal muscle HIF-1 alpha results in altered exercise endurance SO PLOS BIOLOGY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; PHOSPHOFRUCTOKINASE DEFICIENCY; HYPOXIA; GLYCOLYSIS; HUMANS; GROWTH AB The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia is thus a critical parameter in muscle function, influencing production of ATP, utilization of energy-producing substrates, and manufacture of exhaustion-inducing metabolites. Glycolysis is the central source of anaerobic energy in animals, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). To determine the role of HIF-1alpha in regulating skeletal muscle function, we tissue-specifically deleted the gene encoding the factor in skeletal muscle. Significant exercise-induced changes in expression of genes are decreased or absent in the skeletal-muscle HIF-1alpha knockout mice (HIF-1alpha KOs); changes in activities of glycolytic enzymes are seen as well. There is an increase in activity of rate-limiting enzymes of the mitochondria in the muscles of HIF-1alpha KOs, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway. This is corroborated by a finding of no significant decreases in muscle ATP, but significantly decreased amounts of lactate in the serum of exercising HIF-1alpha KOs. This metabolic shift away from glycolysis and toward oxidation has the consequence of increasing exercise times in the HIF-1alpha KOs. However, repeated exercise trials give rise to extensive muscle damage in HIF-1alpha KOs, ultimately resulting in greatly reduced exercise times relative to wild-type animals. The muscle damage seen is similar to that detected in humans in diseases caused by deficiencies in skeletal muscle glycogenolysis and glycolysis. Thus, these results demonstrate an important role for the HIF-1 pathway in the metabolic control of muscle function. C1 Univ Calif San Diego, Sch Med, Div Biol, Mol Biol Sect, San Diego, CA 92103 USA. Univ Calif San Diego, Sch Med, Div Physiol, San Diego, CA 92103 USA. Yale Univ, Sch Med, Cardiol Div, New Haven, CT USA. Harvard Univ, Sch Med, Joslin Diabet Fdn, Boston, MA USA. RP Johnson, RS (reprint author), Univ Calif San Diego, Sch Med, Div Biol, Mol Biol Sect, San Diego, CA 92103 USA. EM rjohnson@biomail.ucsd.edu OI Kim, Matthew/0000-0001-5316-5181; Johnson, Randall/0000-0002-4084-6639 NR 22 TC 107 Z9 110 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2004 VL 2 IS 10 BP 1540 EP 1548 AR e288 DI 10.1371/journal.pbio.0020288 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 865XI UT WOS:000224737100010 PM 15328538 ER PT J AU Lambert, MJ Hawkins, EJ AF Lambert, MJ Hawkins, EJ TI Measuring outcome in professional practice: Considerations in selecting and using brief outcome instruments SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID PSYCHOTHERAPY; QUESTIONNAIRE; METAANALYSIS; VALIDITY; PROGRESS; TIME AB Despite external pressures (e.g., quality assurance, therapist accountability) to measure outcome in psychotherapy, less than a third of clinicians choose to monitor outcome. A growing body of evidence suggests that monitoring patient progress can enhance patient outcome, particularly for patients who are at risk of not responding to treatment. To facilitate the adoption of routine assessment of patient outcome, recommendations for selecting an appropriate outcome instrument are suggested. In addition, procedures for implementing routine assessment of outcome and the use of outcome results are discussed. C1 Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lambert, MJ (reprint author), Brigham Young Univ, Dept Psychol, 272 TLRB, Provo, UT 84602 USA. EM michael_lambert@byu.edu NR 33 TC 31 Z9 36 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD OCT PY 2004 VL 35 IS 5 BP 492 EP 499 DI 10.1037/0735-7028.35.5.492 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 858SD UT WOS:000224211100008 ER PT J AU Fava, M Alpert, JE Carmin, CN Wisniewski, SR Trivedi, MH Biggs, MM Shores-Wilson, K Morgan, D Schwartz, T Balasubramani, GK Rush, AJ AF Fava, M Alpert, JE Carmin, CN Wisniewski, SR Trivedi, MH Biggs, MM Shores-Wilson, K Morgan, D Schwartz, T Balasubramani, GK Rush, AJ TI Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D SO PSYCHOLOGICAL MEDICINE LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; ILLNESS RATING-SCALE; ELDERLY PATIENTS; PANIC DISORDER; FOLLOW-UP; ANXIETY; COMORBIDITY; FLUOXETINE; SERTRALINE; INVENTORY AB Background. Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features. Objective. The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns. Method. Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization factor score of greater than or equal to7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C-30). Results. The prevalence of anxious depression in this population was 46%. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform, disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C-30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features. Conclusion. This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression). C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Illinois, Chicago, IL USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75216 USA. Univ Kansas, Inst Psychiat Res, Wichita, KS 67214 USA. Univ Calif San Diego, San Diego Outpatient Psychiat Serv, San Diego, CA 92103 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM mfava@partners.org RI Biggs, Dr. Melanie/C-1468-2010; Carmin, Cheryl/F-8004-2014; OI Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01MH90003] NR 38 TC 161 Z9 168 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2004 VL 34 IS 7 BP 1299 EP 1308 DI 10.1017/S0033291704002612 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 876PA UT WOS:000225508200016 PM 15697056 ER PT J AU Cooper, JB Taqueti, VR AF Cooper, JB Taqueti, VR TI A brief history of the development of mannequin simulators for clinical education and training SO QUALITY & SAFETY IN HEALTH CARE LA English DT Review ID CARDIOLOGY PATIENT SIMULATOR; CRISIS RESOURCE-MANAGEMENT; REALITY SURGICAL SIMULATOR; COMPUTER MULTIPLE MODEL; CHEST CARDIAC MASSAGE; MOUTH-TO-MOUTH; VIRTUAL-REALITY; ANESTHESIA SIMULATOR; CRITICAL INCIDENTS; OPERATING-ROOM AB Simulation for medical and healthcare applications, although still in a relatively nascent stage of development, already has a history that can inform the process of further research and dissemination. The development of mannequin simulators used for education, training, and research is reviewed, tracing the motivations, evolution to commercial availability, and efforts toward assessment of efficacy of those for teaching cardiopulmonary resuscitation, cardiology skills, anaesthesia clinical skills, and crisis management. A brief overview of procedural simulators and part-task trainers is also presented, contrasting the two domains and suggesting that a thorough history of the 20+ types of simulator technologies would provide a useful overview and perspective. There has been relatively little cross fertilisation of ideas and methods between the two simulator domains. Enhanced interaction between investigators and integration of simulation technologies would be beneficial for the dissemination of the concepts and their applications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cooper, JB (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St CLN 250, Boston, MA 02114 USA. EM jcooper@partners.org NR 102 TC 54 Z9 57 U1 5 U2 13 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD OCT PY 2004 VL 13 SU 1 BP I11 EP I18 DI 10.1136/qshc.2004.009886 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 866BZ UT WOS:000224749200003 PM 15465949 ER PT J AU Blake, MA Kalra, MK Maher, MM Sahani, DV Sweeney, AT Mueller, PR Hahn, PF Boland, GW AF Blake, MA Kalra, MK Maher, MM Sahani, DV Sweeney, AT Mueller, PR Hahn, PF Boland, GW TI Pheochromocytoma: An imaging chameleon SO RADIOGRAPHICS LA English DT Article DE adrenal gland, CT; adrenal gland, MR; adrenal gland, radionuclide studies pheochromocytoma ID CONTRAST-ENHANCED CT; ADRENAL MASSES; ADENOMAS; DIAGNOSIS; WASHOUT; METAIODOBENZYLGUANIDINE; LOCALIZATION; SCINTIGRAPHY; NONADENOMAS; TUMORS AB Pheochromocytomas are rare catecholamine-secreting tumors with many clinical and imaging manifestations. They may produce overwhelming cardiovascular crises if the diagnosis is not made or if appropriate treatment is delayed. It is thus important to recognize both their characteristic and atypical imaging appearances. Pheochromocytomas are encountered, sometimes unexpectedly, across a range of imaging modalities. They are characteristically solid, hypervascular masses with high signal intensity on T2-weighted magnetic resonance (MR) images. A wide spectrum of imaging appearances is seen, however, and pheochromocytomas may mimic other adrenal lesions, both benign and malignant. They may be dark on T2-weighted MR images, in contrast to their more classic bright T2-weighted appearance. Other atypical features include fatty, hemorrhagic, cystic, and calcific changes. Pheochromocytomas may contain sufficient fat to be mistaken for an adenoma at computed tomography (CT) or MR imaging. They may also demonstrate rapid contrast material washout and be mistaken for an adenoma owing to their deenhancement profile; however, their washout pattern can be inconsistent. The appearance of pheochromocytomas at radionuclide imaging is also unpredictable. These characteristics at CT, MR imaging, and scintigraphy pose diagnostic challenges, since they allow pheochromocytomas to mimic many other adrenal masses. Pheochromocytoma is an important, often clinically occult neoplasm with devastating consequences if overlooked. Radiologists must be aware of the various forms that pheochromocytomas can assume at imaging. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. St Elizabeths Med Ctr, Dept Med, Div Endocrinol, Boston, MA USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org NR 28 TC 93 Z9 106 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 OCT PY 2004 VL 24 SI SI BP S87 EP S99 DI 10.1148/rg.24si045506 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 861NR UT WOS:000224424100011 PM 15486252 ER PT J AU Thrall, JH AF Thrall, JH TI Quality and safety revolution in health care SO RADIOLOGY LA English DT Editorial Material DE medicolegal problems; perspectives ID ADVERSE DRUG EVENTS; HOSPITALIZED-PATIENTS; INTENSIVE-CARE; IMAGE QUALITY; CT; PREVENTION; ERRORS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 32 TC 31 Z9 32 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2004 VL 233 IS 1 BP 3 EP 6 DI 10.1148/radiol.2331041059 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 856WC UT WOS:000224075000002 PM 15454614 ER PT J AU Schafer, PW Huisman, TAGM Sorenson, AG Gonzalez, RG Schwamm, LH AF Schafer, PW Huisman, TAGM Sorenson, AG Gonzalez, RG Schwamm, LH TI Diffusion-weighted MR imaging in closed head injury: High correlation with initial Glasgow coma scale score and score on modified Rankin scale at discharge SO RADIOLOGY LA English DT Article DE brain, injuries; brain, MR; magnetic resonance (MR), comparative studies; magnetic resonance (MR), diffusion tensor; trauma ID AXONAL INJURY; BRAIN INJURY; WHITE-MATTER; TRAUMA; STROKE; CT; EDEMA; CLASSIFICATION; FEATURES; HUMANS AB PURPOSE: To determine whether diffusion-weighted magnetic resonance (MR) imaging findings and conventional MR imaging findings correlate with initial Glasgow Coma Scale score and score on modified Rankin scale at discharge. MATERIALS AND METHODS: Twenty-six patients (18 male and eight femald patients; mean age, 25.2 years; age range, 4-72 years) with diffuse axonal injury were examined with diffusion-weighted MR imaging and with fluid-attenuated inversion recovery, T2-weighted fast spin-echo, and T2*-weighted gradient-echo sequences. All images were evaluated by two neuroradiologists in consensus. Tissue volume with trauma-related signal-intensity abnormality on images form each sequence, number of lesions for teach sequence, number of lesions for all sequences, and number of lesions with reduced apparent diffusion coefficient were correlated with scores on Glasgow Coma Scale and modified Rankin scale. Involvement of brainstem, deep gray matter, and corpus callosum were also correlated with clinical scores. Spearman rank correlation coefficients (r) were calculated. RESULTS: The strongest correlation was between signal-intensity abnormality volume on diffusion-weighted images and modified Rankin score (r= 0.772, P < .001). The strength of this correlation did not improve when only volume of lesions with decreased apparent diffusion coefficient was considered. For lesion number, the strongest correlation was between lesion number on images acquired with all sequences and modified Rankin score (r=0.662, P < .001). For lesion location, the strongest correlation was between lesion location in the corpus callosum and modified Rankin score ( r=0.513, P = .007). CONCLUSION: Volume of lesions on diffusion-weighted MR images provides the strongest correlation with a score of subacute on modified Rankin scale at discharge. Total lesion number also correlates well with modified Rankin score. In future, diffusion-weighted images may be useful in determining treatment strategies for acute head injury. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Schafer, PW (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Gray B285, Boston, MA 02114 USA. EM pschaefer@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 41 TC 92 Z9 104 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2004 VL 233 IS 1 BP 58 EP 66 DI 10.1148/radiol.2323031173 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 856WC UT WOS:000224075000011 PM 15304663 ER PT J AU Kalra, MK Maher, MM Kamath, RS Horiuchi, T Toth, TL Halpern, EF Saini, S AF Kalra, MK Maher, MM Kamath, RS Horiuchi, T Toth, TL Halpern, EF Saini, S TI Sixteen-detector row CT of abdomen and pelvis: Study for optimization of Z-axis modulation technique performed in 153 patients SO RADIOLOGY LA English DT Article DE abdomen, CT; computed tomography (CT); image quality computed tomography (CT); radiation exposure pelvis, CT ID NOISE-REDUCTION FILTERS; DOSE REDUCTION; TUBE CURRENT; COMPUTED-TOMOGRAPHY; ONLINE MODULATION; MULTISLICE AB PURPOSE: To retrospectively determine the optimal noise indexes required to obtain diagnostically acceptable computed tomographic (CT) images of the abdomen and pelvis with z-axis modulation. MATERIALS AND METHODS: Ninety-five patients underwent 16-section multi-detector row CT of the abdomen and pelvis with z-axis modulation at noise indexes of 120.5, 11.0, and 12.0 HU with 10-380 mA. Subsequently, 58 patients were scanned at noise indexes of 12.5 and 15.0 HU with 75-380 mA. The weights of all subjects were recorded, and transverse and anteroposterior diameters were measured. The CTimages were evaluated for abnormalities and graded for image quality in terms of noise and diagnostic acceptability by using a five-point scale. Objective noise in the liver parenchyma was measured, and the tube current was recorded at each section in all 153 patients. Statistical analyses were performend to determine the appropriate noise index and to assess the effect of the patient weight and abdominal diameters on image noise and diagnostic acceptability at different noise indexes. Tube current-time products (in milliampere seconds) at various noise indexes were compared with those at CT previously performed without z-axis modulation. RESULTS: No significant difference insubjective image noise or diagnostic acceptaptability was found at noise indexes of 10.5-15.0 HU (p = .14), and objective noise was significantly inferior only at a noise index of 15.0 HU (p = .009). Compared with CT scanning at a 10.5-HU noise index, CT scanning at 12.5- and 15-HU noise indexes yielded, respectively, 10.0% and 41.3% reductions in radiation exposure. Patient weight and abdominal diameters affected subjective image quality. CONCLUSION: Use of a 15.0-HU noise index at 75-380 mA results in acceptable subjective image noise and diagnostic acceptability but acceptability but significantly greater objective image noise at routine abdominal-pelvic CT. For greater image quality demands, a noise index of 12.5 HU results in acceptable image quality demands, a noise index of 12.5 HU results in acceptable image quality and a 19.6% reduction in radiation exposure. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. GE Yokogawa Med Syst, Tokyo, Japan. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kolra@yahoo.com NR 14 TC 95 Z9 105 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2004 VL 233 IS 1 BP 241 EP 249 DI 10.1148/radiol.2331031505 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 856WC UT WOS:000224075000031 PM 15454622 ER PT J AU Bortfeld, T Trofimov, A Shipley, WU Chan, WFA Adams, J DeLaney, TF Kooy, H Kufer, KH Monz, M AF Bortfeld, T Trofimov, A Shipley, WU Chan, WFA Adams, J DeLaney, TF Kooy, H Kufer, KH Monz, M TI Advances in comparative proton therapy treatment planning at NPTC in Boston SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Mass Gen Hosp, NE Proton Therapy Ctr, Boston, MA USA. ITWM, Dept Optimizat, Kaiserslautern, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S122 EP S122 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700268 ER PT J AU Chen, G Rietzel, E AF Chen, G Rietzel, E TI 4D imaging, planning, and treatment of moving targets at MGH SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp Radiotherapy, Dept Radiat Phys, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S11 EP S11 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700026 ER PT J AU Coolens, C Evans, PM Seco, J Webb, S Blackall, J Rietzel, E Chen, GTY AF Coolens, C Evans, PM Seco, J Webb, S Blackall, J Rietzel, E Chen, GTY TI Susceptibility of IMRT dose distributions to deformable organ motion and the impact of beam smoothing SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Inst Canc Res, Sutton, Surrey, England. Inst Canc Res, Chelsea, England. Univ London Kings Coll, Computat Imaging Sci Grp, London WC2R 2LS, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 NR 0 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S176 EP S177 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700386 ER PT J AU DeLaney, T Kepka, L Goldberg, S Suit, H AF DeLaney, T Kepka, L Goldberg, S Suit, H TI Results of radiation therapy for unresected soft tissue sarcomas SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Ctr Oncol MSkl Curie, Dept Radiotherapy, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S99 EP S99 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700216 ER PT J AU Engelsman, M Sharp, GC Bortfeld, T Shimizu, S Shirato, H AF Engelsman, M Sharp, GC Bortfeld, T Shimizu, S Shirato, H TI How much margin reduction is possible through gating or breath-hold? SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. RI Shimizu, Shinichi/G-4477-2010; Shirato, Hiroki/A-7068-2010 OI Shimizu, Shinichi/0000-0003-3143-0479; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S214 EP S215 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700477 ER PT J AU Flampouri, S Doppke, K Aljarrah, K Gierga, D Jiang, SB AF Flampouri, S Doppke, K Aljarrah, K Gierga, D Jiang, SB TI A Monte Carlo study on the effect of respiratory motion on lung IMRT dose distribution SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S341 EP S341 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237701299 ER PT J AU Mazal, A Kooy, H Nauraye, C Schaffner, B Rosenthal, S Kollipara, S Paganetti, H Ferrand, R Rosenwald, JC Chen, G AF Mazal, A Kooy, H Nauraye, C Schaffner, B Rosenthal, S Kollipara, S Paganetti, H Ferrand, R Rosenwald, JC Chen, G TI Dosimetric data for broad beam, pencil beam and Monte Carlo models of clinical proton beams SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Inst Curie, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Varian Med Syst, Baden, Switzerland. RI ferrand, regis/G-9626-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S321 EP S321 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237701248 ER PT J AU Niemierko, A AF Niemierko, A TI What can EUD-based cost functions do that physical cost functions cannot? SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S74 EP S75 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700159 ER PT J AU Paganetti, H AF Paganetti, H TI Calculation of proton RBE values SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 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 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S122 EP S123 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700270 ER PT J AU Paganetti, H Jiang, H Rietzel, E Trofimov, A Gierga, D Adams, JA Chen, GTY AF Paganetti, H Jiang, H Rietzel, E Trofimov, A Gierga, D Adams, JA Chen, GTY TI Application of four-dimensional Monte Carlo in dynamic radiation therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S88 EP S88 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700191 ER PT J AU Rietzel, E Chen, GTY Choi, NC Willett, CG AF Rietzel, E Chen, GTY Choi, NC Willett, CG TI 4D imaging and treatment planning SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, Biophys Abt, D-6100 Darmstadt, Germany. Duke Univ, Durham, NC 27706 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S140 EP S140 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700301 ER PT J AU Taghian, A Raad, RA Assaad, S Casty, A Ancukiewicz, M Yeh, E Attia, K Sullivan, T Boucher, Y Powell, S AF Taghian, A Raad, RA Assaad, S Casty, A Ancukiewicz, M Yeh, E Attia, K Sullivan, T Boucher, Y Powell, S TI Paclitaxel improves oxygenation and decreases the interstitial fluid pressure in breast cancers in patients treated with neoadjuvant chemotherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kantonsspital St Gallen, Abt Internist Onkol, St Gallen, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S327 EP S328 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237701265 ER PT J AU Thieke, C Kuefer, KH Monz, M Scherrer, A Alonso, F Nill, S Thilmann, C Bortfeld, T AF Thieke, C Kuefer, KH Monz, M Scherrer, A Alonso, F Nill, S Thilmann, C Bortfeld, T TI Beyond weight factors: new concepts for defining and analysing dose optimisation SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol Oncol C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Heidelberg Hosp, Dept Radiat Oncol, Heidelberg, Germany. Fraunhofer Inst Ind Math, Dept Optimisat, Kaiserslautern, Germany. German Canc Res Ctr, Dept Med Phys, Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2004 VL 73 SU 1 BP S75 EP S75 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886OH UT WOS:000226237700160 ER PT J AU Jager, RD Aiello, LP Patel, SC Cunningham, ET AF Jager, RD Aiello, LP Patel, SC Cunningham, ET TI Risks of intravitreous injection: A comprehensive review SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Review DE complications; cataract; endophthalmitis; eye hemorrhage; hypotony; injection; intravitreal; iritis; ocular hypertension; pneumatic retinopexy; uveitis; intraocular hemorrhage ID IMMUNE-DEFICIENCY-SYNDROME; TISSUE-PLASMINOGEN ACTIVATOR; ONSET POSTOPERATIVE ENDOPHTHALMITIS; TRIAMCINOLONE ACETONIDE INJECTION; EXUDATIVE MACULAR DEGENERATION; COMPARING PNEUMATIC RETINOPEXY; RANDOMIZED CLINICAL-TRIAL; CIDOFOVIR HPMPC THERAPY; CYTOMEGALOVIRUS RETINITIS; RETINAL-DETACHMENT AB Purpose: To evaluate the prevalence of the most common serious adverse events associated with intravitreous (IVT) injection. Methods: A systematic search of the literature via PubMed from 1966 to March 1, 2004, was conducted to identify studies evaluating the safety of IVT injection. Data submitted in New Drug Applications to the U.S. Food and Drug Administration for drugs administered into the vitreous were included where available. Serious adverse events reported in each study were recorded, and risk per eye and risk per injection were calculated for the following serious adverse events: endophthalmitis, retinal detachment, iritis/uveitis, intraocular hemorrhage, ocular hypertension, cataract, and hypotony. Rare complications also were noted. Results: Data from 14,866 IVT injections in 4,382 eyes were analyzed. There were 38 cases of endophthalmitis (including those reported as pseudoendophthalmitis) for a prevalence of 0.3% per injection and 0.9% per eye. Excluding cases reported specifically as pseudoendophthalmitis, the prevalence of endophthalmitis was 0.2% per injection and 0.5% per eye. Retinal detachment, iritis/uveitis, ocular hypertension, cataract, intraocular hemorrhage, and hypotony were generally associated with lVT injection of specific compounds and were infrequently attributed by the investigators to the injection procedure itself. Retinal vascular occlusions were described rarely in patients after lVT injection, and it was unclear in most cases whether these represented true injection-related complications or chance associations. Conclusion: The risk of serious adverse events reported after IVT injection is low. Nevertheless, careful attention to injection technique and appropriate postinjection monitoring are essential because uncommon injection-related complications may be associated with permanent vision loss. C1 Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA. NYU, Sch Med, Dept Ophthalmol, New York, NY USA. RP Cunningham, ET (reprint author), Eyetech Pharmaceut Inc, 3 Times Sq,12th Floor, New York, NY 10036 USA. EM emmett.cunningham@eyetech.com NR 107 TC 241 Z9 255 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2004 VL 24 IS 5 BP 676 EP 698 DI 10.1097/00006982-200410000-00002 PG 23 WC Ophthalmology SC Ophthalmology GA 866HH UT WOS:000224764100002 PM 15492621 ER PT J AU Aiello, LP Brucker, AJ Chang, S Cunningham, ET D'Amico, DJ Flynn, HW Grillone, LR Hutcherson, S Liebmann, JM O'Brien, TP Scott, IU Spaide, RF Ta, C AF Aiello, LP Brucker, AJ Chang, S Cunningham, ET D'Amico, DJ Flynn, HW Grillone, LR Hutcherson, S Liebmann, JM O'Brien, TP Scott, IU Spaide, RF Ta, C TI Evolving guidelines for intravitreous injections SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID POVIDONE-IODINE; CHEMICAL PREPARATION; INTRAOCULAR SURGERY; OPHTHALMIC SURGERY; CATARACT-SURGERY; ENDOPHTHALMITIS; PROPHYLAXIS; CONJUNCTIVA; EYE; ANTIBIOTICS AB Intravitreous (IVT) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene(TM)) is currently approved by the Food and Drug Administration as an IVT injection, the number of approved IVT injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for IVT injection. The purpose of this document is to identify specific strategies for the delivery of IVT injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of IVT injection, additional clinical experience, and results of clinical trials. C1 Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, Med Ctr, New York, NY USA. Eyetech Pharmaceut Inc, New York, NY USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. ISTA Pharmaceut Inc, Irvine, CA USA. Cyckux Ltd, KKC, Richmond, VA USA. NYU, Med Ctr, Manhattan Eye Ear & Throat Hosp, New York, NY 10016 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Lutherville Timonium, MD USA. Vitreous Retina Macul Consultants, New York, NY USA. Stanford Eye Ctr, Stanford, CA USA. RP Brucker, AJ (reprint author), RETINA, POB 67, Gladwyne, PA 19035 USA. EM brucker@retinajournal.com NR 38 TC 179 Z9 193 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2004 VL 24 IS 5 SU S BP S3 EP S19 DI 10.1097/00006982-200410001-00002 PG 17 WC Ophthalmology SC Ophthalmology GA 867FW UT WOS:000224828800002 PM 15483476 ER PT J AU Gurmankin, AD Baron, J Armstrong, K AF Gurmankin, AD Baron, J Armstrong, K TI Intended message versus message received in hypothetical physician risk communications: Exploring the gap SO RISK ANALYSIS LA English DT Article DE resistance to risk information; risk communication; risk perception ID BREAST-CANCER RISK; UNREALISTIC OPTIMISM; RANDOMIZED TRIAL; HEALTH-PROBLEMS; PERCEPTIONS; SUSCEPTIBILITY; SMOKING; ANXIETY; PROBABILITY; INFORMATION AB We examined the risk perception that is derived from hypothetical physician risk communications. Subjects (n = 217) completed a questionnaire on the Web for $3. Subjects were presented with four hypothetical cancer risk scenarios that included a physician risk communication in one of three risk communication formats: verbal only, verbal plus numeric probability as a percent, and verbal plus numeric probability as a fraction. In each scenario, subjects were asked to imagine themselves as the patient described and to state their perceived personal susceptibility to the cancer (i.e., risk perception) on a 0 to 100 scale, as well as responses to other measures. Subjects' risk perceptions were highly variable, spanning nearly the entire probability scale for each scenario, and the degree of variation was only slightly less in the risk communication formats in which a numeric statement of risk was provided. Subjects were more likely to overestimate than underestimate their risk relative to the stated risk in the numeric versions, and overestimation was associated with the belief that the physician minimized the risk so they wouldn't worry, innumeracy, and worry, as well as decisions about testing for the cancer. These results demonstrate significant gaps between the intended message and the message received in physician risk communications. Implications for medical decisions, patient distress, and future research are discussed. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Univ Penn, Dept Psychol, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Sch Med, Philadelphia, PA 19104 USA. RP Gurmankin, AD (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. EM adg11@cornell.edu NR 69 TC 42 Z9 43 U1 3 U2 10 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 2004 VL 24 IS 5 BP 1337 EP 1347 DI 10.1111/j.0272-4332.2004.00530.x PG 11 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 875ML UT WOS:000225424400023 PM 15563299 ER PT J AU Wu, LZ Griffin, JD AF Wu, LZ Griffin, JD TI Modulation of notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE notch signaling; mastermind; transcriptional co-activator; Mucoepidermoid carcinoma; cervical cancer ID HUMAN-PAPILLOMAVIRUS TYPE-16; CALCIUM-INDUCED DIFFERENTIATION; NEUROGENIC LOCUS MASTERMIND; MINOR SALIVARY-GLAND; MUCOEPIDERMOID-CARCINOMA; DROSOPHILA MASTERMIND; EPITHELIAL-CELLS; E6 ONCOPROTEIN; HUMAN HOMOLOG; INTRACELLULAR DOMAIN AB Notch signaling is mediated by cell-cell interactions and is critical for cell fate determination in many species. Recently, a family of mastermind-like (MAML) transcriptional co-activator genes was identified that encode proteins that cooperate with Notch and CSL to activate transcription. Here, we review our current understanding of the roles of the MAML proteins in Notch signaling, and their involvement in certain human cancers. The mounting biochemical and functional evidence indicate that the MAML genes are critical components of the Notch signaling pathway, likely regulating cellular events involved in both normal development and oncogenesis. (C) 2004 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu FU NCI NIH HHS [R01 CA097148, R01 CA36167] NR 91 TC 53 Z9 58 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 2004 VL 14 IS 5 BP 348 EP 356 DI 10.1016/j.semcancer.2004.04.014 PG 9 WC Oncology SC Oncology GA 848OQ UT WOS:000223477400005 PM 15288260 ER PT J AU Lefort, K Dotto, GP AF Lefort, K Dotto, GP TI Notch signaling in the integrated control of keratinocyte growth/differentiation and tumor suppression SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Notch1; keratinocyte; differentiation; tumorigenesis ID PROTEIN-KINASE-C; NF-KAPPA-B; HUMAN-PAPILLOMAVIRUS TYPE-16; MOUSE SKIN CARCINOGENESIS; EPIDERMAL STEM-CELLS; INVOLUCRIN PROMOTER ACTIVITY; HAIR FOLLICLE MORPHOGENESIS; TRANSIT AMPLIFYING CELLS; FYN TYROSINE KINASE; TERMINAL DIFFERENTIATION AB Oncogenesis is closely linked to abnormalities in cell differentiation. Notch signaling provides an important form of intercellular communication involved in cell fate determination, stem cell potential and differentiation. Here we review the role of this pathway in the integrated growth/differentiation control of the keratinocyte cell type, and the maintenance of normal skin homeostasis. In parallel with the pro-differentiation function of Notch I in keratinocytes, we discuss recent evidence pointing to a tumor suppressor function of this gene in both mouse skin and human cervical carcinogenesis. The possibility that Notch signaling elicits signals with a duality of growth positive and negative function will be discussed. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland. EM gdotto@partners.org NR 179 TC 87 Z9 92 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 2004 VL 14 IS 5 BP 374 EP 386 DI 10.1016/j.semcancer.2004.04.017 PG 13 WC Oncology SC Oncology GA 848OQ UT WOS:000223477400008 PM 15288263 ER PT J AU Canellos, GP AF Canellos, GP TI Lymphoma: Present and future challenges SO SEMINARS IN HEMATOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; 3-WEEKLY CHOP CHEMOTHERAPY; STANDARD REGIMEN CHOP; B-CELL LYMPHOMA; FOLLICULAR LYMPHOMAS; AGGRESSIVE LYMPHOMAS; INDOLENT LYMPHOMA; ELDERLY-PATIENTS; DISEASE; TRIAL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 30 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2004 VL 41 IS 4 SU 7 BP 26 EP 31 DI 10.1053/j.seminhematol.2004.09.005 PG 6 WC Hematology SC Hematology GA 880XZ UT WOS:000225824900005 PM 15768476 ER PT J AU Scott, JA AF Scott, JA TI Artificial neural networks and image interpretation: A ghost in the machine SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article DE artificial intelligence; artificial neural networks; computer assisted diagnosis; image analysis C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD OCT PY 2004 VL 25 IS 5 BP 396 EP 403 DI 10.1053/j.sult.2004.02.005 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 868WW UT WOS:000224944800005 PM 15559122 ER PT J AU Ramnath, RR Kattapuram, SV AF Ramnath, RR Kattapuram, SV TI MR appearance of SONK-like subchondral abnormalities in the adult knee: SONK redefined SO SKELETAL RADIOLOGY LA English DT Article DE SONK; osteoarthritis; subchondral; osteochondral; osteonecrosis ID SPONTANEOUS OSTEONECROSIS; CLASSIFICATION; OSTEOARTHRITIS; FRACTURES; INJURIES; LESIONS; EDEMA AB Objective: To investigate the MR characteristics of SONK-like (spontaneous osteonecrosis of the knee) subchondral abnormalities in the adult atraumatic knee and to recategorize these patients into two subgroups: a subacute to chronic process associated with osteoarthritis and an acute process associated with insufficiency fractures. Design: We retrospectively examined the knee MRIs of 39 patients with non-specific interpretations of osteochondral abnormalities. Patients: There were a total of 52 subchondral lesions without any known traumatic event and no prior surgery. All lesions evaluated had MR features previously ascribed to SONK. Several MR characteristics were then assessed: presence or absence of a line, size, zonal location, T1 and T2 signal, associated marrow edema, associated ipsilateral meniscal tear, and associated ipsilateral cartilage defects. Results and conclusions: The abnormalities with linear components (insufficiency fractures) tended to be larger (P<0.01) and were associated with a severe amount of marrow edema (P<0.0001) consistent with an acute process. The non-linear abnormalities were more associated with cartilage defects (P=0.01) and less marrow edema consistent with osteoarthritis and a subacute to chronic process. This association of SONK-like abnormalities with osteoarthritis and insufficiency fractures casts doubt on the validity of the term "spontaneous osteonecrosis" as it is currently applied, and further investigation into the separate etiologies of these subchondral marrow lesions is needed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kattapuram, SV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,ACC 515, Boston, MA 02114 USA. NR 18 TC 32 Z9 34 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2004 VL 33 IS 10 BP 575 EP 581 DI 10.1007/s00256-004-0777-7 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 862YW UT WOS:000224528400004 PM 15249985 ER PT J AU Jones, RN Fonda, SJ AF Jones, RN Fonda, SJ TI Use of an IRT-based latent variable model to link different forms of the CES-D from the Health and Retirement Study SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 54th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 14-18, 2001 CL CHICAGO, IL SP Gerontol Soc Amer DE depression; psychometrics; epidemiology; longitudinal studies; aged; adult ID ITEM RESPONSE THEORY; FIT INDEXES; DEPRESSION; POPULATION; SADNESS; SYMPTOMS; SAMPLE; SCALES; OLDER; LIFE AB Background The goal of this study was to calibrate depressive symptoms collected using different versions of the Centers for Epidemiologic Studies - Depression (CES-D) instrument in different waves of the Health and Retirement Study (HRS). Method The HRS is a prospective and nationally representative cohort study. This analysis included a sample of HRS participants, adults aged 23-85 years in 1992 who had complete data on depressive symptoms at initial 2- and 4-year follow-up interviews (N = 5,734): Depressive symptoms were assessed with the CES-D. Symptom coverage and response categories varied across study wave. The first wave (1992) used a four-category response, whereas subsequent waves (1994 and 1996) used a two-category response. A structural equations model (SEM) based in Item Response Theory (IRT) was used to calibrate symptoms and generate linked depressive symptom burden scores. Results Linked depressive symptom burden scores, derived from calibrated symptoms, were distributed similarly across HRS wave. Conclusion Our results demonstrate the applicability of an IRT-based SEM to address a common challenge in prospective studies: changes in the content and context of symptom assessment. Future investigations may make use of our linked syndrome scores to further explore other aspects of depression from a longitudinal perspective. C1 Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Jones, RN (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIA NIH HHS [AG008812, AG021153] NR 37 TC 15 Z9 16 U1 2 U2 5 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD OCT PY 2004 VL 39 IS 10 BP 828 EP 835 DI 10.1007/s00127-004-0815-8 PG 8 WC Psychiatry SC Psychiatry GA 860ZU UT WOS:000224386700008 PM 15669664 ER PT J AU Morales, M Mendez-Alvarez, S Martin-Lopez, JV Marrero, C Freytes, C AF Morales, M Mendez-Alvarez, S Martin-Lopez, JV Marrero, C Freytes, C TI Biofilm: the microbial "bunker" for intravascular catheter-related infection SO SUPPORTIVE CARE IN CANCER LA English DT Review DE catheter-related infection; biofilm; polysaccharide intercellular adhesin (PIA); ica-gene cluster ID STAPHYLOCOCCUS-EPIDERMIDIS; CANDIDA-PARAPSILOSIS; INHIBITING PEPTIDE; IN-VIVO; AUREUS; PATHOGENESIS; ADHESION; EXPRESSION; MECHANISM; ALBICANS AB Catheter-related infection in cancer patients remains an important health-care problem with major financial implications. During the last few years a better understanding of the pathogenesis of catheter-related infections and the interaction between microorganisms and catheter surfaces has emerged. Recently the influence of biofilm formation in catheter-related infections has been established. The development of biofilm by the colonizing microbes permits attachment of the organisms to the vascular access device and confers resistance to antibiotics and host defense mechanisms. Strategies to overcome the development of biofilm are being developed to prevent catheter- and other medical device-related infections. C1 Univ Hosp Nuestra Senora de Candelaria, Med Oncol Serv, Santa Cruz de Tenerife 38010, Canary Islands, Spain. Univ La Laguna, Dept Cellular Biol & Microbiol, Santa Cruz de Tenerife, Canary Islands, Spain. Univ Hosp Nuestra Senora de Candelaria, Res Unit, Mol Biol Lab, Santa Cruz de Tenerife 38010, Canary Islands, Spain. Univ Hosp Nuestra Senora de Candelaria, Hematol Serv, Santa Cruz de Tenerife 38010, Canary Islands, Spain. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Morales, M (reprint author), Univ Hosp Nuestra Senora de Candelaria, Med Oncol Serv, Santa Cruz de Tenerife 38010, Canary Islands, Spain. EM mmoralesg@comtf.es NR 48 TC 13 Z9 14 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD OCT PY 2004 VL 12 IS 10 BP 701 EP 707 DI 10.1007/s00520-004-0630-5 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 863SV UT WOS:000224583600003 PM 15095074 ER PT J AU Reiser, I Nishikawa, RM Giger, ML Wu, T Rafferty, E Moore, RH Kopans, DB AF Reiser, I Nishikawa, RM Giger, ML Wu, T Rafferty, E Moore, RH Kopans, DB TI Computerized detection of mass lesions in digital breast tomosynthesis images using two- and three dimensional radial gradient index segmentation SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE computer-aided diagnosis; mass detection; tomosynthesis ID MAMMOGRAPHY AB Initial results for a computerized mass lesion detection scheme for digital breast tomosynthesis (DBT) images are presented. The algorithm uses a radial gradient index feature for the initial lesion detection and for segmentation of lesion candidates. A set of features is extracted for each segmented partition. Performance of two- and three dimensional features was compared. For gradient features, the additional dimension provided no improvement in classification performance. For shape features, classification using 3D features was improved compared to the 2D equivalent features. The preliminary overall performance was 76% sensitivity at 11 false positives per exam, estimated based on DBT image data of 21 masses. A larger database will allow for further development and improvement in our computer aided detection scheme. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ireiser@uchicago.edu OI Nishikawa, Robert/0000-0001-7720-9951; Giger, Maryellen/0000-0001-5482-9728 NR 11 TC 27 Z9 27 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2004 VL 3 IS 5 BP 437 EP 441 PG 5 WC Oncology SC Oncology GA 864ZM UT WOS:000224671900004 PM 15453808 ER PT J AU Brenner, B Grabowski, EF Hellgren, M Kenet, G Massicotte, P Manco-Johnson, M Mathew, P Muntean, W Schlegel, N Nowak-Gottl, U AF Brenner, B Grabowski, EF Hellgren, M Kenet, G Massicotte, P Manco-Johnson, M Mathew, P Muntean, W Schlegel, N Nowak-Gottl, U TI Thrombophilia and pregnancy complications SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE thrombophilia; pregnancy; antithrombotic therapy; fetal loss ID V-LEIDEN MUTATION; MOLECULAR-WEIGHT HEPARIN; LATE FETAL LOSS; GROWTH RESTRICTION; CEREBRAL-PALSY; WOMEN; RISK; METAANALYSIS; ASSOCIATION; DISORDERS AB The implications of currently available data on the association of gestational vascular complications with thrombophilia are presented in this consensus report. Screening is recommended for women with the following previous complications: fetal loss including three or more first trimester loss, two or more second trimester loss, or any stillbirth; early, severe or recurrent preeclampsia and severe intrauterine growth restriction. Maternal antithrombotic therapy is currently evaluated in women with thrombophilia and previous complications. C1 Rambam Med Ctr, Dept Hematol, Thrombosis & Haemostat Unit, IL-31096 Haifa, Israel. Massachusetts Gen Hosp, Cardiovasc Thrombosis Lab, Boston, MA 02114 USA. Gothenburg Univ, Dept Obstet & Gynecol, S-41124 Gothenburg, Sweden. Sahlgrenska Univ Hosp, Uppsala, Sweden. Chaim Sheba Med Ctr, Pediat Coagulat Serv, Tel Hashomer, Israel. Hosp Sick Children, Div Hematol Oncol, Toronto, ON, Canada. Mt States Hemophilia Ctr, Aurora, CO USA. Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM USA. Graz Univ, Dept Pediat, Graz, Austria. Hop Robert Debre, Serv Hematol Biol, Paris, France. Univ Childrens Hosp, Munster, Germany. RP Brenner, B (reprint author), Rambam Med Ctr, Dept Hematol, Thrombosis & Haemostat Unit, POB 9602, IL-31096 Haifa, Israel. EM b_Brenner@rambam.health.gov.il NR 40 TC 17 Z9 19 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 2004 VL 92 IS 4 BP 678 EP 681 DI 10.1160/TH04-02-0096 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 863IW UT WOS:000224555900004 PM 15467895 ER PT J AU Frantisek, S Latz, E Re, F Mandell, L Repik, G Golenbock, D Espevik, T Kurt-Jones, E Finberg, R AF Frantisek, S Latz, E Re, F Mandell, L Repik, G Golenbock, D Espevik, T Kurt-Jones, E Finberg, R TI Importance of extra-and intracellular domains of TLR1 and TLR2 receptors in NF-kappa B signaling SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 1st International Conference on Basic and Clinical Immunogenomics (BCI 2004) CY OCT 03-07, 2004 CL Budapest, HUNGARY SP Agilent Technologies, Beckman Coulter, Bio Rad, IBM, Appl Biosyst, Promega, Kromat, Pfizer, Qiagen, Biomed Hungaria, Intercell, ComGenex, Gedeon Richter Pharmaceut, Astra Zeneca, Bio Sci, Csertex, Abbott Labs Hungary, Biotest, Johnson & Johnson, Aventis, Genodia C1 Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01605 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Norwegian Univ Sci & Technol, Unit Canc Res & Mol Biol, N-7034 Trondheim, Norway. RI Finberg, Robert/E-3323-2010; Latz, Eicke/H-3951-2014 OI Latz, Eicke/0000-0003-1488-5666 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 2004 VL 64 IS 4 BP 378 EP 378 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 854BY UT WOS:000223876400142 ER PT J AU Tsatsanis, KD Foley, C Donehower, C AF Tsatsanis, KD Foley, C Donehower, C TI Contemporary outcome research and programming guidelines for Asperger syndrome and high-functioning autism SO TOPICS IN LANGUAGE DISORDERS LA English DT Article DE Asperger syndrome; high-functioning autism; outcome research; treatment guidelines ID SOCIAL-SKILLS GROUP; BEHAVIORAL TREATMENT; CHILDREN; INTERVENTION; INDIVIDUALS; ADOLESCENTS; DISORDERS; DIAGNOSIS AB In recent years, there has been an extraordinary surge of interest in achieving a greater understanding of the needs of children and adolescents with Asperger syndrome and high-functioning autism, and with this increase in attention, research has provided a range of directions with respect to treatment guidelines. However, there is also a need for empirically supported evidence that can guide parents and professionals in their choices for educational programming for this unique population. A summary of the principal conclusions that can be drawn from the current treatment efficacy research is provided along with practical issues related to navigating the intervention literature, and directions for future research in this field. C1 Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tsatsanis, KD (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 149 13th St,Floor 10, Charlestown, MA 02129 USA. EM Ktsatsanis@partners.org NR 38 TC 19 Z9 19 U1 7 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD OCT-DEC PY 2004 VL 24 IS 4 BP 249 EP 259 PG 11 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 872FU UT WOS:000225193900003 ER PT J AU Tsatsanis, KD AF Tsatsanis, KD TI Heterogeneity in learning style in Asperger syndrome and high-functioning autism SO TOPICS IN LANGUAGE DISORDERS LA English DT Article DE Asperger syndrome; attention; cognitive profiles; executive function; high-functioning autism ID RECEPTIVE LANGUAGE DISORDER; EARLY ADULT LIFE; EXECUTIVE FUNCTION; WORKING-MEMORY; AMNESIC SYNDROME; FOLLOW-UP; CHILDREN; ATTENTION; COMMUNICATION; INDIVIDUALS AB Although children and adolescents with high-functioning autism and Asperger syndrome present with some similar clinical features and challenges, heterogeneity of learning style coupled with the predominance of specific "packages" of materials and methods tends to understate the need for individualization when designing an educational and/or a therapeutic program. Treatment approaches will be enhanced when the core areas of strength and vulnerability are identified and evaluated over the course of development for each individual. A review of those aspects of cognition that are critical to consider when designing an educational program is provided. In addition to profiles on cognitive testing, several areas of specific functioning will be addressed including attention, memory, and executive function. C1 Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tsatsanis, KD (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 149 13th St,Floor 10, Charlestown, MA 02129 USA. EM ktsatsanis@partners.org NR 72 TC 9 Z9 10 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD OCT-DEC PY 2004 VL 24 IS 4 BP 260 EP 270 PG 11 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 872FU UT WOS:000225193900004 ER PT J AU Stowell, CP AF Stowell, CP TI What ever happened to blood substitutes? SO TRANSFUSION LA English DT Editorial Material ID CELL-FREE HEMOGLOBIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02114 USA. RP Stowell, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. EM cstowell@partners.org NR 7 TC 1 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2004 VL 44 IS 10 BP 1403 EP 1404 DI 10.1111/j.1537-2995.2004.44101.x PG 2 WC Hematology SC Hematology GA 858DX UT WOS:000224171600002 PM 15383010 ER PT J AU Niswender, KD Baskin, DG Schwartz, MW AF Niswender, KD Baskin, DG Schwartz, MW TI Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; BLOOD-BRAIN-BARRIER; ELEGANS LIFE-SPAN; FOOD-INTAKE; ARCUATE NUCLEUS; BODY-WEIGHT; DIABETIC HYPERPHAGIA; RECEPTOR SUBSTRATE-2; GLUT4 TRANSLOCATION AB Despite an alarming increase in the burden of obesity worldwide, body adiposity seems to be a regulated physiological variable. Regulation of adiposity occurs through a classical endocrine feedback loop, in which the pancreatic beta-cell-derived hormone insulin and the adipocyte-derived hormone leptin signal the status of body energy stores to the hypothalamus. Recent advances in our understanding of the signal transduction mechanisms used by insulin and leptin in the hypothalamus to modulate neuronal firing suggest that intracellular cross-talk occurs at several levels and is a potentially important determinant of regulated body weight. These pathways are thus an attractive target for pharmacological intervention in the treatment of obesity. C1 Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. VA Puget Sound Hlth Care Syst, Div Endocrinol Metabol, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Niswender, KD (reprint author), Vanderbilt Univ, Ctr Med, 722 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA. EM kevin.niswender@vanderbilt.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK 52989, DK 12829, DK 17047, DK 64857-01]; NINDS NIH HHS [NS 32273] NR 70 TC 164 Z9 168 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 2004 VL 15 IS 8 BP 362 EP 369 DI 10.1016/j.tem.2004.07.009 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865IN UT WOS:000224696000004 PM 15380807 ER PT J AU Feeney, ME AF Feeney, ME TI HIV and children - The developing immune system fights back SO WEST INDIAN MEDICAL JOURNAL LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTE; PERINATALLY INFECTED CHILDREN; DISEASE PROGRESSION; TYPE-1 INFECTION; CELL RESPONSES; VIRAL LOAD; VIREMIA; TRANSMISSION; ASSOCIATION AB Children infected with HIV display great variability in their clinical outcome and rate of progression to AIDS. The reasons for this variability are largely unknown. Increasing evidence from adult studies suggests that the cellular immune response is a critical determinant of viral containment, and likely accounts for much of the observed variability in clinical progression. Detailed studies of the HIV specific immune responses generated by adults with long-term nonprogressive infection have revealed elements of the host immune response that correlate with effective viral control. However, much less is known about the HIV-specific immune responses generated by perinatally infected children. Recent studies have revealed that elements of both the HIV-specific cytotoxic T lymphocyte response (mediated by CD(8+)lymphocytes) and the T-helper response (mediated by CD4+ lymphocytes) differ between adults and children, and these differences could have important implications for the ability to control HIV viraemia. Identification of the precise correlates of viral containment in children could provide important insights into the pathogenesis of vertical infection, and will greatly assist the rational design of HIV vaccines and immunotherapies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Childrens Hosp, Boston, MA 02115 USA. RP Feeney, ME (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St 5th Floor, Charlestown, MA 02129 USA. EM mfeeney@partners.org NR 44 TC 5 Z9 5 U1 0 U2 1 PU UNIV WEST INDIES FACULTY MEDICAL SCIENCES PI KINGSTON PA MONA CAMPUS, KINGSTON 7, JAMAICA SN 0043-3144 J9 W INDIAN MED J JI West Ind. Med. J. PD OCT PY 2004 VL 53 IS 5 BP 359 EP 362 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 881KP UT WOS:000225866700020 PM 15675505 ER PT J AU Kelleher, RJ Govindarajan, A Tonegawa, S AF Kelleher, RJ Govindarajan, A Tonegawa, S TI Translational regulatory mechanisms in persistent forms of synaptic plasticity SO NEURON LA English DT Review ID LONG-TERM POTENTIATION; LOCAL PROTEIN-SYNTHESIS; X MENTAL-RETARDATION; DEPENDENT LATE-PHASE; HIPPOCAMPAL AREA CA1; CAMKII MESSENGER-RNA; DENTATE GYRUS; DENDRITIC SPINES; CYTOPLASMIC POLYADENYLATION; MACROMOLECULAR-SYNTHESIS AB Memory and synaptic plasticity exhibit distinct temporal phases, with long-lasting forms distinguished by their dependence on macromolecular synthesis. Prevailing models for the molecular mechanisms underlying long-lasting synaptic plasticity have largely focused on transcriptional regulation. However, a growing body of evidence now supports a crucial role for neuronal activity-dependent mRNA translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent work has begun to define the signaling mechanisms coupling synaptic activation to the protein synthesis machinery. The ERK and mTOR signaling pathways have been shown to regulate the activity of the general translational machinery, while the translation of particular classes of mRNAs is additionally controlled by gene-specific mechanisms. Rapid enhancement of the synthesis of a diverse array of neuronal proteins through such mechanisms provides the components necessary for persistent forms of UP and LTD. These findings have important implications for the synapse specificity and associativity of protein synthesis-dependent changes in synaptic strength. C1 MIT, Howard Hughes Med Inst, Picower Ctr Learning & Memory, RIKEN MIT Neurosci Res Ctr,Ctr Canc Res,Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. MIT, RIKEN MIT Neurosci Res Ctr, Picower Ctr Learning & Memory,Dept Brain & Cognit, Howard Hughes Med Inst,Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP MIT, Howard Hughes Med Inst, Picower Ctr Learning & Memory, RIKEN MIT Neurosci Res Ctr,Ctr Canc Res,Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tonegawa@mit.edu FU NIMH NIH HHS [P50-MH58880]; NINDS NIH HHS [R01-NS32925, K08-NS02071] NR 113 TC 341 Z9 351 U1 4 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD SEP 30 PY 2004 VL 44 IS 1 BP 59 EP 73 DI 10.1016/j.neuron.2004.09.013 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 858ZY UT WOS:000224232600007 PM 15450160 ER PT J AU Walsh, TJ Teppler, H Donowitz, GR Maertens, JA Baden, LR Dmoszynska, A Cornely, OA Bourque, MR Lupinacci, RJ Sable, CA dePauw, BE AF Walsh, TJ Teppler, H Donowitz, GR Maertens, JA Baden, LR Dmoszynska, A Cornely, OA Bourque, MR Lupinacci, RJ Sable, CA dePauw, BE TI Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DOUBLE-BLIND; IN-VITRO; IMMUNOCOMPROMISED PATIENTS; MK-0991 L-743,872; CANCER; CANDIDIASIS; ASPERGILLOSIS; MULTICENTER; FLUCONAZOLE; INFECTIONS AB BACKGROUND: Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B. METHODS: In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point. RESULTS: Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events. CONCLUSIONS: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia. C1 NCI, NIH, Bethesda, MD 20892 USA. Merck Res Labs, W Point, PA USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Univ Ziekenhuis Leuven, Louvain, Belgium. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Clin Hosp 4, Lublin, Poland. Univ Cologne Klinikum, Cologne, Germany. Univ Hosp St Radboud, Nijmegen, Netherlands. RP Walsh, TJ (reprint author), NCI, NIH, Bldg 10,Rm 13N-240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 513 Z9 562 U1 2 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 30 PY 2004 VL 351 IS 14 BP 1391 EP 1402 DI 10.1056/NEJMoa040446 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 857XT UT WOS:000224153900007 PM 15459300 ER PT J AU Tung, R DeSanctis, R AF Tung, R DeSanctis, R TI Images in clinical medicine: Giant left atrium SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tung, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 SEP 30 PY 2004 VL 351 IS 14 BP 1437 EP 1437 DI 10.1056/NEJMicm030599 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 857XT UT WOS:000224153900012 PM 15459305 ER PT J AU Chakravarti, A Zhai, GG Zhang, M Malhotra, R Latham, DE Delaney, MA Robe, P Nestler, U Song, QH Loeffler, J AF Chakravarti, A Zhai, GG Zhang, M Malhotra, R Latham, DE Delaney, MA Robe, P Nestler, U Song, QH Loeffler, J TI Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms SO ONCOGENE LA English DT Article DE Survivin; radiation resistance; primary human glioblastoma ID ANTI-APOPTOSIS GENE; MALIGNANT GLIOMA; BRAIN-TUMORS; EXPRESSION; CANCER; PROTEIN; INHIBITOR; PROGNOSIS; PROLIFERATION; NEUROBLASTOMA AB The observed radioresistance of human glioblastoma multiforme (GBM) poses a major challenge, which, if overcome, may lead to significant advances in the management of this patient population. There is accumulating evidence from correlative studies that Survivin expression is associated with increased malignant potential of human gliomas. The purpose of this study was to investigate whether Survivin plays a direct role in mediating radiation resistance in primary human glioma cell lines, and, if so, investigating the underlying mechanisms. Our panel of GBM cell lines included two that were relatively radiation resistant (GM20 and GM21) and two that were more radiation sensitive (GM22 and GM23), which demonstrated differential levels of Survivin expression between the two groups. Through the use of adenoviral vectors containing either dominant-negative (pAd-S(T34A)) or wild-type Suvrivin (pAd-S(WT)), we were able to inactivate or overexpress Survivin, respectively. Our findings suggest that Survivin plays a critical role in mediating radiation resistance in primary GBM cells, in part through suppression of apoptotic cell death via a caspase-independent manner. We have identified novel mechanisms by which Survivin may enhance tumor cell survival upon radiation exposure such as regulation of double-strand DNA break repair and tumor cell metabolism, which were most evident in the radiation-resistant cell lines. These differences in Survivin function both in radiation-resistant vs radiation-sensitive cell lines and in the presence vs absence of radiation exposure warrant further investigation and highlight potentially important mechanisms of radiation resistance in these tumors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. Univ Giessen, Dept Neurosurg, Giessen, Germany. RP Chakravarti, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Founders House,Room 536, Boston, MA 02114 USA. EM achakravarti@partners.org RI Nestler, Ulf/D-6503-2014; OI Nestler, Ulf/0000-0002-2963-4344; Malhotra, Rajeev/0000-0003-0120-4630 FU NCI NIH HHS [KO882163CA] NR 38 TC 126 Z9 134 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 30 PY 2004 VL 23 IS 45 BP 7494 EP 7506 DI 10.1038/sj.onc.1208049 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 858FH UT WOS:000224176500006 PM 15326475 ER PT J AU Duan, ZF Brakora, KA Seiden, MV AF Duan, ZF Brakora, KA Seiden, MV TI MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines SO GENE LA English DT Article DE chemotherapy resistance; mitochondrial protein; MDR1; gene expression ID PACLITAXEL RESISTANCE; MULTIDRUG-RESISTANCE; OVARIAN-CANCER; CHEMOSENSITIVITY; GENES AB In the search for novel genes involved in the taxol resistance phenotype, prior studies of gene expression in taxol-resistant cell lines and their paired drug-sensitive parental lines using high-density Affymetrix microarrays identified MGC4175 as an overexpressed transcript. In this report, we characterize MGC4175 and demonstrate that seven of eight taxol- and doxorubicin-resistant cell lines overexpressed MGC4175 as compared to their chemotherapy naive parent lines. Sequence analyses of MGC4175 cDNA and the predicted amino acid sequence did not show significant homology to any known sequence or protein domain, with an open reading frame of 356 bp that is predicted to encode a protein product of 118 amino acids. Both the MGC4175 and MDR1 genes are located at chromosome position 7q21. Southern blot analysis demonstrated that a single copy of MGC4175 is present in the human genome, and MGC4175 overexpression is not caused by genomic amplification or gene arrangement. Human MGC4175 fused to the carboxy terminus of enhanced green fluorescent protein (EGFP) and expressed in U-2OS cells localized the protein to the perinuclear region with further studies colocalizing this protein to the mitochondria. The Cancer Profiling Arrays and the Cancer Cell Line Profiling Array demonstrated that MGC4175 is broadly expressed in various tissues with no significant difference of MGC4175 expression between chemotherapy naive tumor cells and normal cells. However, MGC4175 is overexpressed 1.2- to 12.3-fold after 48 h of taxol induction and 0.65- to 6.5-fold after doxorubicin induction in various human cancer cell lines. In light of the overexpression of MGC4175 in association with taxol exposure, drug resistance, the coexpression of MDR1 and the mitochondrial localization of its protein, we propose to name this transcript MDR1 and Mitochondrial Taxol Resistance Associated Gene (MM-TRAG) and suggest that MM-TRAG may play a role in the development of taxol resistance in human cancer. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Jackson 1029,70 Blossom St, Boston, MA 02114 USA. EM zduan@partners.org OI Duan, Zhenfeng/0000-0002-8543-083X FU NCI NIH HHS [CA 89150] NR 19 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 29 PY 2004 VL 340 IS 1 BP 53 EP 59 DI 10.1016/j.gene.2004.06.013 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 860RA UT WOS:000224359500006 PM 15556294 ER PT J AU Wang, SX Lim, GW Zeng, Q Sung, B Ai, YL Guo, GS Yang, LL Mao, JR AF Wang, SX Lim, GW Zeng, Q Sung, B Ai, YL Guo, GS Yang, LL Mao, JR TI Expression of central glucocorticoid receptors after peripheral nerve injury contributes to neuropathic pain behaviors in rats SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glucocorticoid; spinal; neuropathic pain; NMDA receptor; interleukins; protein kinase C ID CHRONIC CONSTRICTION INJURY; SUPERFICIAL DORSAL HORN; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA LEVELS; SPINAL-CORD; SCIATIC-NERVE; BASOLATERAL AMYGDALA; MOLECULAR-MECHANISMS; POSSIBLE INVOLVEMENT; MORPHINE-TOLERANCE AB Peripheral glucocorticoid receptors (GRs) play a significant role in the anti-inflammatory effects of glucocorticoids; however, the role of central GRs in nociceptive behaviors after peripheral nerve injury (neuropathic pain behaviors) remains unknown. Here we show that the development of neuropathic pain behaviors (thermal hyperalgesia and mechanical allodynia) induced by chronic constriction nerve injury (CCI) in rats was attenuated by either the GR antagonist RU38486 (4 = 2 > 1 = 0.5 mug) or a GR antisense oligonucleotide administered intrathecally twice daily for postoperative days 1-6. The development of thermal hyperalgesia and mechanical allodynia after CCI also was prevented in adrenalectomized rats, whereas the GR agonist dexamethasone (100 mug/kg) given subcutaneously twice daily for postoperative day 1-6 restored CCI-induced neuropathic pain behaviors in the adrenalectomized rats. Mechanistically, CCI induced a time-dependent and region-specific expression of neuronal GRs primarily within the spinal cord dorsal horn ipsilateral to nerve injury, which showed a time course parallel to that of the development of neuropathic pain behaviors. Moreover, the expression of neuronal GR after CCI was mediated in part through an elevated spinal level of interleukin-6 (IL-6) and protein kinase Cgamma (PKCgamma), because intrathecal treatment with an IL-6 antiserum, a PKC inhibitor (cheryrithrine), or PKCgamma knock-out substantially reduced the expression of neuronal GRs as well as neuropathic pain behaviors after CCI. These findings indicate a central role of neuronal GRs in the mechanisms of neuropathic pain behaviors in rats and suggest a potential role for GR antagonists in clinical management of neuropathic pain. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 324, Dept Anesthesia & Crit Care,Pain Ctr,Pain Res Grp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 324, Dept Anesthesia & Crit Care,Pain Ctr,Pain Res Grp, 15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [DA08835]; NINDS NIH HHS [R01 NS 45681, R01 NS 42661] NR 73 TC 74 Z9 80 U1 0 U2 6 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 SEP 29 PY 2004 VL 24 IS 39 BP 8595 EP 8605 DI 10.1523/JNEUROSCI.3058-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 858FB UT WOS:000224175000025 PM 15456833 ER PT J AU Peng, ZC Huang, CS Stell, BM Mody, I Houser, CR AF Peng, ZC Huang, CS Stell, BM Mody, I Houser, CR TI Altered expression of the delta subunit of the GABA(A) receptor in a mouse model of temporal lobe epilepsy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE tonic inhibition; neurosteroids; dentate gyrus; hippocampus; pilocarpine; immunohistochemistry ID CEREBELLAR GRANULE CELLS; RAT HIPPOCAMPUS; DENTATE GYRUS; A RECEPTORS; TONIC INHIBITION; NEURONAL EXCITABILITY; GAMMA-2 SUBUNITS; ALPHA-5 SUBUNIT; MESSENGER-RNA; UP-REGULATION AB delta Subunit-containing GABA(A) receptors are located predominantly at nonsynaptic sites in the dentate gyrus where they may play important roles in controlling neuronal excitability through tonic inhibition and responses to GABA spillover. Immunohistochemical methods were used to determine whether delta subunit expression was altered after pilocarpine-induced status epilepticus in C57BL/6 mice in ways that could increase excitability of the dentate gyrus. In pilocarpine-treated animals, the normal diffuse labeling of the delta subunit in the dentate molecular layer was decreased by 4 d after status epilepticus ( latent period) and remained low throughout the period of chronic seizures. In contrast, diffuse labeling of alpha4 and gamma2 subunits, potentially interrelated GABA(A) receptor subunits, was increased during the chronic period. Interestingly, delta subunit labeling of many interneurons progressively increased after pilocarpine treatment. Consistent with the observed changes in delta subunit labeling, physiological studies revealed increased excitability in the dentate gyrus of slices obtained from the pilocarpine-treated mice and demonstrated that physiological concentrations of the neurosteroid tetrahydrodeoxycorticosterone were less effective in reducing excitability in the pilocarpine-treated animals than in controls. The findings support the idea that alterations in nonsynaptic delta subunit-containing GABA(A) receptors in both principal cells and interneurons could contribute to increased seizure susceptibility in the hippocampal formation in a temporal lobe epilepsy model. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol & Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU BLRD VA [I01 BX000404]; NINDS NIH HHS [NS35985] NR 61 TC 187 Z9 189 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 29 PY 2004 VL 24 IS 39 BP 8629 EP 8639 DI 10.1523/JNEUROSCI.2877-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 858FB UT WOS:000224175000028 PM 15456836 ER PT J AU Scarmeas, N Hadjigeorgiou, GM Papadimitriou, A Dubois, B Sarazin, M Brandt, J Albert, M Marder, K Bell, K Honig, LS Wegesin, D Stern, Y AF Scarmeas, N Hadjigeorgiou, GM Papadimitriou, A Dubois, B Sarazin, M Brandt, J Albert, M Marder, K Bell, K Honig, LS Wegesin, D Stern, Y TI Motor signs during the course of Alzheimer disease SO NEUROLOGY LA English DT Article ID LEWY BODY VARIANT; APOLIPOPROTEIN-E EPSILON-4; EXTRAPYRAMIDAL SIGNS; PARKINSONIAN SIGNS; COGNITIVE DECLINE; CLINICAL-FEATURES; DEMENTIA; ASSOCIATION; MORTALITY; BODIES AB Background: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. Objective: To describe the progression and identify predictors of individual MOSIs in AD. Methods: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. Results: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). Conclusions: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates. C1 Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain,Cognit, New York, NY USA. Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Hosp Salpetriere, Dept Neurol, Paris, France. Univ Thessaly, Dept Neurol, Larisa, Greece. RP Scarmeas, N (reprint author), Columbia Presbyterian Med Ctr, Taub Inst PH, 622 W 168 St,19th Fl, New York, NY 10032 USA. EM ns257@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [M01 RR000645, RR00645]; NIA NIH HHS [R01 AG007370, R01 AG007370-07, Z01 AG007370] NR 49 TC 96 Z9 99 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 28 PY 2004 VL 63 IS 6 BP 975 EP 982 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 857OX UT WOS:000224128500008 PM 15452286 ER PT J AU Flibotte, JJ Hagan, N O'Donnell, J Greenberg, SM Rosand, J AF Flibotte, JJ Hagan, N O'Donnell, J Greenberg, SM Rosand, J TI Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage SO NEUROLOGY LA English DT Article ID IN-HOSPITAL MORTALITY; APOLIPOPROTEIN-E GENOTYPE; ACUTE ISCHEMIC-STROKE; CEREBRAL-HEMORRHAGE; GLUCOSE LEVEL; RISK-FACTORS; HYPERGLYCEMIA; THERAPY; ENLARGEMENT; PREDICTION AB Background: Warfarin increases mortality of intracerebral hemorrhage (ICH). The authors investigated whether this effect reflects increased baseline ICH volume at presentation or increased ICH expansion. Methods: Subjects were drawn from an ongoing prospective cohort study of ICH outcome. The effect of warfarin on baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH age greater than or equal to18 years admitted to the emergency department over a 5-year period. Baseline ICH volume was determined using computerized volumetric analysis. The effect of warfarin on ICH expansion (increase in volume greater than or equal to33% of baseline) was analyzed in 70 consecutive cases in whom ICH volumes were measured on all subsequent CT scans up to 7 days after admission. Multivariable analysis was used to determine warfarin's influence on baseline ICH, ICH expansion, and whether warfarin's effect on ICH mortality was dependent on baseline volume or subsequent expansion. Results: There was no effect of warfarin on initial volume. Predictors of larger baseline volume were hyperglycemia (p<0.0001) and lobar hemorrhage (p<0.0001). Warfarin patients were at increased risk of death, even when controlling for ICH volume at presentation. Warfarin was the sole predictor of expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was detected later in the hospital course compared with non-warfarin patients (p<0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI 0.7 to 8.9, p=0.14) and reduced the marginal effect of warfarin on ICH mortality. Conclusions: Warfarin did not increase ICH volume at presentation but did raise the risk of in-hospital hematoma expansion. This expansion appears to mediate part of warfarin's effect on ICH mortality. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, WACC 836, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, WACC 836, 15 Parkman St, Boston, MA 02114 USA. EM jrosand@partners.org FU NINDS NIH HHS [1 K23 NS42695-01] NR 31 TC 308 Z9 311 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 28 PY 2004 VL 63 IS 6 BP 1059 EP 1064 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 857OX UT WOS:000224128500020 PM 15452298 ER PT J AU Blelloch, RH Hochedlinger, K Yamada, Y Brennan, C Kim, MJ Mintz, B Chin, L Jaenisch, R AF Blelloch, RH Hochedlinger, K Yamada, Y Brennan, C Kim, MJ Mintz, B Chin, L Jaenisch, R TI Nuclear cloning of embryonal carcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FROG RENAL ADENOCARCINOMA; MOUSE EMBRYOS; STEM-CELLS; TERATOCARCINOMA CELLS; TRANSPLANT EMBRYOS; GENE-EXPRESSION; MICE; TUMORS; LINE; PLURIPOTENCY AB Embryonal carcinoma (EC) cells have served as a model to study the relationship between cancer and cellular differentiation given their potential to produce tumors and, to varying degrees, participate in embryonic development. Here, nuclear transplantation was used to assess the extent to which the tumorigenic and developmental potential of EC cells is governed by epigenetic as opposed to genetic alterations. Nuclei from three independent mouse EC cell lines (F9, P19, and METT-1) with differing developmental and tumorigenic potentials all were able to direct early embryo development, producing morphologically normal blastocysts that gave rise to nuclear transfer (NT)-derived embryonic stem (ES) cell lines at a high efficiency. However, when tested for tumor or chimera formation, the resulting NT ES cells displayed an identical potential as their respective donor EC cells, in stark contrast to previously reported NT ES cells derived from transfer of untransformed cells. Consistent with this finding, comparative genomic hybridization identified previously undescribed genetic lesions in the EC cell lines. Therefore, nonreprogrammable genetic modifications within EC nuclei define the developmental and tumorigenic potential of resulting NT ES cells. Our findings support the notion that cancer results from the deregulation of stem cells and further suggest that the genetics of ECs will reveal genes involved in stem cell self-renewal and pluripotency. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. RP Jaenisch, R (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM jaenisch@wi.mit.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [R01 CA093947, R01 CA93947, R01-CA-87-869, T32 CA009382, T32 CA09382] NR 41 TC 119 Z9 128 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 28 PY 2004 VL 101 IS 39 BP 13985 EP 13990 DI 10.1073/pnas.0405015101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 858SG UT WOS:000224211400005 PM 15306687 ER PT J AU Heldwein, EE Macia, E Jing, W Yin, HL Kirchhausen, T Harrison, SC AF Heldwein, EE Macia, E Jing, W Yin, HL Kirchhausen, T Harrison, SC TI Crystal structure of the clathrin adaptor protein 1 core SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADP-RIBOSYLATION FACTOR; PLECKSTRIN HOMOLOGY DOMAINS; SORTING SIGNALS; GOLGI MEMBRANES; COATED VESICLES; AP-1 BINDING; COMPLEXES; PHOSPHORYLATION; MYRISTOYLATION; ENDOCYTOSIS AB The heterotetrameric adaptor proteins (AP complexes) link the outer lattice of clathrin-coated vesicles with membrane-anchored cargo molecules. We report the crystal structure of the core of the AP-1 complex, which functions in the trans-Golgi network (TGN). Packing of complexes in the crystal generates an exceptionally long (1,135-Angstrom) unit-cell axis, but the 6-fold noncrystallographic redundancy yields an excellent map at 4-Angstrom resolution. The AP-1 core comprises N-terminal fragments of the two large chains, beta1 and gamma, and the intact medium and small chains, mu1 and sigma1. Its molecular architecture closely resembles that of the core of AP-2, the plasma-membrane-specific adaptor, for which a structure has been determined. Both structures represent an "inactive" conformation with respect to binding of cargo with a tyrosine-based sorting signal. TGN localization of AP-1 depends on the small GTPase, Arf1, and the phosphoinositide, PI-4-P. We show that directed mutations of residues at a particular corner of the gamma chain prevent recruitment to the TGN in cells and diminish PI-4-P-dependent, but not Arf1-dependent, liposome binding in vitro. C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. RP Harrison, SC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu FU NIGMS NIH HHS [GM066110, GM36548, R01 GM066110, R01 GM036548] NR 42 TC 114 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 SEP 28 PY 2004 VL 101 IS 39 BP 14108 EP 14113 DI 10.1073/pnas.0406102101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 858SG UT WOS:000224211400028 PM 15377783 ER PT J AU Walensky, RP Paltiel, AD Goldie, SJ Gandhi, RT Weinstein, MC Seage, GR Smith, HE Zhang, H Freedberg, KA AF Walensky, RP Paltiel, AD Goldie, SJ Gandhi, RT Weinstein, MC Seage, GR Smith, HE Zhang, H Freedberg, KA TI A therapeutic HIV vaccine: how good is good enough? SO VACCINE LA English DT Article DE HIV/AIDS; therapeutic vaccine; effectiveness ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 CELL COUNTS; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; OPPORTUNISTIC INFECTIONS; CONTROLLED-TRIAL; PLUS INDINAVIR; VIRAL LOAD; HEALTH; EFFICACY AB The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources. (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Gen Med, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [P30 AI042851, K23 AI001794, R01 AI042006] NR 46 TC 14 Z9 14 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 28 PY 2004 VL 22 IS 29-30 BP 4044 EP 4053 DI 10.1016/j.vaccine.2004.03.059 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 857YA UT WOS:000224154700030 PM 15364455 ER PT J AU Gilligan, T Wang, PS Levin, R Kantoff, PW Avorn, J AF Gilligan, T Wang, PS Levin, R Kantoff, PW Avorn, J TI Racial differences in screening for prostate cancer in the elderly SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SERUM TESTOSTERONE LEVELS; HORMONE-BINDING GLOBULIN; AFRICAN-AMERICAN MEN; MEDICARE CLAIMS DATA; WHITE MEN; RADICAL PROSTATECTOMY; UNITED-STATES; HEALTH-PROFESSIONALS; CAUCASIAN MEN; SURVIVAL AB Background: Black men are more likely than white men to be diagnosed as having advanced prostate cancer, and their prostate cancer mortality rates are more than twice as high. Low screening rates among black men may contribute to these disparities, but there are few data on racial differences in prostate cancer screening. Objectives: To present a case-control study of racial differences in the use of prostate-specific antigen (PSA) as a screening test among Medicare beneficiaries in New Jersey and to assess the degree to which race is associated with prostate cancer screening. Methods: The study used a statewide database of claims data from Medicare Parts A and B, Medicaid, and the state's Pharmaceutical Assistance for the Aged and Disabled program. Prevalent cases of prostate cancer were excluded using the state's cancer registry. Of 139 672 men who underwent PSA screening, 34984 were randomly selected along with an identical number of controls matched by month and year of birth. After men with International Classification of Diseases, Ninth Revision, Clinical Modification, or Current Procedural Terminology codes indicative of prostate cancer were excluded, 33 463 case patients and 33 782 control subjects remained. Results: The use of PSA screening was strongly and inversely associated with black race (odds ratio [OR] = 0.50 P < .001), poverty (OR = 0.33; P < .001), and near poverty (OR = 0.69; P < .001). Multivariate logistic regression analysis after age, socioeconomic status, comorbidity, and use of health care services were controlled for revealed that black race remained a strong predictor of not undergoing PSA screening (OR = 0.65; 95% confidence interval, 0.60-0.70). Conclusions: Elderly blacks are substantially less likely to undergo PSA screening than elderly whites. Differences in socioeconomic status and comorbid conditions explain only a small part of the racial differences in screening rates. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Gilligan, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D-1230, Boston, MA 02115 USA. EM Timothy_Gilligan@dfci.harvard.edu OI Gilligan, Timothy/0000-0003-2308-9303 NR 60 TC 72 Z9 73 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 27 PY 2004 VL 164 IS 17 BP 1858 EP 1864 DI 10.1001/archinte.164.17.1858 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 857HV UT WOS:000224108000008 PM 15451760 ER PT J AU Jacobs, GD Pace-Schott, EF Stickgold, R Otto, MW AF Jacobs, GD Pace-Schott, EF Stickgold, R Otto, MW TI Cognitive behavior therapy and pharmacotherapy for insomnia - A randomized controlled trial and direct comparison SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID TREATMENT EFFICACY; ZOLPIDEM; METAANALYSIS; BENZODIAZEPINES; TOLERABILITY; PHARMACOLOGY; MANAGEMENT; WITHDRAWAL; UPDATE AB Background: Chronic sleep-onset insomnia is a prevalent health complaint in adults. Although behavioral and pharmacological therapies have been shown to be effective for insomnia, no placebo-controlled trials have evaluated their separate and combined effects for sleep-onset insomnia. The objective of this study was to evaluate the clinical efficacy of behavioral and Pharmacological therapy, singly and in combination, for chronic sleep-onset insomnia. Methods: This was a randomized, placebo-controlled clinical trial that involved 63 young and middle-aged I adults with chronic sleep-onset insomnia. Interventions included cognitive behavior therapy (CBT), pharmacotherapy, or combination therapy compared with placebo. The main outcome measures were sleep-onset latency as measured by sleep diaries; secondary measures included sleep diary measures of sleep efficiency and total sleep time, objective measures of sleep variables (Nightcap sleep monitor recorder), and measures of daytime functioning. Results: In most measures, CBT was the most sleep effective intervention; it produced the greatest changes in sleep-onset latency and sleep efficiency, yielded the largest number of normal sleepers after treatment, and maintained therapeutic gains at long-term follow-up. The combined treatment provided no advantage over CBT alone, whereas pharmacotherapy produced only moderate improvements during drug administration and returned measures toward baseline after drug use discontinuation. Conclusions: These findings suggest that young and middle-age patients with sleep-onset insomnia can derive significantly greater benefit from CBT than pharmacotherapy and that CBT should be considered a first-line intervention for chronic insomnia. Increased recognition of the efficacy of CBT and more widespread recommendations for its use could improve the quality of life of a large numbers of patients with insomnia. C1 Beth Israel Deaconess Med Ctr, Sleep Disorders Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mind Body Med Inst, Chestnut Hill, MA USA. RP Jacobs, GD (reprint author), Beth Israel Deaconess Med Ctr, Sleep Disorders Ctr, 330 Brookline Ave,TCC-866, Boston, MA 02215 USA. EM gjacobs@caregroup.harvard.edu FU NHLBI NIH HHS [HL59387]; NIDA NIH HHS [DA117440] NR 29 TC 216 Z9 223 U1 2 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 27 PY 2004 VL 164 IS 17 BP 1888 EP 1896 DI 10.1001/archinte.164.17.1888 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 857HV UT WOS:000224108000012 PM 15451764 ER PT J AU Xiong, JP Stehle, T Goodman, SL Arnaout, MA AF Xiong, JP Stehle, T Goodman, SL Arnaout, MA TI A novel adaptation of the integrin PSI domain revealed from its crystal structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR SEGMENT; RISK-FACTOR; POLYMORPHISM; SUBUNIT; COMPLEX; GPIIIA; LIGAND; ALPHA-V-BETA-3; ACTIVATION; RECEPTOR AB Integrin beta-subunits contain an N-terminal PSI (for plexin-semaphorin-integrin) domain that contributes to integrin activation and harbors the PI(A) alloantigen associated with immune thrombocytopenias and susceptibility to sudden cardiac death. Here we report the crystal structure of PSI in the context of the crystallized alpha(V)beta(3) ectodomain. The integrin PSI forms a two-stranded antiparallel beta-sheet flanked by two short helices; its long interstrand loop houses Pl(A) and may face the EGF2 domain. The integrin PSI contains four cysteine pairs connected in a 1-4, 2-8, 3-6, 5-7 pattern. An unexpected feature of the structure is that the final, eighth cysteine is located C-terminal to the Ig-like hybrid domain and is thus separated by the hybrid domain from the other seven cysteines of PSI. This architecture may be relevant to the evolution of integrins and should help refine the current models of integrin activation. C1 Massachusetts Gen Hosp, Renal Unit, Leukocyte Biol & Inflammat Program, Struct Biol Program, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Merck KGaA, Oncol Res, D-64271 Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, Leukocyte Biol & Inflammat Program, Struct Biol Program, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu FU NHLBI NIH HHS [HL70219]; NIDDK NIH HHS [DK48549] NR 21 TC 69 Z9 70 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 2004 VL 279 IS 39 BP 40252 EP 40254 DI 10.1074/jbc.C400362200 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 854PW UT WOS:000223916800002 PM 15299032 ER PT J AU Ranganathan, S Liu, CX Migliorini, MM von Arnim, CAF Peltan, ID Mikhailenko, I Hyman, BT Strickland, DK AF Ranganathan, S Liu, CX Migliorini, MM von Arnim, CAF Peltan, ID Mikhailenko, I Hyman, BT Strickland, DK TI Serine and threonine phosphorylation of the low density lipoprotein receptor-related protein by protein kinase C alpha regulates endocytosis and association with adaptor molecules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAIN; PLASMINOGEN-ACTIVATOR; MEDIATED ENDOCYTOSIS; SIGNAL-TRANSDUCTION; CELLULAR INTERNALIZATION; DEPENDENT REGULATION AB The low density lipoprotein receptor-related protein (LRP) is a large receptor that participates in endocytosis, signaling pathways, and phagocytosis of necrotic cells. Mechanisms that direct LRP to function in these distinct pathways likely involve its association with distinct cytoplasmic adaptor proteins. We tested the hypothesis that the association of various adaptor proteins with the LRP cytoplasmic domain is modulated by its phosphorylation state. Phosphoamino acid analysis of metabolically labeled LRP revealed that this receptor is phosphorylated at serine, threonine, and tyrosine residues within its cytoplasmic domain, whereas inhibitor studies identified protein kinase Calpha(PKCalpha) as a kinase capable of phosphorylating LRP. Mutational analysis identified critical threonine and serine residues within the LRP cytoplasmic domain that are necessary for phosphorylation mediated by PKCalpha. Mutating these threonine and serine residues to alanines generated a receptor that was not phosphorylated and that was internalized more rapidly than wildtype LRP, revealing that phosphorylation reduces the association of LRP with adaptor molecules of the endocytic machinery. In contrast, serine and threonine phosphorylation was necessary for the interaction of LRP with Shc, an adaptor protein that participates in signaling events. Furthermore, serine and threonine phosphorylation increased the interaction of LRP with other adaptor proteins such as Dab-1 and CED-6/GULP. These results indicate that phosphorylation of LRP by PKCalpha modulates the endocytic and signaling function of LRP by modifying its association with adaptor proteins. C1 Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Strickland, DK (reprint author), Univ Maryland, Sch Med, Dept Surg, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM strickla@usa.redcross.org OI Peltan, Ithan/0000-0003-1730-234X FU NHLBI NIH HHS [HL50784, HL54710]; NIA NIH HHS [AG12406] NR 55 TC 40 Z9 44 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 2004 VL 279 IS 39 BP 40536 EP 40544 DI 10.1074/jbc.M407592200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 854PW UT WOS:000223916800041 PM 15272003 ER PT J AU Nam, YJ Mani, K Ashton, AW Peng, CF Krishnamurthy, B Hayakawa, Y Lee, P Korsmeyer, SJ Kitsis, RN AF Nam, YJ Mani, K Ashton, AW Peng, CF Krishnamurthy, B Hayakawa, Y Lee, P Korsmeyer, SJ Kitsis, RN TI Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions SO MOLECULAR CELL LA English DT Article ID CASPASE RECRUITMENT DOMAIN; SIGNALING COMPLEX DISC; CELL-DEATH; CYTOCHROME-C; STRUCTURAL BASIS; BCL-2 FAMILY; MITOCHONDRIAL APOPTOSIS; EFFECTOR DOMAIN; NMR STRUCTURE; PROTEIN ARC AB Death-fold domains constitute an evolutionarily conserved superfamily that mediates apoptotic signaling. These motifs, including CARD (caspase recruitment domain), DID (death domain), and DIED (death effector domain), are believed to exert their effects solely through homotypic interactions. Herein we demonstrate that the CARD-containing protein ARC engages in nontraditional death-fold interactions to suppress both extrinsic and intrinsic death pathways. The extrinsic pathway is disrupted by heterotypic interactions between ARC's CARD and the DDs of Fas and FADD, which inhibit Fas-FADD binding and assembly of the death-inducing signaling complex (DISC). The intrinsic pathway is antagonized by ARC-Bax binding, involving ARC's CARD and the Bax C terminus. This inhibits Bax activation and translocation to the mitochondria. Knockdown of endogenous ARC facilitates DISC assembly and triggers spontaneous Bax activation and apoptosis. Conversely, physiological levels of ARC suppress these events. These studies establish a critical role for nonhomotypic death-fold interactions in the regulation of apoptosis. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Cardiovasc Res Ctr, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Ctr Canc, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Program Mol Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Boston, MA 02115 USA. RP Kitsis, RN (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM kitsis@aecom.yu.edu FU NHLBI NIH HHS [HL60665, HL61550]; NIGMS NIH HHS [GM 07491] NR 53 TC 114 Z9 133 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 24 PY 2004 VL 15 IS 6 BP 901 EP 912 DI 10.1016/j.molcel.2004.08.020 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 857VX UT WOS:000224148400008 PM 15383280 ER PT J AU Marks, PW Harris, NL Zarghamee-Gavami, M Zukerberg, LR Wexler, DJ Axelrod, L AF Marks, PW Harris, NL Zarghamee-Gavami, M Zukerberg, LR Wexler, DJ Axelrod, L TI A 37-year-old woman with paresthesias of the arms and legs - Anatomical diagnosis - Pernicious anemia with autoimmune gastritis and vitamin B12 deficiency. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COBALAMIN C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Marks, PW (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. NR 12 TC 14 Z9 14 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 SEP 23 PY 2004 VL 351 IS 13 BP 1333 EP 1341 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 855TP UT WOS:000223997700013 PM 15385661 ER PT J AU Murff, HJ Spigel, DR Syngal, S AF Murff, HJ Spigel, DR Syngal, S TI Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID SERVICE-CENTRAL-REGISTER; FOLLOW-UP CARE; BREAST-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER; ENDOMETRIAL CANCER; RISK-ASSESSMENT; OVARIAN-CANCER; INHERITED PREDISPOSITION; GENETICS SERVICES AB Context A family history of certain cancers is associated with an increased risk of developing cancer. Both cancer screening and genetic services referral decisions are often based on self-reported pedigree information. Objective To determine the accuracy of self-reported family cancer history information. Data Sources English-language articles were retrieved by searching MEDLINE (1966-June 2004) using Medical Subject Headings family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. Additional articles were identified through bibliography searches. Study Selection Original studies in which investigators validated self-reported family history by reviewing the identified relatives' medical records, death certificate, or cancer registry information were included, as well as studies that evaluated breast, colon, ovarian, endometrial, and prostate cancers. Data Extraction Two of the 3 investigators independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of self-reported family cancer history information. only data from studies that evaluated both positive and negative family cancer histories were included within the analyses. A total of 14 studies met the search criteria and were included in the review. Data Synthesis For patients without a personal history of cancer, the positive and negative LRs of a family history of the following cancers in a first-degree relative were 23.0 (95% confidence interval [CI], 6.4-81.0) and 0.25 (95 % CI, 0.10-0.63) for colon cancer; 8.9 (95% Cl, 5.4-15.0) and 0.20 (95% Cl, 0.08-0.49) for breast cancer; 14.0 (95% Cl, 2.2-83.4) and 0.68 (95% Cl, 0.31-1.52) for endometrial cancer; 34.0 (95% Cl, 5.7-202.0) and 0.51 (95% Cl, 0.13-2.10) for ovarian cancer; and 12.3 (95% Cl, 6.5-24.0) and 0.32 (95 % Cl, 0.18-0.55) for prostate cancer, respectively. Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives. Conclusions Patient-reported family cancer histories for first-degree relatives are accurate and valuable for breast and colon cancer risk assessments. Negative family history reports for ovarian and endometrial cancers are less useful, although the prevalence of these malignancies within families is low. C1 Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN 37212 USA. Dept Vet Affairs, Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN 37212 USA. Sarah Cannon Canc Ctr, Nashville, TN USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Murff, HJ (reprint author), Vanderbilt Univ, Med Ctr, Div Gen Internal Med, 1310 24th Ave S, Nashville, TN 37212 USA. EM harvey.murff@med.va.gov FU NCI NIH HHS [K07CA08453] NR 105 TC 184 Z9 188 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 22 PY 2004 VL 292 IS 12 BP 1480 EP 1489 DI 10.1001/jama.292.12.1480 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 856FT UT WOS:000224031800031 PM 15383520 ER PT J AU Kawasaki, Y Kohno, T Zhuang, ZY Brenner, GJ Wang, HB Van der Meer, C Befort, K Woolf, CJ Ji, RR AF Kawasaki, Y Kohno, T Zhuang, ZY Brenner, GJ Wang, HB Van der Meer, C Befort, K Woolf, CJ Ji, RR TI Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ERK; C-fiber; CREB; dorsal horn; capsaicin; spinal cord slices; pain ID RAT SPINAL-CORD; LONG-TERM POTENTIATION; INFLAMMATORY PAIN HYPERSENSITIVITY; TRANSCRIPTION FACTOR CREB; MAP KINASE; NMDA RECEPTOR; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; INTRADERMAL INJECTION; NUCLEAR TRANSLOCATION AB Molecular mechanisms underlying C-fiber stimulation-induced ERK ( extracellular signal-regulated kinase) activation in dorsal horn neurons and its contribution to central sensitization have been investigated. In adult rat spinal slice preparations, activation of C-fiber primary afferents by a brief exposure of capsaicin produces an eightfold to 10-fold increase inERKphosphorylation (pERK) in superficial dorsal horn neurons. The pERK induction is reduced by blockade of NMDA, AMPA/kainate, group I metabotropic glutamate receptor, neurokinin-1, and tyrosine receptor kinase receptors. The ERK activation produced by capsaicin is totally suppressed by inhibition of either protein kinase A (PKA) or PKC. PKA or PKC activators either alone or more effectively together induce pERK in superficial dorsal horn neurons. Inhibition of calcium calmodulin-dependent kinase ( CaMK) has no effect, but pERK is reduced by inhibition of the tyrosine kinase Src. The induction of cAMP response element binding protein phosphorylation (pCREB) in spinal cord slices in response to C-fiber stimulation is suppressed by preventing ERK activation with the MAP kinase kinase inhibitor 2-(2-diamino-3-methoxyphenyl-4H- 1-benzopyran-4-one (PD98059) and by PKA, PKC, and CaMK inhibitors. Similar signaling contributes to pERK induction after electrical stimulation of dorsal root C-fibers. Intraplantar injection of capsaicin in an intact animal increases expression of pCREB, c-Fos, and prodynorphin in the superficial dorsal horn, changes that are prevented by intrathecal injection of PD98059. Intrathecal PD98059 also attenuates capsaicin-induced secondary mechanical allodynia, a pain behavior reflecting hypersensitivity of dorsal horn neurons ( central sensitization). We postulate that activation of ionotropic and metabotropic receptors by C-fiber nociceptor afferents activates ERK via both PKA and PKC, and that this contributes to central sensitization through post-translational and CREB-mediated transcriptional regulation in dorsal horn neurons. C1 Brigham & Womens Hosp, Pain Res Ctr, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurol Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ji, RR (reprint author), Brigham & Womens Hosp, Pain Res Ctr, Dept Anesthesiol, Med Res Bldg,Room 604,75 Francis St, Boston, MA 02115 USA. EM rrji@zeus.bwh.harvard.edu OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [NS40698, K08 NS044139, NS39518, R01 NS038253, R01 NS040698] NR 71 TC 228 Z9 249 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 22 PY 2004 VL 24 IS 38 BP 8310 EP 8321 DI 10.1523/JNEUROSCI.2396-04.2004 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 855YA UT WOS:000224009600014 PM 15385614 ER PT J AU Shlipak, MG Massie, BM AF Shlipak, MG Massie, BM TI The clinical challenge of cardiorenal syndrome SO CIRCULATION LA English DT Editorial Material DE heart failure; kidney; natriuretic peptides; vasodilation ID CONGESTIVE-HEART-FAILURE; WORSENING RENAL-FUNCTION; VENTRICULAR SYSTOLIC DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; NATRIURETIC PEPTIDE; INTRAVENOUS NESIRITIDE; INSUFFICIENCY; THERAPY; CREATININE; ANTAGONIST C1 Vet Affairs Med Ctr, Cardiol Div 111C, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. San Francisco VAMC, Gen Internal Med Sect, San Francisco, CA USA. RP Massie, BM (reprint author), Vet Affairs Med Ctr, Cardiol Div 111C, 4150 Clement St, San Francisco, CA 94121 USA. EM barry.massie@med.va.gov FU NHLBI NIH HHS [R01 HL073208-01] NR 26 TC 89 Z9 110 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 21 PY 2004 VL 110 IS 12 BP 1514 EP 1517 DI 10.1161/01.CIR.0000143547.55093.17 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 855MP UT WOS:000223977700001 PM 15381655 ER PT J AU Chi, HH Messas, E Levine, RA Graves, DT Amar, S AF Chi, HH Messas, E Levine, RA Graves, DT Amar, S TI Interleukin-1 receptor signaling mediates atherosclerosis associated with bacterial exposure and/or a high-fat diet in a murine apolipoprotein E heterozygote model - Pharmacotherapeutic implications SO CIRCULATION LA English DT Article DE atherosclerosis; infection; interleukins; cardiovascular diseases; Porphyromonas gingivalis ID C-REACTIVE PROTEIN; FACTOR BINDING-PROTEIN; APOE-DEFICIENT MICE; CARDIOVASCULAR-DISEASE; PERIODONTAL PATHOGENS; CHLAMYDIA-PNEUMONIAE; CYTOKINE PRODUCTION; STREAK FORMATION; I RECEPTOR; ANTAGONIST AB Background-Current data demonstrate that progressive atherosclerosis is associated with activation of the inflammatory process, as evidenced by systemic elevations of molecules such as tumor necrosis factor, interleukin (IL)-6, and IL-1. It has been postulated that inflammatory events within an atherogenic lesion are induced by oxidized LDL. Recent evidence suggests that infectious agents, including those that cause periodontal disease, may also play an important role. Studies presented here tested the hypothesis that IL-1 receptor (IL-1R1) signaling plays a crucial role in bacteria- and/or high-fat diet (HFD)-enhanced atherogenesis. Methods and Results-Ten-week-old ApoE(+/-) mice lacking either 1 IL-1R1 allele (ApoE(+/-)/IL-1R1(+/-)) or 2 IL-1R1 alleles (ApoE(+/-)/IL-1R1(-/-)) fed either an HFD or regular chow were inoculated intravenously with live Porphyromonas gingivalis (P gingivalis) (10(7) CFU), an important periodontal pathogen, or vehicle once per week for 14 or 24 consecutive weeks. Histomorphometry of plaque cross-sectional area in the proximal aortas, en face measurement of plaque area over the aortic trees, and ELISA for systemic proinflammatory mediators were performed. Atherosclerotic lesions of proximal aortas and aortic tree were substantially reduced in ApoE(+/-)/IL-1R1(-/-) mice than in ApoE(+/-)/IL-1R1(+/-) mice challenged with P gingivalis. At 24 weeks after P gingivalis inoculation, proximal aortic lesion size quantified by histomorphometry was 5-fold-reduced in chow-fed ApoE(+/-)/IL-1R1(-/-) mice than in ApoE(+/-)/IL-1R1(+/-) mice (P<0.05). In the HFD group, ApoE(+/-)/IL-1R1(-/-) mice exhibited marked attenuation of the progression of atherosclerotic lesions (78% to 97%), with and without P gingivalis inoculation (P<0.05) Conclusion-Ablation of IL-1R1 under P gingivalis challenge and/or an HFD reduced the progression of atherosclerotic plaques. These results indicate that IL-1 plays a crucial role in bacteria- and/or HFD-enhanced atherogenesis. C1 Boston Univ, Dept Periodontol & Oral Biol, Sch Dent Med, Dept Pathol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Amar, S (reprint author), Boston Univ, Dept Periodontol & Oral Biol, Sch Dent Med, Dept Pathol, 700 Albany St,W201E, Boston, MA 02118 USA. EM samar@bu.edu OI Amar, Salomon/0000-0002-0017-5930 FU NHLBI NIH HHS [HL076801]; NIDCR NIH HHS [DE12482] NR 50 TC 104 Z9 108 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 21 PY 2004 VL 110 IS 12 BP 1678 EP 1685 DI 10.1161/01.CIR.0000142085.39015.31 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 855MP UT WOS:000223977700026 PM 15353494 ER PT J AU Carvalho, P Pellman, D AF Carvalho, P Pellman, D TI Mitotic spindle: Laser microsurgery in yeast cells SO CURRENT BIOLOGY LA English DT Editorial Material ID FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; ANAPHASE-B; MICROTUBULES; ELONGATION; MECHANISM; ALIGNMENT; MITOSIS; MIDZONE AB Laser microsurgery has led to remarkable discoveries in a number of cell types. Two recent studies have shown that this classical technology can now be employed with small yeast cells. This advance will enable regional ablation to be combined with facile genetic manipulation in a eukaryotic cell. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Biomed Sci Abel Salazar, Oporto, Portugal. RP Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu OI Carvalho, Pedro/0000-0002-9691-5277 NR 20 TC 3 Z9 3 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD SEP 21 PY 2004 VL 14 IS 18 BP R748 EP R750 DI 10.1016/j.cub.2004.09.010 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 857BC UT WOS:000224089300009 PM 15380083 ER PT J AU Liu, XQ Bulgakov, OV Wen, XH Woodruff, ML Pawlyk, B Yang, J Fain, GL Sandberg, MA Makino, CL Li, TS AF Liu, XQ Bulgakov, OV Wen, XH Woodruff, ML Pawlyk, B Yang, J Fain, GL Sandberg, MA Makino, CL Li, TS TI AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; RETINITIS-PIGMENTOSA; BETA-SUBUNIT; RD MOUSE; PHOTORECEPTOR DYSTROPHY; TRANSGENIC MICE; GAMMA-SUBUNIT; A-WAVE; GENE; MUTATIONS AB Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is a member of the FK-506-binding protein family expressed specifically in retinal photoreceptors. Mutations in AIPL1 cause Leber congenital amaurosis, a severe early-onset retinopathy that leads to visual impairment in infants. Here we show that knockdown of AIPL1 expression in mice also produces a retinopathy but over a more extended time course. Before any noticeable pathology, there was a reduction in the level of rod cGMP phosphodiesterase (PDE) proportional to the decrease in AIPL1 expression, whereas other photoreceptor proteins were unaffected. Consistent with less PDE in rods, flash responses had a delayed onset, a reduced gain, and a slower recovery of flash responses. We suggest that AIPL1 is a specialized chaperone required for rod PDE biosynthesis. Thus loss of AIPL1 would result in a condition that phenocopies retinal degenerations in the rd mouse and in a subgroup of human patients. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Howe Lab, Sch Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Sch Med, Boston, MA 02114 USA. EM tli@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [EY14104, EY01844, EY10309, P30 EY014104, R01 EY011358, R29 EY011358, R37 EY001844, R01 EY001844, R01 EY010309, EY11358] NR 49 TC 59 Z9 60 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 SEP 21 PY 2004 VL 101 IS 38 BP 13903 EP 13908 DI 10.1073/pnas.0405160101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 856UF UT WOS:000224069800038 PM 15365173 ER PT J AU Goggins, W Gao, W Tsao, H AF Goggins, W Gao, W Tsao, H TI Association between female breast cancer and cutaneous melanoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cutaneous melanoma; breast cancer ID MALIGNANT-MELANOMA; PRIMARY NEOPLASMS; RISK; LYMPHOMA AB Epidemiologic studies have provided suggestive evidence of a link between cutaneous melanoma (CM) and breast cancer (BC). Moreover, carriers of mutations in the breast cancer predisposition gene, BRCA2, have an increased risk of melanoma while carriers of mutations in the melanoma sus- ceptibility gene, CDKN2A, exhibit a higher than expected risk of breast cancer. These findings raise the possibility that pathways involved in the development of CM and BC overlap and that survivors of one cancer may be prone to develop the other. To this end, we set out to determine if survivors of female BC in the Surveillance, Epidemiology and End Result (SEER) database are at increased risk for CM and vice versa. We followed female BC patients registered in the 19731999 SEER database for development of a second CM and female CM patients for the development of a second BC. The expected number of cases was then compared to the observed number of cases using standardized incidence ratios. Overall, we found a modest but statistically significant increased risk of CM among female BC survivors and vice versa. Among young BC patients, we observed a 46% elevated risk of a second CM. Women who underwent radiation therapy exhibited a 42% increased risk for CM. The risks of BC among female CM survivors and CM among BC survivors were also elevated, albeit to a much lesser degree (overall, 11% and 16%, respectively). We found a mutual association between female BC and CM. The elevated risk for CM, especially among younger BC patients, suggests that the genetic observations from high-risk groups may also be operative at a much lower level in the general BC population. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Jinan Univ, Postdoctoral Mobile Stn Clin Med, Guangzhou, Peoples R China. Chinese Univ Hong Kong, Ctr Biostat & Epidemiol, Shatin, Hong Kong, Peoples R China. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org RI Gao, Wei/G-8653-2011 OI Gao, Wei/0000-0001-8298-3415 NR 15 TC 36 Z9 37 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 20 PY 2004 VL 111 IS 5 BP 792 EP 794 DI 10.1002/ijc.20322 PG 3 WC Oncology SC Oncology GA 845SD UT WOS:000223263700021 PM 15252852 ER PT J AU Lichterfeld, M Kaufmann, DE Yu, XG Mui, SK Addo, MM Johnston, MN Cohen, D Robbins, GK Pae, E Alter, G Wurcel, A Stone, D Rosenberg, ES Walker, BD Altfeld, M AF Lichterfeld, M Kaufmann, DE Yu, XG Mui, SK Addo, MM Johnston, MN Cohen, D Robbins, GK Pae, E Alter, G Wurcel, A Stone, D Rosenberg, ES Walker, BD Altfeld, M TI Loss of HIV-1-specific CD8(+) T cell proliferation after acute HIV-1 infection and restoration by vaccine-induced HIV-1-specific CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HIV-1; CD8(+) T cells; CD4(+) T cells; vaccine; protective immunity ID VIRUS TYPE-1 INFECTION; IMMUNE-RESPONSES; ANTIRETROVIRAL THERAPY; GP120-DEPLETED HIV-1; EFFECTOR ACTIVITY; AUTOLOGOUS VIRUS; VIRAL LOAD; VIREMIA; INTERLEUKIN-2; INDIVIDUALS AB Virus-specific CD8(+) T cells are associated with declining viremia ill acute human immunodeficiency virus (HIV)1 infection, but do not correlate with control of viremia in chronic infection, suggesting a progressive functional defect not measured by interferon gamma assays presently used. Here, we demonstrate that HIV-1-specific CD8(+) T cells proliferate rapidly upon encounter with cognate antigen in acute infection, but lose this capacity with ongoing viral replication. This functional defect can be induced in vitro by depletion of CD4(+) T cells or addition of interleukin 2-neutralizing antibodies, and can be corrected in chronic infection in vitro by addition of autologous CD4(+) T cells isolated during acute infection and in vivo by vaccine-mediated induction of HIV-1-specific CD4(+) T helper cell responses. These data demonstrate a loss of HIV-1-specific CD8+ T cell function that not only correlates with progressive infection, but also can be restored in chronic infection by augmentation of HIV-1-specific T helper cell function. This identification of a reversible defect in cell-mediated immunity in chronic HIV-1 infection has important implications for immunotherapeutic interventions. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. Fenway Community Hlth Care Ctr, Boston, MA 02115 USA. Lemuel Shattuck Hosp, Boston, MA 02130 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org RI Robbins, Gregory/F-7988-2011 NR 32 TC 253 Z9 258 U1 1 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 20 PY 2004 VL 200 IS 6 BP 701 EP 712 DI 10.1084/jem.20041270 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 857GX UT WOS:000224105500002 PM 15381726 ER PT J AU Davidson, AJ Zon, LI AF Davidson, AJ Zon, LI TI The 'definitive' (and 'primitive') guide to zebrafish hematopoiesis SO ONCOGENE LA English DT Review DE zebrafish; blood; hematopoietic stem cell; embryo; leukemia; hematopoiesis ID T-CELL LEUKEMIA; ACUTE MYELOID-LEUKEMIA; HOMEOBOX GENE CDX2; TRANSGENIC ZEBRAFISH; DANIO-RERIO; HOX GENES; IN-VIVO; VERTEBRATE DEVELOPMENT; POSITIONAL CLONING; EXPRESSION PATTERN AB Progressive advances using zebrafish as a model organism have provided hematologists with an additional genetic system to study blood cell formation and hematological malignancies. Despite extensive evolutionary divergence between bony fish (teleosts) and mammals, the molecular pathways governing hematopoiesis have been highly conserved. As a result, most (if not all) of the critical hematopoietic transcription factor genes identified in mammals have orthologues in zebrafish. As in other vertebrates, all of the teleost blood lineages are believed to originate from a pool of pluripotent, self-renewing hematopoietic stem cells. Here, we provide a detailed review of the timing, anatomical location, and transcriptional regulation of zebrafish 'primitive' and 'definitive' hematopoiesis as well as discuss a model of T-cell leukemia and recent advances in blood cell transplantation. Given that many of the regulatory genes that control embryonic hematopoiesis have been implicated in oncogenic pathways in adults, an understanding of blood cell ontogeny is likely to provide insights into the pathophysiology of human leukemias. C1 Childrens Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Div Hematol Oncol, Dept Med, KARP7,1 Blackfan Circle, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 115 TC 211 Z9 225 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 20 PY 2004 VL 23 IS 43 BP 7233 EP 7246 DI 10.1038/sj.onc.1207943 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 855TZ UT WOS:000223998800009 PM 15378083 ER PT J AU Chan, RC Chau, AH Karl, WC Nadkarni, S Khalil, AS Iftimia, N Shishkov, M Tearney, GJ Kaazempur-Mofrad, MR Bouma, BE AF Chan, RC Chau, AH Karl, WC Nadkarni, S Khalil, AS Iftimia, N Shishkov, M Tearney, GJ Kaazempur-Mofrad, MR Bouma, BE TI OCT-based arterial elastography: robust estimation exploiting tissue biomechanics SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CIRCUMFERENTIAL STRESS; STRAIN AB We present a novel multi-resolution variational framework for vascular optical coherence elastography (OCE). This method exploits prior information about arterial wall biomechanics to produce robust estimates of tissue velocity and strain, reducing the sensitivity of conventional tracking methods to both noise- and strain-induced signal decorrelation. The velocity and strain estimation performance of this new estimator is demonstrated in simulated OCT image sequences and in benchtop OCT scanning of a vascular tissue sample. (C) 2004 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Elect Engn & Comp Engn, Boston, MA 02215 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Chan, RC (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM rchan@nmr.mgh.harvard.edu; alyx@mit.edu NR 17 TC 62 Z9 62 U1 2 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 20 PY 2004 VL 12 IS 19 BP 4558 EP 4572 DI 10.1364/OPEX.12.004558 PG 15 WC Optics SC Optics GA 855KG UT WOS:000223971500025 PM 19484007 ER PT J AU Yuan, SP Joseph, EM AF Yuan, SP Joseph, EM TI The small heart mutation reveals novel roles of Na+/K+-ATPase in maintaining ventricular cardiomyocyte morphology and viability in zebrafish SO CIRCULATION RESEARCH LA English DT Article DE apoptosis; cardiac; development; heart failure; organogenesis; Na+/K+-ATPase; Danio rerio ID NA,K-ATPASE ALPHA-SUBUNIT; GENES; NA+,K+-ATPASE; INHIBITION; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION; ORGANOGENESIS; APOPTOSIS; EMBRYO AB Forward genetic screens in zebrafish have been used to identify mutations in genes with important roles in organogenesis. One of these mutants, small heart, develops a diminutive and severely malformed heart and multiple developmental defects of the brain, ears, eyes, and kidneys. Using a positional cloning approach, we identify that the mutant gene encodes the zebrafish Na+/K+-ATPase alpha1B1 protein. Disruption of Na+/K+-ATPase alpha1B1 function via morpholino "knockdown" or pharmacological inhibition with ouabain phenocopies the mutant phenotype, in a dose-dependent manner. Heterozygosity for the mutation sensitizes embryos to ouabain treatment. Our findings present novel genetic and morphological details on the function of the Na+/K+-ATPase alpha1B1 in early cardiac morphogenesis and the pathogenesis of the small heart malformation. We demonstrate that the reduced size of the mutant heart is caused by dysmorphic ventricular cardiomyocytes and an increase in ventricular cardiomyocyte apoptosis. This study provides a new insight that Na+/K+-ATPase alpha1B1 is required for maintaining ventricular cardiomyocyte morphology and viability. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Yuan, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM yuan@cvrc.mgh.harvard.edu FU NIDDK NIH HHS [DK 43351] NR 36 TC 18 Z9 19 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 17 PY 2004 VL 95 IS 6 BP 595 EP 603 DI 10.1161/01.RES.0000141529.48143.6e PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 854IM UT WOS:000223896300009 PM 15297381 ER PT J AU Chen, K Holschneider, DP Wu, WH Rebrin, I Shih, JC AF Chen, K Holschneider, DP Wu, WH Rebrin, I Shih, JC TI A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGGRESSIVE-BEHAVIOR; DEFICIENT MICE; PLUS-MAZE; B GENES; MOLECULAR-BASIS; NORRIE DISEASE; A-DEFICIENT; MAO-B; RECEPTOR; SEROTONIN AB A spontaneous monoamine oxidase A (MAO A) mutation (A863T) in exon 8 introduced a premature stop codon, which produced MAO A/B double knock-out ( KO) mice in a MAO B KO mouse colony. This mutation caused a nonsense-mediated mRNA decay and resulted in the absence of MAO A transcript, protein, and catalytic activity and abrogates a DraI restriction site. The MAO A/B KO mice showed reduced body weight compared with wild type mice. Brain levels of serotonin, norepinephrine, dopamine, and phenylethylamine increased, and serotonin metabolite 5-hydroxyindoleacetic acid levels decreased, to a much greater degree than in either MAO A or B single KO mice. Observed chase/ escape and anxiety-like behavior in the MAO A/B KO mice, different from MAO A or B single KO mice, suggest that varying monoamine levels result in both a unique biochemical and behavioral phenotype. These mice will be useful models for studying the molecular basis of disorders associated with abnormal monoamine neurotransmitters. C1 Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90089 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Shih, JC (reprint author), Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, 1985 Zonal Ave,Rm 528, Los Angeles, CA 90089 USA. EM jcshih@usc.edu FU NIMH NIH HHS [R37 MH039085, R01 MH NS62148, R37 MH039085-23, R37 MH38635]; NINDS NIH HHS [K23 NS062148] NR 58 TC 67 Z9 68 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 17 PY 2004 VL 279 IS 38 BP 39645 EP 39652 DI 10.1074/jbc.M405550200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 852YA UT WOS:000223791500055 PM 15272015 ER PT J AU Solomons, JTG Zimmerly, EM Burns, S Krishnamurthy, N Swan, MK Krings, S Muirhead, H Chirgwin, J Davies, C AF Solomons, JTG Zimmerly, EM Burns, S Krishnamurthy, N Swan, MK Krings, S Muirhead, H Chirgwin, J Davies, C TI The crystal structure of mouse phosphoglucose isomerase at 1.6 angstrom resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phosphoglucoseisomerase; aldose-ketose isomerase; enzyme mechanism; cytokine; X-ray crystallography ID AUTOCRINE MOTILITY FACTOR; CONFORMATIONAL-CHANGES; RABBIT; NEUROLEUKIN; PHOSPHATE; ENZYME; DIFFERENTIATION; 6-PHOSPHATE; HISTIDINE; LOCATION AB Phosphoglucose isomerase (PGI) is an enzyme of glycolysis that interconverts, glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) but, outside the cell, is a multifunctional cytokine. High-resolution crystal structures of the enzyme from mouse have been determined in native form and in complex with the inhibitor erythrose 4-phosphate, and with the substrate glucose 6-phosphate. In the substrate-bound structure, the glucose sugar is observed in both straight-chain and ring forms. This structure supports a specific role for Lys518 in enzyme-catalyzed ring opening and we present a "push-pull" mechanism in which His388 breaks the O5-C1 bond by donating a proton to the ring oxygen atom and, simultaneously, Lys518 abstracts a proton from the Cl hydroxyl group. The reverse occurs in ring closure. The transition from ring form to straight-chain substrate is achieved through rotation of the C3-C4 bond, which brings the C1-C2 region into close proximity to Glu357, the base catalyst for the isomerization step. The structure with G6P also explains the specificity of PGI for glucose 6-phosphate over mannose 6-isomerase (M6P). To isomerize M6P to F6P requires a rotation of its C2-C3 bond but in PGI this is sterically blocked by Gln511. (C) 2004 Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Vet Adm Med Ctr, Res Serv, San Antonio, TX 78230 USA. Univ Bristol, Sch Med Sci, Bristol BS8 1TD, Avon, England. Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. RP Davies, C (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM davies@musc.edu FU NIGMS NIH HHS [R25GM067084] NR 36 TC 26 Z9 27 U1 1 U2 9 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 SEP 17 PY 2004 VL 342 IS 3 BP 847 EP 860 DI 10.1016/j.jmb.2004.07.085 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 853OX UT WOS:000223838000012 PM 15342241 ER PT J AU Humbles, AA Lloyd, CM McMillan, SJ Friend, DS Xanthou, G McKenna, EE Ghiran, S Gerard, NP Yu, CN Orkin, SH Gerard, C AF Humbles, AA Lloyd, CM McMillan, SJ Friend, DS Xanthou, G McKenna, EE Ghiran, S Gerard, NP Yu, CN Orkin, SH Gerard, C TI A critical role for eosinophils in allergic airways remodeling SO SCIENCE LA English DT Article ID SUBEPITHELIAL FIBROSIS; BRONCHIAL-ASTHMA; INFLAMMATION; EXPRESSION; HYPERREACTIVITY; BIOPSIES; GATA-1; MOUSE; LEADS AB Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Humbles, AA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM alison.humbles@childrens.harvard.edu; c.lloyd@imperial.ac.uk OI Lloyd, Clare/0000-0001-8977-6726 FU Wellcome Trust [087618] NR 29 TC 534 Z9 560 U1 6 U2 31 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 SEP 17 PY 2004 VL 305 IS 5691 BP 1776 EP 1779 DI 10.1126/science.1100283 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 856IS UT WOS:000224039500042 PM 15375268 ER PT J AU Brugge, WR Lauwers, GY Sahani, D Fernandez-del Castillo, C Warshaw, AL AF Brugge, WR Lauwers, GY Sahani, D Fernandez-del Castillo, C Warshaw, AL TI Cystic neoplasms of the pancreas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PAPILLARY MUCINOUS TUMORS; PATHOLOGICAL CORRELATION; SEROUS CYSTADENOMA; FLUID ANALYSIS; DIFFERENTIAL-DIAGNOSIS; NEEDLE-ASPIRATION; LESIONS; EUS; CT; MANAGEMENT C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 57 TC 377 Z9 414 U1 2 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 16 PY 2004 VL 351 IS 12 BP 1218 EP 1226 DI 10.1056/NEJMra031623 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 853WS UT WOS:000223861300010 PM 15371579 ER PT J AU Chae, CU Afridi, NA Karchmer, AW Torchiana, DF Houser, SL AF Chae, CU Afridi, NA Karchmer, AW Torchiana, DF Houser, SL TI Case 29-2004: A 75-year-old woman with acute onset of chest pain followed by fever - Acute bacterial endocarditis with aortic-root abscess, due to infection by S-anginosus (S-milleri group) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CARDIAC CONDUCTION ABNORMALITIES; STREPTOCOCCUS-MILLERI; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; VALVE ENDOCARDITIS; DUKE CRITERIA; DIAGNOSIS; REPLACEMENT; DETERMINANTS; MANAGEMENT C1 Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chae, CU (reprint author), Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02114 USA. NR 32 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 16 PY 2004 VL 351 IS 12 BP 1240 EP 1248 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 853WS UT WOS:000223861300014 PM 15371582 ER PT J AU Morrow, DA Sabatine, MS Antman, EM Cannon, CP Braunwald, E Theroux, P AF Morrow, DA Sabatine, MS Antman, EM Cannon, CP Braunwald, E Theroux, P TI Usefulness of Tirofiban among patients treated without percutaneous coronary intervention (TIMI high risk patients in PRISM-PLUS) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLYCOPROTEIN IIB/IIIA RECEPTOR; WAVE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; INHIBITION; BENEFIT; REGISTRY; STRATIFICATION; THERAPIES; SCORE AB Although the efficacy of glycoprotein IIb/IIIa inhibition in non-ST-elevation acute coronary syndromes is greatest in patients who undergo percutaneous coronary intervention (PCI), it was hypothesized that high-risk patients managed without PCI also benefit. The TIMI risk score was calculated for 1,570 patients randomized to tirofiban plus heparin versus heparin in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. In high-risk patients (score :4) treated without PCI, tirofiban reduced the risk for death, myocardial infarction, and refractory ischemia at 30 days (28.8% vs 21.9%; odds ratio [OR] 0.69, p = 0.04). This benefit was similar in magnitude as that for patients who underwent PCI (32.4% vs 22.2%; OR 0.60, p = 0.06). No benefit was evident in low-risk patients. (C) 2004 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 15 TC 10 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2004 VL 94 IS 6 BP 774 EP 776 DI 10.1016/j.amjcard.2004.05.065 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 858RZ UT WOS:000224210700018 PM 15374786 ER PT J AU Petryshen, TL Rockwell, G Aldinger, KA Kirby, AN Wade, CM Waggoner, SG Daly, MJ Sklar, P AF Petryshen, TL Rockwell, G Aldinger, KA Kirby, AN Wade, CM Waggoner, SG Daly, MJ Sklar, P TI Identification of genes involved in prepulse inhibition, an endophenotype of schizophrenia, in consomic mouse strains using an innovative haplotype and expression mapping approach SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 13 EP 13 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600052 ER PT J AU Bertram, L Hiltunen, M Parkinson, M Mullin, K Menon, R Elliott, KJ Wagner, SL Blacker, D Becker, KD Tanzi, RE AF Bertram, L Hiltunen, M Parkinson, M Mullin, K Menon, R Elliott, KJ Wagner, SL Blacker, D Becker, KD Tanzi, RE TI Family-based association of ubiquilin 1 (UBQLN1) and Alzheimer's disease in two independent samples SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Massachusetts Gen Hosp, Charlestown, MA USA. Neurogenet Inc, La Jolla, CA 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 16 EP 16 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600061 ER PT J AU Petryshen, TL Kirby, AN Pato, CN Tahl, AR Middleton, FA Rockwell, G Schwab, SG Wildenauer, DB Aldinger, KA Waggoner, SG Morley, CP McGann, L Gentile, KL Medeiros, H Azevedo, MH Daly, MJ Pato, MT Sklar, P AF Petryshen, TL Kirby, AN Pato, CN Tahl, AR Middleton, FA Rockwell, G Schwab, SG Wildenauer, DB Aldinger, KA Waggoner, SG Morley, CP McGann, L Gentile, KL Medeiros, H Azevedo, MH Daly, MJ Pato, MT Sklar, P TI The chromosome 5 GABA A receptor genes GABRA1 and GABRB2 confer risk of schizophrenia and are correlated with altered GABA pathway transcript levels SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. SUNY Syracuse, Syracuse, NY USA. Univ Western Australia, Perth, WA 6009, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 18 EP 18 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600068 ER PT J AU Faraone, SV Arbeitman, L Fagerness, H Kirby, A Daly, M Doyle, A Smoller, JW Sklar, P AF Faraone, SV Arbeitman, L Fagerness, H Kirby, A Daly, M Doyle, A Smoller, JW Sklar, P TI Haplotype block analysis finds association between the dopamine transporter gene and comorbid ADHD and bipolar disorder but not ADHD without bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 20 EP 21 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600076 ER PT J AU Smoller, JW Yamaki, LH Fagerness, J Racette, S Biederman, J Laird, NM Tsuang, MT Rosenbaum, JF Sklar, P AF Smoller, JW Yamaki, LH Fagerness, J Racette, S Biederman, J Laird, NM Tsuang, MT Rosenbaum, JF Sklar, P TI Association of the corticotropin releasing hormone gene with anxious temperament in children at risk for panic disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 24 EP 24 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600090 ER PT J AU Joo, YH Sanders, RD Almasy, L Gur, RE Wood, J Dayal, M Keshavan, M Nimgaonkar, VL AF Joo, YH Sanders, RD Almasy, L Gur, RE Wood, J Dayal, M Keshavan, M Nimgaonkar, VL TI Neurological soft signs in large extended multiplex schizophrenia families: Heritability estimation and their relationship with neuropsychological tests SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Univ Penn, Philadelphia, PA 19104 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 57 EP 57 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600213 ER PT J AU Fan, JB Sklar, P AF Fan, JB Sklar, P TI Meta-analysis shows association between serotonin transporter gene intron 2 VNTR and schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 84 EP 85 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600327 ER PT J AU Paschou, P Feng, Y Pakstis, AJ Speed, WC De Mille, MC Kidd, JR Jaghori, B Kurlan, R Pauls, DL Sandor, P Barr, CL Kidd, KK AF Paschou, P Feng, Y Pakstis, AJ Speed, WC De Mille, MC Kidd, JR Jaghori, B Kurlan, R Pauls, DL Sandor, P Barr, CL Kidd, KK TI 17q25 implicated in Tourette syndrome susceptibility: A study of two independent family samples SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. Univ Rochester, Sch Med, Dept Neurol, Cognit & Behav Neurol Unit, Rochester, NY 14627 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Hosp Sick Children, Dept Psychiat, Brain & Behav Programme, Toronto, ON M5G 1X8, Canada. 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 94 EP 94 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600363 ER PT J AU Haddad, SA Fagerness, J Yamaki, LH Andresen, KA Santangelo, SL AF Haddad, SA Fagerness, J Yamaki, LH Andresen, KA Santangelo, SL TI A genetic investigation of autism using extremely discordant sib pairs SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Harvard Univ, Sch Publ Hlth, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 95 EP 95 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600367 ER PT J AU Kim, JW Fagerness, J Arbeitman, L Doyle, A Petty, C Biederman, J Faraone, SV Sklar, P AF Kim, JW Fagerness, J Arbeitman, L Doyle, A Petty, C Biederman, J Faraone, SV Sklar, P TI Fine mapping of chromosomal regions implicated in ADHD SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Pediat Psychopharmacol Unit, 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 95 EP 95 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600366 ER PT J AU Smoller, JW Arbeitman, L Fagerness, J Doyle, AE Perlis, R Petty, C Faraone, SV Sklar, P AF Smoller, JW Arbeitman, L Fagerness, J Doyle, AE Perlis, R Petty, C Faraone, SV Sklar, P TI Linkage disequilibrium analyses of candidate loci for ADHD: Association between the 5HT1B receptor gene and the inattentive subtype of ADHD SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 100 EP 100 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600384 ER PT J AU van der Meulen, EM Bakker, SC de Kovel, CGF Pauls, DL Sinke, RJ Buitelaar, JK AF van der Meulen, EM Bakker, SC de Kovel, CGF Pauls, DL Sinke, RJ Buitelaar, JK TI Suggestive evidence for linkage on odd symptom severity in a genomewide quantitative trait locus analysis of dutch affected sibpairs with ADHD SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Unit Psychiat & Neurodev Genet, Boston, MA USA. Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. Univ Med Ctr Nijmegen, Dept Human Genet, Nijmegen, Netherlands. Univ Med Ctr Nijmegen, Dept Psychiat, Nijmegen, Netherlands. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 106 EP 107 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600406 ER PT J AU Medina, RA Escamilla, MA Walss-Bass, C Raventos, H Montero, AP Dassori, A Armas, R Contreras, S AF Medina, RA Escamilla, MA Walss-Bass, C Raventos, H Montero, AP Dassori, A Armas, R Contreras, S TI Increased frequency of AD18S70 allele in a factor-derived cluster of patients with non-affective psychosis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Costa Rica, San Jose, Costa Rica. Univ Calif San Francisco, San Francisco, CA 94143 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 139 EP 139 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600533 ER PT J AU Orourke, J Platko, JV Pauls, D AF Orourke, J Platko, JV Pauls, D TI Candidate gene selection for developmental dyslexia: A bioinformatics approach SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tufts Univ, Medford, MA 02155 USA. Harvard Univ, Cambridge, MA 02138 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 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 15 PY 2004 VL 130B IS 1 BP 153 EP 153 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 852GE UT WOS:000223742600588 ER PT J AU Guadagnoli, E Normand, SLT DiSalvo, TG Palmer, RH McNeil, BJ AF Guadagnoli, E Normand, SLT DiSalvo, TG Palmer, RH McNeil, BJ TI Effects of treatment recommendations and specialist intervention on care provided by primary care physicians to patients with myocardial infarction or heart failure SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-CARE; RANDOMIZED CONTROLLED-TRIAL; MEDICARE PATIENTS; ELDERLY PATIENTS; CASE-MANAGEMENT; UNITED-STATES; OUTCOMES; IMPROVE; MEDICATIONS; GUIDELINES AB PURPOSE: To assess the effects of an intervention involving dissemination of treatment recommendations to primary care physicians treating outpatients with acute myocardial infarction or heart failure. METHODS: The study comprised 509 patients with myocardial infarction and 323 patients with heart failure who were discharged from hospital. The primary care physicians caring for these patients were assigned randomly to either the intervention or control group; the intervention group was mailed practice guidelines immediately after patient discharge, and patients were cited by name. During a 6-month assessment period, the records of primary care physicians (and cardiologists, if any) were reviewed to assess mean conformance with the guidelines, using seven measures of care for myocardial infarction and eight measures of care for heart failure. RESULTS: After adjusting for demographic and clinical characteristics of patients, and the number of eligible measures per patient, we observed no effect of the intervention on care of patients with myocardial infarction (odds ratio [OR] = 0.98; 95% confidence interval [CI]: 0.81 to 1.17) or heart failure (OR = 1.25; 95% CI: 0.96 to 1.59). However, there was a higher likelihood of conformance with measures for patients with infarction (OR = 1.56; 95% CI: 1.29 to 1.87) or heart failure (OR = 1.71; 95% CI: 1.29 to 2.23) who had also been seen by a cardiologist during the 6-month assessment period. CONCLUSION: Mailing treatment recommendations did not improve the quality of care of recently discharged patients with myocardial infarction or heart failure. However, efforts to include cardiologists in the care of these patients might be worthwhile. (C) 2004 by Elsevier Inc. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Heart Failure Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Guadagnoli, E (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Guadagnoli@hcp.med.harvard.edu FU AHRQ HHS [HS 09487] NR 36 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD SEP 15 PY 2004 VL 117 IS 6 BP 371 EP 379 DI 10.1016/j.amjmed.2004.04.013 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 855VT UT WOS:000224003700001 PM 15380493 ER PT J AU Seshadri, P Iqbal, N Stern, L Williams, M Chicano, KL Daily, DA McGrory, J Gracely, EJ Rader, DJ Samaha, FF AF Seshadri, P Iqbal, N Stern, L Williams, M Chicano, KL Daily, DA McGrory, J Gracely, EJ Rader, DJ Samaha, FF TI A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; INSULIN-RESISTANCE ATHEROSCLEROSIS; ISCHEMIC-HEART-DISEASE; WEIGHT-LOSS; CORONARY ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; PARTICLE-SIZE; RISK; SUBCLASSES; PLASMA AB PURPOSE: To compare the effects of a low- carbohydrate diet and a conventional (fat- and calorie- restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. METHODS: We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low- carbohydrate or conventional diet for 6 months. RESULTS: Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = -0.26 mg/dL, P = 0.03) but more frequently developed detectable chytomicrons (44% vs. 22%,.P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level ( > 3 mg/dL, n 48) experienced a greater decrease in C-reactive protein levels on a low- carbohydrate diet (adjusted difference = -2.0 mg/dL, P = 0.005), independent of weight loss. CONCLUSION: In this 6-month study involving severely obese subjects, we found an overall favorable effect of a lowcarbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. 9)2004 by Elsevier Inc. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Hlth Syst, Dept Internal Med, Div Endocrinol & Cardiol, Philadelphia, PA 19104 USA. Drexel Univ, Dept Family Community & Prevent Med, Coll Med, Philadelphia, PA 19104 USA. RP Samaha, FF (reprint author), Philadelphia VA Med Ctr, 8th Floor,MC 111C,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM rick.samaha@med.va.gov NR 32 TC 88 Z9 90 U1 1 U2 9 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 15 PY 2004 VL 117 IS 6 BP 398 EP 405 DI 10.1016/j.amjmed.2004.04.009 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 855VT UT WOS:000224003700004 PM 15380496 ER PT J AU Isomoto, H Nakazato, M Ueno, H Date, Y Nishi, Y Mukae, H Mizuta, Y Ohtsuru, A Yamashita, S Kohno, S AF Isomoto, H Nakazato, M Ueno, H Date, Y Nishi, Y Mukae, H Mizuta, Y Ohtsuru, A Yamashita, S Kohno, S TI Low plasma ghrelin levels in patients with Helicobacter pylori - Associated gastritis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PEPTIDE; ENDOCRINE; HUMANS C1 Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 852, Japan. Nagasaki Univ, Sch Med, Dept Mol Med, Atom Bomb Dis Inst, Nagasaki 852, Japan. Miyazaki Med Coll, Dept Internal Med 3, Miyazaki 88916, Japan. RP Isomoto, H (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Jackson 706,55 Fruit St, Boston, MA 02114 USA. EM hajimei2002@yahoo.co.jp OI Yamashita, Shunichi/0000-0001-6399-6261 NR 13 TC 58 Z9 59 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 15 PY 2004 VL 117 IS 6 BP 429 EP 432 DI 10.1016/j.amjmed.2004.01.030 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 855VT UT WOS:000224003700008 PM 15380500 ER PT J AU Cummings, DE AF Cummings, DE TI Helicobacter pylori and ghrelin: Interrelated players in body-weight regulation? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID NONULCER DYSPEPSIA; GASTRIC-CARCINOMA; FOOD-INTAKE; INFECTION; APPETITE; GROWTH; ERADICATION; PEPTIDE; HUMANS; RISK C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111-Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu NR 29 TC 21 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 15 PY 2004 VL 117 IS 6 BP 436 EP 439 DI 10.1016/j.amjmed.2004.07.034 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 855VT UT WOS:000224003700010 PM 15380502 ER PT J AU Chen, BK Sassi, R Axelson, D Hatch, JP Sanches, M Nicoletti, M Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Chen, BK Sassi, R Axelson, D Hatch, JP Sanches, M Nicoletti, M Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adolescence; affective disorders; development; mood disorders; MRI; neuroimaging ID TEMPORAL-LOBE STRUCTURES; DEVELOPING HUMAN BRAIN; MAGNETIC-RESONANCE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; MOOD DISORDERS; FACIAL EXPRESSIONS; HEALTHY CONTROLS; MRI; SCHIZOPHRENIA AB Background: In vivo imaging studies in adult bipolarpatients have suggested enlargement of the amygdala. It is not known whether this abnormality is already present early in the illness course or whether it develops later in life. We conducted a morphometric MRI study to examine the size of specific temporal lobe structures in adolescents and young adults with bipolar disorder and healthy control subjects, as well as their relationship with age, to examine possible neurodevelopmental abnormalities. Methods: Subjects included 16 DSM-IV bipolarpatients (16 +/- 3 years) and 21 healthy controls (mean age SD = 17 +/- 4 years). Measures of amygdala, bippocampus, temporal gray matter, temporal lobe, and intracranial volumes (ICV) were obtained. Results: There was a trend to smaller left amygdala volumes inpatients (mean volumes +/- SD = 1.58 +/- .42 mL) versus control subjects (1.83 +/- .4 mL; F = 3.87, df = 1,32, p =.06). Bipolar patients did not show significant differences in right or left bippocampus, temporal lobe gray matter, temporal lobe, or right amygdala volumes (analysis of covariance, age, gender, and JCV as covariates, p >.05) compared with healthy control subjects. Furthermore, there was a direct correlation between left amygdala volumes and age (r =.50, p =.047) in patients, whereas in healthy controls there was an inverse correlation (r = -. 48, p =.03). Conclusions: The direct correlation between left amygdala volumes and age in bipolar patients, not present in healthy control subjects, may reflect abnormal developmental mechanisms in bipolar disorder, C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. IRCCS, Brescia, Italy. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 55123, MH 01736, MH 30915, MH 59929] NR 46 TC 110 Z9 113 U1 1 U2 6 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 SEP 15 PY 2004 VL 56 IS 6 BP 399 EP 405 DI 10.1016/j.biopsych.2004.06.024 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 853UU UT WOS:000223855200004 PM 15364037 ER PT J AU Bai, J He, F Novikova, SI Undie, AS Dracheva, S Haroutunian, V Lidow, MS AF Bai, J He, F Novikova, SI Undie, AS Dracheva, S Haroutunian, V Lidow, MS TI Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins SO BIOLOGICAL PSYCHIATRY LA English DT Article DE calcyon; cerebral cortex; humans; monkeys; neuronal calcium sensor-1; postmortem tissue; protein and mRNA levels ID DORSOLATERAL PREFRONTAL CORTEX; PRIMATE CEREBRAL-CORTEX; CALCIUM SENSOR NCS-1; WORKING-MEMORY; D1 RECEPTORS; CYTOARCHITECTONIC DEFINITION; ANTIPSYCHOTIC-DRUGS; ELDERLY-PATIENTS; NAIVE PATIENTS; UP-REGULATION AB Background: Dopamine receptor-interacting proteins constitute a pan of the dopamine system that is involved in regulation Of dopamine receptor-associated intracellular signaling. Previously, we demonstrated that two such proteins, the D1 receptor-interacting protein calcyon and the D2 receptor-interacting protein neuronal calcium sensor-1 (NCS-1), were elevated in the prefrontal cortex of schizophrenia cases from the Stanley Foundation Neuropathology Consortium. Methods: The aim of this study was to confirm and expand these findings. We employed Western blot and real-time reverse transcriptase polymerase chain reaction analyses to compare prefrontal (area 46) and occipital (area 17) conical levels of calcyon and NCS-1 proteins and mRNAs between schizophrenia (n = 3 7) and control (h = 30) cohorts from the Brain Collection of the Mount Sinai Medical School/Bronx Veterans Administration Medical Center. Results: The schizophrenia cohort showed significant up-regulation of calcyon protein and message levels in both prefrontal and occipital cortical regions, both of which also displayed schizophrenia-associated up-regulation of NCS-1 message. Protein levels of NCS-1 were elevated only in the prefrontal conex. All increases in protein levels were correlated with those of corresponding messages. Furthermore, scbizopbrenia-associated alterations in the levels of calcyon and NCS-1 messages were correlated. Conclusions. Up-regulation of calcyon and NCS-1 in the second schizophrenia cohort strengthens the proposition that abnormalities of the dopamine system in this disease may lie in altered levels of dopamine receptor-interacting proteins. Also, up-regulation of both calcyon and NCS-1 in the cortex of schizophrenia patients can be attributed largely to an enhanced transcription or reduced degradation of their messages, Finally, our findings suggest that elevations in the expressions of calcyon and NCS-1 in schizophrenia may have the same underlying cause. C1 Univ Maryland, Dept Biomed Sci, Baltimore, MD 21201 USA. Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. CUNY Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Dept Psychiat, New York, NY 10029 USA. RP Lidow, MS (reprint author), Univ Maryland, Dept Biomed Sci, 5-A-12,HHH,666 W Baltimore St, Baltimore, MD 21201 USA. EM mlidow@umaryland.edu OI Undieh, Ashiwel/0000-0003-1823-5230 FU NIMH NIH HHS [P50 MH44866, R01-MH064673, P50 MH066392] NR 63 TC 59 Z9 60 U1 4 U2 6 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 SEP 15 PY 2004 VL 56 IS 6 BP 427 EP 440 DI 10.1016/j.biopsych.2004.06.022 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 853UU UT WOS:000223855200008 PM 15364041 ER PT J AU Pillai, S AF Pillai, S TI A mastermind revealed SO BLOOD LA English DT Editorial Material ID ZONE B-CELLS AB Retroviral transduction of hematopoietic stem cells with a dominant interfering form of Mastermind has revealed an in vivo role in vertebrates for the Mastermind-like family of Notch regulators during lymphocyte development. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2004 VL 104 IS 6 BP 1593 EP 1593 DI 10.1182/blood-2004-06-2460 PG 1 WC Hematology SC Hematology GA 853HT UT WOS:000223818600003 ER PT J AU Jiang, JR Paez, JG Lee, JC Bo, RH Stone, RM DeAngelo, DJ Galinsky, I Wolpin, BM Jonasova, A Herman, P Fox, EA Boggon, TJ Eck, MJ Weisberg, E Griffin, JD Gilliland, DG Meyerson, M Sellers, WR AF Jiang, JR Paez, JG Lee, JC Bo, RH Stone, RM DeAngelo, DJ Galinsky, I Wolpin, BM Jonasova, A Herman, P Fox, EA Boggon, TJ Eck, MJ Weisberg, E Griffin, JD Gilliland, DG Meyerson, M Sellers, WR TI Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; INHIBITOR; DISEASE; MODEL; MALIGNANCIES; RECEPTORS; INDUCE AB The FLT3 receptor is activated by jux-tamembrane insertion mutations and by activation loop point mutations in patients with acute myelold leukemia (AML). In a systematic tyrosine kinase gene exon resequencing study, 21 of 24 FLT3 exons were sequenced in samples from 53 patients with AML, 9 patients with acute lymphoblastic leukemia (ALL), and 3 patients with myelodysplasia samples. Three patients had novel point mutations at residue N841 that resulted in a change to isoleucine in 2 samples and to tyrosine in 1 sample. Introduction of FLT3-N841I cDNA into Ba/F3 cells led to interleukin-3 (IL-3)-independent proliferation, receptor phosphorylation, and constitutive activation of signal transducer and activator of transcription 5 (STAT5) and extracellular regulatory kinase (ERK), suggesting that the N841I mutation confers constitutive activity to the receptor. An FLT3 inhibitor (PKC412) inhibited the growth of Ba/F3-FLT3N841I cells (IC50 10 nM), but not of wild-type Ba/F3 cells cultured with IL-3. PKC412 also reduced tyrosine phosphorylation of the mutant receptor and inhibited STAT5 phosphorylation. Examination of the FLT3 autoinhibited structure showed that N841 is the key residue in a hydrogen-bonding network that likely stabilizes the activation loop. These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D720C, Boston, MA 02115 USA. EM william_sellers@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NIDDK NIH HHS [DK50654]; PHS HHS [C66996] NR 25 TC 53 Z9 55 U1 0 U2 7 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 SEP 15 PY 2004 VL 104 IS 6 BP 1855 EP 1858 DI 10.1182/blood-2004-02-0712 PG 4 WC Hematology SC Hematology GA 853HT UT WOS:000223818600044 PM 15178581 ER PT J AU Chen, YC Chen, JH Richard, K Chen, PY Christiani, DC AF Chen, YC Chen, JH Richard, K Chen, PY Christiani, DC TI Lung adenocarcinorna and human papillomavirus infection SO CANCER LA English DT Article DE human papillomavirus (HPV); lung adenocarcinoma; smoking; infection ID SQUAMOUS-CELL CARCINOMA; POLYMERASE-CHAIN-REACTION; P53 PROTEIN ACCUMULATION; NONSMOKING WOMEN; CANCER RISK; CERVICAL ADENOCARCINOMA; ADENOSQUAMOUS CARCINOMA; INCREASING INCIDENCE; CIGARETTE-SMOKING; GENETIC-ANALYSIS AB Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation. (C) 2004 American Cancer Society. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA USA. Natl Taiwan Univ, Dept Internal Med, Taipei, Taiwan. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Natl Hlth Res Inst, Div Biostat & Bioinformat, Taipei, Taiwan. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 655 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Chen, Yen-Ching/D-1098-2010 OI Chen, Yen-Ching/0000-0002-8159-7202 NR 85 TC 43 Z9 44 U1 0 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 SEP 15 PY 2004 VL 101 IS 6 BP 1428 EP 1436 DI 10.1002/cncr.20538 PG 9 WC Oncology SC Oncology GA 851VV UT WOS:000223715100020 PM 15368331 ER PT J AU Krysan, K Dalwadi, H Sharma, S Pold, M Dubinett, S AF Krysan, K Dalwadi, H Sharma, S Pold, M Dubinett, S TI Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer SO CANCER RESEARCH LA English DT Article ID DOWN-REGULATION; POOR-PROGNOSIS; MELANOMA-CELLS; IN-VIVO; PROLIFERATION; INHIBITION; CARCINOMA; INDUCTION; INVASION; MARKER AB Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion, and promotion of tumor cell resistance to apoptosis. In our previous studies using non-small cell lung cancer (NSCLC) cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations, we demonstrated that constitutive overexpression of COX-2 leads to stabilization of the inhibitor of apoptosis protein survivin resulting in the elevated apoptosis resistance of COX-2-overexpressing cells. Genetic or pharmacologic suppression of COX-2 activity increased proteasomal degradation of survivin and cellular response to apoptosis induction. Our data show that expression of survivin in non-small cell lung cancer cells can be significantly down-regulated by RNA interference. Whereas COX-2-overexpressing NSCLC cells have significantly higher apoptosis resistance than the parental cells, inhibition of survivin expression by small interfering RNA decreases apoptosis resistance to the level of the parental non-small cell lung cancer. We conclude that COX-2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer. C1 Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr,Div Pulm & Crit Care, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, S (reprint author), Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr,Div Pulm & Crit Care, 37-131 CHS 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU NCI NIH HHS [P50 CA90388] NR 20 TC 82 Z9 96 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2004 VL 64 IS 18 BP 6359 EP 6362 DI 10.1158/0008-5472.CAN-04-1681 PG 4 WC Oncology SC Oncology GA 857BG UT WOS:000224089700001 PM 15374938 ER PT J AU Qin, M Escuadro, B Dohadwala, M Sharma, S Batra, RK AF Qin, M Escuadro, B Dohadwala, M Sharma, S Batra, RK TI A novel role for the coxsackie adenovirus receptor in mediating tumor formation by lung cancer cells SO CANCER RESEARCH LA English DT Article ID HUMAN BLADDER-CANCER; CELLULAR RECEPTOR; GENE-THERAPY; MECHANISM; CAR; ENDOCYTOSIS; EXPRESSION; ADHESION; VIRUSES; BINDING AB The Coxsackie Adenovirus Receptor (CAR) has primarily been studied in its role as the initial cell surface attachment receptor for Coxsackie and group C adenoviruses. Recent reports suggest that CAR mediates homotypic intercellular adhesion as part of the tight and/or adherens junction. Thus, CAR is well positioned to participate in intercellular interactions and signaling. Using an antisense (AS)-CAR plasmid vector, we silenced surface CAR expression in lung cancer cells that possessed a high basal expression of this molecule and monitored the resultant tumorigenesis. AS-CAR transfectants exhibit a profound loss in the ability to generate xenografts in scid/scid mice. The emergence of delayed-onset tumors in animals that received injection with AS-CAR transfectants correlates with the resurfacing of CAR expression, suggesting that such expression and tumor emergence are temporally related. To study the mechanism underlying the differences in tumorigenicity, control and AS-CAR cells were compared in terms of their in vitro growth potential. Whereas only subtle differences in the proliferative capacity of the two populations were evident when assayed with growth on plastic, significant differences became apparent when one compared the relative ability of these populations to form colonies in soft agar. These data indicate that silencing surface CAR expression abrogates xenograft tumorigenesis ill vivo and colony formation in vitro and invoke the novel possibility that CAR expression is needed for the efficient formation of tumors by a subset of lung cancer cells. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rbatra@ucla.edu FU NCI NIH HHS [R01-CA78654, R01 CA078654-03]; PHS HHS [P50-90388] NR 21 TC 19 Z9 26 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 SEP 15 PY 2004 VL 64 IS 18 BP 6377 EP 6380 DI 10.1158/0008-5472.CAN-04-1490 PG 4 WC Oncology SC Oncology GA 857BG UT WOS:000224089700005 PM 15374942 ER PT J AU Yamini, B Yu, XH Gillespie, GY Kufe, DW Weichselbaum, RR AF Yamini, B Yu, XH Gillespie, GY Kufe, DW Weichselbaum, RR TI Transcriptional targeting of adenovirally delivered tumor necrosis factor alpha by temozolomide in experimental glioblastoma SO CANCER RESEARCH LA English DT Article ID ISOLATED LIMB PERFUSION; MALIGNANT GLIOMA; GENE-THERAPY; PHASE-I; SYSTEM; CISPLATIN; MULTIFORME; APOPTOSIS; SURVIVAL; CELLS AB Temozolomide is an oral alkylating agent shown to have modest efficacy in the treatment of glioblastoma multiforme. Tumor necrosis factor a (TNF-alpha) is a polypeptide cytokine with synergistic antitumor activity in combination therapy with alkylating agents. We investigated the combined use of Ad.Egr-TNF, a replication-defective adenoviral vector encoding the cDNA for TNF-alpha under the control of chemo-inducible elements of the egrl gene promoter, and intraperitoneal temozolomide in an intracranial human malignant glioma model. In hind limb U87MG xenografts, temozolomide produced a 6.4-fold greater induction of TNF-alpha after infection with Ad.Egr-TNF compared with Ad.Egr-TNF alone at 96 hours (P < 0.02). TNF-alpha and temozolomide combination leads to a synergistic decrease in U87 cell viability at 72 hours compared with either treatment alone (P < 0.001). Median survival for animals treated with Ad.Egr-TNF alone, temozolomide alone, and Ad.Egr-TNF/temozolomide was 21, 28, and 74 days, respectively (P < 0.001 by log-rank). Flow cytometric assessment of apoptosis revealed a synergistic increase in U87 cell apoptosis in vitro at 72 hours (P < 0.05), and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling JUNEL) evaluation of tumor sections revealed significantly increased TUNEL-positive cells after combination treatment compared with either treatment alone (P < 0.05). In conclusion, combination treatment with transcriptionally activated intratumoral TNF-alpha and systemic temozolomide significantly prolongs survival in an experimental glioblastoma multiforme model. C1 Univ Chicago, Dept Surg, Sect Neurosurg, Chicago, IL USA. Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, Chicago, IL USA. Univ Alabama, Dept Surg, Div Neurosurg, Brain Tumor Res Labs, Birmingham, AL USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Yamini, B (reprint author), Univ Chicago Hosp, Sect Neurosurg, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM byamini@surgery.bsd.uchicago.edu FU NCI NIH HHS [5P50CA97427] NR 20 TC 31 Z9 35 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2004 VL 64 IS 18 BP 6381 EP 6384 DI 10.1158/0008-5472.CAN-04-2117 PG 4 WC Oncology SC Oncology GA 857BG UT WOS:000224089700006 PM 15374943 ER PT J AU Cools, J Mentens, N Furet, P Fabbro, D Clark, JJ Griffin, JD Marynen, P Gilliland, DG AF Cools, J Mentens, N Furet, P Fabbro, D Clark, JJ Griffin, JD Marynen, P Gilliland, DG TI Prediction of resistance to small molecule FLT3 inhibitors: Implications for molecularly targeted therapy of acute leukemia SO CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; IMATINIB; PKC412; PHASE; CELLS; MUTATIONS; EFFICACY; CANCER; SAFETY AB Mutations in the receptor tyrosine kinase FLT3 occur frequently in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Small molecules that selectively inhibit FLT3 kinase activity induce apoptosis in blasts from AMI, patients with FLT3 mutations and prolong survival in animal models of FLT3-induced myeloproliferative disease. A spectrum of structurally different small molecules with activity against FLT3 have been described, and their efficacy for treatment of AML and ALL is now being investigated in clinical trials. Here, we describe the results of an in vitro screen designed to identify mutations in the ATP-binding pocket of FLT3 that confer resistance to tyrosine kinase inhibitors. Mutations at four different positions (Ala-627, Asn-676, Phe-691, and Gly-697) were identified that confer varying degrees of resistance to PKC412, SU5614, or K-252a. FLT3 proteins mutated at Ala-627, Asn-676, or Phe-691 remained sensitive to higher concentrations of the inhibitors, but the G697R mutation conferred high-level resistance to each of these inhibitors as well as to six additional experimental inhibitors. These data provide insights into potential mechanisms of acquired resistance of FLT3 to small molecule inhibitors and indicate that the G697R mutation may be a clinically problematic resistance mutation that warrants proactive screening for additional inhibitors. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA USA. Katholieke Univ Leuven VIB, Dept Human Genet, Louvain, Belgium. Novartis Pharma, Basel, Switzerland. RP Cools, J (reprint author), Dept Human Genet, V1B4,Campus Gasthuisberg O&N Box 602,Herestr 49, B-3000 Louvain, Belgium. EM jan.cools@med.kuIeuven.ac.be FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654] NR 21 TC 109 Z9 111 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2004 VL 64 IS 18 BP 6385 EP 6389 DI 10.1158/0008-5472.CAN-04-2148 PG 5 WC Oncology SC Oncology GA 857BG UT WOS:000224089700007 PM 15374944 ER PT J AU Pold, M Krysan, K Pold, A Dohadwala, M Heuze-Vourc'h, N Mao, JT Riedl, KL Sharma, S Dubinett, SM AF Pold, M Krysan, K Pold, A Dohadwala, M Heuze-Vourc'h, N Mao, JT Riedl, KL Sharma, S Dubinett, SM TI Cyclooxygenase-2 modulates the insulin-like growth factor axis in non-small-cell lung cancer SO CANCER RESEARCH LA English DT Article ID IGF-BINDING PROTEIN-3; I RECEPTOR PATHWAY; BREAST-CANCER; PROSTAGLANDIN BIOSYNTHESIS; CARCINOMA CELLS; FACTOR (IGF)-I; PLASMA-LEVELS; UP-REGULATION; EXPRESSION; APOPTOSIS AB Constitutive overexpression of cyclooxygenase-2 (COX-2) occurs frequently in several different malignancies, including lung, colon, breast, and prostate cancer. Clinical studies have established elevated serum insulin-like growth factor (IGF-I) content and IGF-I:IGF-binding protein 3 (IGFBP-3) ratio as risk factors for these same malignancies. Therefore, we sought to determine the link between COX-2 expression and the IGF axis in COX-2 gene-modified human non-small-cell lung cancer (NSCLC) cells. Overexpression of COX-2 in NSCLC cells enhanced the antiapoptotic and mitogenic effects of IGF-I and IGF-II, facilitated the autophosphorylation of the type 1 IGF receptor, increased class IA phosphatidylinositol 3'-kinase activity, and decreased expression of IGFBP-3. Thus, these findings show that COX-2 augments the stimulatory arm of the IGF axis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [P50 CA90388] NR 50 TC 26 Z9 28 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2004 VL 64 IS 18 BP 6549 EP 6555 DI 10.1158/0008-5472.CAN-04-1225 PG 7 WC Oncology SC Oncology GA 857BG UT WOS:000224089700030 PM 15374967 ER PT J AU Tworoger, SS Eliassen, AH Rosner, B Sluss, P Hankinson, SE AF Tworoger, SS Eliassen, AH Rosner, B Sluss, P Hankinson, SE TI Plasma prolactin concentrations and risk of postmenopausal breast cancer SO CANCER RESEARCH LA English DT Article ID PROGESTERONE RECEPTORS; TRANSGENIC MICE; HORMONE LEVELS; WOMEN; ESTROGEN; EXPRESSION; CARCINOMA; GROWTH; CELLS; GLYCOSYLATION AB Prolactin is important in human breast development, and substantial laboratory and in vitro data suggest a role in mammary carcinogenesis. Therefore, we conducted a prospective case-control study nested within the Nurses' Health Study cohort to examine, in detail, the association between plasma prolactin concentrations and postmenopausal breast cancer by cancer invasiveness, estrogen receptor/progesterone receptor status, and other subject characteristics, including postmenopausal hormone use. Blood samples were collected from 1989 to 1990 and prolactin was measured by microparticle enzyme immunoassay. The analysis included 851 cases of postmenopausal breast cancer diagnosed after blood collection and before June 2000, in which there were one or two controls (n = 1,275) matched on age, postmenopausal hormone use, fasting status, and time of day and month of blood collection. Prolactin was associated with a modestly increased risk of postmenopausal breast cancer [relative risk, top versus bottom quartile, 1.34; 95% confidence interval (0), 1.02-1.76; P-trend = 0.011. The association differed by estrogen receptor/ progesterone receptor status (P-heterogeneity = 0.03). The relative risk was 1.78 (95% CI, 1.28, 2.50; P-trend < 0.001) for estrogen receptor+/ progesterone receptor+, 0.76 (95% CI, 0.43, 1.32; P-trend = 0.28) for estrogen receptor -/progesterone receptor-, and 1.94 (95% CI, 0.99,3.78; P-trend = 0.12) for estrogen receptor+ /progesterone receptor- breast cancers. Associations generally were similar for ductal and lobular carcinomas (P-heterogeneity = 0.43) and by tumor size (P-heterogeneity = 0.24). Among estrogen receptor +/progesterone receptor+ cancers, the association did not significantly differ by postmenopausal hormone use, years between blood draw and diagnosis, or after adjustment for estradiol (relative risk, 1.93; 95% CI, 1.16, 3.22; P-trend = 0.01). Our prospective data suggest that plasma prolactin concentrations are associated with an increased risk of postmenopausal breast cancer, particularly for estrogen receptor+ /progesterone receptor+ cancers, and independently of estradiol. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit Lab, Boston, MA 02114 USA. RP Tworoger, SS (reprint author), Channing Labs, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM nhsst@channing.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [P01 CA87969, CA49449, P50 CA089393, T32 CA090001] NR 49 TC 136 Z9 138 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2004 VL 64 IS 18 BP 6814 EP 6819 DI 10.1158/0008-5472.CAN-04-1870 PG 6 WC Oncology SC Oncology GA 857BG UT WOS:000224089700064 PM 15375001 ER PT J AU Atkins, MB Avigan, DE Bukowski, RM Childs, RW Dutcher, JP Eisen, TG Figlin, RA Finke, JH Flanigan, RC George, DJ Goldberg, SN Gordon, MS Iliopoulos, O Kaelin, WG Linehan, WM Lipton, A Motzer, RJ Novick, AC Stadler, WM Teh, BT Yang, JC King, L AF Atkins, MB Avigan, DE Bukowski, RM Childs, RW Dutcher, JP Eisen, TG Figlin, RA Finke, JH Flanigan, RC George, DJ Goldberg, SN Gordon, MS Iliopoulos, O Kaelin, WG Linehan, WM Lipton, A Motzer, RJ Novick, AC Stadler, WM Teh, BT Yang, JC King, L TI Innovations and challenges in renal cancer: Consensus statement from the first international conference SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; HOGG-DUBE-SYNDROME; CELL CARCINOMA; KIDNEY; MUTATIONS C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Bethesda, MD 20892 USA. New York Med Coll, Our Lady Mercy Med Ctr, Ctr Comprehens Canc, Bronx, NY USA. Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Duke Univ, Med Ctr, Durham, NC USA. Arizona Canc Ctr, Scottsdale, AZ USA. Massachusetts Gen Hosp, Ctr Canc, Med Oncol Labs, Boston, MA USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI USA. InforMED Commun Inc, Casisle, MA USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, 300 Brookline Ave,KS-158, Boston, MA 02215 USA. EM matkins@bidmc.harvard.edu NR 20 TC 20 Z9 21 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2004 VL 10 IS 18 SU S BP 6277S EP 6281S DI 10.1158/1078-0432.CCR-040720 PN 2 PG 5 WC Oncology SC Oncology GA 856XY UT WOS:000224080600001 PM 15448017 ER PT J AU Kaelin, WG AF Kaelin, WG TI The von Hippel-Lindau tumor suppressor gene and kidney cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Innovations and Challenges in Renal Cancer CY MAR 19-20, 2004 CL Cambridge, MA ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; RENAL-CELL CARCINOMA; TRANSMEMBRANE CARBONIC-ANHYDRASES; NUCLEAR-CYTOPLASMIC TRAFFICKING; BIOLOGICALLY-ACTIVE PRODUCT; TYROSINE KINASE INHIBITOR; RNA-POLYMERASE-II; MAMMALIAN TARGET; PROLINE HYDROXYLATION AB The von Hippel-Lindau tumor suppressor gene (VHL), which resides on chromosome 3p25, is mutated or silenced in >50% of sporadic clear cell renal cell carcinomas. Germline VHL mutations give rise to VHL disease, which is characterized by an increased risk of blood vessel tumors (hemangioblastomas) and renal cell carcinomas. In this setting, VHL inactivation gives rise to premalignant renal cysts. Additional genetic alterations are presumably required for conversion of these cysts to renal cell carcinomas. Restoration of VHL function in VHL-/- renal cell carcinomas is sufficient to inhibit tumorigenesis in vivo. On the basis of these and other data, VHL appears to be a critical gatekeeper with respect to the development of renal cell carcinoma. The VHL gene product, pVHL, is the substrate recognition module of an E3 ubiquitin ligase that targets the hypoxia-inducible factor (HIF) for destruction in the presence of oxygen. Hypoxic cells, or cells lacking pVHL, accumulate high levels of HIF, which activates the transcription of a variety of genes, including vascular endothelial growth factor, platelet-derived growth factor B, and transforming growth factor alpha. We have demonstrated that inhibition of HIF is necessary and sufficient for tumor suppression by pVHL in renal cell carcinoma nude mouse xenograft assays. This provides a rationale for treating VHL-/- renal cell carcinoma with inhibitors of HIF or its downstream targets. Genotype-phenotype correlations in VHL disease suggest, however, that pVHL has targets in addition to HIF. Elucidating these targets should provide a more complete picture of how pVHL suppresses tumor growth. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu NR 92 TC 100 Z9 105 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2004 VL 10 IS 18 SU S BP 6290S EP 6295S DI 10.1158/1078-0432.CCR-sup-040025 PN 2 PG 6 WC Oncology SC Oncology GA 856XY UT WOS:000224080600003 PM 15448019 ER PT J AU Skates, S Iliopoulos, O AF Skates, S Iliopoulos, O TI Molecular markers tor early detection of renal carcinoma: Investigative approach SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Innovations and Challenges in Renal Cancer CY MAR 19-20, 2004 CL Cambridge, MA ID TUMOR-SUPPRESSOR GENE; CELL CARCINOMA; OVARIAN-CANCER; URINARY PROTEINS; IDENTIFICATION; MUTATIONS; SERUM; PROTEOMICS; TECHNOLOGY; BIOMARKER AB Molecular markers for renal cell carcinoma could guide early detection of localized disease in defined populations at high risk for the disease or early disease recurrence after nephrectomy for renal cell carcinoma. In addition, sensitive and specific markers may provide surrogate end points for clinical trials of treatment and/or disease prevention. Powerful techniques of genomic and proteomic analysis of human renal carcinoma cell lines, tumor samples, and biological fluids, such as plasma and urine, obtained from patients with renal cell carcinoma, are likely to identify candidate markers. Careful selection among early candidate markers and further testing in independent patient populations are required for marker validation. C1 Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Hematol Oncol Unit, Dept Med, Boston, MA 02114 USA. RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Biostat, 55 Fruit St,Jackson 904, Boston, MA 02114 USA. EM oiliopoulos@partners.org NR 29 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2004 VL 10 IS 18 SU S BP 6296S EP 6301S DI 10.1158/1078-0432.CCR-050010 PN 2 PG 6 WC Oncology SC Oncology GA 856XY UT WOS:000224080600004 PM 15448020 ER PT J AU Atkins, MB Regan, M McDermott, D AF Atkins, MB Regan, M McDermott, D TI Update on the role of interleukin 2 and other cytokines in the treatment of patients with Stage IV renal carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Innovations and Challenges in Renal Cancer CY MAR 19-20, 2004 CL Cambridge, MA ID RECOMBINANT HUMAN INTERLEUKIN-12; 5-YEAR FOLLOW-UP; CELL CARCINOMA; INTERFERON-ALPHA; PHASE-II; SUBCUTANEOUS INTERLEUKIN-2; MALIGNANT-MELANOMA; RANDOMIZED-TRIAL; CLINICAL-TRIALS; CANCER AB Immunoreactive cytokines have been the mainstay of treatment of renal cancer for the past 15 years. Most research has focused on interferon alpha (IFN-alpha) and interleukin 2 (IL-2). IFN-alpha has been shown in Phase III studies to produce a modest survival advantage over inactive or non-IFN-containing regimens. Its general tolerability, multiple proposed mechanisms of action, and familiarity have prompted IFN-alpha, to be studied in combination with a variety of agents with potential activity against renal cell carcinoma. These various studies may justify an increased role for IFN-alpha in the treatment of renal cancer in the foreseeable future. High-dose bolus IL-2 remains the only treatment for stage IV renal cancer approved by the United States Food and Drug Administration. Food and Drug Administration approval was granted in 1992 based on the ability of this agent to produce durable complete responses in a small number of patients. Unfortunately, the toxicity, expense, and restricted accessibility of high-dose IL-2 make it a poor standard. Regimens involving lower doses of IL-2 either alone or in combination with IFN-alpha have generally produced fewer tumor regressions of less overall quality. Recent efforts have focused on trying to identify factors predictive of response to IL-2 therapy so that this treatment could be limited to those most likely to benefit. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr Renal Canc Program, Boston, MA USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Kirstein Room 153, Boston, MA 02215 USA. EM Matkins@bidmc.harvard.edu FU NCI NIH HHS [P50 CA101942-01] NR 35 TC 50 Z9 56 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2004 VL 10 IS 18 SU S BP 6342S EP 6346S DI 10.1158/1078-0432.CCR-040029 PN 2 PG 5 WC Oncology SC Oncology GA 856XY UT WOS:000224080600012 PM 15448028 ER PT J AU Darouiche, RO AF Darouiche, RO TI Echinocandins: Ask not what they can do for esophageal candidiasis - Ask what studies of esophageal candidiasis can do for them SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID AMPHOTERICIN-B; DOUBLE-BLIND; INVASIVE CANDIDIASIS; MULTICENTER TRIAL; FLUCONAZOLE; CASPOFUNGIN; CANDIDEMIA; EFFICACY; OROPHARYNGEAL; ANIDULAFUNGIN C1 Baylor Coll Med, Ctr Protheses Infect, Houston, TX 77030 USA. Michael E Debakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX USA. Michael E Debakey Vet Affairs Med Ctr, Ctr Protheses Infect, Houston, TX USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Protheses Infect, 1333 Moursund Ave,Ste A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 17 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2004 VL 39 IS 6 BP 850 EP 852 DI 10.1086/423391 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JD UT WOS:000227491500016 PM 15472818 ER PT J AU Cornelison, DDW Wilcox-Adelman, SA Goetinck, PF Rauvala, H Rapraeger, AC Olwin, BB AF Cornelison, DDW Wilcox-Adelman, SA Goetinck, PF Rauvala, H Rapraeger, AC Olwin, BB TI Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration SO GENES & DEVELOPMENT LA English DT Article DE muscle regeneration; satellite cell; stem cell; myogenesis ID SATELLITE CELLS; EXPRESSION; DIFFERENTIATION; QUIESCENT AB Syndecan-3 and syndecan-4 function as coreceptors for tyrosine kinases and in cell adhesion. Syndecan-3(-/-) mice exhibit a novel form of muscular dystrophy characterized by impaired locomotion, fibrosis, and hyperplasia of myonuclei and satellite cells. Explanted syndecan-3(-/-) satellite cells mislocalize MyoD, differentiate aberrantly, and exhibit a general increase in overall tyrosine phosphorylation. Following induced regeneration, the hyperplastic phenotype is recapitulated. While there are fewer apparent defects in syndecan-4(-/-) muscle, explanted satellite cells are deficient in activation, proliferation, MyoD expression, myotube fusion, and differentiation. Further, syndecan-4(-/-) satellite cells fail to reconstitute damaged muscle, suggesting a unique requirement for syndecan-4 in satellite cell function. C1 Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Helsinki, Ctr Neurosci, Dept Biosci, FIN-00014 Helsinki, Finland. Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Olwin, BB (reprint author), Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. EM bradley.olwin@colorado.edu OI Cornelison, DDW/0000-0003-4287-7524; Rauvala, Heikki/0000-0001-7809-9811 FU NIAMS NIH HHS [AR39467, R01 AR039467]; NICHD NIH HHS [HD21881, HD37490, R01 HD037490]; NIGMS NIH HHS [GM48850, R01 GM048850] NR 20 TC 158 Z9 167 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 15 PY 2004 VL 18 IS 18 BP 2231 EP 2236 DI 10.1101/gad.1214204 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 853NX UT WOS:000223835400004 PM 15371336 ER PT J AU Ho, M Post, CM Donahue, LR Lidov, HGW Bronson, RT Goolsby, H Watkins, SC Cox, GA Brown, RH AF Ho, M Post, CM Donahue, LR Lidov, HGW Bronson, RT Goolsby, H Watkins, SC Cox, GA Brown, RH TI Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency SO HUMAN MOLECULAR GENETICS LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; RECOMBINANT INBRED MOUSE; CHROMOSOME SUBSTITUTION STRAINS; MIYOSHI MYOPATHY; SJL/J MICE; AGGRESSIVE-BEHAVIOR; GENETIC DISSECTION; COMPLEX TRAITS; ANIMAL-MODELS; PROTEIN AB Limb girdle muscular dystrophy type 2B and Miyoshi myopathy are clinically distinct forms of muscular dystrophy that arise from defects in the dysferlin gene. Here, we report two novel lines of dysferlin-deficient mice obtained by (a) gene targeting and (b) identification of an inbred strain, A/J, bearing a retrotransposon insertion in the dysferlin gene. The mutations in these mice were located at the 3' and 5' ends of the dysferlin gene. Both lines of mice lacked dysferlin and developed a progressive muscular dystrophy with histopathological and ultrastructural features that closely resemble the human disease. Vital staining with Evans blue dye revealed loss of sarcolemmal integrity in both lines of mice, similar to that seen in mdx and caveolin-3 deficient mice. However, in contrast to the latter group of animals, the dysferlin-deficient mice have an intact dystrophin glycoprotein complex and normal levels of caveolin-3. Our findings indicate that muscle membrane disruption and myofiber degeneration in dysferlinopathy were directly mediated by the loss of dysferlin via a new pathogenic mechanism in muscular dystrophies. We also show that the mutation in the A/J mice arose between the late 1970s and the early 1980s, and had become fixed in the production breeding stocks. Therefore, all studies involving the A/J mice or mice derived from A/J, including recombinant inbred, recombinant congenic and chromosome substitution strains, should take into account the dysferlin defect in these strains. These new dysferlin-deficient mice should be useful for elucidating the pathogenic pathway in dysferlinopathy and for developing therapeutic strategies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15261 USA. RP Ho, M (reprint author), Natl Canc Ctr, Div Med Sci, 11 Hosp Dr, Singapore 169610, Singapore. EM dmshmf@nccs.com.sg NR 57 TC 107 Z9 107 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 15 PY 2004 VL 13 IS 18 BP 1999 EP 2010 DI 10.1093/hmg/ddh212 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 854ZB UT WOS:000223941400003 PM 15254015 ER PT J AU Oh, WK Kantoff, PW Weinberg, V Jones, G Rini, BI Derynck, MK Bok, R Smith, MR Bubley, GJ Rosen, RT DiPaola, RS Small, EJ AF Oh, WK Kantoff, PW Weinberg, V Jones, G Rini, BI Derynck, MK Bok, R Smith, MR Bubley, GJ Rosen, RT DiPaola, RS Small, EJ TI Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID IN-VITRO; THERAPIES; IDENTIFICATION; COMPLEMENTARY; EXTRACTS; CELLS AB Purpose To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC). Patients and Methods A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered, At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES. Results Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines greater than or equal to 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots. Conclusion PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency. (C) 2004 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Rutgers State Univ, Dept Food Sci, Piscataway, NJ 08855 USA. Rutgers State Univ, Ctr Adv Food Technol, Piscataway, NJ 08855 USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. RP Small, EJ (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 1600 Divisadero St,A718, San Francisco, CA 94115 USA. EM smalle@medicine.ucsf.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 21 TC 76 Z9 80 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 15 PY 2004 VL 22 IS 18 BP 3705 EP 3712 DI 10.1200/JCO.2004.10.195 PG 8 WC Oncology SC Oncology GA 855HR UT WOS:000223964500010 PM 15289492 ER PT J AU D'Amico, AC Renshaw, AA Cote, K Hurwitz, M Beard, C Loffredo, M Chen, MH AF D'Amico, AC Renshaw, AA Cote, K Hurwitz, M Beard, C Loffredo, M Chen, MH TI Impact of the percentage of positive prostate cores on prostate cancer-specific mortality for patients with low or favorable intermediate-risk disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; CLINICAL UTILITY; ANTIGEN; PROGRESSION; DATABASE; BIOPSIES AB Purpose We investigated whether pretreatment factors predicted time to prostate cancer-specific mortality (PCSM) after conventional-dose and conformal radiation therapy (CRT). Patients and Methods Between 1988 and 2002, 421 patients with low (prostate-specific antigen [PSA] level less than or equal to 10 ng/mL and biopsy Gleason score less than or equal to 6) or favorable intermediate-risk (PSA > 10 to 15 ng/mL or biopsy Gleason score 3 + 4, but not both factors) disease underwent CRT (median dose, 70.4 Gy). Cox regression multivariable analysis was performed to determine whether the PSA level, Gleason score, T category, or the percentage of positive cores (% PC) predicted time to PCSM after CRT. After a median follow-up of 4.5 years, 117 (28%) patients have died. Results The % PC was the only significant predictor (Cox P less than or equal to .03). The relative risk of PCSM after CRT for patients with greater than or equal to 50% as compared with less than 50% PC was 10.4 (95% CI, 1.2 to 87; Cox P = .03), 6.1 (95% CI, 1.3 to 28.6; Cox P = .02), and 12.5 (95% CI, 1.5 to 107; Cox P = .02) in men with a PSA less than or equal to 10 and Gleason score less than or equal to 6, PSA less than or equal to 10 and Gleason score less than or equal to 7, and PSA less than or equal to 15 and Gleason score :! 6, respectively. By 5 years after CRT, 5% to 9% compared with less than 1 % (log-rank P less than or equal to .01) of these patients experienced PCSM if they had greater than or equal to 50% compared with less than 50% PC, respectively. Conclusion CRT dose-escalation techniques, the addition of hormonal therapy, or both should be considered in the management of patients with low or favorable intermediate-risk disease and greater than or equal to 50% PC. (C) 2004 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dept Radiat Oncol & Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AC (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu NR 19 TC 73 Z9 75 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 SEP 15 PY 2004 VL 22 IS 18 BP 3726 EP 3732 DI 10.1200/JCO.2004.01.164 PG 7 WC Oncology SC Oncology GA 855HR UT WOS:000223964500013 PM 15365069 ER PT J AU Fagerlie, SR Koretsky, T Torok-Storb, B Bagby, GC AF Fagerlie, SR Koretsky, T Torok-Storb, B Bagby, GC TI Impaired type IIFN-induced Jak/STAT signaling in FA-C cells and abnormal CD4(+) Th cell subsets in Fancc(-/-) mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FANCONI-ANEMIA PROTEIN; HUMAN-PAPILLOMAVIRUS HPV; INTERFERON-GAMMA; TH1/TH2 BALANCE; IFN-GAMMA; HEMATOPOIETIC-CELLS; PERIPHERAL-BLOOD; FAMILY-MEMBERS; I INTERFERONS; CANCER AB The Fanconi anemia (FA) group C protein, FANCC, interacts with STAT1 following stimulation with IFN-gamma and is required for proper docking of STAT1 at the IFN-gamma receptor a-chain (IFN-gammaRa, IFN-gammaR1). Consequently, loss of a functional FANCC results in decreased activation of STATI following IFN-gamma stimulation. Because type I IFN receptors influence the function of type II receptors, and vice versa, we conducted experiments designed to determine whether type I IFN-induced activation of other STAT proteins is compromised in FA-C cells and found that activation of STAT 1, 3, and 5 is diminished in type I IFN-stimulated cells bearing Fance -inactivating mutations. We also determined that the reduced activation of STATs was accompanied by significant reduction of type I IFN-induced tyrosine kinase 2 and Jak1 phosphorylation. Because tyrosine kinase 2 plays a role in differentiation of Th cells, we quantified cytokine secretion from CD4(+) cells and in vitro generated CD4(+) Th cell subsets from splenocytes of Fancc null mice to that of heterozygous mice and discovered reduced CD4(+) IFN-gamma secretion in the Fancc(-/-) mouse, indicating impaired Th1 differentiation. We suggest that Fancc mutations result in a subtle immunological defect owing to the failure of FANCC to normally support Jak/STAT signaling. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Fagerlie, SR (reprint author), Fred Hutchinson Canc Res Ctr, D1-100,1100 Fairview Ave N, Seattle, WA 98109 USA. EM sfagerli@fhcrc.org FU NHLBI NIH HHS [HL48546, HL62923, HL72321] NR 74 TC 15 Z9 15 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2004 VL 173 IS 6 BP 3863 EP 3870 PG 8 WC Immunology SC Immunology GA 854CN UT WOS:000223878000035 PM 15356134 ER PT J AU Lu, CF Shimaoka, M Salas, A Springer, TA AF Lu, CF Shimaoka, M Salas, A Springer, TA TI The binding sites for competitive antagonistic, allosteric antagonistic, and agonistic antibodies to the I domain of integrin LFA-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; BONE-MARROW TRANSPLANTATION; POLYMERASE CHAIN-REACTION; VERSUS-HOST DISEASE; MONOCLONAL-ANTIBODIES; LEUKOCYTE-ADHESION; OVERLAP EXTENSION; STRUCTURAL BASIS; INSERTED DOMAIN; LIGAND-BINDING AB We explore the binding sites for mAbs to the alpha 1 domain of the integrin alpha(L)beta(2) that can competitively inhibit, allosterically inhibit, or activate binding to the ligand ICAM-1. Ten mAbs, some of them clinically important, were mapped to species-specific residues. The results are interpreted with independent structures of the alpha(L) I domain determined in seven different crystal lattices and in solution, and which are present in three conformational states that differ in affinity for ligand. Six mAbs bind to adjacent regions of the beta1-alpha1 and alpha3-alpha4 loops, which show only small (mean, 0.8 Angstrom; maximum, 1.8 Angstrom) displacements among the eight I domain structures. Proximity to the ligand binding site and to noncontacting portions of the ICAM-1 molecule explains competitive inhibition by these mAbs. Three mAbs bind to a segment of seven residues in the beta5-alpha6 loop and alpha6 helix, in similar proximity to the ligand binding site, but on the side opposite from the beta1-alpha1/alpha3-alpha4 epitopes, and far from noncontacting portions of ICAM-1. These residues show large displacements among the eight structures in response to lattice contacts (mean, 3.6 Angstrom; maximum, 9.4 Angstrom), and movement of a buried Phe in the beta5-alpha6 loop is partially correlated with affinity change at the ligand binding site. Together with a lack of proximity to noncontacting portions of ICAM-1, these observations explain variation among this group of mAbs, which can either act as competitive or allosteric antagonists. One agonistic mAb binds distant from the ligand binding site of the I domain, to residues that show little movement (mean, 0.5 Angstrom; maximum, 1.0 Angstrom). Agonism by this mAb is thus likely to result from altering the orientation of the I domain with respect to other domains within an intact integrin alpha(L)beta(2) heterodimer. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu OI Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798] NR 46 TC 32 Z9 32 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2004 VL 173 IS 6 BP 3972 EP 3978 PG 7 WC Immunology SC Immunology GA 854CN UT WOS:000223878000047 PM 15356146 ER PT J AU Reilly, CM Mishra, N Miller, JM Joshi, D Ruiz, P Richon, VM Marks, PA Gilkeson, GS AF Reilly, CM Mishra, N Miller, JM Joshi, D Ruiz, P Richon, VM Marks, PA Gilkeson, GS TI Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; NITRIC-OXIDE SYNTHASE; CLASS-II EXPRESSION; MRL-LPR MICE; MHC CLASS-I; IFN-GAMMA; INTERFERON-GAMMA; LUPUS NEPHRITIS; GENE-EXPRESSION; MURINE LUPUS AB Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus. In this study, we determined whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor: 1) inhibits inflammatory mediator production in vitro and 2) modulates lupus progression in vivo. Mesangial cells isolated from 10-wk-old MRL/lpr mice were stimulated with LPS/IFN-gamma and incubated with SAHA. TNF-alpha, IL-6, NO, and inducible NO synthase expression were inhibited by SAHA. We then treated MRL/lpr mice with daily injections of SAHA from age 10 to 20 wk. The animals treated with SAHA had decreased spleen size and a concomitant decrease in CD4(-)CD8(-) (double-negative) T cells compared with controls. Serum autoantibody levels and glomerular IgG and C3 deposition in SAHA-treated mice were similar to controls. In contrast, proteinuria and pathologic renal disease were significantly inhibited in the mice receiving SAHA. These data indicate that SAHA blocks mesangial cell inflammatory mediator production in vitro and disease progression in vivo in MRL/lpr mice. C1 Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24060 USA. Edward Via Coll Osteopath Med, Blacksburg, VA 24060 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC 29405 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Univ Miami, Med Ctr, Dept Immunopathol, Coral Gables, FL 33124 USA. Aton Pharmaceut, Tarrytown, NY 10580 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Rheumatol Sect, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Clin Immunol Sect, Winston Salem, NC 27109 USA. RP Reilly, CM (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24060 USA. EM chreilly@vconi.vt.edu; nmishra@wfubine.edu FU NIAMS NIH HHS [R01 AR 47451] NR 51 TC 100 Z9 103 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2004 VL 173 IS 6 BP 4171 EP 4178 PG 8 WC Immunology SC Immunology GA 854CN UT WOS:000223878000069 PM 15356168 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Improving periorbital appearance in the "morphologically prone" SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT World Congress of the International-Confederation-for-Plastic-Reconstructive-and-Aesthetic-Sur gery CY AUG 13, 2003 CL Sydney, AUSTRALIA SP Int Confederat Plast, Reconstruct & Aesthet Surg ID INTERNAL-FIXATION DEVICES; MIDFACIAL REJUVENATION; CLASSIFICATION-SYSTEM; OPERATIVE MANAGEMENT; PROMINENT EYE; BLEPHAROPLASTY; CANTHOPEXY AB Patients with prominent eyes are predisposed to lower lid descent and rounding of the palpebral fissure. This deformity may be exaggerated and symptomatic after conventional lower blepharoplasty. Normalization of the periorbital appearance in "morphologically prone" patients involves three basic maneuvers. Augmenting the projection of the infraorbital rim with an alloplastic implant effectively changes the skeletal morphology, thereby providing support for the lower lid and midface soft tissues. Subperiosteal freeing and elevation of the lower lid and midface recruits soft tissues and allows lower lid repositioning. Lateral canthopexy restores palpebral fissure shape and provides additional lid support. The technique can be adapted for morphologically prone patients who are first seeking improvement in their periorbital appearance or for those whose lid malposition and round eye appearance have been exaggerated by previous lower blepharoplasty. This surgery has been effective treatment for 13 morphologically prone patients operated on over a 4-year period. C1 Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, 15 Parkman St,WACC,Suite 453, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 24 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP 15 PY 2004 VL 114 IS 4 BP 980 EP 987 DI 10.1097/01.FRS.0000133202.32981.08 PG 8 WC Surgery SC Surgery GA 851NY UT WOS:000223693000026 PM 15468407 ER PT J AU Silveri, MM Pollack, MH Diaz, CI Nassar, LE Mendelson, JH Yurgelun-Todd, DA Renshaw, PF Kaufman, MJ AF Silveri, MM Pollack, MH Diaz, CI Nassar, LE Mendelson, JH Yurgelun-Todd, DA Renshaw, PF Kaufman, MJ TI Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE P-31 MRS; T2-RT; heroin; methadone maintenance; PCr; phospholipids ID VIVO P-31 MRS; BLOOD-FLOW; TECHNETIUM-99M-HMPAO SPECT; GLUCOSE-UTILIZATION; POLYDRUG ABUSERS; WITHDRAWAL; BRAIN; ADDICTS; SPECTROSCOPY; PERFUSION AB Cerebral bioenergetic and phospholipid abnormalities have been reported in hero in-dependent subjects. The goal of the present study was to characterize the neurochemical profile of subjects voluntarily enrolled in a methadone maintenance (MM) treatment program to overcome their heroin addiction. Participants included 43 hero in-dependent subjects during their first month of MM and 15 age-matched healthy individuals. Phosphorus magnetic resonance spectroscopy (P-31 MRS) and transverse relaxation times (T2-RT), which can reflect steady state cerebral perfusion and metabolism, were acquired at 1.5 T from an axial slice prescribed through the orbitofrontal and occipital cortices, including basal ganglia and frontal cortex. MM subjects exhibited reduced phosphocreatine (PCr) levels (-15.3%), elevated phosphodiesters (+ 12.9%, PDE) and significantly longer T2-RT (+) 2.1%) compared with healthy comparison subjects. When MM subjects were stratified into subgroups based on treatment duration, we found a treatment duration effect on metabolite values but not T2-RT; reduced PCr was observed only after 8+ days of MM, and phosphomonoesters (PME) were elevated in the 15-28 day MM group. Taken together, these cross-sectional data suggest that the first month of MM treatment may be associated with altered cerebral bioenergetics and phospholipid metabolite levels. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brain Imaging Ctr, McLean Hosp,Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp,Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Habit Management Inst, Boston, MA USA. RP Kaufman, MJ (reprint author), Harvard Univ, Sch Med, Brain Imaging Ctr, McLean Hosp,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM kaufman@mclean.harvard.edu FU NIDA NIH HHS [DA11231, DA017323, DA07252, DA90448] NR 41 TC 12 Z9 12 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 15 PY 2004 VL 131 IS 3 BP 217 EP 226 DI 10.1016/j.pscychresns.2004.05.003 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 864BV UT WOS:000224608800004 PM 15465291 ER PT J AU Villarreal, G Hamilton, DA Graham, DP Driscoll, I Qualls, C Petropoulos, H Brooks, WM AF Villarreal, G Hamilton, DA Graham, DP Driscoll, I Qualls, C Petropoulos, H Brooks, WM TI Reduced area of the corpus callosurn in posttraumatic stress disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE magnetic resonance imaging; white matter; automated tissue segmentation; genu; stress ID INTERHEMISPHERIC-TRANSFER DEFICIT; CHILDHOOD SEXUAL-ABUSE; HIPPOCAMPAL VOLUME; MAGNETIC-RESONANCE; HYPERACTIVITY DISORDER; BRAIN-DEVELOPMENT; MATTER VOLUME; ALEXITHYMIA; MORPHOLOGY; MRI AB Magnetic resonance imaging (MR-1) studies have revealed decreases in the mid-sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress disorder (PTSD), but at present no data are available in adult PTSD patients. We have previously reported decreased whole-brain white matter (WM) volume in adults with PTSD and now report corpus callosum area from the same sample. MRI was used to obtain whole-brain images in 12 adult patients with PTSD and 10 matched controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid-sagittal area of the CC and seven sub-regions of this structure were calculated. In PTSD patients, the total CC area, absolute and normalized to total brain parenchyma, was smaller compared with control values. Several absolute and normalized CC sub-regions were also smaller in PTSD patients: genu (region 2), mid-body (region 5) and isthmus (region 6). There was also a trend for the anterior mid-body (area 4) to be smaller in PTSD patients. No differences were found in the rostrum (region 1), rostral body (region 3) or splenium (region 7). Adult patients with PTSD had decreased CC area after correcting for total brain tissue, indicating that these differences are not attributable to generalized white matter atrophy. These findings are similar to previous results in children with PTSD and suggest specific changes in the CC. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 New Mexico VA Healthcare Syst, PTSD Program 116A, Albuquerque, NM 87108 USA. Univ Lethbridge, Canadian Ctr Behav Neurosci, Lethbridge, AB T1K 3M4, Canada. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ New Mexico, Biomed Res Inst New Mexico, VAMC, Albuquerque, NM 87108 USA. Univ Washington, Neuroimaging Res Grp, Seattle, WA 98115 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66160 USA. RP Villarreal, G (reprint author), New Mexico VA Healthcare Syst, PTSD Program 116A, 1501 San Pedro Dr SE, Albuquerque, NM 87108 USA. EM Gerardo.Villarreal@med.va.gov RI Hamilton, Derek/H-4447-2013; Graham, David /J-1158-2014; OI Hamilton, Derek/0000-0001-7021-3288; brooks, william/0000-0001-6227-7636 FU NCRR NIH HHS [RR15636]; NICHD NIH HHS [HD41237]; NINDS NIH HHS [NS35708, NS39123] NR 49 TC 48 Z9 55 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 15 PY 2004 VL 131 IS 3 BP 227 EP 235 DI 10.1016/j.pscychresns.2004.05.002 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 864BV UT WOS:000224608800005 PM 15465292 ER PT J AU Koth, LL Rodriguez, MW Bernstein, XL Chan, S Huang, XZ Charo, IF Rollins, BJ Erle, DJ AF Koth, LL Rodriguez, MW Bernstein, XL Chan, S Huang, XZ Charo, IF Rollins, BJ Erle, DJ TI Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2 SO RESPIRATORY RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IDIOPATHIC PULMONARY-FIBROSIS; BRONCHOALVEOLAR LAVAGE FLUID; INTERSTITIAL LUNG-DISEASES; HISTAMINE-RELEASING FACTOR; CHEMOKINE RECEPTOR 2; CELL-DEFICIENT MICE; CHEMOTACTIC PROTEIN-1; ACTIVATING FACTOR; GRANULOMA-FORMATION AB Background: Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods: To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results: We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion: We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. Conclusion: We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. C1 Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Erle, DJ (reprint author), Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA. EM lkoth@itsa.ucsf.edu; mwrod@itsa.ucsf.edu; xinliub@itsa.ucsf.edu; salinac@itsa.ucsf.edu; benny@itsa.ucsf.edu; icharo@gladstone.ucsf.edu; Barrett_Rollins@dfci.harvard.edu; erle@itsa.ucsf.edu NR 50 TC 23 Z9 27 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD SEP 15 PY 2004 VL 5 IS 11-12 AR 12 DI 10.1186/1465-9921-5-12 PG 12 WC Respiratory System SC Respiratory System GA 859HK UT WOS:000224253800002 PM 15377395 ER PT J AU Malhotra, A Trinder, J Fogel, R Stanchina, M Patel, SR Schory, K Kleverlaan, D White, DP AF Malhotra, A Trinder, J Fogel, R Stanchina, M Patel, SR Schory, K Kleverlaan, D White, DP TI Postural effects on pharyngeal protective reflex mechanisms SO SLEEP LA English DT Article DE pharynx; posture; sleep; breathing; genioglossus; lung; tensor palatini; respiration; upper airway; vestibular ID OBSTRUCTIVE SLEEP-APNEA; GENIOGLOSSUS MUSCLE ACTIVATION; NEGATIVE AIRWAY PRESSURE; AWAKE CATS; NORMAL MEN; HUMANS; RESPONSES; RESPONSIVENESS; ANESTHESIA; STIMULI AB Study Objectives: Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion. Design: We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses. Setting: Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital. Subjects/Participants: 17 normal subjects. Measurements and Results: We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum [%max] +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness. Conclusions: We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep. C1 Brigham & Womens Hosp, BIDMC, Sleep Disorders Res Program, Sleep Med Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Melbourne, Dept Psychol, Melbourne, Vic, Australia. Brown Univ, Rhode Isl Hosp, Div Pulm, Providence, RI 02903 USA. RP Malhotra, A (reprint author), Brigham & Womens Hosp, BIDMC, Sleep Disorders Res Program, Sleep Med Div, 75 Francis St, Boston, MA 02115 USA. EM amalhotra1@partners.org OI Taylor, Darci/0000-0002-3595-1354 FU NCRR NIH HHS [M01 RR002635, MO1 RR02635]; NHLBI NIH HHS [R01 HL048531, P50 HL060292, R01 HL073146, R01 HL48531, T32 HL007633, T32 HL07633, 1 P50 HL60292, R01 HL073146-02]; NIA NIH HHS [K23 AG024837, K23 AG024837-03] NR 40 TC 43 Z9 44 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 PD SEP 15 PY 2004 VL 27 IS 6 BP 1105 EP 1112 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 861VB UT WOS:000224445600010 PM 15532204 ER PT J AU Dodel, R Peter, H Walbert, T Spottke, A Noelker, C Berger, K Siebert, U Oertel, WH Kesper, K Becker, HF Mayer, G AF Dodel, R Peter, H Walbert, T Spottke, A Noelker, C Berger, K Siebert, U Oertel, WH Kesper, K Becker, HF Mayer, G TI The socioeconomic impact of narcolepsy SO SLEEP LA English DT Article ID QUALITY-OF-LIFE; PRACTICE PARAMETERS; DIAGNOSIS; MODAFINIL; DISEASE; COSTS AB Study Objective: To evaluate the economic burden of patients suffering from narcolepsy. Design: Cross-sectional study. Participants: 75 narcoleptic patients diagnosed at the Hephata Klinik, Germany, who met the International Classification of Sleep Disorders criteria for narcolepsy. Measurements: A standardized telephone interview was used to inquire about the disease and its burden. In addition, health-related quality of life scales (SF-36 and EQ-5D) were mailed to the patients. Complete data were available for 75 patients. Direct and indirect costs were calculated from the societal perspective. All costs (mean +/- SD) were calculated in 2002 Euros. Results: Total annual costs were 14,790 Euro +/- 16,180 (US-$15,410) per patient. Direct costs were 3,180 Euro +/- 3,540 (US-$3,310), which consisted of hospital costs (1,210 Euro +/- 2,210; US-$1,260), drug costs (narcolepsy medication: 1,020 Euro +/- 1,420; US-$1,060), ambulatory care (90 Euro +/- 90; US-$40), and ambulatory diagnostics (20 Euro +/- 30; US-$20). More than 50% of the drug costs were due to the newer wake-promoting drugs. Total annual indirect costs amounted to 11,390 Euro +/- 15,740 (US-$11,860) per patient and were mainly attributable to early retirement due to the disease. Narcolepsy was listed as being the cause of unemployment by 32 patients. In patients with sleep attacks, there was a significant correlation between early retirement and higher indirect costs compared to patients without these attacks. Conclusions: Narcolepsy causes a high socioeconomic burden, which is comparable to other chronic neurologic diseases. Indirect costs are considerably higher than direct costs. Measures should be taken to increase public awareness of this disease. Appropriate treatment must be provided in order to increase quality of life and to assist patients continuing in working life. C1 Univ Bonn, Dept Neurol, D-53105 Bonn, Germany. MERG, Munich, Germany. Univ Marburg, Dept Neurol, Marburg, Germany. Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Hephata Klin, Dept Neurol, Schwalmstadt, Germany. RP Dodel, R (reprint author), Univ Bonn, Dept Neurol, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM richard.dodel@ukb.uni-bonn.de NR 36 TC 36 Z9 36 U1 0 U2 2 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 SEP 15 PY 2004 VL 27 IS 6 BP 1123 EP 1128 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 861VB UT WOS:000224445600012 PM 15532206 ER PT J AU Ishimoto, H Isomoto, H Shikuwa, S Wen, CY Suematu, T Ito, M Murata, I Ishibashi, H Kohno, S AF Ishimoto, Hiroshi Isomoto, Hajime Shikuwa, Saburo Wen, Chun Yang Suematu, Takashi Ito, Masahiro Murata, Ikuo Ishibashi, Hiromi Kohno, Shigeru TI Endoscopic identification of Peyer's patches of the terminal ileum in a patient with Crohn's disease SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article AB We presented a 20-year-old patient with Crohn's disease (CD). Colonoscopy revealed longitudinal ulceration in the terminal ileum and rectal aphtoid ulcers. After treatment with mesalamine and total parenteral nutrition, repeat colonoscopy revealed a granular elevated area in the terminal ileum, which appeared as an irregular dome-like elevation with irregularly arranged villi on magnifying endoscopy. Biopsy specimens taken from the region showed microgranulomas and lymphoid hyperplasia. Scanning electron microscopy revealed the presence of M cells, confirming that the area corresponded to Peyer's patches. Peyer's patches by magnifying endoscopy and electron microscopy may provide insights into the pathogenesis of CD. C1 [Isomoto, Hajime] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Ishimoto, Hiroshi; Shikuwa, Saburo; Ishibashi, Hiromi] Natl Nagasaki Med Ctr, Dept Internal Med, Nagasaki 8568562, Japan. [Isomoto, Hajime; Murata, Ikuo; Kohno, Shigeru] Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528501, Japan. [Wen, Chun Yang] Nagasaki Univ, Sch Med, Dept Mol Pathol, Atom Bomb Dis Inst, Nagasaki 8528501, Japan. [Suematu, Takashi] Nagasaki Univ, Sch Med, Cent Electroscope Lab, Nagasaki 8528501, Japan. [Ito, Masahiro] Natl Nagasaki Med Ctr, Dept Pathol, Nagasaki 8568562, Japan. RP Isomoto, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Jackson 706,55 Fruit St, Boston, MA 02114 USA. EM hajimei2002@yahoo.co.jp NR 9 TC 7 Z9 7 U1 0 U2 0 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 15 PY 2004 VL 10 IS 18 BP 2767 EP 2768 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19UK UT WOS:000208097100034 PM 15309739 ER PT J AU Bibbins-Domingo, K Lin, F Vittinghoff, E Barrett-Connor, E Hulley, SB Grady, D Shlipak, MG AF Bibbins-Domingo, K Lin, F Vittinghoff, E Barrett-Connor, E Hulley, SB Grady, D Shlipak, MG TI Predictors of heart failure among women with coronary disease SO CIRCULATION LA English DT Article DE coronary disease; diabetes millitus; heart failure; prevention; women ID LEFT-VENTRICULAR DYSFUNCTION; DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; ESTROGEN/PROGESTIN REPLACEMENT; MICROVASCULAR COMPLICATIONS; BLOOD-PRESSURE; OUTCOMES; SURVIVAL; RISK; CARDIOMYOPATHY AB Background-Although heart failure is common among women with coronary disease, the risk factors for developing heart failure have not been well studied. We determined the risk factors for developing heart failure among postmenopausal women with established coronary disease. Methods and Results-This is a prospective cohort study using data from the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years' duration, and subsequent open-label observational follow-up for 2.7 years (HERS II), performed at 20 US clinical centers between 1993 and 2000. Of the 2763 postmenopausal women with established coronary disease in the HERS trial, we studied the 2391 women with no heart failure at baseline by self-report and physical examination. The primary outcome of this analysis was incident heart failure defined by hospital admission or death from heart failure. During the 6.3+/-1.4-year follow-up, 237 women (10%) developed heart failure. Nine predictors were identified: diabetes (defined as a self-reported history of diabetes on treatment), atrial fibrillation, myocardial infarction, creatinine clearance <40 mL/min, systolic blood pressure >120 mm Hg, current smoking, body mass index >35 kg/m(2), left bundle-branch block, and left ventricular hypertrophy. Randomization to estrogen/progestin was not associated with heart failure (hazard ratio=1.0; 95% CI, 0.7 to 1.3). Diabetes was the strongest risk factor (adjusted hazard ratio=3.1; 95% CI, 2.3 to 4.2). Diabetic women with elevated body mass index or depressed creatinine clearance were at highest risk, with annual incidence rates of 7% and 13%, respectively. Among diabetic women, hyperglycemia was associated with heart failure risk (adjusted hazard ratio=3.0; 95% CI, 1.2 to 7.5 for fasting glucose>300 mg/dL compared with fasting glucose 80 to 150 mg/dL). Conclusions-We identified 9 predictors of heart failure in postmenopausal women with coronary disease. Diabetes was the strongest risk factor, particularly when poorly controlled or with concomitant renal insufficiency or obesity. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ San Francisco, San Francisco VA Med Ctr, Sect Gen Med, San Francisco, CA 94117 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Dept Epidemiol & Biostat, Box 1364, San Francisco, CA 94143 USA. EM bibbinsk@medicine.ucsf.edu NR 42 TC 87 Z9 93 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2004 VL 110 IS 11 BP 1424 EP 1430 DI 10.1161/01.CIR.0000141726.01302.83 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 853MC UT WOS:000223830700015 PM 15353499 ER PT J AU Berger, A MacCarthy, PA Siebert, U Carlier, S Wijns, W Heyndrickx, G Bartunek, J Vanermen, H De Bruyne, B AF Berger, A MacCarthy, PA Siebert, U Carlier, S Wijns, W Heyndrickx, G Bartunek, J Vanermen, H De Bruyne, B TI Long-term patency of internal mammary artery bypass grafts - Relationship with preoperative severity of the native coronary artery stenosis SO CIRCULATION LA English DT Article DE bypass; revascularization; stenosis; surgery ID THORACIC-ARTERY; PRESSURE MEASUREMENTS; COMPETITIVE FLOW; SAPHENOUS-VEIN; BLOOD-FLOW; SURVIVAL; ANGIOGRAPHY; ANGIOPLASTY; PROGRESSION; PREDICTORS AB Background-Internal mammary artery conduits (IMA) have an excellent long-term patency rate. Nevertheless, graft closure does occur and significantly limits future revascularization options. We sought to investigate the relationship between the long-term patency of IMA with clinical and angiographic parameters. Particularly, the preoperative degree of stenosis of the relevant bypassed coronary vessel was assessed to analyze the importance of chronic competitive flow on the arterial graft closure rate. Methods and Results-Consecutive patients in whom occlusion of at least I IMA had been documented at angiography (OCC group) were compared with a group of patients with patent IMA grafts (PAT group). The degree of stenosis in the native coronary artery on which the IMA was placed was analyzed by off-line quantitative coronary angiography. Multivariate stepwise logistic regression was used to identify independent clinical and angiographic predictors of occlusion. The OCC group comprised 96 patients (67 +/- 10 years) with 103 native bypassed arteries analyzed. The PAT group comprised 127 patients (69 8 years) with 170 native bypassed arteries analyzed. Both groups were similar except for gender (42% versus 32% female; P=0.04), height (166 8 versus 169 8 cm; P=0.006), minimum lumen diameter (0.76 +/- 0.7 versus 0.51 +/- 0.5; P=0.001), and diameter stenosis of the native artery (73 +/- 25% versus 84 +/- 16%;.P<0.0001) in OCC versus PAT, respectively. In the multivariate analysis, only percent diameter stenosis was an independent and statistically significant predictor for graft patency. Among IMA placed on coronary arteries with a diameter of stenosis <50% (n=28), the occlusion rate was very high (79%). Conclusion-The degree of stenosis in the native vessel is a major predictor of internal mammary artery bypass graft patency. The association between nonsignificant stenosis of the native artery and high occlusion rate of the arterial bypass conduit raises concerns about the use of IMA in the treatment of native vessels with only mild or moderate stenosis. C1 Onze Lieve Vrouw Hosp, Ctr Cardiovasc, B-9300 Aalst, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Onze Lieve Vrouw Hosp, Dept Cardiovasc Surg, Aalst, Belgium. RP De Bruyne, B (reprint author), Onze Lieve Vrouw Hosp, Ctr Cardiovasc, Moorselbaan 164, B-9300 Aalst, Belgium. EM bernard.de.bruyne@olvz-aalst.be NR 31 TC 11 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2004 VL 110 IS 11 SU S BP II36 EP II40 DI 10.1161/01.CIR.0000141256.05740.69 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856DI UT WOS:000224023600007 PM 15364835 ER PT J AU Collins, JS Evangelista, A Nienaber, CA Bossone, E Fang, JM Cooper, JV Smith, DE O'Gara, PT Myrmel, T Gilon, D Isselbacher, EM Penn, M Pape, LA Eagle, KA Mehta, RH AF Collins, JS Evangelista, A Nienaber, CA Bossone, E Fang, JM Cooper, JV Smith, DE O'Gara, PT Myrmel, T Gilon, D Isselbacher, EM Penn, M Pape, LA Eagle, KA Mehta, RH CA IRAD TI Differences in clinical presentation, management, and outcomes of acute type a aortic dissection in patients with and without previous cardiac surgery SO CIRCULATION LA English DT Article DE aorta; surgery; risk factors; mortality ID VALVE-REPLACEMENT; ASCENDING AORTA; TASK-FORCE; MORTALITY; RISK; DISEASE AB Background-There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). Methods and Results-In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males (P=0.02), older (P=0.014), and to have a history of previous aortic dissection (P<0.001) or aneurysms (P<0.001). In contrast, PCS patients were less likely to have presenting chest pain (P<0.001). Cardiac tamponade was less common in PCS patients (P=0.007). Fewer AAD patients with PCS underwent surgical repair (P=0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. Conclusions-Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Ciudad Sanitaria & Univ Vall Hebron, E-08035 Barcelona, Spain. Univ Rostock, D-2500 Rostock, Germany. CNR, Brindisi, Italy. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Tromso Hosp, N-9012 Tromso, Norway. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Massachusetts Hosp, Worcester, MA USA. Duke Clin Res Inst, Durham, NC USA. RP Mehta, RH (reprint author), 2802 Leslie Pk Circle, Ann Arbor, MI 48105 USA. EM mehta007@dcri.duke.edu NR 24 TC 13 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2004 VL 110 IS 11 SU S BP II237 EP II242 DI 10.1161/01.CIR.0000138219.67028.2a PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856DI UT WOS:000224023600041 PM 15364869 ER PT J AU Hung, J Papakostas, L Tahta, SA Hardy, BG Bollen, BA Duran, CM Levine, RA AF Hung, J Papakostas, L Tahta, SA Hardy, BG Bollen, BA Duran, CM Levine, RA TI Mechanism of recurrent ischemic mitral regurgitation after annuloplasty - Continued LV remodeling as a moving target SO CIRCULATION LA English DT Article DE mitral regurgitation; ring annuloplasty; left ventricle remodeling ID PAPILLARY-MUSCLE DYSFUNCTION; LEFT-VENTRICULAR SHAPE; HEART-FAILURE; VALVE REPAIR; DILATED CARDIOMYOPATHY; ECHOCARDIOGRAPHIC-ASSESSMENT; RING ANNULOPLASTY; RECONSTRUCTION; SEVERITY; INSIGHTS AB Background-Patients who undergo ring annuloplasty for ischemic mitral regurgitation (MR) often have persistent or recurrent MR. This may relate to persistent leaflet tethering from left ventricle (LV) dilatation that is not relieved by ring annuloplasty. Therefore, the purpose of this study was to test the hypothesis that recurrent MR in patients after ring annuloplasty relates to continued LV remodeling. Methods and Results-Serial echoes were reviewed in 30 patients (aged 72 +/- 11 years) who showed recurrent MR late (47 27 months) versus early (3.8 +/- 5.8 months) after ring annuloplasty for ischemic MR during coronary artery bypass grafting without interval infarction. Patients with intrinsic mitral valve disease were excluded. Echocardiographic measures of MR (vena contracta and jet area/left atrial area) and LV remodeling (LV dimensions, volumes, and sphericity) were assessed at each stage. The degree of MR increased from mild to moderate, on average, from early to late postoperative stages, without significant change in LV ejection fraction. Changes in MR paralleled increases in LV volumes and sphericity index at end-systole and end-diastole. The only independent predictor of late postoperative MR was LV sphericity index at end-systole. Conclusions-Recurrent MR late after ring annuloplasty is associated with continued LV remodeling, emphasizing its dynamic relation to the LV. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK 508, Boston, MA 02114 USA. Int Heart Inst Montana, Missoula, MT USA. Univ Montana, Missoula, MT USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK 508, Boston, MA 02114 USA. EM Jhung@partners.org FU NHLBI NIH HHS [K23 HL04504, K24 HL67434, R01 HL38176] NR 48 TC 34 Z9 34 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2004 VL 110 IS 11 SU S BP II85 EP II90 DI 10.1161/01.CIR.0000138192.65015.45 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856DI UT WOS:000224023600016 PM 15364844 ER PT J AU Ikonomidis, JS Gibson, WC Butler, JE McClister, DM Sweterlitsch, SE Thompson, RP Mukherjee, R Spinale, FG AF Ikonomidis, JS Gibson, WC Butler, JE McClister, DM Sweterlitsch, SE Thompson, RP Mukherjee, R Spinale, FG TI Effects of deletion of the tissue inhibitor of matrix metalloproteinases-1 gene on the progression of murine thoracic aortic aneurysms SO CIRCULATION LA English DT Article DE mouse; aneurysm; aorta; thorax; TIMP-1 ID NATURAL-HISTORY; PERIARTERIAL APPLICATION; THORACOABDOMINAL AORTA; CARDIOPULMONARY BYPASS; CIRCULATORY ARREST; SURGICAL-TREATMENT; CALCIUM-CHLORIDE; MATRIX-METALLOPROTEINASE-9; MODEL; INFLAMMATION AB Objective-The cause of thoracic aortic aneurysms (TAAs) is poorly understood. Previous work has suggested an association between development of aortic aneurysms and matrix metalloproteinase (MMP) activity. We hypothesized that removal of the primary endogenous aortic MMP inhibitor (TIMP) through TIMP-1 gene deletion will increase TAA progression. Methods and Results-The descending thoracic aortas of wild-type 129 SvE and TIMP-1 gene knockout (TIMP-1(-/-)) mice were exposed to 0.5 mol/L CaCl2 for 15 minutes, with terminal studies performed at 4 or 8 weeks. TAA lumen diameter was measured using confocal microscopy and normalized to the ascending aorta. In addition, sections were studied with in situ zymography and immunohistochemistry staining for MMP-9. Both wild-type [TAA/ascending ratio (mean+/-SEM): control, 0.85+/-0.02 (n=14); 4 weeks, 1.00+/-0.03 (n=13); 8 weeks, 1.05+/-0.10 (n=9)] and TfMP-1(-/-) [control, 0.98+/-0.04 (n= 11); 4 weeks, 1.10+/-0.03 (n =21); 8 weeks, 1.22+/-0.09 (n=10)] groups developed aneurysms at 4 and 8 weeks compared with their respective controls (P<0.05). TIMP-1(-/-) animals developed larger aneurysms than the corresponding wild-type group (P<0.05). Aneurysms in the TIMP-1(-/-) group were larger at 8 weeks than at 4 weeks (P<0.05), which was not seen in the wild-type aneurysm groups. Both groups showed presence of MMP-9 in 4 and 8 weeks, most prominently in the adventitia and outer media. In situ zymographic activity was increased in the 8-week TIMP-1(-/-) group compared with wild-type. Conclusions-Deletion of the TIMP-1 gene results in increased and continued progression of aneurysm formation compared with wild-type mice in a unique TAA model caused at least in part by an alteration in the balance between gelatinase activity and its endogenous inhibition. Therapeutic strategies aimed at modifying MMP activity may reduce or prevent the progression of TAAs. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Suite 409 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NCRR NIH HHS [P20 RR 16434]; NHLBI NIH HHS [R01 HL 059165-07] NR 43 TC 2 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2004 VL 110 IS 11 SU S BP II268 EP II273 DI 10.1161/01.CIR.0000138384.68947.20 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856DI UT WOS:000224023600046 PM 15364874 ER PT J AU Furie, KL Rosenberg, R Thompson, JL Bauer, K Mohr, JP Rosner, B Sciacca, R Barzegar, S Thornell, B Costigan, T Kistler, JP AF Furie, KL Rosenberg, R Thompson, JL Bauer, K Mohr, JP Rosner, B Sciacca, R Barzegar, S Thornell, B Costigan, T Kistler, JP TI Thrombin generation in noncardioembolic stroke subtypes - The Hemostatic System Activation Study SO NEUROLOGY LA English DT Article ID ATRIAL-FIBRILLATION; PROTHROMBIN ACTIVATION; MARKERS; COAGULATION; HUMANS; RISK; WARFARIN; STATE; MEN AB Background: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study ( HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). Methods: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization ( within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. Results: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic ( 1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/ year ( p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients ( RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. Conclusion: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke. C1 Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. MIT, Cambridge, MA 02139 USA. Columbia Univ, Columbia Presbyterian Hosp, New York, NY USA. RP Furie, KL (reprint author), Massachusetts Gen Hosp, Stroke Serv, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM kfurie@partners.org FU NCRR NIH HHS [M01-RR-01066]; NINDS NIH HHS [K23 NS42720, R01 NS33765] NR 20 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 14 PY 2004 VL 63 IS 5 BP 777 EP 784 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 853ME UT WOS:000223830900005 PM 15365123 ER PT J AU Spiegel, BMR Gralnek, IM Bolus, R Lin, C Dulai, GS Mayer, EA Naliboff, B AF Spiegel, BMR Gralnek, IM Bolus, R Lin, C Dulai, GS Mayer, EA Naliboff, B TI Clinical determinants of health-related quality of life in patients with irritable bowel syndrome SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GASTROINTESTINAL DISORDERS; MODEL; DEPRESSION; SYMPTOMS; ANXIETY; SYSTEM; STRESS; COSTS; PAIN; FEAR AB Background: Current guidelines recommend routine assessment of health-related quality of life (HRQOL) in patients with irritable bowel syndrome (IBS). However, physicians rarely have the time to measure HRQOL with the appropriate methodological rigor, and data suggest that HRQOL in patients with IBS is often estimated using inaccurate clinical gestalt. The identification of predictive factors could allow physicians to better assess HRQOL without using misleading clinical clues. We, therefore, sought to identify determinants of HRQOL in patients with IBS. Methods: We examined 770 patients, 18 years or older, with IBS at a university-based referral center. Subjects completed a symptom questionnaire, the Symptoms Checklist-90 items psychometric checklist, and the 36-Item Short-Form Health Survey. The main outcome was HRQOL as measured by the mental and physical component scores of the 36-Item Short-Form Health Survey. We first developed a list of hypothesis-driven HRQOL predictors, and then performed multivariate regression analysis to measure the independent association of each predictor with HRQOL. Results: Seven factors (r(2)=0.39) independently predicted physical HRQOL: (1) more than 5 physician visits per year, (2) tiring easily, (3) low in energy, (4) severe symptoms, (5) predominantly painful symptoms, (6) the feeling that there is "something seriously wrong with body," and (7) symptom flares for longer than 24 hours. Eight factors (r(2)=0.36) independently predicted mental HRQOL: (1) feeling tense, (2) feeling nervous, (3) feeling hopeless, (4) difficulty sleeping, (5) tiring easily, (6) low sexual interest, (7) IBS symptom interference with sexual function, and (8) low energy. Conclusions: Health-related quality of life in patients with IBS is primarily related to extraintestinal symptoms rather than traditionally elicited gastrointestinal symptoms. These findings suggest that rather than focusing on physiological epiphenomena (stool characteristics and subtype of IBS) and potentially misleading clinical factors (age and disease duration), physicians might be better served to gauge global symptom severity, address anxiety, and eliminate factors contributing to chronic stress in patients with IBS. C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Digest Healthcare Qual & Outcomes,VA Greater, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gastroenterol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Digest Healthcare Qual & Outcomes,VA Greater, 11301 Wilshire Blvd,Bldg 115,Room 215B, Los Angeles, CA 90073 USA. EM bspiegel@ucla.edu FU NCRR NIH HHS [K23RR-16188]; NIDDK NIH HHS [DK-07180, P50 DK-64539, R01 DK-07768, R01 DK-48351] NR 37 TC 94 Z9 94 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 13 PY 2004 VL 164 IS 16 BP 1773 EP 1780 DI 10.1001/archinte.164.16.1773 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 853MO UT WOS:000223831900009 PM 15364671 ER PT J AU Kim, SY Choi, EC Jo, YW Henson, JW Kim, HS AF Kim, SY Choi, EC Jo, YW Henson, JW Kim, HS TI Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1 beta: critical role of nuclear factor-1 SO VIROLOGY LA English DT Article DE JC virus; progressive multifocal leukoencephalopathy; AIDS; PMA; IL-1 beta; NF-1; PKC pathway ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CELL-SPECIFIC REGULATION; LARGE T-ANTIGEN; MOLECULAR-BIOLOGY; KAPPA-B; NITRIC-OXIDE; HUMAN BRAIN; PROTEIN; ELEMENT; DISEASE AB JC virus causes the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML) under immunosuppressive states such as AIDS. During the pathogenesis of AIDS, HIV-infected microglia secrete cytokines including interleukin-1 and tumor necrosis factor-alpha TNF-alpha), which affect neuronal cells resulting in dysfunction of the CNS. We hypothesized that extracellular stimuli released from HIV-infected microglia may reactivate JC virus by affecting neighboring oligodendrocytes. In the present study, we found that phorbol myristate acetate (PMA) and interleukin-1beta (IL-1beta) dramatically increased JC virus transcription in glial cells. Site-directed mutagenesis and gel shift analyses revealed that PMA and IL-1beta strongly induced nuclear factor-1 (NF-1) binding to the JC virus enhancer region, increasing transcriptional activity of the viral early promoter. Additionally, we demonstrated that protein kinase C (PKC) pathways were involved in the PMA/IL-1beta-mediated up-regulation of the JC virus early promoter. These findings may represent one of the possible mechanisms for higher incidence of PML among AIDS patients. (C) 2004 Elsevier Inc. All rights reserved. C1 Ewha Womans Univ, Sch Med, Ewha Inst Neurosci, Dept Neurosci, Seoul 110783, South Korea. Ewha Womans Univ, Sch Med, Med Res Ctr, Seoul 110783, South Korea. Seoul Natl Univ, Coll Pharm, Seoul, South Korea. Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul, South Korea. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kim, HS (reprint author), Ewha Womans Univ, Sch Med, Ewha Inst Neurosci, Dept Neurosci, 70 Jongno 6-Ga, Seoul 110783, South Korea. EM ecchoi@snu.ac.kr; hskimp@mm.ewha.ac.kr NR 33 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 13 PY 2004 VL 327 IS 1 BP 60 EP 69 DI 10.1016/j.virol.2004.06.021 PG 10 WC Virology SC Virology GA 851DB UT WOS:000223664500007 PM 15327898 ER PT J AU Kim, KT Ongusaha, PP Hong, YK Kurdistani, SK Nakamura, M Lu, KP Lee, SW AF Kim, KT Ongusaha, PP Hong, YK Kurdistani, SK Nakamura, M Lu, KP Lee, SW TI Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-MYC; CELLS; GENE; PROTEIN; P53; DIFFERENTIATION; EXPRESSION; TUBULIN; DRG-1; MICROTUBULES AB Mutations in the Drg1/RTP/Rit42 gene are commonly identified in hereditary neuropathies of the motor and sensory systems. This gene was also identified as a p53 target gene and a differentiation-related, putative metastatic suppressor gene in human colon and prostate cancer. In this study, we show that the Rit42 protein is a microtubule-associated protein that localizes to the centrosomes and participates in the spindle checkpoint in a p53-dependent manner. When ectopically expressed and exposed to spindle inhibitors, Rit42 inhibited polyploidy in several p53-deficient tumor cell lines and increased the population of cells in mitotic arrest. Blocking endogenous Rit42 expression by small interfering RNA in normal human mammary epithelial cells resulted in the disappearance of astral microtubules, and dividing spindle fiber formation was rarely detected. Moreover, these cells underwent microtubule inhibitor-induced reduplication, leading to a polyploidy state. Our findings imply that Rit42 plays a role in the regulation of microtubule dynamics and the maintenance of euploidy. C1 Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu OI Kurdistani, Siavash/0000-0003-3295-3511 FU NCI NIH HHS [CA80058, CA82211] NR 29 TC 35 Z9 36 U1 1 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 SEP 10 PY 2004 VL 279 IS 37 BP 38597 EP 38602 DI 10.1074/jbc.M400781200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 851KN UT WOS:000223684100066 PM 15247272 ER PT J AU Vagin, O Turdikulova, S Sachs, G AF Vagin, O Turdikulova, S Sachs, G TI The H,K-ATPase beta subunit as a model to study the role of N-glycosylation in membrane trafficking and apical sorting SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; TRANS-GOLGI NETWORK; DARBY CANINE KIDNEY; EPITHELIAL-CELLS; PLASMA-MEMBRANE; GASTRIC H+,K+-ATPASE; ENDOPLASMIC-RETICULUM; TRANSPORTING ATPASE; EXPRESSION; SIGNALS AB The role of N-glycosylation in trafficking of an apical membrane protein, the gastric H, K-ATPase beta subunit linked to yellow fluorescent protein, was analyzed in polarized LLC-PK1 cells by confocal microscopy and surface-specific biotinylation. Deletion of the N-glycosylation sites at N1, N3, N5, and N7 but not at N2, N4, and N6 significantly slowed endoplasmic reticulum-to-Golgi trafficking, impaired apical sorting, and enhanced endocytosis from the apical membrane, resulting in decreased apical expression. Golgi mannosidase inhibition to prevent carbohydrate chain branching and elongation resulted in faster internalization and degradation of the beta subunit, indicating that terminal glycosylation is important for stabilization of the protein in the apical membrane and protection of internalized protein from targeting to the degradation pathway. The decrease in the apical content of the beta subunit was less with mannosidase inhibition compared with that found in the N1, N3, N5, and N7 site mutants, suggesting that the core region sugars are more important than the terminal sugars for apical sorting. C1 Vet Affairs Greater Los Angeles Hlth Care Syst W, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Vagin, O (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst W, Bldg 113,Rm 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM olgav@uvla.edu FU NIDDK NIH HHS [DK41301, DK53462, DK46917, DK17294] NR 32 TC 47 Z9 48 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 SEP 10 PY 2004 VL 279 IS 37 BP 39026 EP 39034 DI 10.1074/jbc.M405453200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 851KN UT WOS:000223684100117 PM 15247221 ER PT J AU Shalizi, CR Shalizi, KL Haslinger, R AF Shalizi, CR Shalizi, KL Haslinger, R TI Quantifying self-organization with optimal predictors SO PHYSICAL REVIEW LETTERS LA English DT Article ID COMPLEXITY; MECHANICS AB Despite broad interest in self-organizing systems, there are few quantitative, experimentally applicable criteria for self-organization. The existing criteria all give counter-intuitive results for important cases. In this Letter, we propose a new criterion, namely, an internally generated increase in the statistical complexity, the amount of information required for optimal prediction of the system's dynamics. We precisely define this complexity for spatially extended dynamical systems, using the probabilistic ideas of mutual information and minimal sufficient statistics. This leads to a general method for predicting such systems and a simple algorithm for estimating statistical complexity. The results of applying this algorithm to a class of models of excitable media (cyclic cellular automata) strongly support our proposal. C1 Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. RP Shalizi, CR (reprint author), Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. EM cshalizi@umich.edu; kshalizi@umich.edu; robhh@nmr.mgh.harvard.edu NR 29 TC 60 Z9 60 U1 2 U2 10 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD SEP 10 PY 2004 VL 93 IS 11 AR 118701 DI 10.1103/PhysRevLett.93.118701 PG 4 WC Physics, Multidisciplinary SC Physics GA 852ZB UT WOS:000223794400065 PM 15447385 ER PT J AU Lipton, JM Westra, S Haverty, CE Roberts, D Harris, NL Insoft, RM Friedmann, A Billett, A Lehmann, L AF Lipton, JM Westra, S Haverty, CE Roberts, D Harris, NL Insoft, RM Friedmann, A Billett, A Lehmann, L TI Newborn twins with thrombocytopenia, coagulation defects, and hepatosplenomegaly - Familial hemophagocytic lymphohistiocytosis, caused by a mutation in the perforin gene SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PRF1 MUTATIONS; EXPRESSION; REVEALS C1 Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Schneider Childrens Hosp, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY USA. Massachusetts Gen Hosp, Serv Gynecol Obstet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Lipton, JM (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. NR 29 TC 21 Z9 21 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 9 PY 2004 VL 351 IS 11 BP 1120 EP 1130 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 852CX UT WOS:000223733900013 PM 15356310 ER PT J AU Weinstein, AR Sesso, HD Lee, IM Cook, NR Manson, JE Buring, JE Gaziano, JM AF Weinstein, AR Sesso, HD Lee, IM Cook, NR Manson, JE Buring, JE Gaziano, JM TI Relationship of physical activity vs body mass index with type 2 diabetes in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; RISK-FACTOR; MELLITUS; EXERCISE; HEALTH; PREVENTION; DISEASE; OBESITY; WEIGHT AB Context Physical inactivity and body mass index (BMI) are established independent risk factors in the development of type 2 diabetes; however, their comparative importance and joint relationship with diabetes are unclear. Objective To examine the relative contributions and joint association of physical activity and BMI with diabetes. Design, Setting, and Participants Prospective cohort study of 37878 women free of cardiovascular disease, cancer, and diabetes with 6.9 years of mean follow-up. Weight, height, and recreational activities were reported at study entry. Normal weight was defined as a BMI of less than 25; overweight, 25 to less than 30; and obese, 30 or higher. Active was defined as expending more than 1000 kcal on recreational activities per week. Main Outcome Measure Incident type 2 diabetes, defined as anew self-reported diagnosis of diabetes. Results During the follow-up, 1361 cases of incident diabetes occurred. Individually, BMI and physical Activity were significant predictors of incident diabetes. Compared with normal-weight individuals, the multivariate-adjusted hazard ratio (HR) was 3.22 (95% confidence interval [CI], 2.69-3.87) for overweight individuals and 9.09 (95% CI, 7.62-10.8) for obese individuals. For overall activity (kilocalories expended per week), compared with the least active first quartile, the multivariate-adjusted HRs were 0.91 (95% CI, 0.79-1.06) for the second quartile, 0.86 (95% CI, 0.74-1.01) for the third, and 0.82 (95% CI, 0.70-0.97) for the fourth (P for trend=.01). In the combined analyses, overweight and obese participants, whether active or inactive, had significantly elevated risks, compared with normal-weight active individuals. The multivariate-adjusted HRS were 1.15 (95% CI, 0.83-1.59) for normal-weight inactive, 3.68 (95% CI, 2.63-5.15) for overweight active, 4.16 (95% CI, 3.05-5.66) for overweight inactive, 11.5 (95% CI, 8.34-15.9) for obese active, and 11.8 (95% CI, 8.75-16.0) for obese inactive participants. Conclusions Although BMI and physical inactivity are independent predictors of incident diabetes, the magnitude of the association with BMI was greater than with physical activity in combined analyses. These findings underscore the critical importance of adiposity as a determinant of diabetes. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. RP Weinstein, AR (reprint author), Womens Hlth Ctr Hlth Care Associates, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Atrium Suite, Boston, MA 02115 USA. EM aweinste@bidmc.harvard.edu FU NCI NIH HHS [CA-4799]; NHLBI NIH HHS [HL-65727, HL-43851] NR 27 TC 185 Z9 193 U1 0 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 2004 VL 292 IS 10 BP 1188 EP 1194 DI 10.1001/jama.292.10.1188 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 851ZA UT WOS:000223723800018 PM 15353531 ER PT J AU Artoni, A Li, JH Mitchell, B Ruan, J Takagi, J Springer, TA French, DL Coller, BS AF Artoni, A Li, JH Mitchell, B Ruan, J Takagi, J Springer, TA French, DL Coller, BS TI Integrin beta 3 regions controlling binding of murine mAb 7E3: Implications for the mechanism of integrin alpha IIb beta 3 activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCOPROTEIN-IIIA; EXTRACELLULAR SEGMENT; CRYSTAL-STRUCTURE; LIGAND-BINDING; ALPHA-V-BETA-3; ANTIBODY; RECEPTOR; DOMAINS; GENE; ALPHA-IIB-BETA-3 AB Abciximab, a derivative of the murine mAb 7E3, protects against ischemic complications of percutaneous coronary interventions by inhibiting ligand binding to the alphaIIbbeta3 receptor. In this study we identified regions on integrin beta3 that control 7E3 binding. Murine/human amino acid substitutions were created in two regions of the betaA domain that previous studies found to influence 7E3 binding: the C177-C184 loop and K125-N133. The T182N substitution and a K125Q mutation reduced 7E3 binding to human beta3 in complex with alphaIIb. The introduction of both the human C177-C184 region and human W129 into murine beta3 was necessary and sufficient to permit 7E3 binding to the human alphaIIb/murine 133 complex. Although we cannot exclude allosteric effects, we propose that 7E3 binds between C177-C184 and W129, which are within 15 Angstrom of each other in the crystal structure and close to the beta3 metal ion-dependent adhesion site. We previously demonstrated that 7E3 binds more rapidly to activated than unactivated platelets. Because it has been proposed that alphaIIbbeta3 changes from a bent to an extended conformation upon activation, we hypothesized that 7E3 binds less well to the bent than the extended conformation. in support of this hypothesis we found that 7E3 bound less well to an alphaIIbbeta3 construct locked in a bent conformation, and unlocking the conformation restored 7E3 binding. Thus, our data are consistent with alphaIIbbeta3 existing in variably bent conformations in equilibrium with each other on unactivated platelets, and activation resulting in alphaIIbbeta3 adopting a more extended conformation. C1 CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10021 USA. RP Coller, BS (reprint author), CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. EM collerb@rockefeller.edu FU NCRR NIH HHS [M01 RR000102, M01-RR00102]; NHLBI NIH HHS [HL 19278, R01 HL019278] NR 31 TC 54 Z9 58 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 7 PY 2004 VL 101 IS 36 BP 13114 EP 13120 DI 10.1073/pnas.0404201101 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 853AT UT WOS:000223799100005 PM 15277669 ER PT J AU Zavala-Ruiz, Z Strug, I Walker, BD Norris, PJ Stern, LJ AF Zavala-Ruiz, Z Strug, I Walker, BD Norris, PJ Stern, LJ TI A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen presentation; receptors; antigen; protein conformation ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; CRYSTAL-STRUCTURE; FLANKING RESIDUES; STRUCTURAL BASIS; CLIP PEPTIDE; AMINO-ACIDS; RECEPTOR; HLA-DR1; MOLECULES AB T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Blood Syst Res Inst, San Francisco, CA 94118 USA. RP Stern, LJ (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. EM lawrence.stern@umassmed.edu FU NIAID NIH HHS [R01-AI38996, K08 AI001698, K08 AI001698-04, R01 AI038996, R01-AI01698]; NIGMS NIH HHS [F31-GM64859, F31 GM064859] NR 53 TC 44 Z9 45 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 SEP 7 PY 2004 VL 101 IS 36 BP 13279 EP 13284 DI 10.1073/pnas.0403371101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 853AT UT WOS:000223799100034 PM 15331779 ER PT J AU Winter, HS Brandt, LJ AF Winter, HS Brandt, LJ TI Acid-related disorders from pediatrics to geriatrics: Reducing risks and optimizing outcomes - Introduction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID PREVALENCE; DYSPEPSIA; COMMUNITY C1 Montefiore Med Ctr, Dept Med, Div Gastroenterol, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Dept Pediat, Pediat IBD Ctr, Boston, MA 02114 USA. RP Brandt, LJ (reprint author), Montefiore Med Ctr, Dept Med, Div Gastroenterol, 111 E 210th St, Bronx, NY 10467 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 6 PY 2004 VL 117 SU 5A BP 1S EP 1S DI 10.1016/j.amjmed.2004.07.018 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 853SA UT WOS:000223846700001 PM 15478845 ER PT J AU Bannert, H Muranyi, W Ogryzko, VV Nakatani, Y Flugel, RM AF Bannert, H Muranyi, W Ogryzko, VV Nakatani, Y Flugel, RM TI Coactivators p300 and PCAF physically and functionally interact with the foamy viral trans-activator SO BMC MOLECULAR BIOLOGY LA English DT Article ID NUCLEAR FACTOR-I; DNA-BINDING; HISTONE ACETYLTRANSFERASES; CBP; ACTIVATION; PROMOTER; CBP/P300; PROTEIN; DOMAIN; CELLS AB Background: Foamy virus Bel1/Tas trans-activators act as key regulators of gene expression and directly bind to Bel1 response elements (BRE) in both the internal and the 5' LTR promoters leading to strong transcriptional trans-activation. Cellular coactivators interacting with Bel1/Tas are unknown to date. Results: Transient expression assays, co-immunoprecipitation experiments, pull-down assays, and Western blot analysis were used to demonstrate that the coactivator p300 and histone acetyltransferase PCAF specifically interact with the retroviral trans-activator Bel1/Tas in vivo. Here we show that the Bel1/Tas-mediated trans-activation was enhanced by the coactivator p300, histone acetyltransferases PCAF and SRC-1 based on the crucial internal promoter BRE. The Bel1/Tas-interacting region was mapped to the C/H1 domain of p300 by co-immunoprecipitation and pull-down assays. In contrast, coactivator SRC-1 previously reported to bind to the C-terminal domain of p300 did not directly interact with the Bel1 protein but nevertheless enhanced Bel1/Tas-mediated trans-activation. Cotransfection of Bel1/Tas and p300C with an expression plasmid containing the C/H1 domain partially inhibited the p300C-driven trans-activation. Conclusions: Our data identify p300 and PCAF as functional partner molecules that directly interact with Bel1/Tas. Since the acetylation activities of the three coactivators reside in or bind to the C-terminal regions of p300, a C/H1 expression plasmid was used as inhibitor. This is the first report of a C/H1 domain-interacting retroviral trans-activator capable of partially blocking the strong Bel1/Tas-mediated activation of the C-terminal region of coactivator p300. The potential mechanisms and functional roles of the three histone and factor acetyltransferases p300, PCAF, and SRC-1 in Bel1/Tas-mediated trans-activation are discussed. C1 German Canc Res Ctr, Dept Retroviral Gene Express, D-6900 Heidelberg, Germany. Univ Heidelberg, Inst Hyg, Abt Virol, D-69120 Heidelberg, Germany. Andre Lwoff Inst, CNRS, UR 079, F-94801 Villejuif, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Flugel, RM (reprint author), German Canc Res Ctr, Dept Retroviral Gene Express, D-6900 Heidelberg, Germany. EM h.bannert@dkfz-heidelberg.de; walter.muranyi@urz.uni-heidelberg.de; v.ogryzko@vjf.cnrs.fr; nakatani@mac.com; r.m.fluegel@dkfz-heidelberg.de RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 32 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD SEP 6 PY 2004 VL 5 AR 16 DI 10.1186/1471-2199-5-16 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 855SL UT WOS:000223993900002 PM 15350211 ER PT J AU Kampman, KM Pettinati, H Lynch, KG Dackis, C Sparkman, T Weigley, C O'Brien, CP AF Kampman, KM Pettinati, H Lynch, KG Dackis, C Sparkman, T Weigley, C O'Brien, CP TI A pilot trial of topiramate for the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; topiramate; clinical trial; GABA; glutamate ID NUCLEUS-ACCUMBENS; INDUCED REINSTATEMENT; WITHDRAWAL SYMPTOMS; TREATMENT ATTRITION; PREFRONTAL CORTEX; SEEKING BEHAVIOR; DOPAMINE NEURONS; GABA; INCREASES; SEVERITY AB Background: Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence. Methods: The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT). Results: Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi(2) = 3.9, d.f. = 1, P = 0.05). Conclusion: Topiramate may be effective for the treatment of cocaine dependence. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman_k@mail.trc.upenn.edu FU NIDA NIH HHS [DA12756] NR 46 TC 174 Z9 180 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 6 PY 2004 VL 75 IS 3 BP 233 EP 240 DI 10.1016/j.drugalcdep.2004.03.008 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 846JY UT WOS:000223313000002 PM 15283944 ER PT J AU Li, HW Liu, H Sage, C Huang, MQ Chen, ZY Heller, S AF Li, HW Liu, H Sage, C Huang, MQ Chen, ZY Heller, S TI Islet-1 expression in the developing chicken inner ear SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE hair cell; cochlea; vestibular; neuron; auditory ID SENSORY ORGAN GENERATION; LIM HOMEOBOX GENES; DIFFERENTIAL EXPRESSION; AVIAN OTOCYST; HAIR-CELLS; STEM-CELLS; NEURONS; PAX2; SPECIFICATION; NEUROGENESIS AB The cell types of the inner ear originate from the otic placode, a thickened layer of ectoderm adjacent to the developing hindbrain. The placode invaginates and forms the otic pit, which pinches off as a small vesicle called the otocyst. Presumptive cochleovestibular neurons delaminate from the anterior ventral part of the otocyst and form the cochleovestibular ganglion of the inner ear. Here we show that the LIM/homeodomain protein islet-1 is expressed in cells of the ventral part of the otic placode and that this ventral expression is maintained at the otic pit and the otocyst stages. Auditory and vestibular neurons originate from this islet-1-positive zone of the otocyst, and these neurons maintain islet-1 expression until adulthood. We also demonstrate that islet-1 becomes up-regulated in the presumptive sensory epithelia of the inner ear in regions that are defined by the expression domains of BMP4. The up-regulation of islet-1 in developing inner ear hair and supporting cells is accompanied by down-regulation of Pax-2 in these cell types. Islet-1 expression in hair and supporting cells persists until early postnatal stages, when the transcriptional regulator is down-regulated in hair cells. Our data is consistent with a role for islet-1 in differentiating inner ear neurons and sensory epithelia cells, perhaps in the specification of cellular subtypes in conjunction with other LIM/homeodomain proteins. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Fudan Univ, Eye Ear Nose & Throat Hosp, Dept Otolaryngol, Shanghai 200031, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. RP Heller, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM hellers@epl.meei.harvard.edu FU NIDCD NIH HHS [P30 DC05209, DC006167, DC04546, DC04563] NR 43 TC 46 Z9 46 U1 0 U2 7 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 SEP 6 PY 2004 VL 477 IS 1 BP 1 EP 10 DI 10.1002/cne.20190 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 844LT UT WOS:000223160400001 PM 15281076 ER PT J AU Barata, JT Silva, A Brandao, JG Nadler, LM Cardoso, AA Boussiotis, VA AF Barata, JT Silva, A Brandao, JG Nadler, LM Cardoso, AA Boussiotis, VA TI Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell acute lymphoblastic leukemia; IL-7; PI3K-Akt; MEK-Erk; Glut1 ID GLYCOGEN-SYNTHASE KINASE-3; STIMULATES TYROSINE PHOSPHORYLATION; FORKHEAD TRANSCRIPTION FACTOR; CYCLE PROGRESSION; SIGNALING PATHWAY; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; DOWN-REGULATION; SURVIVAL; APOPTOSIS AB Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by tip-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27(kip1). Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)-Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK-Erk pathway in T-ALL cells; however, inhibition of the MEK-Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7-mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7-mediated Bcl-2 up-regulation, p27(kip1) down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7-induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Lisbon, Sch Med, Inst Mol Med, Tumor Biol Unit, P-1649028 Lisbon, Portugal. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Room Mayer 547, Boston, MA 02115 USA. EM vassiliki-boussiotis@dfci.harvard.edu RI Barata, Joao/D-9181-2015 OI Barata, Joao/0000-0002-4826-8976 FU NCI NIH HHS [P01 CA068484, P01-CA68484]; NIAID NIH HHS [AI 46548, R01 AI046548] NR 62 TC 142 Z9 148 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 6 PY 2004 VL 200 IS 5 BP 659 EP 669 DI 10.1084/jem.20040789 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 854IC UT WOS:000223895300012 PM 15353558 ER PT J AU Johnson, SW Wu, YN AF Johnson, SW Wu, YN TI Multiple mechanisms underlie burst firing in rat midbrain doparnine neurons in vitro SO BRAIN RESEARCH LA English DT Article DE apamin; nifedipine; N-methyl-D-aspartate; substantia nigra; ventral tegmental area ID DOPAMINE-CONTAINING NEURONS; APAMIN; INVITRO; CONDUCTANCE; CHANNELS; NUCLEUS AB Both apamin and NMDA evoke burst firing in dopamine neurons recorded intracellularly in slices of rat midbrain. However, apamin-induced bursting required injection of depolarizing currents, and was mimicked by Bay K8644 and blocked by nifedipine. In contrast, NMDA-induced bursting required hyperpolarizing currents and was not blocked by nifedipine. Our results show that burst firing can be evoked in dopamine neurons via two different mechanisms. (C) 2004 Elsevier B.V. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, RD-61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NIMH NIH HHS [MH40416] NR 17 TC 47 Z9 47 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 SEP 3 PY 2004 VL 1019 IS 1-2 BP 293 EP 296 DI 10.1016/j.brainres.2004.06.022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 851UI UT WOS:000223710800036 PM 15306267 ER PT J AU Mostoslavsky, R Alt, FW Rajewsky, K AF Mostoslavsky, R Alt, FW Rajewsky, K TI The lingering enigma of the allelic exclusion mechanism SO CELL LA English DT Review ID B-CELL DEVELOPMENT; LIGHT CHAIN GENES; KAPPA-L-CHAIN; V(D)J RECOMBINATION; EXPRESSION; REARRANGEMENTS; LOCUS; GENERATION; SELECTION; RECEPTORS AB B lymphocytes produce diverse antibody specificities by "randomly" assembling antibody genes from germline segments. Yet, though each B lymphocyte has multiple allelic loci for the different antibody chains, each clonally derived mature B lymphocyte expresses a single species of antibody with a unique specificity via a process termed allelic exclusion. Despite some progress, the precise mechanism of allelic exclusion remains an enigma. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; rajewsky@cbr.med.harvard.edu NR 31 TC 75 Z9 77 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 3 PY 2004 VL 118 IS 5 BP 539 EP 544 DI 10.1016/j.cell.2004.08.023 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852BN UT WOS:000223730300005 PM 15339659 ER PT J AU Ehrlich, M Boll, W van Oijen, A Hariharan, R Chandran, K Nibert, ML Kirchhausen, T AF Ehrlich, M Boll, W van Oijen, A Hariharan, R Chandran, K Nibert, ML Kirchhausen, T TI Endocytosis by random initiation and stabilization of clathrin-coated pits SO CELL LA English DT Article ID MEDIATED ENDOCYTOSIS; VESICLE FORMATION; PLASMA-MEMBRANE; AP COMPLEXES; DYNAMIN; FIBROBLASTS; RECEPTOR; CELL; DIFFUSION; SIGNALS AB Clathrin-coated vesicles carry traffic from the plasma membrane to endosomes. We report here the real-time visualization of cargo sorting and endocytosis by clathrin-coated pits in living cells. We have detected the formation of coats by monitoring incorporation of fluorescently tagged clathrin or its adaptor AP-2; we have also followed clathrin-mediated uptake of transferrin and of single LDL or reovirus particles. The intensity of a cargo-loaded clathrin cluster grows steadily during its lifetime, and the time required to complete assembly is proportional to the size of the cargo particle. These results are consistent with a nucleation-growth mechanism and an approximately constant growth rate. There are no strongly preferred nucleation sites. A proportion of the nucleation events are weak and short lived. Cargo incorporation occurs primarily or exclusively in a newly formed coated pit. Our data lead to a model in which coated pits initiate randomly but collapse unless stabilized, perhaps by cargo capture. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Indian Inst Sci, Dept Comp Sci, Bangalore 560012, Karnataka, India. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu RI Chandran, Kartik/I-2232-2012; OI van Oijen, Antoine/0000-0002-1794-5161 FU NIGMS NIH HHS [GM36548] NR 30 TC 455 Z9 463 U1 6 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD SEP 3 PY 2004 VL 118 IS 5 BP 591 EP 605 DI 10.1016/j.cell.2004.08.017 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852BN UT WOS:000223730300010 PM 15339664 ER PT J AU Das, J Addona, GH Sandberg, WS Husain, SS Stehle, T Miller, KW AF Das, J Addona, GH Sandberg, WS Husain, SS Stehle, T Miller, KW TI Identification of a general anesthetic binding site in the diacylglycerol-binding domain of protein kinase C delta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN SERUM-ALBUMIN; PHORBOL ESTER; INHALED ANESTHETICS; ADENYLATE KINASE; ALPHA; INHIBITION; HALOTHANE; NONEQUIVALENT; ACTIVATION; MEMBRANES AB Protein kinase C (PKC) is an important signal transduction protein that has been proposed to interact with general anesthetics at its cysteine-rich diacylglycerol/ phorbol ester-binding domain C1, a tandem repeat of C1A and C1B subdomains. To test this hypothesis, we expressed, purified, and characterized the high affinity phorbol-binding subdomain, C1B, of mouse protein kinase Cdelta, and studied its interaction with general anesthetic alcohols. When the fluorescent phorbol ester, sapintoxin-D, bound to PKCdelta C1B in buffer at a molar ratio of 1: 2, its fluorescence emission maximum, lambda(max), shifted from 437 to 425 nm. The general anesthetic alcohols, butanol and octanol, further shifted lambda(max) of the PKCdelta C1B-bound sapintoxin-D in a concentration-dependent, saturable manner to similar to415 nm, suggesting that alcohols interact at a discrete allosteric binding site. To identify this site, PKCdeltaC1B was photolabeled with three photoactivable diazirine alcohol analogs, 3-azioctanol, 7-azioctanol, and 3-azibutanol. Mass spectrometry showed photoincorporation of all three alcohols in PKCdeltaC1B at a stoichiometry of 1: 1 in the labeled fraction. The photolabeled PKCdeltaC1B was subjected to tryptic digest, the fragments were separated by online chromatography and sequenced by mass spectrometry. Each azialcohol photoincorporated at Tyr-236. Inspection of the known structure of PKCdeltaC1B shows that this residue is situated adjacent to the phorbol ester binding pocket, and within similar to10 Angstrom of the bound phorbol ester. The present results provide direct evidence for an allosteric anesthetic site on protein kinase C. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM 07592, GM 069726, GM 58448] NR 38 TC 36 Z9 36 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 3 PY 2004 VL 279 IS 36 BP 37964 EP 37972 DI 10.1074/jbc.M405137200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 849QK UT WOS:000223554600090 PM 15234976 ER PT J AU Kondo, T Kahn, CR AF Kondo, T Kahn, CR TI Altered insulin signaling in retinal tissue in diabetic states SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INDUCED DOWN-REGULATION; NITRIC-OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR INACTIVATION; ANIMAL-MODELS; UP-REGULATION; RISK-FACTORS; RETINOPATHY; EXPRESSION AB Both type 1 and type 2 diabetes can lead to altered retinal microvascular function and diabetic retinopathy. Insulin signaling may also play a role in this process, and mice lacking insulin receptors in endothelial cells are protected from retinal neovascularization. To define the role of diabetes in retinal function, we compared insulin signaling in the retinal vasculature of mouse models of type 1 ( streptozotocin) and type 2 diabetes (ob/ob). In streptozotocin mice, in both retina and liver, insulin receptor (IR) and insulin receptor substrate (IRS)-2 protein and tyrosine phosphorylation were increased by insulin, while IRS-1 protein and its phosphorylation were maintained. By contrast, in ob/ob mice, there was marked down-regulation of IR, IRS-1, and IRS-2 protein and phosphorylation in liver; these were maintained or increased in retina. In both mice, Phosphatidylinositol 3,4,5-trisphosphate generation by acute insulin stimulation was enhanced in retinal endothelial cells. On the other hand, protein levels and phosphorylation of PDK1 and Akt were decreased in retina of both mice. Interestingly, phosphorylation of p38 mitogen-activated protein kinase and ERK1 were responsive to insulin in retina of both mice but were unresponsive in liver. HIF-1alpha and vascular endothelial growth factor were increased and endothelial nitric-oxide synthase was decreased in retina. These observations indicate that, in both insulin-resistant and insulin-deficient diabetic states, there are alterations in insulin signaling, such as impaired PDK/Akt responses and enhanced mitogen-activated protein kinases responses that could contribute to the retinopathy. Furthermore, insulin signaling in retinal endothelial cells is differentially altered in diabetes and is also differentially regulated from insulin signaling in classical target tissues such as liver. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK31036, DK53105, DK33201] NR 44 TC 62 Z9 64 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 3 PY 2004 VL 279 IS 36 BP 37997 EP 38006 DI 10.1074/jbc.M401339200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 849QK UT WOS:000223554600093 PM 15201286 ER PT J AU Entingh-Pearsall, A Kahn, CR AF Entingh-Pearsall, A Kahn, CR TI Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BROWN ADIPOCYTE DIFFERENTIATION; TYROSINE KINASE; SIGNAL TRANSDUCTION; HYBRID RECEPTORS; TRANSGENIC MICE; ADIPOSE-TISSUE; GLUCOSE-UPTAKE; CELLS; SUBSTRATE; PROTEIN AB Insulin and insulin-like growth factor-I (IGF-I) receptors are highly homologous tyrosine kinase receptors that share many common steps in their signaling pathways and have ligands that can bind to either receptor with differing affinities. To define precisely the signaling specific to the insulin receptor (IR) or the IGF-I receptor, we have generated brown preadipocyte cell lines that lack either receptor ( insulin receptor knockout (IRKO) or insulin-like growth factor receptor knockout (IGFRKO)). Control preadipocytes expressed fewer insulin receptors than IGF-I receptors ( 20,000 versus 60,000), but during differentiation, insulin receptor levels increased so that mature adipocytesexpressed slightly more insulin receptors than IGF-I receptors ( 120,000 versus 100,000). In these cells, insulin stimulated IR homodimer phosphorylation, whereas IGF-I activated both IGF-I receptor homodimers and hybrid receptors. Insulin-stimulated IRS-1 phosphorylation was significantly impaired in IRKO cells but was surprisingly elevated in IGFRKO cells. IRS-2 phosphorylation was unchanged in either cell line upon insulin stimulation. IGF-I-dependent phosphorylation of IRS-1 and IRS-2 was ablated in IGFRKO cells but not in IRKO cells. In control cells, both insulin and IGF-I produced a dose-dependent increase in phosphorylated Akt and MAPK, although IGF-I elicited a stronger response at an equivalent dose. In IRKO cells, the insulin-dependent increase in phospho-Akt was completely abolished at the lowest dose and reached only 20% of the control stimulation at 10 nM. Most interestingly, the response to IGF-I was also impaired at low doses, suggesting that IR is required for both insulin-and IGF-I-dependent phosphorylation of Akt. Most surprisingly, insulin-or IGF-I-dependent phosphorylation of MAPK was unaltered in either receptor-deficient cell line. Taken together, these results indicate that the insulin and IGF-I receptors contribute distinct signals to common downstream components in response to both insulin and IGF-I. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. RP Kahn, CR (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK33301, DK07260] NR 43 TC 77 Z9 84 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 3 PY 2004 VL 279 IS 36 BP 38016 EP 38024 DI 10.1074/jbc.M313201200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 849QK UT WOS:000223554600095 PM 15247278 ER PT J AU Perez-Villamil, B Mirasierra, M Vallejo, M AF Perez-Villamil, B Mirasierra, M Vallejo, M TI The homeoprotein Alx3 contains discrete functional domains and exhibits cell-specific and selective monomeric binding and transactivation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOMATOSTATIN GENE-TRANSCRIPTION; ARISTALESS-RELATED GENES; HOMEODOMAIN PROTEIN; HOMEOBOX GENE; PAIRED CLASS; MESSENGER-RNAS; EXPRESSION; DNA; CART1; PROLINE AB Alx3 is a paired class aristaless-like homeoprotein expressed during embryonic development. Transcriptional transactivation by aristaless-like proteins has been associated with cooperative dimerization upon binding to artificially generated DNA consensus sequences known as P3 sites, but natural target sites in genes regulated by Alx3 are unknown. We report the cloning of a cDNA encoding the rat homolog of Alx3, and we characterize the protein domains that are important for transactivation, dimerization, and binding to DNA. Two proline-rich domains located amino-terminal to the homeodomain (Pro1 and Pro2) are necessary for Alx3-dependent transactivation, whereas another one (Pro3) located in the carboxyl terminus is dispensable but contributes to enhance the magnitude of the response. We confirmed that transcriptional activity of Alx3 from a P3 site correlates with cooperative dimerization upon binding to DNA. However, Alx3 was found to bind selectively to non-P3-related TAAT-containing sites present in the promoter of the somatostatin gene in a specific manner that depends on the nuclear protein environment. Cell-specific transactivation elicited by Alx3 from these sites could not be predicted from in vitro DNA-binding experiments by using recombinant Alx3. In addition, transactivation did not depend on cooperative dimerization upon binding to cognate somatostatin DNA sites. Our data indicate that the paradigm according to which Alx3 must act homodimerically via cooperative binding to P3-like sites is insufficient to explain the mechanism of action of this homeoprotein to regulate transcription of natural target genes. Instead, Alx3 undergoes restrictive or permissive interactions with nuclear proteins that determine its binding to and transactivation from TAAT target sites selected in a cell-specific manner. C1 Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Vallejo, M (reprint author), Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Calle Arturo Duperier 4, Madrid 28029, Spain. EM mvallejo@iib.uam.es OI Mirasierra, Mercedes/0000-0002-0023-8903 FU NIDDK NIH HHS [DK-49670] NR 52 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 3 PY 2004 VL 279 IS 36 BP 38062 EP 38071 DI 10.1074/jbc.M400800200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 849QK UT WOS:000223554600101 PM 15226305 ER PT J AU Walensky, LD Kung, AL Escher, I Malia, TJ Barbuto, S Wright, RD Wagner, G Verdine, GL Korsmeyer, SJ AF Walensky, LD Kung, AL Escher, I Malia, TJ Barbuto, S Wright, RD Wagner, G Verdine, GL Korsmeyer, SJ TI Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix SO SCIENCE LA English DT Article ID CELL-PENETRATING PEPTIDES; CHROMOSOMAL BREAKPOINT; PROTEIN TRANSDUCTION; FOLLICULAR LYMPHOMA; NMR STRUCTURE; CYTOCHROME-C; DEATH; DOMAIN; BAK; MACROPINOCYTOSIS AB BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. RP Verdine, GL (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM verdine@chemistry.harvard.edu; stantey_korsmeyer@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [R37CA50239]; NHLBI NIH HHS [K08 HL074049, K08HL074049] NR 31 TC 757 Z9 783 U1 8 U2 155 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 SEP 3 PY 2004 VL 305 IS 5689 BP 1466 EP 1470 DI 10.1126/science.1099191 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 852NK UT WOS:000223761900050 PM 15353804 ER PT J AU Chen, IA Roberts, RW Szostak, JW AF Chen, IA Roberts, RW Szostak, JW TI The emergence of competition between model protocells SO SCIENCE LA English DT Article ID FATTY-ACID VESICLES; UNILAMELLAR VESICLES; GROWTH; CHOLESTEROL; MEMBRANES; BILAYERS; LIFE AB The transition from independent molecular entities to cellular structures with integrated behaviors was a crucial aspect of the origin of life. We show that simple physical principles can mediate a coordinated interaction between genome and compartment boundary, independent of any genomic functions beyond self-replication. RNA, encapsulated in fatty acid vesicles, exerts an osmotic pressure on the vesicle membrane that drives the uptake of additional membrane components, leading to membrane growth at the expense of relaxed vesicles, which shrink. Thus, more efficient RNA replication could cause faster cell growth, leading to the emergence of Darwinian evolution at the cellular level. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. RP Szostak, JW (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute; NIGMS NIH HHS [T32 GM007753, T32 GM008313, T32-GM07753, T32-GM08313] NR 20 TC 189 Z9 200 U1 11 U2 83 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 SEP 3 PY 2004 VL 305 IS 5689 BP 1474 EP 1476 DI 10.1126/science.1100757 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 852NK UT WOS:000223761900052 PM 15353806 ER PT J AU Tanzi, RE Moir, RD Wagner, SL AF Tanzi, RE Moir, RD Wagner, SL TI Clearance of Alzheimer's A beta peptide: The many roads to perdition SO NEURON LA English DT Editorial Material ID BLOOD-BRAIN-BARRIER; AMYLOID-BETA; TRANSGENIC MICE; DISEASE; PROTEIN; RECEPTOR; NEPRILYSIN; PRECURSOR; INSULIN; ACCUMULATION AB The amyloid hypothesis of Alzheimer's disease (AD) maintains that the accumulation of the amyloid beta protein (Abeta) is a critical event in disease pathogenesis. A great deal of both academic and commercial research has focused on the mechanisms by which Abeta is generated. However, investigations into the mechanisms underlying Abeta clearance have blossomed over the last several years. This minireview will summarize pathways involved in the removal of cerebral Abeta, including enzymatic degradation and receptor-mediated efflux out of the brain. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Massgen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. Neurogenetics Inc, La Jolla, CA 92037 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Massgen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. NR 26 TC 282 Z9 302 U1 4 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 2 PY 2004 VL 43 IS 5 BP 605 EP 608 DI 10.1016/j.neuron.2004.08.024 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 851NN UT WOS:000223691900006 PM 15339642 ER PT J AU Calon, F Lim, GP Yang, FS Morihara, T Teter, B Ubeda, O Rostaing, P Triller, A Salem, N Ashe, KH Frautschy, SA Cole, GM AF Calon, F Lim, GP Yang, FS Morihara, T Teter, B Ubeda, O Rostaing, P Triller, A Salem, N Ashe, KH Frautschy, SA Cole, GM TI Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model SO NEURON LA English DT Article ID AMYLOID-PRECURSOR-PROTEIN; POLYUNSATURATED FATTY-ACIDS; NICOTINIC ACETYLCHOLINE-RECEPTOR; LONG-TERM POTENTIATION; TRANSGENIC MICE; A-BETA; COGNITIVE IMPAIRMENT; LIPID-PEROXIDATION; PHOSPHATIDYLINOSITOL 3-KINASE; POSTSYNAPTIC DENSITY-95 AB Learning and memory depend on dendritic spine actin assembly and docosahexaenoic acid (DHA), an essential n-3 (omega-3) polyunsaturated fatty acid (PFA). High DHA consumption is associated with reduced Alzheimer's disease (AD) risk, yet mechanisms and therapeutic potential remain elusive. Here, we report that reduction of dietary n-3 PFA in an AD mouse model resulted in 80%-90% losses of the p85alpha subunit of phosphatidylinositol 3-kinase and the postsynaptic actin-regulating protein drebrin, as in AD brain. The loss of postsynaptic proteins was associated with increased oxidation, without concomitant neuron or presynaptic protein loss. N-3 PFA depletion increased caspase-cleaved actin, which was localized in dendrites ultrastructurally. Treatment of n-3 PFA-restricted mice with DHA protected against these effects and behavioral deficits and increased antiapoptotic BAD phosphorylation. Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially AD. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA 91343 USA. INSERM, Lab Biol Cellulaire Synapse Normale & Pathol, U497, Ecole Normale Super, F-75005 Paris, France. NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, Rockville, MD 20852 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. RP Cole, GM (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. EM gmcole@ucla.edu FU NIA NIH HHS [P50 AG05142, AG10685, AG16793, P01 AG16570, P50 AG 16570, P50 AG005142, P50 AG016570, R01 AG010685, R01 AG013741, R01 AG016793, R01 AG13741]; NINDS NIH HHS [NS43946, R01 NS043946] NR 81 TC 433 Z9 458 U1 7 U2 49 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 2 PY 2004 VL 43 IS 5 BP 633 EP 645 DI 10.1016/j.neuron.2004.08.013 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 851NN UT WOS:000223691900010 PM 15339646 ER PT J AU Ingelsson, M Jesneck, J Irizarry, MC Hyman, BT Rebeck, GW AF Ingelsson, M Jesneck, J Irizarry, MC Hyman, BT Rebeck, GW TI Lack of association of the cholesterol 24-hydroxylase (CYP46) intron 2 polymorphism with Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE lipoprotein; genetics; LXR; efflux; APOE; neuropathology; amyloid ID BETA-SECRETASE; IN-VIVO; RISK; A-BETA-42; BRAIN; ACCUMULATION; DIAGNOSIS; PROTEIN; GENE AB An association was recently reported between an increased risk of Alzheimer's disease and an intron 2 AA genotype of CYP46, the enzyme hydroxylating cholesterol to 24S-hydroxycholesterol. Moreover, CYP46 AA-carriers were found to have increased levels of amyloid-beta and tau in brain and cerebrospinal fluid. We determined the CYP46 intron 2 genotype in a cohort of 178 AD and 105 non-demented control subjects, but found no significant association with AD for any of the individual genotypes or alleles. Further, in an autopsy confirmed subset of this cohort, the proposed CYP46 risk genotype was not associated with any increase in the brain levels of amyloid-beta40, amyloid-beta42 or in the levels of amyloid plaques and neurofibrillary tangles. Despite growing evidence implicating cholesterol metabolism in AD risk and Abeta generation, our data does not support a robust genetic relationship between the CYP46 intron 2 polymorphism and AD risk or neuropathology. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Georgetown Univ, Dept Neurosci, Box 571464,3970 Reservoir Rd,NW, Washington, DC 20057 USA. EM gwr2@georgetown.edu FU NIA NIH HHS [AG05134, AG14473] NR 21 TC 31 Z9 35 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 2 PY 2004 VL 367 IS 2 BP 228 EP 231 DI 10.1016/j.neulet.2004.06.011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 852UW UT WOS:000223783200022 PM 15331159 ER PT J AU Betancourt, JR AF Betancourt, JR TI Becoming a physician: Cultural competence - Marginal or mainstream movement? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Betancourt, JR (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 3 TC 108 Z9 112 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 2 PY 2004 VL 351 IS 10 BP 953 EP 955 DI 10.1056/NEJMp048033 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 850UB UT WOS:000223637400002 PM 15342800 ER PT J AU Hughes, KS Schnaper, LA Berry, D Cirrincione, C McCormick, B Shank, B Wheeler, J Champion, LA Smith, TJ Smith, BL Shapiro, C Muss, HB Winer, E Hudis, C Wood, W Sugarbaker, D Henderson, I C Norton, L AF Hughes, KS Schnaper, LA Berry, D Cirrincione, C McCormick, B Shank, B Wheeler, J Champion, LA Smith, TJ Smith, BL Shapiro, C Muss, HB Winer, E Hudis, C Wood, W Sugarbaker, D Henderson, I C Norton, L CA Canc Leukemia Grp B Radiation Therapy Oncology Grp Eastern Cooperative Oncology Grp TI Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CONSERVATIVE SURGERY; RADIATION-THERAPY; CLINICAL-TRIALS; RANDOMIZED-TRIAL; TOTAL MASTECTOMY; CARCINOMA AB BACKGROUND: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival. RESULTS: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. CONCLUSIONS: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer. C1 Massachusetts Gen Hosp, Div Surg Oncol, Avon Comprehens Breast Evaluat Ctr, Breast Ovarian Canc Genet & Risk Assessment Progr, Boston, MA 02114 USA. Greater Baltimore Med Ctr, Baltimore, MD USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mt Sinai Sch Med, New York, NY USA. Sutter Hlth, Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. Morristown Mem Hosp, Morristown, NJ USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Vermont, Burlington, VT USA. Dana Farber Partners Canc Ctr, Boston, MA USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Calif San Francisco, Mountain View, CA USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Avon Comprehens Breast Evaluat Ctr, Breast Ovarian Canc Genet & Risk Assessment Progr, 100 Blossom St,Cox 626, Boston, MA 02114 USA. EM kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU NCI NIH HHS [CA21060, CA02599, CA03927, CA04326, CA04457, CA07968, CA08025, CA11789, CA12046, CA12449, CA26806, CA31946, CA31983, CA32291, CA33601, CA35279, CA37135, CA41287, CA47545, CA47555, CA47559, CA47577, CA60138, CA74811, CA77298, CA77406, CA77440, CA77651, CA77658] NR 22 TC 454 Z9 474 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 2 PY 2004 VL 351 IS 10 BP 971 EP 977 DI 10.1056/NEJMoa040587 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 850UB UT WOS:000223637400007 PM 15342805 ER PT J AU Welt, CK Chan, JL Bullen, J Murphy, R Smith, P DePaoli, AM Karalis, A Mantzoros, CS AF Welt, CK Chan, JL Bullen, J Murphy, R Smith, P DePaoli, AM Karalis, A Mantzoros, CS TI Recombinant human leptin in women with hypothalamic amenorrhea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; ANOREXIA-NERVOSA; BONE METABOLISM; BODY-FAT; NEUROENDOCRINE; OBESITY; DEFICIENCY; THERAPY; WEIGHT; ONSET AB BACKGROUND: Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. METHODS: Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (+/-SD) of 8.5+/-8.1 months. RESULTS: Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH levels and LH pulse frequency after two weeks and increased maximal follicular diameter, the number of dominant follicles, ovarian volume, and estradiol levels over a period of three months. Three patients had an ovulatory menstrual cycle (P<0.05 for the comparison with an expected rate of spontaneous ovulation of 10 percent); two others had preovulatory follicular development and withdrawal bleeding during treatment (P<0.05). Recombinant leptin significantly increased levels of free triiodothyronine, free thyroxine, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, bone alkaline phosphatase, and osteocalcin but not cortisol, corticotropin, or urinary N-telopeptide. CONCLUSIONS: Leptin administration for the relative leptin deficiency in women with hypothalamic amenorrhea appears to improve reproductive, thyroid, and growth hormone axes and markers of bone formation, suggesting that leptin, a peripheral signal reflecting the adequacy of energy stores, is required for normal reproductive and neuroendocrine function. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, 330 Brookline Ave,Stoneman 816, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-1066, M01-RR-01032]; NHLBI NIH HHS [K30-HL-04095]; NIDDK NIH HHS [DK-58785, P30 DK40561] NR 40 TC 421 Z9 437 U1 2 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 SEP 2 PY 2004 VL 351 IS 10 BP 987 EP 997 DI 10.1056/NEJMoa040388 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 850UB UT WOS:000223637400009 PM 15342807 ER PT J AU Tsao, H Atkins, MB Sober, AJ AF Tsao, H Atkins, MB Sober, AJ TI Medical progress - Management of cutaneous melanoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SENTINEL LYMPH-NODE; COOPERATIVE-ONCOLOGY-GROUP; HIGH-DOSE INTERFERON-ALPHA-2B; HIGH-RISK MELANOMA; THICK GREATER-THAN-OR-EQUAL-TO-4-MM MELANOMA; RANDOMIZED CONTROLLED TRIALS; METASTATIC MELANOMA; MALIGNANT-MELANOMA; PHASE-III; PROGNOSTIC-FACTORS C1 Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Biol Therapy Program, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Cutaneous Oncol Program, Boston, MA 02215 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, BArtlett 622,48 Blossom St, Boston, MA 02114 USA. NR 119 TC 494 Z9 512 U1 0 U2 20 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 2 PY 2004 VL 351 IS 10 BP 998 EP 1012 DI 10.1056/NEJMra041245 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 850UB UT WOS:000223637400010 PM 15342808 ER PT J AU Shaffer, K Small, JE AF Shaffer, K Small, JE TI Blended learning in medical education: Use of an integrated approach with web-based small group modules and didactic instruction for teaching radiologic anatomy SO ACADEMIC RADIOLOGY LA English DT Article DE medical education; web-based education; radiologic anatomy ID GROSS-ANATOMY; CLINICAL-ANATOMY; HEALTH-CARE; CURRICULUM; DEPARTMENTS; SCHOOL; INFORMATION; DISSECTION; STUDENTS; PROFILE AB Rationale and Objectives. To describe the development of and assess student satisfaction with a blended learning method for teaching radiologic anatomy that integrates web-based instruction with small group and didactic teaching. Materials and Methods. In 2002 the teaching of radiologic anatomy to first-year medical students was changed from Group learning (20-30 students with a preceptor and films at a viewbox) to a blended learning model that included a brief didactic introduction followed by small group (7-8 students) web-based structured learning modules with rotating tab instructors. In 2003 the modules were changed to include self-study cases prior to the lab, follow-up cases, and twice-weekly optional review sessions. Students and lab instructors were surveyed for their response to the content and design of the sessions. Results. Course surveys in 2001, with a response rate of 84%, showed 58 negative comments regarding inconsistency between various instructors.. Individual response rates for 2002 for radiologic anatomy teaching sessions (RadLab) surveys ranged from 56%-81%. dropping as the course progressed. All RadLabs were rated "very useful" or "useful," except the cardiovascular lab, which was not designed as an interactive module. In 2003, after redesign of the cardiovascular lab in the same format as the other labs, all RadLabs were rated 2.4 or better (useful). Conclusion. An integration of computers with small and large group didactic instruction allow optimal use of faculty, conform to accepted theories of adult learning, and are well-accepted by students. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shaffer, K (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM kshaffer@partners.org OI Shaffer, Kitt/0000-0001-6488-6988 NR 34 TC 49 Z9 52 U1 5 U2 37 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2004 VL 11 IS 9 BP 1059 EP 1070 DI 10.1016/j.acra.2004.05.018 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 854UN UT WOS:000223929000012 PM 15350588 ER PT J AU Kampov-Polevoy, AB Eick, C Boland, G Khalitov, E Crews, FT AF Kampov-Polevoy, AB Eick, C Boland, G Khalitov, E Crews, FT TI Sweet liking, novelty seeking, and gender predict alcoholic status SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE sweet liking; novelty seeking; alcoholism; genetic risk ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; PITUITARY BETA-ENDORPHIN; SUBSTANCE USE DISORDERS; FAMILY-HISTORY; DISINHIBITORY PSYCHOPATHOLOGY; OPIOID INVOLVEMENT; SENSATION SEEKING; HEDONIC RESPONSE; SACCHARIN INTAKE; TASTE RESPONSES AB Background: The relationship between a hedonic response to sweet taste and a propensity to excessive alcohol drinking is supported by both animal and human studies. There is evidence indicating that the tendency to rate more concentrated sweet solutions as the most pleasurable (i.e., sweet liking) is associated with the genetic vulnerability to alcoholism. However, sweet liking by itself is insufficient to predict the alcoholic status of the individual. Our previous study indicated that alcoholic status can be predicted by a combination of hedonic response to sweet taste and personality profile as measured by the Tridimensional Personality Questionnaire (TPQ). This study was designed to further test this hypothesis. Methods: Participants were 165 patients admitted to a residential treatment program for the treatment of alcoholism, drug dependence and/or interpersonal problems secondary to substance-abusing family members. In addition to a routine medical examination, on the 24th day after admission, patients completed the TPQ, the standard sweet taste test was conducted, and paternal family history of alcoholism was evaluated. Results: Sweet liking was strongly associated with a paternal history of alcoholism. The odds of receiving an alcohol dependence diagnosis were shown to increase, on the average, by 11% for every one-point increase in the TPQ novelty-seeking score in sweet-liking but not in sweet-disliking subjects. Gender contributed independently to the probability of alcohol dependence, with males exhibiting higher rates of alcoholism than females. Conclusions: These findings support the hypothesis that a hedonic response to sweet taste is associated with a genetic risk for alcoholism. Alcoholic status may be predicted by a combination of sweet liking, the TPQ novelty-seeking score, and gender in a mixed group of alcoholic, polysubstance-dependent, and psychiatric patients. C1 Bronx Vet Affairs Med Ctr, Div Addict Psychiat, Mt Sinai Sch Med, Bronx, NY 10468 USA. Pavillon Int, Mill Spring, NC USA. Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27515 USA. RP Kampov-Polevoy, AB (reprint author), Bronx Vet Affairs Med Ctr, Div Addict Psychiat, Mt Sinai Sch Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kampov@earthlink.net NR 85 TC 54 Z9 55 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2004 VL 28 IS 9 BP 1291 EP 1298 DI 10.1097/01.ALC.0000137808.69482.75 PG 8 WC Substance Abuse SC Substance Abuse GA 856VV UT WOS:000224074300003 PM 15365298 ER PT J AU Ramirez, FC Holland, JF Harker, J Leung, FW AF Ramirez, FC Holland, JF Harker, J Leung, FW TI Effect of acid on duodenal blood flow and mucus secretion measured by reflectance spectrophotometry: a prospective, randomized-controlled study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RAT DUODENUM; MUCOSAL HEMODYNAMICS; ADAPTIVE CYTOPROTECTION; GASTRODUODENAL MUCOSA; ENDOSCOPIC ASSESSMENT; GEL THICKNESS; GASTRIC-ULCER; INJURY; ACIDIFICATION AB Background: In animals, hydrochloric acid increases blood flow and mucus secretion in the duodenal mucosa. A significant correlation between index of haemoglobin oxygen saturation and mucosal blood flow, and between change in index of haemoglobin concentration and mucus thickness, respectively, has been demonstrated by reflectance spectrophotometry. Aim: To examine the effect of topical hydrochloric acid upon mucosal blood flow and mucus secretion in the human duodenum. Methods: This prospective study of 120 patients undergoing routine upper endoscopy, examined the effect of topical 0.1 N hydrochloric acid or 0.9% saline on the duodenal bulb in a randomized, double-blind fashion. Duodenal mucosal index of haemoglobin oxygen saturation and index of haemoglobin concentration were measured by endoscopic reflectance spectrophotometry before and after hydrochloric acid or saline. Results: Baseline index of haemoglobin oxygen saturation, calculated blood flow and index of haemoglobin concentration measurements were comparable between hydrochloric acid (n = 60) and saline (n =60) treated groups. A history of current use of non-steroidal anti-inflammatory drug was associated with a significantly lower baseline index of haemoglobin oxygen saturation and calculated blood flow. Hydrochloric acid resulted in a significant increase in index of haemoglobin oxygen saturation and calculated blood flow, but a decrease in index of haemoglobin concentration, reflecting an increase in mucus thickness compared with saline. Conclusions: Our observations in humans confirm data in animal studies that topical exposure to hydrochloric acid induces an increase in duodenal mucosal blood flow and mucus secretion. Post hoc analysis of the data also revealed that attenuation of basal duodenal mucosal blood flow is associated with a history of current non-steroidal anti-inflammatory drug use. Endoscopic reflectance spectrophotometry appears to be adequate to assess factors that influence duodenal defence mechanisms of blood flow and mucus secretion in humans. C1 Carl T Hayden VA Med Ctr, Res & Med Serv, Phoenix, AZ 85012 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Los Angeles, CA USA. RP Ramirez, FC (reprint author), Carl T Hayden VA Med Ctr, Res & Med Serv, 650 E Indian Sch Rd, Phoenix, AZ 85012 USA. EM francisco.ramirez2@med.va.gov NR 41 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD SEP 1 PY 2004 VL 20 IS 5 BP 517 EP 525 DI 10.1111/j.1365-2036.2004.02122.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 850VR UT WOS:000223643000004 PM 15339323 ER PT J AU Jewell, KD Black, DA Bankson, DD AF Jewell, KD Black, DA Bankson, DD TI Comparison of chemiluminescent and enzyme immunoassays for the detection of hepatitis B core antibody. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 83nd ASCP Annual Meeting CY OCT, 2004 CL San Antonio, TX SP ASCP C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Lab Med, Seattle, WA USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2004 VL 122 IS 3 MA 9 BP 456 EP 456 PG 1 WC Pathology SC Pathology GA 849RO UT WOS:000223558500023 ER PT J AU Luckey, CJ Goldrath, AW Benoist, C Mathis, D AF Luckey, CJ Goldrath, AW Benoist, C Mathis, D TI Memory-specific transcripts in CD8+T cells are enriched in long-term hematopoietic stem cells. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 83nd ASCP Annual Meeting CY OCT, 2004 CL San Antonio, TX SP ASCP C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2004 VL 122 IS 3 MA 11 BP 456 EP 456 PG 1 WC Pathology SC Pathology GA 849RO UT WOS:000223558500024 ER PT J AU Wigren, C Clarridge, JE AF Wigren, C Clarridge, JE TI Translating 16S rDNA sequencing identification into cost effective phenotypic testing. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 83nd ASCP Annual Meeting CY OCT, 2004 CL San Antonio, TX SP ASCP C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2004 VL 122 IS 3 MA 12 BP 456 EP 457 PG 2 WC Pathology SC Pathology GA 849RO UT WOS:000223558500025 ER PT J AU Allison, KH Black, DA Garbin, J Bankson, DD AF Allison, KH Black, DA Garbin, J Bankson, DD TI Evaluation of a specific oxycodone assay for urine drug of abuse screening. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 83nd ASCP Annual Meeting CY OCT, 2004 CL San Antonio, TX SP ASCP C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Lab Med, Seattle, WA USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2004 VL 122 IS 3 MA 14 BP 457 EP 458 PG 2 WC Pathology SC Pathology GA 849RO UT WOS:000223558500027 ER PT J AU Abraham, NS Fallone, CA Mayrand, S Huang, J Wieczorek, P Barkun, AN AF Abraham, NS Fallone, CA Mayrand, S Huang, J Wieczorek, P Barkun, AN TI Sedation versus no sedation in the performance of diagnostic upper gastrointestinal endoscopy: A Canadian randomized controlled cost-outcome study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Diseases Week 2003 CY 2003 CL Orlando, FL ID CONSCIOUS SEDATION; PATIENT TOLERANCE; NATIONWIDE SURVEY; THROAT SPRAY; ESOPHAGOGASTRODUODENOSCOPY; GASTROSCOPY AB BACKGROUND: Sedation is not required to perform a technically adequate gastroscopy (EGDE), but does improve patient satisfaction, comfort, and willingness to repeat particularly in the elderly and those with decreased pharyngeal sensitivity. The comparative cost-efficacy of sedation versus no sedation remains poorly characterized. AIM: To compare the cost-efficacy of diagnostic EGDE with and without sedation in an adult ambulatory Canadian population. METHODS: A double-blind randomized controlled trial assigned patients to sedation versus placebo. "Successful endoscopy" was considered an EGDE rated 4/4 in technical adequacy (1 = inadequate to 4 = totally adequate), and 1-2/5 in patient self-reported comfort (1 = acceptable to 5 = unacceptable). Secondary outcomes included recovery room time, patient satisfaction alone, and willingness to repeat the procedure. Cost data were obtained using a published, institutional activity-based costing methodology. Analysis was intention to treat using standard univariate and multivariate methods. RESULTS: 419 patients (mean age 54.5, 48% male) were randomized (N = 210 active vs N = 209 placebo). Among patients randomized to active medication 76% of procedures were "successful" (placebo 46%), 79% were satisfied with their level of comfort (placebo 47%), and willingness to repeat was 81% (placebo 65%). We observed a 10% crossover rate from placebo to active medications. The use of sedation was the major determinant of successful endoscopy (OR = 3.8; 95% Cl: 2.5-5.7), but contributed to an increased recovery room time (29 vs 15 min; p < 0.0001). The expected cost of an additional successful endoscopy using sedation was $90.06 (CDN). In a planned subgroup analysis, among the elderly (>75; N = 53) unsedated endoscopy became the dominant approach. Indeed, in this population, a trend was observed favoring the effectiveness of placebo (63%) versus active medication (57%) (OR = 0.75; 95% Cl: 0.25-2.3) and was less costly resulting in $450 savings/unsedated EGDE. CONCLUSIONS: In the average Canadian ambulatory adult population, sedated diagnostic EGDE is more costly but remains an efficacious strategy by increasing the rate of successful endoscopies, patient satisfaction, and willingness to repeat. However, among the elderly (>75 yr), an unsedated strategy may be more cost-efficacious. C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. McGill Univ, Ctr Hlth, Div Gastroenterol, Montreal, PQ, Canada. McGill Univ, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ, Canada. RP Abraham, NS (reprint author), Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Div Gastroenterol, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 63 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2004 VL 99 IS 9 BP 1692 EP 1699 DI 10.1111/j.1572-0241.2004.40157.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 850XY UT WOS:000223648900014 PM 15330904 ER PT J AU Kanwal, F Hays, RD Kilbourne, AM Dulai, GS Gralnek, IM AF Kanwal, F Hays, RD Kilbourne, AM Dulai, GS Gralnek, IM TI Are physician-derived disease severity indices associated with health-related quality of life in patients with end-stage liver disease? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; CLINICAL-PRACTICE; MEDICAL OUTCOMES; VIRUS-INFECTION; INSTRUMENT; ALLOCATION; CIRRHOSIS; IMPACT; SYSTEM; MODEL AB OBJECTIVES: Model for end-stage liver disease (MELD) score is now often used as an overall indicator of health status for patients with end-stage liver disease. However, there are no data evaluating the associations between MELD scores and patient reports of health-related quality of life (HRQOL). METHODS: Two hundred-three patients with end-stage liver disease completed a disease-targeted HRQOL instrument (the LDQOL 1.0). Patients also rated the severity of their liver disease and reported number of disability days attributed to their liver disease in the preceding month. MELD and Child Turcott Pugh (CTP) scores were calculated for all patients. Associations of MELD and CTP scores with patient-derived outcomes were estimated. RESULTS: The mean MELD and CTP scores were 12 and 7, respectively, indicating mild severity of liver disease. HRQOL of patients was generally poor, with the mean SF-36 physical and mental component summary scores of 35 and 40. Seventy percent of patients rated their liver disease symptoms as moderate to severe. Similarly, 70% reported being disabled from their liver disease. MELD was associated with physical functioning scale and the physical component summary (PCS) score in patients with end-stage liver disease. In contrast, CTP score was significantly associated with physical functioning, role limitations due to physical health problems, PCS score, effects of liver disease, sexual functioning, and sexual problems. Both MELD and CTP scores correlated with self-rated severity of liver disease symptoms but not with self-reported disability days. CONCLUSIONS: Despite objectively mild liver disease, the subjective HRQOL of this cohort was severely impaired. CTP score was more closely associated with patient-reported estimates of HRQOL than the MELD score. CTP or disease-specific HRQOL instruments may compliment MELD by providing insights into outcomes of importance to patients with low risk of mortality. C1 Univ Calif Los Angeles, Ctr Study Digest Healthcare Qual & Outcomes, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Pittsburgh, CURE Digest Dis Res Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Study Digest Healthcare Qual & Outcomes, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Neurovisceral Sci & Womens Hlth, Pittsburgh, PA USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equit Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. UCLA Ctr Hlth Sci, Div Digest Dis, Los Angeles, CA USA. UCLA Div Internal Med Hlth Serv Res, Los Angeles, CA USA. RAND Corp, Hlth Sci Program, Santa Monica, CA USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, Ctr Study Digest Healthcare Qual & Outcomes, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd CURE Bldg 115,Room 215, Los Angeles, CA 90073 USA. RI Hays, Ronald/D-5629-2013 NR 37 TC 49 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2004 VL 99 IS 9 BP 1726 EP 1732 DI 10.1111/j.1572-0241.2004.30300.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 850XY UT WOS:000223648900020 PM 15330910 ER PT J AU Durcan, MJ Johnston, JA White, J Gonzales, D Sachs, DPL Rigotti, N Niaura, R AF Durcan, MJ Johnston, JA White, J Gonzales, D Sachs, DPL Rigotti, N Niaura, R TI Bupropion SR for relapse prevention: A "slips-allowed" analysis SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE bupropion; smoking cessation; relapse prevention; slips allowed analysis ID SMOKING CESSATION; SUSTAINED-RELEASE; ABSTINENCE; PREDICTORS AB Objective: To assess the efficacy of bupropion SR on smoking abstinence using a "slips allowed" analysis. Methods: Retrospective analysis, which did not consider brief episodic "slips" as a return to regular smoking, of data from a multicenter, randomized, double-blind, placebo-controlled relapse prevention study. Results: Using a slips-allowed analysis, median time to relapse on bupropion SR was 65 weeks versus 30 weeks on placebo. This is compared to 32 and 20 weeks, respectively, using a traditional analysis not allowing for slips. Conclusion: Bupropion SR is efficacious for the prevention of smoking relapse. A slips-allowed analysis may provide a more clinically relevant assessment of efficacy. C1 GlaxoSmithKline, Parsippany, NJ 07054 USA. Innovaa Res, Chapel Hill, NC USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Oregon Hlth Sci Univ, Smoking Cessaton Serv, Portland, OR 97201 USA. Palo Alto Ctr Pulm Dis Prevent, Palo Alto, CA USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Miriam Hosp, Ctr Behav Med, Providence, RI 02906 USA. RP Durcan, MJ (reprint author), GlaxoSmithKline, 1500 Littleton Rd, Parsippany, NJ 07054 USA. EM Michael.J.Durcan@GSK.com NR 15 TC 8 Z9 8 U1 0 U2 0 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD SEP-OCT PY 2004 VL 28 IS 5 BP 456 EP 463 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 891AX UT WOS:000226554800008 PM 15482975 ER PT J AU Abroms, LC Fagan, P Eisenberg, ME Lee, HSH Remba, N Sorensen, G AF Abroms, LC Fagan, P Eisenberg, ME Lee, HSH Remba, N Sorensen, G TI The STRENGTH Ezine: An application of e-mail for health promotion in adolescent girls SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE e-mail; Internet; health promotion; adolescents; cancer prevention ID INTERNET; QUESTIONNAIRE; COMMUNICATION; PROGRAM; YOUTH AB Purpose. Few studies have investigated the efficacy of e-mail for promoting behavior change. This study evaluates the participation in and outcomes associated with an e-mail-based health promotion program. Methods. Adolescent girls aged 15 to 17 years were recruited at a shopping mall. Participants with an e-mail address were assigned to the interactive e-mail magazine (Ezine) group (n = 37), whereas those not reporting an e-mail address were assigned to the non-Ezine group (n = 33). Participants in the Ezine group received the health Ezine, which included a quiz and an advice column, on a weekly basis. Results. Results indicate that among the Ezine group, there was a high recall of the Ezine (81.1%), and more than one third of the participants replied to Ezine volumes with quiz answers or an advice question (36.6%). Differences in health behavior change between the Ezine and non-Ezine groups were not significant. Conclusions. E-mails on health-related matters can generate moderate levels of involvement in adolescent girls. Given the widespread use of e-mail, more studies are needed on the effective application of e-mail for health behavior change. C1 George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, Washington, DC 20037 USA. NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Minnesota, Div Gen Pediat & Adolescent Med, Natl Teen Pregnancy Prevent Res Ctr, Minneapolis, MN USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Abroms, LC (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, 2175 K St NW,Room 7015, Washington, DC 20037 USA. EM sphlca@gwumc.edu NR 14 TC 9 Z9 9 U1 1 U2 4 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2004 VL 19 IS 1 BP 28 EP 32 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 853OR UT WOS:000223837400005 PM 15460098 ER PT J AU Long, KZ Nanthakumar, N AF Long, KZ Nanthakumar, N TI Energetic and nutritional regulation of the adaptive immune response and trade-offs in ecological immunology SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID VITAMIN-A-DEFICIENCY; ENTEROTOXIGENIC ESCHERICHIA-COLI; T-CELL SUBPOPULATIONS; ORAL CHOLERA VACCINE; DENDRITIC CELLS; MEXICAN CHILDREN; ZINC-DEFICIENCY; EVOLUTIONARY ECOLOGY; CYTOKINE PRODUCTION; IMMUNOGLOBULIN-A AB Ecological Immunology views immunocompetence as a costly process involving trade-off decisions among competing nutrient demands by different life-history traits. This review examines immunocompetence fitness costs in light of recent work on the role the energetic and nutritional status of the host plays in the regulation of the adaptive T-helper lymphocyte response. Three phenotypically distinct T-lymphocyte populations have been identified: the Th1 response, important in protecting against intracellular infections; the Th2 response, important in protecting against noninvasive infections such as helminthes; and the Th3 or Treg population, which down-regulates polarized Th1 or Th2 responses. A strong Th1 response is protective against intracellular infections, while a Th2 response is protective against noninvasive infections. Adequate zinc and energy intake leads to a dominant Th1 response and a downregulated Th2 response, while deficiencies of either of these results in activation of the Th2 response and downregulation of the Th1 response. In contrast, adequate vitamin A intake leads to an activated Th2 response and downregulation of the Th1 response, while vitamin A deficiency reverses these patterns. These differential immune regulatory effects of energy and nutrient intake will have distinct effects on specific stages of the natural history of different pathogen infections where the protective roles of the Th1-Th2 responses are distinct. Accordingly, fitness costs of immunocompetence are more complex than currently proposed since trade-offs in energetic and nutritional resources produce cross-regulatory effects on immune system subcomponents. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Long, KZ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 1663 Tremont St, Boston, MA 02115 USA. EM klong@hsph.harvard.edu FU NIDDK NIH HHS [K01 DK06142-02] NR 69 TC 37 Z9 42 U1 0 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD SEP-OCT PY 2004 VL 16 IS 5 BP 499 EP 507 DI 10.1002/ajhb.20064 PG 9 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 849DH UT WOS:000223518400001 PM 15368598 ER PT J AU Wijsman, EM Daw, EW Yu, CE Payami, H Steinbart, EJ Nochlin, D Conlon, EM Bird, TD Schellenberg, GD AF Wijsman, EM Daw, EW Yu, CE Payami, H Steinbart, EJ Nochlin, D Conlon, EM Bird, TD Schellenberg, GD TI Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID 2-LOCUS LINKAGE ANALYSIS; RECEPTOR-RELATED PROTEIN; RNA-BINDING PROTEINS; AGE-OF-ONSET; APOLIPOPROTEIN-E; GENETIC-LINKAGE; MISSENSE MUTATIONS; EXTENDED PEDIGREES; MARKOV-CHAINS; TYPE-4 ALLELE AB Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and complex disease for which only one locus, APOE, has been definitively identified. Difficulties in identifying additional loci are likely to stem from inadequate linkage analysis methods. Nonparametric methods suffer from low power because of limited use of the data, and traditional parametric methods suffer from limitations in the complexity of the genetic model that can be feasibly used in analysis. Alternative methods that have recently been developed include Bayesian Markov chain Monte Carlo methods. These methods allow multipoint linkage analysis under oligogenic trait models in pedigrees of arbitrary size; at the same time, they allow for inclusion of covariates in the analysis. We applied this approach to an analysis of LOFAD on five chromosomes with previous reports of linkage. We identified strong evidence of a second LOFAD gene on chromosome 19p13.2, which is distinct from APOE on 19q. We also obtained weak evidence of linkage to chromosome 10 at the same location as a previous report of linkage but found no evidence for linkage of LOFAD age-at-onset loci to chromosomes 9, 12, or 21. C1 Univ Washington, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Neuropathol Lab, Seattle, WA 98104 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Wijsman, EM (reprint author), Univ Washington, Div Med Genet, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu FU NIA NIH HHS [R01 AG021544, AG 08017, AG 21544, P50 AG005136, R01 AG011762, U24 AG021886, R37 AG011762, AG 05136, AG 11762, P30 AG008017]; NIGMS NIH HHS [R01 GM046255, GM 46255, R37 GM046255] NR 75 TC 74 Z9 77 U1 0 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 SEP PY 2004 VL 75 IS 3 BP 398 EP 409 DI 10.1086/423393 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 845VA UT WOS:000223272200005 PM 15248153 ER PT J AU Kyogoku, C Langefeld, CD Ortmann, WA Lee, A Selby, S Carlton, VEH Chang, M Ramos, P Baechler, EC Batliwalla, FM Novitzke, J Williams, AH Gillett, C Rodine, P Graham, RR Ardlie, KG Gaffney, PM Moser, KL Petri, M Begovich, AB Gregersen, PK Behrens, TW AF Kyogoku, C Langefeld, CD Ortmann, WA Lee, A Selby, S Carlton, VEH Chang, M Ramos, P Baechler, EC Batliwalla, FM Novitzke, J Williams, AH Gillett, C Rodine, P Graham, RR Ardlie, KG Gaffney, PM Moser, KL Petri, M Begovich, AB Gregersen, PK Behrens, TW TI Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELL SIGNAL-TRANSDUCTION; RHEUMATOID-ARTHRITIS; T-CELLS; KINASE; COHORT; MICE; PEP AB We genotyped 525 independent North American white individuals with systemic lupus erythematosus (SLE) for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 white control individuals. The R620W SNP was associated with SLE (genotypic P=.00009), with estimated minor (T) allele frequencies of 12.67% in SLE cases and 8.64% in controls. A single copy of the T allele (W620) increases risk of SLE (odds ratio [OR]=1.37; 95% confidence interval [CI] 1.07-1.75), and two copies of the allele more than double this risk (OR=4.37; 95% CI 1.98-9.65). Together with recent evidence showing association of this SNP with type 1 diabetes and rheumatoid arthritis, these data provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity. C1 Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Wake Forest Univ, Bowman Gray Sch Med, Biostat Sect, Winston Salem, NC USA. N Shore Long Isl Jewish Res Inst, Robert S Boas Ctr Genom & Genet, Manhasset, NY USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Genom Collaborat Inc, Cambridge, MA USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Behrens, TW (reprint author), Univ Minnesota, Sch Med, Dept Med, 6-126 Basic Sci Biomed Engn Bldg,312 Church St SE, Minneapolis, MN 55455 USA. EM behre001@umn.edu RI Gillespie, Emily/N-1265-2013 OI Gillespie, Emily/0000-0001-5261-3931 FU NCRR NIH HHS [M01-RR00052, M01 RR000052]; NIAMS NIH HHS [R01 AR043727, R01 AR32274, R01 AR43727] NR 15 TC 428 Z9 441 U1 1 U2 12 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 SEP PY 2004 VL 75 IS 3 BP 504 EP 507 DI 10.1086/423790 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 845VA UT WOS:000223272200015 PM 15273934 ER PT J AU Park, HJ Kubicki, M Westin, CF Talos, IF Brun, A Peiper, S Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Park, HJ Kubicki, M Westin, CF Talos, IF Brun, A Peiper, S Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI Method for combining information from white matter fiber tracking and gray matter parcellation SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SURFACE-BASED ANALYSIS; DIFFUSION TENSOR; ECHO AB We introduce a method for combining fiber tracking from diffusion-tensor (DT) imaging with cortical gray matter parcellation from structural high-spatial-resolution 3D spoiled gradient-recalled acquisition in the steady state images. We applied this method to a tumor case to determine the impact of the tumor on white matter architecture. We conclude that this new method for combining structural and DT imaging data is useful for understanding cortical connectivity and the localization of fiber tracts and their relationship with cortical anatomy and brain abnormalities. C1 Boston VA Hlth Care Syst, Brockton Div, Clin Neurosci Div, Neurosci Lab,Dept Psychiat, Brockton, MA USA. Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, MR Imaging Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA USA. Yonsei Univ, Coll Med, Dept Diagnost Radiol, Seoul, South Korea. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst,Brockton Div, 116A,940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [P41 RR013218, P41 RR013218-030003, P41-RR13218, R01 RR011747, R01 RR011747-038223]; NIMH NIH HHS [R01 MH 50747, K02 MH 01110, K05 MH070047, K05 MH070047-01, R01 MH 40799, R01 MH040799, R01 MH040799-16, R01 MH050740, R01 MH050740-12, R03 MH068464, R03 MH068464-01] NR 12 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2004 VL 25 IS 8 BP 1318 EP 1324 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 857IO UT WOS:000224110000004 PM 15466325 ER PT J AU Gupta, R Bartling, SH Basu, SK Ross, WR Becker, H Pfoh, A Brady, T Curtin, HD AF Gupta, R Bartling, SH Basu, SK Ross, WR Becker, H Pfoh, A Brady, T Curtin, HD TI Experimental flat-panel high-spatial-resolution volume CT of the temporal bone SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Neuroradiology CY MAY 11-17, 2002 CL Vancouver, CANADA SP Amer Soc Neuroradiol ID COMPUTED TOMOGRAPHIC EVALUATION; MIDDLE-EAR; IMPLANT AB BACKGROUND AND PURPOSE: A CT scanner employing a digital flat-panel detector is capable of very high spatial resolution as compared with a multi-section CT (MSCT) scanner. Our purpose was to determine how well a prototypical volume CT (VCT) scanner with a flat-panel detector system defines fine structures in temporal bone. METHODS: Four partially manipulated temporal-bone specimens were imaged by use of a prototypical cone-beam VCT scanner with a flat-panel detector system at an isometric resolution of 150 mum at the isocenter. These specimens were also depicted by state-of-the-art multisection CT (MSCT). Forty-two structures imaged by both scanners were qualitatively assessed and rated, and scores assigned to VCT findings were compared with those of MSCT. RESULTS: Qualitative assessment of anatomic structures, lesions, cochlear implants, and middle-ear hearing aids indicated that image quality was significantly better with VCT (P < .001). Structures near the spatial-resolution limit of MSCT (e.g., bony covering of the tympanic segment of the facial canal, the incudo-stapedial joint, the proximal vestibular aqueduct, the interscalar septum, and the modiolus) had higher contrast and less partial-volume effect with VCT. CONCLUSION: The flat-panel prototype provides better definition of fine osseous structures of temporal bone than that of currently available MSCT scanners. This study provides impetus for further research in increasing spatial resolution beyond that offered by the current state-of-the-art scanners. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. GE Global Res Ctr, Niskayuna, NY USA. Hannover Med Sch, Dept Neuroradiol, Hannover, Germany. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA USA. RP Gupta, R (reprint author), Dept Radiol, 14 Fruit St,Founders House 216, Boston, MA 02114 USA. NR 15 TC 63 Z9 65 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2004 VL 25 IS 8 BP 1417 EP 1424 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 857IO UT WOS:000224110000024 PM 15466345 ER PT J AU Wolfberg, AJ Michels, KB Shields, W O'Campo, P Bronner, Y Bienstock, J AF Wolfberg, AJ Michels, KB Shields, W O'Campo, P Bronner, Y Bienstock, J TI Dads as breastfeeding advocates: Results from a randomized controlled trial of an educational intervention SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE breastfeeding; fathers ID LOW-INCOME WOMEN; FATHERS ATTITUDES; PROMOTION PROGRAM; MOTHERS; KNOWLEDGE; INCREASE AB Objective: Recognizing that an expectant father may influence a mother's decision to breast- or formula-feed, we tested the effectiveness of a simple, educational intervention that was designed to encourage fathers to advocate for breastfeeding and to assist his partner if she chooses to breastfeed. Study design: We conducted a randomized controlled trial in which expectant fathers (n = 59) were assigned randomly to attend either a 2-hour intervention class on infant care and breastfeeding promotion (intervention) or a class on infant care only (control group). The classes, which were led by a peer-educator, were interactive and informal and utilized different media to create an accessible environment for participants. Couples were recruited during the second trimester from a university obstetrics practice. Results: Overall, breastfeeding was initiated by 74% of women whose partners attended the intervention class, as compared with 41% of women whose partners attended the control class (P = .02). Conclusion: Expectant fathers can be influential advocates for breastfeeding, playing a critical role in encouraging a woman to breastfeed her newborn infant. (C) 2004 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. Morgan State Univ, Publ Hlth Program, Baltimore, MD 21239 USA. Johns Hopkins Univ, Sch Med, Div Maternal Fetal Med, Dept Gynecol & Obstet, Baltimore, MD 21218 USA. RP Wolfberg, AJ (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM awolfberg@partners.org NR 16 TC 92 Z9 97 U1 0 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2004 VL 191 IS 3 BP 708 EP 712 DI 10.1016/j.ajog.2004.05.019 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 860EZ UT WOS:000224326600005 PM 15467529 ER PT J AU Kashyap, SR Belfort, R Berria, R Suraamornkul, S Pratipranawatr, T Finlayson, J Barrentine, A Bajaj, M Mandarino, L DeFronzo, R Cusi, K AF Kashyap, SR Belfort, R Berria, R Suraamornkul, S Pratipranawatr, T Finlayson, J Barrentine, A Bajaj, M Mandarino, L DeFronzo, R Cusi, K TI Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; free fatty acids; insulin signal transduction ID FREE FATTY-ACIDS; INTRAMYOCELLULAR LIPID-CONTENT; PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE ACTIVITY; SKELETAL-MUSCLE; GLUCOSE-UPTAKE; CARBOHYDRATE-METABOLISM; NONDIABETIC SUBJECTS; NIDDM PARENTS; RISK-FACTORS AB Muscle insulin resistance develops when plasma free fatty acids (FFAs) are acutely increased to supraphysiological levels (similar to1,500 - 4,000 mumol/l). However, plasma FFA levels >1,000 mumol/l are rarely observed in humans under usual living conditions, and it is unknown whether insulin action may be impaired during a sustained but physiological FFA increase to levels seen in obesity and type 2 diabetes mellitus (T2DM) (similar to600 - 800 mumol/l). It is also unclear whether normal glucose-tolerant subjects with a strong family history of T2DM (FH+) would respond to a low-dose lipid infusion as individuals without any family history of T2DM ( CON). To examine these questions, we studied 7 FH+ and 10 CON subjects in whom we infused saline ( SAL) or low- dose Liposyn ( LIP) for 4 days. On day 4, a euglycemic insulin clamp with [3-H-3] glucose and indirect calorimetry was performed to assess glucose turnover, combined with vastus lateralis muscle biopsies to examine insulin signaling. LIP increased plasma FFA similar to 1.5-fold, to levels seen in T2DM. Compared with CON, FH+ were markedly insulin resistant and had severely impaired insulin signaling in response to insulin stimulation. LIP in CON reduced insulin-stimulated glucose disposal (R-d) by 25%, insulin-stimulated insulin receptor tyrosine phosphorylation by 17%, phosphatidylinositol 3-kinase activity associated with insulin receptor substrate-1 by 20%, and insulin-stimulated glycogen synthase fractional velocity over baseline (44 vs. 15%; all P < 0.05). In contrast to CON, a physiological elevation in plasma FFA in FH+ led to no further deterioration in Rd or to any additional impairment of insulin signaling. In conclusion, a 4-day physiological increase in plasma FFA to levels seen in obesity and T2DM impairs insulin action/insulin signaling in CON but does not worsen insulin resistance in FH+. Whether this lack of additional deterioration in insulin signaling in FH+ is due to already well-established lipotoxicity, or to other molecular mechanisms related to insulin resistance that are nearly maximally expressed early in life, remains to be determined. C1 Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Diabet Div, Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu RI Bajaj, Mandeep/B-6060-2009; Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 FU NCRR NIH HHS [M01-RR-01346]; NIDDK NIH HHS [R01-DK-24092] NR 67 TC 52 Z9 55 U1 0 U2 2 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 SEP PY 2004 VL 287 IS 3 BP E537 EP E546 DI 10.1152/ajpendo.00541.2003 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 848CL UT WOS:000223444700020 PM 15126243 ER PT J AU Koutkia, P Canavan, B Breu, J Johnson, ML Grinspoon, SK AF Koutkia, P Canavan, B Breu, J Johnson, ML Grinspoon, SK TI Nocturnal ghrelin pulsatility and response to growth hormone secretagogues in healthy men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE approximate entropy; cross-approximate entropy; synchronicity ID PRADER-WILLI-SYNDROME; GH-RELEASING HORMONE; CIRCULATING GHRELIN; OCTREOTIDE THERAPY; ACYLATED PEPTIDE; MESSENGER-RNA; HUMAN OBESITY; WEIGHT-LOSS; SECRETION; HUMANS AB The physiological importance of endogenous ghrelin in the regulation of growth hormone (GH) secretion is still unknown. To investigate the regulation of ghrelin secretion and pulsatility, we performed overnight ghrelin and GH sampling every 20 min for 12 h in eight healthy male subjects [ age 37 +/- 5 (SD) years old, body mass index 27.2 +/- 2.9 kg/m(2)]. Simultaneous GH and ghrelin levels were assessed to determine the relatedness and synchronicity between these two hormones in the fasted state during the overnight period of maximal endogenous GH secretion. Pulsatility analyses were performed to determine simultaneous hormonal dynamics and investigate the relationship between GH and ghrelin by use of cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 3.0 +/- 2.1 ghrelin pulses/12 h and 3.3 +/- 0.9 GH pulses/12 h. The mean normalized ghrelin entropy (ApEn) was 0.93 +/- 0.09, indicating regularity in ghrelin hormone secretion. The mean normalized X-ApEn was significant between ghrelin and GH (0.89 +/- 0.12), demonstrating regularity in cosecretion. In addition, we investigated the ghrelin response to standard GH secretagogues [GH-releasing hormone ( GHRH) alone and combined GHRH-arginine] in separate testing sequences separated by 1 wk. Our data demonstrate that, in contrast to GHRH alone, which had little effect on ghrelin, combined GHRH and arginine significantly stimulated ghrelin with a maximal peak at 120 min, representing a change of 66 +/- 14 pg/ml ( P = 0.001 by repeated- measures ANOVA and P = 0.02 for GHRH vs. combined GHRH-arginine by MANOVA). We demonstrate relatedness between ghrelin and GH pulsatility, suggesting either that ghrelin participates in the pulsatile regulation of GH or that the two hormones are simultaneously coregulated, e. g., by somatostatin or other stimuli. Furthermore, the differential effects of GHRH alone vs. GHRH-arginine suggest that inhibition of somatostatin tone may increase ghrelin. These data provide further evidence of the physiological regulation of ghrelin in relationship to GH. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. Univ Virginia, Hlth Med Sci Ctr, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-00088]; PHS HHS [R01-063639] NR 57 TC 31 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2004 VL 287 IS 3 BP E506 EP E512 DI 10.1152/ajpendo.00548.2003 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 848CL UT WOS:000223444700016 PM 15138154 ER PT J AU Satoh, A Gukovskaya, AS Nieto, JM Cheng, JH Gukovsky, I Reeve, JR Shimosegawa, T Pandol, SJ AF Satoh, A Gukovskaya, AS Nieto, JM Cheng, JH Gukovsky, I Reeve, JR Shimosegawa, T Pandol, SJ TI PKC-delta and -epsilon regulate NF-kappa B activation induced by cholecystokinin and TNF-alpha in pancreatic acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE phosphatidylcholine-specific phospholipase C; phosphatidylinositol-specific phospholipase C; Src kinases; translocation; tyrosine phosphorylation ID PROTEIN-KINASE-C; TUMOR-NECROSIS-FACTOR; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE-C; B/REL ACTIVATION; INFLAMMATORY RESPONSE; INTRACELLULAR CA2+; ENZYME SECRETION; PHOSPHATIDYLCHOLINE; RAT AB Although NF-kappaB plays an important role in pancreatitis, mechanisms underlying its activation remain unclear. We investigated the signaling pathways mediating NF-kappaB activation in pancreatic acinar cells induced by high-dose cholecystokinin-8 (CCK-8), which causes pancreatitis in rodent models, and TNF-alpha, which contributes to inflammatory responses of pancreatitis, especially the role of PKC isoforms. We determined subcellular distribution and kinase activities of PKC isoforms and NF-kappaB activation in dispersed rat pancreatic acini. We applied isoform-specific, cell-permeable peptide inhibitors to assess the role of individual PKC isoforms in NF-kappaB activation. Both CCK-8 and TNF-alpha activated the novel isoforms PKC-delta and -epsilon and the atypical isoform PKC-zeta but not the conventional isoform PKC-alpha. Inhibition of the novel PKC isoforms but not the conventional or the atypical isoform resulted in the prevention of NF-kappaB activation induced by CCK-8 and TNF-alpha. NF-kappaB activation by CCK-8 and TNF-alpha required translocation but not tyrosine phosphorylation of PKC-delta. Activation of PKC-delta, PKC-epsilon, and NF-kappaB with CCK-8 involved both phosphatidylinositol-specific PLC and phosphatidylcholine (PC)-specific PLC, whereas with TNF-alpha they only required PC-specific PLC for activation. Results indicate that CCK-8 and TNF-alpha initiate NF-kappaB activation by different PLC pathways that converge at the novel PKCs (delta and epsilon) to mediate NF-kappaB activation in pancreatic acinar cells. These findings suggest a key role for the novel PKCs in pancreatitis. C1 W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. Tohoku Univ, Grad Sch Med, Div Gastroenterol, Miyagi 9808574, Japan. RP Gukovskaya, AS (reprint author), W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Bldg 258,Rm 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIAAA NIH HHS [P50-AA-11999]; NIDDK NIH HHS [DK-59508] NR 58 TC 103 Z9 109 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2004 VL 287 IS 3 BP G582 EP G591 DI 10.1152/ajpgi.00087.2004 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 848DB UT WOS:000223446400012 PM 15117677 ER PT J AU Engel, D Peshock, R Armstong, RC Sivasubramanian, N Mann, DL AF Engel, D Peshock, R Armstong, RC Sivasubramanian, N Mann, DL TI Cardiac myocyte apoptosis provokes adverse cardiac remodeling in transgenic mice with targeted TNF overexpression SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tumor necrosis factor; cell death; caspase; congestive heart failure; magnetic resonance imaging ID NECROSIS-FACTOR-ALPHA; FAILING HUMAN HEART; CELL-DEATH; CARDIOMYOCYTE APOPTOSIS; MYOCARDIAL EXPRESSION; CASPASE INHIBITOR; FAILURE; BCL-2; INJURY; RATS AB Although cardiac myocyte apoptosis has been detected in explanted hearts from patients with end-stage dilated and ischemic cardiomyopathy, the relative contribution of apoptotic cell death to left ventricular (LV) remodeling and cardiac decompensation is not known. To determine whether progressive cardiac myocyte apoptosis contributes to the transition from a hypertrophic to a dilated cardiac phenotype that is observed in transgenic myosin heavy chain secreted TNF (MHCsTNF) mice with cardiac restricted overexpression of tumor necrosis factor ( TNF), we assessed cardiac myocyte apoptosis ( using a DNA ligase technique) in MHCsTNF mice and littermate control mice in relation to serial changes in LV structure, which was assessed using MRI. The prevalence of cardiac myocyte apoptosis increased progressively from 4 to 12 wk as the hearts of the MHCsTNF mice underwent the transition from a concentric hypertrophic to a dilated cardiac phenotype. Treatment of the MHCsTNF mice with the broad-based caspase inhibitor N-[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4- oxo-5-fluoropentanoic acid significantly decreased cardiac myocyte apoptosis and significantly attenuated LV wall thinning and adverse cardiac remodeling. Additional studies suggested that the TNF-induced decrease in Bcl-2 expression and activation of the intrinsic mitochondrial death pathway were responsible for the cardiac myocyte apoptosis observed in the MHCsTNF mice. These studies show that progressive cardiac myocyte apoptosis is sufficient to contribute to adverse cardiac remodeling in the adult mammalian heart through progressive LV wall thinning. C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Idun Pharmaceut, San Diego, CA 92121 USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, 6565 Fannin St,MS 524, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL-42250-10/10, P50 HL-O6H, R01 HL-58081-01, R01 HL-61543-01] NR 38 TC 66 Z9 67 U1 2 U2 4 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 SEP PY 2004 VL 287 IS 3 BP H1303 EP H1311 DI 10.1152/ajpheart.00053.2004 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 847MZ UT WOS:000223398600040 PM 15317679 ER PT J AU Altemeier, WA Matute-Bello, G Frevert, CW Kawata, Y Kajikawa, O Martin, TR Glenny, RW AF Altemeier, WA Matute-Bello, G Frevert, CW Kawata, Y Kajikawa, O Martin, TR Glenny, RW TI Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE acute lung injury; innate immunity; transcription factor-1; nuclear factor-kappa B ID RESPIRATORY-DISTRESS-SYNDROME; FACTOR-KAPPA-B; INTERLEUKIN-8 GENE-EXPRESSION; HEMORRHAGIC-SHOCK; INJURY; ACTIVATION; INFLAMMATION; RABBITS; MODEL; STRETCH AB Previous animal studies have identified a role for activation of innate immunity in the pathogenesis of ventilator-associated lung injury. These studies have used large tidal volume ventilation to study the effect of alveolar overdistension on induction of inflammatory pathways. We hypothesized an alternative mechanism for the pathogenesis of lung injury in which moderate tidal volume ventilation does not independently cause clinical inflammation but rather interacts with innate immune activation by bacterial products, resulting in an enhanced inflammatory response. We measured cytokine expression and lung injury in normal and lipopolysaccharide (LPS)-treated anesthetized rabbits randomized to either spontaneous respiration or mechanical ventilation. Outcome parameters were analyzed by two-way factorial analysis of variance to identify synergism between ventilation and systemic LPS. Mechanical ventilation alone resulted in minimal cytokine expression in the lung but did enhance LPS-induced expression of tumor necrosis factor-alpha, the CXC chemokines interleukin-8 and growth-related protein-alpha, and the CC chemokine monocyte chemoattractant protein-1. Increased mRNA expression and activation of the transcription factors nuclear factor-kappaB and activator protein-1 accompanied the cytokine responses. We conclude that moderate volume ventilation strategies augment the innate immune response to bacterial products in the lung and may play a role in the development of acute lung injury in patients with sepsis. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Healthcare Syst, Med Res Serv, Seattle, WA 98108 USA. RP Altemeier, WA (reprint author), Box 356500,1959 NE Pacific St, Seattle, WA 98195 USA. EM billa@u.washington.edu FU NHLBI NIH HHS [HL-24163, HL-30542, HL-71020, K08 HL071020] NR 39 TC 98 Z9 102 U1 0 U2 2 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 SEP PY 2004 VL 287 IS 3 BP L533 EP L542 DI 10.1152/ajplung.00004.2004 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 845NG UT WOS:000223251000014 PM 15145786 ER PT J AU Lee, DBN Jamgotchian, N Allen, SG Kan, FWK Hale, IL AF Lee, DBN Jamgotchian, N Allen, SG Kan, FWK Hale, IL TI Annexin A2 heterotetramer: role in tight junction assembly SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE annexin II; zonula occludens-1; occludin; claudin-1; hemifusion ID CELL-CELL CONTACTS; EPITHELIAL-CELLS; MEMBRANE-FUSION; II TETRAMER; MDCK CELLS; E-CADHERIN; MESENCHYMAL TRANSITION; MOLECULAR PHYSIOLOGY; POSSIBLE INVOLVEMENT; ZONULA OCCLUDENS-1 AB The tight junction has been characterized as a domain of focal fusions of the exoplasmic leaflets of the lipid bilayers from adjacent epithelial cells. Approximating membranes to within fusion distance is a thermodynamically unfavorable process and requires the participation of membrane-bridging or -fusion proteins. No known tight junction protein exhibits such activities. Annexin A2 (A2), in particular its heterotetramer (A2t), is known to form junctions between lipid bilayer structures through molecular bridging of their external leaflets. We demonstrate abundant A2 expression in Madin-Darby canine kidney II monolayers by two-dimensional gel electrophoresis. Confocal immunofluorescence microscopic analysis suggests the bulk of A2 is located along the apical and lateral plasma membrane in its tetrameric configuration, consisting of two A2 and two p11 (an 11-kDa calmodulin-related protein, S100A10) subunits. Immunocytochemistry and ultrastructural immunogold labeling demonstrate colocalization of the A2 subunit with bona fide tight junction proteins, zonula occludens-1, occludin, and claudin-1, at cell-cell contacts. The extracellular addition of a synthetic peptide, targeted to disrupt the binding between A2 and p11, completely aborts tight junction assembly in calcium chelation studies. We propose A2t as a member of a new class of tight junction proteins responsible for the long-observed convergence of adjacent exoplasmic lipid leaflets in tight junction assembly. C1 Vet Affairs Greater Los Angeles Healthcare Syst, VISN 22, Epithelial Transport Lab, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. RP Lee, DBN (reprint author), Vet Adm Med Ctr, Dept Med 111, 16111 Plummer St, Sepulveda, CA 91343 USA. EM dbnlee@ucla.edu FU NHLBI NIH HHS [T32HL-07656]; NIDDK NIH HHS [1R01DK/HD-51948] NR 90 TC 27 Z9 28 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 2004 VL 287 IS 3 BP F481 EP F491 DI 10.1152/ajprenal.00175.2003 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 844RT UT WOS:000223178000017 PM 15113748 ER PT J AU Silberstein, C Bouley, R Huang, Y Fang, PK Pastor-Soler, N Brown, D Van Hoek, AN AF Silberstein, C Bouley, R Huang, Y Fang, PK Pastor-Soler, N Brown, D Van Hoek, AN TI Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE water transport; freeze-fracture; LLC-PK(1) cells; orthogonal arrays; intramembraneous particles ID INSENSITIVE WATER CHANNEL; GASTRIC PARIETAL-CELL; ORTHOGONAL ARRAYS; PLASMA-MEMBRANES; KNOCKOUT MICE; BASOLATERAL MEMBRANES; DIABETES-INSIPIDUS; MOLECULAR-CLONING; COLLECTING TUBULE; BRATTLEBORO RATS AB Aquaporin-4 (AQP4) water channels exist as heterotetramers of M1 and M23 splice variants and appear to be present in orthogonal arrays of intramembraneous particles (OAPs) visualized by freeze-fracture microscopy. We report that AQP4 forms OAPs in rat gastric parietal cells but not in parietal cells from the mouse or kangaroo rat. Furthermore, the organization of principal cell OAPs in Brattleboro rat kidney is perturbed by vasopressin (arginine vasopressin). Membranes of LLC-PK(1) cells expressing M23-AQP4 showed large, abundant OAPs, but none were detectable in cells expressing M1-AQP4. Measurements of osmotic swelling of transfected LLC-PK(1) cells using videomicroscopy, gave osmotic water permeability coefficient (P(f)) values (in cm/s) of 0.018 (M1-AQP4), 0.019 (M23-AQP4), and 0.003 (control). Quantitative immunoblot and immunofluorescence showed an eightfold greater expression of M1- over M23-AQP4 in the cell lines, suggesting that single-channel p(f) (cm(3)/s) is much greater for the M23 variant. Somatic fusion of M1- and M23-AQP4 cells (P(f) = 0.028 cm/s) yielded OAPs that were fewer and smaller than in M23 cells alone, and M1-to-M23 expression ratios (similar to1: 4) normalized to AQP4 in M1 or M23 cells indicated a reduced single-channel p(f) for the M23 variant. Expression of an M23-AQP4-Ser(111E) mutant produced similar to1.5-fold greater single-channel p(f) and OAPs that were up to 2.5-fold larger than wild-type M23-AQP4 OAPs, suggesting that a putative PKA phosphorylation site Ser(111) is involved in OAP formation. We conclude that the higher-order organization of AQP4 in OAPs increases single-channel osmotic water permeability by one order of magnitude and that differential cellular expression levels of the two isoforms could regulate this organization. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Van Hoek, AN (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM vanhoek@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-55864, DK-38542] NR 46 TC 96 Z9 105 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 2004 VL 287 IS 3 BP F501 EP F511 DI 10.1152/ajprenal.00439.2003 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 844RT UT WOS:000223178000019 PM 15149973 ER PT J AU Goff, DC Bottiglieri, T Arning, E Shih, V Freudenreich, O Evins, AE Henderson, DC Baer, L Coyle, J AF Goff, DC Bottiglieri, T Arning, E Shih, V Freudenreich, O Evins, AE Henderson, DC Baer, L Coyle, J TI Folate, homocysteine, and negative symptoms in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID METABOLISM; GLUTAMATE AB Objective: Because glutamate carboxypeptidase II (GCPII) regulates both folate absorption and activation of N-methyl-D-aspartic acid receptors, the authors examined relationships between serum folate concentrations and clinical symptoms in schizophrenia patients. Method: For 91 outpatients with schizophrenia, clinical assessments were performed and serum folate, homocysteine, B-12, glycine, and serine concentrations were measured. Results: Serum folate concentrations were significantly lower than in a representative sample from the Framingham Offspring Study. Folate concentration correlated inversely with the Scale for Assessment of Negative Symptoms total score and was lower in patients with the deficit syndrome than in nondeficit patients. Homocysteine concentration correlated with the severity of extrapyramidal symptoms. Conclusions: These findings could reflect several possible mechanisms, including low dietary intake of folate, low GCPII activity, cigarette smoking, and the involvement of folate in the synthesis of neurotransmitters. Additional studies are needed to clarify these findings. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Baylor Univ, Med Ctr, Inst Met Dis, Dallas, TX USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [MH-02025, MH-60450] NR 13 TC 76 Z9 76 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2004 VL 161 IS 9 BP 1705 EP 1708 DI 10.1176/appi.ajp.161.9.1705 PG 4 WC Psychiatry SC Psychiatry GA 853BH UT WOS:000223800600028 PM 15337665 ER PT J AU Buczek-Thomas, JA Lucey, EC Stone, PJ Chu, CL Rich, CB Carreras, I Goldstein, RH Foster, JA Nugent, MA AF Buczek-Thomas, JA Lucey, EC Stone, PJ Chu, CL Rich, CB Carreras, I Goldstein, RH Foster, JA Nugent, MA TI Elastase mediates the release of growth factors from lung in vivo SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; PULMONARY FIBROBLAST-CULTURES; TGF-BETA; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; NEUTROPHIL ELASTASE; MACROPHAGE ELASTASE; INDUCED EMPHYSEMA; INDUCED INJURY; MESSENGER-RNA AB Uncontrolled elastase activity is involved in the development of several types of lung disease. Previous reports demonstrated that growth factors are liberated from pulmonary matrix storage sites by elastase; however, release of these entities in vivo is not well defined. In the present study, we investigated the release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-beta), after intratracheal instillation of porcine pancreatic elastase into mice. We found that elastase promoted a time-dependent release of FGF-2 and TGF-beta, from the lung into bronchoalveolar lavage (BAL) fluid. A large fraction of the TGF-beta(1) in BAL fluid was in the active form (similar to 60%), suggesting that elastase might participate 9in the activation of TGF-beta(1) from its latent form. Analysis of the levels of FGF-2 and TGF-beta(1) in mouse blood indicated that the growth factors in BAL fluid were not entirely derived from blood. Moreover, elastase treatment of pulmonary fibroblasts cultures caused the release of TGF-beta(1), suggesting that the TGF-beta(1) in BAL fluid could have come from lung cells/matrix. Additional in vitro studies also indicated that TGF-beta(1) plays a role in upregulating elastin mRNA levels. These data suggest that elastase releases growth factors from lung that participate in elastolytic injury responses. C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Pulm Ctr, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Nugent, MA (reprint author), Boston Univ, Sch Med, Dept Biochem, K420,715 Albany St, Boston, MA 02118 USA. EM nugent@biochem.bumc.bu.edu FU NHLBI NIH HHS [P01 HL 46902, HL 10332] NR 35 TC 32 Z9 33 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 2004 VL 31 IS 3 BP 344 EP 350 DI 10.1165/rcmb.20043-04200C PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 851OC UT WOS:000223693400012 PM 15191913 ER PT J AU Oljeski, SA Homer, MJ Krackov, WS AF Oljeski, SA Homer, MJ Krackov, WS TI Incorporating ethics education into the radiology residency curriculum: A model SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Tufts Univ, New England Med Ctr, Sch Med, Dept Radiol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Homer, MJ (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Dept Radiol, 750 Washington St,Box 388, Boston, MA 02111 USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2004 VL 183 IS 3 BP 569 EP 572 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849YR UT WOS:000223578100005 PM 15333336 ER PT J AU Tuncali, K vanSonnenberg, E Shankar, S Mortele, KJ Cibas, ES Silverman, SG AF Tuncali, K vanSonnenberg, E Shankar, S Mortele, KJ Cibas, ES Silverman, SG TI Evaluation of patients referred for percutaneous ablation of renal tumors: Importance of a preprocedural diagnosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID NEPHRON-SPARING SURGERY; NEGATIVE PREDICTIVE-VALUE; RADIO-FREQUENCY ABLATION; CELL CARCINOMA; RADIOFREQUENCY ABLATION; CLINICAL-EXPERIENCE; MASSES; MANAGEMENT; KIDNEY; BIOPSY AB OBJECTIVE. Percutaneous ablation of renal cell carcinoma has the potential to be as effective as partial nephrectomy. Because the entire tumor cannot be examined at pathology, diagnosis relies solely on imaging and percutaneous biopsy. Diagnoses of cancer have been rendered using imaging alone in some clinical trials of percutaneous ablation. If these trials inadvertently included benign masses, the efficacy of ablation was overestimated. Therefore, we sought to determine the prevalence of benign masses in a population of patients referred for percutaneous tumor ablation of presumed renal cell carcinoma. SUBJECTS AND METHODS. Twenty-seven patients were referred by urologists for MRI-guided cryotherapy of suspected renal cell carcinoma. Renal masses ranged from 1.0 to 4.6 cm (mean, 2.2 cm) in diameter. The CT, MRI, and percutaneous biopsy findings were tabulated and compared with surgical and imaging follow-up. RESULTS. Ten patients (37%) had a benign renal mass, including three angiomyolipomas, that had no evidence of fat on CT or MRI. Three masses were proven benign by biopsy, three by imaging, and four by a combination of biopsy and imaging. The masses in the remaining 17 patients were ablated. Biopsy revealed malignant cells in 10, suspicious cells in four, and atypical cells in two; one was nondiagnostic. CONCLUSION. A substantial percentage of patients refer-red for percutaneous ablation of renal tumors had benign masses. If CT or MRI alone cannot be used to diagnose a benign entity, patients should undergo a biopsy before the treatment session. C1 Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Cytol, Boston, MA 02115 USA. RP Tuncali, K (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. EM ktuncali@partners.org NR 37 TC 56 Z9 56 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 SEP PY 2004 VL 183 IS 3 BP 575 EP 582 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849YR UT WOS:000223578100007 PM 15333338 ER PT J AU Maher, MM Hahn, PF Gervais, DA Seoighe, B Ravenscroft, JB Peter, M AF Maher, MM Hahn, PF Gervais, DA Seoighe, B Ravenscroft, JB Peter, M TI Portable abdominal CT: Analysis of quality and clinical impact in more than 100 consecutive cases SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; COMPUTED-TOMOGRAPHY; INTRAHOSPITAL TRANSPORT; CONTRAST AB OBJECTIVE. Our aim was to determine portable abdominal CT image quality and clinical content in a consecutive series of scans obtained in ICUs at a single center. MATERIALS AND METHODS. All helical portable abdominal CT scans obtained between June 1999 and December 2000 were reviewed by two observers. Image quality was assessed for feature detection and overall quality compared with the patients contemporaneous stationary CT scans. Hospital records were used to determine patient demographics, scanning indications, and clinical impact and to verify portable CT findings when possible. RESULTS. One hundred twenty-two helical portable CT scans (47 contrast-enhanced) and 41 contemporaneous stationary CT scans in 107 patients were included. IV contrast material improved portable CT scan quality, but quality scores for portable CT scans were consistently lower than those for stationary CT scans, both with and without contrast material. Thirty-three conditions suspected before scanning were supported by findings on portable CT scans, which detected evidence of infection in 18 and hemorrhage in 16 cases and motivated seven laparotomies and six percutaneous drainage procedures. Thirty-three portable CT scans (27%) contributed to a change in patient treatment. Results of surgery or autopsy confirmed portable CT findings in 12 of 17 cases. CONCLUSION. Although image quality is interior to conventional stationary CT, portable abdominal CT provides important diagnostic information without requiting patient transport outside the ICU. Radiologists should avoid overconfident interpretation of portable CT scans. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM phahn@partners.org NR 17 TC 4 Z9 4 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 SEP PY 2004 VL 183 IS 3 BP 663 EP 670 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849YR UT WOS:000223578100022 PM 15333353 ER PT J AU Turner, BG Rhea, JT Thrall, JH Small, AB Novelline, RA AF Turner, BG Rhea, JT Thrall, JH Small, AB Novelline, RA TI Trends in the use of CT and radiography in the evaluation of facial trauma, 1992-2002: Implications for current costs SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INJURIES; FRACTURES; PATIENT AB OBJECTIVE. CT has replaced conventional radiography of the face in many trauma centers. Concern exists that increased costs are associated with increased use of CT. Our goal was to compare the amount of CT and radiography performed for facial trauma at a level 1 trauma center in 1992 and in 2002 and to determine hospital costs for the imaging of these patients. MATERIALS AND METHODS. The changes in volume and types of facial imaging examinations were determined comparing 1992 and 2002. Hospital costs of different imaging examinations were determined for 2002. Current costs of imaging facial trauma were compared with what 2002 costs would have been if the practice pattern in 1992 had continued. RESULTS. In 1992, 890 patients were evaluated for facial trauma. Six hundred seventy-one had only radiography, 153 only CT of the face, and 66 both CT and radiography. In 2002, 828 patients were evaluated. Five hundred eighty-four patients had only CT of the face; 228, only radiography; and 16, both CT and radiography. The number of facial imaging examinations per patient in 1992 and 2002 was 1.23 and 1.03, respectively. The 2002 hospital cost of a facial CT examination was $121 and of a facial radiography series was $154. Using CT instead of radiography for evaluating facial injury resulted in an overall cost savings of 22% per patient in 2002. CONCLUSION. The availability of CT has not resulted in increased use of facial imaging. The increased use of CT from 1992 to 2002 results in decreased current costs for the hospital. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,POB 9657, Boston, MA 02114 USA. NR 8 TC 13 Z9 13 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 SEP PY 2004 VL 183 IS 3 BP 751 EP 754 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849YR UT WOS:000223578100036 PM 15333366 ER PT J AU Li, G DeFrate, LE Sun, H Gill, TJ AF Li, G DeFrate, LE Sun, H Gill, TJ TI In vivo elongation of the anterior cruciate ligament and posterior cruciate ligament during knee flexion SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE in vivo knee kinematics; anterior cruciate ligament (ACL); posterior cruciate ligament (PCL); soft tissue biomechanics ID SITU FORCES; POSTEROLATERAL STRUCTURES; ROBOTIC TECHNOLOGY; MUSCLE LOADS; 2 BUNDLES; KINEMATICS; GRAFT; RECONSTRUCTION; DEFICIENCY; INSERTION AB Background: Most knowledge regarding cruciate ligament function is based on in vitro experiments. Purpose: To investigate the in vivo elongation of the functional bundles of the anterior cruciate ligament and posterior cruciate ligament during weightbearing flexion. Hypothesis: The biomechanical role of functional bundles of the anterior cruciate ligament and posterior cruciate ligament under in vivo loading is different from that measured in cadavers. Study Design: In vivo biomechanical study Methods: Elongation of the anterior cruciate ligament and posterior cruciate ligament was measured during a quasi-static lunge using imaging and 3-dimensional computer-modeling techniques. Results: The anterior-medial bundle of the anterior cruciate ligament had a relatively constant length from full extension to 90degrees of flexion. The posterior-lateral bundle of the anterior cruciate ligament decreased in length with flexion. Both bundles of the posterior cruciate ligament had increased lengths with flexion. Conclusion: The data did not demonstrate the reciprocal function of the 2 bundles of the anterior cruciate ligament or the posterior cruciate ligament with flexion observed in previous studies. Instead, the data suggest that there is a reciprocal function between the anterior cruciate ligament and posterior cruciate ligament with flexion. The anterior cruciate ligament plays a more important role in low-flexion angles, whereas the posterior cruciate ligament plays a more important role in high flexion. Clinical Relevance: Understanding the biomechanical role of the knee ligaments in vivo is essential to reproduce the structural behavior of the ligament after injury (especially for 2-bundle reconstructions) and thus improve surgical outcomes. C1 Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 34 TC 77 Z9 82 U1 5 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP PY 2004 VL 32 IS 6 BP 1415 EP 1420 DI 10.1177/0363546503262175 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 847SO UT WOS:000223415400005 PM 15310565 ER PT J AU Tingart, MJ Apreleva, M Lehtinen, J Zurakowski, D Warner, JJP AF Tingart, MJ Apreleva, M Lehtinen, J Zurakowski, D Warner, JJP TI Anchor design and bone mineral density affect the pull-out strength of suture anchors in rotator cuff repair - Which anchors are best to use in patients with low bone quality? SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE rotator cuff repair; bone mineral density; suture anchor; anchor design; pull-out strength ID MECHANICAL STRENGTH AB Background: Different metal and biodegradable suture anchors are available for rotator cuff repair. Poor bone quality may result in anchor loosening and tendon rerupture. Hypotheses: Higher bone mineral density is associated with higher pull-out strength of suture anchors. Depending on anchor placement, pull-out strengths of anchors are different within the greater tuberosity. Study Design: Cadaveric biomechanical study. Methods: Trabecular and cortical bone mineral densities were determined for different regions within the greater tuberosity. Metal screw-type and biodegradable hook-type anchors were cyclically loaded. Results: Mean failure load of metal and biodegradable anchors was 273 N and 162 N, respectively, for the proximal part (P < .01) and 184 N and 112 N, respectively, for the distal part (P < .01). Both types of anchors showed higher failure loads in the proximal-anterior and -middle parts of the greater tuberosity than in the distal part (P < .01). A significant positive correlation was found between cortical bone mineral density and failure load of metal anchors (P < .01). Conclusion: Bone quality, anchor type, and anchor placement have a significant impact on anchor failure loads. Clinical Relevance: Suture anchors should be placed in the proximal-anterior and -middle parts of the greater tuberosity. In the distal parts, biodegradable hook-like anchors should be used with caution. C1 Univ Regensburg, Dept Orthopaed Surg, D-93047 Regensburg, Germany. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. RP Tingart, MJ (reprint author), Univ Regensburg, Dept Orthopaed Surg, Silbernagelgasse 9, D-93047 Regensburg, Germany. EM markus.tingar@gmx.de NR 22 TC 76 Z9 80 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP PY 2004 VL 32 IS 6 BP 1466 EP 1473 DI 10.1177/0363546503262644 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 847SO UT WOS:000223415400012 PM 15310572 ER PT J AU Deshmukh, AV Wilson, DR Zilberfarb, JL Perlmutter, GS AF Deshmukh, AV Wilson, DR Zilberfarb, JL Perlmutter, GS TI Stability of acromioclavicular joint reconstruction - Biomechanical testing of various surgical techniques in a cadaveric model SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE acromioclavicular; coracoclavicular; ligament; instability; suture anchor ID SEPARATION; DISLOCATION; REPAIR AB Background: Despite reports of excellent results with the Weaver-Dunn coracoacromial ligament transfer, many authors recommend augmenting the transfer with supplemental fixation. The authors of this study sought to determine whether there is a biomechanical basis for this assertion and which augmentative method, if any, most closely restored acromioclavicular motion to normal. Hypothesis: Augmentative coracoclavicular fixation provides better restoration of normal acromioclavicular joint laxity and an increased failure load when compared with the Weaver-Dunn reconstruction alone. Study Design: Controlled laboratory cadaveric study. Methods: Native acromioclavicular joint motion was measured using an infrared optical measurement system. Acromioclavicular and coracoclavicular ligaments were then cut, and 1 of 6 reconstructions was performed: Weaver-Dunn, suture cerclage, and 4 different suture anchors. Acromioclavicular joint motion was reassessed, a cyclic loading test was performed, and the failure load was recorded. Results: After Weaver-Dunn reconstruction, mean anteroposterior laxity increased from 8.8 +/- 2.9 mm in the native state to 41.9 +/- 7.6 mm (P less than or equal to .01), and mean superior laxity increased from 3.1 +/- 1.5 mm to 13.6 +/- 4.4 mm (P less than or equal to .01). Weaver-Dunn reconstructions failed at a lower load (177 +/- 9 N) than all other reconstructions (range, 278-369 N) (P less than or equal to .05). Reconstruction using augmentative fixation allowed less acromioclavicular motion than Weaver-Dunn reconstruction (P less than or equal to .05) but more motion than the native ligaments (P less than or equal to .05). Specifically, mean superior laxity after reconstruction ranged between 6.5 and 9.0 mm compared with the native ligaments (3.1 +/- 1.5 mm) and the Weaver-Dunn reconstructions (13.6 +/- 4.4 mm). Mean anteroposterior laxity after the reconstructions tested ranged between 21.8 and 33.2 mm, compared with the native ligaments (8.8 +/- 2.9 mm) and the Weaver-Dunn reconstructions (41.9 +/- 7.6 mm). Conclusion: Although none of the augmentative methods tested restored acromioclavicular stability to normal, all proved superior to the Weaver-Dunn reconstruction alone. Clinical Relevance: This study suggests that when performing acromioclavicular reconstruction, supplemental fixation should be used because it provides more stability and pull-out strength than the Weaver-Dunn reconstruction alone. C1 Kaiser Permanente Med Ctr, Dept Orthopaed, Los Angeles, CA 90034 USA. Univ British Columbia, Dept Orthopaed, Div Orthopaed Engn Res, Vancouver, BC V5Z 1M9, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Deshmukh, AV (reprint author), Kaiser Permanente Med Ctr, Dept Orthopaed, 6041 Cadillac Ave, Los Angeles, CA 90034 USA. NR 27 TC 58 Z9 64 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP PY 2004 VL 32 IS 6 BP 1492 EP 1498 DI 10.1177/0363546504263699 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 847SO UT WOS:000223415400016 PM 15310576 ER PT J AU Park, SE Stamos, BD DeFrate, LE Gill, TJ Li, GA AF Park, SE Stamos, BD DeFrate, LE Gill, TJ Li, GA TI The effect of posterior knee capsulotomy on posterior tibial translation during posterior cruciate ligament tibial inlay reconstruction SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE knee capsule; posterior cruciate ligament (PCL) reconstruction; posterior stability; tibial inlay ID IN-VITRO; POSTEROLATERAL STRUCTURES; GRAFT; INJURIES; FORCES; TUNNEL; REPLACEMENT; DEFICIENCY; TENSION; LAXITY AB Purpose: To measure the biomechanical effect of the surgical capsulotomy made during a posterior cruciate ligament reconstruction using the tibial inlay technique. Hypothesis: The posterior capsule contributes to posterior tibial stability. Study Design: Controlled laboratory experiment. Methods: Six knee specimens were tested on a robotic testing system from 0degrees to 120degrees of flexion with the posterior cruciate ligament intact and resected and with a posterior capsulotomy identical to that performed during tibial inlay reconstruction (sham surgery). A longitudinal incision with medial and lateral soft tissue stripping sufficient to mount an inlay bone block and pass an Achilles tendon graft into the knee was made in the oblique popliteal ligament, muscle belly of the popliteus, and posterior capsule. The posterior tibial translation was measured under a posterior tibial load of 130 N at multiple flexion angles. Results: Capsulotomy increased the posterior laxity compared with the posterior cruciate ligament-resected knee at every flexion angle. An additional 0.97 +/- 0.48 mm, 0.65 +/- 0.47 mm, 0.56 +/- 0.33 mm, 0.48 +/- 0.38 mm, and 0.94 +/- 0.60 mm of posterior laxity was recorded at 0degrees, 30degrees, 60degrees, 90degrees, and 120degrees of flexion, respectively. These values were all statistically significant (P < .001). Conclusions: A posterior capsulotomy alone, without associated posteromedial or posterolateral disruption, produces additional posterior tibial translation in vitro compared with posterior cruciate ligament-deficient knee with intact capsule. Clinical Relevance: Damage to the posterior capsule may contribute to the, residual posterior laxity noted clinically after posterior cruciate ligament reconstruction. C1 Massachusetts Gen Hosp, Bioengn Lab, Boston, MA USA. MIT, Dept Engn Mech, Cambridge, MA USA. RP Li, GA (reprint author), 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 31 TC 19 Z9 22 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP PY 2004 VL 32 IS 6 BP 1514 EP 1519 DI 10.1177/0363546504265594 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 847SO UT WOS:000223415400020 PM 15310580 ER PT J AU Chew, LD Bradley, KA Flum, DR Cornia, PB Koepsell, TD AF Chew, LD Bradley, KA Flum, DR Cornia, PB Koepsell, TD TI The impact of low health literacy on surgical practice SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE health literacy; VA clinic; preoperative instructions; adherence to medication ID AFFAIRS AB Background: We sought to determine the prevalence of low health literacy (LHL) among patients in a preoperative clinic, the characteristics associated with LHL, and the association between LHL and adherence to preoperative instructions. Methods: We conducted a cohort study and interviewed patients at a VA preoperative clinic. We administered a health literacy test and collected sociodemographic information. When patients returned for their scheduled surgical procedures, adherence to preoperative instructions was, assessed. Results: Of 332 participants, 12% (n = 40) had LHL. Low health literacy was more prevalent among older adults (more than 65 years) compared with those under age 65. Patients with LHL were more likely to be nonadherent to preoperative medication instructions (odds ratio = 1.9; 95% confidence interval: 0.8 to 4.8), but this was of borderline statistical significance. Conclusions: Low health literacy was common among older patients and appeared to be associated with lower adherence to preoperative medication instructions. Published by Excerpta Medica, Inc. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Univ Washington, Div Gen Internal Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Chew, LD (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. EM lchew@u.washington.edu NR 10 TC 46 Z9 46 U1 2 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2004 VL 188 IS 3 BP 250 EP 253 DI 10.1016/j.amjsurg.2004.04.005 PG 4 WC Surgery SC Surgery GA 854RQ UT WOS:000223921400009 PM 15450829 ER PT J AU Deshpande, V Fernandez-del Castillo, C Muzikansky, A Deshpande, A Zukerberg, L Warshaw, AL Lauwers, GY AF Deshpande, V Fernandez-del Castillo, C Muzikansky, A Deshpande, A Zukerberg, L Warshaw, AL Lauwers, GY TI Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CK19; pancreas; neuroendocrine tumor; prognosis ID NEUROENDOCRINE TUMORS; CELL-DIFFERENTIATION; CLASSIFICATION; PROLIFERATION; NEOPLASMS; CRITERIA AB The prediction of the behavior of pancreatic endocrine tumors (PETs) is a difficult exercise. CK19, a marker of pancreatic ductal cells, does not stain normal islet cells. Our aim was to evaluate the prognostic value of traditional parameters, including the Capella classification, as well as CK19. We evaluated the clinicopathologic features of 101 curatively resected PETs. The influence on survival of size, functional status of tumor, growth pattern, nuclear grade, mitoses (>2/10 HPF), vascular and perineural invasion, and necrosis was determined. Immunohistochemistry for Ki-67 and CK19 was performed in 45 and 54 cases, respectively. Cases were categorized as per the Capella classification as: benign, borderline, low-grade, and high-grade malignant. The different variables were tested by standard univariate and multivariate analyses. Mitoses (P = 0.03), solid pattern (P = 0.04), necrosis (P = 0.01), vascular invasion (P = 0.003), perineural invasion (P = 0.02), CK19 staining (P = 0.0008), and Ki-67 (P = 0.02) were significant prognostic indicators by univariate analysis while the Capella classification was not significant. By multivariate analysis, only CK19 was significant (P = 0.0008). None of the CK19-negative cases died of disease, while 10 of 28 CK19-positive cases died of disease and 3 are alive with disease. The Capella classification includes malignant tumors in its benign and borderline categories. CK19 is a powerful predictor of survival and can potentially segregate benign and malignant PETs. We suggest that all PETs with any one of the following features be diagnosed as malignant: presence of necrosis, vascular invasion, perineural invasion, or CK19 positivity. We hypothesize that a subgroup of PETs may share a common histogenesis with pancreatic adenocarcinomas. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 21 TC 73 Z9 76 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 SEP PY 2004 VL 28 IS 9 BP 1145 EP 1153 DI 10.1097/01.pas.0000135525.11566.b4 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 849RT UT WOS:000223559000003 PM 15316313 ER PT J AU Henley, JD Young, RH Wade, CL Ulbright, TM AF Henley, JD Young, RH Wade, CL Ulbright, TM TI Seminomas with exclusive intertubular growth - A report of 12 clinically and grossly inconspicuous tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE seminoma; intertubular pattern; testicular atrophy ID GERM-CELL TUMORS; TUBULAR SEMINOMA; TESTIS AB Intertubular growth in seminoma is characterized by seminoma cells, either singly or in small Clusters, between preserved seminiferous tubules. It is a common, although focal, pattern in many seminomas where it is admixed with the usual sheet-like and nested arrangements and does not pose any diagnostic problems in such cases. We describe, in contrast, the clinicopathologic features of 12 cases with exclusively intertubular growth and which were typically diagnostically problematic. The 12 patients lacked overt clinical signs of a primary testicular mass. Three presented with infertility, 2 with cryptorchidism, 2 with metastases, 1 with pain and testicular atrophy, and the presentation was unknown in 4. On gross examination, no mass was apparent in 9 cases with available data, but ill-defined firm areas or foci of whitish-brown discoloration were occasionally noted. Microscopically, the process was characterized by individual, dispersed turner cells or small clusters of cells growing between the seminiferous tubules. The tumor cells were often obscured by a lymphocytic infiltrate or, less commonly, nodules of hyperplastic Leydig cells. Common associated findings were tubular atrophy with sclerosis and thickening of tubular basement membranes and intratubular germ cell neoplasia, unclassified type. Immunostains against placental-like alkaline phosphatase and c-KIT (CD117) highlighted the seminoma cells in all cases examined. In pure form, intertubular seminoma is both clinically and pathologically inconspicuous and may be misdiagnosed as atrophy, scar, or orchitis. C1 Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Horner Wright Pathol Labs, Boston, MA USA. RP Henley, JD (reprint author), Univ Hosp 3465, Dept Surg Pathol, 550 N Univ Blvd, Indianapolis, IN 46202 USA. EM jhenley@iupui.edu NR 18 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2004 VL 28 IS 9 BP 1163 EP 1168 DI 10.1097/01.pas.0000132742.12221.82 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 849RT UT WOS:000223559000005 PM 15316315 ER PT J AU Fishman, JA Patience, C AF Fishman, JA Patience, C TI Xenotransplantation: Infectious risk revisited SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE clinical trials; cytomegalovirus; ethics; herpesvirus; infection; pig; porcine endogenous retrovirus; swine; transplantation; viral recombination; xenotransplantation ID PORCINE ENDOGENOUS RETROVIRUS; INFLUENZA-A VIRUSES; TO-BABOON XENOTRANSPLANTATION; KIDNEY ALLOGRAFT TOLERANCE; LIVING PIG-TISSUE; MINIATURE SWINE; HUMAN-CELLS; ENDOTHELIAL-CELLS; LYMPHOPROLIFERATIVE DISEASE; PRODUCTIVE INFECTION AB Xenotransplantation is a possible solution for the shortage of tissues for human transplantation. Multiple hurdles exist to clinical xenotransplantation, including immunologic barriers, metabolic differences between pigs - the source species most commonly considered - and humans, and ethical concerns. Since clinical trials were first proposed almost 10 years ago, the degree of risk for infection transmitted from the xenograft donor to the recipient has been extensively investigated. A number of potential viral pathogens have been identified including porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine lymphotropic herpesvirus (PLHV). Sensitive diagnostic assays have been developed for each virus. Human-tropic PERV are exogenous recombinants between PERV-A and PERV-C sequences and are present in only a subset of swine. Porcine cytomegalovirus can be excluded from herds of source animals by early weaning of piglets. In contrast, the risks associated with PLHV remain undefined. Microbiologic studies and assays for potential xenogeneic pathogens have furthered understanding of risks associated with xenotransplantation. Thus far, clinical xenotransplantation of pig tissues has not resulted in transmission of viral infection to humans; significant risks for disease transmission from swine to humans have not been confirmed. If immunologic hurdles can be overcome, it is reasonable to initiate carefully monitored clinical trials. C1 Massachusetts Gen Hosp, Infect Dis Unit, Transplantat Infect Dis & Compromised Host Progra, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Transplantat Infect Dis & Compromised Host Progra, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Immerge BioTherapeut Inc, Cambridge, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Transplantat Infect Dis & Compromised Host Progra, Boston, MA 02114 USA. EM jfishman@partners.org FU NIAID NIH HHS [P01 AI45897] NR 78 TC 105 Z9 111 U1 1 U2 17 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2004 VL 4 IS 9 BP 1383 EP 1390 DI 10.1111/j.1600-6143.2004.00542.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 845ZJ UT WOS:000223283900001 PM 15307825 ER PT J AU Kawai, T Sogawa, H Boskovic, S Abrahamian, G Smith, RN Wee, SL Andrews, D Nadazdin, O Koyama, I Sykes, M Winn, HJ Colvin, RB Sachs, DH Cosimi, AB AF Kawai, T Sogawa, H Boskovic, S Abrahamian, G Smith, RN Wee, SL Andrews, D Nadazdin, O Koyama, I Sykes, M Winn, HJ Colvin, RB Sachs, DH Cosimi, AB TI CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE CD154 blockade; kidney transplantation; mixed chimerism; tolerance ID BONE-MARROW TRANSPLANTATION; DONOR-SPECIFIC TOLERANCE; MONOCLONAL-ANTIBODY; CD40 LIGAND; COSTIMULATORY BLOCKADE; CYNOMOLGUS MONKEYS; ISLET ALLOGRAFTS; T-CELLS; REJECTION; REGIMEN AB Costimulatory blockade with anti-CD154 monoclonal antibody (aCD154) prolongs allograft survival in nonhuman primates, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding CD154 blockade to a chimerism inducing nonmyeloablative regimen in primates. We observed a significant improvement of donor bone marrow (DBM) engraftment, which has been associated with a lower incidence of acute rejection and long-term survival of renal allografts without the need for previously required splenectomy. Among the long-term survivors, four never showed evidence of rejection, with the longest survival exceeding 1700 days following discontinuation of immunosuppression. Nevertheless, late chronic rejection was observed in three of eight recipients, indicating the necessity of further modifications of the regimen. Control recipients receiving no DBM or donor splenocytes in place of DBM rejected their allografts. Thus, DBM engraftment with, at least, transient mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Modification of the original mixed chimerism approach, by the addition of costimulatory blockade, has been shown to enhance mixed chimerism and induce renal allograft tolerance with less morbidity in nonhuman primates. C1 Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02115 USA. EM tkawai@partners.org FU NHLBI NIH HHS [P0I-HL18646]; NIAID NIH HHS [R21 AI037692, 5R01 AI50987-03, R01 AI037692, R01 AI037692-09, R01 AI037692-10, R21 AI037692-06]; PHS HHS [R0I A137692] NR 29 TC 115 Z9 116 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2004 VL 4 IS 9 BP 1391 EP 1398 DI 10.1111/j.1600-6143.2004.00523.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 845ZJ UT WOS:000223283900002 PM 15307826 ER PT J AU Cudkowicz, M Zhang, H Qureshi, M Schoenfeld, D AF Cudkowicz, M Zhang, H Qureshi, M Schoenfeld, D TI Maximum voluntary isometric contraction (MVIC) SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Conference on Amyotrophic Lateral Sclerosis Clinical Trials CY JUN 13-15, 2003 CL Westchester, NY SP Muscular Dystrophy Assoc ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; GABAPENTIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Biostat Ctr, Boston, MA USA. RP Cudkowicz, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD SEP PY 2004 VL 5 SU 1 BP 84 EP 85 DI 10.1080/17434470410019744 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 865VG UT WOS:000224731500023 PM 15512881 ER PT J AU Heaton, JT Goldstein, EA Kobler, JB Zeitels, SM Randolph, GW Walsh, MJ Gooey, JE Hillman, RE AF Heaton, JT Goldstein, EA Kobler, JB Zeitels, SM Randolph, GW Walsh, MJ Gooey, JE Hillman, RE TI Surface electromyographic activity in total laryngectomy patients following laryngeal nerve transfer to neck strap muscles SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE alaryngeal speech; artificial larynx; electromyography; larynectomy; nerve regeneration; nerve transfer; recurrent laryngeal nerve; voice ID POSTERIOR CRICOARYTENOID MUSCLE; FUNDAMENTAL VOICE FREQUENCY; RECURRENT LARYNGEAL; TOPOGRAPHIC ANATOMY; SKELETAL-MUSCLE; COMMUNICATION; PARALYSIS; SPEECH AB Hands-free triggering and pitch control would improve electrolarynx devices, which are inconvenient to use and sound unnatural. The present study tested the strategy of salvaging voice-related neural signals for hands-free electrolarynx control either by transferring cut recurrent laryngeal nerves (RLNs) to denervated neck strap muscles or by preserving strap muscles with their normal innervation. An RLN nerve transfer was performed at the time of total laryngectomy in 8 individuals, and in 5 of these subjects, strap muscles with intact ansa cervicalis innervation were also preserved for comparison. Neck surface electromyography performed over the strap muscles was used periodically for more than 1 year on phonatory and nonphonatory tasks. Signals were eventually obtained in all subjects from both RLN-innervated and ansa-innervated strap muscles that correlated with speech production. After 1 year, RLN-driven signals were larger than ansa-driven signals in magnitude, and their timing appeared better correlated with intended phonation. The results show that neck surface electromyography is an effective control source for hands-free electrolarynx activation, and that RLN transfer may provide the best approach for obtaining phonation-related activity. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Vet Affairs Boston Hlth Care Syst, Boston, MA 02215 USA. Massachusetts Gen Hosp Inst Hlth Prof, Dept Commun Sci & Disorders, Boston, MA USA. RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 1 Bowdoin Sq, Boston, MA 02114 USA. NR 37 TC 10 Z9 12 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 SEP PY 2004 VL 113 IS 9 BP 754 EP 764 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 853MS UT WOS:000223832300015 PM 15453536 ER PT J AU Gold, JP Begg, WB Fullerton, D Mathisen, D Olinger, G Orringer, M Verrier, E AF Gold, JP Begg, WB Fullerton, D Mathisen, D Olinger, G Orringer, M Verrier, E TI Successful implementation of a novel internet hybrid surgery curriculum - The early phase outcome of thoracic surgery Prerequisite Curriculum e-learning project SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Surgical-Association CY APR 15-17, 2004 CL San Francisco, CA SP Amer Surg Assoc ID CD-ROM; EDUCATION; KNOWLEDGE; DIRECTORS; PROGRAM; ONLINE; SKILLS AB Background: The internet CD-ROM thoracic surgery (TS) e-learning system was implemented in 2001 as a prospective randomized trial testing resident acceptance and educational impact of a unique web-based curriculum system on prematriculated TS residents. The Prerequisite Curriculum (PRC) contains 75 segments organized with textbook and case-based navigational systems. Methods: Web-based technology tracked the PRC use for each resident. Of 142 residents, 138 thoracic surgery residents matching in 2001 for 2002 matriculation participated in a prospective randomized trial comparing the PRC system to a control group. Two sets of in-training exams, as well as resident and faculty knowledge/performance surveys, were used from July 2001 through January 2004 for ongoing, blinded multidimensional evaluation. Results: Most residents (55/69) responded to the written prematriculation surveys and indicated they used the PRC (43/55), averaging 1.45 hours weekly. The PRC was rated as easy to use (8.3/10), a valuable study guide (7.7/10), and superior to traditional texts and journals for preresidency preparation (7.9/10). Web-based tracking revealed that 47/69 actually used the PRC. Sessions averaged 23.3 minutes with an average of 148 sessions over the prematriculation year. The in-training exam performance when evaluated at 1 and 9 months into the TS residency revealed a positive correlation between examination performance and PRC use. After TS residency matriculation, the self-evaluated knowledge and performance satisfaction scores were superior among PRC users in all categories. Simultaneous TS faculty evaluations of the same resident groups demonstrated smaller, but significant group differences. Conclusion: The implementation of the TS PRC has been exciting and successful. Future multidisciplinary curricular progress will hopefully continue to build upon this e-leaming strategy. C1 Thorac Surg Directors Assoc, Arlington, VA 22206 USA. Albert Einstein Coll Med, Dept Cardiothorac Surg, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Div Cardiothorac Surg, Denver, CO USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA. RP Begg, WB (reprint author), Thorac Surg Directors Assoc, 4900B S 31 St, Arlington, VA 22206 USA. NR 36 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2004 VL 240 IS 3 BP 499 EP 507 DI 10.1097/01.sla.0000137139.63446.35 PG 9 WC Surgery SC Surgery GA 849DS UT WOS:000223519500020 PM 15319721 ER PT J AU LaMuraglia, GM Brewster, DC Moncure, AC Dorer, DJ Stoner, MC Trehan, SK Drummond, EC Abbott, WM Cambria, RP AF LaMuraglia, GM Brewster, DC Moncure, AC Dorer, DJ Stoner, MC Trehan, SK Drummond, EC Abbott, WM Cambria, RP TI Carotid endarterectomy at the millennium SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Surgical-Association CY APR 15-17, 2004 CL San Francisco, CA SP Amer Surg Assoc ID HIGH-RISK PATIENTS; ARTERY STENOSIS; CEREBROVASCULAR-DISEASE; RECURRENT STENOSIS; RANDOMIZED-TRIAL; VASCULAR-SURGERY; ANGIOPLASTY; OUTCOMES; RESTENOSIS; CORONARY AB Objectives: Carotid endarterectomy (CEA) is supported by level 1 evidence as the standard treatment of severe carotid stenosis in both symptomatic and asymptomatic patients. As interventional techniques are emerging for treatment of this disease, this study was undertaken to provide a contemporary surgical standard for comparison to carotid stenting. Patients and methods: During the interval 1989 to 1999, 2236 isolated CEAs were performed on 1897 patients (62% male, 36% symptomatic, 4.6% reoperative procedures). Study endpoints included perioperative events, patient survival, late incidence of stroke, anatomic durability of CEA, and resource utilization changes during the study. Variables associated with complications, long-term and stroke free survival, restenosis, and resource utilization were analyzed by univariate and multivariate analysis. Results: Perioperative complications occurred in 5.5% of CEA procedures, including any stroke/death (1.4%), neck hematoma (1.7%), cardiac complications (0.5%), and cranial nerve injury (0.4%). Actuarial survival at 5 and 10 years was 72.4% (95% confidence interval [CI] 69.3-73.5) and 44.7% (95% CI 41.7+/-47.9) respectively, with coronary artery disease (P < 0.0018), chronic obstructive pulmonary disease (P < 0.00018) and diabetes mellitus (P < 0.0011) correlating with decreased longevity. The age- and sex-adjusted incidence of any stroke during follow-up was reduced by 22% (upper 0.35, lower 0.08) of predicted with the patient classification of hyperlipidemia (P < 0.0045) as the only protective factor. Analysis of CEA anatomic durability during a median follow-up period of 5.9 years identified a 7.7% failure rate (severe restenosis/occlusion, 4.5%; or reoperative CEA, 3.2%) with elevated serum cholesterol (P < 0.017) correlating with early restenosis. Resource utilization diminished (first versus last 2-year interval periods) for average hospital length of stay from 10.3 +/- 1.5 days to 4.3 +/- 0.7 days (P < 0.01) and preoperative contrast angiography from 87% +/- 1.4% to 10.3% +/- 4%. Conclusions: These data delineate the safety, durability, and effectiveness in long-term stroke prevention of CEA. They provide a standard to which emerging catheter-based therapies for carotid stenosis should be compared. C1 Harvard Univ, Dept Surg,Med Sch, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr,Med Practices Evaluat Unit, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Dept Surg,Med Sch, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Gen Surg Serv, ACC 464,15 Parkman St, Boston, MA 02114 USA. EM glamuraglia@partners.org FU Medical Research Council [G0500987] NR 57 TC 51 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2004 VL 240 IS 3 BP 535 EP 544 DI 10.1097/01.sla.0000137142.26925.3c PG 10 WC Surgery SC Surgery GA 849DS UT WOS:000223519500028 PM 15319725 ER PT J AU Multani, AS Pathak, S Cabrera, NG Naylor, ML Laud, P Lombard, D DePinho, RA Chang, S AF Multani, Asha S. Pathak, Sen Cabrera, Noelia G. Naylor, Maria L. Laud, Purnima Lombard, David DePinho, Ronald A. Chang, Sandy TI ESSENTIAL ROLE OF LIMITING TELOMERES IN THE PATHOGENESIS OF WERNER SYNDROME SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Multani, Asha S.; Pathak, Sen; Cabrera, Noelia G.; Laud, Purnima; Chang, Sandy] Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Naylor, Maria L.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Naylor, Maria L.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Naylor, Maria L.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lombard, David] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5D MA 338 BP 3572 EP 3572 PG 1 WC Oncology SC Oncology GA V80CV UT WOS:000205415300338 ER PT J AU Barchiesi, F Spreghini, E Maracci, M Fothergill, AW Baldassarri, I Rinaldi, MG Scalise, G AF Barchiesi, F Spreghini, E Maracci, M Fothergill, AW Baldassarri, I Rinaldi, MG Scalise, G TI In vitro activities of voriconazole in combination with three other antifungal agents against Candida glabrata SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; SCEDOSPORIUM-PROLIFICANS; CRYPTOCOCCUS-NEOFORMANS; INVASIVE CANDIDIASIS; FLUCONAZOLE; TERBINAFINE; ITRACONAZOLE; ALBICANS; THERAPY; INFECTION AB Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC index of less than or equal to0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to less than or equal to1.0 mug/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was greater than or equal to2.0 mug/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo. C1 Univ Politecn Marche, Ist Malattie Infett & Med Publ, I-60020 Ancona, Italy. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Barchiesi, F (reprint author), Univ Politecn Marche, Ist Malattie Infett & Med Publ, Azienda Osped Umberto 1,Via Conca, I-60020 Ancona, Italy. EM l.infettive@ao-umbertoprimo.marche.it RI Spreghini, Elisabetta/G-9378-2012 NR 39 TC 17 Z9 23 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2004 VL 48 IS 9 BP 3317 EP 3322 DI 10.1128/AAC.48.9.3317-3322.2004 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 850PV UT WOS:000223625800016 PM 15328091 ER PT J AU Maslow, JN Lautenbach, E Glaze, T Bilker, W Johnson, JR AF Maslow, JN Lautenbach, E Glaze, T Bilker, W Johnson, JR TI Colonization with extraintestinal pathogenic Escherichia coli among nursing home residents and its relationship to fluoroquinolone resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INFECTIONS; KLEBSIELLA; STRAINS; URINARY AB In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic Escherichia coli (ExPEC), 22% were colonized with adhesin-positive E. coli, and 51% were colonized with fluoroquinolone-resistant E. coli. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance. C1 Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA 19104 USA. Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Mucosal & Vaccine Res Ctr, Minneapolis, MN 55455 USA. RP Maslow, JN (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, 151,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM joel.maslow@med.va.gov FU AHRQ HHS [U18-HS10399, U18 HS010399]; NIAID NIH HHS [U01 AI032783, AI32783]; NIDDK NIH HHS [DK-02987-01] NR 15 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2004 VL 48 IS 9 BP 3618 EP 3620 DI 10.1128/AAC.48.9.3618-3620.2004 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 850PV UT WOS:000223625800067 PM 15328142 ER PT J AU McNeil, MR Hula, WD Matthews, CT Doyle, PJ AF McNeil, MR Hula, WD Matthews, CT Doyle, PJ TI Resource theory and aphasia: A fugacious theoretical dismissal SO APHASIOLOGY LA English DT Editorial Material ID PERFORMANCE; BOTTLENECK C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 11 TC 1 Z9 2 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD SEP PY 2004 VL 18 IS 9 BP 836 EP 839 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 845WK UT WOS:000223275800005 ER PT J AU Curiel-Lewandrowski, C Williams, CM Swindells, KJ Tahan, SR Astner, S Frankenthaler, RA Gonzalez, S AF Curiel-Lewandrowski, C Williams, CM Swindells, KJ Tahan, SR Astner, S Frankenthaler, RA Gonzalez, S TI Use of in vivo confocal microscopy in malignant melanoma - An aid in diagnosis and assessment of surgical, and nonsurgical therapeutic approaches SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SCANNING LASER MICROSCOPY; PIGMENTED SKIN-LESIONS; LENTIGO MALIGNA; IMIQUIMOD; BENIGN AB Background: Melanomas with poorly defined borders, lack of pigmentation, lentiginous extension, and location in cosmetically sensitive regions represent diagnostic and therapeutic challenges. Repeated surgical reexcisions are frequently required to achieve tumor-free margins. The use of reflectance mode confocal microscopy as an noninvasive method has shown to be a promising tool for diagnosing pigmented lesions in vivo. Observations: We report 3 clinical cases of melanoma: amelanotic melanoma (case 1), locally recurrent melanoma (case 2), and lentigo maligna melanoma (case 3). In case 1, in vivo confocal microscopy was instrumental in making the diagnosis and in monitoring the response to imiquimod therapy for in situ residual disease. It was also used to successfully delineate preoperative surgical margins in cases 2 and 3. Conclusion: As new methods for treating melanoma emerge and become more available, confocal microscopy can play a significant role by improving sensitivity in diagnosis, by increasing rates of successful initial excision, and by serving as a noninvasive means of monitoring therapy. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Beth Israel Deasoness Med Ctr,Dept Dermatol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Internal Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dermatopathol Sect, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cutaneous Oncol Program, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol, Boston, MA 02114 USA. RP Curiel-Lewandrowski, C (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Beth Israel Deasoness Med Ctr,Dept Dermatol, 330 Brookline Ave, Boston, MA 02215 USA. EM ccuriel@bidmc.harvard.edu FU PHS HHS [1999/P/008597] NR 22 TC 65 Z9 70 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2004 VL 140 IS 9 BP 1127 EP + DI 10.1001/archderm.140.9.1127 PG 7 WC Dermatology SC Dermatology GA 853NT UT WOS:000223835000012 PM 15381554 ER PT J AU Kesari, S AF Kesari, S TI Digital rendition of visual migraines SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kesari, S (reprint author), Dana Farber Canc Inst, Shields Warren 430,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2004 VL 61 IS 9 BP 1464 EP 1465 DI 10.1001/archneur.61.9.1464 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 852JG UT WOS:000223751000020 PM 15364697 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Moser, A Brockhurst, RJ Hayes, KC Johnson, CA Anderson, EJ Gaudio, AR Willett, WC Schaefer, E AF Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Moser, A Brockhurst, RJ Hayes, KC Johnson, CA Anderson, EJ Gaudio, AR Willett, WC Schaefer, E TI Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINOID-BINDING PROTEIN; HUMPHREY FIELD ANALYZER; FATTY-ACIDS; VISUAL-FIELDS; PLASMA; SUPPLEMENTATION; FASTPAC; CELLS; PHOSPHOLIPIDS; PREVALENCE AB Objective: To determine whether a therapeutic dose of docosahexaenoic acid (DHA), an omega-3 fatty acid, will slow the course of retinal degeneration in adult patients with retinitis pigmentosa who are also receiving vitamin A. Design: Randomized, controlled, double-masked trial of 221 patients, aged 18 to 55 years, evaluated over a 4-year interval. Patients were given either 1200 mg/d of docosahexaenoic acid or control capsules. All were given 15 000 IU/d of vitamin A (given as retinyl palmitate). Randomization considered genetic type and baseline dietary w-3 fatty acid intake. Main Outcome Measures: The primary outcome measure was the total point score for the 30-2 program of the Humphrey field analyzer; secondary outcome measures were the total point score for the 30-2 and 30/60-1 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Rentinopathy Study visual acuity. Results: No significant differences in decline in ocular function were found between the docosahexaenoicacid plus vitamin A (DHA+A) group and control plus vitamin A (control+A) group over a 4-year interval among all 221 randomized patients or among the 208 patients who completed all 4 follow-up visits. The mean annual rate of loss of sensitivity for the Humphrey Field Analyzer 30-2 program was 37 dB for the DHA+A group and 38 dB for the control+A group (P = .88). For the Humphrey Field Analyzer 30-2 and 30/60-1 programs combined, the mean annual rates of loss of field sensitivity were 57 dB for the DHA+A group and 60 dB (P = .73) for control+A group. No toxic adverse effects were observed. No significant differences by treatment group assignment were observed within genetic types or within the category of baseline w-3 fatty acid intake. Conclusion: In patients assigned to receive 15 000 IU/d of vitamin A, this randomized trial showed that 1200 mg/d of docosahexacnoic acid supplementation over a 4-year interval did not, on average, slow the course of disease in patients with retinitis pigmentosa. C1 Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Kennedy Krieger Inst, Peroxisomal Dis Lab, Baltimore, MD USA. Brandeis Univ, Foster Biomed Res Lab, Waltham, MA 02254 USA. Devers Eye Inst, Portland, OR USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Tufts Univ, Ctr Aging, Jean Mayer US Dept Agr Human Nutr Res, Lipid Metab Lab, Boston, MA USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [U10 EY 11030] NR 55 TC 57 Z9 59 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2004 VL 122 IS 9 BP 1297 EP 1305 DI 10.1001/archopht.122.9.1297 PG 9 WC Ophthalmology SC Ophthalmology GA 852AB UT WOS:000223726500005 PM 15364708 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Moser, A Brockhurst, RJ Hayes, KC Johnson, CA Anderson, EJ Gaudio, AR Willett, WC Schaefer, E AF Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Moser, A Brockhurst, RJ Hayes, KC Johnson, CA Anderson, EJ Gaudio, AR Willett, WC Schaefer, E TI Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment - Subgroup analyses SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINOID-BINDING PROTEIN; FATTY-ACIDS; SUPPLEMENTATION; OMEGA-3-FATTY-ACIDS; MEMBRANES; TRIAL; BRAIN AB Objective: To determine whether docosahexaenoic acid will slow the course of retinal degeneration in subgroups of patients with retinitis pigmentosa who are receiving vitamin A. Design: A cohort of 208 patients with retinitis pigmentosa, aged 18 to 55 years, were randomly assigned to 1200 mg of docosahexaenoic acid plus 15000 IU/d of vitamin A given as retinyl palmitate (DHA+A group) or control fatty acid plus 15000 IU/d of vitamin A (control+A group) and followed up over 4 years. Seventy percent of the patients in each group were taking. vitamin A, 15000 IU/d, prior to entry. We compared rates of decline in ocular function in the DHA+A vs control+A groups among the subgroups defined by use or nonuse of vitamin A prior to entry. We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level, dietary omega-3 fatty acid intake, or duration of vitamin A use. Main outcome measures were Humphrey Field Analyzer visual field sensitivity, 30-Hz electroretinogram amplitude, and visual acuity. Results: Among patients not taking vitamin A prior to entry, those in the DHA+A group had a slower declinein field sensitivity and electroretinogram amplitude than those in the control+A group over the first 2 years (P = .01 and P = .03, respectively); these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry. In the entire cohort, red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years (test for trend, P =. 05). This was particularly evident over the first 2 years among those not on vitamin A prior to entry (test for trend, P = .003). In the entire control+A group, dietary w-3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years (intake, <0.20 vs greater than or equal to0.20 g/d; P = .02). The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude (P = .008). Conclusions: For patients with retinitis pigmentosa beginning vitamin A therapy, addition of docosahexaenoic acid, 1200 mg/d, slowed the course of disease for 2 years. Among patients on vitamin A for at least 2 years, a diet rich in omega-3 fatty acids (greater than or equal to0.20 g/d) slowed the decline in visual field sensitivity. C1 Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02114 USA. Tufts Univ, Ctr Aging, Jean Mayer US Dept Agr Human Nutr Res, Lipid Metab Lab, Boston, MA 02111 USA. Kennedy Krieger Inst, Peroxisomal Dis Lab, Baltimore, MD USA. Brandeis Univ, Foster Biomed Res Lab, Waltham, MA USA. Devers Eye Inst, Portland, OR USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [U10 EY 11030] NR 16 TC 80 Z9 84 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2004 VL 122 IS 9 BP 1306 EP 1314 DI 10.1001/archopht.122.9.1306 PG 9 WC Ophthalmology SC Ophthalmology GA 852AB UT WOS:000223726500006 PM 15364709 ER PT J AU Abramson, DH Melson, MR Servodidio, C AF Abramson, DH Melson, MR Servodidio, C TI Visual fields in retinoblastoma survivors SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR RETINOBLASTOMA; SUBCONJUNCTIVAL CARBOPLATIN; BILATERAL RETINOBLASTOMA; CHEMOTHERAPY; RADIATION; MELANOMA; CHEMOREDUCTION; RADIOTHERAPY; IRRADIATION; MANAGEMENT AB Objective: To describe the visual field defects in retinoblastoma survivors and relate those defects to characteristics such as tumor size, tumor location, and treatment modality. Methods: Thirty-one patients treated for retinoblastoma were included in this study. Humphrey visual fields were determined in 33 eyes. Results: Twenty-seven patients (29 eyes, 68 tumors) had sufficient diagnosis and treatment data available for further analysis. Twenty-six of the 27 patients had both absolute and relative visual field defects. Four types of visual field defects were observed and correlated with location of the tumor and therapy to the individual tumors: (1) no residual defect, (2) absolute scotoma, (3) arcuate and sector scotoma, and (4) "pseudo"-visual field defects caused by relative enophthalmos resulting from radiation. Conclusions: Patients with retinoblastoma demonstrate a variety of long-term visual field defects after treatment for their intraocular disease. Characteristics that determine the size and type of defects are tumor size, tumor location, and treatment method. C1 Mem Sloan Kettering Canc Ctr, Ophthalmol Oncol Serv, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Ophthalmol Oncol Serv, Dept Radiat Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Ophthalmol Oncol Serv, Dept Pediat, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Hartford Hosp, Dept Radiat Oncol, Hartford, CT 06115 USA. RP Abramson, DH (reprint author), Mem Sloan Kettering Canc Ctr, Ophthalmol Oncol Serv, Dept Surg, 70E 66th St, New York, NY 10021 USA. EM ICANCERMD@aol.com NR 27 TC 7 Z9 7 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2004 VL 122 IS 9 BP 1324 EP 1330 DI 10.1001/archopht.122.9.1324 PG 7 WC Ophthalmology SC Ophthalmology GA 852AB UT WOS:000223726500008 PM 15364711 ER PT J AU Kamil, SH Eavey, RD Vacanti, MP Vacanti, CA Hartnick, C AF Kamil, SH Eavey, RD Vacanti, MP Vacanti, CA Hartnick, C TI Tissue-engineered cartilage as a graft source for laryngotracheal reconstruction - A pig model SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; ELASTIC CARTILAGE; CHONDROCYTES; CHILDREN; ENVIRONMENT; SUPPORT AB Objective: To evaluate the feasibility of using tissue-engineered cartilage for laryngotracheal reconstruction in the pig model. Design: Auricular cartilage was harvested from 3 young swine. The cartilage was digested, processed, and suspended and a cell culture was obtained. The cells were then suspended in 3 mL of a 30% solution of a biodegradable polymer (Pluronic F-127) (polyethylene oxide/polypropylene oxide copolymer) at a cellular concentration of 50 X 101 cells/mL. This suspension was then implanted subcutaneously into each pig's dorsum. Eight weeks after implantation, the cartilage was harvested with the surrounding perichondrial capsule. An anterior cartilage graft laryngotracheal reconstruction was performed. Bronchoscopy was performed at 3 postoperative weeks to demonstrate airway patency. The animals were killed at 3 months, and specimens were obtained for histological analysis. Setting: An animal research facility. Subjects: Three young Yorkshire swine. Results: All 3 pigs survived to the 3-month postoperative interval with no evidence of stridor or airway distress. Interval bronchoscopy revealed a normal patent airway with a mucosalized graft. Histopathologic analysis revealed incorporation of the tissue-engineered cartilage graft in the cricoid area, which correlated with results of bronchoscopic evaluation. Conclusion: Tissue-engineered auricular cartilage served as a viable graft in the pig model and might be an alternative cartilage source for laryngotracheal reconstruction. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Pediat Otolaryngol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Pediat Otolaryngol Serv, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu NR 19 TC 27 Z9 30 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD SEP PY 2004 VL 130 IS 9 BP 1048 EP 1051 DI 10.1001/archotol.130.9.1048 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 852ZV UT WOS:000223796500008 PM 15381591 ER PT J AU Shin, JJ Hartnick, CJ AF Shin, JJ Hartnick, CJ TI Otologic manifestations of ectodermal dysplasia SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 04-05, 2003 CL NASHVILLE, TN SP Amer Soc Pediat Otolaryngol ID OTOLARYNGOLOGIC MANIFESTATIONS; MANAGEMENT; CHILDREN AB Objectives: To determine the range and prevalence of otologic disorders in patients with ectodermal dysplasia (ED) and provide a general review of its multiple otolaryngological manifestations. Design: Case series. Setting: Ectodermal dysplasia family conference Patients: Sixty-nine individuals with ED were evaluated. The average age was I I years (range, 1-56 years). Most were male patients (44 [64%]), and most had Christ-Siemens-Touraine syndrome/hypohidrotic ED (42 [61%]), with the remaining having Hay-Wells, Clouston, and ectrodactyly ED clefting syndromes and unclassified types of ED. Interventions: Questionnaire including a quality-of-life assessment modeled after the Otitis Media 6 instrument, physical examination, screening audiogram, and tympanometry. Results: Of the 69 patients, 15 (22%) had a known history of hearing loss, and over half reported some level of difficulty processing verbal information (30 patients [43%] reported speech problems and 4 patients [ 6%] required hearing aids). A history of otitis media was common, with 15 patients (21%) presenting with tympanostomy tubes in place. The mean +/-SD quality-of-life rating was 2.0 +/- 1.1 (range 1-7), with lower scores suggesting less of a problem. On physical examination, 18 patients (26%) had pinna anomalies. One case of advanced cholesteatoma and 2 cases of external auditory canal stenosis were identified. Of the 24 patients who received 4-tone screening audiogram, 2 (8%) had a highest pure-tone average threshold of 50 to 65 dB, whereas 5 patients (21%) had a 30- to 45-dB threshold, with the remaining having a 0- to 25-dB threshold. Conclusion: In our study, which is, to our knowledge, the largest reported collection of ED patients evaluated for otologic disease, most patients were found to have I or more otologic abnormalities, ranging from auricular anomaly to complications of otitis media to profound hearing loss. C1 Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Harvard Program Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 12 TC 7 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD SEP PY 2004 VL 130 IS 9 BP 1104 EP 1107 DI 10.1001/archotol.130.9.1104 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 852ZV UT WOS:000223796500016 PM 15381599 ER PT J AU Tang, ZQ Jing, W Lindeman, N Harris, NL Ferry, JA AF Tang, ZQ Jing, W Lindeman, N Harris, NL Ferry, JA TI One patient, two lymphomas - Simultaneous primary gastric marginal zone lymphoma and primary duodenal follicular lymphoma SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID B-CELL LYMPHOMA; HELICOBACTER-PYLORI; GASTROINTESTINAL-TRACT; SMALL-INTESTINE; MALT LYMPHOMA; TISSUE; ERADICATION AB We report the case of a 73-year-old man who presented with a 2- to 3-month history of epigastric discomfort and guaiac-positive stool. An upper gastrointestinal endoscopy revealed a diffuse erythematous nodular mucosa and submucosal thickening in the stomach. Diffuse mucosal nodularity was also found in the second portion of the duodenum. A complete workup with histologic, immunohistochemical, and molecular studies revealed 2 distinct, apparently unrelated lymphomas, namely, a gastric marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in a background of Helicobacter pylori gastritis and a grade 1/3 duodenal follicular lymphoma. The patient was then treated with an H pylori eradication regimen. No therapy was given for his duodenal follicular lymphoma because his symptoms were thought to be due to the gastric disease and because the duodenal lesion was small. A 6-month follow-up with upper gastrointestinal endoscopy revealed only focal biopsy scarring in the stomach and an apparently normal duodenum. The follow-up biopsies revealed significant regression of his mucosa-associated lymphoid tissue lymphoma, but persistence of his duodenal follicular lymphoma. The combination of these 2 lymphomas in the same patient and the different clinical responses to antibiotic treatment make this case unique. C1 Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Diagnost Mol Lab, Boston, MA 02115 USA. RP Ferry, JA (reprint author), Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 15 TC 14 Z9 14 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 SEP PY 2004 VL 128 IS 9 BP 1035 EP 1038 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 852AG UT WOS:000223727000015 PM 15335250 ER PT J AU Lazovich, DA Forster, J Sorensen, G Emmons, K Stryker, J Demierre, MF Hickle, A Remba, N AF Lazovich, DA Forster, J Sorensen, G Emmons, K Stryker, J Demierre, MF Hickle, A Remba, N TI Characteristics associated with use or intention to use indoor tanning among adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID NONMELANOMA SKIN-CANCER; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; SUNSCREEN USE; RISK-FACTORS; SUNBED USE; PLANNED BEHAVIOR; ULTRAVIOLET-A; UNITED-STATES; PYRIMIDINE DIMERS AB Background: Indoor tanning is a popular behavior that may increase skin cancer risk. Objective: To examine characteristics associated with use or intention to use indoor tanning among adolescents. Methods: A telephone interview was conducted with 1273 adolescents, aged 14 to 17 years, in the Minneapolis-St Paul, Minn, and Boston, Mass, metropolitan areas. Questions included demographic and phenotypic characteristics, knowledge, attitudes, social factors, use of indoor tanning, and intention to tan indoors. Results: Twelve percent of boys and 42% of girls had tanned indoors, Among nontanners, 22.4% planned to start, and 77.2% of tanners planned to continue tanning indoors. Nontanners and tanners at risk for future indoor tanning use were each significantly more likely to be female, less likely to use sun protection, less knowledgeable about skin cancer risks, more likely to agree that tans were attractive, and more strongly influenced by social factors compared with their low-risk counterparts. Conclusions: Our data suggest that intention to tan indoors may identify a group of adolescents at risk for adopting the behavior; prospective studies are needed for confirmation. C1 Univ Minnesota, Div Epidemiol, St Paul, MN 55108 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Dept Dermatol, Boston, MA 02215 USA. RP Lazovich, DA (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM lazovich@epi.umn.edu FU NCI NIH HHS [1R01 CA 079593] NR 66 TC 72 Z9 73 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2004 VL 158 IS 9 BP 918 EP 924 DI 10.1001/archpedi.158.9.918 PG 7 WC Pediatrics SC Pediatrics GA 852IW UT WOS:000223750000011 PM 15351760 ER PT J AU Petri, MA Mease, PJ Merrill, JT Lahita, RG Iannini, MJ Yocum, DE Ginzler, EM Katz, RS Gluck, OS Genovese, MC Van Vollenhoven, R Kalunian, KC Manzi, S Greenwald, MW Buyon, JP Olsen, NJ Schiff, MH Kavanaugh, AF Caldwell, JR Ramsey-Goldman, R St Clair, EW Goldman, AL Egan, RM Polisson, RP Moder, KG Rothfield, NF Spencer, RT Hobbs, K Fessler, BJ Calabrese, LH Moreland, LW Cohen, SB Quarles, BJ Strand, V Gurwith, M Schwartz, KE AF Petri, MA Mease, PJ Merrill, JT Lahita, RG Iannini, MJ Yocum, DE Ginzler, EM Katz, RS Gluck, OS Genovese, MC Van Vollenhoven, R Kalunian, KC Manzi, S Greenwald, MW Buyon, JP Olsen, NJ Schiff, MH Kavanaugh, AF Caldwell, JR Ramsey-Goldman, R St Clair, EW Goldman, AL Egan, RM Polisson, RP Moder, KG Rothfield, NF Spencer, RT Hobbs, K Fessler, BJ Calabrese, LH Moreland, LW Cohen, SB Quarles, BJ Strand, V Gurwith, M Schwartz, KE TI Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus - Results of a multicenter randomized, double-blind, placebo-controlled trial SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT Annual Meeting of the British-Society-for-Rheumatology CY APR, 2003 CL Manchester, ENGLAND SP British Soc Rheumatol ID IL-6 SECRETION; T-CELLS; DEHYDROEPIANDROSTERONE; INTERLEUKIN-2; ANDROGENS; THERAPY; MICE; SLE; BIOSYNTHESIS; RELIABILITY AB Objective. To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms. Methods. Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (greater than or equal to10 mg/day), antimalarials, and immunosuppressive agents; dosages were required to be stable for greater than or equal to6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale). Results. A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group. Conclusion. In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated. C1 Johns Hopkins Univ, Med Ctr, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA. Rheumatol Associates, Seattle, WA USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Liberty Hlth, Jersey, NJ USA. Carondelet Med Grp, Tucson, AZ USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. SUNY Brooklyn, Hlth Sci Ctr, Brooklyn, NY USA. Rheumatol Associates, Chicago, IL USA. Stanford Univ, Sch Med, Stanford, CA USA. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Advances Med, Rancho Mirage, CA USA. NYU, Sch Med, New York, NY USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Denver Arthrit Clin, Denver, CO USA. Halifax Clin Res Inst, Daytona Beach, FL USA. Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. Duke Univ, Med Ctr, Durham, NC USA. Ctr Rheumat Dis, Milwaukee, WI USA. Arthrit Ctr Lexington, Lexington, KY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin Fdn, Rochester, MN USA. Univ Connecticut, Med Ctr, Farmington, CT USA. Colorado Arthrit Ctr, Englewood, CO USA. Univ Alabama, Sch Med, Birmingham, AL USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. St Paul Med Ctr, Dallas, TX USA. RP Petri, MA (reprint author), Johns Hopkins Univ, Med Ctr, Dept Med, Div Rheumatol, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@welch.jhu.edu NR 43 TC 73 Z9 77 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 SEP PY 2004 VL 50 IS 9 BP 2858 EP 2868 DI 10.1002/art.20427 PG 11 WC Rheumatology SC Rheumatology GA 853AU UT WOS:000223799200017 PM 15452837 ER PT J AU Ang, DC Choi, H Kroenke, K Wolfe, F AF Ang, DC Choi, H Kroenke, K Wolfe, F TI Co-morbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Indiana Univ, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Arthrit Res Ctr Fdn, Wichita, KS 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 SEP PY 2004 VL 50 IS 9 SU S BP S484 EP S484 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001303 ER PT J AU Brey, RL Fox, PT Narayana, S Martinez, MJ Naqibuddin, M Holliday, SL Wallace, DJ Weisman, MH Petri, M AF Brey, RL Fox, PT Narayana, S Martinez, MJ Naqibuddin, M Holliday, SL Wallace, DJ Weisman, MH Petri, M TI Brain imaging findings in an SLE inception cohort: Brain CONECTIONS. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UTHSCSA, San Antonio, TX USA. Johns Hopkins Univ, Baltimore, MD USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 SEP PY 2004 VL 50 IS 9 SU S BP S194 EP S194 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000456 ER PT J AU Choi, H Liu, SM Curhan, G AF Choi, H Liu, SM Curhan, G TI Intake of purine-rich foods, protein, dairy products, and serum uric acid level - The Third National Health and Nutrition Examination Survey SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 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 SEP PY 2004 VL 50 IS 9 SU S BP S340 EP S340 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000883 ER PT J AU Choi, H Poe, D Wise, C Rahman, M Matteson, EL AF Choi, H Poe, D Wise, C Rahman, M Matteson, EL TI Etanercept therapy for immune-mediated cochleovestibular disorders: An open-label, pilot clinical trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Virginia Commonwealth Univ, Med Coll Virginia, Div Rheumatol, Richmond, VA 23298 USA. Mayo Clin, Rheumatol Unit, Rochester, MN USA. NR 0 TC 2 Z9 2 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 SEP PY 2004 VL 50 IS 9 SU S BP S235 EP S236 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000584 ER PT J AU Choi, H Curhan, G AF Choi, H Curhan, G TI Beer, liquor, and wine consumption and serum uric acid level - The Third National Health and Nutrition Examination Survey. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 SEP PY 2004 VL 50 IS 9 SU S BP S480 EP S480 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001293 ER PT J AU Chou, RC Mackool, BT Strasswimmer, JM Liu, V Moschella, SL Kay, J AF Chou, RC Mackool, BT Strasswimmer, JM Liu, V Moschella, SL Kay, J TI Thalidomide therapy improves skin thickening and joint contractures in nephrogenic fibrosing dermopathy SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lahey Clin Fdn, Burlington, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S635 EP S636 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001761 ER PT J AU Cooper, GS Schur, PH Fraser, PA AF Cooper, GS Schur, PH Fraser, PA TI Frequencies of anti-nuclear antibodies (ANA) in a population-based sample of healthy individuals: Possible associations of high titer ANA with occupational exposures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Environm Sci, Res Triangle Pk, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. CBR, Biomed Res Inst, 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 SEP PY 2004 VL 50 IS 9 SU S BP S485 EP S485 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001306 ER PT J AU Gillett, CD Langfeld, C Ortmann, W Graham, R Rodine, P Williams, A Selby, S Gaffney, P Moser, K Behrens, T AF Gillett, CD Langfeld, C Ortmann, W Graham, R Rodine, P Williams, A Selby, S Gaffney, P Moser, K Behrens, T TI Fine mapping of systemic lupus erythematosus (SLE) supports heterogenic susceptibility on chromosome 16q12 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Minnesota, Minneapolis, MN USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S121 EP S121 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000242 ER PT J AU Herrera, M Gonzalez, E Kulkarni, H Correa, P Holliday, SL Brey, RL Rovin, BH Anaya, JM Ahuja, SK AF Herrera, M Gonzalez, E Kulkarni, H Correa, P Holliday, SL Brey, RL Rovin, BH Anaya, JM Ahuja, SK TI Genetic evidence for the common variants/multiple disease hypothesis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UTHSCSA, San Antonio, TX USA. CIB, Medellin, Colombia. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Ohio State Univ, Columbus, OH 43210 USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 1 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 SEP PY 2004 VL 50 IS 9 SU S BP S120 EP S120 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000239 ER PT J AU Holliday, SL Saklad, AR Fischbach, M Garcia-Cavasos, R Padilla, PA Brey, RL AF Holliday, SL Saklad, AR Fischbach, M Garcia-Cavasos, R Padilla, PA Brey, RL TI Risk factors for cognitive dysfunction in SLE: San Antonio lupus study of neuropsychiatric disease (SALUD). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. UTHSCSA, San Antonio, TX 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 SEP PY 2004 VL 50 IS 9 SU S BP S256 EP S257 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000639 ER PT J AU Hsu, HC Zhou, T Yang, PA Wu, Q Zhou, JL Wang, Z Liu, D Mountz, JD AF Hsu, HC Zhou, T Yang, PA Wu, Q Zhou, JL Wang, Z Liu, D Mountz, JD TI Generation of kidney- or joint-specific pathogenic hybridomas derived from the spleen of a mouse of the BXD2 strain, which exhibit both lupus and an erosive arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S220 EP S221 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000536 ER PT J AU Kahn, KL Liu, HH MacLean, C Fitzpatrick, D Chen, WP Wong, A Bulpitt, K Bradley, M Harker, J Traina, S Mittman, B Rubenstein, L Hahn, B Paulus, H AF Kahn, KL Liu, HH MacLean, C Fitzpatrick, D Chen, WP Wong, A Bulpitt, K Bradley, M Harker, J Traina, S Mittman, B Rubenstein, L Hahn, B Paulus, H TI Depression in patients with rheumatoid arthritis (RA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RAND, Santa Monica, CA 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 SEP PY 2004 VL 50 IS 9 SU S BP S322 EP S322 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000829 ER PT J AU Kahn, KL MacLean, CH Liu, HH Fitzpatrick, D Wong, A Bulpitt, K Bradley, M Harker, J Mittman, B Rubenstein, LZ Hahn, BH Paulus, HE AF Kahn, KL MacLean, CH Liu, HH Fitzpatrick, D Wong, A Bulpitt, K Bradley, M Harker, J Mittman, B Rubenstein, LZ Hahn, BH Paulus, HE TI Variations in adherence to recommended process for rheumatoid arthritis (RA) patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RAND, Santa Monica, CA 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 SEP PY 2004 VL 50 IS 9 SU S BP S322 EP S322 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000828 ER PT J AU Kane, MA Fishbein, R Breen, K Hogan, N Finger, W Peterson, J Kline-Schoder, R AF Kane, MA Fishbein, R Breen, K Hogan, N Finger, W Peterson, J Kline-Schoder, R TI Comparison of head mounted and flat screen displays in a virtual reality-enhanced range of motion system for treating adhesive capsulitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Creare Res & Dev Inc, E Hanover, NJ USA. Creare Res & Dev Inc, Hanover, NM 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S472 EP S473 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001270 ER PT J AU Lee, YH Kaufman, KM Harley, JB Sestak, AL AF Lee, YH Kaufman, KM Harley, JB Sestak, AL TI The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: A meta-analysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Oklahoma, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 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 SEP PY 2004 VL 50 IS 9 SU S BP S204 EP S205 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000488 ER PT J AU McLaurin, EY Holliday, SL Wing, NF Russell, IJ Brey, RL AF McLaurin, EY Holliday, SL Wing, NF Russell, IJ Brey, RL TI Cognitive functioning in patients with fibromyalgia compared to patients with lupus and normal controls. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UTHSCSA, San Antonio, TX USA. Vet Affairs Med Ctr, San Antonio, TX 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 SEP PY 2004 VL 50 IS 9 SU S BP S494 EP S494 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001335 ER PT J AU Naqibuddin, M Wallace, DJ Weisman, MH Holliday, SL Wing, NF Brey, RL Petri, M AF Naqibuddin, M Wallace, DJ Weisman, MH Holliday, SL Wing, NF Brey, RL Petri, M TI Cognitive functioning in recently-diagnosed systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX 78285 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S195 EP S195 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000459 ER PT J AU Quinones, MP Ahuja, SK Reddick, RL Jimenez, F Melby, PM Kuziel, WA Ahuja, SS AF Quinones, MP Ahuja, SK Reddick, RL Jimenez, F Melby, PM Kuziel, WA Ahuja, SS TI Role of chemokine receptor-2 in autoimmune arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Austin, TX 78712 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 SEP PY 2004 VL 50 IS 9 SU S BP S442 EP S442 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001180 ER PT J AU Saklad, AR Holliday, SL Fischbach, M Brey, RL AF Saklad, AR Holliday, SL Fischbach, M Brey, RL TI Psychiatric diagnoses in adults SLE patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UTHSCSA, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 SEP PY 2004 VL 50 IS 9 SU S BP S195 EP S196 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000461 ER PT J AU Ton, FN Gunawardene, SC Neer, RM AF Ton, FN Gunawardene, SC Neer, RM TI Parathyroid hormone's effects on bone resorption and formation markers in women with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S498 EP S498 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001345 ER PT J AU Ton, FN Gunawardene, SC Lee, H Neer, RM AF Ton, FN Gunawardene, SC Lee, H Neer, RM TI Effects of low dose prednisone on bone metabolism. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S495 EP S496 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001339 ER PT J AU Traina, SB MacLean, CH Park, GS Paulus, HE Harker, JO Wong, AL Rubenstein, LZ Fitzpatrick, D Louie, R Liu, HH Chen, WP Hahn, BH Kahn, KL AF Traina, SB MacLean, CH Park, GS Paulus, HE Harker, JO Wong, AL Rubenstein, LZ Fitzpatrick, D Louie, R Liu, HH Chen, WP Hahn, BH Kahn, KL TI Mental health scores and social support are not associated with disease duration in rheumatoid arthritis patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RAND, Santa Monica, CA 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 SEP PY 2004 VL 50 IS 9 SU S BP S321 EP S321 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000826 ER PT J AU Wong, AL Harker, JO Park, GS Paulus, HE AF Wong, AL Harker, JO Park, GS Paulus, HE TI Longitudinal measurement of RA disease activity in a clinical practice setting: Usefulness of the SDAL SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 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 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S386 EP S387 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001021 ER PT J AU Yigitbas, E Uner, G Hurwitz, S Ding, WZ Tatayoglu, G Balci, B Duzova, A Ozaltin, F Ozen, S Besbas, N Topaloglu, R Yilmaz, E Bakkaloglu, A Ozguc, M Kansu, E Fraser, PA AF Yigitbas, E Uner, G Hurwitz, S Ding, WZ Tatayoglu, G Balci, B Duzova, A Ozaltin, F Ozen, S Besbas, N Topaloglu, R Yilmaz, E Bakkaloglu, A Ozguc, M Kansu, E Fraser, PA TI YMICA exon 5 microsatellite alleles modulate disease expression in Familial Mediterranean Fever (FMF) patients in Turkey SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Hacettepe Inst Oncol, Ankara, Turkey. Brigham & Womens Hosp, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA USA. Hacettepe Med Sch, Dept Med Biol, Ankara, Turkey. Hacettepe Med Sch, Dept Pediat Rheumatol & Nephrol, Ankara, Turkey. 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 SEP PY 2004 VL 50 IS 9 SU S BP S518 EP S519 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001407 ER PT J AU Maemura, T Shin, M Ishii, O Mochizuki, H Vacanti, JP AF Maemura, T Shin, M Ishii, O Mochizuki, H Vacanti, JP TI Initial assessment of a tissue engineered stomach derived from syngeneic donors in a rat model SO ASAIO JOURNAL LA English DT Article ID QUALITY-OF-LIFE; TOTAL GASTRECTOMY; POUCH RECONSTRUCTION; GASTRIC-CARCINOMA; EPITOPE AB The objective of this study is to assess the feasibility of creating a tissue engineered stomach using isolated stomach epithelium organoid unit from syngeneic adult donors and a biodegradable polymer scaffold in a rat model. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, a tissue engineered stomach that replaces the mechanical and metabolic functions of a normal stomach is proposed. Stomach epithelium organoid units were isolated from syngeneic adult rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of recipient adult rats. All constructs were harvested for histologic and immunohistochemical examination at designated time points. Cyst-like structures were formed that showed the development of vascularized tissue with a neomucosa. Immunohistochemical staining for a-actin smooth muscle, gastric mucin, and proton pump indicated the presence of a smooth muscle layer and gastric epithelium, as well as the existence of parietal cells of the stomach mucosa, respectively. Epithelium derived stomach organoid units seeded on biodegradable polymers were transplanted in donor rats and have been shown to vascularize, survive, and regenerate into complex tissue resembling a native stomach. These initial results are encouraging, and studies are currently underway to further assess this approach. C1 Natl Def Med Coll, Dept Surg 1, Tokorozawa, Saitama 3598513, Japan. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Maemura, T (reprint author), Natl Def Med Coll, Dept Surg 1, Namiki 3-2, Tokorozawa, Saitama 3598513, Japan. NR 14 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 2004 VL 50 IS 5 BP 468 EP 472 DI 10.1097/01.MAT.0000138579.25835.F5 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 857IQ UT WOS:000224110200011 PM 15497387 ER PT J AU Richardson, A Liu, F Adamo, ML Van Remmen, H Nelson, JF AF Richardson, A Liu, F Adamo, ML Van Remmen, H Nelson, JF TI The role of insulin and insulin-like growth factor-1 in mammalian ageing SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE insulin; insulin-like growth factor-1; caloric restriction; dwarf mice ID AGE-1 PI3 KINASE; LIFE-SPAN; CALORIE RESTRICTION; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; DWARF MICE; SKELETAL-MUSCLE; GLUCOSE-METABOLISM; STRESS RESISTANCE; PROTEIN-SYNTHESIS AB Research with invertebrates over the past 10 years has suggested that alterations in insulin and/or insulin-like growth factor I (IGF-I) signalling result in increased lifespan and retard ageing. In this chapter, we describe the current research in mammalian systems with respect to the role of insulin or IGF-I in ageing. Using rodent models of caloric restriction and genetic mouse models, e.g. the Ames and Snell dwarf mice, fat-specific insulin receptor knockout mice (FIRKO) and mice that are heterozygous for the IGF-I receptor (IgfIr(+/-)), investigators have shown that a reduction in plasma levels of insulin and/or IGF-I or reductions in insulin/IGF-I signalling appear to be correlated with increased longevity and retarded ageing. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. Geriatr Res Educ & Clin Ctr & Res Serv, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Ctr Hlth Sci, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Ctr Hlth Sci, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu NR 76 TC 42 Z9 45 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X EI 1532-1908 J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD SEP PY 2004 VL 18 IS 3 BP 393 EP 406 DI 10.1016/j.beem.2004.02.002 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847KQ UT WOS:000223391700007 PM 15261845 ER PT J AU Banerjee, P Reichardt, W Weissleder, R Bogdanov, A AF Banerjee, P Reichardt, W Weissleder, R Bogdanov, A TI Novel hyperbranched dendron for gene transfer in vitro and in vivo SO BIOCONJUGATE CHEMISTRY LA English DT Article ID LOW-MOLECULAR-WEIGHT; POLYAMIDOAMINE DENDRIMERS; PEI/DNA COMPLEXES; DELIVERY-SYSTEMS; BLOCK-COPOLYMERS; MAMMALIAN-CELLS; DNA COMPLEXES; PLASMID DNA; MOUSE LUNG; THERAPY AB Novel byperbranched dendron (HD) polymers were synthesized using a low molecular weight poly-(ethyleneimine) core (BPEI). Using successive attachment of ethyleneimine moieties to the PEI core, the relative ratio of linear-to-branched structures was lowered from 1.17 to 0.70. We found that the more extensive branching of PEI enables the condensation of plasmid DNA into nanostructures with a size of 70-100 nm. The obtained complexes were stable at least for 3 weeks at 4degreesC. The HD-DNA complexes prepared using secondary and tertiary amine-containing dendrons exerted a very low cytotoxicity in vitro during a coincubation with cells for 48 h. Using firefly luciferase as a marker of protein expression, we established that HD complexes were efficient in transfecting cells in the presence of serum. Under optimized conditions, the transfection activity at a nitrogen-to-phosphate (N/P) ratio of 6 was approximately six times higher than that of the commercially available polycationic transfection reagent. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene showed the increase of the signal in the liver and in submandibular lymph nodes in live mice. Our preliminary in vivo gene expression data demonstrates the potential of HD polymers as in vivo transfection agents that could be potentially useful for lymph node gene delivery. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu RI Reichardt, Wilfried/K-6727-2013 FU NCI NIH HHS [P50 CA86355] NR 51 TC 33 Z9 34 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2004 VL 15 IS 5 BP 960 EP 968 DI 10.1021/bc0342128 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 854WL UT WOS:000223934300003 PM 15366948 ER PT J AU Schellenberger, EA Sosnovik, D Weissleder, R Josephson, L AF Schellenberger, EA Sosnovik, D Weissleder, R Josephson, L TI Magneto/optical annexin V, a multimodal protein SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SUPERPARAMAGNETIC NANOPARTICLES; PHOSPHATIDYLSERINE EXPOSURE; TUMOR APOPTOSIS; TAT PEPTIDE; CELL-DEATH; FERROFLUID; ASYMMETRY; DISEASE; AGENT; ASSAY AB Multimodal proteins, or proteins labeled with both fluorescent and magnetic reporter groups, can be used in a wide range of applications including FACS or fluorescence microscopy, MRI and or near-infrared based optical imaging, or to fractionate cells by magnetic cell sorting. A problem with multimodal proteins, however, is the need to maximize bioactivity, often achieved by minimizing the number of modification points of the protein, while attaching fluorescent and magnetic labels. Here we describe the synthesis of a magneto/optical form of annexin V, achieved by reacting the amino-CLIO nanoparticle with Cy5.5 and SPDP, to produce a fluorescent, sulfhydryl reactive nanoparticle. A single reactive sulfhydryl group was added to annexin V by reaction with SATA that preserved the protein's ability to bind apoptotic Jurkat T cells. Reacting SATAylated annexin V with an SPDP activated nanoparticle yielded Anx-CLIO-Cy5.5, a magneto/optical form of annexin V. The binding of Anx-CLIO-Cy5.5 was specific for apoptotic Jurkat T cells and had an EC50 of 3.66 nM. This was comparable to the strength of the interaction of unmodified annexin V with apoptotic cells, measured as the displacement of FITC-annexin by annexin V (2.4 nM). Our conjugation strategy preserves the strength of the interaction between annexin V and apoptotic cells, while yielding a probe, Anx-CLIO-Cy5.5, that is readily detectable by standard MR imaging or NIRF optical methods. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU NCI NIH HHS [CA91807, P50CA86355, R01CA86782, R24 CA92782] NR 40 TC 145 Z9 150 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2004 VL 15 IS 5 BP 1062 EP 1067 DI 10.1021/bc049905i PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 854WL UT WOS:000223934300015 PM 15366960 ER PT J AU Thornley, L Lehmann, LE Sung, L Holmes, C Spear, HM Brennan, L Vangel, M Bechard, L Richardson, P Duggan, C Guinan, EC AF Thornley, L Lehmann, LE Sung, L Holmes, C Spear, HM Brennan, L Vangel, M Bechard, L Richardson, P Duggan, C Guinan, EC TI A multiagent strategy to decrease regimen-related toxicity in children undergoing allogeneic hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE regimen-related toxicity; hematopoietic stem cell transplantation; ursodeoxycholic; acid; folinic acid; vitamin E; parenteral nutrition ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST DISEASE; HEPATIC VENOOCCLUSIVE DISEASE; FOLINIC ACID RESCUE; VITAMIN-E; URSODEOXYCHOLIC ACID; PARENTERAL-NUTRITION; RANDOMIZED-TRIAL; ACUTE GRAFT AB Regimen-related toxicity (RRT) is a frequent cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this pilot study, we examined the feasibility and potential efficacy of administering a fixed combination of agents as a novel approach to reducing RRT in children undergoing HSCT. Thirty-seven patients were treated with ursodeoxycholic acid, folinic acid, vitamin E, and parenteral nutrition titrated to measured energy expenditure in the peritransplantation period. Outcomes were compared with those in historical controls (n = 131). Compliance with oral ursodeoxycholic acid and vitamin E of at least 90% was achieved in a mean of 86% (95% confidence interval, 75%-97%) of patients. In the study group, we observed (1) reduced prevalence and severity of mucositis (P = .008 and .004, respectively); (2) less severe hepatic toxicity (P = .007); and (3) shorter time to engraftment (P = .02) compared with the control group. These benefits appeared most pronounced among high-risk patients. The administration of this regimen, including oral medications, is feasible during the peri transplantation period, and it is well tolerated. The decreased RRT observed in comparison to historical controls suggests that combination approaches deserve exploration as a means of reducing the morbidity of HSCT. (C) 2004 American Societyfor Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Univ Toronto, Hosp Sick Children, Div Pediat Hematol Oncol, Toronto, ON M5G 1X8, Canada. Harvard Univ, Childrens Hosp, Sch Med, Dept Nursing, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Gastroenterol Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Eva_Guinan@dfci.harvard.edu NR 45 TC 13 Z9 13 U1 1 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2004 VL 10 IS 9 BP 635 EP 644 DI 10.1016/j.bbmt.2004.06.004 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 851HX UT WOS:000223677300006 ER PT J AU Porter, AE Taak, P Hobbs, LW Coathup, MJ Blunn, GW Spector, M AF Porter, AE Taak, P Hobbs, LW Coathup, MJ Blunn, GW Spector, M TI Bone bonding to hydroxyapatite and titanium surfaces on femoral stems retrieved from human subjects at autopsy SO BIOMATERIALS LA English DT Article DE hydroxyapatite; degradation; plasma spraying; electron microscopy ID COATED IMPLANTS; DISSOLUTION; COMPONENTS; COATINGS AB The success of clinical results obtained with many hydroxyapatite (HA)-coated prosthetic designs has deflected attention front the need to extend the life of the HA coating on the device. In the Current study the percentages of HA and titanium surfaces to which bone was bonded, on HA-coated and non-coated titanium femoral stems retrieved from human subjects, were evaluated. Plasma-sprayed hydroxyapatite (PSHA)-coated devices demonstrated wide variability in the percentage of the PSHA coating remaining on the stems. The coating was missing from a substantial portion of a stem after only about 6 months of implantation. The percentage of revealed metal to which bone was bonded was significantly less than the percentage of the HA coating demonstrating Such bonding. The revealed metal to which bone was bonded was comparable to the same value for a separate group of non-PSHA-coated titanium stems. If HA-coatings degrade over time precipitous decline in performance may occur even after several functional years. Many ultrastructural features of the bone bonded to the HA coatings on these implants from human subjects were comparable to those found on HA-coated devices implanted in a canine model. (C) 2003 Elsevier Ltd. All rights reserved. C1 MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. Univ Cambridge Darwin Coll, Dept Mat Sci & Met, Cambridge CB3 9EU, England. Royal Natl Orthopaed Hosp, Stanford, Middx, England. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Porter, AE (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. EM aep30@cam.ac.uk NR 22 TC 46 Z9 48 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2004 VL 25 IS 21 BP 5199 EP 5208 DI 10.1016/j.biomaterials.2003.12.018 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 820DG UT WOS:000221366400011 PM 15109844 ER PT J AU Younis, HF Kaazempur-Mofrad, MR Chan, RC Isasi, AG Hinton, DP Chau, AH Kim, LA Kamm, RD AF Younis, HF Kaazempur-Mofrad, MR Chan, RC Isasi, AG Hinton, DP Chau, AH Kim, LA Kamm, RD TI Hemodynamics and wall mechanics in human carotid bifurcation and its consequences for atherogenesis: investigation of inter-individual variation SO BIOMECHANICS AND MODELING IN MECHANOBIOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; COMPUTATIONAL FLUID-DYNAMICS; PROTEIN-1 GENE-EXPRESSION; AORTIC ENDOTHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; FINITE-ELEMENT-ANALYSIS; NF-KAPPA-B; SHEAR-STRESS; ARTERY BIFURCATION; PULSATILE FLOW AB Finite element simulations of fluid-solid interactions were used to investigate inter-individual variations in flow dynamics and wall mechanics at the carotid artery bifurcation, and its effects on atherogenesis, in three healthy humans (normal volunteers: NV1, NV2, N-V4). Subject-specific calculations were based on MR images of structural anatomy and ultrasound measurements of flow at domain boundaries. For all subjects, the largest contiguous region of low wall shear stress (WSS) occurred at the carotid bulb, WSS was high (6-10 Pa) at the apex, and a small localized region of WSS > 10 Pa occurred close to the inner wall of the external carotid artery (ECA). NV2 and NV4 had a "spot" of low WSS distal to the bifurcation at the inner wall of the ECA. Low WSS patches in the common carotid artery (CCA) were contiguous with the carotid bulb low WSS region in NV1 and NV2, but not in NV4. In all three subjects, areas of high oscillatory shear index (OSI) were confined to regions of low WSS. Only NV4 exhibited high levels of OSI on the external adjoining wall of the ECA and CCA. For all subjects, the maximum wall shear stress temporal gradient (WSSTG) was highest at the flow divider (reaching 1,000 Pa/s), exceeding 300 Pa/s at the walls connecting the ECA and CCA, but remaining below 250 Pa/s outside of the ECA. In all subjects, (maximum principle) cyclic strain (CS) was greatest at the apex (NV1: 14%; NV2: 11%; NV4: 6%), and a second high CS region occurred at the ECA CCA adjoining wall (NV1: 11%, NV2: 9%, NV4: 5%). Wall deformability was included in one simulation (NV2) to verify that it had little influence on the parameters studied. Location and magnitude of low WSS were similar, except for the apex (differences of up to 25%). Wall distensibility also influenced OSI, doubling it in most of the CCA, separating the single high OSI region of the carotid bulb into two smaller regions, and shrinking the ECA internal and external walls' high OSI regions. These observations provide further evidence that significant intra-subject variability exists in those factors thought to impact atherosclerosis. C1 MIT, Dept Engn Mech, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Younis, HF (reprint author), MIT, Dept Engn Mech, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rdkamm@mit.edu OI /0000-0002-7232-304X FU NHLBI NIH HHS [HL61794] NR 72 TC 104 Z9 113 U1 2 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1617-7959 J9 BIOMECH MODEL MECHAN JI Biomech. Model. Mechanobiol. PD SEP PY 2004 VL 3 IS 1 BP 17 EP 32 DI 10.1007/s10237-004-0046-7 PG 16 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 948ZD UT WOS:000230753300003 PM 15300454 ER PT J AU Wang, ML Williamson, JM Redline, S AF Wang, ML Williamson, JM Redline, S TI A semiparametric method for analyzing matched case-control family studies with a continuous outcome and proband sampling SO BIOMETRICS LA English DT Article DE aggregation; association; estimating function; family study; matched case-control study; nuisance; semiparametric ID SLEEP HEART HEALTH; CARDIOVASCULAR-DISEASE; GENETIC EPIDEMIOLOGY; ESTIMATING EQUATIONS; AGGREGATION; APNEA; ASSOCIATION; INTERCLASS; LIKELIHOOD; DESIGNS AB We consider matched case-control familial studies which match a group of patients, called "case probands," with a group of disease-free subjects, called "control probands," using a set of family-level matching variables. Family members of each proband are then recruited into the study. Of interest here is the familial aggregation of the response variable and the effects of subject-specific covariates on the response. We propose an estimating equation approach to jointly estimate the main effects and intrafamilial correlations for matched family studies with a continuous outcome. Only knowledge of the first two joint moments of the response variable is required. The induced estimators for the main effects and intrafamilial correlations are consistent and asymptotically normally distributed. We apply the proposed method to sleep apnea data. A simulation study demonstrates the usefulness of our approach. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Div Clin Epidemiol, Cleveland, OH 44106 USA. RP Wang, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM mwang@jimmy.harvard.edu FU NHLBI NIH HHS [HL 46380] NR 23 TC 2 Z9 2 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 644 EP 650 DI 10.1111/j.0006-341X.2004.00213.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200013 PM 15339286 ER PT J AU Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, JN Zon, LI Kanki, JP Look, AT AF Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, JN Zon, LI Kanki, JP Look, AT TI The pu. 1 promoter drives myeloid gene expression in zebrafish SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR PU.1; GERM-LINE TRANSMISSION; TRANSGENIC ZEBRAFISH; DEVELOPMENTAL BIOLOGY; ETS ONCOGENE; DNA-BINDING; SPI-1; HEMATOPOIESIS; GATA-1; CELLS AB PU.1 is a member of the Ets family of transcription factors and plays an essential role in the development of both myeloid and lymphoid cells. To examine zebrafish pu.1 (zpu.1) expression in sub-populations of blood cells during zebrafish development, we linked a 9-kb zebrafish genomic fragment upstream of the zpu.1 initiator codon to green fluorescent protein (GFP) and microinjected this construct to generate stable transgenic lines. GFP-positive fluorescent myeloid precursors were observed migrating from the anterolateral mesoderm in living embryos from 16 to 28 hours after fertilization (hpf) in a pattern that overlaps the expression pattern of endogenous zpu.1 mRNA. Analysis of larval histologic sections revealed GFP-expressing hematopoietic cells in the developing zebrafish kidney. Flow cytometric analysis of cells from adult whole kidney marrow revealed 2 discrete subpopulations of GFP-positive cells, which after cell sorting exhibited either myeloid or early lymphold morphology. Thus, the zebrafish zpu.1 promoter fragment used here is capable of driving reporter gene expression in subsets of embryonic and adult hematopoietic cells. These transgenic lines will be useful to dissect the cellular and molecular control of myeloid cell differentiation, and this promoter fragment may prove useful in the development of zebrafish models of acute myeloid leukemia. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU NCI NIH HHS [CA 93152, CA 96785, CA 006516] NR 32 TC 89 Z9 94 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1291 EP 1297 DI 10.1182/blood-2003-09-3105 PG 7 WC Hematology SC Hematology GA 849MX UT WOS:000223544000019 PM 14996705 ER PT J AU Traver, D Winzeler, A Stern, HM Mayhall, EA Langenau, DM Kutok, JL Look, AT Zon, LI AF Traver, D Winzeler, A Stern, HM Mayhall, EA Langenau, DM Kutok, JL Look, AT Zon, LI TI Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation SO BLOOD LA English DT Article ID COLONY-FORMING CELLS; MOUSE BONE-MARROW; STEM-CELLS; CARASSIUS AURATUS; SPLEEN COLONIES; X-IRRADIATION; CFU-S; 5-FLUOROURACIL; IDENTIFICATION; PROGENITORS AB The study of hematopoiesis has been greatly facilitated by transplantation of blood cell populations into recipient animals. Efficient engraftment of donor cells generally requires ablation of the host hematopoietic system. The zebrafish has recently emerged as a developmental and genetic system to study hematopoiesis. To enable the study of hematopoietic stem cell (HSC) biology, immune cell function, and leukemogenesis in zebrafish, we have developed hematopoietic cell transplantation (HCT) into adult recipient animals conditioned by 7 irradiation. Dose-response experiments showed that the minimum lethal dose (MILD) of 40 Gy led to the specific ablation of hematolymphoid cells and death by 14 days after irradiation. Sublethal irradiation doses of 20 Gy predominantly ablated lymphocytes and permitted transplantation of a lethal T-cell leukemia. Finally, transplantation of hematopoietic cells carrying transgenes yielding red fluorescent erythrocytes and green fluorescent leukocytes showed that HCT is sufficient to rescue the MLD, that recipient hematolymphoid tissues were repopulated by donor-derived cells, and that donor blood cell lineages can be independently visualized in living recipients. Together, these results establish transplantation assays to test for HSC function and oncogenic transformation in zebrafish. (C) 2004 by The American Society of Hematology. C1 Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, 1 Blackfan Circle,Rm 07211, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NCI NIH HHS [CA 68484, CA 06516]; NIDDK NIH HHS [5K08 DK 061849] NR 39 TC 90 Z9 96 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1298 EP 1305 DI 10.1182/blood-2004-01-0100 PG 8 WC Hematology SC Hematology GA 849MX UT WOS:000223544000020 PM 15142873 ER PT J AU Lee, SJ Zahrieh, D Agura, E MacMillan, ML Maziarz, RT McCarthy, PL Ho, VT Cutler, C Alyea, EP Antin, JH Soiffer, RJ AF Lee, SJ Zahrieh, D Agura, E MacMillan, ML Maziarz, RT McCarthy, PL Ho, VT Cutler, C Alyea, EP Antin, JH Soiffer, RJ TI Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; RECEPTOR MONOCLONAL-ANTIBODY; T-CELLS; CARDIAC TRANSPLANTATION; RENAL-TRANSPLANTATION; CLINICAL-TRIALS; PHASE-III; THERAPY; INTERLEUKIN-2-RECEPTOR; PROPHYLAXIS AB The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted. A total of 102 evaluable subjects of the targeted 166 were enrolled at 5 participating sites. Methylprednisolone at a dose of 2 mg/kg or daily equivalent was given in conjunction with daclizumab 1 mg/kg or placebo on study days 1, 4, 8, and weekly as long as clinically indicated. The groups were balanced for clinical characteristics. GVHD response rates by study day 42 were similar (53% vs 51%; P = .85). The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosterolds plus daclizumab (77% vs 94%; P = .02). Overall survival at 1 year was, also inferior in the combination arm (29% vs 60%; P = .002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. The combination of corticosteroids and daclizumab should not be used as initial therapy of a cute GVHD. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol & Biostat, Boston, MA 02115 USA. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Minnesota, Minneapolis, MN 55455 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol & Biostat, Boston, MA 02115 USA. EM stephanie_lee@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL 070149] NR 31 TC 131 Z9 138 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1559 EP 1564 DI 10.1182/blood-2004-03-0854 PG 6 WC Hematology SC Hematology GA 849MX UT WOS:000223544000055 PM 15138163 ER PT J AU Liu, TX Becker, MW Hsu, K Deng, M Clarke, MF Look, AT AF Liu, TX Becker, MW Hsu, K Deng, M Clarke, MF Look, AT TI Loss of CTNNA1 in MDS and/or AML with del(5q) SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA DE del(5q); MDS/AML; CTNNA1 C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 103 EP 103 PG 1 WC Hematology SC Hematology GA 851TV UT WOS:000223709500007 ER PT J AU Becker, MW Xi, TG Hsu, LK Deng, M Liu, R Hess, A Clarke, MF Look, AT AF Becker, MW Xi, TG Hsu, LK Deng, M Liu, R Hess, A Clarke, MF Look, AT TI Loss of CTNNA1 in MDS and/or AML with del(5q) SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA DE del(5q)MDS/AML vertical bar CTNNA1 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Michigan, Div Hematol Oncol Internal Med, Ann Arbor, MI 48109 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 105 EP 105 PG 1 WC Hematology SC Hematology GA 851TV UT WOS:000223709500011 ER PT J AU Leukemias, M Berman, J Hsu, K Liu, TX Deng, M Langenau, D Kanki, J Look, AT AF Leukemias, M Berman, J Hsu, K Liu, TX Deng, M Langenau, D Kanki, J Look, AT TI Transgenic zebrafish model of Hoxa9 and Meis1 mediated myeloid leukemias SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 105 EP 106 PG 2 WC Hematology SC Hematology GA 851TV UT WOS:000223709500012 ER PT J AU Heinrichs, S Look, AT AF Heinrichs, S Look, AT TI SiRNA-mediated knockdown of HOXB9 and HOXA10 in an AM cell line results in a reduction of the growh rate SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 107 EP 107 PG 1 WC Hematology SC Hematology GA 851TV UT WOS:000223709500016 ER PT J AU Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, J Zon, LI Kanki, JP Look, AT AF Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, J Zon, LI Kanki, JP Look, AT TI Expression of pu.1 in embryonic and adult transgenic zebrafish SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 107 EP 107 PG 1 WC Hematology SC Hematology GA 851TV UT WOS:000223709500018 ER PT J AU Wu, WS Xu, D Look, AT AF Wu, WS Xu, D Look, AT TI SLUG plays an essential role in the radioprotection of hematopoietic progenitors in vivo by antagonizing p53-mediated apoptotic pathways SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT Workshop on Malignant Stem Cells in Leukemia and Solid Tumors CY MAY 07-09, 2004 CL Cambridge, CANADA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2004 VL 33 IS 2 BP 110 EP 110 PG 1 WC Hematology SC Hematology GA 851TV UT WOS:000223709500024 ER PT J AU Cutler, C Antin, JH AF Cutler, C Antin, JH TI Sirolimus for GVHD prophylaxis in allogeneic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Review DE sirolimus; GVHD prophylaxis; allogeneic stem cell transplantation ID VERSUS-HOST-DISEASE; HEMOLYTIC-UREMIC SYNDROME; LOW-DOSE METHOTREXATE; HUMAN DENDRITIC CELLS; LONG-TERM TRIAL; THROMBOTIC MICROANGIOPATHY; CALCINEURIN-INHIBITOR; MAMMALIAN TARGET; RENAL-TRANSPLANTATION; KIDNEY-TRANSPLANTATION AB Sirolimus is a novel macrolide immunosuppressant widely used in solid organ transplantation. We have conducted three clinical trials using this compound as prophylaxis against GVHD after allogeneic stem cell transplantation. Our studies have demonstrated excellent GVHD control even when mismatched and unrelated donors were used. The morbidity and mortality associated with transplantation were reduced due to the omission or reduction in methotrexate dose. Furthermore, CMV reactivation and fungal infection rates were low. However, we have noted that sirolimus may be associated with increased rates of thrombotic microangiopathy after transplantation. Sirolimus has other uses, such as the treatment of established acute and chronic GVHD, and may be useful for treatment of post transplant lymphoproliferative disorder and perhaps as an antineoplastic agent against a wide variety of hematologic and solid neoplasms. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, 44 Binney St,D1B22, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149] NR 56 TC 42 Z9 42 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2004 VL 34 IS 6 BP 471 EP 476 DI 10.1038/sj.bmt.1704604 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 850ZN UT WOS:000223653000001 PM 15273708 ER PT J AU Hettiaratchy, SP Melendy, E Randolph, MA Butler, PEM Sachs, DH Huang, CA Lee, WPA AF Hettiaratchy, SP Melendy, E Randolph, MA Butler, PEM Sachs, DH Huang, CA Lee, WPA TI Composite tissue allotransplantation without long-term immunosuppression in a large animal model SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT 4th Meeting of the Society-of-Academic-and-Research-Surgery CY JAN, 2004 CL Belfast, IRELAND SP Soc Acad Res Surg C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg,Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 SEP PY 2004 VL 91 IS 9 BP 1213 EP 1213 PG 1 WC Surgery SC Surgery GA 851TI UT WOS:000223707900050 ER PT J AU Waldman, KL AF Waldman, KL TI The psychologist's companion: A guide to scientific writing for students and researchers SO BULLETIN OF THE MENNINGER CLINIC LA English DT Book Review C1 Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. RP Waldman, KL (reprint author), Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD FAL PY 2004 VL 68 IS 4 BP 364 EP 365 PG 2 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 892TZ UT WOS:000226674200020 ER PT J AU Waldman, KL AF Waldman, KL TI Psychological approaches to PAIN management: A practitioner's handbook. SO BULLETIN OF THE MENNINGER CLINIC LA English DT Book Review C1 Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. RP Waldman, KL (reprint author), Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD FAL PY 2004 VL 68 IS 4 BP 365 EP 366 PG 2 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 892TZ UT WOS:000226674200021 ER PT J AU Pierce, MC Sheridan, RL Park, BH Cense, B de Boer, JF AF Pierce, MC Sheridan, RL Park, BH Cense, B de Boer, JF TI Collagen denaturation can be quantified in burned human skin using polarization-sensitive optical coherence tomography SO BURNS LA English DT Article DE biomedical imaging; burn depth; birefringence; collagen ID DEPTH; BIREFRINGENCE; TISSUE; ULTRASOUND; DIAGNOSIS; PERFUSION; TRIAL; AID AB Quantifiable prognostic indicators are of considerable practical value following thermal injury. Collagen is a major component of the skin, and is known to undergo denaturation at the elevated temperatures associated with burns. The purpose of this study was to determine whether a recently developed, non-invasive imaging technique could detect and quantify collagen denaturation in burned human skin. Polarization-sensitive optical coherence tomography (PS-OCT) imaging was used to quantify collagen birefringence in normal human skin, and in skin excised from burn patients. Images were acquired and displayed in 1 s, and demonstrated qualitative differences between normal and partial-thickness burned human skin. Birefringence loss due to thermal denaturation of collagen was quantified, with mean phase retardation rates for samples of 26 normal and 26 burned skin sites determined to be 0.401 +/- 0.020 and 0.249 +/- 0.017degrees/mum, respectively (mean +/- S.E.M.), with this difference in sample means shown to be statistically significant (P < 0.000001). Analysis of the accuracy of the technique indicated that PS-OCT measurements may be made with resolution sufficient to distinguish between burns of varying severity. In conclusion, PS-OCT is capable of imaging and quantifying collagen denaturation in burned human skin, providing a new parameter against which post-injury outcome may be compared. (C) 2004 Elsevier Ltd and ISBI. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma & Burns, Boston, MA USA. RP Pierce, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,BAR 714, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [1R24 EY12877] NR 30 TC 77 Z9 84 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD SEP PY 2004 VL 30 IS 6 BP 511 EP 517 DI 10.1016/j.burns.2004.02.004 PG 7 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 850ZB UT WOS:000223651800001 PM 15302415 ER PT J AU Anhang, R Goodman, A Goldie, SJ AF Anhang, R Goodman, A Goldie, SJ TI HPV communication: Review of existing research and recommendations for patient education SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTIONS; SHARED DECISION-MAKING; CERVICAL-CANCER; UNDETERMINED SIGNIFICANCE; PSYCHOSOCIAL IMPACT; GENITAL WARTS; WOMEN; KNOWLEDGE; ABNORMALITIES; CONSEQUENCES AB The potential for human papillomavinus (HPV) DNA testing in cervical cancer prevention programs has been a topic at the forefront of cervical cancer policy discussions in recent years. To prevent some of the anxiety and psychological distress often experienced on HPV diagnosis and during the period of management, mass patient education must accompany the incorporation of HPV DNA testing into screening protocols. To contribute to a growing body of work that provides an empiric basis for development of effective counseling messages about HPV and HPV testing, this paper highlights women's most common information gaps and psychosocial concerns and describes the different perspectives offered by women's usual sources of information about HPV, including the crucial role of the clinical community in creating a shared decision making environment in which screening decisions and results can be discussed. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. RP Anhang, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA-93435-2] NR 65 TC 85 Z9 94 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 2004 VL 54 IS 5 BP 248 EP 259 PG 12 WC Oncology SC Oncology GA 958YE UT WOS:000231483300005 PM 15371283 ER PT J AU Gentleman, R AF Gentleman, R TI Some perspectives on statistical computing SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE computing; software; training of statisticians ID COMPUTATIONAL STATISTICS AB The author argues for an increased emphasis on computing in the training of statisticians and in their professional practice. He describes some of the current technological challenges and demonstrates the importance for statisticians of becoming more active in computational aspects of their work and specifically in producing software for carrying out statistical procedures. Such a reorientation will require substantial changes in thinking, pedagogy and infrastructure; the author mentions some of the conditions required to achieve these goals. C1 Harvard Univ, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harvard Univ, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. EM rgentlem@jimmy.harvard.edu NR 32 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0319-5724 EI 1708-945X J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 2004 VL 32 IS 3 BP 209 EP 226 DI 10.2307/3315925 PG 18 WC Statistics & Probability SC Mathematics GA 868IZ UT WOS:000224908600001 ER PT J AU Kulke, MH Kim, H Clark, JW Enzinger, PC Lynch, TJ Morgan, JA Vincitore, M Michelini, A Fuchs, CS AF Kulke, MH Kim, H Clark, JW Enzinger, PC Lynch, TJ Morgan, JA Vincitore, M Michelini, A Fuchs, CS TI A phase II trial of gemcitabine for metastatic neuroendocrine tumors SO CANCER LA English DT Article DE neuroendocrine tumors; carcinoid; pancreatic islet cell; gemcitabine ID ISLET-CELL-CARCINOMA; ONCOLOGY-GROUP; STREPTOZOCIN; DOXORUBICIN; COMBINATION; THERAPY; PHEOCHROMOCYTOMA; CHEMOTHERAPY; FLUOROURACIL; DACARBAZINE AB BACKGROUND. Treatment with traditional cytotoxic chemotherapy regimens containing streptozocin or dacarbazine has resulted in only marginal benefit for patients with metastatic neuroendocrine tumors. The use of these regimens has been further limited by their potential toxicity. Gemcitabine is generally well tolerated and possesses demonstrated activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine in the treatment of patients with metastatic neuroendocrine tumors. METHODS. Eighteen patients with metastatic neuroendocrine tumors were treated with gemcitabine administered on a standard weekly schedule. Patients were followed for evidence of toxicity, response, and survival. RESULTS. Gemcitabine was well tolerated. However, no radiologic or biochemical responses were observed. Although the majority of patients (65%) experienced disease stabilization as their best response to therapy, the overall median survival duration was only 11.5 months. CONCLUSIONS. The minimal activity of gemcitabine highlighted the need for novel treatment approaches. (C) 2004 American Cancer Society. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu NR 19 TC 53 Z9 53 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 SEP 1 PY 2004 VL 101 IS 5 BP 934 EP 939 DI 10.1002/cncr.20466 PG 6 WC Oncology SC Oncology GA 848HQ UT WOS:000223458600008 PM 15329900 ER PT J AU Hughes, LL Gray, RJ Solin, LJ Robert, NJ Martino, S Tripathy, D Ingle, JN Wood, WC Williams, N Feuer, G AF Hughes, LL Gray, RJ Solin, LJ Robert, NJ Martino, S Tripathy, D Ingle, JN Wood, WC Williams, N Feuer, G CA Eastern Cooperative Oncology Grp TI Efficacy of radiotherapy for ovarian ablation - Results of a Breast Intergroup study SO CANCER LA English DT Article DE radiotherapy (RT); ovarian ablation; breast carcinoma; tamoxifen ID PREMENOPAUSAL PATIENTS; CANCER; CARCINOMA; THERAPY AB BACKGROUND. in 1994, the Eastern Cooperative Oncology Group (ECOG) initiated for the Breast Intergroup a randomized clinical trial (E3193) in premenopausal patients with early-stage breast carcinoma (lymph node-negative and receptor-positive, with tumors measuring less than or equal to 3 cm) comparing tamoxifen as adjuvant systemic therapy with tamoxifen and ovarian ablation by one of three different methods. Ovarian ablation could be accomplished either via radiotherapy (RT) (20 Gray [Gy]/10 fractions to a modified pelvic volume), surgical oophorectomy, or goserelin/leuprolide injections as per patient/physician choice. In the current study, we report the efficacy of pelvic RT with this dose-fractionation scheme in the induction of ovarian ablation. METHODS. Twenty-two of 174 patients (13%) who were randomized to treatment with tamoxifen and ovarian ablation received RT for ovarian ablation. RT quality assurance was performed. Of the 22 patients, 19 were treated per protocol, I patient had a minor violation (20 elapsed days for 10 RT fractions), and 2 patients had major violations (1 patient who was treated with RT as per protocol but who was treated at a non-Intergroup center, and 1 patient who was treated at a dose of 15 Gy/5 fractions). RESULTS. No acute Grade 3 or 4 (according to the Common Toxicity Criteria of the National Cancer Institute) toxicities were reported during RT. Of the 22 patients receiving RT, evaluable follow-up data were available for 20 patients. Based on postmenopausal levels of estradiol or follicle-stimulating hormone at varying intervals after the completion of RT, 15 of 20 patients (75%) achieved successful ovarian ablation with RT. At a median follow-up of 54 months (range, 21-66 months), no Grade 3 or 4 complications from RT were observed. CONCLUSIONS. Ovarian ablation by RT as performed in the current trial (given at a dose of 20 Gy in 10 fractions to a modified pelvic treatment volume) was found to be effective for ovarian ablation in the majority of patients, but may take some months to be complete. Consequently, patients should be evaluated to ascertain that ablation has been accomplished. (C) 2004 American Cancer Society. C1 WellStar Kennestone Hosp, Dept Radiat Oncol, Marietta, GA 30060 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Fairfax No Virgina Hematol Oncol Practice, Vienna, Austria. John Wayne Canc Inst, Santa Monica, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Emory Univ Hosp, Atlanta, GA 30322 USA. RP Hughes, LL (reprint author), WellStar Kennestone Hosp, Dept Radiat Oncol, 55 S Med Dr,Suite 100, Marietta, GA 30060 USA. EM LHughesmd@aol.com FU NCI NIH HHS [CA11789, CA13650, CA21115, CA22318, CA31946, CA32102, CA66636] NR 13 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 BP 969 EP 972 DI 10.1002/cncr.20481 PG 4 WC Oncology SC Oncology GA 848HQ UT WOS:000223458600013 PM 15329905 ER PT J AU Allport, JR Patil, VRS Weissleder, R AF Allport, JR Patil, VRS Weissleder, R TI Murine neuronal progenitor cells are preferentially recruited to tumor vasculature via alpha(4)-integrin and SDF-1 alpha-dependent mechanisms SO CANCER BIOLOGY & THERAPY LA English DT Article DE cell adhesion molecules; cell-to-cell interactions; CXC chemokines; endothelium; stem cells ID NEURAL STEM-CELLS; BONE-MARROW; E-SELECTIN; MONOCYTE TRANSMIGRATION; ADHESION MOLECULES; ENDOTHELIAL-CELLS; IN-VITRO; EXPRESSION; BRAIN; VIVO AB Recent studies have described neuronal progenitor cell recruitment to tumors in vivo, however, the mechanisms mediating this recruitment are not yet understood. When C17.2 murine neuronal progenitors stably expressing luciferase (C17.2-luc) were adoptively transferred into mice carrying subcutaneous Lewis lung carcinomas they accumulated at 1% injected dose/g of tumor tissue. C17.2-luc demonstrated significantly greater accumulation and transmigration on tumor-derived endothelium (TEC) than on normal endothelium under physiologically relevant flow conditions. Function blocking of alpha(4)-integrin reduced recruitment of C17.2-luc cells to normal endothelium but not to TEC, however, function blocking of SDF-1alpha reduced overall accumulation of C17.2-luc on TEC and specifically reduced transendothelial migration. Together, these data suggest that recruitment of C17.2-luc cells to TEC is mediated via SDF-1alpha/CXCR4 activation that results in modification of alpha(4)-integrin and results in improved recruitment of C17.2-luc cells. C1 Massachusetts Gen Hosp, CMIR, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. RP Allport, JR (reprint author), Massachusetts Gen Hosp, CMIR, Dept Radiol, 149,13th Sr,Rm 5416, Charlestown, MA 02129 USA. EM jennifer_allport@hms.harvard.edu FU NCI NIH HHS [CA79443-01A1, CA96978-01, CA85240-02, CA86355-02] NR 34 TC 18 Z9 19 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP PY 2004 VL 3 IS 9 BP 838 EP 844 PG 7 WC Oncology SC Oncology GA 898RT UT WOS:000227094600016 PM 15254391 ER PT J AU Letai, A Sorcinelli, MD Beard, C Korsmeyer, SJ AF Letai, A Sorcinelli, MD Beard, C Korsmeyer, SJ TI Antiapoptotic BCL-2 is required for maintenance of a model leukemia SO CANCER CELL LA English DT Article ID TRANSGENIC MICE; C-MYC; CELL-DEATH; CHROMOSOMAL BREAKPOINT; FOLLICULAR LYMPHOMA; TUMOR-CELLS; ANTIMYCIN-A; EXPRESSION; APOPTOSIS; GENE AB Resistance to apoptosis, often achieved by the overexpression of antiapoptotic proteins, is common and perhaps required in the genesis of cancer. However, it remains uncertain whether apoptotic defects are essential for tumor maintenance. To test this, we generated mice expressing a conditional BCL-2 gene and constitutive c-myc that develop lymphoblastic leukemia. Eliminating BCL-2 yielded rapid loss of leukemic cells and significantly prolonged survival, formally validating BCL-2 as a rational target for cancer therapy. Loss of this single molecule resulted in cell death, despite or perhaps attributable to the presence of other oncogenic events. This suggests a generalizable model in which aberrations inherent to cancer generate tonic death signals that would otherwise kill the cell if not opposed by a requisite apoptotic defect(s). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu FU NCI NIH HHS [K08 CA10254, P01 CA92625] NR 45 TC 116 Z9 118 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2004 VL 6 IS 3 BP 241 EP 249 DI 10.1016/j.ccr.2004.07.011 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 859CM UT WOS:000224239900008 PM 15380515 ER PT J AU Torres-Arzayus, MI de Mora, JF Yuan, J Vazquez, F Branson, R Rue, M Sellers, WR Brown, M AF Torres-Arzayus, MI de Mora, JF Yuan, J Vazquez, F Branson, R Rue, M Sellers, WR Brown, M TI High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene SO CANCER CELL LA English DT Article ID GROWTH-FACTOR-I; BREAST-CANCER CELLS; STEROID-RECEPTOR COACTIVATOR-1; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; MAMMARY TUMORIGENESIS; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; AMPLIFICATION; VIRUS AB The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, 44 Biney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Rue, Montserrat/B-5663-2009; Font de Mora, Jaime/H-6304-2015; OI Rue, Montserrat/0000-0002-7862-9365; Font de Mora, Jaime/0000-0002-6816-2095; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [5 P01 CA80111-05] NR 56 TC 260 Z9 263 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2004 VL 6 IS 3 BP 263 EP 274 DI 10.1016/j.ccr.2004.06.027 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 859CM UT WOS:000224239900010 PM 15380517 ER PT J AU Feskanich, D Ma, J Fuchs, CS Kirkner, GJ Hankinson, SE Hollis, BW Giovannucci, EL AF Feskanich, D Ma, J Fuchs, CS Kirkner, GJ Hankinson, SE Hollis, BW Giovannucci, EL TI Plasma vitamin D metabolites and risk of colorectal cancer in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON-CANCER; SERUM 25-HYDROXYVITAMIN-D; DIETARY CALCIUM; NURSES HEALTH; MEN; CARCINOGENESIS; INHIBITION; DECREASES; PRODUCTS; ADENOMAS AB Objective: Experimental evidence suggests that 1,25-dihydroxyvitamin D and its precursor, 25-hydroxyvitamin D [25(OH)D], may aid in the prevention of colorectal cancer. We therefore examined risk in relation to plasma concentrations of these vitamin D metabolites. Methods: In a nested case-control study among women in the Nurses' Health Study, we identified 193 colorectal cancer cases, ages 46 to 78 years, diagnosed up to 11 years after blood collection. Two controls were matched per case on year of birth and month of blood draw. Odds ratios (OR) for risk of colorectal cancer were calculated using conditional logistic regression adjusted for body mass index, physical activity, smoking, family history, use of hormone replacement therapy, aspirin use, and dietary intakes. Results: We found a significant inverse linear association between plasma 25(OH)D and risk of colorectal cancer (P=0.02). Among women in the highest quintile, the OR (95% confidence interval) was 0.53 (0.27-1.04). This inverse association remained strong when limited to women greater than or equal to60 years at blood collection (P=0.006) but was not apparent among the younger women (P=0.70). Benefit from higher 25(OH)D concentrations was observed for cancers at the distal colon and rectum (P=0.02) but was not evident for those at the proximal colon (P=0.81). In contrast to 25(OH)D, we did not observe an association between 1,25-dihydroxyvitamin D and colorectal cancer, although risk was elevated among the women in the highest quintile if they were also in the lower half of the 25(OH)D distribution (OR, 2.52; 95% confidence interval, 1.04-6.11). Conclusion: From these results and supporting evidence from previous studies, we conclude that higher plasma levels of 25(OH)D are associated with a lower risk of colorectal cancer in older women, particularly for cancers at the distal colon and rectum. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, 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. Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. RP Feskanich, D (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM diane.feskanich@channing.harvard.edu NR 45 TC 245 Z9 254 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2004 VL 13 IS 9 BP 1502 EP 1508 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 851SF UT WOS:000223704900012 PM 15342452 ER PT J AU McDougal, WS AF McDougal, WS TI Does Gleason pattern 5 on prostate biopsy specimens accurately predict treatment outcomes in prostate cancer? SO CANCER JOURNAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB-1102, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2004 VL 10 IS 5 BP 290 EP 290 DI 10.1097/00130404-200409000-00004 PG 1 WC Oncology SC Oncology GA 868IF UT WOS:000224906600004 PM 15530256 ER PT J AU Duda, DG Fukumura, D Munn, LL Booth, MF Brown, EB Huang, PG Seed, B Jain, RK AF Duda, DG Fukumura, D Munn, LL Booth, MF Brown, EB Huang, PG Seed, B Jain, RK TI Differential transplantability of tumor-associated stromal cells SO CANCER RESEARCH LA English DT Article ID ANGIOGENESIS; CANCER; MICROENVIRONMENT; MICE; HETEROGENEITY; MICROSCOPY; XENOGRAFTS; VESSELS; GROWTH AB At the time of transplantation, tumor fragments contain "passenger" cells: endothelial cells and other stromal cells from the original host. Here, we investigated the fate of genetically labeled endothelial and nonendothelial stromal cells after transplantation in syngeneic mice. We report that angiogenic stroma associated with tumor or adipose tissue persists when transplanted, remains functional, and governs the initial neovascudarization of grafted tissue fragments for more than 4 weeks after implantation. Surprisingly, the passenger endothelial cells survive longer than other stromal cells, which are replaced by host-activated fibroblasts after 3 weeks. The transplantability of tumor stroma suggests that the anglogenic potential of a tumor xenograft, which determines its viability, depends on the presence of passenger endothelial cells and other stromal cells within the xenograft. These studies of tumor tissue transplantation provide a platform for exploring the role of epithelial-stromal interactions in studies of tumor heterogeneity and drug resistance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,EL Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,EL Steele Lab Tumor Biol, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124-08, P01-CA80124, R01 CA085140-09, R24-CA85140] NR 23 TC 37 Z9 38 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 5920 EP 5924 DI 10.1158/0008-5472.CAN-04-1268 PG 5 WC Oncology SC Oncology GA 850IA UT WOS:000223603200002 PM 15342367 ER PT J AU Kelly, K Alencar, H Funovics, M Mahmood, U Weissleder, R AF Kelly, K Alencar, H Funovics, M Mahmood, U Weissleder, R TI Detection of invasive colon cancer using a novel, targeted, library-derived fluorescent peptide SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; COLONOSCOPIES; EXPRESSION AB Sensitive methods to detect the earliest forms of colorectal cancers remain a challenge despite the development of serum and stool biomarkers. We reasoned that fluorescent affinity ligands derived from library screens can be developed to improve the detection and localization of early malignant lesions by endoscopy. We have developed an imaging agent for real-time endoscopic tumor detection in a murine model using a previously identified phage library-derived colon cancer-specific cyclic peptide and fluorescent moieties. The modified peptide had a 24 minute blood half life and tumoral accumulation was 6.9% of injected dose/g, similar to7-fold higher than a scrambled control peptide. Orthotopic colonic tumors (HT29) were readily detectable by fluorescence endoscopy even when tumors were submucosal. These results show proof-of-principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5404, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu FU NCI NIH HHS [CA86355, CA92782]; NIBIB NIH HHS [EB02102] NR 19 TC 97 Z9 98 U1 4 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 6247 EP 6251 DI 10.1158/0008-5472.CAN-04-0817 PG 5 WC Oncology SC Oncology GA 850IA UT WOS:000223603200046 PM 15342411 ER PT J AU Huang, PL AF Huang, PL TI Nitric oxide and cerebral ischernic preconditioning SO CELL CALCIUM LA English DT Article DE nitric oxide; cerebral ischemia; preconditioning ID PROTEIN-KINASE AKT; HEAT-SHOCK-PROTEIN; ISCHEMIC TOLERANCE; MICE LACKING; ARTERY OCCLUSION; SYNTHASE GENE; GERBIL HIPPOCAMPUS; NEURONAL SURVIVAL; ENDOTHELIAL-CELLS; KNOCKOUT MICE AB Nitric oxide (NO) is an important mediator of cerebral blood flow and metabolism. As a vasodilator, NO regulates cerebral blood flow, and couples regional brain perfusion with metabolic activity. Following cerebral ischemia, NO levels rise significantly due to activation of neuronal nitric oxide synthase by NMDA receptor mediated calcium entry. Depending on its tissue and enzymatic source, NO may be protective or toxic. This article reviews the effects of NO following cerebral ischemia, the signaling pathways through which NO acts, and its potential roles in cerebral ischemic preconditioning, (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Div Cardiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Harvard Univ, Sch Med, Div Cardiol, 149 13th St, Charlestown, MA 02129 USA. EM phuang1@partners.org NR 56 TC 57 Z9 59 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD SEP-OCT PY 2004 VL 36 IS 3-4 BP 323 EP 329 DI 10.1016/j.ceca.2004.02.007 PG 7 WC Cell Biology SC Cell Biology GA 843DR UT WOS:000223056500015 PM 15261488 ER PT J AU Pardee, AB Li, CJ Reddy, GPV AF Pardee, AB Li, CJ Reddy, GPV TI Regulation in S phase by E2F SO CELL CYCLE LA English DT Article ID CELL-CYCLE PROGRESSION; DNA-DAMAGE; UBIQUITIN-LIGASE; IN-VIVO; SIGNAL-TRANSDUCTION; PROTEIN COMPLEXES; INDUCED APOPTOSIS; DEGRADATION; PROTEASOME; PROMOTER AB The DNA synthetic S phase of the unperturbed cell cycle is a closed system, as compared to regulation of G(1) by external growth factors. The E2F family provides internal control in S phase by transcribing genes required for deoxynucleotide triphosphate (dNTP) and DNA synthesis. Furthermore, over expression of E2F-1 activates programmed cell death ( apoptosis), a safeguarding signal of aberrant growth of cells that have become carcinogenic. Mechanisms for control of E2F-1 are thus essential. The hypothesis is proposed that deoxythymidine triphosphate ( dTTP) allosterically feedback controls E2F-1 to regulate both DNA synthesis and apoptosis. This may act either upon production of E2F-1 or its degradation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. ArQule Inc, ArQule Biomed Inst, Woburn, MA USA. Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 936A, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu FU NIDDK NIH HHS [DK57864] NR 77 TC 22 Z9 23 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2004 VL 3 IS 9 BP 1091 EP 1094 PG 4 WC Cell Biology SC Cell Biology GA 877MD UT WOS:000225573800001 PM 15467444 ER PT J AU Singer, DE Albers, GW Dalen, JE Go, AS Halperin, JL Manning, WJ AF Singer, DE Albers, GW Dalen, JE Go, AS Halperin, JL Manning, WJ TI Antithrombotic therapy in atrial fibrillation SO CHEST LA English DT Article DE antithrombotic; atrial fibrillation; mitral stenosis; prophylaxis; stroke ID CORONARY-ARTERY-BYPASS; DIRECT THROMBIN INHIBITOR; DIRECT-CURRENT CARDIOVERSION; RANDOMIZED CONTROLLED-TRIAL; ORAL ANTICOAGULANT-THERAPY; SPONTANEOUS ECHO CONTRAST; FIXED MINIDOSE WARFARIN; ADJUSTED-DOSE WARFARIN; OPEN-HEART-SURGERY; HIGH-RISK PATIENTS AB This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade I recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of greater than or equal to 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of greater than or equal to 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiograhy (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 26). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C). C1 Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. EM dsinger@partner.org NR 198 TC 218 Z9 232 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2004 VL 126 IS 3 SU S BP 429S EP 456S DI 10.1378/chest.126.3_suppl.429S PG 28 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 859WP UT WOS:000224298900012 PM 15383480 ER PT J AU Aquino, SL Fischman, MJ AF Aquino, SL Fischman, MJ TI Does whole-body 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography have an advantage over thoracic positron emission tomography for staging patients with lung cancer? SO CHEST LA English DT Article DE cancer staging; carcinoma, non-small cell lung; lung cancer; neoplasms; radiography, thoracic; tomography, emission-computed ID FLUORINE-18-FDG PET; METASTASES; CARCINOMA AB Background: Whole-body (WB) positron emission tomography (PET) with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is more accurate than other imaging studies for detecting lung cancer and extrathoracic metastatic disease. Thoracic PET (from the skull base through the kidneys) may be equally as useful as WB PET (skull base to mid-thigh). With the recent introduction of hybrid CT-PET systems, use of thoracic PET would minimize radiation dose. Methods: A retrospective review of a series of WB PET scans performed in our department was performed to identify patients evaluated for a solitary pulmonary nodule or newly diagnosed lung cancer who had distant extracranial and extrathoracic metastases detected by PET. All patients with true extrathoracic metastases were documented by ancillary radiologic and clinical data. Patients were staged according to the American joint Committee on Cancer TNM system based on findings within the confines of a thoracic PET and WB PET. Comparison was made between staging based on thoracic and WB PET to determine if there was a significant difference. Results: Of 1,026 studies, distant extracranial metastases were described in 35 patients with lung cancer. Findings were determined to be false-positive in nine patients. Of the 26 patients with true metastases on WB PET, 25 patients had metastatic lesions within the confines of thoracic PET. Relative to WB PET, the sensitivity of thoracic PET is 96.2% (95% confidence interval, 1 to 99.3%) for detection of distant metastases. Only one patient had an isolated metastasis that was detected only by WB PET. This patient would have been staged IIIB by thoracic PET as opposed to stage IV by WB PET. Conclusions: Thoracic PET, when compared to WB PET, is 96.2% sensitive for detecting extrathoracic metastases in patients with newly diagnosed non-small cell lung cancer. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM saquino@partners.org NR 19 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2004 VL 126 IS 3 BP 755 EP 760 DI 10.1378/chest.126.3.755 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 857WC UT WOS:000224148900020 PM 15364753 ER PT J AU Plotkin, SR Betensky, RA Hochberg, FH Grossman, SA Lesser, GJ Nabors, LB Chon, B Batchelor, TT AF Plotkin, SR Betensky, RA Hochberg, FH Grossman, SA Lesser, GJ Nabors, LB Chon, B Batchelor, TT TI Treatment of relapsed central nervous system lymphoma with high-dose methotrexate SO CLINICAL CANCER RESEARCH LA English DT Review ID PRIMARY CNS LYMPHOMA; CHEMOTHERAPY; RADIOTHERAPY AB Purpose: Over the past decade, high-dose methotrexate has emerged as the single most effective agent in the initial treatment of primary nervous system lymphoma. However, the majority of patients who respond initially to treatment relapse. The optimal management of these patients has not been determined. We performed a multicenter, retrospective study of high-dose methotrexate in patients with relapsed central nervous system lymphoma. Experimental Design: Patients with relapsed disease were eligible if they achieved a complete response to initial treatment with methotrexate-based chemotherapy or received methotrexate after gross total resection or interstitial radiation. All of the patients were retreated with a regimen containing high-dose methotrexate ( greater than or equal to3 g/m(2)). Results: Twenty-two patients with a median age of 58 years were included in the study. Overall response rates were 91 % to first salvage (20 of 22 patients) and 100 % to second salvage (4 of 4 patients). Median survival was 61.9 months after first relapse (95% confidence interval, 42.1-infinity) and 91.9 months overall (95% confidence interval, 47.2-infinity). Toxicity was primarily hematologic with 10 episodes of grade 3 or 4 toxicity during 566 cycles of chemotherapy. Conclusions: These results indicate that high-dose methotrexate remains effective for relapsed central nervous system lymphoma in patients who initially respond to methotrexate and raise the possibility of deferring more toxic salvage regimens in this select group of patients. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Alabama, Sch Med, Birmingham, AL USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. EM splotkin@partners.org NR 15 TC 81 Z9 82 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5643 EP 5646 DI 10.1158/1078-0432.CCR-04-0159 PG 4 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700002 PM 15355887 ER PT J AU Mashour, GA Driever, PH Hartmann, M Drissel, SN Zhang, TG Scharf, B Felderhoff-Muser, U Sakuma, S Friedrich, RE Martuza, RL Mautner, VF Kurtz, A AF Mashour, GA Driever, PH Hartmann, M Drissel, SN Zhang, TG Scharf, B Felderhoff-Muser, U Sakuma, S Friedrich, RE Martuza, RL Mautner, VF Kurtz, A TI Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1 SO CLINICAL CANCER RESEARCH LA English DT Article ID ANGIOGENIC FACTOR MIDKINE; SCHWANN-CELLS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; RECEPTOR EXPRESSION; GENE-PRODUCT; NF1; SERUM; PLEIOTROPHIN; SURVIVAL; DISEASE AB Purpose: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. Experimental Design: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. Results: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. Conclusions: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis. C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, Charlestown, MA 02129 USA. Humboldt Univ, Charite, Ctr Med, Berlin, Germany. Klinikum Nord Ochsenzoll, Hamburg, Germany. Cell Signals Inc, Kanagawa, Japan. RP Kurtz, A (reprint author), Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, 149 13th St, Charlestown, MA 02129 USA. EM kurtza@helix.mgh.harvard.edu FU NINDS NIH HHS [NS37895] NR 53 TC 26 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5677 EP 5683 DI 10.1158/1078-0432.CCR-03-0769 PG 7 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700008 PM 15355893 ER PT J AU Dring, AM Davies, FE Fenton, JAL Roddam, PL Scott, K Gonzalez, D Rollinson, S Rawstron, AC Rees-Unwin, KS Li, C Munshi, NC Anderson, KC Morgan, GJ AF Dring, AM Davies, FE Fenton, JAL Roddam, PL Scott, K Gonzalez, D Rollinson, S Rawstron, AC Rees-Unwin, KS Li, C Munshi, NC Anderson, KC Morgan, GJ TI A global expression-based analysis of the consequences of the t(4;14) translocation in myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; MULTIPLE-MYELOMA; CHROMOSOMAL TRANSLOCATION; OLIGONUCLEOTIDE ARRAYS; FGFR3 EXPRESSION; CELL LYMPHOMA; PLASMA-CELLS; GENE; T(4/14)(P16,Q32); DYSREGULATION AB Purpose: Our purpose in this report was to define genes and pathways dysregulated as a consequence of the t(4;14) in myeloma, and to gain insight into the downstream functional effects that may explain the different prognosis of this subgroup. Experimental Design: Fibroblast growth factor receptor 3 (FGFR3) overexpression, the presence of immunoglobulin heavy chain-multiple myeloma SET domain (IgH-MMSET) fusion products and the identification of t(4;14) breakpoints were determined in a series of myeloma cases. Differentially expressed genes were identified between cases with (n = 55) and without (n = 24) a t(4;14) by using global gene expression analysis. Results: Cases with a t(4;14) have a distinct expression pattern compared with other cases of myeloma. A total of 127 genes were identified as being differentially expressed including MMSET and cyclin D2, which have been previously reported as being associated with this translocation. Other important functional classes of genes include cell signaling, apoptosis and related genes, oncogenes, chromatin structure, and DNA repair genes. Interestingly, 25% of myeloma cases lacking evidence of this translocation had up-regulation of the MMSET transcript to the same level as cases with a translocation. Conclusions: t(4;14) cases form a distinct subgroup of myeloma cases with a unique gene signature that may account for their poor prognosis. A number of non-t(4;14) cases also express MMSET consistent with this gene playing a role in myeloma pathogenesis. C1 Univ Leeds, Sch Med, Acad Unit Haematol & Oncol, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Royal Marsden Hosp, Surrey, England. RP Davies, FE (reprint author), Univ Leeds, Sch Med, Acad Unit Haematol & Oncol, Algernon Firth Bldg, Leeds LS2 9JT, W Yorkshire, England. EM F.E.Davies@leeds.ac.uk NR 33 TC 33 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5692 EP 5701 DI 10.1158/1078-0432.CCR-04-0467 PG 10 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700010 PM 15355895 ER PT J AU Heymach, JV Desai, J Manola, J Davis, DW McConkey, DJ Harmon, D Ryan, DP Goss, G Quigley, T Van den Abbeele, AD Silverman, SG Connors, S Folkman, J Fletcher, CDM Demetri, GD AF Heymach, JV Desai, J Manola, J Davis, DW McConkey, DJ Harmon, D Ryan, DP Goss, G Quigley, T Van den Abbeele, AD Silverman, SG Connors, S Folkman, J Fletcher, CDM Demetri, GD TI Phase II study of the antiangiogenic agent SU5416 in patients with advanced soft tissue sarcomas SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; NITRIC-OXIDE SYNTHASE; C-KIT; FACTOR ANTIBODY; CLINICAL-TRIAL; SOLID TUMORS; SERUM-LEVELS AB Purpose: SU5416 (semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor (VEGF) receptor-2 and KIT receptor tyrosine kinases. This Phase H study was conducted to investigate the safety and efficacy of SU5416 for patients with soft tissue sarcomas. Experimental Design: Thirteen patients with locally advanced or metastatic soft tissue sarcomas were treated with SU5416 via intravenous infusion at a dose of 145 mg/m(2) twice weekly. In selected cases tumor biopsies were taken before and after 2 months of treatment. Results: The median progression-free survival was 1.8 months. Median overall survival was 22.8 months. No objective tumor responses were observed. There was evidence of shorter survival among patients with high baseline urine VEGF levels (P = 0.04). No grade 4 toxicities were observed. The most common grade 3 toxicities were headache and thrombosis. Other less serious toxicities included fatigue, nausea, and abdominal pain. The median systolic blood pressure increased from 118 mmHg at baseline to 133 after 1 month of treatment (P = 0.01). Post-treatment tumor biopsies showed no significant decreases in VEGF receptor phosphorylation compared with baseline in 3 evaluable patients. One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months. Conclusions: SU5416 was relatively well tolerated but did not demonstrate significant antitumor activity against advanced soft tissue sarcoma. Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Nucl Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, SW530,44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org FU NCI NIH HHS [CA-06516] NR 53 TC 75 Z9 79 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5732 EP 5740 DI 10.1158/1078-0432.CCR-04-0157 PG 9 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700015 PM 15355900 ER PT J AU Mundt, AJ Vijayakumar, S Nemunaitis, J Sandler, A Schwartz, H Hanna, N Peabody, T Senzer, N Chu, K Rasmussen, CS Kessler, PD Rasmussen, HS Warso, M Kufe, DW Das Gupta, T Weichselbaum, RR AF Mundt, AJ Vijayakumar, S Nemunaitis, J Sandler, A Schwartz, H Hanna, N Peabody, T Senzer, N Chu, K Rasmussen, CS Kessler, PD Rasmussen, HS Warso, M Kufe, DW Das Gupta, T Weichselbaum, RR TI A phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; ALPHA GENE-THERAPY; IONIZING-RADIATION; INTERFERON-GAMMA; TNF-ALPHA; POSTOPERATIVE RADIOTHERAPY; CANCER-PATIENTS; MELPHALAN; TOXICITY AB Purpose: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor alpha under control of a radiationinduced promoter. The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity. Experimental Design: TNFerade was administered in combination with single-daily fractionated radiation therapy in 14 patients with soft tissue sarcoma of the extremities. Three escalating dose levels of TNFerade (4 X 10(9) -4 X 10(11) particle units) were planned, given in 1 log increments by intratumoral injections, twice weekly during week 1 and once weekly during weeks 2-5 of radiation therapy. Results: TNFerade was well tolerated with no dose-limiting toxicities noted. Grade 1-2 chills (50.0%), fever (43.0%), fatigue (36.0%), and flu-like symptoms (21.0%) were the most common side effects. Serum-tumor necrosis factor alpha levels were low in all of the patients (< 15 pg/mL). No patients had virus-detected blood, sputum, or urine cultures. Of the 13 evaluable patients, 11 received TNFerade preoperatively, and 2 received the treatment for palliation. Eleven patients (85%) showed objective or pathological tumor responses (2 complete and 9 partial), and I had stable disease. Partial responses were achieved despite some of these tumors being very large (up to 675 cm(2)). Of the 11 patients who underwent surgery, 10 (91%) showed a pathological complete response/partial response. Conclusion: TNFerade + radiation therapy was well tolerated in the treatment of patients with soft-tissue sarcoma of the extremity. The high number of objective responses observed warrants additional studies of this approach in a larger controlled prospective trial. C1 Univ Chicago, Sch Med, Dept Radiat Oncol, Ctr Med, Chicago, IL 60637 USA. US Oncol, Dallas, TX USA. Vanderbilt Univ, Ctr Med, Nashville, TN USA. Univ Kentucky, Med Ctr, Lexington, KY USA. GenVec, Gaithersburg, MD USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Mundt, AJ (reprint author), Univ Chicago, Sch Med, Dept Radiat Oncol, Ctr Med, 5738 S Maryland Ave,CAM 1340,MC 9006, Chicago, IL 60637 USA. EM amundt@radonc.uchicago.edu NR 37 TC 65 Z9 67 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5747 EP 5753 DI 10.1158/1078-0432.CCR-04-0296 PG 7 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700017 PM 15355902 ER PT J AU Morrow, DA AF Morrow, DA TI Preprocedural C-reactive protein for risk prediction before percutaneous coronary intervention (PCI): A US perspective SO CLINICAL CHEMISTRY LA English DT Editorial Material ID STENT IMPLANTATION; PROGNOSTIC VALUE; UNSTABLE ANGINA; PLASMA-LEVELS; RESTENOSIS; ANGIOPLASTY; EVENTS; INFLAMMATION; ASSOCIATION C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 16 TC 0 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2004 VL 50 IS 9 BP 1489 EP 1491 DI 10.1373/clinchem.2004.034314 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 848YJ UT WOS:000223503800001 PM 15331494 ER PT J AU Grover, S Stoffel, EM Bussone, L Tschoegl, E Syngal, S AF Grover, Shilpa Stoffel, Elena M. Bussone, Laoti Tschoegl, Elizabeth Syngal, Sapna TI Physician Assessment of Family Cancer History and Referral for Genetic Evaluation in Colorectal Cancer Patients SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: An accurate family history is an essential component of cancer risk assessment. Our aim was to determine the concordance of family history assessments made by physicians with patients' self-reports and the frequency of referral for genetic evaluation in high-risk colorectal cancer (CRC) patients. Methods: A self-administered family cancer history questionnaire was completed by 387 consecutive CRC patients at their first visit to a gastroenterology cancer clinic. Physician notes from the first visit were reviewed to determine the concordance of the family cancer history with patients' self-reported history. Prevalence of individuals that satisfied the Bethesda guidelines for hereditary colon cancer were compared with actual rates of referral. Regression analyses were used to determine factors associated with a comprehensive physician evaluation of family history. Results: Oncologists documented a comprehensive family history in 59% (184 of 311) of patients with a first- or second-degree relative with cancer. Young age at diagnosis and a first-degree relative with CRC were not associated with a more comprehensive family history assessment. An increasing number of cancers per family was a strong predictor of a less comprehensive family history assessment (odds ratio = 0.63; P < 0.0001). Seventy-five of 387 (19%) CRC patients met Bethesda guidelines for genetics assessment, however, only 13 of 75 (17%) were referred. Conclusions: Increased complexity in family cancer history leads to a decrease in accuracy of family history, suggesting the need for systematic approaches to facilitate family history assessment. Familial cancer risk remains largely unrecognized and referral rates for genetic evaluation for CRC syndromes are low. C1 [Grover, Shilpa; Stoffel, Elena M.; Bussone, Laoti; Tschoegl, Elizabeth; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02114 USA. [Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,Smith 209, Boston, MA 02114 USA. EM ssyngal@partners.org FU National Institutes of Health [K07CA08453] FX Supported in part by a National Institutes of Health grant K07CA08453 for studying identification and cancer screening in hereditary colon cancer families (to S.S.). NR 28 TC 92 Z9 93 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2004 VL 2 IS 9 BP 813 EP 819 DI 10.1053/S1542-3565(04)00352-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KU UT WOS:000208072100012 PM 15354282 ER PT J AU Aberg, JA Gallant, JE Anderson, J Oleske, JM Libman, H Currier, JS Stone, VE Kaplan, JE AF Aberg, JA Gallant, JE Anderson, J Oleske, JM Libman, H Currier, JS Stone, VE Kaplan, JE TI Primary care guidelines for the management of persons infected with human immunodeficiency virus: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; B CORE ANTIGEN; PROTEASE INHIBITORS; VIROLOGICAL FAILURE; PATIENT COMPLIANCE; LACTIC ACIDEMIA; DRUG-RESISTANCE; RISK-FACTORS; VIRAL LOAD; USA PANEL C1 NYU, New York, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Aberg, JA (reprint author), NYU, Bellevue Hosp Ctr, AIDS Clin Trials Unit, Bellevue C&D Bldg,Rm 558, New York, NY 10016 USA. EM judith.aberg@med.nyu.edu RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 FU NIAID NIH HHS [AI-56933, AI-38855] NR 75 TC 111 Z9 118 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2004 VL 39 IS 5 BP 609 EP 629 DI 10.1086/423390 PG 21 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 847CU UT WOS:000223367500001 PM 15356773 ER PT J AU Spacek, LA Hurley, BP Acheson, DWK Granok, A Currie, A Doing, K Sears, CL AF Spacek, LA Hurley, BP Acheson, DWK Granok, A Currie, A Doing, K Sears, CL TI Shiga toxin-producing Escherichia coli as a possible etiological agent of chronic diarrhea SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC-TREATMENT; O157-H7; RISK; INFECTIONS; DEATH AB We identified Shiga toxin-producing Escherichia coli (STEC) as the likely etiologic pathogen for chronic diarrhea in 2 patients, 1 of whom was immunocompromised with acquired immunodeficiency syndrome, and 1 of whom was immunocompetent. Both were treated with antibiotics, and neither developed systemic complications of the infection. These cases suggest that STEC infection should be considered in the differential diagnosis of chronic diarrhea. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. US FDA, College Pk, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Infect Dis Associates, Nashua, NH USA. Affiliated Labs, Bangor, ME USA. RP Spacek, LA (reprint author), Johns Hopkins Univ, Sch Med, 1830 E Monument St,Rm 401, Baltimore, MD 21205 USA. EM lspacek@jhmi.edu FU NIAID NIH HHS [T32-AI 07291] NR 16 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2004 VL 39 IS 5 BP E46 EP E48 DI 10.1086/422877 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 847CU UT WOS:000223367500030 PM 15356801 ER PT J AU Mendez, MR AF Mendez, MR TI Aphemia-like syndrome from a right supplementary motor area lesion SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE aphemia; aphasia; SMA ID APHASIA; DISORDER; SPEECH AB Lesions in the left supplementary motor area (SMA) can result in a transcortical motor aphasia with nonfluent spontaneous verbal output and relatively preserved repetition. Reading and writing are proportionally affected. We report a patient with an ischemic lesion in the right SMA. He had impaired articulation and normal repetition plus preserved reading and writing, consistent with an aphemia. This patient supports the dissociation of articulatory fluency and linguistic fluency and suggests that both SMAs affect the initiating of articulatory movements required to produce words whereas the left SMA also affects linguistic aspects of speech. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Reed Neurol Res Ctr, Dept Neurol, Neurobehav Unit,VA Greater Los Angeles Healthcare, Los Angeles, CA 90073 USA. RP Mendez, MR (reprint author), Univ Calif Los Angeles, Reed Neurol Res Ctr, Dept Neurol, Neurobehav Unit,VA Greater Los Angeles Healthcare, 116AF,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu NR 17 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD SEP PY 2004 VL 106 IS 4 BP 337 EP 339 DI 10.1016/j.clineuro.2003.12.008 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 849EW UT WOS:000223522500013 PM 15297011 ER PT J AU Soares, CN Joffe, H Steiner, M AF Soares, CN Joffe, H Steiner, M TI Menopause and mood SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Review ID ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; HEALTH INITIATIVE MEMORY; CENTRAL-NERVOUS-SYSTEM; POSTMENOPAUSAL WOMEN; HOT FLASHES; TRANSDERMAL ESTRADIOL; PLUS PROGESTIN; DEPRESSIVE SYMPTOMS C1 Harvard Univ, Ctr Womens Mental Hlth, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. McMaster Univ, Womens Hlth Concerns Clin, Hamilton, ON, Canada. RP Soares, CN (reprint author), Harvard Univ, Ctr Womens Mental Hlth, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM csoares@partners.org RI Steiner, Meir /B-2121-2016 NR 139 TC 14 Z9 14 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2004 VL 47 IS 3 BP 576 EP 591 DI 10.1097/01.grf.0000129918.00756.d5 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 959PR UT WOS:000231530700009 PM 15326420 ER PT J AU Cashen, DV Parisien, RC Raskin, K Hornicek, FJ Gebhardt, MC Mankin, HJ AF Cashen, DV Parisien, RC Raskin, K Hornicek, FJ Gebhardt, MC Mankin, HJ TI Survival data for patients with malignant schwannoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY 2003 CL Chicago, IL SP Musculoskeletal Tumor Soc ID NERVE-SHEATH TUMORS; VON RECKLINGHAUSENS DISEASE; SOFT-TISSUE SARCOMA; NEUROFIBROMATOSIS TYPE-1; EXTREMITY; SYSTEM; NEUROFIBROSARCOMA; NEOPLASMS; ORIGIN AB Malignant schwannomas are uncommon sarcomas that arise from the sheath of Schwarm surrounding peripheral nerve fibers. These tumors may arise spontaneously in adult patients or may occur with reportedly increased frequency in patients with neurofibromatosis Type I. The tumors have had a reputation for malignancy with rapid metastasis, especially when they arise in relation to neurofibromatosis. We have reviewed the experience of the connective tissue oncology unit with patients with these tumors during the past 25 years. There were 80 malignant schwannomas identified in 41 females and 39 males with a mean age of 36 17 years. The largest numbers of tumors were seen in the thigh, shoulder, and pelvis but they also occurred in more central (abdomen and thorax) and distal (forearm, hand and foot) locations. The Musculoskeletal Tumor Society stages showed that the majority of the patients had Stage II (high grade but not metastasized) tumors; however, additionally, 10 of the patients had metastases at outset (Stage III). Patient gender was not a factor but stage was a notable determinant of survival. Anatomic location also had a significant effect. Overall, the entire series of patients had a survival of 85% at 11 +/- 5 years and even more remarkable was the fact that there was no difference between the numbers and outcome statistics for tumors arising spontaneously and those occurring in patients with neurofibromatosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Orthopaed Gray 6, Boston, MA 02114 USA. EM hmankin@partners.org NR 47 TC 52 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2004 IS 426 BP 69 EP 73 DI 10.1097/01.blo.0000131256.82455.c5 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 851TO UT WOS:000223708600012 PM 15346054 ER PT J AU Mankin, HJ Gunnoe, J Farid, Y Hornicek, FJ Gebhardt, MC AF Mankin, HJ Gunnoe, J Farid, Y Hornicek, FJ Gebhardt, MC TI Long-term effects of connective tissue cancer treatment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY 2003 CL Chicago, IL SP Musculoskeletal Tumor Soc ID QUALITY-OF-LIFE; FUNCTION ASSESSMENT QUESTIONNAIRE; HEALTH SURVEY SF-36; NEOADJUVANT CHEMOTHERAPY; LIMB SALVAGE; DOSE-INTENSITY; OSTEOSARCOMA; EXTREMITY; REPLACEMENT; RELIABILITY AB In 1999, we began a study to assess the long-term effect of connective tissue cancer treatment on clinical, social, and psychologic aspects of the lives of surviving patients. A specially designed computer program generated an 85-item questionnaire, which was sent to more than 2000 patients with malignant bone and soft tissue neoplasms. Twelve hundred forty-four patients responded. The data were entered into a computer system and were correlated with the clinical information already contained in the system for the individual patients. Although there are many possible uses for these data, we chose to do a study comparing the lifestyle and physical and sociologic problems for 144 patients treated with chemotherapy and surgery for high-grade osteosarcoma against a control population consisting of 61 patients treated surgically for benign giant cell tumors of bone. The data show a remarkable degree of compensation on the part of the patients with the malignant tumors in terms of some problems but some significant differences particularly in physical status and functional limitations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Orthopaed Gray 6, Boston, MA 02114 USA. EM hmankin@partners.org NR 33 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2004 IS 426 BP 74 EP 86 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 851TO UT WOS:000223708600013 PM 15346055 ER PT J AU Baddley, JW Moser, SA AF Baddley, JW Moser, SA TI Emerging fungal resistance SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID ANTIFUNGAL DRUG-RESISTANCE; AMPHOTERICIN-B RESISTANCE; BLOOD-STREAM INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; CANDIDA-KRUSEI INFECTION; IN-VITRO SUSCEPTIBILITY; ASPERGILLUS-FUMIGATUS; CRYPTOCOCCUS-NEOFORMANS; 1,3-BETA-D-GLUCAN SYNTHASE; ITRACONAZOLE RESISTANCE AB There has been an increase in systemic fungal infections over the past several decades, partially because of an increasing number of critically ill patients, surgical procedures, and immunosuppressive therapies, as well as the use of more invasive diagnostic and therapeutic medical procedures. Concomitant with this increase in infections has been the increase in azole-resistant Candida species and opportunistic molds with intrinsic resistance to many of the currently available antifungal agents. This review focuses on antifungal resistance, with emphasis on emerging resistance patterns and emerging fungi that are intrinsically resistant to antifungal agents. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Moser, SA (reprint author), Univ Alabama, Dept Pathol, 619 19th St S, Birmingham, AL 35294 USA. EM moser@uab.edu RI Moser, Stephen/A-1168-2008 NR 94 TC 24 Z9 24 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2004 VL 24 IS 3 BP 721 EP + DI 10.1016/j.cll.2004.05.003 PG 16 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 852JQ UT WOS:000223752000008 PM 15325062 ER PT J AU Bracha, HS AF Bracha, HS TI Freeze, flight, fight, fright, faint: Adaptationist perspectives on the acute stress response spectrum SO CNS SPECTRUMS LA English DT Review ID BLOOD-INJURY PHOBIA; AUTONOMIC SPACE; VASOVAGAL SYNCOPE; VAGAL TONE; DISORDER; EVOLUTIONARY; ANXIETY; TRAUMA; FEARS; PROPRANOLOL AB This article reviews the existing evolutionary perspectives on the acute stress response habitual faintness and blood-injection-injury type-specific Phobia (BIITS phobia). In this article, an alternative evolutionary perspective, based on recent advances in evolutionary psychology, is proposed. Specifically, that fear-induced faintness (eg, fainting following the sight of a syringe, blood, or following a trivial skin injury) is a distinct Homo sapiens-specific extreme-stress survival response to an inescapable threat. The article suggests that faintness evolved in response to middle paleolithic intra-group and inter-group violence (of con-specifics) rather than as a pan-mammalian defense response, as is presently assumed. Based on recent literature, freeze, flight, fight, fright, faint Provides a more complete description of the human acute stress response sequence than current descriptions. Faintness, one of three primary physiological reactions involved in WITS phobia, is extremely rare in other phobias. Since heritability estimates are higher for faintness than for fears or phobias I the author suggests that trait-faintness may be a useful complement to trait-anxiety as an endophenotype in research on the human fear circuitry. Some implications for the forthcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as well as for clinical, health services, and transcriptomic research are briefly discussed. C1 US Dept Vet Affairs, Spark M Matsunaga Med Ctr, Natl Ctr PTSD, Pacific Isl Hlth Care Syst, Honolulu, HI 96813 USA. RP Bracha, HS (reprint author), US Dept Vet Affairs, Spark M Matsunaga Med Ctr, Natl Ctr PTSD, Pacific Isl Hlth Care Syst, 1132 Bishop St,307, Honolulu, HI 96813 USA. NR 71 TC 77 Z9 79 U1 6 U2 50 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2004 VL 9 IS 9 BP 679 EP 685 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VK UT WOS:000226891700015 PM 15337864 ER PT J AU Fischer, H Fransson, P Wright, CI Backman, L AF Fischer, Hakan Fransson, Peter Wright, Christopher I. Backman, Lars TI Enhanced occipital and anterior cingulate activation in men but not in women during exposure to angry and fearful male faces SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article AB Blood-oxygenation-level-dependent signal was measured with functional magnetic resonance imaging in 24 healthy young subjects (12 men and 12 women) during viewing of angry, fearful, and neutral male and female face pictures. Exposure to angry male as opposed to angry female faces activated the visual cortex and the anterior cingulate gyrus significantly more in men than in women. A similar sex-differential brain activation pattern was present during exposure to fearful but not neutral faces. Previous behavioral studies indicate enhanced physiological arousal in men but not in women during exposure to angry male as opposed to female faces, and brain imaging studies have shown that the occipital cortex and the anterior cingulate gyrus are influenced by activity in the autonomic nervous system as well as by visual attention. Hence, we suggest that the elevated occipital and anterior cingulate activation in men during confrontation with other angry and fearful males may reflect enhanced vigilance in a potentially dangerous situation. C1 [Fischer, Hakan; Backman, Lars] Karolinska Inst, S-11382 Stockholm, Sweden. [Fransson, Peter] Karolinska Hosp, S-10401 Stockholm, Sweden. [Wright, Christopher I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wright, Christopher I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wright, Christopher I.] Harvard Univ, Sch Med, Boston, MA USA. RP Fischer, H (reprint author), Karolinska Inst, Aging Res Ctr, Box 6401, S-11382 Stockholm, Sweden. EM hakan.fischer@neurotec.ki.se RI Fransson, Peter/M-5679-2014 OI Fransson, Peter/0000-0002-1305-9875 FU Sasakawa Young Leaders' Fellowship Fund, Faculty of Humanities and Social Sciences, Uppsala University; Swedish Research Council FX This research was supported by grants from the Sasakawa Young Leaders' Fellowship Fund, Faculty of Humanities and Social Sciences, Uppsala University (H. F.), and the Swedish Research Council (H. F. and L. B.). We thank Johan Sandblom and the staff at the Karolinska Hospital MR center for providing excellent data collection conditions. Correspondence should be addressed to H. Fischer, Aging Research Center, Karolinska Institute, Box 6401, 113 82 Stockholm, Sweden (e-mail: hakan.fischer@neurotec.ki.se). NR 39 TC 14 Z9 14 U1 5 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2004 VL 4 IS 3 BP 326 EP 334 DI 10.3758/CABN.4.3.326 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V32MO UT WOS:000208955500005 PM 15535168 ER PT J AU Safren, SA Hendriksen, ES Mayer, KH Mimiaga, MJ Pickard, R Otto, MW AF Safren, SA Hendriksen, ES Mayer, KH Mimiaga, MJ Pickard, R Otto, MW TI Cognitive-behavioral therapy for HIV medication adherence and depression SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID SELF-REPORTED ADHERENCE; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; CLINICAL-TRIALS; VIRAL LOAD; INCREASE ADHERENCE; RATING-SCALE; PREDICTORS; AIDS; INFECTION AB For patients with HIV, depression is a common, distressing condition that can interfere with a critical self-care behavior- adherence to antiretroviral therapy. The present study describes a cognitive-behavioral treatment designed to integrate cognitive-behavioral their therapy for depression with our previously tested. approach to improving adherence to antiretroviral therapy for HTV Each session addresses HIV medication adherence in the context Of modules for activity scheduling, cognitive restructuring, problem-solving training, and relaxation training/diaphragmatic breathing. We present the design of the intervention and outcome of 5 cases. All of the patients presented below were men who have sex with men who were infected with HTV through sexual transmission. Generally, these patients showed improvements in both depression and medication adherence. C1 Fenway Community Hlth, Res & Evaluat Dept, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. Miriam Hosp, Providence, RI 02906 USA. RP Safren, SA (reprint author), Fenway Community Hlth, Res & Evaluat Dept, 16 Haviland St, Boston, MA 02115 USA. EM ssafren@partners.org NR 50 TC 31 Z9 31 U1 0 U2 4 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FAL PY 2004 VL 11 IS 4 BP 415 EP 424 DI 10.1016/S1077-7229(04)80058-0 PG 10 WC Psychology, Clinical SC Psychology GA 916WU UT WOS:000228418100008 ER PT J AU Baggish, AL MacGillivray, TE Hoffman, W Newell, JB Lewandrowski, KB Lee-Lewandrowski, E Anwaruddin, S Siebert, U Januzzi, JL AF Baggish, AL MacGillivray, TE Hoffman, W Newell, JB Lewandrowski, KB Lee-Lewandrowski, E Anwaruddin, S Siebert, U Januzzi, JL TI Postoperative troponin-T predicts prolonged intensive care unit length of stay following cardiac surgery SO CRITICAL CARE MEDICINE LA English DT Article DE troponins; cardiac surgery; outcomes; complications; length of stay; intensive care unit ID MORTALITY; DURATION; COSTS AB Objective: To evaluate the use of postoperative cardiac troponin T (cTnT) for the prediction of prolonged intensive care unit length of stay following cardiac surgery. Design: Prospective, single-center, observational cohort study of patients following cardiac surgical procedures. The enrollment period was from October through December 2000. Patients were enrolled on admission to the intensive care unit and followed until hospital discharge. Setting. The cardiac surgical intensive care unit of the Massachusetts General Hospital. Patients. A total of 222 consecutive patients were enrolled. Interventions. None. Measurements and Main Results. Perioperative clinical factors and serum concentrations of cTnT measured every 8 hrs after surgery were recorded. These clinical factors and the results of serum cTnT measurement were correlated with the need for prolonged intensive care unit length of stay (defined as >24 hrs). Univariable analysis identified factors predictive of prolonged intensive care unit length of stay. Stepwise logistic regression identified independent predictors of prolonged intensive care unit length of stay. Multiple linear regression was used to explore the direct relationship between cTnT concentrations at several postoperative time points and intensive care unit length of stay. At each time point assessed, cTnT concentrations from patients requiring a prolonged intensive care unit length of stay were significantly higher (all p < .001) than in those individuals with normal length of stay. In contrast, creatine kinase isoenzymes were not significantly different between patients with normal or prolonged intensive care unit length of stay. Multivariable analysis demonstrated that an immediate postoperative cTnT concentration 1.58 ng/mL was the strongest predictor of a prolonged intensive care unit length of stay (odds ratio, 5.6; 95% confidence interval, 2.9-10.8). Multiple linear regression analysis revealed that intensive care unit length of stay increased by 0.32 days with each incremental 1.0 ng/mL increase in cTnT measured at 18-24 hrs postprocedure. Conclusions. Elevated postoperative cTnT concentrations can prospectively identify patients requiring prolonged intensive care unit length of stay after cardiac surgery. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Clin Chem, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 14 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2004 VL 32 IS 9 BP 1866 EP 1871 DI 10.1097/01.CCM.0000139692.19371.7C PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 854JH UT WOS:000223898400008 PM 15343014 ER PT J AU Brugge, W AF Brugge, W TI Advanced endoscopy: a personal perspective SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, W (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2004 VL 20 IS 5 BP 459 EP 459 DI 10.1097/00001574-200409000-00007 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 848GF UT WOS:000223454900006 ER PT J AU Keroack, M AF Keroack, M TI Video capsule endoscopy SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE wireless; video; capsule; encloscopy ID SMALL-BOWEL ENDOSCOPY; PUSH-ENTEROSCOPY; CROHNS-DISEASE; DIAGNOSIS; MANAGEMENT AB Purpose of review The small bowel has been a difficult organ for gastroenterologists to evaluate. Small bowel radiographs and CT scanning have not had a high diagnostic rate, especially in patients presenting with small bowel bleeding. The video capsule "endoscope" has allowed for the direct visualization of the small bowel mucosa. This new technique provides direct viewing of the entire small bowel much like conventional endoscopy. Recent findings A series of studies have shown that video capsule endoscopy (VCE) is superior to barium radiography studies, CT scanning, and push enteroscopy for diagnosing disorders of the small bowel. Numerous case reports of angioectasias, Crohn disease, small bowel tumors, and other small bowel disorders have been reported. A recent study proposes that VCE helped to direct therapy and had a great impact in patient care. Summary Capsule endoscopy provides higher rates and more accurate diagnosis of small bowel diseases. The future of this technology could improve the ability to visualize the small bowel and improve the treatment of patients with small bowel disorders. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keroack, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM mkeroack@partners.org NR 26 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2004 VL 20 IS 5 BP 474 EP 481 DI 10.1097/00001574-200409000-00010 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 848GF UT WOS:000223454900009 PM 15689682 ER PT J AU Brugge, WR AF Brugge, WR TI Approaches to the drainage of pancreatic pseudocysts SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE pancreatic pseudocyst; cyst-gastrostomy; external drainage; endoscopic cyst-gastrostomy; pancreatitis ID TERM FOLLOW-UP; TRANSMURAL DRAINAGE; ENDOSCOPIC DRAINAGE; ECHO ENDOSCOPE; MANAGEMENT; PERFORMANCE; LESIONS AB Purpose of review Review the current methods for the drainage of pancreatic pseudocysts, focusing on the recent developments in the new methods of endoscopic drainage. Recent findings Pancreatic pseudocysts are collections of inflammatory fluid associated with acute and chronic pancreatitis. A leak in the pancreatic ductal system is most commonly the source of the fluid accumulation in these inflammatory cavities adjacent to the pancreas. Although most pseudocysts are not symptomatic and many resolve spontaneously over time, drainage of pseudocysts is occasionally required. There are several different approaches to the drainage: surgical, radiologic, and endoscopic. Surgical drainage is accomplished using the creation of a large anastomosis between the gastrointestinal tract and the pseudocyst cavity. Radiologically, pseudocysts are drained externally using a percutaneous, transabdominal drainage catheter. Endoscopy has offered the most recent advance, using the placement of transgastric or transduodenal stents. Most recently, therapeutic endoscopic ultrasound scopes have been used to introduce large stents that provide drainage into the upper gastrointestinal tract. Summary Of the three methods for the drainage of a pancreatic pseudocyst, only the endoscopic approach can provide minimally invasive internal drainage. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM WBRUGGE@PARTNERS.Org NR 17 TC 18 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2004 VL 20 IS 5 BP 488 EP 492 DI 10.1097/00001574-200409000-00012 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 848GF UT WOS:000223454900011 PM 15689684 ER PT J AU Mount, DB AF Mount, DB TI Novel physiology for an orphan transporter SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material ID PROTEIN-COUPLED RECEPTORS; OSMOTIC-STRESS; ANION-EXCHANGER; COTRANSPORTER; FAMILY; GENE; IDENTIFICATION; EXPRESSION; SLC26A6; GLYCINE C1 VA Boston Healthcare Syst, Div Renal, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA USA. RP Mount, DB (reprint author), Vet Adm Med Ctr W Roxbury, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM dmount@rics.bwh.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2004 VL 13 IS 5 BP 521 EP 523 DI 10.1097/00041552-200409000-00007 PG 3 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 850EB UT WOS:000223592900006 PM 15300158 ER PT J AU Sinenko, SA Kim, EK Wynn, R Manfruelli, P Ando, I Wharton, KA Perrimon, N Mathey-Prevot, B AF Sinenko, SA Kim, EK Wynn, R Manfruelli, P Ando, I Wharton, KA Perrimon, N Mathey-Prevot, B TI Yantar, a conserved arginine-rich protein is involved in Drosophila hemocyte development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE hemocyte development; melanotic masses; lamellocytes; lymph glands; Yantar; Lozenge ID LARVAL HEMATOPOIESIS; TRANSCRIPTION FACTOR; MELANOGASTER; BLOOD; GENE; DIFFERENTIATION; PATHWAY; JAK; SPECIFICATION; SUPPRESSION AB To identify novel factors involved in Drosophila hematopoiesis, we screened a collection of lethal recessive mutations that also affected normal hemocyte composition in larvae. We present the characterization of the gene yantar (ytr) for which we isolated null and hypomorphic mutations that were associated with severe defects in hemocyte differentiation and proliferation; ytr is predominantly expressed in the hematopoietic tissue during larval development and encodes an evolutionary conserved protein which is predominantly localized in the nucleus. The hematopoietic phenotype in ytr mutants is consistent with a defect or block in differentiation of precursor hemocytes: mutant larvae have enlarged lymph glands (LGs) and have an excess of circulating hemocytes. In addition, many cells exhibit both lamellocyte and crystal cell markers. Ytr function has been preserved in evolution as hematopoietic specific expression of the Drosophila or mouse Ytr proteins rescue the differentiation defects in mutant hemocytes. (C) 2004 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. Korea Univ, Natl Creat Res Initiat Ctr Cell Death, Seoul 136701, South Korea. Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. Hungarian Acad Sci, Inst Genet, Biol Res Ctr, Szeged, Hungary. RP Sinenko, SA (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St,M647, Boston, MA 02115 USA. EM sergey_sinenko@dfci.harvard.edu RI Sinenko, Sergey/C-3703-2016 FU NHLBI NIH HHS [R01 HL62434] NR 46 TC 25 Z9 25 U1 3 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2004 VL 273 IS 1 BP 48 EP 62 DI 10.1016/j.ydbio.2004.05.022 PG 15 WC Developmental Biology SC Developmental Biology GA 846WV UT WOS:000223351100004 PM 15302597 ER PT J AU Matos, M Park, R Mathis, D Benoist, C AF Matos, M Park, R Mathis, D Benoist, C TI Progression to islet destruction in a cyclophosphamide-induced transgenic model - A microarray overview SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; T-CELL; NOD MICE; INTERFERON-GAMMA; ACTIVE DIABETOGENESIS; GENE OVEREXPRESSION; MOUSE PANCREAS; B-LYMPHOCYTES; REG GENE; RECEPTOR AB Type 1 diabetes appears to progress not as an uncontrolled autoimmune attack on the pancreatic islet beta-cells, but rather in a highly regulated manner. Leukocytic infiltration of the pancreatic islets by autoimmune cells, or insulitis, can persist for long periods of time before the terminal destruction of beta-cells. To gain insight on the final stage of diabetogenesis, we have studied progression to diabetes in a CD4(+) T-cell receptor transgenic variant of the NOD mouse model, in which diabetes can be synchronously induced within days by a single injection of cyclophosphamide. A time-course analysis of the gene expression profiles of purified islets was performed using microarrays. Contrary to expectations, changes in transcripts subsequent to drug treatment did not reflect a perturbation of gene expression in CD4(+) T-cells or a reduction in the expression of genes characteristic of regulatory T-cell populations. Instead, there was a marked decrease in transcripts of genes specific to B-cells, followed by an increase in transcripts of chemokine genes (cxcl1, cxcl5, and ccl7) and of other genes typical of the myelo-monocytic lineages. Interferon-gamma dominated the changes in gene expression to a striking degree, because close to one-half of the induced transcripts issued from interferon-gamma-regulated genes. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Pediat Endocrinol, Boston, MA 02115 USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIAID NIH HHS [P01 AI 39671] NR 41 TC 29 Z9 31 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2004 VL 53 IS 9 BP 2310 EP 2321 DI 10.2337/diabetes.53.9.2310 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 851JL UT WOS:000223681300016 PM 15331540 ER PT J AU Murff, HJ Rothman, RL Byrne, DW Syngal, S AF Murff, HJ Rothman, RL Byrne, DW Syngal, S TI The impact of family history of diabetes on glucose testing and counseling behavior in primary care SO DIABETES CARE LA English DT Article ID PHYSICAL-ACTIVITY; RISK; MELLITUS; MEN C1 VA Tennessee Valley Healthcare Syst, GRECC, Dept Vet Affairs, Nashville, TN 37212 USA. Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Vanderbilt Diabet Res & Training Ctr, Nashville, TN USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Murff, HJ (reprint author), VA Tennessee Valley Healthcare Syst, GRECC, Dept Vet Affairs, 1310 24th Ave, Nashville, TN 37212 USA. EM harvey.murff@med.va.gov NR 13 TC 12 Z9 12 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2004 VL 27 IS 9 BP 2247 EP 2248 DI 10.2337/diacare.27.9.2247 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 851JP UT WOS:000223681700026 PM 15333494 ER PT J AU Whittemore, R Melkus, GD Sullivan, A Grey, M AF Whittemore, Robin D'Eramo Melkus, Gail Sullivan, Amy Grey, Margaret TI A nurse-coaching intervention for women with type 2 diabetes SO DIABETES EDUCATOR LA English DT Article AB PURPOSE the purpose of this pilot study was to determine the efficacy of a 6-month nurse-coaching intervention that was provided after diabetes education for women with type 2 diabetes. METHODS In this pilot study, 53 women were randomized to the nurse-coaching intervention or a standard care control condition. The nurse-coaching intervention consisted of 5 individualized sessions and 2 follow-up phone calls over 6 months. The nurse-coaching sessions included educational, behavioral, and affective strategies. Data were collected on physiologic adaptation ( hemoglobin A1c [A1C] and body mass index [BMI]), self-management ( dietary and exercise), psychosocial adaptation (diabetes-related distress and integration), and treatment satisfaction at baseline, 3 months, and 6 months. RESULTS Women in the treatment group demonstrated better diet self-management, less diabetes-related distress, better integration, and more satisfaction with care, and had trends of better exercise self-management and BMI. The A1C levels improved in both groups at 3 months, yet the difference between the groups was not significant. Attendance at nurse-coaching sessions was 96%. CONCLUSIONS This nurse-coaching intervention demonstrates promise as a means of improving self-management and psychosocial outcomes in women with type 2 diabetes. C1 Yale Sch Nursing, New Haven, CT 06536 USA. Joslin Diabet Ctr, New London, CT USA. RP Whittemore, R (reprint author), Diabet Educator, 367 W Chicago Ave, Chicago, IL 60610 USA. EM robin.whittemore@yale.edu FU NINR NIH HHS [F32NR07823] NR 58 TC 46 Z9 48 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD SEP-OCT PY 2004 VL 30 IS 5 BP 795 EP 804 DI 10.1177/014572170403000515 PG 10 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA V43QI UT WOS:000202949200012 PM 15510531 ER PT J AU Moates, JM Magnuson, MA AF Moates, JM Magnuson, MA TI The Pal elements in the upstream glucokinase promoter exhibit dyad symmetry and display cell-specific enhancer activity when multimerised SO DIABETOLOGIA LA English DT Article DE dimer; dyad symmetry; enhancer; glucokinase; inverted repeat; methylation interference; promoter ID INSULIN GENE-TRANSCRIPTION; ISLET BETA-CELLS; RETINOIC ACID; THYROID-HORMONE; HOMEOBOX FACTOR; EXPRESSION; ACTIVATION; BINDING; RECEPTORS; DIFFERENTIATION AB Aims/hypothesis. The upstream glucokinase (betaGK) promoter has previously been shown to contain two 9-bp sequences, termed the Pal motifs, that are conserved in humans, rats and mice. These motifs are necessary for expression of the betaGK promoter in pancreatic beta cell lines and pituitary corticotrope cell lines. DNA probes containing the Pal motifs bind cell-type-specific protein complexes, but these motifs have not been completely characterised. Methods. Methylation interference and ultraviolet-crosslinking analysis were utilised to characterise, at the single nucleotide level, sites of protein binding within the elements themselves. To determine the function of these elements, mutational analysis of the betaGK promoter and of multimerised GK promoter sequences was performed. Results. Both Pal elements are 14 bp in length and have dyad symmetry. However, while the Pal-1 element is a perfect inverted repeat (GTCACCA-TGGTGAC), the Pal-2 element (GTCACCA-TAGAAAC) is an imperfect repeat. Ultraviolet-crosslinking analysis using nuclear extracts prepared from hamster insulinoma tumour (HIT) cells revealed that the three resolvable complexes that bind to the Pal-1 and Pal-2 elements contain different ratios of three proteins of different size (similar to90, 110 and 150 M-r). Mutation of a single nucleotide binding site abrogates betaGK promoter activity. Multimerised repeats of the Pal-1 element augment transcription in HIT cells, but not in baby hamster kidney (BHK) cells. Conclusions/interpretation. These results suggest that different combinations of three proteins of different size bind to the Pal elements, probably as homodimers and heterodimers. Together, these results indicate that the beta(2)GK promoter contains two novel 14-bp elements that, when multimerised, exhibit enhancer activity specific to neuroendocrine cells. C1 Univ Alabama, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL 35294 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Nashville Vet Affairs Med Ctr, Nashville, TN 37212 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. RP Moates, JM (reprint author), Univ Alabama, Dept Med, Div Endocrinol Diabet & Metab, Rm 706 BDB,1808 7th Ave S, Birmingham, AL 35294 USA. EM mmoates@uab.edu RI Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 FU NIDDK NIH HHS [DK42502, DK42612] NR 33 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2004 VL 47 IS 9 BP 1632 EP 1640 DI 10.1007/s00125-004-1497-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 863TE UT WOS:000224584700021 PM 15365616 ER PT J AU Si, MW Thorson, JA Lauwers, GY DalCin, P Furman, J AF Si, MW Thorson, JA Lauwers, GY DalCin, P Furman, J TI Hepatocellular lymphoepithelioma-like carcinoma associated with Epstein Barr virus - A hitherto unrecognized entity SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE lymphoepithelioma-like carcinoma; Epstein-Barr virus; hepatocellular carcinoma; cirrhosis; immunosuppression ID POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; GASTRIC-CARCINOMA; LYMPHOID STROMA; NASOPHARYNGEAL CARCINOMA; URINARY-BLADDER; HIGH PREVALENCE; UTERINE CERVIX; INFECTION; STOMACH AB Objective: Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with a dense lymphoid stroma. It has been reported in diverse organs and shows variable association with Epstein-Barr virus (EBV). Only a few EBV positive cases have been observed in the hepatobiliary system, all of which were considered to be cholangiocarcinomas. We report a unique case of hepatocellular LELC arising in a cirrhotic liver with EBV demonstrated in the tumor cells. Methods and Results: A 39-year-old Hispanic female underwent an orthotopic liver transplant for end stage liver disease secondary to chronic hepatitis C. A high-grade hepatocellular carcinoma with a dense lymphocytic infiltrate was found in the explant as well as in a portal lymph node. Three months posttransplant, the patient developed numerous hepatic nodules with enlarged periaortic and portacaval lymph nodes. Biopsy of the hepatic nodules showed a recurrent hepatocellular carcinoma devoid of a dense lymphocytic infiltrate. Both the primary and recurrent tumors were positive for EBV by molecular studies. The patient eventually expired from liver failure over a 6-week period. Conclusion: This case represents the first report of EBV-positive hepatocellular LELC. It is particularly interesting given the precipitous clinical outcome, which was possibly related to immunosuppresive therapy. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Furman, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM furmanj@uthscsa.edu NR 54 TC 15 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2004 VL 13 IS 3 BP 183 EP 189 DI 10.1097/01.pas.0000124336.90615.8d PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 849XU UT WOS:000223575800009 PM 15322431 ER PT J AU Davis, AE AF Davis, AE TI Biological effects of C1 inhibitor SO DRUG NEWS & PERSPECTIVES LA English DT Review ID MOLECULAR-WEIGHT KININOGEN; HEREDITARY ANGIONEUROTIC-EDEMA; INCREASED VASCULAR-PERMEABILITY; PLASMINOGEN-ACTIVATOR RECEPTOR; HUMAN-ENDOTHELIAL-CELLS; SERINE PROTEASES MASPS; CL-ESTERASE INHIBITOR; FACTOR-XII; C1-ESTERASE INHIBITOR; REPERFUSION INJURY AB C1 inhibitor is a serine proteinase inhibitor (serpin) that regulates activation of both the complement and contact systems. Regulation of complement system activation takes place through inactivation of the classical pathway proteases, C1r and C1s, the lectin pathway protease, MASP2, and perhaps via inhibition of alternative pathway activation by reversible binding to C3b. Regulation of contact system activation takes place through inactivation of plasma kallikrein and coagulation factor Xlla. Deficiency of C1 inhibitor results in hereditary angioedema, which is characterized by recurrent episodes of localized angioedema of the skin, gastrointestinal mucosa or upper respiratory mucosa. A variety of clinical, in vitro and animal experiments indicate that the mediator of increased vascular permeability in hereditary angioedema is bradykinin. Animal models suggest that in addition to its utility in therapy of hereditary angioedema, C1 inhibitor may prove useful in a variety of other diseases including septic shock, reper-fusion injury, hyperacute transplant rejection, traumatic and hemorrhagic shock, and the increased vascular permeability associated with thermal injury, interleukin-2 therapy and cardiopulmonary bypass. The therapeutic effect in these disease models very likely results from a combination of complement system activation, contact system activation and perhaps from other activities of C1 inhibitor. These other activities include a direct interaction with endotoxin, which may help to prevent endotoxic shock and an interaction with selectin molecules on endothelial cells, which may serve both to concentrate C1 inhibitor at sites of inflammation and to inhibit the transmigration of leukocytes across the endothelium. (C) 2004 Prous Science. All rights reserved. C1 Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR, Biomed Res Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu NR 113 TC 42 Z9 42 U1 0 U2 5 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD SEP PY 2004 VL 17 IS 7 BP 439 EP 446 DI 10.1358/dnp.2004.17.7.863703 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 862JF UT WOS:000224486100005 PM 15514703 ER PT J AU Duan, XB Yarmush, DM Berthiaume, F Jayaraman, A Yarmush, ML AF Duan, XB Yarmush, DM Berthiaume, F Jayaraman, A Yarmush, ML TI A mouse serum two-dimensional gel map: Application to profiling burn injury and infection SO ELECTROPHORESIS LA English DT Article DE acute-phase proteins; burn injury; lipopolysaccharide; mouse serum two-dimensional gel map ID ACUTE-PHASE RESPONSE; GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; HUMAN-PLASMA-PROTEINS; MASS-SPECTROMETRY; RAT SERUM; INTERFERON-GAMMA; DEFICIENT MICE; LIVER PROTEINS; SECRETED FORM AB With the importance of mouse as a model to study human diseases and the human and rat plasma/serum two-dimensional (2-D) maps being extensively annotated, this study was aimed at constructing a detailed mouse serum 2-D map. Serum proteins from two different inbred strains of mice (BALB/cJ and C57BL/6J) and mice subjected to two different inflammatory stimuli (20% burn injury and lipopolysaccharide (LPS) injection) were separated on overlapping gels covering pH 3-8 and stained with SYPRO Ruby dye. The tryptic peptides from the resolved spots were analyzed by mass spectrometry, leading to the identification of 38 different gene products. With the exception of major urinary proteins found in abundance in male C57BL/6J mice, little strain difference of the mouse serum 2-D was observed. Many proteins detected in the mouse serum 2-D map were not reported in human or rat serum 2-D maps including epidermal growth factor receptor. Three major murine acute-phase proteins (APPs), haptoglobin, serum amyloid A, and serum amyloid P, were highly induced by both inflammatory stimuli. Image analysis shows that the variations of APPs between these two inflammatory models were not uniform although LPS (100 mug/animal) in general was more effective than 20% burn injury in inducing APPs. Serum amyloid A, much more sensitive to endotoxin than burn injury, may represent a sensitive marker to differentiate these two different inflammatory states. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Dept Surg, Boston, MA 02115 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIGMS NIH HHS [R01-GM-65474] NR 59 TC 27 Z9 31 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 2004 VL 25 IS 17 BP 3055 EP 3065 DI 10.1002/ELPS.200406039 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 854YB UT WOS:000223938700022 PM 15349948 ER PT J AU Quivy, JP Roche, D Kirschner, D Tagami, H Nakatani, Y Almouzni, G AF Quivy, JP Roche, D Kirschner, D Tagami, H Nakatani, Y Almouzni, G TI A CAF-1 dependent pool of HP1 during heterochrornatin duplication SO EMBO JOURNAL LA English DT Article DE chromatin assembly; heterochromatin; nuclear organization; replication in vivo ID CHROMATIN ASSEMBLY FACTOR-1; DNA-REPLICATION SITES; MAMMALIAN-CELLS; HISTONE H3; FACTOR-I; PERICENTRIC HETEROCHROMATIN; EPIGENETIC CONTROL; LYSINE 9; PROTEINS; ORGANIZATION AB To investigate how the complex organization of heterochromatin is reproduced at each replication cycle, we examined the fate of HP1-rich pericentric domains in mouse cells. We find that replication occurs mainly at the surface of these domains where both PCNA and chromatin assembly factor 1 (CAF-1) are located. Pulse-chase experiments combined with high-resolution analysis and 3D modeling show that within 90 min newly replicated DNA become internalized inside the domain. Remarkably, during this time period, a specific subset of HP1 molecules (alpha and gamma) coinciding with CAF-1 and replicative sites is resistant to RNase treatment. Furthermore, these replication-associated HP1 molecules are detected in Suv39 knockout cells, which otherwise lack stable HP1 staining at pericentric heterochromatin. This replicative pool of HP1 molecules disappears completely following p150CAF-1 siRNA treatment. We conclude that during replication, the interaction of HP1 with p150CAF-1 is essential to promote delivery of HP1 molecules to heterochromatic sites, where they are subsequently retained by further interactions with methylated H3-K9 and RNA. C1 CNRS, UMR 218, Inst Curie, Sect Rech, F-75248 Paris 05, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Almouzni, G (reprint author), CNRS, UMR 218, Inst Curie, Sect Rech, 26 Rue Ulm, F-75248 Paris 05, France. EM genevieve.almouzni@curie.fr FU NIGMS NIH HHS [GM065939-02, R01 GM065939] NR 49 TC 125 Z9 125 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2004 VL 23 IS 17 BP 3516 EP 3526 DI 10.1038/sj.emboj.7600362 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852CM UT WOS:000223732800008 PM 15306854 ER PT J AU Cerny, J Feng, Y Yu, A Miyake, K Borgonovo, B Klumperman, J Meldolesi, J McNeil, PL Kirchhausen, T AF Cerny, J Feng, Y Yu, A Miyake, K Borgonovo, B Klumperman, J Meldolesi, J McNeil, PL Kirchhausen, T TI The small chemical vacuolin-1 inhibits Ca2+-dependent lysosomal exocytosis but not cell resealing SO EMBO REPORTS LA English DT Article DE chemical genetics; membrane repair; exocytosis ID PLASMA-MEMBRANE DISRUPTION; REGULATED EXOCYTOSIS; REPAIR; FIBROBLASTS; VESICLES; SURFACE AB Resealing after wounding, the process of repair following plasma membrane damage, requires exocytosis. Vacuolins are molecules that induce rapid formation of large, swollen structures derived from endosomes and lysosomes by homotypic fusion combined with uncontrolled fusion of the inner and limiting membranes of these organelles. Vacuolin-1, the most potent compound, blocks the Ca2+-dependent exocytosis of lysosomes induced by iono-mycin or plasma membrane wounding, without affecting the process of resealing. In contrast, other cell structures and membrane trafficking functions including exocytosis of enlargeosomes are unaffected. Because cells heal normally in the presence of vacuolin-1, we suggest that lysosomes are dispensable for resealing. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Charles Univ Prague, Dept Physiol Anim & Dev Biol, Prague 2, Czech Republic. Harvard Univ, Sch Med, ICCB, Inst Chem & Cell Biol, Boston, MA 02115 USA. Med Coll Georgia, Dept Anat & Cellular Biol, Augusta, GA 30912 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Univ Vita Salute San Raffaele, DIBIT, Dept Neurosci, I-20132 Milan, Italy. San Raffaele Inst, I-20132 Milan, Italy. Univ Med Ctr, Dept Cell Biol, NL-3584 Utrecht, Netherlands. Inst Biomembranes, NL-3584 Utrecht, Netherlands. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu RI Cerny, Jan/C-1887-2012 FU NIGMS NIH HHS [GM62566, P01 GM062566] NR 22 TC 63 Z9 63 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2004 VL 5 IS 9 BP 883 EP 888 DI 10.1038/sj.embor.7400243 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 850UE UT WOS:000223638200013 PM 15332114 ER PT J AU Eisenhofer, G Bornstein, SR Brouwers, FM Cheung, NKV Dahia, PL de Krijger, RR Giordano, TJ Greene, LA Goldstein, DS Lehnert, H Manger, WM Maris, JM Neumann, HPH Pacak, K Shulkin, BL Smith, DI Tischler, AS Young, WF AF Eisenhofer, G Bornstein, SR Brouwers, FM Cheung, NKV Dahia, PL de Krijger, RR Giordano, TJ Greene, LA Goldstein, DS Lehnert, H Manger, WM Maris, JM Neumann, HPH Pacak, K Shulkin, BL Smith, DI Tischler, AS Young, WF TI Malignant pheochromocytoma: current status and initiatives for future progress SO ENDOCRINE-RELATED CANCER LA English DT Review ID NEUROFIBROMATOSIS KNOCKOUT MICE; METASTATIC PHEOCHROMOCYTOMA; SPORADIC PHEOCHROMOCYTOMAS; ADRENAL PHEOCHROMOCYTOMA; REFRACTORY NEUROBLASTOMA; OCTREOTIDE SCINTIGRAPHY; NEUROENDOCRINE TUMORS; TARGETED RADIOTHERAPY; INCREASED EXPRESSION; CELL-LINES AB Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies. C1 NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus Med Ctr, Rotterdam, Netherlands. Univ Michigan, Ann Arbor, MI 48109 USA. Columbia Univ, New York, NY USA. Univ Magdeburg, Sch Med, D-39106 Magdeburg, Germany. Natl Hypertens Assoc, New York, NY USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Med Univ Klin, Freiburg, Germany. Mayo Clin, Rochester, MN USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Eisenhofer, G (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov OI Giordano, Thomas/0000-0003-0641-8873 NR 91 TC 191 Z9 202 U1 0 U2 4 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2004 VL 11 IS 3 BP 423 EP 436 DI 10.1677/erc.1.00829 PG 14 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 860KR UT WOS:000224343000003 PM 15369446 ER PT J AU Gottsch, ML Cunningham, MJ Smith, JT Popa, SM Acohido, BV Crowley, WF Seminara, S Clifton, DK Steiner, RA AF Gottsch, ML Cunningham, MJ Smith, JT Popa, SM Acohido, BV Crowley, WF Seminara, S Clifton, DK Steiner, RA TI A role for kisspeptins in the regulation of gonadotropin secretion in the mouse SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; GALANIN-LIKE PEPTIDE; MESSENGER-RNA; NEUROPEPTIDE-Y; INSITU HYBRIDIZATION; HORMONE NEURONS; LH-RELEASE; FEMALE RAT; KISS-1; ESTROGEN AB Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH. C1 Univ Washington, Sch Med G424, Dept Physiol & Biophys, Seattle, WA 98195 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Steiner, RA (reprint author), Univ Washington, Sch Med G424, Dept Physiol & Biophys, Hlth Sci Bldg,Box 357290,1959 NE Pacific St, Seattle, WA 98195 USA. EM steiner@u.washington.edu RI Smith, Jeremy/I-3401-2013 OI Smith, Jeremy/0000-0002-3450-9505 FU NICHD NIH HHS [R01 HD 27142, R01 HD015788, U54 HD028138, U54 HD029164, U54 HD12629, U54 HD28138]; NIDDK NIH HHS [R01 DK61517] NR 28 TC 636 Z9 653 U1 2 U2 56 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4073 EP 4077 DI 10.1210/en.2004-0431 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600013 PM 15217982 ER PT J AU Tfelt-Hansen, J Yano, S Bandyopadhyay, S Carroll, R Brown, EM Chattopadhyay, N AF Tfelt-Hansen, J Yano, S Bandyopadhyay, S Carroll, R Brown, EM Chattopadhyay, N TI Expression of pituitary tumor transforming gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: Function and regulation of PTTG in U87 astrocytoma cells SO ENDOCRINOLOGY LA English DT Article ID CALCIUM-SENSING RECEPTOR; MOLECULAR-CLONING; K+ CHANNEL; GROWTH; ACID; CANCER; AGONISTS; KINASE; GAMMA; BRAIN AB Human securin, pituitary tumor transforming gene (PTTG), is a protooncogene. Here we report expressions of PTTG and its interacting protein, PTTG-binding factor in human astrocytic cells. PTTG expression was higher in malignant cells than in primary astrocytes, whereas PTTG-binding factor was not. Using a xenotransplantable, glioma cell line (U87),. we observed that knocking down PTTG mRNA by RNA silencing inhibited serum-induced proliferation by approximately 50%. Furthermore, in U87 cells PTTG expression was up-regulated by promalignant ligands epithelial growth factor (EGF) and TGFalpha, both at the protein and mRNA levels. PTTG induction by EGF receptor (EGFR) ligands could be blocked by the specific EGFR inhibitor, AG1478. Hepatocyte growth factor (HGF) also induced PTTG but to a lesser extent than EGF. Although EGF stimulates HGF secretion in U87 cells, the effect of EGF on PTTG mRNA expression is independent of HGF as neutralizing antibody against HGF failed to abolish EGF-induced up-regulation of PTTG mRNA. PTTG mRNA was unchanged by incubating U87 cells with the promalignant growth factor TGFbeta, apoptosis inducing TNFalpha and ligands for nuclear receptors, such as retinoic acid and retinoid X receptors and peroxisome proliferator-activated receptor-gamma, known for their growth-inhibitory and apoptosis-inducing effects on gliomas. In addition, 17beta-estradiol and Ca2+, known to activate, PTTG expression, did not change PTTG mRNA levels in U87 cells. In summary, we show higher PTTG expression in astrocytoma than normal astrocytes and secondly, PTTG is involved in glioma cell growth. Finally, regulation of its expression has glioma-specific features and is selectively regulated by promalignant cytokines including EGFR ligands and HGF. C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Copenhagen, Hvidovre Hosp, Dept Clin Biochem & Endocrinol, DK-2650 Hvidovre, Denmark. Massachusetts Gen Hosp, Dept Psychiat Neurosci, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tfelt-Hansen, J (reprint author), Univ Copenhagen, Dept Cardiol, Mol Cardiol Lab, 20 Juliane Maries Vej,Sect 9312, DK-2100 Copenhagen O, Denmark. EM tfelt@dadlnet.dk OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599; Chattopadhyay, Naibedya/0000-0003-2473-0246 FU NIAMS NIH HHS [AR02215]; NIDDK NIH HHS [DK41415, DK48830, DK52005] NR 37 TC 40 Z9 43 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4222 EP 4231 DI 10.1210/en.2003-1661 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600030 PM 15178645 ER PT J AU Hermann, TS Ihlemann, N Dominguez, H Rask-Madsen, C Kober, L Torp-Pedersen, C AF Hermann, TS Ihlemann, N Dominguez, H Rask-Madsen, C Kober, L Torp-Pedersen, C TI Prolonged local forearm hyperinsulinernia induces sustained enhancement of nitric oxide-dependent vasodilation in healthy subjects SO ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH LA English DT Article DE endothelium; insulin; nitric oxide; vasodilation ID MUSCLE BLOOD-FLOW; STIMULATED ENDOTHELIAL FUNCTION; SYMPATHETIC NEURAL ACTIVATION; INSULIN-MEDIATED VASODILATION; SKELETAL-MUSCLE; GLUCOSE-UPTAKE; DIABETES-MELLITUS; NO EVIDENCE; IN-VIVO; HUMANS AB Systemic hyperinsulinemia induces enhancement of endothelium-dependent vasodilation of healthy subjects. During systemic infusion of insulin, endothelium-dependent vasodilation may be improved through a decrease in the concentration of free fatty acids. To explore the direct effect of continued insulin on the vascular endothelium, the authors infused insulin in the brachial artery for 4 h and measured the effect on endothelium-dependent vasodilation in the human forearm. Thirty-six experiments were performed in healthy subjects, mean age 47.7 +/- 1.1 years. Endothelium-dependent and -independent vasodilatation was studied during intra-arterial infusion of serotonin and sodium nitroprusside (SNP), respectively. Forearm blood flow was measured by plethysmography. Intra-arterial insulin was infused for 240 min at a constant rate and blood flow was measured hourly during stimulation of endothelium-dependent and -independent vasodilation. N-G-monomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = (.)016. This increase was maintained for 4 It and was blocked by L-NMMA. The SNP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Rigshosp, Ctr Heart, DK-2100 Copenhagen, Denmark. Bispebjerg Univ Hosp, Dept Cardiol Y, DK-2400 Copenhagen, Denmark. RP Torp-Pedersen, C (reprint author), Dept Cardiol Y, Bldg 40,Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. EM ctp@heart.dk RI Torp-Pedersen, Christian/E-5931-2013 NR 48 TC 6 Z9 8 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1062-3329 J9 ENDOTHELIUM-J ENDOTH JI Endothelium PD SEP-DEC PY 2004 VL 11 IS 5-6 BP 231 EP 239 DI 10.1080/106233320490904098 PG 9 WC Cell Biology; Peripheral Vascular Disease SC Cell Biology; Cardiovascular System & Cardiology GA 887LD UT WOS:000226306700002 PM 15763942 ER PT J AU Nelson, KM Geiger, AM Mangione, CM AF Nelson, KM Geiger, AM Mangione, CM TI Racial and ethnic variation in response to mailed and telephone surveys among women in a managed care population SO ETHNICITY & DISEASE LA English DT Article DE data collection/methods; ethnic groups; health surveys ID CERVICAL-CANCER; HEALTH SURVEY; ANGLO WOMEN; RESPONDENTS; NONRESPONSE; HISPANICS; BEHAVIOR; LATINAS; BELIEFS; BREAST AB Purpose: To describe the characteristics of participants who completed a mailed survey, compared to those initial non-responders who completed the same survey over the telephone. Study Design and Patient Populations: We conducted a mailed survey, in both Spanish and English, among women with abnormal Pap smears, who were members of a large managed care organization. Telephone follow up for non-responders was performed by a bilingual interviewer. A 20-minute long distance telephone card was offered as an incentive to individuals who completed the telephone survey. We used bivariate and multivariate analyses to describe the population characteristics of respondents who replied by mail, as compared to those who completed the survey by telephone. Results: Of the 1049 potentially eligible participants, 733 women completed the survey, for an overall response rate of 70%. Fifty-six percent (N=411) of the surveys were received by mail, and 44% (N=322) were completed by telephone. Thirty-four percent of the telephone surveys were completed in Spanish, compared to 13% of the mailed surveys (P<.001). Telephone respondents were less satisfied with their health care than were those who responded by mail. Conclusions: Among this insured cohort of women, Latinas who completed the survey in Spanish were more likely to participate in a telephone survey that offered an incentive, than in a mailed survey. These findings should be considered when planning health surveys in this population. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. So Calif Permanente Med Grp, Dept Res & Evaluat, Pasadena, CA USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RP Nelson, KM (reprint author), VA Puget Sound Med Ctr, S-111 GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM karin.nelson@med.va.gov FU NCI NIH HHS [1F32 CA 88495-01] NR 23 TC 3 Z9 3 U1 1 U2 1 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2004 VL 14 IS 4 BP 580 EP 583 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866GK UT WOS:000224761800017 PM 15724779 ER PT J AU Cannon, CP AF Cannon, CP TI Revascularisation for everyone? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID WAVE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; CONSERVATIVE STRATEGIES; UNSTABLE ANGINA; TRIAL; ANGIOPLASTY; THERAPY C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM cpcannon@partners.org NR 9 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2004 VL 25 IS 17 BP 1471 EP 1472 DI 10.1016/j.ehj.2004.05.019 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856JA UT WOS:000224040300001 PM 15342161 ER PT J AU Rumsfeld, JS Masoudi, FA AF Rumsfeld, JS Masoudi, FA TI Heart failure disease management works, but will it succeed? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID QUALITY-OF-CARE; TASK-FORCE; GUIDELINES; PROGRAM AB This editorial refers to "The effectiveness of disease management programmes in reducing hospital readmission in older patients with heart failure: a systematic review and meta-analysis of published reports" by J. Gonseth et al. on page 1570 and "Heart failure clinics and outpatient management: review of the evidence and call for quality assurance" by F. Gustafssofi and J.M.O. Arnold on page 1596(dagger). C1 Univ Colorado, Denver Hlth Med Ctr, Denver VA Med Ctr, Hlth Sci Ctr, Denver, CO 80220 USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Denver Hlth Med Ctr, Denver VA Med Ctr, Hlth Sci Ctr, Cardiol CV Outcomes Res 111B,1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfetd@med.va.gov NR 15 TC 11 Z9 13 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2004 VL 25 IS 18 BP 1565 EP 1567 DI 10.1016/j.ehj.2004.08.004 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856PC UT WOS:000224056100003 PM 15351155 ER PT J AU Kosslyn, SM Thompson, WL Shephard, JM Ganis, G Bell, D Danovitch, J Wittenberg, LA Alpert, NM AF Kosslyn, SM Thompson, WL Shephard, JM Ganis, G Bell, D Danovitch, J Wittenberg, LA Alpert, NM TI Brain rCBF and performance in visual imagery tasks: Common and distinct processes SO EUROPEAN JOURNAL OF COGNITIVE PSYCHOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; INDIVIDUAL-DIFFERENCES; MENTAL-IMAGERY; CEREBRAL HEMISPHERES; FMRI; PET; PERCEPTION; ROTATION; OBJECTS; BOLD AB The present study was designed to discover whether variations in normalised regional cerebral blood flow (rCBF) in different brain areas predict variations in performance of different imagery tasks. Positron emission tomography (PET) was used to assess brain activity as 16 participants performed four imagery tasks. These tasks were designed so that performance was particularly sensitive to the participant's ability to form images with high resolution, to generate images from distinct segments, to parse imaged forms into parts while inspecting them, or to transform (rotate) images. Response times and error rates were recorded. Multiple regression analyses revealed that variations in most brain areas predicted variations in performance of only one task, thus demonstrating that the four tasks tap largely independent imagery processes. However, we also found that some underlying processes were recruited by more than one task, particularly those implemented in the occipito-parietal sulcus, the medial frontal cortex, and Area 18. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Univ British Columbia, Sch Med, Vancouver, BC V5Z 1M9, Canada. RP Kosslyn, SM (reprint author), Harvard Univ, Dept Psychol, 832 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM smk@wjh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618 NR 37 TC 17 Z9 18 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0954-1446 J9 EUR J COGN PSYCHOL JI Eur. J. Cogn. Psychol. PD SEP PY 2004 VL 16 IS 5 BP 696 EP 716 DI 10.1080/09541440340000475 PG 21 WC Psychology, Experimental SC Psychology GA 845WJ UT WOS:000223275700005 ER PT J AU Su, MWC Pyarajan, S Chang, JH Yu, CL Jin, YJ Stierhof, YD Walden, P Burakoff, SJ AF Su, MWC Pyarajan, S Chang, JH Yu, CL Jin, YJ Stierhof, YD Walden, P Burakoff, SJ TI Fratricide of CD8(+) cytotoxic T lymphocytes is dependent on cellular activation and perforin-mediated killing SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CTL; cytotoxicity; antigens/peptides/epitopes; signal transduction ID MAPK SIGNALING PATHWAY; CHORIOMENINGITIS VIRUS; PERSISTENT INFECTION; ZETA-PHOSPHORYLATION; SELF-DESTRUCTION; INTERFERON-GAMMA; COGNATE PEPTIDES; IN-VITRO; CELLS; RECEPTOR AB CD8(+) CTL mediate the destruction of cells displaying foreign peptides in association with class I MHC molecules. Since CD8(+) CTL themselves express class I MHC molecules, a phenomenon known as "fratricide" can be elicited by T cells presenting antigens to other CTL. To gain insight into this mechanism, fratricide was induced in a clone of class I-restricted CD8(+) CTL by incubating the T cells with their agonist ligand, an octamer peptide derived from chicken ovalbumin. Our results indicate that agonist peptide not only stimulates proliferation and cytolysis of CTL but also initiates signaling pathways that are pertinent to T cell activation, including the mobilization of transcription factors. Also consistent with T cell activation, fratricide induced the transcription and translation of the pro-inflammatory cytokines TNF-alpha and IFN-gamma. Finally, the essential role of perforin, as opposed to Fas/FasL, in fratricide was demonstrated by the selective inhibition of cytolysis with an inhibitor of the perforin pathway, the absence of FasL expression on T cells and the presence of lytic granules visible by electron microscopy. Collectively, these findings reveal that fratricide is mediated by T cell activation and perforin-mediated cytolysis. These results may have implications for the regulation of CD8(+) CTL in immune responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Univ Tubingen, ZMBP Ctr Plant Mol Biol, Tubingen, Germany. Humboldt Univ, Dept Dermatol, Charite, Sch Med, Berlin, Germany. RP Burakoff, SJ (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, 540 1st Ave SK13, New York, NY 10016 USA. EM Steven.burakoff@med.nyu.edu RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NIAID NIH HHS [AI07498, AI17258] NR 48 TC 12 Z9 14 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2004 VL 34 IS 9 BP 2459 EP 2470 DI 10.1002/eji.200425096 PG 12 WC Immunology SC Immunology GA 853EU UT WOS:000223810400012 PM 15307178 ER PT J AU Wyszynski, DF Holmes, LB AF Wyszynski, D. F. Holmes, L. B. TI The AED (antiepileptic drug) pregnancy registry: A six-year experience SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 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 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 11 EP 11 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992100036 ER PT J AU Bar, M Borgohain, R Hayes, F Warnock, CR Conklin, H Whitehouse, H Morrell, M AF Bar, M. Borgohain, R. Hayes, F. Warnock, C. R. Conklin, H. Whitehouse, H. Morrell, M. TI Reproductive endocrine characteristics of women with newly diagnosed or inadequately controlled epilepsy - a baseline analysis SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 FN Poruba, Ostrava, Czech Republic. Massachusetts Gen Hosp, Boston, MA USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. GlaxoSmithKline Inc, Greenford, Middx, England. Columbia Presbyterian Med Ctr, New York, NY 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 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 77 EP 77 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992100262 ER PT J AU Trehin, R Merkle, HP AF Trehin, R Merkle, HP TI Chances and pitfalls of cell penetrating peptides for cellular drug delivery SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Review DE cell penetrating peptides; cellular drug delivery; endocytosis; permeation; biological barriers; toxicity ID HIV-1 TAT PROTEIN; HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR-LOCALIZATION SEQUENCE; ARGININE-RICH PEPTIDES; EFFICIENT INTRACELLULAR DELIVERY; VECTOR-MEDIATED STRATEGY; VP22-GFP FUSION PROTEINS; POLY-L-ARGININE; BASIC DOMAIN; IN-VIVO AB Over the past decade, several classes and/or prototypes of cell penetrating peptides (CPP) have been identified and investigated in multiple aspects. CPP represent peptides, which show the ability to cross the plasma membrane of mammalian cells, and may thus give rise to the intracellular delivery of problematic therapeutic cargos, such as peptides, proteins, oligonucleotides, plasmids and even nanometer-sized particles, which otherwise cannot cross the plasma membrane. Most of the currently recognized CPP are of cationic nature and derived from viral, insect or mammalian proteins endowed with membrane translocation properties. The exact mechanisms underlying the translocation of CPP across the cellular membrane are still poorly understood. However, several similarities in translocation can be found. Early studies on CPP translocation mechanisms tended to suggest that the internalization of these peptides was neither significantly inhibited by low temperature, depletion of the cellular adenosine triphosphate (ATP) pool, nor by inhibitors of endocytosis. Moreover, chemical modification of the peptide sequence, such as the synthesis of retro-, enantio- or retroenantio-analogs, appeared not to affect the internalization properties. Therefore, translocation was concluded to result from direct, physical transfer through the lipid bilayer of the cell membrane. Later studies, however, showed convincing evidence for the involvement of endocytosis as the dominating mechanism for cellular internalization. In addition to describing the general properties of the commonly recognized classes of CPP, in this review we will also point out some limitations and typical pitfalls of CPP as carriers for therapeutics. In particular we will comment on emerging discrepancies with the current dogma, on cell-to-cell variability, biological barrier permeability, metabolic fate, toxicity and immunogenicity of CPP. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, CMIR, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Zurich, Switzerland. RP Trehin, R (reprint author), Massachusetts Gen Hosp, CMIR, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM rtrehin@partners.org RI Merkle, Hans/A-4381-2014 NR 132 TC 140 Z9 151 U1 3 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD SEP PY 2004 VL 58 IS 2 BP 209 EP 223 DI 10.1016/j.ejpb.2004.02.018 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 849GQ UT WOS:000223527100003 PM 15296950 ER PT J AU Ozsunar, Y Koseoglu, K Huisman, TAGM Koroshetz, W Sorensen, AG AF Ozsunar, Y Koseoglu, K Huisman, TAGM Koroshetz, W Sorensen, AG TI MRI measurements of water diffusion: impact of region of interest selection on ischemic quantification SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE brain; diffusion; brain; ischemia; brain; infarction; magnetic resonance; anisotropy; region of interest; technique ID CEREBRAL BLOOD-VOLUME; ACUTE STROKE; PERFUSION MRI; HEMORRHAGIC TRANSFORMATION; TEMPORAL EVOLUTION; FOCAL ISCHEMIA; RAT-BRAIN; COEFFICIENT; ANISOTROPY; TENSOR AB Objective: To investigate the effect of ADC heterogeneity on region of interest (ROI) measurement of isotropic and anisotropic water diffusion in acute (< 12 h) cerebral infarctions. Methods and materials: Full diffusion tensor images were retrospectively analyzed in 32 patients with acute cerebral infarction. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in ischemic lesions and in the corresponding contralateral, normal appearing brain by using four ROIs for each patient. The 2 x 2 pixel square Rolls were placed in the center, the lateral rim and the medial rim of the infarction. In addition, the whole volume of the infarction was measured using a free hand method. Each ROI value obtained from the ischemic lesion was normalized using contralateral normal ROI values. Results: The localization of the Rots in relation to the ischemic lesion significantly affected ADC measurement (P < 0.01, using Friedman test), but not FA measurement (P = 0.25). Significant differences were found between ADC values of the center of the infarction versus whole volume (P < 0.01), and medial rim versus whole volume of infarction (P < 0.001) with variation of relative ADC values up to 11%. The differences of absolute ADC for these groups were 22 and 23%, respectively. The lowest ADC was found in the center, followed by medial rim, lateral rim and whole volume of infarction. Conclusion: ADC quantification may provide variable results depending on ROI method. The ADC and FA values, obtained from the center of infarction tend to be lower compared to the periphery. The researchers who try to compare studies or work on ischemic quantification should be aware of these differences and effects. (C) 2003 Published by Elsevier Ireland Ltd. C1 Adnan Mendares Univ, Sch Med, Dept Radiol, TR-09100 Aydin, Turkey. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Ozsunar, Y (reprint author), Adnan Mendares Univ, Sch Med, Dept Radiol, TR-09100 Aydin, Turkey. EM yozsunar@adu.edu.tr FU NINDS NIH HHS [NS38477]; OCPHP CDC HHS [PR014075] NR 40 TC 11 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD SEP PY 2004 VL 51 IS 3 BP 195 EP 201 DI 10.1016/j.ejrad.2003.09.013 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 848VU UT WOS:000223497000001 PM 15294325 ER PT J AU Reinisch, CM Weninger, W Mayer, C Paiha, K Lassmann, H Tschachler, E AF Reinisch, CM Weninger, W Mayer, C Paiha, K Lassmann, H Tschachler, E TI New insights into the nerve end organ of human skin SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 1st International Meeting on Neurobiology of the Skin CY FEB 13-15, 2004 CL Munster, GERMANY C1 Univ Vienna, Sch Med, Brain Res Inst, Dept Dermatol, Vienna, Austria. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Univ Vienna, Sch Med, Brain Res Inst, Inst Mol Pathol, Vienna, Austria. Univ Vienna, Sch Med, Brain Res Inst, Div Neuroimmunol, Vienna, Austria. CERIES, Neuilly, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD SEP PY 2004 VL 13 IS 9 BP 579 EP 580 PG 2 WC Dermatology SC Dermatology GA 850DG UT WOS:000223590800056 ER PT J AU Schroder, JN Williams, ML Koch, WJ AF Schroder, JN Williams, ML Koch, WJ TI Gene delivery approaches to heart failure treatment SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE adenovirus; beta-adrenergic signalling; calcium regulation; gene therapy; heart failure; intracoronary delivery ID ADRENERGIC-RECEPTOR KINASE; ADENOASSOCIATED VIRUS VECTORS; REPLICATION-DEFECTIVE ADENOVIRUS; CARDIAC SARCOPLASMIC-RETICULUM; HUMAN DILATED CARDIOMYOPATHY; LEFT-VENTRICULAR FUNCTION; FAILING HUMAN HEARTS; MYOCYTES IN-VITRO; BETA(2)-ADRENERGIC RECEPTOR; TRANSGENIC MICE AB Heart failure remains a leading cause of worldwide morbidity and morality. Despite recent advances in treatment and our increasing knowledge of pathophysiology and the molecular derangements involved in the failing of the heart, our ability to affect the underlying cardiac disease processes is limited. In recent years, there has been considerable interest in myocardial gene transfer as both an investigational and potential therapeutic modality. Ultimately, the goal of any such strategy is to reprogramme failing cardiac myocytes and correct the aberrant molecular events causing heart failure. So far, viral vectors have been utilised with success more frequently than any other method of gene delivery in animal models. Studies in animal models and in failing human cardiomyocytes in culture targeting specific molecular pathways, including the beta-adrenergic receptor cascade and the myocyte intracellular calcium handling system, have shown encouraging results and offer hope that gene manipulation may provide novel adjunctive therapeutic modalities for human heart failure. C1 Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Koch, WJ (reprint author), Thomas Jefferson Univ, Ctr Translat Med, 1025 Walnut St,Room 410, Philadelphia, PA 19107 USA. EM walter.koch@jefferson.edu NR 101 TC 4 Z9 6 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2004 VL 4 IS 9 BP 1413 EP 1422 DI 10.1517/14712598.4.9.1413 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 853RQ UT WOS:000223845600005 PM 15335309 ER PT J AU Shea, JA Beers, BB McDonald, VJ Quistberg, A Ravenell, KL Asch, DA AF Shea, JA Beers, BB McDonald, VJ Quistberg, A Ravenell, KL Asch, DA TI Assessing health literacy in African American and Caucasian adults: Disparities in rapid estimate of adult literacy in medicine (REALM) scores SO FAMILY MEDICINE LA English DT Article ID KNOWLEDGE; ASSOCIATION; CARE AB Background and Objectives: The influence of literacy on health and health care is an important area of investigation. Studies with a literacy focus are most valuable when literacy is assessed with psychometrically sound instruments. Methods: This study used a prospective cohort sample of 1,610 primary care patients. Patients provided sociodemographics and took the Rapid Estimate of Adult Literacy in Medicine (REALM), a 66-item word pronunciation literacy test. Results: The sample was 65% African American; 66% were men; 51% had a high school education or less. REALM scores were significantly related to education, age, and race but not gender When stratified by education, differences between African Americans and Caucasians remained significant. Using 19 different strategies to shorten the 66-item instrument, reliability coefficients above .80 were maintained. Conclusions: The REALM is a robust assessment of health literacy. However, the discordance in scores between African Americans and Caucasians with similar educational attainment needs to be further addressed. A much shorter instrument would still have internally consistent scores and potentially be more useful in clinical settings. C1 Univ Penn, CHERP, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Shea, JA (reprint author), Univ Penn, CHERP, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu RI Quistberg, D Alex/C-7953-2009 OI Quistberg, D Alex/0000-0001-9730-2686 NR 24 TC 46 Z9 48 U1 1 U2 2 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD SEP PY 2004 VL 36 IS 8 BP 575 EP 581 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 852BQ UT WOS:000223730600011 PM 15343419 ER PT J AU Chew, LD Bradley, KA Boyko, EJ AF Chew, LD Bradley, KA Boyko, EJ TI Brief questions to identify patients with inadequate health literacy SO FAMILY MEDICINE LA English DT Article ID MANAGED CARE ORGANIZATION; MEDICARE ENROLLEES; HOSPITAL ADMISSION; DIAGNOSTIC-TEST; KNOWLEDGE; SKILLS; INSTRUMENT; EDUCATION; ABILITY; ADULTS AB Background and Objectives: No practical method for identifying patients with low heath literacy exists. We sought to develop screening questions for identifying patients with inadequate or marginal health literacy. Methods: Patients (n=332) at a VA preoperative clinic completed in-person interviews that included 16 health literacy screening questions on a 5-point Likert scale, followed by a validated health literacy measure, the Short Test of Functional Health Literacy in Adults (STOHFLA). Based on the STOFHLA, patients were classified as having either inadequate, marginal, or adequate health literacy. Each of the 16 screening questions was evaluated and compared to two comparison standards: (1) inadequate health literacy and (2) inadequate or marginal health literacy on the STOHFLA. Results: Fifteen participants (4.5%) had inadequate health literacy and 25 (7.5%) had marginal health literacy on the STOHFLA. Three of the screening questions, "How often do you have someone help you read hospital materials?" "How confident are you filling out medical forms by yourself?" and "How often do you have problems learning about your medical condition because of difficulty understanding written information?" were effective in detecting inadequate health literacy (area under the receiver operating characteristic curve of 0.87, 0.80, and 0.76, respectively). These questions were weaker for identifying patients with marginal health literacy. Conclusions: Three questions were each effective screening tests for inadequate health literacy in this population. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Ctr Excellence, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Chew, LD (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lchew@u.washington.edu FU NIAAA NIH HHS [K23AA00313] NR 29 TC 454 Z9 457 U1 4 U2 54 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD SEP PY 2004 VL 36 IS 8 BP 588 EP 594 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 852BQ UT WOS:000223730600013 PM 15343421 ER PT J AU Cerpa, WF Barria, MI Chacon, MA Suazo, M Gonzalez, M Opazo, C Bush, AI Inestrosa, NC AF Cerpa, WF Barria, MI Chacon, MA Suazo, M Gonzalez, M Opazo, C Bush, AI Inestrosa, NC TI The N-terminal copper-binding domain of the amyloid precursor protein protects against Cu2+ neurotoxicity in vivo SO FASEB JOURNAL LA English DT Article DE water maze; intracerebral injection ID ALZHEIMERS-DISEASE; SUPEROXIDE-DISMUTASE; TYROSINE NITRATION; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; NEURITE OUTGROWTH; OXIDATIVE STRESS; SCIATIC-NERVE; APP; PEROXYNITRITE; REDUCTION AB The amyloid precursor protein (APP) contains a Cu binding domain (CuBD) localized between amino acids 135 and 156 (APP(135-156)), which can reduce Cu2+ to Cu1+ in vitro. The physiological function of this APP domain has not yet being established; nevertheless several studies support the notion that the CuBD of APP is involved in Cu homeostasis. We used APP synthetic peptides to evaluate their protective properties against Cu2+ neurotoxicity in a bilateral intra-hippocampal injection model. We found that human APP135-156 protects against Cu2+-induced neurotoxic effects, such as, impairment of spatial memory, neuronal cell loss, and astrogliosis. APP135-156 lacking two histidine residues showed protection against Cu2+; however, APP135-156 mutated in cysteine 144, a key residue in the reduction of Cu2+ to Cu1+, did not protect against Cu2+ neurotoxicity. In accordance with recent reports, the CuBD of the Caenorhabditis elegans, APL-1 protected against Cu2+ neurotoxicity in vivo. We also found that Cu2+ neurotoxicity is associated with an increase in nitrotyrosine immunofluorescence as well as with a decrease in Cu2+ uptake. The CuBD of APP therefore may play a role in the detoxification of brain Cu. C1 Pontificia Univ Catolica Chile, FONDAP, Biomed Ctr,Gac Ciencias Biol, Ctr Regulac Celular & Patol Joaquin V Luco, Santiago, Chile. Univ Chile, Inst Nutr & Tecnol Alimentos, Santiago 11, Chile. Mental Hlth Res Inst Victoria, Parkville, Vic 3010, Australia. Harvard Univ, Genet & Aging Res Unit, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Inestrosa, NC (reprint author), Pontificia Univ Catolica Chile, FONDAP, Biomed Ctr,Gac Ciencias Biol, Ctr Regulac Celular & Patol Joaquin V Luco, Alameda 340, Santiago, Chile. EM ninestr@genes.bio.puc.cl RI Gonzalez, Mauricio/I-2772-2013; Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 42 TC 23 Z9 25 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2004 VL 18 IS 12 BP 1701 EP + DI 10.1096/fj.03-1349fje PG 27 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 859DQ UT WOS:000224243200045 PM 15345692 ER PT J AU Burgess, CM Wang, WB Powers, D Alper, M Toner, M Toth, TL AF Burgess, CM Wang, WB Powers, D Alper, M Toner, M Toth, TL TI The survival of human failed to fertilize MII-stage oocytes cryopreserved by microinjection of trehalose. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 ViaCell Inc, Cambridge, MA USA. Boston IVF, Waltham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O292 BP S117 EP S117 DI 10.1016/j.fertnstert.2004.07.297 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800291 ER PT J AU Sokmensuer, LK Palaniappan, S Toner, M Toth, TL Wright, DL AF Sokmensuer, LK Palaniappan, S Toner, M Toth, TL Wright, DL TI A microfluidic chemotaxis system to select motile and mature sperm. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P544 BP S327 EP S328 DI 10.1016/j.fertnstert.2004.07.886 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800867 ER PT J AU Song, IO Jeong, KH Bakowska, JC Breakefield, XO Kaiser, UB AF Song, IO Jeong, KH Bakowska, JC Breakefield, XO Kaiser, UB TI GnRH is expressed in GnRH-deficient hypogonadal (hpg) mice after GnRH gene transfer with a herpes simplex virus (HSV) amplicon vector. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrine,Dept Med, Boston, MA 02115 USA. Sungkyunkwan Univ, Samgsung Cheil Hosp, Dept Ob & Gyn, Sch Med,Div Reprod Endocrinol, Seoul, South Korea. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Neuroendocrine, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P498 BP S311 EP S312 DI 10.1016/j.fertnstert.2004.07.840 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800822 ER PT J AU Styer, AK Gonzalez, RR Lynch, MP Rueda, BR AF Styer, AK Gonzalez, RR Lynch, MP Rueda, BR TI The role of leptin in endometrial proliferation. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02115 USA. Boston Biomed Res Inst, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P492 BP S309 EP S309 DI 10.1016/j.fertnstert.2004.07.834 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800816 ER PT J AU Turlure, F Devroe, E Silver, PA Engelman, A AF Turlure, F Devroe, E Silver, PA Engelman, A TI Human cell proteins and human immunodeficiency virus DNA integration SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HIV-1; integration; integrase; integration cofactor; DNA recombination; review ID TO-AUTOINTEGRATION FACTOR; TYPE-1 PREINTEGRATION COMPLEXES; REVERSE TRANSCRIPTION COMPLEXES; AMINO-ACID-RESIDUES; UBIQUITIN-CONJUGATING ENZYME; BACTERIOPHAGE-MU TRANSPOSASE; RETROVIRAL CDNA INTEGRATION; CARBOXYL-TERMINAL DOMAINS; STRESS-RELATED GENES; VIRAL NUCLEIC-ACIDS AB Integration, catalyzed by the viral integrase (IN) protein, is a crucial step in the life cycle of all retroviruses including human immunodeficiency virus type 1 (HIV-1). Although purified HIV-1 IN protein is sufficient to catalyze the DNA breakage and joining steps of integration in the absence of any other protein factor, a number of studies indicate that cellular proteins participate in the integration process in cells. These host cell proteins have been proposed to act through binding the pre-integrated viral cDNA substrate, by directly interacting with the IN protein, and/or by repairing the single-stranded DNA gaps that occur at viral/chromosomal DNA junctions during integration. In this paper we summarize the identification and potential roles of specific cell factors in HIV-1 integration. We also present experimental results of human cell proteins that coimmunoprecipitated with HIV-1 IN following its expression in HeLa cells and discuss these results in light of the previously-identified integration cofactors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dept Canc Cell Biol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI39394, AI52014] NR 216 TC 115 Z9 125 U1 1 U2 9 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 3187 EP 3208 DI 10.2741/1472 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200098 PM 15353349 ER PT J AU Lauer, GM Barnes, E Lucas, M Timm, J Ouchi, K Kim, AY Day, CL Robbins, GK Casson, DR Reiser, M Dusheiko, G Allen, TM Chung, RT Walker, BD Klenerman, P AF Lauer, GM Barnes, E Lucas, M Timm, J Ouchi, K Kim, AY Day, CL Robbins, GK Casson, DR Reiser, M Dusheiko, G Allen, TM Chung, RT Walker, BD Klenerman, P TI High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection SO GASTROENTEROLOGY LA English DT Article ID CD8(+) T-CELLS; CLASS-II GENOTYPE; LYMPHOCYTE-RESPONSES; DENDRITIC CELLS; VIRAL CLEARANCE; HCV INFECTION; CD4(+); IDENTIFICATION; ASSOCIATION; SPECIFICITY AB Background & Aims: Cellular immune responses are thought to play a key role in the resolution of primary HCV infection. Although it has been consistently shown that CD4+ T-cell responses are maintained in those with spontaneous resolution but lost in those with persistent infection, the role of CD8+ T-cell responses remains controversial. Previous studies have largely focused on limited HLA alleles and predefined CD8+ T-cell epitopes, and, thus, comprehensive studies remain to be performed. Methods: To understand the composition of the immune response associated with spontaneous resolution, we comprehensively mapped CD8+ T-cell responses in 20 HLA-diverse persons with resolved HCV infection, using HCV peptides spanning the entire genome. We analyzed the magnitude, breadth, function, and phenotype using ELISpot, class-I tetramers, intracellular cytokine staining, and cytolytic assays. We studied in parallel HCV-specific responses and viral sequence variation in persistent infection. Results: Responses in individuals with resolved infection were strong and broad with robust proliferation in response to antigen. Responses in those persistently infected were rarely detected ex vivo and, when present, were narrowly directed and weak. However, they also proliferated in vitro. Dominant target epitopes differed among individuals in both cohorts, despite frequently shared HLA-alleles. Conclusions: These data indicate that persisting, strong CD8+ T-cell responses are observed in the majority of persons with resolved HCV infection and provide support for strategies to boost CD8+ T-cell responses for the prevention or treatment of HCV infection but also highlight the diversity of responses that may need to be elicited to provide protection. C1 Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 3SY, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Royal Free Hosp, Ctr Hepatol, London NW3 2QG, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Med Univ Klin, Knappschaftskrankenhaus, Bochum, Germany. RP Klenerman, P (reprint author), Univ Oxford, Nuffield Dept Clin Med, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM paul.klenerman@medawar.oxford.ac.uk RI Robbins, Gregory/F-7988-2011; Yang, Chen/G-1379-2010; Day, Cheryl/J-9844-2012; Allen, Todd/F-5473-2011 FU NIAID NIH HHS [AI31563, R01 AI031563] NR 43 TC 215 Z9 222 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2004 VL 127 IS 3 BP 924 EP 936 DI 10.1053/j.gastro.2004.06.015 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853NO UT WOS:000223834500028 PM 15362047 ER PT J AU Podolsky, DK AF Podolsky, DK TI The AGA and future trends in gastroenterology: CT colonography SO GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2004 VL 127 IS 3 BP 985 EP 986 DI 10.1053/j.gastro.2004.08.010 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853NO UT WOS:000223834500033 PM 15362052 ER PT J AU Lau, DTY Membreno, FE AF Lau, DTY Membreno, FE TI Antiviral therapy for treatment-naive hepatitis B virus patients SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TERM-FOLLOW-UP; E-ANTIGEN SEROCONVERSION; ADEFOVIR DIPIVOXIL THERAPY; INTERFERON-ALPHA TREATMENT; LAMIVUDINE THERAPY; UNITED-STATES; ACUTE EXACERBATION; HBEAG SEROCONVERSION; COMBINATION THERAPY; POSITIVE PATIENTS AB Hepatitis B virus infection is a major public health problem worldwide, responsible for considerable morbidity and mortality from chronic liver disease. It is estimated that there are 350 million hepatitis B virus carriers globally. The prevalence of chronic hepatitis B infection varies greatly in different regions of the world. In the United States, approximately 1.5 million people are infected and 50,000 to 100,000 new cases are reported annually despite the availability of effective vaccines. This article reviews various antiviral therapies for treatment-naive hepatitis B virus patients. C1 Univ Texas, Med Branch, Dept Internal Med, Div Gastroenterol & Hepatol, Galveston, TX 77555 USA. Denver Vet Affairs Med Ctr, Eastern Colorado Hlth Care Syst, Gastroenterol & Hepatol Sect, Denver, CO 80220 USA. RP Lau, DTY (reprint author), Univ Texas, Med Branch, Dept Internal Med, Div Gastroenterol & Hepatol, 4106 McCullough Bldg,301 Univ Blvd, Galveston, TX 77555 USA. EM dalau@utmb.edu NR 68 TC 4 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2004 VL 33 IS 3 BP 581 EP + DI 10.1016/j.gtc.2004.04.008 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 852JU UT WOS:000223752400009 PM 15324945 ER PT J AU Eloubeidi, MA Gress, FG Savides, TJ Wiersema, MJ Kochman, ML Ahmad, NA Ginsberg, GG Erickson, RA DeWitt, J Van Dam, J Nickl, NJ Levy, MJ Clain, JE Chak, A Sivak, MV Wong, R Isenberg, G Scheiman, JM Bounds, B Kimmey, MB Saunders, MD Chang, KJ Sharma, A Nguyen, P Lee, JG Edmundowicz, SA Early, D Azar, R Etemad, B Chen, YK Waxman, I Shami, V Catalano, MF Wilcox, CM AF Eloubeidi, MA Gress, FG Savides, TJ Wiersema, MJ Kochman, ML Ahmad, NA Ginsberg, GG Erickson, RA DeWitt, J Van Dam, J Nickl, NJ Levy, MJ Clain, JE Chak, A Sivak, MV Wong, R Isenberg, G Scheiman, JM Bounds, B Kimmey, MB Saunders, MD Chang, KJ Sharma, A Nguyen, P Lee, JG Edmundowicz, SA Early, D Azar, R Etemad, B Chen, YK Waxman, I Shami, V Catalano, MF Wilcox, CM TI Acute pancreatitis after EUS-guided FNA of solid pancreatic masses: a pooled analysis from EUS centers in the United States SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy/Digestive Disease Week 2003 CY MAY 18-21, 2003 CL ORLANDO, FL SP Amer Soc Gastrointestinal Endoscopy ID FINE-NEEDLE-ASPIRATION; COMPLICATIONS 30 DAYS; ENDOSCOPIC ULTRASOUND; BIOPSY; ENDOSONOGRAPHY; DIAGNOSIS; MANAGEMENT; CARCINOMA; LESIONS; CANCER AB Background: The aim of this study was to determine the frequency and the severity of pancreatitis after EUS-guided FNA of solid pancreatic masses. A survey of centers that offer training in EUS in the United States was conducted. Methods: A list of centers in which training in EUS is offered was obtained from the Web site of the American Society for Gastrointestinal Endoscopy. Designated program directors were contacted via e-mail. The information requested included the number of EUS-guided FNA procedures performed for solid pancreatic masses, the number of cases of post-procedure pancreatitis, and the method for tracking complications. For each episode of pancreatitis, technical details were obtained about the procedure, including the location of the mass, the type of fine needle used, the number of needle passes, and the nature of the lesion. Results: Nineteen of the 27 programs contacted returned the questionnaire (70%). In total, 4909 EUS-guided FNAs of solid pancreatic masses were performed in these 19 centers over a mean of 4 years (range 11 months to 9 years). Pancreatitis occurred after 14 (0.29%): 95% CI[0.16, 0.48] procedures. At two centers in which data on complications were prospectively collected, the frequency of acute pancreatitis was 0.64%, suggesting that the frequency of pancreatitis in the retrospective cohort (0.26%) was under-reported (p = 0.22). The odds that cases of pancreatitis would be reported were 2.45 greater for the prospective compared with the retrospective cohort (95% CI[0.55, 10.98]). The median duration of hospitalization for treatment of pancreatitis was 3 days (range 1-21 days). The pancreatitis was classified as mild in 10 cases, moderate in 3, and severe in one; one death (proximate cause, pulmonary embolism) occurred after the development of pancreatitis in a patient with multiple comorbid conditions. Conclusions: EUS-guided FNA of solid pancreatic masses is infrequently associated with acute pancreatitis. The procedure appears to be safe when performed by experienced endosonographers. The frequency of post EUS-guided FNA pancreatitis may be underestimated by retrospective analysis. C1 Univ Alabama, Endoscop Ultrasound Program, Birmingham, AL 35294 USA. SUNY Stony Brook, Stony Brook, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. Mayo Clin, Rochester, MN USA. Univ Penn, Philadelphia, PA 19104 USA. Scott & White Mem Hosp & Clin, Temple, TX USA. Indiana Univ, Med Ctr, Indianapolis, IN 46204 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Kentucky, Louisville, KY USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Calif Irvine, Orange, CA 92668 USA. Washington Univ, Barnes Jewish Hosp, St Louis, MO USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Colorado, Denver, CO 80202 USA. Univ Chicago, Chicago, IL 60637 USA. GI Consultants, Milwaukee, WI USA. RP Eloubeidi, MA (reprint author), Univ Alabama, Endoscop Ultrasound Program, 1530 3rd Ave,S ZRB 636, Birmingham, AL 35294 USA. OI Edmundowicz, Steven/0000-0002-6541-3485 NR 22 TC 78 Z9 82 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2004 VL 60 IS 3 BP 385 EP 389 AR PII S0016-5107(04)01714-6 DI 10.1016/S0016-5107(04)01714-6 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853UR UT WOS:000223854900011 PM 15332028 ER PT J AU Hinton, DE Pich, V Chhean, D Pollack, MH Barlow, DH AF Hinton, DE Pich, V Chhean, D Pollack, MH Barlow, DH TI Olfactory-triggered panic attacks among Cambodian refugees attending a psychiatric clinic SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE olfactory; panic attacks; trauma; panic disorder; posttraumatic stress disorder; Cambodia; refugees; southeast Asia ID POSTTRAUMATIC-STRESS-DISORDER; MULTIPLE CHEMICAL-SENSITIVITY; ANXIETY SENSITIVITY; ANTICIPATORY NAUSEA; MOTION SICKNESS; SYMPTOMS; TRAUMA; SCALE; PERSPECTIVE; PREVALENCE AB Olfactory panic attacks have not been systematically assessed in a psychiatric population by any previous studies. Among Cambodian refugees attending a psychiatric clinic, the present investigation determines the following: (a) 1-month current prevalence of olfactory-triggered panic attacks, (b) associated psychopathology (Hopkins Symptom Checklist and the Structured Clinical Interview for DSM-IV-diagnosed postraumatic stress disorder [PTSD]), and (c) frequency in events of olfactory panic of catastrophic cognitions (Panic Attack Cognitions Scale [PACQ]) and flashbacks (Clinician-Administered PTSD flashback scale). Forty-five percent of 100 consecutive psychiatric patients were found to have suffered an olfactory-triggered panic attack in the previous month; having current olfactory panic attacks was highly correlated with psychopathology (e.g., to PTSD diagnosis: and chi(2)=50.0; df=1; p<.001); and during olfactory-triggered panic attacks, catastrophic cognitions and flashbacks were common. Possible mechanisms for generation of high rates of olfactory-triggered panic attacks in this population are discussed (the "traumatic memory/catastrophic cognitions/interoceptive conditioning/escalating arousal", or "TCIE" model of panic generation) as are treatment implications. (C) 2004 Elsevier Inc. All rights reserved. C1 Arbour Counseling Serv, SE Asian Clin, Lowell, MA 01852 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02114 USA. RP Hinton, DE (reprint author), Arbour Counseling Serv, SE Asian Clin, 10 Bridge St,Simpson Block, Lowell, MA 01852 USA. EM devon_binton@hms.harvard.edu NR 52 TC 17 Z9 17 U1 5 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2004 VL 26 IS 5 BP 390 EP 397 DI 10.1016/j.genhosppsych.2004.04.007 PG 8 WC Psychiatry SC Psychiatry GA 869JL UT WOS:000224979100007 PM 15474639 ER PT J AU Schneider, KA DiGianni, LM Patenaude, AF Klar, N Stopfer, JE Calzone, DA Li, FP Weber, BL Garber, JE AF Schneider, KA DiGianni, LM Patenaude, AF Klar, N Stopfer, JE Calzone, DA Li, FP Weber, BL Garber, JE TI Accuracy of cancer family histories: Comparison of two breast cancer syndromes SO GENETIC TESTING LA English DT Article ID COLORECTAL-CANCER; COLON-CANCER; VALIDATION AB Cancer risk programs rely on accurately reported family history information. This study compares the accuracy with which cancer sites and ages at diagnosis are reported by Li-Fraumeni syndrome (LFS) and hereditary breast-ovarian cancer syndrome (HBOCS) families undergoing genetic testing. We analyzed the accuracy of 191 cancer diagnoses among first-degree (FDRs) and second-degree (SDRs) relatives reported by 32 LFS and 52 HBOCS participants in genetic testing programs. Cancer diagnoses of relatives were more accurately reported in the HBOCS cohort (78%) than in the LFS cohort (52%). Almost all breast cancer diagnoses were accurately reported, whereas 74% of ovarian cancer diagnoses and only 55% of other LFS-related cancers were accurately reported. Age at diagnosis was accurate within 5 years for 60% of LFS relatives and 53% of HBOCS relatives. Factors correlating with accurate reporting of cancer history included: being member of BRCA1 family, higher education level, female historian, degree of closeness to affected relative, and having fewer than 5 affected FDRs and SDRs. Relying on verbal histories would not have altered eligibility for genetic testing among HBOCS historians, but fewer than half of LFS historians provided information that would have led to TP53 testing. Our data suggest that it may not be necessary to confirm breast cancer diagnoses routinely; however, documentation of other cancer types remains important for appropriate risk assessment and follow-up. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Care Ontario, Div Pediat Oncol, Toronto, ON M5G 2L7, Canada. Univ Penn, Canc Risk Evaluat Program, Philadelphia, PA 19104 USA. Univ Penn, Dept Med & Genet, Philadelphia, PA 19104 USA. NCI, CCR, Genet Branch, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Schneider, KA (reprint author), Dana Farber Canc Inst, 44 Binney St SM335, Boston, MA 02115 USA. EM Katherine_Schneider@dfci.harvard.edu FU NHGRI NIH HHS [5R01 HG00725, 5R01 HG01244] NR 19 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2004 VL 8 IS 3 BP 222 EP 228 DI 10.1089/gte.2004.8.222 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 875QR UT WOS:000225437300002 PM 15727243 ER PT J AU Ogino, S Wilson, RB Gold, B Hawley, P Grody, WW AF Ogino, S Wilson, RB Gold, B Hawley, P Grody, WW TI Bayesian analysis for cystic fibrosis risks in prenatal and carrier screening SO GENETICS IN MEDICINE LA English DT Article DE CFTR; counseling; cystic fibrosis; probability; screening AB Purpose: Risk assessment is an essential component of genetic counseling and testing, and Bayesian analysis plays a central role in complex risk calculations. We previously developed generalizable Bayesian methods to calculate the autosomal recessive disease risk of a fetus when one or no mutation is detected, and another, independent risk factor is present. Our methods are particularly useful for calculating the CF disease risk for a fetus with echogenic bowel. In genetics practice, however, there are other scenarios for which our previous methods are inadequate. Methods and Results: We provide herein methods for calculating genetic risks in a variety of common clinical scenarios. These scenarios include the following: (1) different mutation panels that have been used for the parents and for a fetus; (2) genetic testing results available on the proband or other relatives, in addition to the consultand; (3) fetal ultrasound negative for echogenic bowel with a positive family history; and (4) a consultand with a mixed ethnic background. Conclusion: Our Bayesian methods have proven their versatility through application to many different common genetic counseling scenarios. These methods permit autosomal recessive disease and carrier probabilities to be calculated accurately, taking into account all relevant information. Our methods allow accurate genetic risk estimates for patients and their family members for CF or other autosomal recessive disorders. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Ctr Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Human Genet Sect, Lab Genomic Divers, Frederick, MD 21701 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Lab Med Human Genet & Pediat, Los Angeles, CA 90024 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 NR 13 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP-OCT PY 2004 VL 6 IS 5 BP 439 EP 449 DI 10.1097/01.GIM.0000139511.83336.8F PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 855HZ UT WOS:000223965400008 PM 15371910 ER PT J AU Hattori, N Abe, T Hattori, N Suzuki, M Matsuyama, T Yoshida, S Li, E Shiota, K AF Hattori, N Abe, T Hattori, N Suzuki, M Matsuyama, T Yoshida, S Li, E Shiota, K TI Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells SO GENOME RESEARCH LA English DT Article ID DE-NOVO; MAMMALIAN DEVELOPMENT; CYTOSINE-5 METHYLTRANSFERASES; MAINTENANCE METHYLATION; VERTEBRATE GENOMES; GENE MARKERS; EXPRESSION; PROMOTER; DNMT3A; EPIGENETICS AB Many CpG islands have tissue-dependent and differentially methylated regions (T-DMRs) in normal cells and tissues. To elucidate how DNA methyltransferases (Dnmts) participate in methylation of the genomic components, we investigated the genome-wide DNA methylation pattern of the T-DMRs with Dnmt1-, Dnmt3a-, and/or Dnmt3b-deficient ES cells by restriction landmark genomic scanning (RLGS). Approximately 1300 spots were detected in wild-type ES cells. In Dnmt1(-/-) ES cells, additional 236 spots emerged, indicating that the corresponding loci are methylated by Dnmt1 in wild-type ES cells. Intriguingly, in Dnmt3a(-/-)Dnmt3b(-/-) ES cells, the same 236 spots also emerged, and no additional spots appeared differentially. Therefore, Dnmt1 and Dnmt3a/3b share targets in CpG islands. Cloning and virtual image RLGS revealed that 81% of the RLGS spots were associated with genes, and 62% of the loci were in CpG islands. By contrast to the previous reports that demethylation at repeated sequences was severe in Dnmt1(-/-) cells compared with Dnmt3a(-/-)Dnmt3b(-/-) cells, a complete loss of methylation was observed at RLGS loci in Dnmt3a(-/-)Dnmt3b(-/-) cells, whereas methylation levels only decreased to 16% to 48% in the Dnmt1(-/-) cells. We concluded that there are CpG islands with T-DMR as targets shared by Dnmt1 and Dnmt3a/3b and that each Dnmt has target preferences depending oil the genomic components. C1 Univ Tokyo, Lab Cellular Biochem, Grad Sch Agr & Life Sci, Tokyo 1138657, Japan. RIKEN, Plant Funct Lab, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Shiota, K (reprint author), Univ Tokyo, Lab Cellular Biochem, Grad Sch Agr & Life Sci, Tokyo 1138657, Japan. EM ashiota@mail.ecc.u-tokyo.ac.jp OI Matsuyama, Tomoki/0000-0002-4473-7720 NR 45 TC 65 Z9 69 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2004 VL 14 IS 9 BP 1733 EP 1740 DI 10.1101/gr.2431504 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 851HJ UT WOS:000223675900008 PM 15310660 ER PT J AU Lemos, B Yunes, JA Vargas, FR Moreira, MAM Cardoso, AA Seuanez, HN AF Lemos, B Yunes, JA Vargas, FR Moreira, MAM Cardoso, AA Seuanez, HN TI Phylogenetic footprinting reveals extensive conservation of Sonic Hedgehog (SHH) regulatory elements SO GENOMICS LA English DT Article ID FLOOR PLATE; POLARIZING ACTIVITY; MOUSE GENOME; LIMB BUD; GENE; EXPRESSION; IDENTIFICATION; TRANSCRIPTION; SEQUENCES; PROMOTER AB Sonic Hedgehog (SHH) plays a fundamental role in numerous developmental processes including morphogenesis of limbs, nervous system, and teeth. Using a Bayesian alignment algorithm for phylogenetic footprinting we analyzed similar to28 kb of noncoding DNA in the SHH locus of human and mouse. This showed that the length of conserved noncoding sequences (4196 nt) shared by these species was approximately 3 times larger than the SHH coding sequence (1386 nt). Most segments were located in introns (53%) or within 2-kb regions upstream (16%) or downstream (20%) of the first and last SHH codon. Even though regions more than 2 kb upstream or downstream of the first and last SHH codon represented 57% (16 kb) of the sequence compared, they accounted for only 11% (494 nt) of the total length of conserved noncoding segments. One region of 650 nt downstream of SHH was identified as a putative scaffold/matrix attachment region (SMAR). Human-mouse analysis was complemented by sequencing in apes, monkeys, rodents, and bats, thus further confirming the evolutionary conservation of some segments. Gel-shift assays indicated that conserved segments are targeted by nuclear proteins and showed differences between two cell types that expressed different levels of SHH, namely human endothelial cells and breast cancer cells. The relevance of these findings with respect to regulation of SHH expression during normal and pathologic development is discussed. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Natl Canc Inst, Div Genet, Rio De Janeiro, Brazil. RP Lemos, B (reprint author), Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. EM blemos@oeb.harvard.edu FU NCI NIH HHS [P01 CA 68484] NR 49 TC 4 Z9 5 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2004 VL 84 IS 3 BP 511 EP 523 DI 10.1016/j.ygeno.2004.05.009 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 847QD UT WOS:000223409100007 PM 15498458 ER PT J AU Yu, CE Devlin, B Galloway, N Loomis, E Schellenberg, GD AF Yu, CE Devlin, B Galloway, N Loomis, E Schellenberg, GD TI ADLAPH: A molecular haplotyping method based on allele-discriminating long-range PCR SO GENOMICS LA English DT Article DE molecular haplotyping; long-range PCR; apolipoprotein E; APOE ID HUMAN APOLIPOPROTEIN-E; SINGLE-NUCLEOTIDE POLYMORPHISMS; EXPECTATION-MAXIMIZATION ALGORITHM; LINKAGE DISEQUILIBRIUM; ALZHEIMERS-DISEASE; E GENE; DNA-POLYMERASE; GENOTYPE DATA; HUMAN GENOME; APOE GENE AB We present a method, called Allele-Discriminating Long and Accurate PCR Haplotyping (ADLAPH), for directly determining haplotypes from an extended genomic region. This method uses allele-discriminating primers in long-range PCR to amplify only one of the two chromosome homologues for the region of interest. Haplotypes are then determined from these phase-separated PCR fragments by conventional single nucleotide polymorphism (SNP) genotyping methods. This simple robust procedure makes it practical for high-throughput haplotyping of unrelated individuals, and potentially allows direct observation of haplotype information for up to 40 kb or more. We demonstrate the feasibility of this molecular haplotyping procedure by generating apolipoprotein E (APOE) haplotypes from 100 unrelated subjects. Published by Elsevier Inc. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Washington, Sch Med, Div Neurogenet, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Yu, CE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. EM changeyu@u.washington.edu FU NIA NIH HHS [AG21544, P50 AG05136]; NIMH NIH HHS [MH057881, R01 MH057881] NR 53 TC 15 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2004 VL 84 IS 3 BP 600 EP 612 DI 10.1016/j.ygeno.2004.06.003 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 847QD UT WOS:000223409100017 PM 15498468 ER PT J AU Ravicz, ME Rosowski, JJ Merchant, SN AF Ravicz, ME Rosowski, JJ Merchant, SN TI Mechanisms of hearing loss resulting from middle-ear fluid SO HEARING RESEARCH LA English DT Article DE middle car; umbo velocity; otitis media; effusion; viscosity; conductive hearing loss ID HUMAN TEMPORAL BONES; ACOUSTIC INPUT IMPEDANCE; DOPPLER VIBROMETER LDV; HUMAN-CADAVER EARS; SOUND-PRESSURE; OTITIS-MEDIA; EFFUSIONS; CHILDREN; STAPES; TYMPANOMETRY AB Fluid in the middle ear, a defining feature of otitis media with effusion (OME), is commonly associated with a 20- to 30-dB conductive hearing loss. The effects and relative importance of various mechanisms leading to conductive hearing loss were investigated in a human temporal bone preparation. Umbo velocity in response to ear-canal sound was measured with a laser vibrometer while saline and silicone fluids of viscosity 5-12,000 cSt were introduced into the middle ear to contact part or all of the tympanic membrane (TM) and fill part or all of the middle ear. At low frequencies, reductions in umbo velocity (DeltaV(U)) of up to 25 dB depended on the percentage of the original middle-ear air space that remained air-filled, which suggests that the primary mechanism in hearing loss at low frequencies is a reduction of the admittance of the middle-ear air space due to displacement of air with fluid. At higher frequencies, DeltaV(U) (of up to 35 dB) depended on the percentage of the TM contacted by fluid, which suggests that the primary mechanism at high frequencies is an increase in tympanic membrane mass by entrained fluid. The viscosity of the fluid had no significant effect on umbo velocity. DeltaV(U) for the fluid-filled middle ear matched hearing losses reported in patients whose middle ear was believed to be completely filled with fluid. The difference between DeltaV(U) for a partly-filled middle ear and hearing losses reported in patients whose middle ear was believed to be incompletely fluid-filled is consistent with the reported effect of middle-ear underpressure (commonly seen in OME) on umbo velocity. Small amounts of air in the middle ear are sufficient to facilitate umbo motion at low frequencies. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM mer@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC004798, R01 DC04798] NR 48 TC 46 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 2004 VL 195 IS 1-2 BP 103 EP 130 DI 10.1016/j.heares.2004.05.010 PG 28 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 856JI UT WOS:000224041100011 PM 15350284 ER PT J AU Jiang, Z Wu, CL Woda, BA Iczkowski, KA Chu, PG Tretiakova, MS Young, RH Weiss, LM Blute, RD Brendler, CB Krausz, T Xu, JC Rock, KL Amin, MB Yang, XJ AF Jiang, Z Wu, CL Woda, BA Iczkowski, KA Chu, PG Tretiakova, MS Young, RH Weiss, LM Blute, RD Brendler, CB Krausz, T Xu, JC Rock, KL Amin, MB Yang, XJ TI Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker SO HISTOPATHOLOGY LA English DT Article DE alpha-methylacyl-CoA racemase; AMACR; biomarker; P504S; prostate cancer ID DIFFERENTIALLY EXPRESSED GENES; ANTIGEN; HYPERPLASIA; MICROARRAY; DISCOVERY; P504S; FAT AB Aim: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. Methods and results: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). Conclusions: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests. C1 Univ Massachusetts, Sch Med, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Florida, Gainesville, FL USA. Vet Affairs Med Ctr, Gainesville, FL 32608 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Chicago, Chicago, IL 60637 USA. Corixa Corp, Seattle, WA USA. Emory Univ, Sch Med, Atlanta, GA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Yang, XJ (reprint author), NW Mem Hosp, Feinberg 7-334,251 E Huron St, Chicago, IL 60611 USA. EM xyang@northwestern.edu NR 27 TC 84 Z9 94 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD SEP PY 2004 VL 45 IS 3 BP 218 EP 225 DI 10.1111/j.1365-2559.2004.01930.x PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 850DA UT WOS:000223590200002 PM 15330799 ER PT J AU McGibbon, CA Goldvasser, D Krebs, DE Scarborough, DM AF McGibbon, CA Goldvasser, D Krebs, DE Scarborough, DM TI Instant of chair-rise lift-off can be predicted by foot-floor reaction forces SO HUMAN MOVEMENT SCIENCE LA English DT Article DE chair rise; lift-off time; foot-floor reaction forces; force plates ID SIT-TO-STAND; DYNAMIC STABILITY; ELDERLY SUBJECTS; AGE; PERFORMANCE; MOVEMENTS; STRENGTH; STRATEGIES; MECHANICS; RESIDENTS AB Objective: To develop a predictive model of the lift-off event during chair rise in healthy subjects, using foot-floor reaction forces. Background An important event during chair rise is lift-off from the seat: the transition from the inherently stable three-point contact to the unstable two-point contact. There is no consistent or generally agreed upon method for estimating the time of lift-off when an instrumented seat is unavailable. Methods: Twenty healthy volunteers were divided into a testing set and training set. Each subject performed repeated chair rise trials at different speeds. Seat-floor and foot-floor forces, recorded with two force platforms, were used to develop a model of the lift-off event. Results: The magnitude of the vertical foot-floor reaction at lift-off (F0VF) was linearly related (R-2 = 0.71, P < 0.001) to the peak vertical foot-floor reaction force (FMVF). A linear model was developed for the training group, which enabled prediction of lift-off time for the testing group with an absolute average error of 6 ms (about 1 data frame at 150 Hz). The linear model derived for the entire sample was: F0VF = 28.14 + FMVF (*) (0.6434). Conclusions: The lift-off event for healthy subjects performing chair rise can be accurately predicted from foot-floor reaction forces, without requiring an instrumented seat. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, 40 Parkman St RSL 010, Boston, MA 02114 USA. EM cmcgibbon@partners.org FU NCCIH NIH HHS [R21AT000553]; NIA NIH HHS [R01 AG12561, R01 AG11255] NR 30 TC 11 Z9 12 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9457 J9 HUM MOVEMENT SCI JI Hum. Mov. Sci. PD SEP PY 2004 VL 23 IS 2 BP 121 EP 132 DI 10.1016/j.humov.2004.04.005 PG 12 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 865SL UT WOS:000224723000003 PM 15474173 ER PT J AU Mrak, RE Yasargil, MG Mohapatra, G Earel, J Louis, DN AF Mrak, RE Yasargil, MG Mohapatra, G Earel, J Louis, DN TI Atypical extraventricular neurocytoma with oligodendroglioma-like spread and an unusual pattern of chromosome 1P and 19Q loss SO HUMAN PATHOLOGY LA English DT Article DE neurocytoma; oligodendroglioma; electron microscopy; chromosomal analysis; loss of heterozygosity; fluorescence in situ hybridization ID HYBRIDIZATION; DIAGNOSIS; SURVIVAL; FEATURES; GLIOMAS; TUMORS AB An insular cortex tumor in a 54-year-old woman showed unequivocal neurocytic features, including open nuclei, distinct nucleoli, and strong synaptophysin immunoreactivity. Ultrastructurally, there were neuritic-type processes with microtubules and hillock-like attachments, and there were dense-core granules. Atypical features were mitotic activity, prominent vasculature, and small foci of necrosis. Peripherally, there was oligodendroglia-like histology with single-cell infiltration of white matter and perineuronal spread in cortex. Fluorescence in situ hybridization analysis with chromosome I and 19 probes showed 3 copies of 1q and 2 copies of 1p and showed 2 copies of 19q and 4 copies of 19p. This yielded a 1p-19q loss of heterozygosity pattern similar to that seen in oligodendrogliomas, although the actual chromosomal abnormality is distinct. This tumor, best classified as an atypical neurocytoma with oligodendroglia-like spread, supports suggestions of a close histogenic relationship between oligodendroglial and neurocytic tumors. This case also illustrates the limitations of relying exclusively on loss of heterozygosity analysis for tumor classification. Hum PATHOL 35:1156-1159. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurosurg, Little Rock, AR 72205 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Mol Neurooncol Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Mrak, RE (reprint author), Univ Arkansas Med Sci, Dept Pathol, 517,4301 W Markham St, Little Rock, AR 72205 USA. NR 19 TC 40 Z9 42 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2004 VL 35 IS 9 BP 1156 EP 1159 DI 10.1016/j.humpath.2004.05.005 PG 4 WC Pathology SC Pathology GA 860OB UT WOS:000224351800016 PM 15343519 ER PT J AU Cariani, PA AF Cariani, PA TI Temporal codes and computations for sensory representation and scene analysis SO IEEE TRANSACTIONS ON NEURAL NETWORKS LA English DT Review DE autocorrelation; multiplexing; neural networks; neural timing nets; temporal coding ID METRIC-SPACE ANALYSIS; VISUAL-CORTEX; FIRING PATTERNS; SPIKE TRAINS; INFORMATION; NEURONS; STIMULATION; SPEECH; SYSTEM; PITCH AB This paper considers a space of possible temporal codes, surveys neurophysiological and psychological evidence for their use in nervous systems, and presents examples of neural timing networks that operate in the time-domain. Sensory qualities can be encoded temporally by means of two broad strategies: stimulus-driven temporal correlations (phase-locking) and stimulus-triggering of endogenous temporal response patterns. Evidence for stimulus-related spike timing patterns exists in nearly every sensory modality, and such information can be potentially utilized for representation of stimulus qualities, localization of sources, and perceptual grouping. Multiple strategies for temporal (time, frequency, and code-division) multiplexing of information for transmission and grouping are outlined. Using delays and multiplications (coincidences), neural timing networks perform time-domain signal processing operations to compare, extract and separate temporal patterns. Separation of synthetic double vowels by a recurrent neural timing network is used to illustrate how coherences in temporal fine structure can be exploited to build up and separate periodic signals with different fundamentals. Timing nets constitute a time-domain scene analysis strategy based on temporal pattern invariance rather than feature-base labeling, segregation and binding of channels. Further potential implications of temporal codes and computations for new kinds of neural networks are explored. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM cariani@epl.meei.harvard.edu NR 107 TC 25 Z9 25 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1045-9227 EI 1941-0093 J9 IEEE T NEURAL NETWOR JI IEEE Trans. Neural Netw. PD SEP PY 2004 VL 15 IS 5 BP 1100 EP 1111 DI 10.1109/TNN.2004.833305 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 853AN UT WOS:000223798400017 PM 15484887 ER PT J AU Sumen, C Mempel, TR Mazo, IB von Andrian, UH AF Sumen, C Mempel, TR Mazo, IB von Andrian, UH TI Intravital microscopy: Visualizing immunity in context SO IMMUNITY LA English DT Review ID T-CELL-ACTIVATION; IMMUNOLOGICAL SYNAPSE FORMATION; CD8-ALPHA(+) DENDRITIC CELLS; SECONDARY LYMPHOID-TISSUE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW MICROVESSELS; HIGH ENDOTHELIAL VENULES; IN-VIVO; PLASMA-CELLS; ANTIGEN PRESENTATION AB Recent advances in photonics, particularly multi-photon microscopy (MPM) and new molecular and genetic tools are empowering immunologists to answer long-standing unresolved questions in living animals. Using intravital microscopy (IVM) investigators are dissecting the cellular and molecular underpinnings controlling immune cell motility and interactions in tissues. Recent IVM work showed that T cell responses to antigen in lymph nodes are different from those observed in vitro and appear dictated by factors uniquely relevant to intact organs. Other IVM models, particularly in the bone marrow, reveal how different anatomic contexts regulate leukocyte development, immunity, and inflammation. This article will discuss the current state of the field and outline how IVM can generate new discoveries and serve as a "reality check" for areas of research that were formerly the exclusive domain of in vitro experimentation. 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 Pediat, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949, HL62524]; NIAID NIH HHS [AI061663]; NIAMS NIH HHS [AR042689] NR 146 TC 207 Z9 209 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2004 VL 21 IS 3 BP 315 EP 329 DI 10.1016/S1074-7613(04)00237-7 PG 15 WC Immunology SC Immunology GA 856GY UT WOS:000224034900003 PM 15357943 ER PT J AU Reche, PA Glutting, JP Zhang, H Reinherz, EL AF Reche, PA Glutting, JP Zhang, H Reinherz, EL TI Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles SO IMMUNOGENETICS LA English DT Article DE epitopes; major histocompatibility complex; prediction; profile; proteasome ID CLASS-I MOLECULES; T-CELL-RECEPTOR; HISTOCOMPATIBILITY COMPLEX-MOLECULES; ANTIGEN PRESENTATION; INDEPENDENT BINDING; SEQUENCE WEIGHTS; PROTEIN ANTIGENS; NEURAL-NETWORK; PSI-BLAST; MOTIFS AB We introduced previously an on-line resource, RANKPEP that uses position specific scoring matrices (PSSMs) or profiles for the prediction of peptide-MHC class I (MHCI) binding as a basis for CD8 T-cell epitope identification. Here, using PSSMs that are structurally consistent with the binding mode of MHC class II (MHCII) ligands, we have extended RANKPEP to prediction of peptide-MHCII binding and anticipation of CD4 T-cell epitopes. Currently, 88 and 50 different MHCI and MHCII molecules, respectively, can be targeted for peptide binding predictions in RANKPEP. Because appropriate processing of antigenic peptides must occur prior to major histocompatibility complex (MHC) binding, cleavage site prediction methods are important adjuncts for T-cell epitope discovery. Given that the C-terminus of most MHCI-restricted epitopes results from proteasomal cleavage, we have modeled the cleavage site from known MHCI-restricted epitopes using statistical language models. The RANKPEP server now determines whether the C-terminus of any predicted MHCI ligand may result from such proteasomal cleavage. Also implemented is a variability masking function. This feature focuses prediction on conserved rather than highly variable protein segments encoded by infectious genomes, thereby offering identification of invariant T-cell epitopes to thwart mutation as an immune evasion mechanism. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM reche@research.dfci.harvard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900] NR 82 TC 177 Z9 197 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 2004 VL 56 IS 6 BP 405 EP 419 DI 10.1007/s00251-004-0709-7 PG 15 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 863IS UT WOS:000224555500003 PM 15349703 ER PT J AU Huang, FC Werne, A Li, Q Galyov, EE Walker, WA Cherayil, BJ AF Huang, FC Werne, A Li, Q Galyov, EE Walker, WA Cherayil, BJ TI Cooperative interactions between flagellin and SopE2 in the epithelial interleukin-8 response to Salmonella enterica serovar typhimurium infection SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; INTESTINAL EPITHELIA; NUCLEAR RESPONSES; GENE-EXPRESSION; PROINFLAMMATORY RESPONSE; NEUTROPHIL MIGRATION; BACTERIAL FLAGELLIN; SIGNALING PATHWAYS AB Flagellin is an important stimulus for epithelial interleukin-8 (IL-8) secretion because of its ability to activate Toll-like receptor 5 (TLR5). SopE2, a Salmonella guanine nucleotide exchange factor (GEF), is also involved in intestinal inflammation. To clarify the proinflammatory mechanisms of these proteins, we examined their effects on IL-8 secretion and intracellular signaling in T84 epithelial cells. A Salmonella strain lacking SopE2 (and its homolog SopE) induced lower levels of IL-8 than the wild type and exhibited reduced activation of mitogen-activated protein kinases (MAPKs). Overexpression of wild-type SopE2 in this strain restored MAPK activation and augmented IL-8 production, whereas a mutant lacking GEF activity failed to increase IL-8 expression. Additional effects on signaling were demonstrated in transient transfection experiments, in which SopE2 enhanced the ability of TRAF6, a signal transducer downstream of TLR5, to activate the NF-kappaB transcription factor in 293 cells. Flagellin was also found to be required for IL-8 induction in T84 cells. In its absence, the ability of SopE2 overexpression to increase IL-8 secretion was impaired. Part of this impairment was related to the decreased motility of the flagellin-deficient strain, but lack of flagellin also affected translocation of SopE2 into the infected cells. Our results indicate that flagellin and SopE2 interact functionally at multiple levels to increase IL-8 secretion by epithelial cells-flagellin facilitating the translocation of SopE2, and SopE2 enhancing signaling pathways activated by flagellin. These observations offer a mechanistic explanation for the involvement of these proteins in the pathogenesis of Salmonella-induced gastroenteritis. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Pediat Gastroenterol & Nutr Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 83305, Taiwan. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp East, Pediat Gastroenterol Unit, Room 3400,Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU Biotechnology and Biological Sciences Research Council [D18830]; NIAID NIH HHS [R01AI48815, R01 AI048815]; NICHD NIH HHS [R01HD31852, R01 HD031852, R37HD12437, R37 HD012437]; NIDDK NIH HHS [P30 DK040561, P30DK40561, P01DK33506, P01 DK033506] NR 49 TC 39 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2004 VL 72 IS 9 BP 5052 EP 5062 DI 10.1128/IAI.72.9.5052-5062.2004 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 849ZM UT WOS:000223580400015 PM 15321998 ER PT J AU Martin, SI Kaye, KM AF Martin, SI Kaye, KM TI Beta-lactam antibiotics: newer formulations and newer agents SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE OTITIS-MEDIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; AMOXICILLIN-POTASSIUM CLAVULANATE; COMMUNITY-ACQUIRED PNEUMONIA; SKIN-STRUCTURE INFECTIONS; URINARY-TRACT INFECTIONS; APPROPRIATE ORAL-THERAPY; DOUBLE-BLIND MULTICENTER; IN-VITRO ACTIVITIES; CEFDITOREN PIVOXIL AB beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended-spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Channing Lab, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kaye, KM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Channing Lab, Div Infect Dis, 181 Longwood Ave, Boston, MA 02115 USA. EM kkaye@rics.bwh.harvard.edu RI Martin, Stanley/E-3600-2011 NR 77 TC 9 Z9 9 U1 1 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2004 VL 18 IS 3 BP 603 EP + DI 10.1016/j.idc.2004.04.006 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 851HW UT WOS:000223677200010 PM 15308278 ER PT J AU Lio, PA Kaye, ET AF Lio, PA Kaye, ET TI Topical antibacterial agents SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; CATHETER-SITE CARE; POVIDONE-IODINE; INTRANASAL MUPIROCIN; SILVER SULFADIAZINE; BACTERICIDAL ACTIVITY; ESCHERICHIA-COLI; WOUND-INFECTION; HAND SANITIZER; HUMAN SKIN AB Decreased systemic toxicity, ease of application, and increased concentration at the target site are some of the important advantages topical antibacterial agents offer. This article reviews the literature on selected indications of these agents and provides in-depth examination of specific agents for the prophylaxis and treatment of skin and wound infections. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Boston, MA 02115 USA. RP Lio, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St,Bartlett 616, Boston, MA 02114 USA. EM plio@partners.org NR 93 TC 22 Z9 22 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2004 VL 18 IS 3 BP 717 EP + DI 10.1016/j.idc.2004.04.008 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 851HW UT WOS:000223677200015 PM 15308283 ER PT J AU Sands, BE Cuffari, C Katz, J Kugathasan, S Onken, J Vitek, C Orenstein, W AF Sands, BE Cuffari, C Katz, J Kugathasan, S Onken, J Vitek, C Orenstein, W TI Guidelines for immunizations in patients with inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; ulcerative colitis; inflammatory bowel disease; vaccination; immunization; immune suppression ID MEASLES-VIRUS INFECTION; SYSTEMIC LUPUS-ERYTHEMATOSUS; LIVER-TRANSPLANT RECIPIENTS; POLYMERASE-CHAIN-REACTION; CROHNS-DISEASE; ULCERATIVE-COLITIS; SACCHAROMYCES-CEREVISIAE; INFLUENZA VACCINE; T-CELLS; VARICELLA AB During the past 2 decades, medical therapy for Crohn's disease (CD) and ulcerative colitis (UC) has grown to incorporate a variety of immune-suppressing agents. At the same time, basic insights into the aberrant mucosal immune response underlying inflammatory bowel disease (IBD) have expanded dramatically. The interplay of host susceptibility to infection and the safety and efficacy of immunization for vaccine-preventable diseases has been explored in other immune-mediated disease states but only rarely in IBD. The purpose of this review is to formulate best-practice recommendations for immunization in children and adults with IBD by considering the effects of the IBD disease state and its treatments on both the safety and efficacy of immunization. To do so, we first considered the routine recommendations for immunization of children, adults and distinct populations at increased risk for vaccine-preventable disease. Because it was rarely possible to examine direct data on safety and efficacy of immunization in IBD populations, we relied to a large extent upon extrapolation from similar Populations and from knowledge of basic mechanisms. The literature suggests that efficacy of immunization may be diminished in some patients whose immune status is compromised by immune suppression. However, except for live agent vaccines, most immunizations may be safely administered to patients with IBD even when immune compromised. Conversely, protection against vaccine-preventable illness may be of even greater benefit to those at risk for morbid or lethal complications of infections because of an immune compromised state. We Conclude that for most patients with IBD, recommendations for immunization do not deviate from recommended schedules for the general population. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA. Univ Hosp Cleveland, Div Gastroenterol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Duke Univ, Sch Med, Div Gastroenterol, Durham, NC USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Crohns & Colitis Fdn Amer, New York, NY USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 63 TC 125 Z9 133 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2004 VL 10 IS 5 BP 677 EP 692 DI 10.1097/00054725-200409000-00028 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853DY UT WOS:000223807900028 PM 15472534 ER PT J AU Feissel, M Michard, F Faller, JP Teboul, JL AF Feissel, M Michard, F Faller, JP Teboul, JL TI The respiratory variation in inferior vena cava diameter as a guide to fluid therapy SO INTENSIVE CARE MEDICINE LA English DT Article DE fluid responsiveness; echography; inferior vena cava; septic shock; mechanical ventilation ID MECHANICALLY VENTILATED PATIENTS; POSITIVE-PRESSURE VENTILATION; SEPSIS-INDUCED HYPOTENSION; END-EXPIRATORY PRESSURE; STROKE VOLUME VARIATION; ARTERIAL PULSE; LUNG-INFLATION; CYCLIC CHANGES; VENOUS RETURN; RESPONSIVENESS AB Objective: To investigate whether the respiratory variation in inferior vena cava diameter (DeltaD(IVC)) could be related to fluid responsiveness in mechanically ventilated patients. Design: Prospective clinical study. Setting: Medical ICU of a non-university hospital. Patients: Mechanically ventilated patients with septic shock (n=39). Interventions: Volume loading with 8 mL/kg of 6% hydroxyethylstarch over 20 min. Measurements and results: Cardiac output and DeltaD(IVC) were assessed by echography before and immediately after the standardized volume load. Volume loading induced an increase in cardiac output from 5.7+/-2.0 to 6.4+/-1.9 L/min (P<0.001) and a decrease in &UDelta;D-IVC from 13.8&PLUSMN;13.6 vs 5.2&PLUSMN;5.8% (P<0.001). Sixteen patients responded to volume loading by an increase in cardiac output greater than or equal to15% (responders). Before volume loading, the DeltaD(IVC) was greater in responders than in non-responders (25+/-15 vs 6+/-4%, P<0.001), closely correlated with the increase in cardiac output (r=0.82, P<0.001), and a 12% DeltaD(IVC) cut-off value allowed identification of responders with positive and negative predictive values of 93% and 92%, respectively. Conclusion: Analysis of DeltaD(IVC) is a simple and non-invasive method to detect fluid responsiveness in mechanically ventilated patients with septic shock. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Ctr Hosp Belfort, Belfort, France. Hop Bicetre, Paris Sud Med Sch, Le Kremlin Bicetre, France. RP Michard, F (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM fmichard@partners.org NR 20 TC 284 Z9 314 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2004 VL 30 IS 9 BP 1834 EP 1837 DI 10.1007/s00134-004-2233-5 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 871BS UT WOS:000225104900021 PM 15045170 ER PT J AU Izikson, L Vanderpool, J Brodsky, G Mihm, MC Zembowicz, A AF Izikson, L Vanderpool, J Brodsky, G Mihm, MC Zembowicz, A TI Combined basal cell carcinoma and Langerhans cell histiocytosis of the scrotum in a patient with occupational exposure to coal tar and dust SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article AB The patient was a 77-year-old male former smoker, with history of several basal cell carcinomas (BCCs) in sun-protected areas around the waistline, who presented with another small ulceration on the anterior right upper scrotum near the base of the penis. BCC was suspected clinically and the lesion was treated with cryosurgery. The tumor recurred, became raised, and began to bleed. On examination, it was found to be a 3 cm x 4 cm, raised, light and dark gray variegated lesion with fissures, crusted bloody scale, and necrosis. There were no other penile, testicular, or scrotal lesions or masses. There was no regional lymphadenopathy. An excisional biopsy was performed. It showed nodular BCC surrounded by a cellular proliferation of round histiocytic cells with convoluted, lobulated and reniform nuclei and abundant cytoplasm (Fig. 1). The histiocytic proliferation was associated with numerous eosinophils. Histological features and immunohistochemical phenotype, including expression of CD1a and S-100 antigens by histiocytic cells, were all consistent with Langerhans cell histiocytosis. As expected, BCC expressed keratin. The patient had no history of exposure to ionizing radiation, chemotherapy, immunosuppressive medications, prior lymphoma or other malignancy. However, he spent 4 years on a ship loading coal into the furnace of a steam engine, during which he slept in adjacent quarters that were covered with coal dust. Additionally, he had a several-year history of occupational skin exposure to machine oil, oil refinery waste, sulfur waste, hydraulic fluid, and asbestos. He also reported a history of nude sunbathing. His current medical problems include pleural asbestosis, poorly controlled type II diabetes, and congestive heart failure. His past dermatologic history includes intertrigo, onychomycosis, and an unknown skin lesion removed from the face 40 years ago. Recent clinical follow-up and imaging studies, including chest X-ray and bone scan, showed no evidence of visceral lesions, lytic bone lesions, or other signs of systemic involvement by Langerhans cell histiocytosis. The scrotal lesion was re-excised and the patient remains disease-free more than 1 year after the diagnosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Dermatopathol Unit,Div Dermatopathol, Boston, MA 02114 USA. Harvard Vanguard Med Associates, Boston, MA USA. RP Zembowicz, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Dermatopathol Unit,Div Dermatopathol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 11 TC 9 Z9 9 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD SEP PY 2004 VL 43 IS 9 BP 678 EP 680 DI 10.1111/j.1365-4632.2004.02178.x PG 3 WC Dermatology SC Dermatology GA 852MM UT WOS:000223759400013 PM 15357751 ER PT J AU Becker, AE Franko, DL Nussbaum, K Herzog, DB AF Becker, AE Franko, DL Nussbaum, K Herzog, DB TI Secondary prevention for eating disorders: The impact of education, screening, and referral in a college-based screening program SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE screening program; secondary prevention; eating disorders ID INTERVENTION AB Objective: The first National Eating Disorders Screening Program (NEDSP), conducted on more than 400 college campuses in 1996, was an educational and two-stage screening program designed to detect potentially clinically significant disordered eating attitudes and behaviors and offer referrals for further evaluation when warranted. The current study assessed the impact of the NEDSP on participants. Method: A randomly, selected subset of this sample (n = 289) was contacted approximately 2 years after the NEDSP to assess the impact of the program on knowledge and treatment-seeking behaviors for eating disorders. Results: For greater than 80% of the participants, the program made participants aware of the danger of eating disorders and the availability of treatment. Of those who received a recommendation for further clinical evaluation of disordered eating (n = 109), nearly one half (47.7%) followed up on this recommendation and kept at least a first appointment and 39.4% actually sought treatment subsequent to the NEDSP. Discussion: The results of the current study suggest that educational and screening programs may be a promising strategy for secondary prevention of eating disorders. They also suggest that awareness of the risks of disordered eating and available treatment may not be sufficient to motivate individuals to adhere to recommendations to seek treatment. Clinicians should, therefore, be vigilant for nonadherence to treatment recommendations and proactive in facilitating treatment. (C) 2004 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Harvard Eating Disorders Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Loyola Univ, Dept Psychol, Chicago, IL 60611 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Harvard Eating Disorders Ctr, WAC 725,15 Parkman St, Boston, MA 02114 USA. EM d.franko@neu.edu NR 8 TC 31 Z9 32 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2004 VL 36 IS 2 BP 157 EP 162 DI 10.1002/eat.20023 PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 846OZ UT WOS:000223326500003 PM 15282685 ER PT J AU Kempuraj, D Konstantinidou, A Boscolo, P Ferro, F Di Giannantonio, M Conti, CMV Merlitti, D Petrarca, C Castellani, ML Doyle, R Theoharides, TC AF Kempuraj, D Konstantinidou, A Boscolo, P Ferro, F Di Giannantonio, M Conti, CMV Merlitti, D Petrarca, C Castellani, ML Doyle, R Theoharides, TC TI Cytokines and the brain SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Editorial Material DE cytokines; brain; neurology; psychiatry; stress ID HUMAN MAST-CELLS; ACUTE STRESS; ALZHEIMERS-DISEASE; PANIC DISORDER; BARRIER PERMEABILITY; CHEMOKINE RECEPTORS; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; MAJOR DEPRESSION C1 Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Model Neurol Ctr, Thessaloniki, Greece. Univ Chieti, Dept Med & Sci Ageing, Chieti, Italy. Univ Chieti, Div Psychiat, Chieti, Italy. Univ Chieti, Div Immunol, Chieti, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Kempuraj, D (reprint author), Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. EM duraisamy.kempuraj@tufts.edu RI Theoharides, Theoharis/E-5596-2010; OI MERLITTI, DANIELE/0000-0002-9742-4146 NR 51 TC 25 Z9 25 U1 1 U2 1 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD SEP-DEC PY 2004 VL 17 IS 3 BP 229 EP 232 PG 4 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 868NH UT WOS:000224919800001 PM 15461855 ER PT J AU Demidova, TN Hamblin, MR AF Demidova, TN Hamblin, MR TI Photodynamic therapy targeted to pathogens SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Review DE bacteria; photosensitizer conjugate; fungus; localized infection ID GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE; METHYLENE-BLUE; IN-VIVO; STAPHYLOCOCCUS-AUREUS; 5-AMINOLEVULINIC ACID; WOUND INFECTIONS; ESCHERICHIA-COLI; ACNE-VULGARIS; INACTIVATION AB Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS) together with low intensity visible light, which, in the presence of oxygen, produce cytotoxic species. PS can be targeted to its destination cell or tissue and, in addition, the irradiation can be spatially confined to the lesion giving PDT the advantage of dual selectivity. This promising approach can be used for various applications including microbial inactivation and the treatment of infections. Resistance to PDT has not been shown and multiantibiotic-resistant strains are as easily killed as naive strains. It is known that Gram (+) bacteria are more sensitive to PDT as compared to Gram (-) species. However, the use of cationic PS or agents that increase the permeability of the outer membrane allows for the effective killing of Gram (-) organisms. Some PS have an innate positive charge, but our approach is to link PS to a cationic molecular vehicle such as poly-L-lysine. This modification dramatically increases PS binding to and penetrating through the negatively charged bacterial permeability barrier. Due to focused light delivery the use of PDT is possible only for localized infections. Nonetheless numerous diseases can be treated. Selectivity of the PS for microbes over host cells, accurate delivery of the PS into the infected area, and PDT dose adjustment help minimize side effects and give PDT an advantage over conventional therapy. There are only a few reports about the use of antimicrobial PDT in animal models and clinical trials. We have used genetically modified bioluminescent bacteria to follow the effect of PDT in infected wounds, burns, and soft tissue infections in mice. Not only were bacteria infecting wounds, burns, and abscesses killed, but mice were saved from death due to sepsis and wound healing was improved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01-AI050875, R01 AI050875, R01 AI050875-01A2, R01 AI050875-02] NR 47 TC 170 Z9 178 U1 0 U2 16 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD SEP-DEC PY 2004 VL 17 IS 3 BP 245 EP 254 PG 10 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 868NH UT WOS:000224919800004 PM 15461858 ER PT J AU Zimmermann, CE Harris, G Thurmuller, P Troulis, MJ Perrott, DH Rahn, B Kaban, LB AF Zimmermann, CE Harris, G Thurmuller, P Troulis, MJ Perrott, DH Rahn, B Kaban, LB TI Assessment of bone formation in a porcine mandibular distraction wound by computed tomography SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE distraction osteogenesis; computed tomography; bone formation ID TRABECULAR BONE; CANINE MODEL; HEALING FRACTURES; REGENERATE-BONE; QUANTITATIVE CT; OSTEOGENESIS; ULTRASOUND; DENSITY; STIFFNESS; SCANS AB The purpose of this study was to document the progression of bone formation in a porcine mandibular distraction wound, at various distraction rates and fixation times, using three-dimensional computed tomography. Bone formation was assessed in a 0-day latency model (n = 24 minipigs) using distraction rates of 1, 2, or 4 mm/day to create a 12 mm distraction gap. Animals were sacrificed at 0, 8, 16, or 24 days fixation. For experimental and control sides, three-dimensional data from computed tomographic scans were used to calculate the percent bone volume in the regions of interest. Standardized plain radiographs were used to evaluate bone formation with a semiquantitative scale: 0, 1, 2, 3. Mean percent bone volume and radiographic bone fill scores (pooled sample) increased with fixation time from 16.8% and 0.17 at 0 days, to 64% and 2.0 at 24 days fixation. Mandibles distracted at I mm/day had higher CT values and bone fill scores than mandibles distracted at 2 or 4 mm/day. At 24 days fixation, the maximum percent bone volume (64%-1 mm/day; 24 days fixation) remained below control values (81.3%). The results of this study indicate that despite high bone fill scores on plain radiographs, the highest percent CT bone volume achieved in this model was 64%. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Radiol,3D Reconstruct Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. AO Res Inst, Davos, Switzerland. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM lkaban@Partners.org NR 49 TC 15 Z9 15 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD SEP PY 2004 VL 33 IS 6 BP 569 EP 574 DI 10.1016/j.ijom.2004.01.022 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 849ZR UT WOS:000223580900009 PM 15308257 ER PT J AU Spencer, KM Nestor, PG Niznikiewicz, MA Valdman, O Shenton, ME McCarley, RW AF Spencer, KM Nestor, PG Niznikiewicz, MA Valdman, O Shenton, ME McCarley, RW TI Hyperpriming of attention shifting in schizophrenia: Experiment and simulation SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 20 EP 20 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900039 ER PT J AU Choi, NC Park, SD Lynch, T Wright, C Ancukiewicz, M Wain, J Donahue, D Mathisen, D AF Choi, NC Park, SD Lynch, T Wright, C Ancukiewicz, M Wain, J Donahue, D Mathisen, D TI Twice-daily radiotherapy as concurrent boost technique during two chemotherapy cycles in neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: Mature results of phase II study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE neoadjuvant chemoradiotherapy; twice-daily radiotherapy; concurrent boost radiotherapy; esophageal carcinoma ID SQUAMOUS-CELL CARCINOMA; TERM-FOLLOW-UP; RADIATION-THERAPY; PREOPERATIVE CHEMORADIATION; ACCELERATED FRACTIONATION; SURGICAL RESECTION; RANDOMIZED-TRIAL; CANCER; SURGERY; ADENOCARCINOMA AB Purpose: To determine the toxicities of neoadjuvant chemoradiotherapy using a three-drug regimen (cisplatin, 5-fluorouracil, and paclitaxel) and a conventional radiotherapy (RT) schedule combined with a concurrent boost technique during chemotherapy cycles, and to determine the rate of tumor response, overall survival, and impact of pathologic tumor response on survival. Methods and Materials: The eligibility criteria included resectable adenocarcinoma or squamous cell carcinoma (T2-T3N0-N1M0), performance score less than or equal to2, and no significant comorbidities for trimodality therapy. Chemotherapy consisted of two cycles of cisplatin, 5-fluorouracil, and paclitaxel. A concurrent boost technique was used in RT for 2 levels of radiation doses: 58.5 Gy in 34 fractions within 5 weeks to the gross tumor volume and 45 Gy in 25 fractions within 5 weeks to the clinical target volume by administering a boost dose of 13.5 Gy in 9 fractions, 1.5 Gy/fraction, as a second daily fraction for 9 days on Days 1-5 and 29-32 of the chemotherapy cycles. Results: We enrolled 46 patients in the study. The paclitaxel dose was started at 75 mg/m(2) (n = 7) and escalated to 125 mg/m2 (n = 5), at which point, dose-limiting toxicities occurred. Thereafter, paclitaxel at 100 mg/m2 was used for an additional 34 patients. Toxicities included Grade 4 neutropenia (22%), febrile neutropenia requiring hospital admission (20%), Grade 3 (48%) and Grade 4 (7%) acute esophagitis, and paclitaxel-associated anaphylaxis (4%). Of the 46 patients, 3 (6.5%) died of treatment-related complications, 1 of pneumonia during induction therapy and 2 of postoperative complications (5% of the 40 patients who underwent resection). The histopathologic tumor response was a pathologic complete response (pT0N0) in 18 (45%) of 40 patients who underwent resection and 18 (39%) of all 46 registered patients. Minimal residual disease (pT1N0) at the primary site was present in 5 (11%) and residual disease in 23 (50%) of all 46 patients. The minimal follow-up for all long-term survivors (n = 16) was 5.5 years. The median survival time was 34 months, and the overall survival rate was 57%, 50%, and 37% at 2, 3, and 5 years, respectively. The 5-year overall survival (56% vs. 24%, p = 0.0214) and disease-free survival (48% vs. 6%) were significantly better statistically for patients with a pathologic complete response and minimal residual disease than for those with residual disease. All long-term survivors beyond 5.5 years without recurrence accrued from patient cohorts with a pathologic complete response or minimal residual disease. Conclusion: An incorporation of twice-daily RT as a concurrent boost to the conventional daily RT schedule during chemotherapy cycles is feasible and warrants additional study for radiation dose intensification. Such research would be prudent for both improved long-term survival and organ preservation in esophageal carcinoma. (C) 2004 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Choi, NC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM nchoi@partners.org NR 54 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2004 VL 60 IS 1 BP 111 EP 122 DI 10.1016/j.ijrobp.2004.03.031 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UN UT WOS:000223854500015 PM 15337546 ER PT J AU Davis, S AF Davis, S TI Clinical sequelae affecting quality of life in the HIV-infected patient SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE fatigue; pain; depression; sleep disturbances ID IMMUNODEFICIENCY-VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; ANEMIA; PAIN; PREVALENCE; DISTRESS; AIDS; DISORDERS; DISEASE; FATIGUE AB Physical and mental changes resulting from HIV infection and its treatment can affect a. patient's quality of life (QOL). Some of the most commonly reported symptoms affecting QOL in HIV infected patients are fatigue, pain, anxiety/depression, and sleep disturbances. Fatigue often has a multifactorial etiology, including advanced HIV disease, opportunistic infections, poor nutrition, hormonal insufficiency, and anemia. Pain is one of the most overlooked factors by clinicians. Anxiety/depression and sleep disturbances are experienced by many HIV-infected individuals and are highly correlated with the perception. and progression of disease. Although these common clinical symptoms impact QOL in HIV-positive patients, there are no established guidelines for treating them. As pain, anxiety/depression, and sleep disturbances can influence fatigue, as well as each other, the HIV care provider should monitor them closely because their severity reflects the clinical course of HIV as well as the overall well-being of the patient. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Davis, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 35 TC 14 Z9 14 U1 7 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD SEP-OCT PY 2004 VL 15 IS 5 SU S BP 28S EP 33S DI 10.1177/1055329004269478 PG 6 WC Nursing SC Nursing GA 857YC UT WOS:000224155000005 PM 15587606 ER PT J AU Notarangelo, L Casanova, JL Fischer, A Puck, J Rosen, F Seger, R Geha, R AF Notarangelo, L Casanova, JL Fischer, A Puck, J Rosen, F Seger, R Geha, R CA Int Union Immunological Soc Primar TI Primary immunodeficiency diseases: An update SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE primary immunodeficiency diseases; T cells; B cells; phagocytes; complement; immune dysregulation syndromes; innate immunity ID CLASSIFICATION AB Although relatively rare, primary immune deficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into Immoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known primary immunodeficiency diseases was created by a committee convened by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 100 PIDs has been elucidated. This update results from the latest meeting of this committee in Sintra, Portugal, June 2003, which followed 2(1)/(2) days of scientific discussions. C1 Univ Brescia Spedali Civili, Dept Pediat, Brescia, Italy. Hop Necker Enfants Malad, Paris, France. NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Univ Kinderklin, Zurich, Switzerland. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Geha, R (reprint author), Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 4 TC 90 Z9 97 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 677 EP 687 DI 10.1016/j.jaci.2004.06.044 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600032 PM 15356576 ER PT J AU Vogt, DS King, DW King, LA Savarese, VW Suvak, MK AF Vogt, DS King, DW King, LA Savarese, VW Suvak, MK TI War-zone exposure and long-term general life adjustment among Vietnam veterans: Findings from two perspectives SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC EVENTS; MISSISSIPPI SCALE; MILITARY SERVICE; NATIONAL SAMPLE; PREVALENCE; HEALTH; PSYCHOLOGY; EXPERIENCE; FEMALE AB This two-part investigation examined associations between service in Vietnam and indices of long-term general life adjustment using a national sample of male and female members of the Vietnam generation. In Study 1, we documented reasonably high levels of satisfaction and attainment among Vietnam veterans, levels that differed minimally, on average, from those who served elsewhere and those who never served in the military. In Study 2, dimensions of war-zone stressor exposure were only marginally related to satisfaction and attainment, in contrast with research documenting strong relationships with psychopathology. These findings support the importance of expanding our thinking about dimensions of mental illness and mental health. C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Vogt, DS (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@med.va.gov NR 70 TC 17 Z9 17 U1 4 U2 4 PU V H WINSTON & SON INC PI PALM BEACH PA 360 SOUTH OCEAN BLVD, PH-B, PALM BEACH, FL 33480 USA SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD SEP PY 2004 VL 34 IS 9 BP 1797 EP 1824 DI 10.1111/j.1559-1816.2004.tb02586.x PG 28 WC Psychology, Social SC Psychology GA 881DG UT WOS:000225843000002 ER PT J AU Plumb, JC Orsillo, SM Luterek, JA AF Plumb, JC Orsillo, SM Luterek, JA TI A preliminary test of the role of experiential avoidance in post-event functioning SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 11-14, 1999 CL TORONTO, CANADA SP Assoc Adv Behav Therapy DE posttraumatic stress disorder; experiential avoidance; trauma ID POSTTRAUMATIC-STRESS-DISORDER; PTSD SYMPTOMS; SEXUAL ABUSE; TRAUMA; VETERANS; EXPOSURE; EMOTION; SCALE; WAR; PREDICTORS AB Experiential avoidance is the unwillingness to experience unwanted thoughts, emotions, or bodily sensations and an individual's attempts to alter, avoid, or escape those experiences. The aim of the current studies was to broaden previous research indicating that experiential avoidance often leads to the development and maintenance of psychological distress. Results indicated that experiential avoidance is significantly correlated with psychological distress and post-traumatic symptomatology over and above other measures of psychological functioning. Limitations and implications for treatment and prevention of psychological distress are discussed. (C) 2004 Elsevier Ltd. All rights reserved. C1 Boston VA Healthcare Syst 116B3, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Temple Univ, Dept Psychiat, Philadelphia, PA 19122 USA. RP Plumb, JC (reprint author), Boston VA Healthcare Syst 116B3, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer_plumb@hotmail.com NR 40 TC 68 Z9 69 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD SEP PY 2004 VL 35 IS 3 BP 245 EP 257 DI 10.1016/j.jbtep.2004.04.011 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 844IC UT WOS:000223150500004 PM 15262220 ER PT J AU Chen, PC Park, YJ Chang, LC Kohane, DS Bartlett, RH Langer, R Yang, VC AF Chen, PC Park, YJ Chang, LC Kohane, DS Bartlett, RH Langer, R Yang, VC TI Injectable microparticle-gel system for prolonged and localized lidocaine release. I. In vitro characterization SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE lidocaine; poly(D,L-lactic acid); biodegradable microspheres; poloxamer; postoperative pains ID LOADED BIODEGRADABLE NANOSPHERES; EPIDURAL ANALGESIA; PAIN RELIEF; BUPIVACAINE AB Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the infusion is continuous. Continuous infusion, however, requires hospitalization of the patients, thereby increasing medical costs. In addition, it also causes systemic accumulation of the drug. We reported herein a novel treatment for the postoperative pain by applying to the surgical site a biodegradable microsphere-gel system for prolonged and localized release of encapsulated anesthetic drugs. This lidocaine-containing biodegradable poly(D,L-lactic acid) (PLA) microsphere system, although being established previously by other investigators, was hindered by a burst release and a followed rapid release of the drug within several hours in vitro. In this article, we demonstrated that by a step-by-step modification of the formulation, prolonged release of lidocame, up to several days in vitro, could be achieved. Differential scan-ning calorimetry revealed a lower glass transition temperature for these lidocaine-loaded microspheres comparing to that of lidocaine-free microspheres. This decreased 7 1 explained for the tendency of the lidocaine-loaded microspheres to physically fuse at higher temperatures. In vitro studies showed that microspheres, when loaded with 35% lidocaine, yielded a threefold increase in the degradation rate. The molecular weight of PLA of the drug-loaded microspheres was reduced by 50% within a period of 1 month. Based on the results (of prolonged lidocaine release and rapid PLA microsphere degradation), this lidocaine-loaded PLA microsphere system could offer a simple solution to the treatment of postoperative pain. (C) 2004 Wiley Periodicals, Inc. C1 Univ Michigan, Coll Pharm, Albert B Prescott Prof Pharmaceut Sci, Coll Pharm, Ann Arbor, MI 48109 USA. Natl Def Med Ctr, Sch Pharm, Taipei, Taiwan. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Seoul Natl Univ, Coll Dent, Seoul 110749, South Korea. RP Yang, VC (reprint author), Univ Michigan, Coll Pharm, Albert B Prescott Prof Pharmaceut Sci, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM vcyang@umich.edu FU NHLBI NIH HHS [HL 55461] NR 20 TC 31 Z9 31 U1 1 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD SEP 1 PY 2004 VL 70A IS 3 BP 412 EP 419 DI 10.1002/jbm.a.30086 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 845YJ UT WOS:000223281100006 PM 15293314 ER PT J AU Chen, PC Kohane, DS Park, YJ Bartlett, RH Langer, R Yang, VC AF Chen, PC Kohane, DS Park, YJ Bartlett, RH Langer, R Yang, VC TI Injectable microparticle-gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE lidocame; poly(glycolic-co-lactic acid); poloxamer; microspheres; anesthetic ID SCIATIC-NERVE BLOCKADE; BUPIVACAINE AB Current treatment protocols for postoperative pain are beset by either the short duration of the anesthetic effect or requirement of hospitalization of the patients. We reported herein a novel treatment by applying to the surgical site a biodegradable microparticle-gel system for prolonged and localized release of encapsulated anesthetic drugs. In a previous publication, lidocaine-loaded poly(D,L-lactic acid) microspheres were fabricated and their formulations were optimized. hi vitro characterization of these lidocaine-loaded microspheres, however, revealed a shortcoming of this system; that is, microspheres tend to fuse physically. Fusion of the microspheres could hinder their clinical applications, as it would clog the needle. In this article, we demonstrated that fabricating microspheres with high molecular weight (similar to60 KDa) poly(lactic-co-glycolic acid) would increase the glass transition temperature of the microspheres after lidocaine loading, thereby increasing their mechanical stability and eliminating their fusion during storage. Such microspheres containing 31% (w/w) lidocaine in the presence or absence of 25% (w/v) poloxamer 407 gel were then evaluated in vivo by monitoring the sensory and motor functions of the rats after sciatic nerve block, using the previously established hot-plate and weight-bearing testing methods. Results showed that microspheres formulated with poloxamer 407 get yielded the longest duration of sensory and motor block for a period of approximately 8.5 h, compared to 5 h by microspheres in saline, 5 h by lidocaine in poloxamer 407 gel, and 2 h by lidocaine in saline. This study suggests that the microsphere-gel system containing lidocaine could potentially be applied clinically to the treatment of postoperative pain. (C) 2004 Wiley Periodicals, Inc. C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Seoul Natl Univ, Coll Dent, Seoul 110749, South Korea. RP Yang, VC (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM vcyang@umich.edu FU NHLBI NIH HHS [HL 55461] NR 10 TC 43 Z9 46 U1 2 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD SEP 1 PY 2004 VL 70A IS 3 BP 459 EP 466 DI 10.1002/jbm.a.30101 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 845YJ UT WOS:000223281100012 PM 15293320 ER PT J AU Harness, NG Jupiter, JB Orbay, JL Raskin, KB Fernandez, DL AF Harness, NG Jupiter, JB Orbay, JL Raskin, KB Fernandez, DL TI Loss of fixation of the volar lunate facet fragment infractures of the distal part of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID INTRAARTICULAR FRACTURES; COLLES FRACTURES; YOUNG-ADULTS; WRIST JOINT; SUPINATION; END AB Background: The purpose of the present study is to report on a cohort of patients with a volar shearing fracture of the distal end of the radius in whom the unique anatomy of the distal cortical rim of the radius led to failure of support of a volar ulnar lunate facet fracture fragment. Methods: Seven patients with a volar shearing fracture of the distal part of the radius who lost fixation of a volar lunate facet fragment with subsequent carpal displacement after open reduction and internal fixation were evaluated at an average of twenty-four months after surgery. One fracture was classified as B3.2 and six were classified as B3.3 according to the AO comprehensive classification system. All seven fractures initially were deemed to have an adequate reduction and internal fixation. Four patients required repeat open reduction and internal fixation, and one underwent a radiocarpal arthrodesis. At the time of the final follow-up, all patients were assessed with regard to their self-reported level of functioning and with use of Sarmiento's modification of the system of Gartland and Werley. Results: At a mean of two years after the injury, six patients had returned to their previous level of function. The result was considered to be excellent for one patient, good for four, and fair for two. The average wrist extension was 480, or 75% of that of the uninjured extremity. The average wrist flexion was 37degrees, or 64% of that of the uninjured extremity. The one patient who underwent radiocarpal arthrodesis had achievement of a solid union. The four patients who underwent repeat internal fixation had maintenance of reduction of the lunate facet fragment. The two patients who declined additional operative intervention had persistent dislocation of the carpus with the volar lunate facet fragment. Conclusions: The stability of comminuted fractures of the distal part of the radius with volar fragmentation is determined not only by the reduction of the major fragments but also by the reduction of the small volar lunate fragment. The unique anatomy of this region may prevent standard fixation devices for distal radial fractures from supporting the entire volar surface effectively. It is preferable to recognize the complexity of the injury prior to the initial surgical intervention and to plan accordingly. Level of Evidence: Therapeutic study, Level I (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Miami Hand Ctr & Hand Innovat Inc, Miami, FL 33176 USA. NYU, Hosp Joint Dis, Dept Orthopaed Surg, New York, NY USA. Lindenhofspital, Dept Orthopaed Surg, Bern, Switzerland. RP Harness, NG (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 15 Parkman St,ACC 527, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 27 TC 59 Z9 62 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2004 VL 86A IS 9 BP 1900 EP 1908 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 852ZJ UT WOS:000223795200007 PM 15342751 ER PT J AU Battaglino, R Fu, J Spate, U Ersoy, U Joe, M Sedaghat, L Stashenko, P AF Battaglino, R Fu, J Spate, U Ersoy, U Joe, M Sedaghat, L Stashenko, P TI Serotonin regulates osteoclast differentiation through its transporter SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone; osteoclasts; differentiation; serotonin; neural regulation ID BONE-MINERAL DENSITY; NECROSIS-FACTOR RECEPTOR; CENTRAL-NERVOUS-SYSTEM; IMMUNE-SYSTEM; MAJOR DEPRESSION; MESSENGER-RNA; EXPRESSION; MECHANISMS; PEPTIDE; LIGAND AB 5-HTT mediates antidepressant-sensitive clearance of 5-HT after its release into neural synapses. We found increased expression of 5-HTT in RANKL-induced osteoclast-like cells. Fluoxetine, an inhibitor of 5-HTT, reduced osteoclast differentiation but not activation. Reserpine, an inhibitor of 5-HT intracellular transport, potentiated differentiation. These results indicate a role for 5-HTT in osteoclast function and suggest that commonly used antidepressive agents may affect bone mass. Introduction: Interactions between the serotonergic and skeletal systems are suggested by various clinical observations but are poorly understood. Materials and Methods: Using gene microarrays, we found that the serotonin transporter (5-HTT) was strongly expressed in RANKL-induced osteoclasts. Using RANKL stimulation of RAW264.7 cells and mouse bone marrow cells as a model system for osteoclast differentiation, we studied the possible role/s of the different components of the serotonin (5-HT) system on the differentiation process. Results: Osteoclast 5-HTT exhibited typical 5-HT uptake activity that was inhibitable by fluoxetine (Prozac). Fluoxetine reduced osteoclast differentiation but did not inhibit the activation of preformed osteoclasts, whereas the addition of 5-HT itself enhanced differentiation. Fluoxetine-treated osteoclast precursors had reduced NF-kappaB activation and elevated inhibitory protein kappaBalpha (1kappaBalpha) levels compared with untreated cells. 5-HT, on the other hand, resulted in activation of NF-kappaB. Reserpine inhibition of intracellular transport of 5-HT into cytoplasmic vesicles potentiated RANKL-Induced osteoclast formation, suggesting the importance of intracellular 5-HT in regulating osteoclast differentiation. Reserpine also modestly enhanced the expression of the osteoclast inarker TRACP in the absence of RANKL. Conclusions: Taken together, these data suggest that the 5-HT system plays an important role in bone horneostasis through effects on osteoclast differentiation and implies that commonly used antidepressive agents may affect bone mass. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashenko@forsyth.org RI battaglino, ricardo/D-2892-2015 NR 59 TC 110 Z9 120 U1 1 U2 7 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1420 EP 1431 DI 10.1359/JBMR.040606 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500005 PM 15312242 ER PT J AU Smith, MR AF Smith, MR TI Treatment-related osteoporosis in men with prostate cancer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1568 EP 1568 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500042 ER PT J AU Krupski, TL Smith, MR Lee, WC Pashos, CL Brandman, J Wang, Q Botteman, M Litwin, MS AF Krupski, TL Smith, MR Lee, WC Pashos, CL Brandman, J Wang, Q Botteman, M Litwin, MS TI Adverse bone effects in men with prostate cancer on androgen deprivation therapy SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. ABT Associates Inc, Clin Trials, Bethesda, MD USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1581 EP 1581 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500086 ER PT J AU McGovern, K Fallon, MA Goode, M Smith, M AF McGovern, K Fallon, MA Goode, M Smith, M TI Changes in bone mineral density during initial and long-term gonadotropin-releasing hormone agonist therapy for prostate cancer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1587 EP 1588 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500108 ER PT J AU Cook, RJ Coleman, RE Saad, F Smith, M Lipton, A Lee, KA Brown, JE Zheng, M Hei, YJ Major, P AF Cook, RJ Coleman, RE Saad, F Smith, M Lipton, A Lee, KA Brown, JE Zheng, M Hei, YJ Major, P TI The predictive value of bone resorption and formation markers in patients with prostate cancer metastatic to bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Weston Pk Hosp, Sheffield, S Yorkshire, England. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Milton S Hershey Med Ctr, Hershey, PA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. McMaster Univ, Hamilton Reg Canc Ctr, Hamilton, ON, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1596 EP 1596 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500136 ER PT J AU Mansour, M Holmvang, G Ruskin, J AF Mansour, M Holmvang, G Ruskin, J TI Role of imaging techniques in preparation for catheter ablation of atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article ID ANATOMY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Cardiac Arrhythmia Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 3 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2004 VL 15 IS 9 BP 1107 EP 1108 DI 10.1046/j.1540-8167.2004.04438.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 852UI UT WOS:000223781600022 PM 15363090 ER PT J AU Maria, BL Deidrick, KM Roach, ES Gutmann, DH AF Maria, BL Deidrick, KM Roach, ES Gutmann, DH TI Tuberous sclerosis complex: Pathogenesis, diagnosis, strategies, therapies, and future research directions SO JOURNAL OF CHILD NEUROLOGY LA English DT Editorial Material C1 Med Univ S Carolina, Childrens Res Inst, Charleston, SC 29425 USA. Univ Missouri, Dept Psychol, Columbia, MO USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27109 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63130 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Connecticut Childrens Med Ctr, Dept Pediat, Hartford, CT USA. Connecticut Childrens Med Ctr, Div Pediat Neurol, Hartford, CT USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol & Psychiat, Boston, MA USA. RP Maria, BL (reprint author), Med Univ S Carolina, Childrens Res Inst, 135 Rutledge Ave,Suite 476,POB 250561, Charleston, SC 29425 USA. EM mariabl@muse.edu NR 0 TC 10 Z9 12 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2004 VL 19 IS 9 BP 632 EP 642 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 938GT UT WOS:000229988600002 PM 15563008 ER PT J AU Prather, P de Vries, PJ AF Prather, P de Vries, PJ TI Behavioral and cognitive aspects of tuberous sclerosis complex SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Child-Neurology-Society CY OCT 01-04, 2003 CL MIAMI BEACH, FL SP Child Neruol Soc ID ATTENTION DEFICITS; EPILEPSY; AUTISM; PREVALENCE; DISORDERS; CHILDREN; TSC1; DISABILITY; SEVERITY; SEIZURES AB Tuberous sclerosis complex is a multisystem genetic disorder. Of all the possible manifestations of this complex disorder, the cognitive and behavioral problems represent the area of greatest concern to parents and caregivers. This review outlines the current evidence regarding global intellectual abilities, behavioral problems, psychiatric diagnoses, learning disorders, and specific neuropsychologic deficits for which individuals with tuberous sclerosis complex are at particularly increased risk, and outlines approaches to intervention. Approximately half of individuals diagnosed with tuberous sclerosis complex present with global intellectual impairment and developmental psychopathologies. Those with normal intellectual abilities are also at high risk of specific neuropsychologic deficits and behavioral, learning, and other psychiatric disorders. There is no evidence for an inevitable decline in cognition or behavior, and any such changes should be investigated. The evolving neurocognitive literature suggests that frontal brain systems might be most consistently disrupted by tuberous sclerosis complex-related neuropathology, thus leading to abnormalities in regulatory and goal-directed behaviors. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Cambridge, Dev Psychiat Sect, Cambridge, England. RP Prather, P (reprint author), 23 Pleasant St, Newton, MA 02459 USA. EM pprather@partners.org NR 77 TC 94 Z9 96 U1 1 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2004 VL 19 IS 9 BP 666 EP 674 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 938GT UT WOS:000229988600006 PM 15563012 ER PT J AU Thiele, EA AF Thiele, EA TI Managing epilepsy in tuberous sclerosis complex SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Child-Neurology-Society CY OCT 01-04, 2003 CL MIAMI BEACH, FL SP Child Neruol Soc ID LONG-TERM-FOLLOW; POSITRON-EMISSION-TOMOGRAPHY; INFANTILE SPASMS; WEST-SYNDROME; SURGICAL-TREATMENT; REFRACTORY EPILEPSY; EPILEPTOGENIC TUBER; RANDOMIZED TRIAL; VIGABATRIN; CHILDREN AB Epilepsy is very common in tuberous sclerosis complex and occurs in 80 to 90% of affected individuals during their lifetime. Onset usually occurs during childhood, and up to one third of children with tuberous sclerosis complex will develop infantile spasms. Although not completely understood, the incidence of epilepsy is thought to relate to the neuropathologic features of the disorder, including cortical tubers and other dysgenetic features. Individuals with tuberous sclerosis complex frequently have epileptiform features to their electroencephalograms. Treatment of epilepsy in tuberous sclerosis complex is similar to epilepsy resulting from other causes and includes anticonvulsant medications, the vagus nerve stimulator, and the ketogenic diet. Vigabatrin has been shown to be particularly effective in treating infantile spasms in the setting of tuberous sclerosis complex. Epilepsy surgery has a very important role in the management of children and adults with pharmacoresistant epilepsy in tuberous sclerosis complex. C1 Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, VBK 830,55 Fruit St, Boston, MA 02114 USA. EM ethiele@partners.org NR 61 TC 97 Z9 105 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2004 VL 19 IS 9 BP 680 EP 686 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 938GT UT WOS:000229988600008 PM 15563014 ER PT J AU Woods, SP Rippeth, JD Frol, AB Levy, JK Ryan, E Soukup, VM Hinkin, CH Lazzaretto, D Cherner, M Marcotte, TD Gelman, BB Morgello, S Singer, EJ Grant, I Heaton, RK AF Woods, SP Rippeth, JD Frol, AB Levy, JK Ryan, E Soukup, VM Hinkin, CH Lazzaretto, D Cherner, M Marcotte, TD Gelman, BB Morgello, S Singer, EJ Grant, I Heaton, RK TI Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID NEUROPSYCHOLOGICAL IMPAIRMENT; INFECTED INDIVIDUALS; PERFORMANCE STATUS; WORKING-MEMORY; DISEASE; DISORDERS; CLASSIFICATION; SCHIZOPHRENIA; COEFFICIENTS; DYSFUNCTION AB We examined the interrater reliability (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV. C1 Univ Calif San Diego, HIV Neurobehav Res Ctr, Dept Psychiat 0603H, San Diego, CA 92103 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Baylor Coll Med, Houston, TX 77030 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. RP Woods, SP (reprint author), Univ Calif San Diego, HIV Neurobehav Res Ctr, Dept Psychiat 0603H, 150 W Washington St,2nd Floor, San Diego, CA 92103 USA. EM spwoods@ucsd.edu FU NIMH NIH HHS [P30 MH62512-01, R24MH59656, R24MH59724, R24MH59745]; NINDS NIH HHS [R24NS38841, R24NS45491] NR 68 TC 153 Z9 154 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD SEP PY 2004 VL 26 IS 6 BP 759 EP 778 DI 10.1080/13803390490509565 PG 20 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 865LX UT WOS:000224705700004 PM 15370374 ER PT J AU Franco, GEL O'Neil, TK Litscher, SJ Urban-Piette, M Blank, RD AF Franco, GEL O'Neil, TK Litscher, SJ Urban-Piette, M Blank, RD TI Accuracy and precision of PIXImus densitometry for ex vivo mouse long bones SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE bone mineral density (BMD); bone mineral content (BMC); dual energy X-ray absorptiometry (DXA) mouse; accuracy; precision ID QUANTITATIVE TRAIT LOCI; X-RAY ABSORPTIOMETRY; MINERAL DENSITY; INBRED STRAINS; FAN-BEAM; MICE; C57BL/6J; STRENGTH; C3H/HEJ; FEMUR AB Many densitometric studies in mice assess bone mineral density (BMD) at specified regions of interest, often using ex vivo specimens. In the present study, we sought to determine the precision and accuracy of ex vivo densitometry of mouse bones, comparing two software versions and two data acquisition techniques. The newer software allows manual adjustment of the threshold value for bone, improving the ability to analyze bone edges correctly. Root mean square standard deviations were 2-3 mg/cm(2), with coefficients of variation ranging between 3% and 5% for femora and humeri and between 6% and 7% for radii. The regression coefficients for bone mineral content as a function of ash mass were near 1 for femora and humeri, but considerably lower for radii. Coefficients of determination were inversely related to bone size, with R-2 values exceeding 0.9 at the femur, 0.8 at the humerus, and ranging between 0.3 and 0.6 at the radius. We found that our instrument has a position artifact, with BMD and bone mineral content dependent on the specimen's coordinates in the scanned field. Our findings establish the limitations of ex vivo densitometry with the PIXImus and support our recommendation that investigators seek position artifacts in their instruments. C1 Univ Wisconsin, Sch Med, Dept Med, Endocrinol Sect, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP Blank, RD (reprint author), Univ Wisconsin, Sch Med, Dept Med, Endocrinol Sect, H4-556 CSC 5148,600 Highland Ave, Madison, WI 53792 USA. EM rdb@medicine.wisc.edu NR 14 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 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD FAL PY 2004 VL 7 IS 3 BP 326 EP 333 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850QP UT WOS:000223627800012 ER PT J AU Lara-Castro, C Garvey, WT AF Lara-Castro, C Garvey, WT TI Diet, insulin resistance, and obesity: Zoning in on data for Atkins dieters living in South Beach SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIGH-CARBOHYDRATE DIET; LOW-FAT DIET; CARDIOVASCULAR RISK-FACTORS; CONJUGATED LINOLEIC-ACID; CORONARY-ARTERY DISEASE; TREATMENT PANEL-III; WEIGHT-LOSS; METABOLIC SYNDROME; SATURATED FAT; GLUCOSE-METABOLISM AB Insulin resistance is a central pathogenic factor for the metabolic syndrome and is associated with both generalized obesity and the accumulation of fat in the omental and intramyocellular compartments. In the context of the current obesity epidemic, it is imperative to consider diets in terms of their ability to both promote weight loss and ameliorate insulin resistance. Weight loss under any dietary formulation depends on hypocaloric intake, and only moderate weight loss (5 - 10%) is sufficient to augment insulin sensitivity. However, increments in insulin sensitivity may be more directly related to loss of intramyocellular or omental fat rather than loss of total body weight per se. The widespread acceptance of popular low-carbohydrate high-fat diets (e.g. Atkins Diet, Zone Diet, South Beach diet) further underscores the need to evaluate dietary interventions regarding their safety and metabolic effects. These high-fat diets have been shown to be safe in the short term; however, their long-term safety has not been established. With respect to insulin sensitivity, diets enriched in saturated fats can induce insulin resistance, whereas fat substitution with monounsaturated fats can enhance insulin sensitivity. On the other hand, high-fiber, high-carbohydrate diets comprised of foods with low caloric density can similarly be used for effective weight reduction and to ameliorate insulin resistance. Although some data suggest that low-glycemic index diets are most advantageous in this regard, these effects may have more to do with increments in dietary fiber than differences in available carbohydrates. Popular low-carbohydrate, high-fat diets are being fervently embraced as an alternative to challenging modifications in lifestyle and intentional calorie reduction. Current data do not support such unbridled enthusiasm for these diets, particularly in relationship to high-fiber, high-carbohydrate diets emphasizing intake of fresh vegetables and fruits. Long-term studies to determine the efficacy and safety of both popular and experimental diets are warranted. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Garvey, WT (reprint author), Univ Alabama, Dept Nutr Sci, Webb 232,1675 Univ Blvd, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU NCRR NIH HHS [M01-RR-1070, M01-RR-00032]; NHLBI NIH HHS [P01 HL-55782]; NIDDK NIH HHS [DK-38764] NR 95 TC 55 Z9 56 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4197 EP 4205 DI 10.1210/jc.2004-0683 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600001 PM 15356006 ER PT J AU Florez, JC AF Florez, JC TI Editorial: Phenotypic consequences of the peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism: The weight of the evidence in genetic association studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID BODY-MASS INDEX; DECREASED RISK; E23K VARIANT; PPAR-GAMMA; TYPE-2; METAANALYSIS; DISEASE; SUSCEPTIBILITY; SUBSTITUTION; NEPHROPATHY C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Wellman 8, Boston, MA 02114 USA. EM jcflorez@partners.org FU NIDDK NIH HHS [1 K23 DK65978-01] NR 20 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4234 EP 4237 DI 10.1210/jc.2004-1402 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600008 PM 15356013 ER PT J AU Adams, JM Taylor, AE Crowley, WF Hall, JE AF Adams, JM Taylor, AE Crowley, WF Hall, JE TI Polycystic ovarian morphology with regular ovulatory cycles: Insights into the pathophysiology of polycystic ovarian syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; P450C17-ALPHA ACTIVITY; LUTEINIZING-HORMONE; MASS-SPECTROMETRY; FREE TESTOSTERONE; MENSTRUAL-CYCLE; NORMAL WOMEN; INSULIN; SECRETION; SERUM AB To determine the relevance of polycystic ovarian morphology (PCOM) to the pathophysiology of polycystic ovarian syndrome (PCOS), biochemical features associated with PCOS were examined in 68 women with an established history of regular ovulatory cycles and no clinical evidence of hyperandrogenism. Ovarian morphology was objectively assessed by pelvic ultrasound. LH, FSH, estradiol (E(2)), testosterone (T), androstenedione (Delta(4)A), SHBG, and dehydroepiandrosterone sulfate (DHEAS) were measured at baseline in the early follicular phase (EFP) in all subjects. LH, FSH, E(2), and progesterone (P(4)) were then measured daily for a complete menstrual cycle in 16 women with normal ovarian morphology and in 26 women with PCOM. T, Delta(4)A, SHBG, and DHEAS levels were measured in pools of three daily samples in each of the EFP, midcycle, and midluteal phases. An additional 26 normal women (13 with normal ovarian morphology and 13 with PCOM) were studied in the EFP to assess pulsatile LH secretion, insulin and glucose levels, and the ovarian response to human chorionic gonadotropin. At baseline, there were no differences in body mass index or hirsutism scores between women with PCOM and normal ovaries. In daily samples across the menstrual cycle LH, FSH, E(2), and P(4) did not differ between women with PCOM and those with normal ovaries, and there was no difference in LH pulse amplitude or frequency in the EFP frequent sampling studies. In women with PCOM, T ( P < 0.01), free T ( P < 0.005), and DHEAS ( P < 0.01) levels were higher at baseline in the EFP, and SHBG was lower (P < 0.05). Differences in Delta(4)A did not reach significance ( P = 0.14). T, free T, Delta(4)A, and DHEAS were also increased in PCOM across the menstrual cycle ( P < 0.05). In addition, 17-hydroxyprogesterone (P < 0.02), Delta(4)A (P < 0.01), and T (P < 0.01) responses to human chorionic gonadotropin were greater in women with PCOM. Fasting glucose was not different between the two groups, but fasting insulin was higher ( P<0.02) in PCOM women as was insulin resistance calculated from homeostatic model assessment ( P < 0.01). These studies demonstrate that PCOM in nonhirsute women with documented ovulatory cycles is associated with normal E(2), P(4), and gonadotropin dynamics, but higher androgen and insulin levels and lower SHBG levels. Taken together, these findings suggest that PCOM with ovulatory cycles exists as a discrete entity, represents the mildest form of ovarian hyperandrogenism, and is associated with greater insulin resistance than in women with normal ovarian morphology. The absence of any neuroendocrine abnormality in women with PCOM and ovulatory cycles suggests that gonadotropin dysfunction is not required for increased androgen secretion, but may be critical for development of the anovulatory disorder associated with PCOS. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NICHD NIH HHS [U54-HD-29164, P30-HD-28138] NR 62 TC 98 Z9 105 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4343 EP 4350 DI 10.1210/jc.2003-031600 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600027 PM 15356031 ER PT J AU Miller, KK Grinspoon, S Gleysteen, S Grieco, KA Ciampa, J Breu, J Herzog, DB Klibanski, A AF Miller, KK Grinspoon, S Gleysteen, S Grieco, KA Ciampa, J Breu, J Herzog, DB Klibanski, A TI Preservation of neuroendocrine control of reproductive function despite severe undernutrition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; ANOREXIA-NERVOSA; HYPOTHALAMIC AMENORRHEA; BONE TURNOVER; LEPTIN LEVELS; YOUNG-WOMEN; OSTEOPENIA; WEIGHT; PREVALENCE; DIAGNOSIS AB Anorexia nervosa (AN) is characterized by low weight and self-imposed caloric restriction and leads to severe bone loss. Although amenorrhea due to acquired GnRH deficiency is nearly universal in AN, a subset of patients maintains menses despite low weight. The mechanisms underlying continued GnRH secretion despite low weight in these patients and the impact of gonadal hormone secretion on bone mineral density (BMD) in such eumenorrheic, low-weight patients remain unknown. We hypothesized that 1) eumenorrheic women with AN would have higher body fat and levels of nutritionally dependent hormones, including leptin and IGF-I, than amenorrheic women with AN and comparable body mass index; and 2) BMD would be higher in these women. We also investigated whether the severity of eating disorder symptomatology differed between the groups. We studied 116 women: 1) 42 low-weight women who fulfilled all Diagnostic and Statistical Manual of Mental Disorders (fourth edition) diagnostic criteria for AN, except for amenorrhea; and 2) 74 women with AN and amenorrhea for at least 3 months. The two groups were similar in body mass index (17.1+/-0.2 vs. 16.8+/-0.2 kg/m(2)), percent ideal body weight (78.2+/-0.8% vs. 76.7+/-0.8%), duration of eating disorder (70+/-13 vs. 59+/-9 months), age of menarche (13.2+/-0.3 vs. 13.5+/-0.2 yr), and exercise (4.5+/-1.0 vs. 4.2+/-0.5 h/wk). As expected, eumenorrheic patients had a higher mean estradiol level (186.6+/-19.0 vs. 59.4+/-2.5 nmol/liter; P<0.0001) than amenorrheic subjects. Mean percent body fat, total body fat mass, and truncal fat were higher in eumenorrheic than amenorrheic patients [20.9 +/- 0.9% vs. 16.7 +/- 0.6% (P=0.0001); 9.8 +/- 0.5 vs. 7.8 +/- 0.3 kg (P=0.0009); 3.4 +/- 0.2 vs. 2.7 +/- 0.1 kg (P=0.006)]. The mean leptin level was higher in the eumenorrheic compared with the amenorrheic group (3.7 +/- 0.3 vs. 2.8 +/- 0.2 ng/ml; P=0.04). Serum IGF-I levels were also higher in the eumenorrheic than in the amenorrheic group (41.8 +/- 3.7 vs. 30.8 +/- 2.3 nmol/liter; P=0.02). There were only minor differences in severity of eating disorder symptomatology, as measured by the Eating Disorders Inventory, and where differences were observed, eumenorrheic subjects manifested more severe symptomatology than amenorrheic subjects. Mean BMD at the posterior-anterior and lateral spine were low in both groups, but were higher in patients with eumenorrhea than in those with amenorrhea [posterioranterior spine T-score, -0.9 +/- 0.1 vs. -1.9 +/- 0.1 (P<0.0001); lateral spine T-score, -1.2+/-0.1 vs. -2.3+/-0.2 (P<0.0001)]. In contrast, preservation of menstrual function was not protective at the total hip (total hip T-score, -0.9 +/- 0.1 vs. -1.1 +/- 0.1; P=0.27), trochanter, or femoral neck. In summary, patients with eumenorrhea had more body fat and higher serum leptin levels than their amenorrheic counterparts of similar weight. Moreover, reduced bone density was observed in both groups, but was less severe at the spine, but not the hip, in women with undernutrition and preserved menstrual function than in amenorrheic women of similar weight. Therefore, fat mass may be important for preservation of normal menstrual function in severely undernourished women, and this may be in part mediated through leptin secretion. In addition, nutritional intake and normal hormonal function may be independent contributors to maintenance of trabecular bone mass in low-weight women. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01-RR-01066-27, M01-RR-01066-27S1]; NIDDK NIH HHS [R01-DK-52625, R03-DK-59297] NR 24 TC 58 Z9 60 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4434 EP 4438 DI 10.1210/jc.2004-0720 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600042 PM 15356043 ER PT J AU Aldhahi, W Armstrong, J Bouche, C Carr, RD Moses, A Goldfine, AB AF Aldhahi, W Armstrong, J Bouche, C Carr, RD Moses, A Goldfine, AB TI beta-cell insulin secretory response to oral hypoglycemic agents is blunted in humans in vivo during moderate hypoglycemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID REPAGLINIDE; GLUCOSE; RELEASE AB Oral hypoglycemic agents bind to the ATP-sensitive potassium channel and lower glucose levels effectively in individuals with diabetes. Although the principle mechanism of action can also promote hypoglycemia, clinically profound hypoglycemia is rare. Decreased stimulation of insulin secretion by these agents at mild hypoglycemia could provide protection from more profound hypoglycemia. Sulfonylureas and meglitinides bind to both shared and unique sites on the ATP-sensitive potassium receptor/channel complex but have different pharmacokinetic profiles. To evaluate the differential ability of both sulfonylureas and meglitinides to stimulate insulin release at modest hypoglycemia, we evaluated dextrose infusion rates necessary to maintain plasma glucose after oral administration of repaglinide (1 mg) or glipizide (5 mg) at euglycemia and again at modest hypoglycemia. Healthy subjects with no family history of diabetes underwent four clamp studies, two performed while maintaining isoglycemia (glucose levels at the fasted value) and two while maintaining modest hypoglycemia of 2.78 mmol/liter (50 mg/dl) induced by low-dose insulin infusion (3.6 pmol/kg.min). There was a marked decrease in the dextrose infusion rate with administration of either repaglinide or glipizide at hypoglycemia compared with drug administration at euglycemia (Pless than or equal to0.006). This was accompanied by a reduction in C peptide secretion (Pless than or equal to0.001). Although each drug demonstrated a unique pharmacokinetic profile, drug absorption was comparable at euglycemia and hypoglycemia. The mechanism accounting for the reduced dextrose requirement during hypoglycemia likely involves a markedly decreased insulin secretory response to the agents during hypoglycemia and suggests that at modest hypoglycemia, low glucose or other metabolite(s) or altered counterregulatory hormone levels are sufficient to inhibit insulin release in response to potent insulin secretagogues. These findings may help to explain the relatively low incidence of severe hypoglycemia with clinical administration of these drugs. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NCRR NIH HHS [M01 RR001032] NR 12 TC 6 Z9 6 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4553 EP 4557 DI 10.1210/jc.2004-0266 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600060 PM 15356061 ER PT J AU Welt, CK Smith, PC Taylor, AE AF Welt, CK Smith, PC Taylor, AE TI Evidence of early ovarian aging in fragile X premutation carriers SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; EDUCATION-NEEDS POPULATION; TISSUE-SPECIFIC EXPRESSION; REGULAR MENSTRUAL CYCLES; CGG REPEAT; INHIBIN-B; DIMERIC INHIBIN; FRAXE ALLELES; ACTIVIN-A AB Up to 28% of female fragile X premutation carriers develop premature ovarian failure. To test the hypothesis that fragile X premutation carriers with ovulatory menstrual cycles exhibit hormone changes characteristic of early ovarian aging, 11 regularly cycling fragile X premutation carriers, 24-41 yr old (34.5 +/- 5.7 yr, mean +/-SD), drew daily blood samples across one menstrual cycle. LH, FSH, estradiol, progesterone (P4), inhibin A, and inhibin B levels were compared with levels in 22 age-matched, regularly cycling women, 23-41 yr old (34.6 +/- 5.8 yr), at each cycle stage. Total cycle (26.1 +/- 1.0 vs. 28.2 +/- 0.4 d; P < 0.05) and follicular phase length (12.9 +/- 0.8 vs. 14.5 +/- 0.4 d; P < 0.05) were decreased in fragile X premutation carriers compared with age-matched controls, whereas luteal phase length was similar (13.2 +/- 0.5 vs. 13.7 +/- 0.3 d; P = not significant). FSH was elevated across the follicular (21.9 +/- 3.5 vs. 11.2 +/- 0.5 IU/liter; P < 0.001) and luteal phases (14.6 +/- 3.9 vs. 7.9 +/- 0.5 IU/liter; P < 0.05) in fragile X premutation carriers compared with age-matched controls. Inhibin B in the follicular phase (77 +/- 11 vs. 104 +/- 6 pg/ml; P < 0.05) and inhibin A (3.4 +/- 0.7 vs. 5.8 +/- 0.5 IU/ml; P < 0.01) and P4 [7.3 +/- 1.0 vs. 10.1 +/- 0.7 ng/ml (23.2 +/- 3.0 vs. 32.1 +/- 2.3 nmol/liter); P < 0.05] in the luteal phase were decreased in fragile X premutation carriers compared with age-matched controls, whereas there was no difference in estradiol or LH. In summary, despite regular ovulatory cycles, FSH was increased in fragile X premutation carriers compared with age-matched controls. The increased FSH was accompanied by decreased inhibin B in the follicular phase and inhibin A and P4 in the luteal phase. These hormonal changes suggest that fragile X premutation carriers exhibit early ovarian aging despite regular menstrual cycles. Early ovarian aging in fragile X premutation carriers likely results from decreased follicle number and function, as reflected by lower inhibin B, inhibin A, and P4 levels. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Groton Labs, Pfizer Global Res & Dev, Groton, CT 06340 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NICHD NIH HHS [U54 HD12303-22] NR 57 TC 94 Z9 98 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4569 EP 4574 DI 10.1210/jc.2004-0347 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600063 PM 15356064 ER PT J AU Eton, DT Cella, D Yost, KJ Yount, SE Peterman, AH Neuberg, DS Sledge, GW Wood, WC AF Eton, DT Cella, D Yost, KJ Yount, SE Peterman, AH Neuberg, DS Sledge, GW Wood, WC TI A combination of distribution- and anchor-based approaches determined minimally important differences (MIDs) for four endpoints in a breast cancer scale SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE breast cancer; minimal important difference; quality of life; health-related; Functional Assessment of Cancer Therapy-Breast questionnaire; clinical significance ID QUALITY-OF-LIFE; CLINICAL-SIGNIFICANCE; FUNCTIONAL ASSESSMENT; MEANINGFUL CHANGE; THERAPY; CHEMOTHERAPY; SURVIVORS; PATIENT; SCORES; TRIAL AB Objective: To determine distribution- and anchor-based minimal important difference (MID) estimates for four scores from the Functional Assessment of Cancer Therapy-Breast (FACT-B): the breast cancer subscale (BCS), Trial Outcome Index (TOI), FACT-G (the general version), and FACT-B. Study Design and Setting: We used data from a Phase III clinical trial in metastatic breast cancer (ECOG study 1193; n = 739) and a prospective observational study of pain in metastatic breast cancer (n = 129). One third and one half of the standard deviation and I standard error of measurement were used as distribution-based criteria. Clinical indicators used to determine anchor-based differences included ECOG performance status, current pain, and response to treatment. Results: FACT-B scores were responsive to performance status and pain anchors, but not to treatment response. By combining the results of distribution- and anchor-based methods, MID estimates were obtained: BCS = 2-3 points, TOI = 5-6 points, FACT-G = 5-6 points, and FACT-B = 7-8 points. Conclusion: Distribution- and anchor-based estimates of the MID do show convergence. These estimates can be used in combination with other measures of efficacy to determine meaningful benefit and provide a basis for sample size estimation in clinical trials. (C) 2004 Elsevier Inc. All rights reserved. C1 Evanston NW Healthcare, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, Evanston, IL 60201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Emory Univ, Atlanta, GA 30322 USA. RP Eton, DT (reprint author), Evanston NW Healthcare, 1001 Univ Pl,Suite 100, Evanston, IL 60201 USA. EM d-eton@northwestern.edu FU NCI NIH HHS [CA13650, CA16116, CA23318, CA32102, CA49883, CA66636] NR 45 TC 151 Z9 152 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2004 VL 57 IS 9 BP 898 EP 910 DI 10.1016/j.jclinepi.2004.01.012 PG 13 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 870YB UT WOS:000225093700004 PM 15504633 ER PT J AU Natarajan, S Nietert, PJ AF Natarajan, S Nietert, PJ TI Hypertension, diabetes, hypercholesterolemia, and their combinations increased health care utilization and decreased health status SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; hypertension; hypercholesterolemia; emergency treatment; hospitalization; office visits; health status ID CORONARY HEART-DISEASE; RESOURCE UTILIZATION; CIGARETTE-SMOKING; ILLNESS BEHAVIOR; RISK-FACTORS; CHOLESTEROL; OUTCOMES; BENEFITS; ACCESS; RATES AB Background and objective: For individuals with hypertension, diabetes, or hypercholesterolemia, the relative magnitude of cardiovascular risk factors and the effect of multiple risk factors remains controversial and both treatment practices and health care usage vary. We sought to determine the effect of hypertension, diabetes, hypercholesterolemia, and their combinations on health care utilization and health status through analysis of data from a large national survey. Methods: We applied the Anderson model to a cross-sectional representative sample (n = 15,107) of the U.S. civilian, noninstitutionalized population (the 1996 Medical Expenditure Panel Survey). Results: For diabetes, additional risk factors did not increase the likelihood of emergency room (ER) visits or hospitalizations but were associated with increased outpatient visits and poorer health status. For hypertension, additional risk factors increased the likelihood of hospitalization (but not ER visits), the number of outpatient visits, and poorer health status. For hypercholesterolemia, additional risk factors were associated with increased likelihood of ER visits, hospitalizations, and poorer health status but not more outpatient visits. Diabetes had the largest effect on health care utilization and health status. Conclusion: These findings re-emphasize the magnitude of diabetes as a major risk factor associated with increased ER visits, hospitalizations, outpatients visits, and lower health status. (C) 2004 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Care Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Natarajan, S (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Care Res, 135 Cannon St,Suite 403,POB 250837, Charleston, SC 29425 USA. EM nataraja@musc.edu OI Nietert, Paul/0000-0002-3933-4986 NR 36 TC 17 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2004 VL 57 IS 9 BP 954 EP 961 DI 10.1016/j.jclinepi.2004.01.011 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 870YB UT WOS:000225093700009 PM 15504638 ER PT J AU Yang, YG Wood, JC Lan, P Wilkinson, RA Sykes, M Fishman, JA Patience, C AF Yang, YG Wood, JC Lan, P Wilkinson, RA Sykes, M Fishman, JA Patience, C TI Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CROSS-SPECIES TRANSMISSION; MINIATURE SWINE; NO EVIDENCE; ORGAN XENOTRANSPLANTATION; HOST-RANGE; NUDE-MICE; IN-VIVO; INFECTION; RECIPIENTS; IDENTIFICATION AB Porcine endogenous retrovirus (PERV) is a potential pathogen in clinical xenotransplantation; transmission of PERV in vivo has been suggested in murine xenotransplantation models. We analyzed the transmission of PERV to human cells in vivo using a model in which immunodeficient NOD/SCID transgenic mice were transplanted with porcine and human lymphohematopoietic tissues. Our results demonstrate, we believe for the first time, that human and pig cells can coexist long-term (up to 25 weeks) without direct PERV infection of human cells. Despite the transplantation of porcine cells that did not produce human-tropic PERV, human cells from the chimeric mice were frequently found to contain PERV sequences. However, this transmission was due to the pseudotyping of PERV-C (a virus without human tropism) by xenotropic murine leukemia virus, rather than to de novo generation of human-tropic PERV. Thus, pseudotyping might account for the PERV transmission previously observed in mice. The absence of direct human cell infection following long-term in vivo coexistence with large numbers of porcine cells provides encouragement regarding the potential safety of using pigs that do not produce human-tropic PERV as source animals for transplantation to humans. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge BioTherapeut Inc, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01-AI45897, P01 AI045897] NR 38 TC 30 Z9 33 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2004 VL 114 IS 5 BP 695 EP 700 DI 10.1172/JCI200421946 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 851RQ UT WOS:000223703300016 PM 15343388 ER PT J AU Kulkarni, RN Jhala, US Winnay, JN Krajewski, S Montminy, M Kahn, CR AF Kulkarni, RN Jhala, US Winnay, JN Krajewski, S Montminy, M Kahn, CR TI PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PANCREATIC BETA-CELLS; RECEPTOR; MICE; GROWTH; TRANSCRIPTION; DISRUPTION; ACTIVATION; APOPTOSIS; MODEL; IRS-1 AB Inadequate compensatory beta cell hyperplasia in insulin-resistant states triggers the development of overt diabetes. The mechanisms that underlie this crucial adaptive response are not fully defined. Here we show that the compensatory islet-growth response to insulin resistance in 2 models - insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice - is severely restricted by PDX-1 heterozygosity. Six-month-old IR/IRS-1 and LIRKO mice both showed up to a 10-fold increase in beta cell mass, which involved epithehal-to-mesenchymal transition. In both models, superimposition of PDX-1 haploin-sufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the beta cells showed apoptosis resulting in premature death of the mice. This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Calif San Diego, Whittier Inst, La Jolla, CA USA. Burnham Inst, La Jolla, CA 92037 USA. Salk Inst Biol Studies, Peptide Biol Labs, San Diego, CA USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Div Res, Room 602,1 Joslin Pl, Boston, MA 02215 USA. EM Kulkarni@joslin.harvard.edu FU NIDDK NIH HHS [K08 DK002885, DK 02885, P30 DK 36836, P30 DK036836, R01 DK 67536, R01 DK067536, R56 DK067536, U19 DK 42502, U19 DK042502] NR 42 TC 177 Z9 184 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2004 VL 114 IS 6 BP 828 EP 836 DI 10.1172/JCI200421845 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 853ZE UT WOS:000223868700014 PM 15372107 ER PT J AU Lin, NU Bellon, JR Winer, EP AF Lin, NU Bellon, JR Winer, EP TI CNS metastases in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID MULTIPLE BRAIN METASTASES; THERAPY-ONCOLOGY-GROUP; CONTRAST-ENHANCED MR; NERVOUS-SYSTEM METASTASES; PARTITIONING ANALYSIS RPA; TRASTUZUMAB-BASED THERAPY; RADIATION-THERAPY; PROGNOSTIC-FACTORS; STEREOTACTIC RADIOSURGERY; CEREBRAL METASTASES AB As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed. (C) 2004 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ewiner@partners.org FU NCI NIH HHS [T32 CA009172] NR 100 TC 315 Z9 325 U1 1 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2004 VL 22 IS 17 BP 3608 EP 3617 DI 10.1200/JCO.2004.01.175 PG 10 WC Oncology SC Oncology GA 851UN UT WOS:000223711300024 PM 15337811 ER PT J AU Ghia, KK Chen, Y Milner, DA Fisher, DC AF Ghia, KK Chen, Y Milner, DA Fisher, DC TI Case 2. Langerhans cell histiocytosis presenting with a skin rash SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ghia, KK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2004 VL 22 IS 17 BP 3640 EP 3642 DI 10.1200/JCO.2004.02.011 PG 3 WC Oncology SC Oncology GA 851UN UT WOS:000223711300028 PM 15337813 ER PT J AU Simon, NM Worthington, JJ Doyle, AC Hoge, EA Kinrys, G Fischmann, D Link, N Pollack, MH AF Simon, NM Worthington, JJ Doyle, AC Hoge, EA Kinrys, G Fischmann, D Link, N Pollack, MH TI An open-label study of levetiracetam for the treatment of social anxiety disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; DOUBLE-BLIND; PHOBIA; PLACEBO; PAROXETINE; DEPRESSION; EFFICACY; STATES; SCALE AB Objective: Social anxiety disorder is a disabling condition characterized by excessive fear and avoidance of social and performance situations. While a variety of effective pharmacotherapies exists, many patients do not fully respond to or tolerate available agents. Preclinical and early clinical experience with levetiracetam, a novel anticonvulsant agent, suggests that levetiracetam has anxiolytic properties and a favorable adverse event profile. Levetiracetam thus warrants Systematic evaluation as a treatment option for anxiety disorders. Method: Twenty adult outpatients who were recruited through advertisement and clinical referral and who met DSM-IV criteria for social anxiety disorder, generalized type, participated in this 8-week open-label, flexible-dose study from November 2002 to December 2003. Participants were required to have scores of : 50 on the Liebowitz Social Anxiety Scale (LSAS) and greater than or equal to4 on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline. The presence of comorbid depression and anxiety disorders were permitted as long as social anxiety disorder was the primary disorder. Levetiracetam was initiated at 250 mg/day for the first week and flexibly titrated up to a maximum of 3000 mg/day (1500 mg b.i.d.). The primary outcome measure was change in the LSAS score at endpoint. Results: There was a clinically significant 20.5-point decrease in LSAS scores in the intent-to-treat, last-observation-carried-forward analysis (t = 3.1; p < .01, N = 20). There were also significant reductions in CGI-S (p < .01) and Hamilton Rating Scale for Anxiety (p < .02) scores. Conclusions: This pilot study supports the safety and potential efficacy of a novel agent, levetiracetam, for the treatment of social anxiety disorder. Larger controlled trials are warranted to confirm these results. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cambridge Hlth Alliance, Boston, MA USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, WAC-812,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 33 TC 47 Z9 47 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2004 VL 65 IS 9 BP 1219 EP 1222 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 856ZA UT WOS:000224083600009 PM 15367048 ER PT J AU Chua, EF Rand-Giovannetti, E Schacter, DL Albert, MS Sperling, RA AF Chua, EF Rand-Giovannetti, E Schacter, DL Albert, MS Sperling, RA TI Dissociating confidence and accuracy: Functional magnetic resonance imaging shows origins of the subjective memory experience SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID ILLUSORY RECOGNITION MEMORY; EVENT-RELATED FMRI; EYEWITNESS MEMORY; EPISODIC RETRIEVAL; FALSE RECOGNITION; SUBSEQUENT-MEMORY; BRAIN ACTIVITY; IDENTIFICATION; HIPPOCAMPAL; FAMILIARITY AB Successful memory typically implies both objective accuracy and subjective confidence, but there are instances when confidence and accuracy diverge. This dissociation suggests that there may be distinct neural patterns of activation related to confidence and accuracy. We used event-related functional magnetic resonance imaging to study the encoding of novel face-name associations, assessed with a postscan memory test that included objective measures of accuracy and subjective measures of confidence. We showed specific neural activity in the left inferior prefrontal cortex associated with trials when subjects expressed high confidence that they had chosen the correct name for the face and made a correct identification. Moreover, we found that this region was also associated with imparting high confidence when subjects chose the incorrect name. However, medial temporal lobe regions showed activity only for high-confidence correct trials. Many functional magnetic resonance imaging studies have shown that the medial temporal lobe and left prefrontal regions are particularly important for the successful formation of memories by using a combination of subjective and objective measures. Our findings suggest that these regions may be differentially involved in the objective and subjective components of memory and that the origins of confidence-accuracy dissociations may be related to incomplete activation of the neural pattern seen in successful encoding. These findings may also aid understanding of eyewitness misidentifications and memory distortions. C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurocognit Studies, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Chua, EF (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurocognit Studies, 221 Longwood Ave, Boston, MA 02115 USA. EM echua@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [P01-AG-04953]; NIMH NIH HHS [MH60941]; NINDS NIH HHS [K23-NS02189] NR 54 TC 28 Z9 28 U1 2 U2 8 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2004 VL 16 IS 7 BP 1131 EP 1142 DI 10.1162/0898929041920568 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 856RX UT WOS:000224063600002 PM 15453969 ER PT J AU Shapiro, M Chren, MM Levy, RM Elder, DE LeBoit, PE Mihm, MC Margolis, DJ Gimotty, PA Ming, ME AF Shapiro, M Chren, MM Levy, RM Elder, DE LeBoit, PE Mihm, MC Margolis, DJ Gimotty, PA Ming, ME TI Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Dermatopathology CY OCT 10-13, 2002 CL PHOENIX, ARIZONA SP Amer Soc Dermatopathol ID CONSENSUS DEVELOPMENT PROGRAM; ACQUIRED MELANOCYTIC NEVI; EARLY MELANOMA; CUTANEOUS MELANOMA; RISK FACTOR; DNA-REPAIR; CONFERENCES; BENIGN; DISSEMINATION; TERMINOLOGY AB Background: Although a nevus with the microscopic features of a 'dysplastic nevus' is commonly seen, the nomenclature used to describe such a lesion has been thought to be inconsistent. A 1992 National Institutes of Health (NIH) Consensus Conference sought to unify nomenclature and suggested that the term 'nevus with architectural disorder' be used along with a comment on melanocytic atypia. Methods: We performed a cross-sectional mail survey to determine preferred terminology as well as the level of adherence to the NIH-recommended nomenclature. All 856 active members of the American Society of Dermatopathology (ASDP) and 1100 (13.0%) of the 8471 active members of the American Academy of Dermatology (AAD) were surveyed. Results: Five hundred and thirty-three ASDP members and 483 AAD members who fulfilled eligibility criteria completed the questionnaire. The term 'dysplastic nevus' was favored by the largest number of responders (favored by 39.1% of ASDP members and 62.3% of AAD members), while the 1992 NIH Consensus Conference-recommended terminology was the second most popular term (25.3% of ASDP and 15.1% of AAD members). Dermatopathologists (OR=1.9, p=0.0001) and those who had dual training in dermatology and dermatopathology (OR=1.6, p=0.02 for ASDP members; OR=2.3, p=0.02 for AAD members) were more likely to adhere to the 1992 NIH Consensus Conference nomenclature. Conclusions: Despite attempts to unify nomenclature for microscopically dysplastic nevi through the NIH Consensus Conference, wide variation in terminology persists. C1 Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USA. RP Ming, ME (reprint author), Hosp Univ Penn, Dept Dermatol, 2 Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM mmingmd@yahoo.com NR 58 TC 31 Z9 31 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD SEP PY 2004 VL 31 IS 8 BP 523 EP 530 DI 10.1111/j.0303-6987.2004.00216.x PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA 840EJ UT WOS:000222839600002 PM 15268706 ER PT J AU Mishory, A Molnar, C Koola, J Li, XB Kozel, FA Myrick, H Stroud, Z Nahas, Z George, MS AF Mishory, A Molnar, C Koola, J Li, XB Kozel, FA Myrick, H Stroud, Z Nahas, Z George, MS TI The maximum-likelihood strategy for determining transcranial magnetic stimulation motor threshold, using parameter estimation by sequential testing is faster than conventional methods with similar precision SO JOURNAL OF ECT LA English DT Article DE transcranial magnetic stimulation; motor threshold; excitability; parameter estimation by sequential testing; algorithm; maximum-likelihood strategy; method ID CORTICOMOTOR THRESHOLD; DEPRESSION AB The resting motor threshold (rMT) is the basic unit of transcranial magnetic stimulation (TMS) dosing. Traditional methods of determining rMT involve finding a threshold of either visible movement or electromyography (EMG) motor-evoked potentials, commonly approached from above and below and then averaged. This time-consuming method typically uses many TMS pulses. Mathematical programs can efficiently determine a threshold by calculating the next intensity needed based on the prior results. Within our group of experienced TMS researchers, we sought to perform an illustrative study to compare one of these programs, the Maximum-Likelihood Strategy using Parameter Estimation by Sequential Testing (MLS-PEST) approach, to a modification of the traditional International Federation of Clinical Neurophysiology (IFCN) method for determining rMT in terms of the time and pulses required and the rMT value. C1 Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Mishory, A (reprint author), Med Univ S Carolina, Brain Stimulat Lab, 502 N,67 President St, Charleston, SC 29425 USA. EM mishory@musc.edu RI Kozel, Frank/I-5366-2012 FU NCRR NIH HHS [R01 RR 14080-02, R01 RR14080-01]; NIAAA NIH HHS [2 P50 AA10761-03]; NINDS NIH HHS [R01 NS40956-1] NR 16 TC 48 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD SEP PY 2004 VL 20 IS 3 BP 160 EP 165 DI 10.1097/00124509-200409000-00007 PG 6 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 856TN UT WOS:000224068000008 PM 15343000 ER PT J AU Warshaw, AL Thayer, SP AF Warshaw, AL Thayer, SP TI Pancreaticoduodenectomy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 0 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 2004 VL 8 IS 6 BP 733 EP 741 DI 10.1016/j.gassur.2004.03.005 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 858LX UT WOS:000224194400014 PM 15358336 ER PT J AU Wade-Martins, R Lawler, S Bursill, C Saeki, Y Channon, K Monaco, AP Chiocca, EA AF Wade-Martins, R Lawler, S Bursill, C Saeki, Y Channon, K Monaco, AP Chiocca, EA TI High capacity viral vectors for genomic DNA transgene delivery: Applications to gene therapy and functional genomics SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 1st Annual Conference of the British-Society-for-Gene-Therapy CY MAR 28-30, 2004 CL Keble Coll, Oxford, ENGLAND SP British Soc Gene Therapy, Schering Healthcare, AstraZeneca, Canc Res, Chron Granulomatous Disorder Res Trust, Gene Therapy Advisroy Comm, Gloria Miles Canc Fdn, Katherine Dormandy Trust haemophilia * Allied Disorders, Int Soc Canc Gene Therapy, Natl Translat Canc Res Network HO Keble Coll C1 Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP PY 2004 VL 6 IS 9 MA 6 BP S4 EP S5 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 859IR UT WOS:000224257100016 ER PT J AU Gordon, HS Paterniti, DA Wray, NP AF Gordon, HS Paterniti, DA Wray, NP TI Race and patient refusal of invasive cardiac procedures SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GA SP Soc Gen Internal Med DE patient acceptance of health care; treatment refusal; ethnic groups; racial variation; coronary artery disease ID CORONARY-REVASCULARIZATION PROCEDURES; UNDERSTANDING RACIAL VARIATION; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR PROCEDURES; SEX-DIFFERENCES; ETHNIC DISPARITIES; CLINICAL METHOD; MEDICAL-CENTER; HEALTH-CARE; VETERANS AB OBJECTIVE: To determine whether patients' decisions are an important determinant of nonuse of invasive cardiac procedures and whether decisions vary by race. DESIGN: Observational prospective cohort. PARTICIPANTS: Patients (N= 681) enrolled at the exercise treadmill or the cardiac catheterization laboratories at a large Veterans Affairs hospital. MEASURES: Doctors' recommendations and patients' decisions were determined by both direct observation of doctor and patient verbal behavior and by review of medical charts. Performance of coronary angiography, angioplasty, and bypass surgery were determined by chart review for a minimum of 3 months follow-up. RESULTS: Coronary angiography was recommended after treadmill testing for 83 of 375 patients and 72 patients underwent angiography. Among 306 patients undergoing angiography, recommendations for coronary angioplasty or bypass surgery were given to 113 and 45 patients and were completed for 98 and 33 patients, respectively. Recommendations were not significantly different by race. However, 4 of 83 (4.8%) patients declined or did not return for recommended angiograms and this was somewhat more likely among black and Hispanic patients, compared with white patients (13% and 33% vs 2%; P= .05). No patients declined angioplasty and 2 of 45 (4.4%) patients declined or did not return for recommended bypass surgery. Other recommended procedures were not completed after further medical evaluation (n= 32). There was no difference (P > .05) by race/ethnicity in doctor-level reasons for nonreceipt of recommended invasive cardiac procedures. CONCLUSIONS: Patient decisions to decline recommended invasive cardiac procedures were infrequent and may explain only a small fraction of racial disparities in the use of invasive cardiac procedures. C1 Baylor Coll Med, Dept Internal Med, Houston Ctr Qual Care & Utilizat Studies, Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Internal Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Calif Davis, Dept Internal Med & Sociol, Ctr Hlth Serv Res Primary Care, Sacramento, CA 95817 USA. RP Gordon, HS (reprint author), Houston VAMC, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hgordon@bcm.tmc.edu RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 31 TC 23 Z9 23 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2004 VL 19 IS 9 BP 962 EP 966 DI 10.1111/j.1525-1497.2004.30131.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 847OL UT WOS:000223404700009 PM 15333061 ER PT J AU Harness, N Jupiter, JB AF Harness, N Jupiter, JB TI The treatment of an osteochondral shearing fracture-dislocation of the head of the proximal phalanx: A case report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE fracture; phalanx; interphalangeal; articular; osteochondral; fixation ID INJURIES; JOINT AB We report the morphology and treatment of a proximal interphalangeal joint dislocation resulting in an injury to the articular surface of the proximal phalanx and avulsion of the radial collateral ligament from its proximal origin. A large osteochondral fragment was sheared from the radial articular surface of the proximal phalanx and remained displaced volarly after reduction of the joint. Plain radiographs and 2- and 3-dimensional computed tomography images were used to evaluate this unusual injury before surgery. Open reduction and internal fixation using a small K-wire and figure-of-eight wire technique restored the articular surface of the head of the proximal phalanx and gave a satisfactory functional result. Copyright (C) 20042004 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Combines Orthopaed Residency, Boston, MA 02115 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 15 Parkman St ACC 527, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2004 VL 29A IS 5 BP 925 EP 930 DI 10.1016/j.jhsa.2004.05.010 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 858XF UT WOS:000224225100023 PM 15465246 ER PT J AU Nelson, DE Kreps, GL Hesse, BW Croyle, RT Willis, G Arora, NK Rimer, BK Viswanath, KV Weinstein, N Alden, S AF Nelson, DE Kreps, GL Hesse, BW Croyle, RT Willis, G Arora, NK Rimer, BK Viswanath, KV Weinstein, N Alden, S TI The Health Information National Trends Survey (HINTS): Development, design, and dissemination SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER CONTROL; COMMUNICATION; RISK; PERCEPTIONS; AMERICANS; KNOWLEDGE; INTERNET; IMPACT AB Little is known about access, sources, and trust of cancer-related information, or factors that facilitate or hinder communication on a populationwide basis. Through a careful developmental process involving extensive input from many individuals and organizations, the National Cancer Institute (NCI) developed the Health Information National Trends Survey ( HINTS) to help fill this gap. This nationally representative telephone survey of 6,369 persons aged greater than or equal to18 years among the general population was first conducted in 2002-2003, and will be repeated biennially depending on availability of funding. The purpose of creating a population survey to be repeated on a cyclical basis is to track trends in the public's rapidly changing use of new communication technologies while charting progress in meeting health communication goals in terms of the public's knowledge, attitudes, and behaviors. The HINTS survey instrument was built upon extant models of health communication and behavior change, taking into account the rapidly changing communication environment. Questions in the survey were drawn from an overall theoretical framework that juxtaposed the "push" aspects of traditional broadcast media against the "pull" aspects of new media. HINTS data will be made widely available for researchers and practitioners; it will help further research in health communication and health promotion and provide useful information for programs, policies, and practices in a variety of settings. C1 NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cambridge, MA USA. Rutgers State Univ, Camden, NJ 08102 USA. NIH, Bethesda, MD 20892 USA. RP Hesse, BW (reprint author), NCI, 6131 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 45 TC 245 Z9 247 U1 5 U2 36 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD SEP-OCT PY 2004 VL 9 IS 5 BP 443 EP 460 DI 10.1080/10810730490504233 PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 861OQ UT WOS:000224426900005 PM 15513791 ER PT J AU Vaidya, C Wright, JE Rosowsky, A AF Vaidya, C Wright, JE Rosowsky, A TI Synthesis and antifolate activity of new pyrrolo[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine inhibitors of dihydrofolate reductase SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID VITRO ANTITUMOR-ACTIVITY; REDUCED FOLATE CARRIER; SIDE-CHAIN; N-ALPHA-(4-AMINO-4-DEOXYPTEROYL)-N-DELTA-HEMIPHTHALOYL-L-ORNITHINE PT523; N(ALPHA)-(4-AMINO-4-DEOXYPTEROYL)-N(DELTA)-HEMIPHTHALOYL-L-ORNITHINE PT523; BIOLOGICAL EVALUATION; PNEUMOCYSTIS-CARINII; AMINOPTERIN ANALOGS; DEAZA ANALOGS AB Three previously undescribed dihydrofolate reductase (DHFR) inhibitors, N-alpha-[4-[N-[2,4-diaminopyrrolo [2,3-d]pyrimidin-5-yl)methyl]amino]benzoyl] -N-delta-hemiphthaloyl-L-ornithine (7), N-alpha-[4-[N-[(2,4-diaminothieno[2,3-d]pyrimidin-5-yl)methyl]amino]benzoyl]- N-delta-hemiphthaloyl-L-ornithine (8), and N-[4-[N-[(2,4-diaminothieno[2,3-d]pyrimidin-5-yl)methyl]amino]benzoyl]-L-glutamic acid (12), were synthesized and their antifolate activity was assessed. The ability of 7 and 8 to bind to DHFR and inhibit the growth of CCRF-CEM human lymphoblastic leukemia cells in culture were dramatically reduced in comparison with the corresponding pteridine analogue, N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (1, PT523). In a similar manner, the antifolate activity of 12 was markedly reduced in comparison with that of the corresponding glutamate analogue, aminopterin (5, AMT). In contrast, 7, 8, and 12 all displayed excellent affinity for the reduced folate carrier (RFC) of CCRF-CEM cells as measured by a standard competitive influx assay. Lack of a consistent correlation between the results of the growth inhibition assays and those of the DHFR and RFC binding assays results suggest that additional factors also play a role in the antifolate activity of these compounds. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 20 TC 2 Z9 3 U1 0 U2 1 PU HETERO CORPORATION PI PROVO PA PO BOX 170, PROVO, UT 84603-0170 USA SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD SEP-OCT PY 2004 VL 41 IS 5 BP 787 EP 793 PG 7 WC Chemistry, Organic SC Chemistry GA 865IB UT WOS:000224694800023 ER PT J AU Matute-Bello, G Lee, JS Frevert, CW Liles, WC Sutlief, S Ballman, K Wong, V Selk, A Martin, TR AF Matute-Bello, G Lee, JS Frevert, CW Liles, WC Sutlief, S Ballman, K Wong, V Selk, A Martin, TR TI Optimal timing to repopulation of resident alveolar macrophages with donor cells following total body irradiation and bone marrow transplantation in mice SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE adoptive transfer; alveolar macrophages; total body irradiation; bone marrow transplantation ID EMIGRATION; MONOCYTES; INJURY AB To determine the time required to repopulate mouse lungs with donor alveolar macrophages following total body irradiation (TBI) and bone marrow transplantation (BMT), C57BI/6 mice were subjected to TBI with 900 cGy, followed by transplantation of bone marrow cells from mice expressing green fluorescent protein (GFP) in their somatic cells. The mice were euthanized at either 30 (n=5), 60 (n=5) or 90 (n=5) days following BMT. Thirty days following transplantation, 87.8+/-3.9% (mean+/-S.E.M.) circulating leukocytes in recipient mice were derived from the donor, as determined by fluorescence activated cell sorting (FACS) analysis for GFP. However, only 46.9+/-7.4% of the resident alveolar cells expressed GFP, indicating incomplete repopulation. By day 60 post-transplantation, the percentage of bronchoalveolar lavage fluid (BALF) cells expressing GFP reached 74.5+/-2.4%, remaining stable 90 days after transplantation (80.4+/-1.9%). We conclude that 60 days after TBI with 900 cGy and bone marrow transplantation, the majority of the lung resident alveolar macrophages is of donor origin. This study provides useful information regarding the time of reconstitution with donor alveolar macrophages in the pulmonary airspaces of recipient mice following marrow transplantation. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Med, Div Pulm & Crit Care, Seattle, WA 98108 USA. VA Puget Sound Healthcare Syst, Med Res Serv, Seattle, WA USA. Univ Washington, Dept Med, Div Allergy & Infect Dis, St Louis, MO 63130 USA. VA Puget Sound Healthcare Syst, Sect Radiat Oncol, Seattle, WA USA. RP Martin, TR (reprint author), Univ Washington, Dept Med, Div Pulm & Crit Care, 1660 S Columbian Way,GMR 151-L, Seattle, WA 98108 USA. EM trmartin@u.washington.edu FU NHLBI NIH HHS [HL62995, HL70178, HL70840]; PHS HHS [65892] NR 11 TC 48 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP PY 2004 VL 292 IS 1-2 BP 25 EP 34 DI 10.1016/j.jim.2004.05.010 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 854WT UT WOS:000223935200003 PM 15350509 ER PT J AU Stoicov, C Whary, M Rogers, AB Lee, FS Klucevsek, K Li, HC Cai, X Saffari, R Ge, ZM Khan, IA Combe, C Luster, A Fox, JG Houghton, JM AF Stoicov, C Whary, M Rogers, AB Lee, FS Klucevsek, K Li, HC Cai, X Saffari, R Ge, ZM Khan, IA Combe, C Luster, A Fox, JG Houghton, JM TI Coinfection modulates inflammatory responses and clinical outcome of Helicobacter felis and Toxoplasma gondii infections SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PYLORI INFECTION; GASTRIC INCISURA; GAMMA-INTERFERON; IMMUNE-RESPONSES; IFN-GAMMA; MICE; ANTRALIZATION; METAPLASIA; EXPRESSION; PHENOTYPE AB The host immune response plays a critical role in determining disease manifestations of chronic infections. Inadequate immune response may fail to control infection, although in other cases the specific immune response may be the cause of tissue damage and disease. The majority of patients with chronic infections are infected by more than one organism yet the interaction between multiple active infections is not known, nor is the impact on disease outcome clear. Using the BALB/c strain of mice, we show that Toxoplasma gondii infection in a host infected with Helicobacter felis alters the natural outcome of T. gondii infection, allowing uncontrolled tachyzoite replication and severe organ damage. Survival rates decrease from 95% in T. gondii infection alone to 50% in dual-infected mice. In addition, infection with T. gondii alters the specific H. felis immune response, converting a previously resistant host to a susceptible phenotype. Gastric mucosal IFN-gamma and IL-12 were significantly elevated and IL-10 substantially reduced in dual-infected mice. These changes were associated with severe gastric mucosal inflammation, parietal cell loss, atrophy, and metaplastic cell changes. These data demonstrate the profound interactions between the immune response to unrelated organisms, and suggest these types of interactions my impact clinical disease. C1 Univ Massachusetts, Sch Med, Div Gastroenterol, Dept Med, Worcester, MA 01605 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA. RP Houghton, JM (reprint author), Univ Massachusetts, Sch Med, Div Gastroenterol, Dept Med, Lazare Res Bldg,Room 209,364 Plantat St, Worcester, MA 01605 USA. EM jeanmarie.houghton@umassmed.edu FU NCI NIH HHS [K22 CA90518, R01 CA03405]; NIAID NIH HHS [AI 33325, K08 AI01697, R01 AI37750] NR 27 TC 52 Z9 54 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2004 VL 173 IS 5 BP 3329 EP 3336 PG 8 WC Immunology SC Immunology GA 849HR UT WOS:000223529800058 PM 15322196 ER PT J AU Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF AF Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF TI Advances in optical coherence tomography imaging for dermatology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE optical imaging; non-invasive imaging ID VIVO HUMAN SKIN; BLOOD-FLOW; DOPPLER TOMOGRAPHY; SPEED; BIREFRINGENCE; TISSUE AB Optical coherence tomography (OCT) is a non-invasive imaging technique, which has previously demonstrated potential for use in dermatology. The purpose of this study is to demonstrate how improvements in image quality, speed, and functionality enable qualitative and quantitative information to be obtained from in vivo human skin. We developed a portable fiber-optic based OCT imaging device that requires only 1 second to simultaneously provide high-resolution images of skin structure, collagen birefringence, and blood flow. Images of normal human skin were acquired in vivo, and features compared with clinical and histologic observations. The layered structure and appendages of skin were apparent in conventional OCT images, and correlated well with corresponding histology. Polarization-sensitive OCT images simultaneously revealed birefringent regions within the dermis corresponding to the location of collagen fibers, as confirmed with polarized light microscopy. Properties of collagen-rich tissues including tendon and scar tissues were quantified. Location of blood flow was also displayed alongside structural and polarization-sensitive images. Significant improvements in OCT technology have been made since its early application in dermatology. In particular, combining the previously described structural and Doppler imaging functions with polarization-sensitive imaging increases the utility of the technique for rapid, non-invasive investigations in the skin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St,BAR 714, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; strasswimmer, john/0000-0002-5790-2633 NR 27 TC 149 Z9 150 U1 1 U2 12 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2004 VL 123 IS 3 BP 458 EP 463 DI 10.1111/j.0022-202X.2004.23404.x PG 6 WC Dermatology SC Dermatology GA 844JU UT WOS:000223155100007 PM 15304083 ER PT J AU Yang, G Niendorf, KB Tsao, H AF Yang, G Niendorf, KB Tsao, H TI A novel methionine-53-valine mutation of p16 in a hereditary melanoma kindred SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CDKN2A; hereditary melanoma; Met53Val ID CDKN2A MUTATIONS; INHIBITION; GENETICS; P14(ARF); MDM2 AB We report a novel germline Met53Val mutation in CDKN2A from a large melanoma-prone family; this mutation occurs in exon 2 of CDKN2A where p16 and alternative reading frame (ARF) both share transcript sequences. The previously reported Met53Ile and the current Met53Val mutations are coupled to distinct Asp68His and Asp67Gly alterations in ARF, respectively. The coincidence of second, independent p16 Met53 alteration that differentially alters ARF suggests that there may be selectivity for targeting the p16 transcript over the ARF transcript. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Anal, Boston, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, 622 Bartlett Hall,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 13 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2004 VL 123 IS 3 BP 574 EP 575 DI 10.1111/j.0022-202X.2004.23400.x PG 2 WC Dermatology SC Dermatology GA 844JU UT WOS:000223155100022 PM 15304098 ER PT J AU Okuyama, R LeFort, K Dotto, GP AF Okuyama, R LeFort, K Dotto, GP TI A dynamic model of keratinocyte stem cell renewal and differentiation: Role of the p21 (WAF1)/(Cip1) and notch1 signaling pathways SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 52nd Annual Montagna Symposium on Biology of Skin CY JUN 13-17, 2003 CL Snowmass Village, CO SP Natl Psoriasis Fdn, Novartis Int AG, Estee Lauder Co, Johnson & Johnson Prod, Avon Prod Inc, Fdn Basic Cutaneous Res, Fujisawa Healthcare Inc, Natl Alopecia Areata Fdn, Orentreich Fdn Advancement Sci, NIAMS, Eugene M Farber Travel Awards Young Investigators, JID Supplement Issue DE notch; p21 (WAF1/Cip1); stem cell; differentiation; skin carcinogenesis; keratinocyte ID HAIR-FOLLICLES; EPIDERMAL DIFFERENTIATION; MEDIATED ACTIVATION; DEPENDENT KINASES; CDK INHIBITORS; MOUSE SKIN; EXPRESSION; FRINGE; GROWTH; DELTA AB We present here a dynamic model of functional equilibrium between keratinocyte stem cells, transit amplifying populations and cells that are reversibly versus irreversibly committed to differentiation. According to this model, the size of keratinocyte stem cell populations can be controlled at multiple levels, including relative late steps in the sequence of events leading to terminal differentiation and by the influences of a heterogeneous extra-cellular environment. We discuss how work in our laboratory, on the interconnection between the cyclin/CDK inhibitor p21(WAF1/CiP1) and the Notch1 signaling pathways, provides strong support to this dynamic model of stem cell versus committed and/or differentiated keratinocyte populations. C1 Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Tohoku Univ, Grad Sch Med, Dept Dermatol, Sendai, Miyagi 980, Japan. RP Dotto, GP (reprint author), Univ Lausanne, Inst Biochem, Chemin Bovaresses 155, CH-1066 Epalinges, Switzerland. EM gdotto@partners.org NR 37 TC 24 Z9 26 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 2004 VL 9 IS 3 BP 248 EP 252 DI 10.1111/j.1087-0024.2004.09308.x PG 5 WC Dermatology SC Dermatology GA 847GP UT WOS:000223381000010 PM 15369220 ER PT J AU Graville, DJ Cohen, JI Rau, MT AF Graville, DJ Cohen, JI Rau, MT TI Acoustic parameters that identify listeners' perceptions of good near-total laryngectomy voice SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID TRACHEOESOPHAGEAL SPEECH; FREQUENCY; SPEAKERS; SHUNT AB Ten near-total laryngectomy (NTL) speakers performed a number of voicing tasks that were recorded for acoustic, temporal, and aerodynamic feature analysis. A paired comparison within groups design was used to objectify the perceptual parameters that constitute good near-total laryngectomized voice. The pairs were judged by three speech-language pathologist who chose which subject sounded "most like normal." The judgments were used to assign the NTL speakers into three groups (Most Like Normal, Middle, Least Like Normal). The analysis revealed that listeners could reliably rate NTL speakers as Most Like Normal (MLN). A correlation was found between listener ratings and the acoustic parameter shimmer (r = .684, p = .021). No other significant correlations were noted. A step-wise regression revealed that speaker rating could be predicted by shimmer, H/N ratio, jitter, weight, and flow. These parameters accounted for 93% of the variance. C1 Oregon Hlth Sci Univ, Dept Otolaryngol, NW Clin Voice & Swallowing, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Graville, DJ (reprint author), Oregon Hlth Sci Univ, Dept Otolaryngol, NW Clin Voice & Swallowing, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM graville@ohsu.edu NR 23 TC 1 Z9 1 U1 0 U2 0 PU DELMAR LEARNING PI CLIFTON PARK PA EXECUTIVE WOODS, 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD SEP PY 2004 VL 12 IS 3 BP 107 EP 116 PG 10 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 853RZ UT WOS:000223846600007 ER PT J AU Biederman, J Petty, C Faraone, SV Seidman, L AF Biederman, J Petty, C Faraone, SV Seidman, L TI Phenomenology of childhood psychosis - Findings from a large sample of psychiatrically referred youth SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE psychosis; delusions; hallucinations; children ID EARLY-ONSET SCHIZOPHRENIA; NONPSYCHOTIC CHILDREN; FOLLOW-UP; EMOTIONAL DISORDERS; YOUNG-CHILDREN; RISK-FACTORS; HALLUCINATIONS; ADOLESCENTS; COMORBIDITY; SYMPTOMS AB Our objective was to evaluate the scope and clinical correlates of psychotic phenomena in psychiatrically referred children and adolescents. Subjects were 1657 psychiatrically referred youth (mean age = 10.9 years) evaluated from 1991 to 2002. DSM-III-R diagnoses were obtained through maternal report by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version. Childhood-onset psychosis was defined by the presence of delusions or hallucinations. Childhood-onset psychosis was identified in 8% of psychiatrically referred youth. It was associated with a chronic course and high levels of impairment. Comorbidity with disruptive, mood, and anxiety disorders was very severe, with only one of the 132 identified youth with psychosis not having at least one comorbidity. In conclusion, childhood-onset psychosis in referred youth is common and highly morbid. It remains an important topic of research deserving full clinical and scientific attention. C1 Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Johnson & Johnson Ctr Pediat Psychopathol, Boston, MA USA. RP Biederman, J (reprint author), 55 Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 47 TC 16 Z9 18 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2004 VL 192 IS 9 BP 607 EP 614 DI 10.1097/01.nmd.0000138228.59938.c3 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 856GS UT WOS:000224034300005 PM 15348977 ER PT J AU Brickman, AM Buchsbaum, MS Bloom, R Bokhoven, P Paul-Odouard, R Haznedar, MM Dahlman, KL Hazlett, EA Aronowitz, J Heath, D Shihabuddin, L AF Brickman, AM Buchsbaum, MS Bloom, R Bokhoven, P Paul-Odouard, R Haznedar, MM Dahlman, KL Hazlett, EA Aronowitz, J Heath, D Shihabuddin, L TI Neuropsychological functioning in first-break, never-medicated adolescents with psychosis SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL Colorado Springs, CO DE cognition; neuropsychological functioning; adolescent; psychosis; schizophrenia ID CHILDHOOD-ONSET SCHIZOPHRENIA; FIRST-EPISODE SCHIZOPHRENIA; GLUCOSE METABOLIC-RATE; 1ST-EPISODE SCHIZOPHRENIA; COGNITIVE IMPAIRMENT; GENDER DIFFERENCES; SEX-DIFFERENCES; STRIATAL SIZE; DEFICITS; DISORDER AB The purpose of the current study was to examine neuropsychological functioning in a group of never-medicated first-break adolescents with psychosis. It is the first report of cognition in a sample of adolescents with psychosis in which all patients were drug-naive. Twenty-nine adolescent patients (mean age = 16.07; SD = 2.00; 15 male and 14 female patients) experiencing their first psychotic episode and 17 age-matched and sex-matched normal volunteers (mean age = 16.88; SD = 2.39; 9 male and 8 female subjects) were recruited and assessed with a neuropsychological battery. Measures of attention, memory, language, executive functioning, perceptual motor processing, and motor speed were obtained. Psychiatric symptomatology, estimated verbal IQ, and parental socioeconomic status were also determined. Patients with psychosis were significantly more impaired than normal volunteers; effect sizes were greatest in the areas of executive functioning, attention, and memory, and significantly smaller in areas of language, perceptual motor processing, and motor speed. The pattern was not altered when differences in verbal IQ and parental socioeconomic status were controlled. Sex and age interactions indicated that younger male patients were particularly impaired. The findings demonstrate neuropsychological deficits in adolescents with psychosis and suggest that cognitive deficits are core symptoms in psychotic disorders. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Neurosci PET Lab, New York, NY 10029 USA. Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimer Dis & Aging Brain, New York, NY USA. Brown Med Sch, Dept Psychait & Behav Med, Providence, RI USA. Bronx Vet Adm Med Ctr, Dept Vet Affairs, Bronx, NY USA. RP Brickman, AM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Neurosci PET Lab, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH56489, MH60023, MH60384S] NR 55 TC 55 Z9 56 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2004 VL 192 IS 9 BP 615 EP 622 DI 10.1097/01.nmd.0000138229.29157.3e PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 856GS UT WOS:000224034300006 PM 15348978 ER PT J AU Hammerness, P AF Hammerness, P TI The development of psychopathology: Nature and nurture SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02115 USA. RP Hammerness, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2004 VL 192 IS 9 BP 640 EP 640 DI 10.1097/01.nmd.0000138322.29220.54 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 856GS UT WOS:000224034300012 ER PT J AU Lessell, S AF Lessell, S TI Friendly fire: Neurogenic visual loss from radiation therapy SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 15-18, 2003 CL ANAHEIM, CA SP Amer Acad Ophthalmol ID INDUCED OPTIC NEUROPATHY; CENTRAL-NERVOUS-SYSTEM; MAGNETIC-RESONANCE SPECTROSCOPY; HYPERBARIC-OXYGEN THERAPY; INDUCED DAMAGE; BRAIN; RADIOSURGERY; IRRADIATION; INJURY; TUMORS AB The author's experience and review of the medical literature suggest that radiation-induced neuro genic visual loss presents on average 18 months after treatment and Usually after cumulative doses of radiation that exceed 50 Gy or single doses to the visual apparatus of Greater than 10 Gy. Visual loss may result from lesions of the disc, retrobulbar segment of the optic nerve, optic chiasm, or retrogeniculate pathways. Magnetic resonance imaging, the best means of demonstrating radiation injury to the visual pathway, may show abnormalities before the loss of vision. The second eye may show clinical manifestations of optic neuropathy many months after the diagnosis in the first involved eye. Spontaneous improvement in visual function may rarely occur. Treatment has been disappointing, but if visual dysfunction is detected early, hyperbaric oxygen might be beneficial. The risk of neurogenic visual loss must be factored into the decision to irradiate the brain. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lessell, S (reprint author), 243 Charles St, Boston, MA 02114 USA. EM simmons_lessell@meei.Harvard.edu NR 54 TC 32 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2004 VL 24 IS 3 BP 243 EP 250 DI 10.1097/00041327-200409000-00014 PG 8 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 851TL UT WOS:000223708300014 PM 15348995 ER PT J AU Jiang, JF Borisenko, GG Osipov, A Martin, I Chen, RW Shvedova, AA Sorokin, A Tyurina, YY Potapovich, A Tyurin, VA Graham, SH Kagan, VE AF Jiang, JF Borisenko, GG Osipov, A Martin, I Chen, RW Shvedova, AA Sorokin, A Tyurina, YY Potapovich, A Tyurin, VA Graham, SH Kagan, VE TI Arachidonic acid-induced carbon-centered radicals and phospholipid peroxidation in cyclo-oxygenase-2-transfected PC12 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE carbon-centered radical formation; cyclo-oxygenase-2 inhibitor; cyclo-oxygenase-2 transfection; PC12 cells; phosphatidylserine oxidation; radical spin-trapping ID PROSTAGLANDIN-H SYNTHASE-2; CEREBRAL-ARTERY OCCLUSION; TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD NEURONS; OXIDATIVE STRESS; OXYGEN RADICALS; ISCHEMIC BRAIN; CYTOCHROME-C; INDUCIBLE CYCLOOXYGENASE AB Cyclo-oxygenase-2 (COX-2) is believed to induce neuronal oxidative stress via production of radicals. While oxygen radicals are not directly involved in COX-2-catalytic cycle, superoxide anion radicals have been repeatedly reported to play a critical role in COX-2-associated oxidative stress. To resolve the controversy, we characterized production of free radicals in PC12 cells in which COX-2 expression was manipulated either genetically or by direct protein transfection and compared them with those generated by a recombinant COX-2 in a cell-free system. Using spin-traps alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone, 5,5-dimethyl-1-pyrroline-N-oxide and 4-((9-acridinecarbonyl) amino)-2,2,6,6- tetramethylpiperidine-1-oxyl (Ac-Tempo), we observed arachidonic acid (AA)-dependent production of carbon-centered radicals by heme-reconstituted recombinant COX-2. No oxygen radicals or thiyl radicals have been detected. COX-2 also catalyzed AA-dependent one-electron co-oxidation of ascorbate to ascorbate radicals. Next, we used two different approaches of COX-2 expression in cells, PCXII cells which express isopropyl-1-thio-beta-D-galactopyranoside inducible COX-2, and PC12 cells transfected with COX-2 using a protein delivery reagent, Chariot. In both models, COX-2-dependent AA-induced generation of carbon-centered radicals was documented using spin-traps and Ac-Tempo. No oxygen radical formation was detected in COX-2-transfected cells by either spin-traps or fluorogenic probe, dihydroethidium. In the presence of ascorbate, AA-induced COX-2-dependent ascorbate radicals were detected. AA caused a significant and selective oxidation of one of the major phospholipids, phosphatidylserine (PS). PS was not a direct substrate for COX-2 but was co-oxidized in the presence of AA. The radical generation and PS oxidation were inhibited by COX-2 inhibitors, niflumic acid, nimesulide, or NS-398. Thus, COX-2 generated carbon-centered radicals but not oxygen radicals or thiyl radicals are responsible for oxidative stress in AA-challenged PC12 cells overexpressing COX-2. C1 Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. NIOSH, Hlth Effects Lab Div, Morgantown, WV USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Cardiovasc Res Ctr, Milwaukee, WI 53226 USA. VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Kagan, VE (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, 3343 Forbes Ave, Pittsburgh, PA 15260 USA. EM kagan+@pitt.edu OI Tyurin, Vladimir/0000-0002-3474-1697; Sorokin, Andrey/0000-0002-5660-0190 FU NINDS NIH HHS [F05 NS 43922, NS 30318, NS 37459, R01 NS037459, R01 NS037459-07] NR 73 TC 44 Z9 47 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2004 VL 90 IS 5 BP 1036 EP 1049 DI 10.1111/j.1471-4159.2004.02577.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 847CN UT WOS:000223366500002 PM 15312159 ER PT J AU Greve, B Weissert, R Bettelli, E Sobel, RA Pasparakis, M Coyle, AJ Kuchroo, V Rajewsky, K Schmidt-Supprian, M AF Greve, B Weissert, R Bettelli, E Sobel, RA Pasparakis, M Coyle, AJ Kuchroo, V Rajewsky, K Schmidt-Supprian, M TI High threshold for autoantigen-specific stimulation and induction of experimental autoimmune encephalomyelitis in T cell-specific IKK2-deficient mice SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Hertie Inst Clin Brain Res, Tubingen, Germany. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. EMBL Monterotondo, Monterotondo, Italy. Millenium Pharmaceut, Cambridge, MA USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 199 BP 61 EP 61 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200204 ER PT J AU Jones, RE Kitzerow, N Estrada, M Moes, N Vandenbark, A Offner, H Whitham, R Bourdette, D AF Jones, RE Kitzerow, N Estrada, M Moes, N Vandenbark, A Offner, H Whitham, R Bourdette, D TI Central nervous system antigen presenting cells develop from distinct subset of bone marrow cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Nancy Davis Ctr Walls, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 211 BP 66 EP 66 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200216 ER PT J AU Lango, RP Stiles, CD Rowitch, DH Alberta, JA John, G Cannella, B Raine, CS AF Lango, RP Stiles, CD Rowitch, DH Alberta, JA John, G Cannella, B Raine, CS TI Early oligodendroglial lineage gene expression in multiple sclerosis (MS) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Albert Einstein Coll Med, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 382 BP 115 EP 115 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200387 ER PT J AU Frenkel, D Huang, Z Maron, R Koldzic, DN Hancock, WW Moskowitz, M Weiner, HL AF Frenkel, D Huang, Z Maron, R Koldzic, DN Hancock, WW Moskowitz, M Weiner, HL TI Immune therapy of stroke: nasal vaccination with MOG reduces stroke size by inducing IL-10 producing CD4+T cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Penn, Philadelphia, PA 19104 USA. RI Moskowitz, Michael/D-9916-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 544 BP 164 EP 164 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200549 ER PT J AU Ottowitz, WE Dougherty, DD Sirota, A Niaura, R Rauch, SL Brown, WA AF Ottowitz, WE Dougherty, DD Sirota, A Niaura, R Rauch, SL Brown, WA TI Neural and endocrine correlates of sadness in women: Implications for neural network regulation of HPA activity SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MEDIAL PREFRONTAL CORTEX; CORTICOTROPIN-RELEASING FACTOR; MOOD DISORDERS; DEPRESSED-PATIENTS; GENDER-DIFFERENCES; NEGATIVE AFFECT; BRAIN ACTIVITY; CORTISOL; STRESS; NEUROCIRCUITRY AB In order to evaluate the suprahypothalamic neuroanatomical sites of relevance to adrenocorticotropic hormone (ACTH) and cortisol regulation, single photon emission computed tomography (SPECT) investigation of induced sadness was combined with a linear regression analysis of these hormone levels during mood induction. Images from eight healthy women were analyzed by statistical parametric mapping (SPM), replicating many findings from prior sadness induction studies. Statistical parametric mapping endocrine covariate analysis showed that the ventromedial pre-frontal, anterior cingulate, and insular cortices may regulate ACTH and the insular cortex may be related to regulation of cortisol during sadness. Dysfunction of these sites may contribute to the cortisol dysregulation observed in some subjects with major depression. C1 St Elizabeth Hosp, Dept Nucl Med, Boston, MA USA. RP Ottowitz, WE (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Bldg 149,2nd Floor,13th St, Charlestown, MA 02129 USA. EM ottowitz@nmr.mgh.harvard.edu FU NIMH NIH HHS [K23 MH-01735] NR 49 TC 27 Z9 27 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2004 VL 16 IS 4 BP 446 EP 455 DI 10.1176/appi.neuropsych.16.4.446 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 881VN UT WOS:000225897600007 PM 15616171 ER PT J AU Frank, LM Stanley, GB Brown, EN AF Frank, LM Stanley, GB Brown, EN TI Hippocampal plasticity across multiple days of exposure to novel environments SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; learning; memory; spatial; adaptive estimation; place cells ID RECEPTIVE-FIELD PLASTICITY; LONG-TERM POTENTIATION; ENTORHINAL CORTEX; PLACE CELLS; UNIT-ACTIVITY; BEHAVING RAT; SPATIAL MAP; NEURONS; MEMORY; LESIONS AB The hippocampus is essential for learning complex spatial relationships, but little is known about how hippocampal neural activity changes as animals learn about a novel environment. We studied the formation of new place representations in rats by examining the changes in place-specific firing of neurons in the CA1 region of the hippocampus and the relationship between these changes and behavioral change across multiple days of exposure to novel places. We found that many neurons showed very rapid changes on the first day of exposure to the novel place, including many cases in which a previously silent neuron developed a place field over the course of a single pass through the environment. Across the population, the largest changes in neural activity occurred on day 2 of exposure to a novel place, but only if the animal had little experience (<4 min) in that location on day 1. Longer exposures on day 1 were associated with smaller changes on day 2, suggesting that hippocampal neurons required 5-6 min of experience to form a stable spatial representation. Even after the representation stabilized, the animals' behavior remained different in the novel places, suggesting that other brain regions continued to distinguish novel from familiar locations. These results show that the hippocampus can form new spatial representations quickly but that stable hippocampal representations are not sufficient for a place to be treated as familiar. C1 Univ Calif San Francisco, Dept Physiol, Keck Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Frank, LM (reprint author), Univ Calif San Francisco, Dept Physiol, Keck Ctr Integrat Neurosci, S-762,513 Parnassus Ave, San Francisco, CA 94143 USA. EM loren@phy.ucsf.edu; brown@neurostat.mgh.harvard.edu OI Frank, Loren/0000-0002-1752-5677 FU NIDA NIH HHS [DA015644, R01 DA015644]; NIMH NIH HHS [F32 MH065108, K02 MH061637, MH59733, MH61673, MH65108, R01 MH059733] NR 50 TC 162 Z9 165 U1 0 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 SEP 1 PY 2004 VL 24 IS 35 BP 7681 EP 7689 DI 10.1523/JNEUROSCI.1958-04.2004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 851ZL UT WOS:000223724900011 PM 15342735 ER PT J AU Liang, QH Liou, AKF Ding, YM Cao, GD Xiao, X Perez, RG Chen, J AF Liang, QH Liou, AKF Ding, YM Cao, GD Xiao, X Perez, RG Chen, J TI 6-hydroxydopamine induces dopaminergic cell degeneration via a caspase-9-mediated apoptotic pathway that is attenuated by caspase-9dn expression SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE MN9D; 6-OHDA; caspase; apoptosis; caspase-9dn ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; FOCAL CEREBRAL-ISCHEMIA; CYTOCHROME-C RELEASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; MITOCHONDRIAL RELEASE; PRIMARY CULTURES; DEATH PROGRAM AB This study showed that primary dopaminergic neurons or the dopaminergic cell line MN9D, when exposed to 15 min of the parkinsonian toxin 6-hydroxydopamine (6-OHDA) in the range of 30-100 muM, underwent delayed degeneration and exhibited hallmarks of apoptosis. These results, along with the absence of any increase in lactate dehydrogenase (LDH) release from the degenerated cells, imply that apoptosis was the dominant mode of cell death. Moreover, a distinct elevation in the measured cellular activities of caspase-9 and -3 but not of caspase-8 points to the caspase-9/caspase-3 cascade as the predominant apoptotic pathway in the degeneration of dopaminergic neurons and MN9D cells. In addition, the presence of caspase-9 or -3 peptide inhibitors but not of caspase-8 inhibitor attenuated cell death significantly, supporting the notion that only the intrinsic apoptotic pathway is utilized to achieve cell death. Finally, overexpression of a mutant caspase-9 with dominant negative phenotype (caspase-9dn) in MN9D cells and primary dopaminergic neurons via the adenovirus and adenoassociated virus gene delivery system, respectively, conferred marked increases in tolerance to the toxicity of 6-OHDA. These results point to the intrinsic caspase-9/caspase-3 cascade as the predominant signaling pathway underlying dopaminergic cell death induced by 6-OHDA and suggest that gene delivery of caspase-9dn can attenuate this pathway and its degenerative consequences. (C) 2004 Wiley-Liss, Inc. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Pittsburgh Inst Neurodegenerat Disorders, Pittsburgh, PA USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S507 Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15261 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [NS44178, NS43802, NS45048, P01 NS059806, R01 NS044178] NR 60 TC 28 Z9 30 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 2004 VL 77 IS 5 BP 747 EP 761 DI 10.1002/jnr.20198 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 852DL UT WOS:000223735300015 PM 15352222 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, RA Panizzon, KL TI Simvastatin provides protection against CA1 traumatic neuronal injury SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 22nd Annual National-Neurotrauma-Society Symposium CY OCT 20-22, 2004 CL San Diego, CA SP Natl Neurotrauma Soc DE statin; CA1; trauma; LTR; neuron C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2004 VL 21 IS 9 MA P268 BP 1330 EP 1330 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 855HC UT WOS:000223962900271 ER PT J AU Panizzon, KL Wallis, RA AF Panizzon, KL Wallis, RA TI Modulation of the mitochondrial ATP-sensitive potassium channel by diazoxide provides protection against CA1 traumatic neuronal injury SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 22nd Annual National-Neurotrauma-Society Symposium CY OCT 20-22, 2004 CL San Diego, CA SP Natl Neurotrauma Soc DE trauma; CA1; mitochondria; potassium channels; ATP C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2004 VL 21 IS 9 MA P271 BP 1331 EP 1331 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 855HC UT WOS:000223962900273 ER PT J AU Bermpohl, D You, Z Lai, C Moskowitz, MA Whalen, MJ AF Bermpohl, D You, Z Lai, C Moskowitz, MA Whalen, MJ TI Cell death and neurologic dysfunction after controlled cortical impact in immature mice deficient in TNF alpha and Fas genes SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 22nd Annual National-Neurotrauma-Society Symposium CY OCT 20-22, 2004 CL San Diego, CA SP Natl Neurotrauma Soc DE immature TBI model; cell death; death receptors C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RI Moskowitz, Michael/D-9916-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2004 VL 21 IS 9 MA P277 BP 1332 EP 1332 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 855HC UT WOS:000223962900278 ER PT J AU Whalen, M Bermpohl, D Qiu, J Dalkara, T Bhide, P Lai, Y Moskowitz, M AF Whalen, M Bermpohl, D Qiu, J Dalkara, T Bhide, P Lai, Y Moskowitz, M TI In vivo propidium iodide and ex vivo TUNEL identifies necrosis and apoptosis in discreet brain cell populations after controlled cortical impact in mice. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 22nd Annual National-Neurotrauma-Society Symposium CY OCT 20-22, 2004 CL San Diego, CA SP Natl Neurotrauma Soc DE traumatic brain injury; necrosis; apoptosis; TUNEL; propidium iodide C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2004 VL 21 IS 9 MA P286 BP 1334 EP 1334 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 855HC UT WOS:000223962900288 ER PT J AU Torabi, M Aquino, SL Harisinghani, MG AF Torabi, M Aquino, SL Harisinghani, MG TI Current concepts in lymph node imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE cancer staging; lymph node imaging; lymph node metastasis; malignant lymphadenopathy; nodal morphology; MRI; CT; PET; ultrasound ID POSITRON-EMISSION-TOMOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; CELL LUNG-CANCER; INITIAL CLINICAL-EXPERIENCE; UTERINE CERVICAL-CARCINOMA; BREAST-CANCER; PROSTATE-CANCER; PATHOLOGICAL CORRELATION; COMPUTED-TOMOGRAPHY; FLUORINE-18-FDG PET AB The accurate identification and characterization of lymph nodes by imaging has important therapeutic and prognostic significance in patients with newly diagnosed cancers. The presence of nodal metastases limits the therapeutic options and also generally indicates worse prognosis in patients. Thus, it becomes crucial to have this information before commencing therapy. Current cross-sectional imaging modalities rely on insensitive size and morphologic criteria and, thus, lack the desired accuracy for characterizing lymph nodes. This is mainly because metastases can be present in non-enlarged lymph nodes and not all enlarged nodes are malignant. PET has overcome some of these limitations but is still constrained by current resolution limits for small nodal metastases. This has fueled the development of targeted techniques for nodal imaging and characterization as outlined in this article. In the past few years, studies have shown that these newer imaging techniques can bridge some of the limitations of existing imaging for nodal characterization and thereby provide the much-needed staging information before the initiation of therapy. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 82 TC 91 Z9 104 U1 2 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2004 VL 45 IS 9 BP 1509 EP 1518 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 853EM UT WOS:000223809500018 PM 15347718 ER PT J AU Halmos, DR Ellis, E Dodson, TB AF Halmos, DR Ellis, E Dodson, TB TI Mandibular third molars and angle fractures SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RISK-FACTOR AB Purpose: The study purpose was to measure associations between mandibular third molar (M3) status/position and risk for angle fracture. Materials and Methods: We designed a multicenter retrospective cohort study composed of patients who presented for operative management of mandible fractures. The primary predictor variable was M3 (present/absent). The secondary predictor variable was M3 position classified using the Pell and Gregory system. The outcome variable was angle fracture (present/absent). Appropriate univariate, bivariate, and multivariate logistic regression analyses were computed. The level of statistical significance was set at P less than or equal to.05. Results: The study sample was composed of 1,450 subjects with a mean age of 30.6 +/- 10.4 years (range, 2 to 87 years). The risk of an angle fracture with and without M3s was 30.1% and 13.7%, respectively (adjusted odds ratio, 2.8; 95% confidence interval, 2.3 to 3.4; P <.001). Based on the Pell and Gregory classification, varying M3 position was associated with varying risks of angle fracture (P <.001). Conclusion: The presence of M3s was associated with a 2.8-fold increased risk for angle fractures. M3 position was associated with a variable risk for angle fracture. Notably, the deep impactions were not associated with an increased risk for fracture. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA. Univ Texas, SW Med Ctr, Dept Surg, Div Oral & Maxillofacial Surg, Dallas, TX USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tdodson@partners.org FU NIDCR NIH HHS [K24 DE000448] NR 13 TC 26 Z9 28 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2004 VL 62 IS 9 BP 1076 EP 1081 DI 10.1016/j.joms.2004.04.012 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 851TT UT WOS:000223709300006 PM 15346357 ER PT J AU Ho, CL Walton, DS AF Ho, CL Walton, DS TI Primary congenital glaucoma: 2004 update SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Review ID REFRACTORY PEDIATRIC GLAUCOMA; DIODE-LASER CYCLOPHOTOCOAGULATION; AQUEOUS-HUMOR FLOW; MITOMYCIN-C; DEVELOPMENTAL GLAUCOMA; INTRAOCULAR-PRESSURE; GENETIC-HETEROGENEITY; TOPICAL BRIMONIDINE; CLINICAL-EXPERIENCE; INFANTILE GLAUCOMA AB Background: Primary congenital glaucoma is the most frequent childhood glaucoma and an important cause of blindness. We describe the current understanding regarding this disease, the evaluation of children with it, and its treatment. Patients and Methods: We accessed information derived from a review of 287 patients with primary congenital glaucoma and current published data related to primary congenital glaucoma. Results: The nomenclature for childhood glaucoma has been inconsistent, but Is clarified for children with primary congenital glaucoma. The epidemiology of primary congenital glaucoma notes its variable Incidence worldwide. Familial occurrence supports autosomal recessive transmission; chromosomal loci have been identified, and the CYP1B1 gene has been identified and clinically correlated. The histopathology of eyes with primary congenital glaucoma confirms the presence of a variable trabecular meshwork anomaly and the absence of an imperforate membrane. Children with primary congenital glaucoma are diagnosed after recognition of corneal signs and symptoms of glaucoma. Conclusions: The examinations of patients with primary congenital glaucoma must be thorough to distinguish this glaucoma from other types of childhood glaucoma, to prepare for surgery, and to follow progress with treatment. Medical treatment must be tailored to the pediatric patient. Goniosurgery is the definitive procedure of choice for most children with primary congenital glaucoma, but other procedures are also used successfully after goniosurgery falls or is determined to be inappropriate. Future success will be determined by physicians who sustain continued progress for children with glaucoma. C1 Singapore Natl Eye Ctr, Singapore, Singapore. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. NR 101 TC 49 Z9 57 U1 1 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD SEP-OCT PY 2004 VL 41 IS 5 BP 271 EP 288 PG 18 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 854XR UT WOS:000223937700004 PM 15478740 ER PT J AU Simon, NM Otto, MW Smits, JA Nicolaou, DC Reese, HE Pollack, MH AF Simon, NM Otto, MW Smits, JA Nicolaou, DC Reese, HE Pollack, MH TI Changes in anxiety sensitivity with pharmacotherapy for panic disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE anxiety sensitivity; panic; pharmacotherapy; Benzodiazepines; ASI; treatment outcome ID BEHAVIOR-THERAPY; ATTACKS; DEPRESSION; AGORAPHOBIA AB Fear of anxiety symptoms (anxiety sensitivity) has been implicated in the etiology and maintenance of panic disorder, and has been shown to improve with cognitive-behavioral treatment. The impact of pharmacotherapy on anxiety sensitivity is less clear. We administered the Anxiety Sensitivity Index (ASI) during a 12-week randomized controlled trial investigating the relative efficacy of paroxetine, paroxetine plus sustained clonazepam, and paroxetine plus brief clonazepam for patients with panic disorder. We found a mean reduction in ASI scores of 9.6 points, which correlated with symptomatic improvement, and did not differ significantly between groups. Our data provides further evidence that pharmacotherapy leads to significant acute reductions in fears of anxiety symptoms in patients with panic disorder, albeit at levels that may be somewhat less than the changes associated with CBT. Implications of these findings are discussed relative to optimizing pharmacologic treatment of panic disorder. (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, WACC-812,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org RI Smits, Jasper/A-4350-2008; OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 NR 35 TC 19 Z9 19 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD SEP-OCT PY 2004 VL 38 IS 5 BP 491 EP 495 DI 10.1016/j.jpsychires.2004.01.004 PG 5 WC Psychiatry SC Psychiatry GA 861VH UT WOS:000224446200005 PM 15380399 ER PT J AU Koenigsberg, HW Teicher, MH Mitropoulou, V Navalta, C New, AS Trestman, R Siever, LJ AF Koenigsberg, HW Teicher, MH Mitropoulou, V Navalta, C New, AS Trestman, R Siever, LJ TI 24-h monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; circadian rhythm; norepinephrine; cortisol; MHPG; Dysregulation ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSION; ENDOGENOUS-DEPRESSION; CIRCADIAN-RHYTHMS; DIURNAL RHYTHM; PHASE-ADVANCE; SECRETION; METABOLITES; ILLNESS; PSYCHONEUROENDOCRINOLOGY AB Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms. Method: Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers. Results: The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls. Conclusions: These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression. Published by Elsevier Ltd. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr 116A, Bronx, NY 10468 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Vet Hlth Adm, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Koenigsberg, HW (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. EM harold.koenigsberg@med.va.gov OI Trestman, Robert/0000-0002-3306-4380 FU NCRR NIH HHS [5M01 RR00071] NR 51 TC 46 Z9 51 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD SEP-OCT PY 2004 VL 38 IS 5 BP 503 EP 511 DI 10.1016/j.jpsychires.2004.03.006 PG 9 WC Psychiatry SC Psychiatry GA 861VH UT WOS:000224446200007 PM 15380401 ER PT J AU Swanson, JM Biederman, J Boellner, SW Lopez, FA AF Swanson, JM Biederman, J Boellner, SW Lopez, FA TI Modafinil as therapy for ADHD in children: A 4-week, doubleblind, placebo-controlled study SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 25-28, 2004 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Univ Calif Irvine, Irvine, CA USA. Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2004 VL 18 IS 3 SU S BP A53 EP A53 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 863HC UT WOS:000224550800207 ER PT J AU Tsapakis, EM Grady, CJ Andersen, SL Tarazi, F Zhang, J Baldessarini, RJ AF Tsapakis, EM Grady, CJ Andersen, SL Tarazi, F Zhang, J Baldessarini, RJ TI Working memory: Regulation by dopamine D-4 receptors in rat brain SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 25-28, 2004 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2004 VL 18 IS 3 SU S BP A62 EP A62 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 863HC UT WOS:000224550800246 ER PT J AU Douglas, G Reilly, C Dooley, MA Page, G Cooper, G Gilkeson, G AF Douglas, G Reilly, C Dooley, MA Page, G Cooper, G Gilkeson, G TI Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; nitric oxide; genetics; predisposition; angiotensin-converting enzyme; African American; polymorphism ID CORONARY-ARTERY-DISEASE; GENE POLYMORPHISM; DELETION POLYMORPHISM; DIABETIC-NEPHROPATHY; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; 5'-FLANKING REGION; HEART-DISEASE; ACE GENE; ASSOCIATION AB Objective. Genetic polymorphisms in the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) are linked with expression and/or progression of renal disease. We hypothesized that polymorphisms in the genes coding for ACE and eNOS may influence the development and/or progression of systemic lupus erythematosus (SLE) and lupus nephritis given their linkage with other renal diseases. Methods. DNA from patients with SLE (n = 227) and their age and sex matched controls (n = 275) from the Carolina Lupus (CLU) Study cohort was assessed for ACE and eNOS polymorphisms. Seventy patients had biopsy-proven lupus nephritis. Two different eNOS polymorphisms (eNOS promoter T-786-->C nucleotide substitution and eNOS 27 base pair tandem repeat in intron 4) and the ACE insertion/deletion (I/D) polymorphism in intron 16 were examined by restriction fragment length polymorphism-polymerase chain reaction. Results. Allele frequency of the eNOS polymorphisms varied significantly between SLE patients and controls. There was no association of these polymorphisms with lupus within ethnic groups. We found no association of the polymorphism with the development of renal disease. No association was observed for the ACE I/D polymorphism with SLE or nephritis, or with ethnicity or sex. Conclusion. eNOS genetic polymorphisms differed significantly across ethnic groups. There was no significant increased risk of SLE and/or lupus nephritis associated with eNOS or ACE polymorphisms in either the African American or Caucasian groups compared to ethnically matched controls. These studies emphasize the need to control for ethnicity when investigating genetic polymorphisms and disease. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Edward Via Virginia Coll Osteopath Med, Dept Physiol, Blacksburg, VA USA. Univ N Carolina, Affiliated Hosp, Dept Med, Chapel Hill, NC USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Gilkeson, G (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. EM gilkeson@musc.edu FU NIAID NIH HHS [AI41764]; NIAMS NIH HHS [AR39162, AR45476] NR 43 TC 22 Z9 22 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2004 VL 31 IS 9 BP 1756 EP 1762 PG 7 WC Rheumatology SC Rheumatology GA 852ZS UT WOS:000223796200016 PM 15338496 ER PT J AU Burman, ML Kivlahan, D Buchbinder, M Broglio, K Zhou, XH Merrill, JO McDonell, MB Fihn, SD Bradley, KA AF Burman, ML Kivlahan, D Buchbinder, M Broglio, K Zhou, XH Merrill, JO McDonell, MB Fihn, SD Bradley, KA CA Ambulatory Care Quality Improveme TI Alcohol-related advice for veterans affairs primary care patients: Who gets it? Who gives it? SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID BEHAVIORAL-COUNSELING INTERVENTIONS; RANDOMIZED CONTROLLED TRIAL; AT-RISK DRINKING; BRIEF PHYSICIAN; DRINKERS; MEDICINE; VA; CONSUMPTION; DISCUSSIONS; PREVENTION AB Objective: Most patients who misuse alcohol do not receive alcohol counseling from their providers. This study evaluated primary care patient and provider characteristics associated with receipt of alcohol-related advice and whether patients were advised to drink less or to abstain. Method: Outpatients from seven Veterans Affairs (VA) general medicine clinics were eligible if they screened positive for alcohol misuse, completed the Alcohol Use Disorders Identification Test (AUDIT) and answered questions about alcohol-related treatment and advice. Hierarchical logistic regression wag used to evaluate patient and provider characteristics associated with patient reports of alcohol-related advice from a primary care provider in the past year. Results: Among 5,191 patients with alcohol misuse in the past year, 1,554 (30%) reported receiving alcohol-related advice from their primary care provider during that time. Of patients advised, 73% reported advice to abstain. The likelihood of reporting advice increased as AUDIT scores increased: from 13% of patients with AUDIT scores <8 to 71% of those with scores greater than or equal to20. After adjustment for important confounders, measures reflecting the severity of alcohol misuse were most strongly associated with receipt of alcohol-related advice. Adjusted analyses also revealed increased odds of receiving advice among patients who reported liver disease, hypertension, current smoking or continuity of care. No measured provider characteristic was associated with giving advice in the fully adjusted model. Conclusions: This multisite VA study found that most patients with alcohol misuse did not receive alcohol counseling from a primary care provider. Moreover, providers predominantly offered advice to abstain, and they appeared to focus on patients with the most severe problems due to drinking or medical contraindications to drinking. C1 Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Case Western Reserve Univ, Dept Anthropol, Cleveland, OH 44106 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Harborview Med Ctr, Div Gen Internal Med, Seattle, WA 98104 USA. RP Bradley, KA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. EM willi@u.washington.edu OI Buchbinder, Mara/0000-0002-2319-662X FU NIAAA NIH HHS [K23 AA 00313] NR 38 TC 52 Z9 52 U1 3 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 2004 VL 65 IS 5 BP 621 EP 630 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 863VE UT WOS:000224590700009 PM 15536772 ER PT J AU Martin, B Alfers, J Kulig, C Clapp, L Bialkowski, D Bridgeford, D Beresford, TP AF Martin, B Alfers, J Kulig, C Clapp, L Bialkowski, D Bridgeford, D Beresford, TP TI Disulfiram therapy in patients with hepatitis C: A 12-month, controlled, follow-up study SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID ALCOHOLIC LIVER-DISEASE; AMINOTRANSFERASE LEVELS; VIRUS-RNA; ANTIBODIES; INTERFERON; CIRRHOSIS; RISK AB Objective: Although abstinence slows liver injury in alcoholic Hepatitis C (HCV) infected patients, few clinicians prescribe disulfiram because of concern over its hepatotoxic effect. Finding no controlled studies on this effect, we investigated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) patterns in seropositive (HCV[-]) and seronegative (HCV[-]) patients who received supervised disulfiram over 12 months. Method: We recorded retrospective aminotransferase measurements from medical records of 26 HCV(+) and 20 HCV(-) cases receiving 1,500 mg disulfiram weekly in divided doses. within groups, paired mean AST and ALT levels at 3, 6, 9 and 12 months were compared with baseline; between groups, nonpaired mean comparisons were used. Results: There were no statistically or clinically significant elevations for the HCV(+) group at any time point. Between-group means were identical at all time points. Conclusions: Although sample size and retrospective design invite replication, the data suggest that disulfiram may be useful for HCV(+) alcohol-dependent patients in slowing hepatic injury by eliminating alcohol use and thereby removing the purported alcohol-HCV hepatotoxic synergy. It may also help to establish the abstinence criteria necessary to qualify for antiviral treatment. If disulfiram is used in HCV treatment, AST and ALT must be monitored closely. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Martin, B (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.beresford@uchsc.edu FU NIAAA NIH HHS [R21 AA014010] NR 23 TC 9 Z9 9 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 2004 VL 65 IS 5 BP 651 EP 657 PG 7 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 863VE UT WOS:000224590700013 PM 15536776 ER PT J AU Patten, LC Belaguli, NS Baek, MJ Fagan, SP Awad, SS Berger, DH AF Patten, LC Belaguli, NS Baek, MJ Fagan, SP Awad, SS Berger, DH TI Serum response factor is alternatively spliced in human colon cancer SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE serum response factor; colon cancer; epithelial cells; alternative splicing ID INTESTINAL EPITHELIAL-CELLS; C-FOS GENE; MESSENGER-RNA; T-CELLS; TRANSCRIPTION; EXPRESSION; RAS; APOPTOSIS; ELEMENT; BINDING AB Background. Serum response factor (SRF) is a transcription factor that plays an important role in cellular differentiation and cell cycle regulation. SRF function is regulated in part by alternative splicing. Little is known about the expression or role of these alternatively spliced isoforms during tumorigenesis. We hypothesized that there is a change in the splice variants during intestinal tumorigenesis and that this change promotes the tumor phenotype. Materials and methods. SRF expression was determined by Western blotting of benign intestinal cells and human colon cancer cell lines. To determine the effect of alternative splicing of SRF on intestinal growth and proliferation, the predominant alternatively spliced isoform of SRF that we identified in colon cancer cells, SRFDelta5, was transfected into IEC-6 cells. IEC-6 and IEC-6SRFDelta5 cells were plated and cell numbers were determined at four time points. Results. Western blotting demonstrates that full-length SRF is the predominant form of SRF in rat IEC-6 cells, normal human colonic mucosa, and HT-29 cells, derived from a well-differentiated human colonic adenocarcinoma. In the colon cancer cell lines derived from poorly differentiated tumors (WiDr, HCT 116, LoVo, and SW480), SRFA5 is the predominant isoform expressed. There was a significant increase in cell survival in IEC-6 cells transfected with SRFA5 compared to parental cells. Conclusion. Our data demonstrate that an alternatively spliced isoform. of SRF, SRFA5, is expressed in human colon cancer cell lines. Additionally, these data demonstrate that expression of SRFA5 may contribute to the tumor phenotype by affecting cell survival. This is the first study to document a change in expression of the alternatively spliced isoform of SRF in human malignancy. (C) 2004 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Houston Vet Aff Hosp, Houston, TX 77030 USA. RP Berger, DH (reprint author), Houston VAMC, Surg Serv, OCL 112,2002 Holocombe Blvd, Houston, TX 77030 USA. EM dhb@bcm.tmc.edu NR 32 TC 12 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2004 VL 121 IS 1 BP 92 EP 100 DI 10.1016/j.jss.2004.02.031 PG 9 WC Surgery SC Surgery GA 847ZU UT WOS:000223437500015 PM 15313381 ER PT J AU Liberman, MC Zuo, J Guinan, JJ AF Liberman, MC Zuo, J Guinan, JJ TI Otoacoustic emissions without somatic motility: Can stereocilia mechanics drive the mammalian cochlea? SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OUTER HAIR-CELLS; BASILAR-MEMBRANE; MECHANOELECTRICAL TRANSDUCER; LOW-LEVEL; DISTORTION; POTENTIALS; FUROSEMIDE; RESPONSES; MODEL; ELECTROMOTILITY AB Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by similar to50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic.(CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear. (C) 2004 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcl@epl.meei.harvard.edu FU NCI NIH HHS [CA21765, P30 CA021765]; NIDCD NIH HHS [DC05168, F32 DC000188, R01 DC000235, DC00235, P30 DC005209, R21 DC005168, DC00188, DC04761, R01 DC000188] NR 35 TC 62 Z9 66 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2004 VL 116 IS 3 BP 1649 EP 1655 DI 10.1121/1.1775275 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 853OJ UT WOS:000223836600036 PM 15478431 ER PT J AU Bagnell, A Bostic, JQ AF Bagnell, A Bostic, JQ TI Building positive behavior support systems in schools: Functional behavioral assessment. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Dalhousie Univ, IWK Childrens Hlth Ctr, Halifax, NS, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bagnell, A (reprint author), Dalhousie Univ, IWK Childrens Hlth Ctr, Halifax, NS, Canada. NR 1 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2004 VL 43 IS 9 BP 1179 EP 1181 DI 10.1097/01.chi.0000132828.82347.70 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 848KU UT WOS:000223467200020 ER PT J AU Bagnell, A Bostic, JQ AF Bagnell, A Bostic, JQ TI Behavior psychology in the schools. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Dalhousie Univ, IWK Childrens Hlth Ctr, Halifax, NS, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Bagnell, A (reprint author), Dalhousie Univ, IWK Childrens Hlth Ctr, Halifax, NS, Canada. NR 1 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2004 VL 43 IS 9 BP 1179 EP 1181 DI 10.1097/01.chi.0000132828.82347.70 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 848KU UT WOS:000223467200021 ER PT J AU Soong, M Rubash, HE Macaulay, W AF Soong, M Rubash, HE Macaulay, W TI Dislocation after total hip arthroplasty SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID CONSTRAINED ACETABULAR COMPONENT; RECURRENT POSTERIOR DISLOCATION; CERAMIC-ON-POLYETHYLENE; FEMORAL-HEAD; CLOSED REDUCTION; RISK-FACTORS; REPLACEMENT; INSTABILITY; OSTEOTOMY; SALVAGE AB Dislocation is one of the most common complications after total hip arthroplasty (THA). Risk factors include neuromuscular and cognitive disorders, patient noncompliance, and previous hip surgery. Surgical considerations that must be addressed include approach, soft-tissue tension, component positioning, impingement, head size, acetabular liner profile, and surgeon experience. Recent improvements in posterior soft-tissue repair after primary THA have shown a reduced incidence of dislocation. When dislocation occurs, a thorough history, physical examination, and radiographic assessment help in choosing the proper intervention. Closed reduction usually is possible, and nonsurgical management frequently succeeds in preventing recurrence. When these measures fail, first-line revision options should target the underlying etiology. This most Often involves tensioning or augmentation of soft tissues, as in capsulorrhaphy or trochanteric advancement; correction of malpositioned components; or improving the head-to-neck ratio. If instability persists, or if a primary THA repeatedly dislocates without a clear cause, a constrained cup or bipolar femoral prosthesis may be as effective as a salvage procedure. C1 Columbia Univ, Ctr Hip & Knee Replacement, New York, NY 10032 USA. Harvard Univ, Combined Orthopaed Residency Program, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Macaulay, W (reprint author), Columbia Univ, Ctr Hip & Knee Replacement, PH 11th Floor,Rm 1146,622 W 168th St, New York, NY 10032 USA. NR 42 TC 74 Z9 88 U1 0 U2 2 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD SEP-OCT PY 2004 VL 12 IS 5 BP 314 EP 321 PG 8 WC Orthopedics SC Orthopedics GA 858KM UT WOS:000224190700005 PM 15469226 ER PT J AU MacNeill, BD Jang, IK Bouma, BE Iftimia, N Takano, M Yabushita, H Shishkov, M Kaufman, CR Houser, SL Aretz, HT DeJoseph, D Halpern, EF Tearney, GJ AF MacNeill, BD Jang, IK Bouma, BE Iftimia, N Takano, M Yabushita, H Shishkov, M Kaufman, CR Houser, SL Aretz, HT DeJoseph, D Halpern, EF Tearney, GJ TI Focal and multi-focal plaque distributions in patients with macrophage acute and stable presentations of coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; MONOCYTE-DERIVED MACROPHAGES; C-REACTIVE PROTEIN; ATHEROSCLEROTIC PLAQUES; UNSTABLE ANGINA; INTRAVASCULAR ULTRASOUND; MYOCARDIAL-INFARCTION; IN-VIVO; RUPTURE; INFLAMMATION AB OBJECTIVES This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome. BACKGROUND The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo. METHODS Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectorls, unstable angina pectoris, and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation. RESULTS A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80). CONCLUSIONS Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy. (C) 2004 by the American College of Cardiology Foundation. C1 Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Kinki Univ, Sch Med, Dept Cardiol, Kinki, Japan. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 703, Boston, MA 02114 USA. EM gtearney@partners.org FU NHLBI NIH HHS [5-R01-HL70039] NR 42 TC 143 Z9 152 U1 1 U2 6 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 SEP 1 PY 2004 VL 44 IS 5 BP 972 EP 979 DI 10.1016/j.jacc.2004.05.066 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850JW UT WOS:000223608200003 PM 15337206 ER PT J AU Gibson, CM Murphy, SA Kirtane, AJ Giugliano, RP Cannon, CP Antman, EM Braunwald, E AF Gibson, CM Murphy, SA Kirtane, AJ Giugliano, RP Cannon, CP Antman, EM Braunwald, E CA TIMI Study Grp TI Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; COMBINATION REPERFUSION THERAPY; TIMI FRAME COUNT; TO-BALLOON TIME; PERFUSION GRADE; THROMBOLYTIC THERAPY; TRIAL; MORTALITY; ANGIOPLASTY; ONSET AB OBJECTIVES We sought to determine if an underlying mechanism of the association between prolonged symptom-to-treatment times and adverse outcomes may be an association of symptom-to-treatment times with impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs). BACKGROUND Prolonged symptom duration among ST-segment elevation myocardial infarction (STEMI) patients undergoing fibrinolytic therapy is associated with adverse outcomes. METHODS Angiography was performed 60 min after fibrinolytic administration in 3,845 Thrombolysis In Myocardial Infarction (TIMI) trial patients. RESULTS The median time from symptom onset to treatment was longer among patients with impaired myocardial perfusion (3.0 h for TMPG 0/1 vs. 2.7 h for TMPG 2/3; p = 0.001). In a multivariate model, impaired tissue perfusion (TMPG 0/1) remained associated with increased time to treatment (odds ratio 1.14 per hour of delay; p = 0.007) even after adjusting for Thrombolysis In Myocardial Infarction flow grade (TFG) 3, left anterior descending infarct location, and baseline clinical characteristics. Impaired myocardial perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) was associated with longer median times to treatment (3.0 h for TMPG 2/3 vs. 2.7 h for TMPG 0/1; p = 0.017), as was abnormal epicardial flow after rescue/adjunctive PCI (3.3 h for TFG 0/1/2 vs. 2.8 h for TFG 3; p = 0.005). Thirty-day mortality was associated with longer time from onset of symptoms to treatment (6.6% mortality for time to treatment >4 h vs. 3.3%; p < 0.001), even among patients undergoing rescue PCI. CONCLUSIONS A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI. These data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired myocardial perfusion, and poor clinical outcomes. (C) 2004 by the American College of Cardiology Foundation C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Dept Med, Boston, MA USA. RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 26 TC 32 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 1 PY 2004 VL 44 IS 5 BP 980 EP 987 DI 10.1016/j.jacc.20043.05.059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850JW UT WOS:000223608200004 PM 15337207 ER PT J AU Alkhoury, F Malo, M Pushpakaran, P Zhang, WY Fleming, E Mozumder, M Hodin, R AF Alkhoury, F Malo, M Pushpakaran, P Zhang, WY Fleming, E Mozumder, M Hodin, R TI Gene regulation by endogenous thyroid hormone receptors in intestinal epithelial cells SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RI pushpakaran, dr prem raj/D-3540-2009 OI pushpakaran, dr prem raj/0000-0002-2289-5277 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S10 EP S10 PG 1 WC Surgery SC Surgery GA 852NA UT WOS:000223760800006 ER PT J AU Kumbhani, DJ Healey, N Thatte, H Crittenden, M Birjiniuk, V Treanor, P Khuri, S AF Kumbhani, DJ Healey, N Thatte, H Crittenden, M Birjiniuk, V Treanor, P Khuri, S TI Readmission after cardiac surgery: The role of intraoperative myocardial acidosis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 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 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S71 EP S71 PG 1 WC Surgery SC Surgery GA 852NA UT WOS:000223760800151 ER PT J AU Renaud, EJ Oliva, E Rueda, B MacLaughlin, D Donahoe, P AF Renaud, EJ Oliva, E Rueda, B MacLaughlin, D Donahoe, P TI Endometrial cancer expresses the Mullerian inhibiting substance (MIS) type II receptor and is growth inhibited by MIS SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S82 EP S83 PG 2 WC Surgery SC Surgery GA 852NA UT WOS:000223760800179 ER PT J AU Stoner, M Albadawi, H Casey, P Hua, H Cambria, R Watkins, M AF Stoner, M Albadawi, H Casey, P Hua, H Cambria, R Watkins, M TI Poly-ADP ribose polymerase inhibition in a murine model of thoracic aortic ischemia reperfusion: Renal and cardiac benefits SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S103 EP S104 PG 2 WC Surgery SC Surgery GA 852NA UT WOS:000223760800230 ER PT J AU Stoner, M Wong, D Agnihotri, A Hua, H Henderson, W Khuri, S Cambria, R Abbott, W AF Stoner, M Wong, D Agnihotri, A Hua, H Henderson, W Khuri, S Cambria, R Abbott, W TI A multicenter prospective analysis of 14,000 carotid endarterectomies SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 Massachusetts Gen Hosp, VA Boston Healthcare Syst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S72 EP S72 PG 1 WC Surgery SC Surgery GA 852NA UT WOS:000223760800154 ER PT J AU Riekse, RG Leverenz, JB McCormick, W Bowen, JD Teri, L Nochlin, D Simpson, K Eugenio, C Larson, EB Tsuang, D AF Riekse, RG Leverenz, JB McCormick, W Bowen, JD Teri, L Nochlin, D Simpson, K Eugenio, C Larson, EB Tsuang, D TI Effect of vascular lesions on cognition in Alzheimer's disease: A community-based study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 8th International Meeting on Alzheimers Disease and Related Disorders CY JUL 20-25, 2002 CL STOCKHOLM, SWEDEN SP Alzheimers Assoc DE Alzheimer's disease; vascular lesions; clinical-neuropathological; autopsy; dementia ID MINI-MENTAL-STATE; CLINICAL-DIAGNOSIS; AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E; ELDERLY PEOPLE; BLOOD-PRESSURE; UNITED-STATES; CASE SERIES; DEMENTIA; CERAD AB Objectives: To investigate whether clinical and neuropathological differences exist between Alzheimer's disease (AD) cases with and without vascular lesions neuropathologically diagnosed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Design: Descriptive observational study. Setting: A community-based registry that identified incident dementia cases. Participants: Of the 124 subjects with available clinical and neuropathological assessments, 30 had AD lesions alone, and 18 had AD with vascular lesions. Patients with other neuropathological findings were excluded. Measurements: Dependent measures included demographic, clinical, and neuropathological characteristics. Neuropathological diagnoses were made using the CERAD criteria and Braak and Braak staging. Results: Of the 124 autopsied cases, 85 cases were diagnosed with neuropathological AD. Of these, 30 had pathology consistent with "pure" AD, whereas 18 had AD pathology with significant vascular lesions (AD/V). There were no differences in age, sex, or education between groups. AD/V cases had higher baseline and final Mini-Mental State Examination (MMSE) scores than pure AD cases, but after adjusting for education, differences in MMSE scores were not statistically significant. The AD/V group had significantly lower Braak staging than the pure AD group, after adjusting for education and final MMSE scores. Conclusion: In this comparison study of AD cases with and without vascular lesions, AD/V cases had less severe AD pathology than those with AD alone, indicating that cerebrovascular disease likely contributes to the severity of cognitive impairment in those with AD. Controlling for vascular risk factors in patients with AD may have a significant effect on severity of dementia. C1 Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA USA. RP Riekse, RG (reprint author), VAPSHCS, MIRECC 116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM riekse@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [U01 AG006781, U01AG06781]; NINDS NIH HHS [R01 NS048595] NR 55 TC 74 Z9 78 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1442 EP 1448 DI 10.1111/j.1532-5415.2004.52405.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900005 PM 15341544 ER PT J AU Chodosh, J Seeman, TE Keeler, E Sewall, A Hirsch, SH Guralnik, JM Reuben, DB AF Chodosh, J Seeman, TE Keeler, E Sewall, A Hirsch, SH Guralnik, JM Reuben, DB TI Cognitive decline in high-functioning older persons is associated with an increased risk of hospitalization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive impairment; dementia; health service utilization ID MENTAL STATUS QUESTIONNAIRE; ALZHEIMERS-DISEASE; DEPRESSIVE SYMPTOMATOLOGY; ELDERLY POPULATION; UNITED-STATES; DEMENTIA; COMMUNITY; IMPAIRMENT; HEALTH; COSTS AB Objectives: To examine hospital use for patients with evidence of cognitive decline indicative of early cognitive impairment. Design: Medicare Part A hospital utilization data were linked to data from the MacArthur Research Network on Successful Aging Community Study to examine the association between baseline cognition and decline in cognitive function over a 3-year period and any hospitalization over that same period. Setting: New Haven, Connecticut, and East Boston, Massachusetts. Participants: Subjects (N=598) were from two sites of the MacArthur Research Network on Successful Aging Community Study, a 7-year cohort study of community-dwelling older persons with high physical and cognitive functioning. Measurements: Multivariate logistic regression was used to determine the association between any hospitalization over 3 years (1988-91) as the outcome variable and baseline cognitive function and decline in cognition over 3 years as primary predictor variables. Decline was based upon repeated (1988 and 1991) measures of delayed verbal recall and the Short Portable Mental Status Questionnaire (SPMSQ). Results: Of 598 subjects, 48 died between 1988 and 1991. No baseline (1988) delayed recall scores or change in recall scores (1988-91) were associated with hospitalization. Although 48.2% declined on verbal memory scores, decline was not associated with risk of hospitalization. Of 494 subjects with complete 3-year data, 31.2% declined at least one point on the SPMSQ, and 4.7% declined more than two points. Among individuals aged 75 and older at baseline, the adjusted odds ratio for hospitalization for those who declined more than 2 points compared with those who declined less was 7.8 (95% confidence interval=2.0-30.8). Conclusion: Although specific memory tests were not associated with hospitalization, high-functioning older persons who experienced decline in overall cognitive function were more likely to be hospitalized. Variation in baseline cognitive function in this high-functioning cohort did not affect hospitalization, but additional research is needed to evaluate associations with other healthcare costs. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Sewall Inc, Bethesda, MD USA. NIA, Bethesda, MD 20892 USA. RP Chodosh, J (reprint author), 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [AG16677] NR 40 TC 40 Z9 40 U1 3 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1456 EP 1462 DI 10.1111/j.1532-5415.2004.52407.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900007 PM 15341546 ER PT J AU Bridevaux, IP Bradley, KA Bryson, CL McDonell, MB Fihn, SD AF Bridevaux, IP Bradley, KA Bryson, CL McDonell, MB Fihn, SD TI Alcohol screening results in elderly male veterans: Association with health status and mortality SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE elderly; alcohol; problem drinking; health status; mortality ID PRIMARY-CARE PATIENTS; QUALITY-OF-LIFE; OLDER-ADULTS; CONSUMPTION; QUESTIONNAIRE; POPULATION; DRINKERS; SF-36; CONSEQUENCES; RELIABILITY AB Objectives: To evaluate the association between alcohol screening results and health status or mortality in elderly patients. Design: Cross-sectional and longitudinal cohort studies. Setting: Primary care clinics at seven Veterans Affairs medical centers. Participants: A total of 16,958 male patients aged 65 and older. Measurements: Alcohol screening questionnaires were used to divide patients into four mutually exclusive groups: drinkers who screened negative or positive for problem drinking and nondrinkers (in the previous year) who screened negative or positive for problem drinking. A subset of patients (n=12,491) completed a measure of health status, the Medical Outcomes Study Short Form (SF-36). All-cause mortality was ascertained using Veterans Affairs data over a mean follow-up of 2.8 years. Results: Forty-eight percent of participants reported drinking in the previous year. Half of the drinkers and nondrinkers screened positive for problem drinking. The SF-36 item scores were consistently higher for drinkers than for nondrinkers and for patients who screened negative for problems than for those who screened positive. Similarly, survival was consistently better in drinkers than nondrinkers (mortality hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.68-0.82) and in patients who screened negative for problem drinking than in those who screened positive (mortality HR=0.87, 95% CI=0.80-0.95). Nondrinkers who screened positive for problem drinking had the poorest health status and survival, whereas drinkers who screened negative for problem drinking had the best health status and survival. Conclusion: Elderly patients who reported drinking alcohol and those who screened negative for problem drinking had consistently better health status and survival than those who did not drink and those who screened positive. C1 VA Puget Sound Hlth Care Syst, HSR&D, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Bridevaux, IP (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, NW Hlth Serv Res & Dev Ctr Excellence, MS 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM Isabelle.Peytremann-Bridevaux@hospd.ch FU NIAAA NIH HHS [K23 AA00313] NR 44 TC 39 Z9 39 U1 3 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1510 EP 1517 DI 10.1111/j.1532-5415.2004.52414.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900014 PM 15341553 ER PT J AU Rubenstein, LZ Solomon, DH Roth, CP Young, RT Shekelle, PG Chang, JT MacLean, CH Kamberg, CJ Saliba, D Wenger, NS AF Rubenstein, LZ Solomon, DH Roth, CP Young, RT Shekelle, PG Chang, JT MacLean, CH Kamberg, CJ Saliba, D Wenger, NS TI Detection and management of falls and instability in vulnerable elders by community physicians SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE falls; geriatrics; instability; gait; vulnerable elders; quality of care ID ASSESSING CARE; OLDER-ADULTS; QUALITY; PREVENTION; PEOPLE AB Objectives: To investigate quality of care for falls and instability provided to vulnerable elders. Design: Six process of care quality indicators (QIs) for falls and instability were developed and applied to community-living persons aged 65 and older who were at increased risk of death or decline. QIs were implemented using medical records and patient interviews. Setting: Northeastern and southwestern United States. Participants: Three hundred seventy-two vulnerable elders enrolled in two senior managed care plans. Measurements: Percentage of QIs satisfied concerning falls or mobility disorders. Results: Of the 372 consenting vulnerable elders with complete medical records, 57 had documentation of 69 episodes of two or more falls or fall with injury during the 13-month study period (14% of patients fell per year, 18% incidence). Double this frequency was reported at interview. An additional 22 patients had documented mobility problems. Clinical history of fall circumstances, comorbidity, medications, and mobility was documented from 47% of fallers and two or more of these four elements from 85%. Documented physical examination was less complete, with only 6% of fallers examined for orthostatic blood pressure, 7% for gait or balance, 25% for vision, and 28% for neurological findings. The evaluation led to specific recommendations in only 26% of cases, but when present they usually led to appropriate treatment modalities. Mobility problems without falls were evaluated with gait or balance examination in 23% of cases and neurological examination in 55%. Conclusion: Community physicians appear to underdetect falls and gait disorders. Detected falls often receive inadequate evaluation, leading to a paucity of recommendations and treatments. Adhering to guidelines may improve outcomes in community-dwelling older adults. C1 Greater Los Angeles VA Med Ctr, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Rubenstein, LZ (reprint author), Greater Los Angeles VA Med Ctr, Ctr Geriatr Res Educ & Clin, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM Lzrubens@ucla.edu NR 13 TC 40 Z9 40 U1 3 U2 10 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1527 EP 1531 DI 10.1111/j.1532-5415.2004.52417.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900017 PM 15341556 ER PT J AU Lorenz, KA Lynn, J AF Lorenz, KA Lynn, J TI Oregon's lessons for improving advance care planning SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID LIFE-SUSTAINING TREATMENT C1 Univ Calif Los Angeles, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. Washington Home Ctr Palliat Care Studies, Washington, DC USA. RP Lorenz, KA (reprint author), Univ Calif Los Angeles, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 7 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1574 EP 1575 DI 10.1111/j.1532-5415.2004.52426.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900026 PM 15341565 ER PT J AU McQueen, L Mittman, BS Demakis, JG AF McQueen, L Mittman, BS Demakis, JG TI Overview of the veterans health administration (VHA) quality enhancement research initiative (QUERI) SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CARE-SYSTEM; REORGANIZATION AB The U.S. Veterans Health Administration (VHA)'s Quality Enhancement Research Initiative (QUERI) is an innovative integration of health services research, policy, and clinical care delivery designed to improve the quality, outcomes, and efficiency of VHA health care through the identification and implementation of evidence-based practices in routine care settings. A total of eight condition-specific QUERI centers are currently in operation, each pursuing an integrated portfolio of activities designed to identify and correct gaps in clinical quality and performance and to derive generalizable scientific knowledge regarding quality improvement processes and methods and their effectiveness. This overview article describes QUERI's mission, history, structure, and activities and provides a brief summary of key findings and impacts. C1 US Dept Vet Affairs 10Q, Off Qual & Performance, Washington, DC 20420 USA. US Dept Vet Affairs, Qual Enhancement Res Initiat, Washington, DC 20420 USA. US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Washington, DC 20420 USA. RP McQueen, L (reprint author), US Dept Vet Affairs 10Q, Off Qual & Performance, 810 Vermont Ave NW, Washington, DC 20420 USA. EM lynn.mcqueen@hq.med.va.gov NR 22 TC 68 Z9 68 U1 0 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2004 VL 11 IS 5 BP 339 EP 343 DI 10.1197/jamia.M1499 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 854JD UT WOS:000223898000001 PM 15187071 ER PT J AU Hynes, DM Perrin, RA Rappaport, S Stevens, JM Demakis, JG AF Hynes, DM Perrin, RA Rappaport, S Stevens, JM Demakis, JG TI Informatics resources to support health care quality improvement in the veterans health administration SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID DATABASES AB Information systems are increasingly important for measuring and improving health care quality. A number of integrated health care delivery systems use advanced information systems and integrated decision support to carry out quality assurance. activities, but none as large as the Veterans Health Administration (VHA). The VHA!s Quality Enhancement Research Initiative (QUERI) is a large-scale, multidisciplinary quality improvement initiative designed to ensure excellence in all areas where VHA provides health care services, including inpatient, outpatient, and long-term care settings. In this paper, we describe the role of information systems in the VHA QUERI process, highlight the major information systems critical to this quality improvement process, and discuss issues associated with the use of these systems. C1 Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, Hines, IL 60141 USA. Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Univ, Maywood, IL 60153 USA. VA Off Informat, Washington, DC USA. US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Washington, DC USA. RP Hynes, DM (reprint author), Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, POB 5000,151V, Hines, IL 60141 USA. EM hynes@research.hines.med.va.gov NR 20 TC 47 Z9 47 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2004 VL 11 IS 5 BP 344 EP 350 DI 10.1197/jamia.M1548 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 854JD UT WOS:000223898000002 PM 15187063 ER PT J AU Owen, RR Thrush, CR Cannon, D Sloan, KL Curran, G Hudson, TR Austen, M Ritchie, M AF Owen, RR Thrush, CR Cannon, D Sloan, KL Curran, G Hudson, TR Austen, M Ritchie, M TI Use of electronic medical record data for quality improvement in schizophrenia treatment SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PRESCRIBING PRACTICES; CARE; OUTCOMES; PERFORMANCE; GUIDELINE; COMPUTER; SYSTEM AB An understanding of the strengths and limitations of automated data is valuable when using administrative or clinical databases to monitor and improve the quality of health care. This study discusses the feasibility and validity of using data electronically extracted from the Veterans Health Administration (VHA) computer database (VistA) to monitor guideline performance for inpatient and outpatient treatment of schizophrenia. The authors also discuss preliminary results and their experience in applying these methods to monitor antipsychotic prescribing using the South Central VA Healthcare Network (SCVAHCN) Data Warehouse as a tool for quality improvement. C1 Vet Adm Med Ctr, Ctr Mental Healthcare & Outcomes Res, Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev Serv, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Coll Med, Dept Psychiat & Behav Sci, Div Hlth Serv Res, Little Rock, AR USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Univ Utah, VA Salt Lake Hlth Care Syst, Salt Lake City, UT USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Owen, RR (reprint author), Vet Adm Med Ctr, Ctr Mental Healthcare & Outcomes Res, Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev Serv, 152 NLR,2200 Ft Roots Dr, N Little Rock, AR 72114 USA. EM owenrichardr@uams.edu NR 38 TC 17 Z9 17 U1 2 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2004 VL 11 IS 5 BP 351 EP 357 DI 10.1197/jamia.M1498 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 854JD UT WOS:000223898000003 PM 15187073 ER PT J AU Goldstein, MK Coleman, RW Tu, SW Shankar, RD O'Connor, MJ Musen, MA Martins, SB Lavori, PW Shlipak, MG Oddone, E Advani, AA Gholami, P Hoffman, BB AF Goldstein, MK Coleman, RW Tu, SW Shankar, RD O'Connor, MJ Musen, MA Martins, SB Lavori, PW Shlipak, MG Oddone, E Advani, AA Gholami, P Hoffman, BB TI Translating research into practice: Organizational issues in implementing automated decision support for hypertension in three medical centers SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID EVIDENCE BASED GUIDELINES; CARE INFORMATION-SYSTEMS; HEALTH-CARE; CONTROLLED-TRIAL; PATIENT RECORD; CHALLENGES; DISEASE AB Information technology can support the implementation of clinical research findings in practice settings. Technology can address the quality gap in health care by providing automated decision support to clinicians that integrates guideline knowledge with electronic patient data to present real-time, patient-specific recommendations. However, technical success in implementing decision support systems may not translate directly into system use by clinicians. Successful technology integration into clinical work settings requires explicit attention to the organizational context. We describe the application of a "sociotechnical" approach to integration of ATHENA DSS, a decision support system for the treatment of hypertension, into geographically dispersed primary care clinics. We applied an iterative technical design in response to organizational input and obtained ongoing endorsements of the project by the organization's administrative and clinical leadership. Conscious attention to organizational context at the time of development, deployment, and maintenance of the system was associated with extensive clinician use of the system. C1 VA Palo Alto Hlth Care Syst, GRECC, Palo Alto, CA 94304 USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Stanford Med Informat, Sch Med, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Cooperat Studies Coordinating Ctr, Palo Alto, CA USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Vet Adm Med Ctr, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. VA Boston Hlth Care Syst, W Roxbury Div, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goldstein, MK (reprint author), VA Palo Alto Hlth Care Syst, GRECC, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM goldstein@stanford.edu FU NLM NIH HHS [LM06245, LM05708] NR 33 TC 47 Z9 47 U1 0 U2 8 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2004 VL 11 IS 5 BP 368 EP 376 DI 10.1197/jamia.M1534 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 854JD UT WOS:000223898000005 PM 15187064 ER PT J AU Rodrigues, ACT Hataishi, R Ichinose, F Bloch, KD Derumeaux, G Picard, MH Scherrer-Crosbie, M AF Rodrigues, ACT Hataishi, R Ichinose, F Bloch, KD Derumeaux, G Picard, MH Scherrer-Crosbie, M TI Relationship of systolic dysfunction to area at risk and infarction size after ischemia-reperfusion in mice SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID EXPERIMENTAL MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR ENLARGEMENT; WALL-MOTION ABNORMALITIES; 2-DIMENSIONAL ECHOCARDIOGRAPHY; MOUSE MODEL; INJURY AB Whereas the extent of wall-motion abnormality (WMA) correlates well with the area at risk (AAR) and infarction size in murine models of nonreperfused myocardial infarction, this relationship is less clear in the setting of ischemia-reperfusion injury. Echocardiography was performed in mice at baseline, after left anterior descending coronary artery ligation (30 minutes) followed by reperfusion (24 hours), and after religation of the left anterior descending coronary artery The extent of WMA before and after religation was compared with the initial infarction size measured by triphenyltetrazolitun chloride and the AAR measured by fluorescent microspheres, respectively. Echocardiography showed left ventricular dilation and dysfunction after ischemia and reperfusion. WMA after religation correlated well with AAR (r(2)=0.70, P<.0001). The correlation between WMA and infarction size was incomplete (r(2)=0.59, P<.0002) in part because of underestimation of nontransmural infarcts. Echocardiography can reliably assess AAR after ischemia-reperfusion in mice; however, it does not allow for precise quantification of the small areas of necrosis that often occur in this setting. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rouen, INSERM E9920, Rouen, France. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Ultrasound Lab, 55 Fruit St,VBK508, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL70896] NR 24 TC 12 Z9 12 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2004 VL 17 IS 9 BP 948 EP 953 DI 10.1016/j.echo.2004.05.014 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 851TN UT WOS:000223708500004 PM 15337959 ER PT J AU Reiser, J Mundel, P AF Reiser, J Mundel, P TI Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol ID T-CELL COSTIMULATION; SLIT DIAPHRAGM; NEPHRIN LOCALIZES; CYTOPLASMIC TAIL; EPITHELIAL-CELL; MICE LACKING; JUNCTION; PROTEINURIA; EXPRESSION; COMPONENT C1 Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA 02115 USA. RP Mundel, P (reprint author), Albert Einstein Coll Med, Dept Med, Div Nephrol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mundel@aecom.yu.edu FU NIDDK NIH HHS [DK064236, DK062472, DK57683] NR 37 TC 37 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 VL 15 IS 9 BP 2246 EP 2248 DI 10.1097/01.ASN.0000136312.46464.33 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 851EK UT WOS:000223668200002 PM 15339973 ER PT J AU Tanaka, T Nangaku, M Miyata, T Inagi, R Ohse, T Ingelfinger, JR Fujita, T AF Tanaka, T Nangaku, M Miyata, T Inagi, R Ohse, T Ingelfinger, JR Fujita, T TI Blockade of calcium influx through L-type calcium channels attenuates mitochondrial injury and apoptosis in hypoxic renal tubular cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CERAMIDE-INDUCED APOPTOSIS; ENDOPLASMIC-RETICULUM; EPITHELIAL-CELLS; CYTOCHROME-C; CA2+ CONCENTRATION; BAX; DEATH; DISEASE; EXPRESSION; GENERATION AB In hypoxia, ATP depletion causes cellular Ca2+ increase, mitochondrial injury, and apoptosis in renal tubular cells. However, the molecular basis of these observations is incompletely delineated. IRPTC, a rat renal proximal tubular cell line, was treated with antimycin A, and disturbances in cytoplasmic calcium ([Ca2+]c) and mitochondrial calcium ion concentration ([Ca2+]m), dissipation of mitochondrial membrane potential (DeltaPsi(m)), cytochrome c release, and resultant apoptosis were examined. Pharmacologic targeting of L-type Ca2+ channels in vitro and in vivo was used to clarify the involvement of voltage-dependent Ca2+ channels during this process. In vitro studies indicated that ATP depletion-induced apoptosis was preceded by increased [Ca2+]c and [Ca2+]m before activation of mitochondrial signaling. Antagonizing L-type Ca2+ channels offset these findings, suggesting [Ca2+]c and [Ca2+]m involvement. Azelnidipine administration ameliorated cellular and mitochondrial Ca2+ accumulation, mitochondrial permeability transition, cytochrome c release, caspase-9 activation, and resultant apoptosis (15.8 +/- 0.8% versus 8.9 +/- 0.7%; P < 0.01). Similar effects of azelnidipine were substantiated in an in vivo ischemia/reperfusion injury model. There were fewer terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling-positive cells in the azelnidipine-treated group (0.322 +/- 0.038/tubule) as compared with the vehicle-treated group (0.450 +/- 0.041; P < 0.05), although the antiapoptotic effect was smaller in vivo than in vitro, partly as a result of distinct levels of Bax expression. It is proposed that voltage-dependent Ca2+ channels are involved in cellular and mitochondrial accumulation of Ca2+ subsequent to ATP depletion and play an important role in regulating mitochondrial permeability transition, cytochrome c release, caspase activation, and apoptosis. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 113, Japan. Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591100, Japan. Tokai Univ, Sch Med, Dept Internal Med, Kanagawa 2591100, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 113, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 FU NHLBI NIH HHS [HL48455] NR 48 TC 58 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 VL 15 IS 9 BP 2320 EP 2333 DI 10.1097/01.ASN.0000138287.46849.82 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 851EK UT WOS:000223668200010 PM 15339981 ER PT J AU Kishimoto, K Yuan, XL Auchincloss, H Sharpe, AH Mandelbrot, DA Sayegh, MH AF Kishimoto, K Yuan, XL Auchincloss, H Sharpe, AH Mandelbrot, DA Sayegh, MH TI Mechanism of action of donor-specific transfusion in inducing tolerance: Role of donor MHC molecules, donor co-stimulatory molecules, and indirect antigen presentation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CARDIAC ALLOGRAFT-REJECTION; LONG-TERM SURVIVAL; REGULATORY T-CELLS; ANTI-CD154 ANTIBODY; CD40 LIGAND; MICE; TRANSPLANTATION; RECIPIENTS; INFUSION; LYMPHOCYTES AB Donor-specific transfusion (DST) can synergize with T cell co-stimulatory blockade in inducing tolerance in several transplant models, but the mechanism of action of DST is poorly characterized. This study used genetically altered mice in an established model of cardiac transplantation to study the role of MHC and co-stimulatory molecule expression on DST cells in mediating the immunomodulatory effects of DST. In addition, to examine the role of indirect antigen presentation in the effect of DST, experiments used recipient mice that do not express MHC class II molecules on peripheral antigen-presenting cells, but do have functional CD4(+) T cells (II(-)4(+)). As previously reported, treatment with DST from wild-type donors in combination with CD154 blockade induced tolerance in wild-type recipients of cardiac allografts. Tolerance in this model is also induced despite the absence of MHC class I and II, CD40, or B7 molecules on transfused cells. In contrast, eliminating the indirect pathway using II(-)4(+) recipients blocked the induction of long-term cardiac allograft survival by DST. These results indicate that the indirect antigen recognition pathway mediates the immunomodulatory effect of DST in inducing transplantation tolerance in vivo. C1 Univ Massachusetts, Med Ctr, Div Renal, Worcester, MA 01655 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Immunol Res Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. RP Univ Massachusetts, Med Ctr, Div Renal, 55 Lake Ave N, Worcester, MA 01655 USA. EM mandelbd@ummhc.org FU NIAID NIH HHS [P01-AI-41521, P01-AI-56299, R01-AI-34965, R01-AI-51559] NR 30 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 VL 15 IS 9 BP 2423 EP 2428 DI 10.1097/01.ASN.0000137883.20961.2D PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 851EK UT WOS:000223668200020 PM 15339991 ER PT J AU Palevsky, PM AF Palevsky, PM TI Acute renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID RADIOCONTRAST-INDUCED NEPHROPATHY; CRITICALLY-ILL PATIENTS; ACUTE TUBULAR-NECROSIS; RECOMBINANT-HUMAN-ERYTHROPOIETIN; INHIBITING LEUKOCYTE ACTIVATION; ACUTE INTERSTITIAL NEPHRITIS; CONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED TRIAL; VASODILATORY SEPTIC SHOCK; AGENT-INDUCED NEPHROPATHY C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. NR 125 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 SU S BP 245 EP 277 PG 33 WC Urology & Nephrology SC Urology & Nephrology GA 888UB UT WOS:000226398600002 ER PT J AU Li, Y Ryan, L AF Li, Y Ryan, L TI Survival analysis with heterogeneous covariate measurement error SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE asymptotic bias analysis; asymptotic relative efficiency; corrected estimator; Cox model; mistimed covariate; Schoenfeld's sample size formula ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME REGRESSION; COX REGRESSION; PREDICTORS; ESTIMATOR; SAMPLE; TESTS; LIFE AB This article is motivated by a time-to-event analysis where the covariate of interest was measured at the wrong time. We show that the problem can be formulated as a special case of survival analysis with heterogeneous covariate measurement error and develop a general analytic framework. We study the asymptotic behavior of the naive partial likelihood estimates and analytically demonstrate that under the heterogeneous measurement error structure and the assumption that all components of the covariate vector and the measurement error vector combined are mutually independent, these naive estimates will shrink toward 0, and that the degree of attenuation increases as the measurement error increases. We also give counterexamples for reverse attenuation when the independence conditions are violated. We use our analytical results to derive a simple bias-correcting estimator that performs well in simulations for small and moderate amounts of measurement error. Our framework can be used to provide insight into the behavior of the commonly used partial likelihood score test for testing no association between a failure outcome and an exposure, for example, in the presence of measurement error or mistiming error. In particular, we derive the asymptotic distribution of the naive partial likelihood score test under a series of local alternatives and discuss the asymptotic relative efficiency. As a result, a simple sample size formula to account for the contamination of covariates is obtained. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM yili@jimmy.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 47 TC 13 Z9 14 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2004 VL 99 IS 467 BP 724 EP 735 DI 10.1198/0162145040000001079 PG 12 WC Statistics & Probability SC Mathematics GA 853VR UT WOS:000223857500021 ER PT J AU Bostwick, DG Hossain, D Qian, JQ Neumann, RM Yang, P Young, RH di Sant'Agnese, PA Jones, EC AF Bostwick, DG Hossain, D Qian, JQ Neumann, RM Yang, P Young, RH di Sant'Agnese, PA Jones, EC TI Phyllodes tumor of the prostate: Long-term followup study of 23 cases SO JOURNAL OF UROLOGY LA English DT Article DE prostate; phyllodes tumor; fibroadenoma; sarcoma; adenosarcoma ID CYSTOSARCOMA-PHYLLODES; LEIOMYOSARCOMA; HYPERPLASIA AB Purpose: Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome. Materials and Methods: A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done. Results: Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34beta-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients. Conclusions: Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated. C1 Bostwick Labs, Richmond, VA 23294 USA. Univ Manitoba, Hlth Sci Ctr, Dept Pathol, Winnipeg, MB, Canada. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Mayo Clin, Dept Urol, Rochester, MI USA. Mayo Clin, Div Epidemiol, Rochester, MI USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Univ Rochester, Ctr Med, Dept Pathol, Rochester, NY USA. RP Bostwick, DG (reprint author), Bostwick Labs, 2807 N Parham Rd, Richmond, VA 23294 USA. EM Bostwick@bostwicklaboratories.com NR 20 TC 47 Z9 57 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2004 VL 172 IS 3 BP 894 EP 899 DI 10.1097/01.ju.0000134580.71261.57 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 847GE UT WOS:000223379900019 PM 15310992 ER PT J AU Korkmaz, CG Korkmaz, KS Manola, J Xi, ZJ Risberg, B Danielsen, H Kung, J Sellers, WR Loda, M Saatcioglu, F AF Korkmaz, CG Korkmaz, KS Manola, J Xi, ZJ Risberg, B Danielsen, H Kung, J Sellers, WR Loda, M Saatcioglu, F TI Analysis of androgen regulated homeobox gene NKX3.1 during prostate carcinogenesis SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; androgens; homeodomain proteins; gene expression ID CANCER; EXPRESSION; CARCINOMA; MODEL; CDNA AB Purpose: NKX3.1 is an androgen regulated gene that is largely specific to the prostate for expression and it is predicted to encode a homeobox protein. Null alleles of NKX3.1 in mice results in impaired prostate development as well as hyperplasia and dysplasia of the prostate. In addition, the NKX3.1 gene maps to a region of high loss of heterozygosity in prostate cancer in humans, suggesting that NKX3.1 might have a direct role in prostate carcinogenesis, possibly functioning as a tumor suppressor protein. Previous studies of the levels of NKX3.1 mRNA or protein in prostate cancer specimens have resulted in conflicting findings. Materials and Methods: To resolve this issue we assessed NKX3.1 expression by mRNA in situ analysis and immunohistochemistry on the same prostate cancer tissue arrays. Results: Data showed that NKX3.1 mRNA and protein levels in prostate cancer specimens are correlated, suggesting that most regulation is at the transcriptional level. There was no correlation of NKX3.1 expression levels with tumor grade or clinical stage. In general there was a suggestion that worse clinical features at surgery were associated with lower IHC stain scores. In particular, extracapsular extension but not seminal vesicle invasion inversely correlated with NKX3.1 expression. Conclusions: Together these data suggest that NKX3.1 does not function as a typical tumor suppressor protein in prostate cancer but it may still have important regulatory roles during prostate cancer progression. C1 Univ Oslo, Dept Mol Biosci, Oslo, Norway. Univ Oslo, Ctr Biotechnol, Oslo, Norway. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Sheffield, Div Genom Med, Sheffield, S Yorkshire, England. RP Saatcioglu, F (reprint author), Univ Oslo, Dept Mol Biosci, Oslo, Norway. RI Risberg, Bjorn/A-6447-2008; Danielsen, Havard/A-7540-2014 NR 20 TC 30 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2004 VL 172 IS 3 BP 1134 EP 1139 DI 10.1097/01.ju.0000136526.78535.b8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 847GE UT WOS:000223379900093 PM 15311057 ER PT J AU Wicky, S Greenfield, A Fan, CM Geller, SC Hamberg, LM Hoffmann, U Waltman, AC AF Wicky, S Greenfield, A Fan, CM Geller, SC Hamberg, LM Hoffmann, U Waltman, AC TI Aortoiliac gadolinium-enhanced CT angiography: Improved results with a 16-detector row scanner compared with a four-detector row scanner SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; CONTRAST AGENT; DTPA AB PURPOSE: To assess the level of vascular enhancement of gadolinium-enhanced aortoiliac computed tomographic (CT) angiography with a 16-detector row CT scanner and to compare it with the results of previous similar studies that used four-detector row CT units. MATERIALS AND METHODS: Eleven gadolinium-enhanced CT angiograms were obtained in 10 consecutive patients with contraindication to iodinated contrast medium with use of a 16-detector row CT scanner. In the region of interest, attenuation measurements (in HU) were obtained from the proximal abdominal aorta to the common femoral arteries during unenhanced, gadolinium-enhanced, and delayed acquisitions. The results were compared to those in the 15 consecutive patients who most recently had similar examinations performed on a four-detector row CT unit. Phantom studies with diluted gadolinium were conducted to compare attenuation between CT units. RESULTS: On four-detector row CT, throughout the scan length, mean enhancement values were 53.8 HU +/- 5.3 and 15.0 HU +/- 2.6 for gadolinium-enhanced and delayed series, respectively. For the 16-detector row CT unit, they were 76.1 HU +/- 3.4 and 21.3 HU +/- 1.3, respectively. As a result of a shorter scan time and a more optimal start time, the 16-detector row CT unit provided significantly greater and more consistent enhancement throughout the scan length compared with the four-detector row CT unit (P = .0106). Similar structures had significantly greater enhancement when 120 kV was applied instead of 140 kV (P = .0495) CONCLUSION: The 16-detector row CT scanner improved gadolinium-enhanced CT angiography results compared with the four-detector row CT unit. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wicky, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM swicky@partners.org NR 10 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2004 VL 15 IS 9 BP 947 EP 954 DI 10.1097/01.RVI.0000130381.73361.7A PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XQ UT WOS:000227678600007 PM 15361562 ER PT J AU Nicewonger, J Suck, G Bloch, D Swaminathan, S AF Nicewonger, J Suck, G Bloch, D Swaminathan, S TI Epstein-Barr virus (EBV) SM protein induces and recruits cellular Sp110b to stabilize mRNAs and enhance EBV lytic gene expression SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR DOMAIN 10; CREB-BINDING-PROTEIN; HUMAN CYTOMEGALOVIRUS; BURKITTS-LYMPHOMA; VIRAL PROTEIN; SAND DOMAIN; LINE AKATA; PML; REPLICATION; INTERFERON AB Promyelocytic leukemia protein (PML) nuclear bodies or nuclear domain 10s (ND10s) are multiprotein nuclear structures implicated in transcriptional and posttranscriptional gene regulation that are disrupted during replication of many DNA viruses. Interferon increases the size and number of PML nuclear bodies and stimulates transcription of several genes encoding PML nuclear body proteins. Moreover, some PML nuclear body proteins colocalize at sites of viral DNA synthesis and transcription. In this study, the relationship between lytic Epstein-Barr virus (EBV) replication and Sp110b, a PML nuclear body protein, was investigated. Sp110b is shown to physically and functionally interact with the EBV protein SM. SM is expressed early in the EBV replicative cycle and posttranscriptionally increases the level of target EBV lytic transcripts. SM bound to Sp110b via two distinct sites in Sp110b in an RNA-independent manner. SM also specifically induced expression of Sp110b during lytic EBV replication and in several cell types. Exogenous expression of Sp110b synergistically enhanced SM-mediated accumulation of intronless and lytic viral transcripts. This synergistic effect was shown to be promoter independent, posttranscriptional, and the result of increased stabilization of target transcripts. Finally, inhibiting Sp110b expression decreased accumulation of an SM-responsive lytic EBV transcript in EBV-infected cells. These findings imply that SM induces Sp110b expression, binds to Sp110b, and utilizes the recruited Sp110b protein to increase the stability of lytic EBV transcripts, indicating that Sp110b is a component of the cellular machinery that EBV utilizes to enhance lytic EBV replication. C1 Univ Florida, Shands Canc Ctr, Dept Med & Mol Genet, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Arthrit Unit, Boston, MA USA. RP Swaminathan, S (reprint author), Univ Florida, Shands Canc Ctr, Dept Med & Mol Genet, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM sswamina@ufl.edu FU NCI NIH HHS [CA811333]; NIDDK NIH HHS [DK051179] NR 47 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9412 EP 9422 DI 10.1128/JVI.78.17.9412-9422.2004 PG 11 WC Virology SC Virology GA 847IT UT WOS:000223386600044 PM 15308735 ER PT J AU Simmons, SF Schnelle, JF AF Simmons, SF Schnelle, JF TI Individualized feeding assistance care for nursing home residents: Staffing requirements to implement two interventions SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LONG-TERM-CARE; FLUID INTAKE; PREDICTORS AB feeding assistance during meals and to individualize care for residents. However, there are few data reflecting the number of residents responsive to feeding assistance during meals and what alternative interventions might be appropriate for other residents. The purpose of this study was to evaluate the effects and staffing requirements of two individualized feeding assistance interventions to improve oral food and fluid intake in NH residents. Methods. Skilled nursing participants (n = 134) in 3 NHs received a 2-day trial of one-on-one feeding assistance during 6 meals. 68 participants who did not increase their oral intake in response to feeding assistance during meals received a 2-day intervention trial during which snacks were offered between meals 3 times daily. As part of both interventions, research staff provided adequate feeding assistance that enhanced the resident's self-feeding ability, social stimulation throughout the meal or snack period, and availability of choices for foods and fluids. Results. 46% significantly increased their oral intake in response to one-on-one mealtime feeding assistance, and the staff time required to implement this intervention was 35 ( +/- 8) minutes/meal per resident compared with usual NH care, which averaged 6 ( +/- 9) minutes. 44% of the participants significantly increased their oral intake in response to the between-meal snack intervention, which required 12 ( +/- 6) minutes of staff time per snack/resident compared with usual NH care (1 +/- 4 minutes). Conclusions. Most participants (90%) significantly increased their daily oral food and fluid intake in response to one of two individualized interventions. The staff time necessary to implement each intervention was significantly greater than the staff time currently being spent on feeding assistance care delivery. Suggestions are made to increase the efficiency of staff time when delivering feeding assistance. C1 Univ Calif Los Angeles, Sch Med, Borun Ctr Gerontol Res, Dept Geriatr,Jewish Home Aging, Reseda, CA 91335 USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Sch Med, Borun Ctr Gerontol Res, Dept Geriatr,Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. EM ssimmons@ucla.edu NR 29 TC 50 Z9 53 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2004 VL 59 IS 9 BP 966 EP 973 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 862VY UT WOS:000224520500016 ER PT J AU Connor, LT Spiro, A Obler, LK Albert, ML AF Connor, LT Spiro, A Obler, LK Albert, ML TI Change in object naming ability during adulthood SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID OLDER-ADULTS; NORMATIVE DATA; COGNITIVE PERFORMANCE; AGE; DECLINE; DEMENTIA; MEMORY; LIFE; EDUCATION; RETRIEVAL AB Using longitudinal data on the Boston Naming Test (Kaplan, Goodglass, & Weintraub, 1983) collected over 20 years from healthy individuals aged 30 to 94, we examined change in lexical retrieval with age, gender, education, and their interactions. We compared results between random-effects longitudinal and traditional cross-sectional models. Random-effects modeling revealed significant linear and quadratic change in lexical retrieval with age; it also showed a Gender X Education interaction, indicating poorest performance for women with less education. Cross-sectional analyses produced greater estimates of change with age than did longitudinal analyses. C1 Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. CUNY, Program Speech & Hearing Sci, New York, NY 10021 USA. RP Connor, LT (reprint author), Washington Univ, Sch Med, Dept Radiol, Box 8225,4525 Scott Ave, St Louis, MO 63110 USA. EM lconnor@npg.wustl.edu FU NIA NIH HHS [AG14345]; NIDCD NIH HHS [DC00081] NR 50 TC 25 Z9 26 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD SEP PY 2004 VL 59 IS 5 BP P203 EP P209 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 854FS UT WOS:000223887600001 PM 15358792 ER PT J AU Fehr, T Ammann, P Garzoni, D Korte, W Fierz, W Rickli, H Wuthrich, RP AF Fehr, T Ammann, P Garzoni, D Korte, W Fierz, W Rickli, H Wuthrich, RP TI Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia SO KIDNEY INTERNATIONAL LA English DT Article DE erythropoietin; chronic renal failure; creatinine clearance; hemoglobin; anemia ID CONGESTIVE-HEART-FAILURE; HOSPITALIZATIONS; PREDICTION; MANAGEMENT; HYPOXIA; KIDNEY AB Background. Chronic renal failure leads to hyporegenerative anemia due to erythropoietin deficiency. The creatinine clearance and hemoglobin levels, at which anemia treatment with recombinant erythropoietin should be started, are unclear. Interpretation of serum erythropoietin levels in the context of renal insufficiency remains controversial and was addressed in this study. Methods. Three hundred and ninety-five patients were randomly chosen out of over 5000 consecutive patients investigated by coronary angiography at a single center between 1997 and 2001. Laboratory values and clinical information were prospectively collected in a central registry. Serum samples were frozen before angiography and now used to measure serum erythropoietin levels and evaluate the relationship between erythropoietin and hemoglobin levels in the context of various degrees of renal insufficiency. Results. The patients with the lowest renal function (creatinine clearance <20 mL/min) had significantly lower hemoglobin levels than the group with normal renal function. However, erythropoietin levels were identical indicating a lower set point for erythropoietin regulation. Above a creatinine clearance of 40 mL/min a significant inverse correlation between erythropoietin and hemoglobin levels was observed and described with the formula erythropoietin [U/L]= 2.5 x (140 - hemoglobin [g/L]) or alternatively Deltaerythropoietin (U/L) =-2.5 xDeltahemoglobin (g/L). Below 40 mL/min no significant correlation was found. Conclusion. A cut-off level for an altered set point of erythropoietin regulation was determined at 40 mL/min creatinine clearance. Above this cut-off hemoglobin negatively regulates erythropoietin. Below the cut-off erythropoietin levels remain stable. Pathophysiologic concepts for this finding and clinical implications in patients with moderate renal failure are discussed. C1 Kantonspital St Gallen, Inst Clin Chem & Hematol, Div Cardiol, St Gallen, Switzerland. Kantonspital St Gallen, Div Nephrol, St Gallen, Switzerland. Kantonspital St Gallen, Inst Clin Immunol & Microbiol, St Gallen, Switzerland. RP Fehr, T (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E CNY 149,13th St, Boston, MA 02129 USA. EM thomas.fehr@tbrc.mgh.harvard.edu NR 22 TC 43 Z9 46 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2004 VL 66 IS 3 BP 1206 EP 1211 DI 10.1111/j.1523-1755.2004.00880.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 845EB UT WOS:000223217700045 PM 15327419 ER PT J AU Kandziolka, L AF Kandziolka, L TI Avoid a double standard SO LAB ANIMAL LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kandziolka, L (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2004 VL 33 IS 8 BP 16 EP 16 DI 10.1038/laban0904-16a PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 852AK UT WOS:000223727400003 PM 15334104 ER PT J AU Nayak, VK Deschler, DG AF Nayak, VK Deschler, DG TI Pedicled temporoparietal fascial flap reconstruction of select intraoral defects SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern Section of the Triological-Society CY JAN 23-25, 2004 CL New York, NY DE temporoparietal fascial flap; oral cavity reconstruction; intraoral defects AB Objectives/Hypothesis: Multiple modalities exist for reconstruction of oral cavity defects following resection. Although microvascular free tissue transfer is often the first choice for complex intraoral defect reconstruction, not all patients are suitable candidates for "free flaps." The authors present their experience with the pedicled temporoparietal fascial flap (TPFF) for reconstruction of selected intraoral defects. Study Design: Retrospective chart review. Methods: Charts of patients who underwent a TPFF for reconstruction of intraoral defects at a tertiary academic institution between 2001 to 2003 were reviewed. Information regarding tumor, surgical procedure, complications, and results was gathered. The anatomy and surgical technique of using the TPFF for intraoral reconstruction were reviewed. Results. Three patients underwent reconstruction of an intraoral defect with a TPFF. All defects were on the lateral buccal space with significant anterior or posterior extension. All patients had specific contraindications for free flaps, including compromised donor site or recipient site vascularity and medical comorbidity. The procedures were uncomplicated. There was no incidence of flap failure, and all flaps accepted a split-thickness skin graft. The average hospital stay was 7 days. An oral diet was begun on the fifth postoperative day. The cosmetic result at the donor site was excellent. Follow-up has ranged from 7 to 30 months. Mild contracture of the flap developed in two patients, limiting mandibular motion. Conclusion: The TPFF is a thin, vascular, durable flap that is a viable option for reconstruction of selected intraoral defects in patients who are not suitable candidates for other methods. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2004 VL 114 IS 9 BP 1545 EP 1548 DI 10.1097/00005537-200409000-00008 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 860CD UT WOS:000224314800008 PM 15475779 ER PT J AU Merchant, SN Burgess, BJ Adams, JC Kashtan, CE Gregory, MC Santi, PA Colvin, R Collins, B Nadol, JB AF Merchant, SN Burgess, BJ Adams, JC Kashtan, CE Gregory, MC Santi, PA Colvin, R Collins, B Nadol, JB TI Temporal bone histopathology in Alport syndrome SO LARYNGOSCOPE LA English DT Article DE Alport syndrome; histopathology; temporal bone; cochlea; HL ID INNER-EAR; IDENTIFICATION; COLLAGEN; GENE AB Objective: To determine the histopathologic abnormalities within the cochlea in Alport syndrome. Background: Alport syndrome, which manifests as hereditary nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes that code for the proportional to 3, proportional to 4, and proportional to 5 chains of type IV collagen. The proportional to 3, proportional to4, and proportional to5 chains of type IV collagen are present in the basement membrane of the organ of Corti. Previous temporal bone studies have failed to identify histopathologic correlates for the SNHL. Methods: We examined temporal bones from nine individuals with a clinical diagnosis of Alport syndrome. One of our cases also had genetic testing that showed a mutation in the type IV collagen proportional to 5 chain gene. Results: By light microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a "zone of separation" between the basilar membrane and overlying cells of the organ of Corti and 2) presence of cells filling the tunnel of Corti and extracellular spaces of Nuel. The cytologic losses of hair cells, stria vascularis, and cochlear neuronal cells were insufficient to account for the observed SNHL in our cases. Electron microscopy was performed in four cases; all four demonstrated the following: 1) the zone of separation that was observed at light microscopy occurred between the basement membrane and the basilar membrane, 2) the cells within the tunnel of Corti and spaces of Nuel were morphologically similar to supporting cells, and 3) the basement membrane of strial capillaries and the spiral vessel (under the basilar membrane) were normal. Conclusions: The histopathologic correlates of cochlear involvement in Alport syndrome are abnormalities of the basement membrane of cells of the organ of Corti and dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of the organ of Corti. We hypothesize that these abnormalities result in SNHL by altering cochlear micromechanics. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Minnesota, Dept Pediat, Div Pediat Nephrol, Minneapolis, MN 55455 USA. Univ Utah, Med Ctr, Dept Med, Salt Lake City, UT 84132 USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM snm@epl.meei.harvard.edu NR 19 TC 10 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2004 VL 114 IS 9 BP 1609 EP 1618 DI 10.1097/00005537-200409000-00020 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 860CD UT WOS:000224314800020 PM 15475791 ER PT J AU Wong, KK Huang, I Kim, YR Tang, HY Yang, ES Kwong, KK Wu, EX AF Wong, KK Huang, I Kim, YR Tang, HY Yang, ES Kwong, KK Wu, EX TI In vivo study of microbubbles as an MR susceptibility contrast agent SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE microbubble; gas bubble; susceptibility contrast; rat liver; drug delivery ID ALBUMIN MICROSPHERES; HEPATIC-LESIONS; IRON-OXIDE; PRESSURE; EXCHANGE; KINETICS; VOLUME; MICE; RATS; AIR AB The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison(R), was studied with rat liver imaging at 7 T. Optison(R) suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (DeltaR(2)*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro DeltaR(2)* measurements of Optison(R) suspension at different concentrations are also reported. (C) 2004 Wiley-Liss, Inc. C1 Univ Hong Kong, Dept Elect & Elect Engn, Jockey Club MRI Engn Ctr, Hong Kong, Hong Kong, Peoples R China. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY 10027 USA. Massachusetts Gen Hosp, MGH, MIT, HMS,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Wu, EX (reprint author), Univ Hong Kong, Dept Elect & Elect Engn, Jockey Club MRI Engn Ctr, Hong Kong, Hong Kong, Peoples R China. EM ewu@eee.hku.hk RI Wong, Kelvin/B-8080-2013; OI Wong, Kelvin/0000-0001-8329-6123 NR 30 TC 20 Z9 21 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2004 VL 52 IS 3 BP 445 EP 452 DI 10.1002/mrm.20181 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849HL UT WOS:000223529200001 PM 15334560 ER PT J AU Kim, YR Savellano, MD Savellano, DH Weissleder, R Bogdanov, A AF Kim, YR Savellano, MD Savellano, DH Weissleder, R Bogdanov, A TI Measurement of tumor interstitial volume fraction: Method and implication for drug delivery SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE angiogenesis; drug delivery; available interstitial volume; water exchange; prostate cancer ID HUMAN-MELANOMA XENOGRAFTS; REGIONAL BLOOD-VOLUME; WATER-EXCHANGE; MONOCLONAL-ANTIBODIES; CONTRAST AGENT; FLUID VOLUME; SOLID TUMORS; IN-VIVO; PERMEABILITY; ANGIOGENESIS AB It is important to evaluate the tumor interstitial volume fraction that is accessible for drug accumulation during the distribution phase in order to determine the potential efficacy of cancer chemotherapy. In this study, we performed simulations of magnetic resonance imaging (MRI) signal intensity using a two-compartment tissue model for quantitative analyses of absolute interstitial volume measurements while we experimentally characterized a mouse tumor model with a dual MR contrastagent method. Previously, consecutive intravenous injections of a strictly intravascular T-1 contrast agent followed by an extravasating agent were used as a strategy for the quantification of both relative blood volume (Rel BV) and relative interstitial volume (Rel ITST) (Weissleder et al. Eur J Cancer 1998; 34:1448-1454; Bogdanov et al. Neoplasia 1991;1:438-435). In the current study, we demonstrate that this approach can be further improved, and that it enables one to accurately evaluate both relative and absolute interstitial volumes. The animal data indicated that a significant difference exists between the absolute interstitial volume fractions of subcutaneously implanted MDA PCa 2b tumor and skeletal muscle tissue (27.5 +/- 9.1 % and 15.9 +/- 0.7%, respectively (P < 0.05)), while only a minor difference was found for the absolute blood volumes (Abs_BV) (Kim et al. Magn Reson Med 2002;47:1110-1120) of these tissues. (C) 2004 Wiley Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu FU NCI NIH HHS [T32-CA79443, R21 CA85657, R01 CA7442, P50CA86355] NR 40 TC 15 Z9 15 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2004 VL 52 IS 3 BP 485 EP 494 DI 10.1002/mrm.20182 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849HL UT WOS:000223529200007 PM 15334566 ER PT J AU Mulkern, RV Huang, J Vajapeyam, S Packard, AB Oshio, K Grinspoon, S AF Mulkern, RV Huang, J Vajapeyam, S Packard, AB Oshio, K Grinspoon, S TI Fat fractions and spectral T-2 values in vertebral bone marrow in HIV- and non-HIV-infected men: A H-1 spectroscopic imaging study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the ISMRM CY 2003 CL TORONTO, CANADA SP ISMRM ID FAST SPIN-ECHO; PROTON-MR-SPECTROSCOPY; MAGNETIC-RESONANCE; SEQUENCES; DENSITY; AGE; TRANSPLANTATION; LIPODYSTROPHY; THERAPY; BRIGHT AB Fat fractions and spectral T-2 values of fat and water within the vertebral marrow of non-HIV- and HIV-infected men were measured with the use of a Carr-Purcell-Meiboom-Gill (CPMG) line scan spectroscopic imaging sequence. The fat fraction for the HIV-infected men (0.29 +/- 0.08) was significantly lower (P < 0.05, Student's unpaired t-test) than the fat fraction found in non-HIV-infected men (0.40 +/- 0.12). The mean water and fat T-2 values did not differ between the two groups, and did not show any systematic dependence on fat fraction over the wide range of fat fractions encountered in this study. The marrow water and fat T-2 values measured with the CPMG approach were markedly longer than the spectral T-2 values reported by other groups using the more common point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) acquisitions. Proton spectroscopic studies of vertebral marrow revealed differences between non-HIV- and HIV-infected men that may prove useful for studying the effects of this disease and/or antiretroviral agents on body composition. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02115 USA. RP Mulkern, RV (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM rmulkern@yahoo.com OI Huang, Jeannie/0000-0002-2742-5557 FU NCRR NIH HHS [MO1 RR01066]; NIDDK NIH HHS [DK 07477, R01 DK 59535]; PHS HHS [A151947, NIH-P30-A142851] NR 30 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2004 VL 52 IS 3 BP 552 EP 558 DI 10.1002/mrm.20205 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849HL UT WOS:000223529200015 PM 15334574 ER PT J AU Lorenz, KA Ettner, SL Rosenfeld, KE Carlisle, D Liu, H Asch, SM AF Lorenz, KA Ettner, SL Rosenfeld, KE Carlisle, D Liu, H Asch, SM TI Accommodating ethnic diversity - A study of California hospice programs SO MEDICAL CARE LA English DT Article DE hospice; palliative care; economics; minority groups ID HEALTH-CARE; SERVICES; BARRIERS; WOMEN AB Background: Studies have confirmed ethnic disparities in the use of hospice services and identified barriers that minorities face in accessing care. Objectives: We sought to determine whether hospices provide services that might affect minority participation. Research Design: We surveyed California hospices to determine whether programs use diverse health care providers and volunteers, offer translation, diverse spiritual care, or outreach materials and whether they plan to expand such services. Linking the data to the California Office of Statewide Health Planning and Development annual home care and hospice survey and 2000 US Census, we used multivariate linear regression to evaluate the relationship of program characteristics (profit status, size, chain/freestanding status, urban/rural location, and proportion of nonwhite residents) to services that might affect minority participation. Subjects: One hundred of 149 programs that we surveyed responded. Results: Many programs offer translation (81%),diverse providers (63%) and volunteers (64%), and culturally diverse spiritual services (52%). Few (21%) were conducting outreach, but 23/25 programs expanding services reported plans to improve outreach. In multivariate models adjusted for program size, chain status, profit status, urban/rural location, proportion of nonwhite residents, we found that larger hospices and those in ethnically diverse zip codes were more likely to offer such services. Larger hospices are more likely to report expanding such services. Conclusions: Many hospices are making efforts to accommodate ethnically diverse patients, but a substantial number are not. Culturally appropriate care and outreach should be addressed in efforts to improve the acceptability and experience of hospice care among minorities. C1 VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Calif Off Statewide Hlth Planning & Dev, Sacramento, CA USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, 11303 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov NR 21 TC 16 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2004 VL 42 IS 9 BP 871 EP 874 DI 10.1097/01.mlr.0000135830.13777.9c PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 851IC UT WOS:000223677800006 PM 15319612 ER PT J AU Stahl, JE Rattner, D Wiklund, R Lester, J Beinfeld, M Gazelle, GS AF Stahl, JE Rattner, D Wiklund, R Lester, J Beinfeld, M Gazelle, GS TI Reorganizing the system of care surrounding laparoscopic surgery: A cost-effectiveness analysis using discrete-event simulation SO MEDICAL DECISION MAKING LA English DT Article DE computer simulation; discrete event shnulotion; anesthesia; cost-effectiveness ID OPERATING-ROOM UTILIZATION; COMPUTER-SIMULATION; BLOCK TIME; CHOLECYSTECTOMY; GALLSTONES; SCHEDULE; MAXIMIZE AB Purpose. To determine the cost-effectiveness of a proposed reorganization of surgical and anesthesia core to balance patient volume and safety Methods. Discrete-event simulation methods were used to compare current surgical practice with a new modular system in which patient care is handed off between 2 anesthesiologists. A health core system's perspective, using hospital and professional costs, was chosen for the cost-effectiveness analysis. Outcomes were patient throughput, flow time, wait time, and resource use. Sensitivity analyses were performed on staffing levels, mortality rates, process times, and scheduled patient volume. Results. The new strategy was more effective (average 4.41 patients/d [median = 5] v. 4.29 [median = 4]) and had similar costs (average cost/patient/d = $5327 v. $5289) to the current strategy with an incremental cost-effectiveness of $318/additional patient treated/d. Surgical mortality rote must be >4% or hand-off delay>15 min before the new strategy is no longer more effective. Conclusion. The proposed system is more cost-effective relative to current practice over a wide range of mortality rates, hand-off times, and scheduled patient volumes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merimac St,10th Floor, Boston, MA 02114 USA. EM james@mgh-ita.org FU AHRQ HHS [1 K08 HS011637-01A1] NR 26 TC 20 Z9 22 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2004 VL 24 IS 5 BP 461 EP 471 DI 10.1177/0272989X04268951 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 855BB UT WOS:000223946800001 PM 15358995 ER PT J AU Wu, T Moore, RH Rafferty, EA Kopans, DB AF Wu, T Moore, RH Rafferty, EA Kopans, DB TI A comparison of reconstruction algorithms for breast tomosynthesis SO MEDICAL PHYSICS LA English DT Article DE tomosynthesis; digital mammography; iterative reconstruction; 3D reconstruction; cone-beam volume imaging ID OF-PLANE STRUCTURES; DIGITAL TOMOSYNTHESIS; FILTERED BACKPROJECTION; MAMMOGRAPHY; REMOVAL AB Three algorithms for breast tomosynthesis reconstruction were compared in this paper, including (1) a back-projection (BP) algorithm (equivalent to the shift-and-add algorithm), (2) a Feldkamp filtered back-projection (FBP) algorithm, and (3) an iterative Maximum Likelihood (ML) algorithm. Our breast tomosynthesis system acquires 11 low-dose projections over a 50degrees angular range using an a-Si (CsI:Tl) flat-panel detector. The detector was stationary during the acquisition. Quality metrics such as signal difference to noise ratio (SDNR) and artifact spread function (ASF) were used for quantitative evaluation of tomosynthesis reconstructions. The results of the quantitative evaluation were in good agreement with the results of the qualitative assessment. In patient imaging, the superimposed breast tissues observed in two-dimensional (2D) mammograms were separated in tomosynthesis reconstructions by all three algorithms. It was shown in both phantom imaging and patient imaging that the BP algorithm provided the best SDNR for low-contrast masses but the conspicuity of the feature details was limited by interplane artifacts; the FBP algorithm provided the highest edge sharpness for microcalcifications but the quality of masses was poor; the information of both the masses and the microcalcifications were well restored with balanced quality by the ML algorithm, superior to the results from the other two algorithms. (C) 2004 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wu, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM twu2@partners.org NR 33 TC 191 Z9 195 U1 2 U2 18 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2004 VL 31 IS 9 BP 2636 EP 2647 DI 10.1118/1.1786692 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 857LF UT WOS:000224117400033 PM 15487747 ER PT J AU Olson, DP Dombkowski, DM Kelliher, AS Pontillo, C Anderson, DC Preffer, FI AF Olson, DP Dombkowski, DM Kelliher, AS Pontillo, C Anderson, DC Preffer, FI TI Differential expression of cell surface antigens on subsets of CD4(+) and CD8(+) T cells SO MEDICAL SCIENCE MONITOR LA English DT Article DE lymphocytes; cell surface molecules; immunophenotype ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; FLOW-CYTOMETRY; FLUORESCENCE INTENSITY; LYMPHOCYTIC-LEUKEMIA; FOLLOW-UP; INFECTION; RECEPTOR AB Background: The assessment of relative antigen density on Tcell subsets is a feature of antigen expression that is infrequently characterized. Defining phenotypic differences is a first step in understanding associated differences in function. Additionally, a better understanding of T cell heterogenity may aid in clinical diagnoses. Materials/Methods: to further elucidate phenotypic differences of Tcell subsets, and begin to determine what information relative antigen density contributes to immunology, we analyzed normal human peripheral blood. T cells for a variety of immunophenotypic (CD2, CD3, CD4, CD5, CD7, CD8, CD45RA, CD45RO, TCRalphabeta) and light scatter characteristics using 6 color flow cytometry. T cell leukemia specimens were also analyzed. Results: Our data show that statistically significant immunophenotypic differences exist between susets of human CD4 and CD8 Tcells. Normal Tcells express different levels of relative antigen density for some antigens compared to malignant T cells. Conclusions: Significant differences are seen in relative antigen density for several cell surface markers between CD4+ and CD8+ Tcells. Nether donor source nor flow cytometric calibration account for these differences. The data are applied to specimens from patients with T-lineage acute lymphoblastic leukemia to show how antigen density can be used clinically in aiding to diagnose disease. The data presented here can be use to further invetigate these cell populations for functional differences. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Preffer, FI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 149 13th St, Boston, MA 02129 USA. EM preffer@helix.mgh.harvard.edu NR 23 TC 3 Z9 3 U1 0 U2 0 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD SEP PY 2004 VL 10 IS 9 BP BR339 EP BR345 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 867HR UT WOS:000224833800005 PM 15328479 ER PT J AU Herndon, JH AF Herndon, JH TI Osteoarthritis in women after menopause SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID REPLACEMENT THERAPY; KNEE; CARTILAGE; ESTROGEN; HAND C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. NR 21 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 SEP-OCT PY 2004 VL 11 IS 5 BP 499 EP 501 DI 10.1097/01.GME.0000135244.19596.30 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 853MB UT WOS:000223830600001 PM 15356400 ER EF